# Patent

## Title
Discovery of candidate biomarkers of in vivo apoptosis by global profiling of  caspase cleavage sites

## Abstract

The present invention relates to the discovery of novel biomarkers of in vivo apoptosis based on a large number of caspase-like cleavage sites. These biomarkers are useful for detection and quantification of apoptosis in a biological sample. The invention also provides synthetic peptides and proteins corresponding to neo-epitopes created by proteolytic processing of these cleavage sites. The synthetic peptides can be used as standards to enable identification and quantitation of these biomarkers using mass spectrometry. The synthetic proteins can be used to generate antibodies and other binding reagents specific for these biomarkers. Methods for detecting apoptosis as well as for diagnosing or for providing a prognosis for a disease or disease state characterized by apoptosis are also provided herein. Finally, the invention provides compositions and kits for performing the methods of the invention.

## Background
CROSS-REFERENCES TO RELATED APPLICATIONS
This application is a continuation of International Application No. PCT/US2009/052297, filed Jul. 30, 2009, which claims priority benefit of U.S. Provisional Application Ser. No. 61/084,845 filed on Jul. 30, 2008, the disclosure of which is incorporated by reference in its entirety for all purposes.


STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT
This invention was made with Government support under grant nos. R01 GM081051 and F32 GM074458, awarded by the National Institutes of Health. The Government has certain rights in the invention.


REFERENCE TO A “SEQUENCE LISTING,” A TABLE, OR A COMPUTER PROGRAM LISTING APPENDIX SUBMITTED AS AN ASCII TEXT FILE
The Sequence Listing written in file 81906-797932_ST25.TXT, created on Apr. 14, 2013, 98,022 bytes, machine format IBM-PC, MS-Windows operating system, is hereby incorporated by reference.
BACKGROUND OF THE INVENTION
The 600 or so proteases encoded in the human genome are involved in a diversity of biological processes. Some function as nonspecific degradative enzymes associated with protein catabolism, indiscriminately and exhaustively cleaving many protein substrates at many sites. In contrast, several others function as selective post-translational modifiers, cleaving a limited set of protein substrates, usually at only one or a few sites. Apoptosis is an important example of a biological process regulated by widespread but specific intracellular proteolysis, predominantly carried out by the caspase family of proteases. This genetically programmed and non-inflammatory form of cell death is a central component of homeostasis, tissue turnover, and development. Since apoptotic turnover of cells lies in direct opposition to the uncontrolled growth of tumor cells, a strong link also exists between apoptosis and cancer. Indeed, the terminal cellular effect of most chemotherapeutic compounds is induction of apoptosis (Kaufmann et al., Exp Cell Res, 2000, 256, 42-9).
The widespread intracellular proteolysis that is a hallmark of apoptosis is predominantly mediated by a family of aspartate-specific proteases termed caspases (Taylor et al., Nat Rev Mol Cell Biol, 2008, 9, 231-41). Apoptosis can be induced by extracellular death ligands, such as Fas ligand, TNF-α, or TRAIL, via the extrinsic pathway to activate caspase-8. It can also be induced by agents such as cytotoxic compounds, radiation, and other environmental stresses via the intrinsic pathway with release of proapoptotic factors from mitochondria to activate caspase-9. Initiator caspases-8 and -9 in turn activate downstream executioner caspases, among them caspases-3 and -7. Caspases then catalyze the inactivation of a multitude of prosurvival/antiapoptotic proteins and activation of antisurvival/proapoptotic proteins. The combined proteolytic events culminate in apoptotic cell death and clearance by phagocytes.
As a specific illustration, after receiving a cell death signal, apoptotic cells execute a cellular program that results in widespread and dramatic cellular changes that can include: (1) cell shrinkage and rounding due to the breakdown of the proteinaceous cytoskeleton; (2) the appearance of a dense cytoplasm and tight packing of cell organelles; (3) chromatin condensation into compact patches against the nuclear envelope; (4) discontinuity of the nuclear envelope and DNA fragmentation; (5) breakdown of the nucleus into several discrete chromatin bodies or nucleosomal units due to the degradation of DNA; (6) blebbing of the cell membrane into irregular buds. Near the conclusion of the apoptotic program, the cell breaks apart into several vesicles called apoptotic bodies, which are then typically phagocytosed.
Because the study of apoptotic pathways has ramifications for development of therapies for treatment of cancer, there is significant interest in gaining a better understanding of caspase proteolysis during apoptosis. For example, identification of new targets of proteolysis in apoptosis can lead to discovery of prosurvival/antiapoptotic factors, which can in turn serve as novel targets for cancer chemotherapy. A number of caspase substrates are active or established drug targets for treating cancer, including topoisomerases I and II, androgen receptor, thymidylate synthase, Bcl-2, IAPs, Mdm2 or Hdm2, PARP, HSP90, HDACs, the proteasome, Akt, MEK, Abl, EGFR, HER2, and VEGF, to name a few.
Products of caspase proteolysis may also serve as useful biomarkers of in vivo apoptosis. For example, serum levels of the caspase cleavage product of cytokeratin-18 have been used as a marker of chemotherapeutic efficacy in prostate, breast, and testicular cancers (Kramer et al., Br J Cancer, 2006, 94, 1592-8; Olofsson et al, Clin Cancer Res, 2007, 13, 3198-208; de Haas et al, Neoplasia, 2008, 10, 1041-8). Although apoptotic cells are typically cleared by phagocytes such as macrophages, it has been hypothesized that local clearance mechanisms are overloaded in cases of high cellular turnover and death, causing dying apoptotic cells to undergo secondary necrosis (Linder et al, Cancer Lett, 2004, 1, 1-9). While the plasma membrane remains intact during apoptosis, it is compromised and ruptured during secondary necrosis. Such secondary necrosis of dying tumor cells is consistent with the observation of what are normally intracellular components such as cytochrome c, DNA, nucleosomes, and cytokeratin-18 in the vasculature of cancer patients during chemotherapy (Beachy et al., Cancer Immunol Immunother, 2008, 57, 759-75).
A logical extension of these findings is that other caspase-derived neo-epitopes besides caspase-cleaved cytokeratin-18 are released into the vasculature of cancer patients undergoing chemotherapy. Such additional caspase-proteolyzed proteins may represent novel prognostic, diagnostic, or pharmacodynamic biomarkers of in vivo apoptosis, predicting likely patient outcome, indicating the most suitable therapeutic regimen, or serving as markers of therapeutic response. Because of tumor and patient heterogeneity, the clinical utility of single biomarker assays can be limited (Anderson et al., Mol Cell Proteomics, 2002, 1, 845-67). A multiparameter diagnostic assay of in vivo apoptosis based on a panel of caspase-derived neo-epitopes would likely be more sensitive and specific for a given type of cancer or therapeutic regimen. Great utility therefore exists in the identification of physiologically relevant caspase cleavage sites. Knowledge of such cleavage sites is required for the preparation of both peptide standards corresponding to neo-epitopes and antibodies that specifically bind to neo-epitopes. These reagents will enable identification and quantitation of caspase-derived neo-epitopes in biological samples such as serum, plasma, or tissue biopsies, and for validation of a given set of caspase-derived neo-epitopes as clinically useful biomarkers of in vivo apoptosis.
BRIEF SUMMARY OF THE INVENTION
The present invention relates generally to 1356 experimentally determined and physiologically relevant caspase-like cleavage sites, a method for discovering additional physiologically relevant caspase cleavage sites, discovery of biomarkers of in vivo apoptosis based on any of these caspase-like cleavage sites, and methods and compositions for detecting and quantitating protein neo-epitopes corresponding to these biomarkers in biological samples, using either peptide standards and mass spectrometry, or antibodies specific to neo-epitopes, or both. The invention also provides compositions and kits for performing the methods of the invention.
Direct and selective labeling of protein α-amines or α-carboxylates is a powerful approach for profiling proteolysis in complex mixtures since it permits direct identification of cleavage sites in protein substrates. Approximately 80% of mammalian proteins are known to be N-terminally acetylated (Brown et al., J Biol. Chem. 1976; 251(4):1009-14). Thus, greater signal over background can be achieved through N-terminal instead of C-terminal labeling. However, such labeling must still be extremely selective for α-amines over lysine ε-amines, which are approximately 25 times more abundant in an average protein. To achieve this selectivity, we have adopted an enzymological approach that makes use of the rationally designed protein ligase subtiligase. This engineered enzyme exhibits absolute selectivity for modification of α-amines (Abrahmsén et al., Biochemistry. 1991; 30(17):4151-9; Chang et al., Proc Natl Acad Sci USA. 1994; 91(26):12544-8).
We have developed a proteomic method utilizing subtiligase that enables capture and sequencing of N-terminal peptides found in complex biochemical mixtures (FIGS. 1A-1 and 1A-2). Proteins in biological samples are N-terminally biotinylated by treatment with subtiligase and peptide glycolate ester substrates specially tailored to our proteomic workflow (FIGS. 1B-1 and 1B-2). Biotinylated samples are exhaustively digested with trypsin, and N-terminal peptides are captured using avidin affinity media. The peptide ester substrate contains a tobacco etch virus (TEV) protease cleavage site to permit facile recovery of captured peptides. An important aspect of our workflow is that recovered peptides retain an N-terminal serinyl-tyrosyl dipeptide modification or 2-aminobutyryl modification, providing a key hallmark to distinguish labeled peptides from contaminating unlabeled peptides using tandem mass spectrometry (LC/MS/MS). In standard protease nomenclature, substrates are cleaved between the P1 (N-terminal) and P1′ (C-terminal) residues, with Pn and Pn′ residues increasing in count by one in both directions away from the scissile bond (Schechter and Berger, 1968). Thus, the Pn′ residues of a cleavage site correspond to N-terminal residues of the labeled peptide identified, while the Pn residues of a cleavage site can be inferred from the protein sequence preceding the identified peptide.
Over 300 publications describing a wide variety of cell types and apoptotic inducers have reported the proteolysis of approximately 360 human proteins in apoptosis, but only approximately 300 caspase cleavage sites in human protein substrates have been reported (Lüthi et al., Cell Death Differ. 2007; 14(4):641-50). We have carried out studies in a number of cancer cell lines, including Jurkat, an acute lymphocytic leukemia cell line, DB, a diffuse large B cell lymphoma cell line, and RPMI 8228, a multiple myeloma cell line, using a variety of apoptotic inducers including etoposide, doxorubicin, staurosporine, and TRAIL. Our combined studies to date have resulted in the identification of approximately 1360 caspase cleavage sites in a approximately 1040 protein substrates. These caspase cleavage sites and additional caspase cleavage sites yet to be discovered in other model systems of human cancers represent a wealth of knowledge and an excellent starting point for discovery of novel biomarkers of in vivo apoptosis, and for preparation of reagents for detection and quantitation of such biomarkers in biological samples.
The present invention provides proteolytic polypeptide biomarkers for the detection and quantitation of apoptosis. In one embodiment of the invention, these biomarkers comprise proteolytic polypeptides generated in response to an apoptotic stimulus. The biomarkers of the present invention may be generated in response to a specific apoptotic stimulus or conversely may be generated by multiple or general apoptotic stimuli. In some embodiments, the proteolytic polypeptide biomarkers of the present invention are generated by the action of a single protease, or by the action of a limited set of proteases activated in response to a specific apoptotic stimulus. In other embodiments, the biomarkers may be generated by the action of a plurality of apoptotic proteases. In a particular embodiment, the proteolytic apoptotic polypeptide biomarkers comprise N-termini or C-termini selected from those found in Table 1.
In one embodiment, the proteolytic biomarkers of the present invention are useful for the detection of apoptosis in an individual. In a specific embodiment, the proteolytic biomarkers are useful for the diagnosis in an individual of a disease characterized by apoptosis. In another embodiment, these biomarkers are useful for providing a prognosis for an individual suffering from a disease characterized by apoptosis. In yet other embodiments, these biomarkers are useful for determining the extent of apoptosis in an individual or the severity, stage, or other relevant characteristics of a disease characterized by apoptosis in an individual. In one particular embodiment, the proteolytic apoptotic biomarkers of the present invention are useful in determining the efficacy of a drug in vitro or in vivo.
In another embodiment, the present invention provides novel proteolytic apoptotic cleavage junctions. In certain embodiments, these cleavage junctions comprise amino acids that are cleavage substrates for proteases activated in response to an apoptotic stimulus. In a particular embodiment, the proteolytic apoptotic cleavage junctions comprise an amino acid sequence selected from those found in Table 3. In a first embodiment, the cleavage junctions of the present invention are useful for detecting apoptosis in a biological sample. In a second embodiment, the cleavage junctions are useful for diagnosing or providing a prognosis for a disease state associated with apoptosis in an individual, or for assessing response to a particular line of therapy. For instance, a protein or polypeptide comprising the cleavage junction can be used in an assay to measure apoptotic protease (e.g., a caspase) activity or levels in a sample. The peptides or polypeptides comprising the junction may be of a variety of lengths, preferably from 7 to 40, 7 to 20, or 10 to 30 amino acids in length.
The present invention also provides proteolytic apoptotic signatures. In one embodiment, the apoptotic signatures of the invention comprise at least one proteolytic polypeptide generated in response to an apoptotic stimulus. In another embodiment of the invention, the apoptotic signatures comprise the levels of one or more proteolytic polypeptides. In a particular embodiment, the apoptotic signatures of the present invention comprise the presence or particular level of one or more proteolytic polypeptides comprising N-termini or C-termini selected from those found in Table 1. In yet other embodiments, the apoptotic signatures of the present invention may comprise one or more ratios of cleaved to uncleaved apoptotic proteolytic sites. In a particular embodiment of the present invention, the apoptotic proteolytic sites are selected from those found in Table 3. In some embodiments, the proteolytic apoptotic signatures of the present invention may correspond to the presence or absence of a disease state in an individual. In other embodiments of the present invention, the proteolytic apoptotic signatures may correspond to a particular level of apoptosis in an individual or in a sample from an individual suffering from a disease characterized by apoptosis. In another embodiment of the present invention, the proteolytic apoptotic signatures may correspond to a prognosis for an individual suffering from a disease characterized by apoptosis. In yet other embodiments, the apoptotic signatures may correspond to a level of efficacy for a drug or to a response level in an individual taking a drug or receiving a treatment for a disease characterized by apoptosis.
In one embodiment, the present invention provides reagents for detecting the proteolytic apoptotic polypeptide biomarkers of the invention. In one embodiment, the reagents comprise synthetic peptides corresponding to an N-terminal or C-terminal sequence selected from those found in Table 1. In a particular embodiment, these synthetic peptides have the same sequence as either an unmodified or modified peptide found in Table 1. In another embodiment, these synthetic peptides contain six or more consecutive residues from a sequence of previous residues found in Table 1, starting from the most C-terminal residue, and possibly extending to further than eight prior residues in the sequence of the full-length protein. In one embodiment, these peptides correspond to the most N-terminal peptide obtained after digestion with trypsin of the C-terminal fragment of the full-length protein following proteolysis during apoptosis at one the cleavage sites found in Table 2. In another embodiment, these peptides correspond to the most C-terminal peptide obtained after digestion with trypsin of the N-terminal fragment of the full-length protein following proteolysis during apoptosis at one the cleavage sites found in Table 1 or 2. In another embodiment, these peptides correspond to the peptides that would be obtained following digestion of the N- and C-terminal fragments of the protein substrate with a protease other than trypsin, including, but not limited to, chymotrypsin, V8, Lys-C, Lys-N, Arg-C, Asp-N, Asp-C, pepsin, and thermolysin. In another particular embodiment, these peptides correspond to the peptides that would be obtained following treatment of the N- and C-terminal fragments of the protein substrate with a chemical cleavage agent such as cyanogen bromide. In a specific embodiment, the synthetic peptides contain stable heavy isotopes of carbon or nitrogen (e.g., 13C or 15N), incorporated by use of the appropriately heavy isotope-labeled amino acid during preparation of the synthetic or modified peptides. In a particular embodiment, the light and heavy versions of the peptides are used as standards in a mass spectrometry approach such as selected reaction monitoring (SRM) or multiple reaction monitoring (MRM) to optimize detection of corresponding peptides in biological samples derived from proteolytic apoptotic polypeptides, and to permit quantitation of such peptides in biological samples.
In another embodiment, the present invention provides reagents for detecting the proteolytic apoptotic polypeptide biomarkers of the invention. In one embodiment, the reagents comprise proteins that bind to the biomarkers with high affinity and specificity. In a particular embodiment, the reagents comprise antibodies, or fragments thereof, generated against the proteolytic apoptotic polypeptides of the present invention. In a specific embodiment, the present invention provides antibodies that bind to a proteolytic apoptotic polypeptide comprising an N-terminal or C-terminal sequence selected from those found in Table 1. In one embodiment, an antibody of the present invention binds to the target proteolytic fragment, but does not substantially bind to the full-length protein or intact proteolytic cleavage junction. In other embodiments, the reagents comprise antibodies generated against antigens comprising apoptotic cleavage sites or junctions. In a specific embodiment, the present invention provides antibodies that bind to an apoptotic cleavage site selected from those listed in Table 3. In one embodiment, the antibodies of the present invention bind to an intact proteolytic cleavage junction, but do not substantially bind to the N-terminal or C-terminal proteolytic polypeptide generated in response to an apoptotic stimulus. In another particular embodiment of the invention, antibodies are provided that bind to the N-terminus or C-terminus of a proteolytic polypeptide comprising a sequence selected from those found in Table 1.
In another embodiment, the present invention provides methods of generating binding reagents to one or more proteolytic apoptotic polypeptide biomarker. In one embodiment of the invention, methods are provided for generating a binding reagent to a single proteolytic polypeptide. In other embodiments, the present invention provides methods of simultaneously generating binding reagents against more than one proteolytic polypeptides of the present invention. In a particular embodiment, the present invention provides methods of generating antibodies against one or more proteolytic apoptotic polypeptide of the invention.
In one embodiment, the present invention provides methods of detecting apoptosis or determining the level of apoptosis in an individual or in a sample from an individual. In one embodiment, the methods comprise detecting a proteolytic apoptotic polypeptide biomarker generated in response to an apoptotic stimulus in a biological sample. In certain embodiments, the methods of the present invention comprise detecting one or more biomarkers comprising an N-terminal or C-terminal sequence selected from those found in Table 1. In other embodiments of the present invention, methods are provided for detecting or determining a proteolytic apoptotic signature. In certain embodiments of the invention, detecting or determining a proteolytic apoptotic signature comprises detecting or determining the level of one or more proteolytic apoptotic polypeptide biomarkers generated in response to an apoptotic signature. In other embodiments, the methods further comprise comparing a first proteolytic apoptotic signature detected in an individual with a second apoptotic signature corresponding to a predetermined apoptotic level or disease state. In certain embodiments of the invention, said second apoptotic signature comprises an average or conglomerate apoptotic signature determined from samples taken from a plurality of individuals suffering from the same disease or disease state associated with apoptosis. In yet other embodiments, the methods of the present invention comprise determining the ratio of the levels of at least one proteolytic apoptotic polypeptide to the levels of at least one intact proteolytic cleavage junction.
In another embodiment, the present invention provides methods for diagnosing or providing a prognosis for a disease associated with apoptosis in an individual, or for tracking therapeutic progress in an individual. In some embodiments of the present invention, the methods comprise detecting one or more proteolytic apoptotic polypeptide biomarkers in a sample from said individual. In other embodiments, the methods of the present invention comprise detecting a proteolytic apoptotic signature in a sample from an individual. In particular embodiments, the methods of the present invention comprise comparing the level of one or more proteolytic apoptotic polypeptide or apoptotic signature in an individual with one or more proteolytic apoptotic signature corresponding to a predetermined disease or disease state. In yet other embodiments, the methods of diagnosing and providing a prognosis provided by the present invention comprise determining the ratio of the levels of at least one proteolytic apoptotic polypeptide to the levels of at least one intact proteolytic cleavage junction. In particular embodiments, these methods further comprise comparing said ratios to predetermined values corresponding to a particular diagnosis or prognosis for a disease state associated with apoptosis. In another embodiment, the methods comprise comparing levels of apoptotic signatures in a patient before the start of therapy, and during the course of therapy.
In one embodiment, the present invention provides kits for use in the detection of proteolytic apoptotic polypeptides. In some embodiments, the kits of the present invention comprise a plurality of light- or heavy-labeled synthetic peptides corresponding to N- and/or C-terminal sequences found in Table 1 that can be used for optimizing detection of corresponding peptides in biological samples derived from proteolytic apoptotic polypeptides, and to permit quantitation of such peptides in biological samples, using mass spectrometry. In other embodiments, the kits of the present invention comprise a plurality of binding reagents that specifically bind to proteolytic polypeptides that are generated in response to an apoptotic stimulus. In a specific embodiment, the kits of the present invention comprise a plurality of binding reagents that bind to polypeptides comprising an N-terminal or C-terminal sequence found in Table 1. In certain embodiments, the binding reagents are antibodies, including polyclonal antibodies, monoclonal antibodies, and fragments thereof. In certain embodiments, the kits of the present invention are useful in the diagnosis or prognosis of a disease characterized by apoptosis in an individual, or for tracking therapeutic progress in an individual that is characterized by an increased level of apoptosis. In yet other embodiments, the present invention provides kits comprising a plurality of binding reagents that specifically bind to proteolytic apoptotic cleavage junctions. In a particular embodiment, the proteolytic apoptotic cleavage junctions comprise amino acid sequences found in Table 3. In still other embodiments, the kits of the present invention comprise at least one binding reagent that specifically binds to a proteolytic apoptotic polypeptide and at least one binding reagent that specifically binds to a proteolytic apoptotic cleavage junction. In other certain embodiments, the kits comprise binding reagents that specifically bind to peptides generated from proteolytic apoptotic polypeptides after treatment with proteases such as trypsin, chymotrypsin, V8, Lys-C, Lys-N, Arg-C, Asp-N, Asp-C, pepsin, or thermolysin, or reagents such as cyanogen bromide, permitting enrichment of these peptides for detection and quantitation using mass spectrometry.
In another aspect, the invention provides a method of modulation apoptosis by administering a siRNA or a shRNA corresponding to an mRNA encoding a protein of Table 1. In this first aspect, the invention also provides a pharmaceutical composition comprising the siRNA molecule or the shRNA molecule and/or an siRNA or shRNA expression vector which comprises a portion of a nucleotide sequence complementary to an mRNA encoding a protein of Table 1. In some embodiments, the siRNA is at least about 15-50 nucleotides in length (e.g., each complementary sequence of the double stranded siRNA is 15-50 nucleotides in length, and the double stranded siRNA is about 15-50 base pairs in length). In some further embodiments still, the length of the siRNA molecule is about 20-30 base nucleotides, about 20-25 or about 24-29 nucleotides in length, e.g., 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 nucleotides in length. In still further embodiments, the siRNA is a small hairpin loop or small hairpin RNA, known as shRNA. In some embodiments, the invention provides a method of treating cancer or inducing apoptosis in a subject in need thereof by administering the siRNA or shRNA or siRNA vector or shRNA vector to the subject. In some embodiments of any of the above the siRNA or shRNA is directed toward a protein having a M value from Table 1 greater than 1, 2, 4, or 8. In other embodiments, siRNA corresponding to a protein of Table 1 or 3 having a plurality of such cleavage sites is used.



BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1A-1, 1A-2, 1B-1, and 1B-2. A subtiligase subtiligase-based method for positive selection of peptides corresponding to N-termini of proteins from complex mixtures. (FIGS. 1A-1 and 1A-2) Workflow for biotinylation of protein N-termini in complex mixtures using subtiligase and a biotinylated peptide ester that contains a TEV protease cleavage site, trypsinization of labeled proteins, capture of biotinylated N-terminal peptides with immobilized avidin, recovery of captured peptides using TEV protease, and analysis of N-terminal peptides by 1D or 2D LC/MS/MS for identification of corresponding proteins and cleavage sites. The representative MS/MS spectrum corresponds to semi-tryptic peptide GSAVNGTSSAETNLEALQK from MEK1 (MP2K1 HUMAN) (SEQ ID NO:178) and identifies a previously unknown caspase-like cleavage site at Asp 16. The a2 and b2 ions at m/z 223 and 251 are characteristic hallmarks of a ligated, serinyl-tyrosyl dipeptive-bearing, N-terminal peptide. (FIGS. 1B-1 and 1B-2) Structure of two biotinylated peptide glycolate esters used in the proteomic workflow. Sequences: (FIG. 1A-2) SYGSAVNGTSSAETNLEALQK (SEQ ID NO:431); MEK1 protein sequence (SEQ ID NO:432); cleavage site (SEQ ID NO:433), (FIG. 1B-1) Ester1 (SEQ ID NO:434), (FIG. 1B-2) Ester2 (SEQ ID NO:435), (FIG. 1A-1) TENLYFQSY (fragment of SEQ ID NO:434).
FIGS. 2A, 2B, and 2C. Classification of unique N-termini identified in untreated and apoptotic Jurkat cells according to Swiss-Prot annotation. (FIG. 2A) Classification of N-termini identified in small-scale and large-scale experiments with untreated cells (131 and 661 unique N-termini, respectively, combined from two experiments in both cases). (FIG. 2B) Classification N-termini identified in small-scale experiments with untreated cells (131 unique N-termini combined from two experiments) and apoptotic cells (244 unique N-termini combined from four experiments). (FIG. 2C) Classification N-termini identified in large-scale experiments with untreated cells (661 unique N-termini combined from two experiments) and apoptotic cells (733 unique N-termini combined from three experiments).
FIGS. 3A and 3B. N-termini derived from caspase-like proteolytic processing are a hallmark of apoptotic cells. (FIG. 3A) Frequencies of P1 and P1′ amino acid residues corresponding to non-homologous N-termini identified in small-scale 1D LC/MS/MS experiments with untreated and apoptotic Jurkat cells. Data are represented as mean±SD (n=2 for untreated and n=4 for apoptotic). (FIG. 3B) Frequencies of P1 and P1′ amino acid residues corresponding to non-homologous N-termini identified in large-scale 2D LC/MS/MS experiments with untreated and apoptotic Jurkat cells. Data are represented as mean±SD (n=2 for untreated and n=3 for apoptotic). “ ” indicates lack of a putative P1 residue in cases where the P1′ residue is an initiator methionine.
FIG. 4. Inferred P1 residues for all N-termini annotated in the human Swiss-Prot database originating from chain, signal peptide, transit peptide, or propeptide processing.
FIGS. 5A and 5B. Analysis of proteolysis of selected proteins, all identified as caspase substrates in proteomic studies, during apoptosis in Jurkat cells following treatment with 50 μM etoposide. Black arrows indicate full-length proteins. Red arrows indicate expected cleavage products for cleavage at the sites identified in our studies. Cleavage products were not detected in all cases. (FIG. 5A) Time courses for the proteolysis of CCTδ, HDAC6, HDAC7, Ku80, LCOR, N-CoR, RBBP7, RCOR2, SHARP, TBLR1, UBP5, and UBP36 indicates full cleavage of HDAC6, HDAC7, N-CoR, RCOR2, SHARP, TBLR1, UBP5, and UBP36, and partial cleavage of CCTδ, Ku80, LCOR, and RBBP7. (FIG. 5B) The cleavage of a representative set of substrates identified in our studies, HDAC7, Ku80, RCOR2, TBLR1, and UBP36, is blocked by the broad-spectrum caspase inhibitor Z-VAD(OMe)-fmk and is thus dependent on caspase activity.
FIGS. 6A, 6B, 6C, 6D, and 6E. Substrate specificity of the caspase-like proteolytic activity in etoposide-treated Jurkat cells. (FIG. 6A) Sequence logo representation (Crooks et al., 2004) of the frequency of amino acid residues in the identified caspase cleavage sites. (FIG. 6B) Sequence logo representation of the in vitro substrate specificity of caspase-3 (Stennicke et al., 2000; Thornberry et al., 1997). (FIG. 6C) Sequence logo representation of the frequency of amino acid residues in known human and human ortholog of rodent caspase cleavage sites (Liithi and Martin, 2007). (FIG. 6D) Frequency of P4-P1 motifs in the identified caspase cleavage sites. (FIG. 6E) Receiver operator characteristic curves showing the discrimination ability of HMMs constructed from three different cleavage site training sets (Jurkat, literature, and merged). Three representative HMM score threshold values for the merged dataset are indicates (TPR=true positive rate, FPR=false positive rate). Sequence: DEVD (SEQ ID NO:430).
FIGS. 7A, 7B, and 7C. Sequence logo representations of prototypical inflammatory, executioner, and initiator caspase substrate specificities. These are exemplified by (FIG. 7A) caspase-1, (FIG. 7B) caspase-3, and (FIG. 7C) caspase-8, based on P4-P1 data adapted from Thornberry et al. (Thornberry et al., J Biol Chem. 1997; 272(29):17907-11) and P1′ data adapted from Stennicke et al. (Stennicke et al., Biochem J. 2000; 350 Pt 2:563-8).
FIG. 8. CID spectrum of the SY-labeled N-terminal peptide AAASAPQM(Oxidation)DVSK from N-CoR (NCOR1_HUMAN) (SEQ ID NO:402) corresponding to the P4-P4′ cleavage site LVD(1826)/AAAS (SEQ ID NO:403).
FIG. 9. CID spectrum of the SY-labeled N-terminal peptide GLSEQENNEK from N-CoR (NCOR1_HUMAN) (SEQ ID NO:404) corresponding to the P4-P4′ cleavage site EIID(385)/GLSE (SEQ ID NO:405).
FIG. 10. CID spectrum of the SY-labeled N-terminal peptide GTAEETEEREQATPR from N-CoR (NCOR1_HUMAN) (SEQ ID NO:406) corresponding to the P4-P4′ cleavage site DKID(555)/GTAE (SEQ ID NO:407).
FIG. 11. CID spectrum of the SY-labeled N-terminal peptide GDVEIPPNKAVVLR from TBLR1 (TBL1R_HUMAN) (SEQ ID NO:408) corresponding to the P4-P4′ cleavage site MEVD(152)/GDVE (SEQ ID NO:409).
FIG. 12. CID spectrum of the SY-labeled homologous N-terminal peptide AVM(Oxidized)PDVVQTR from either TBLR1 (TBL1R_HUMAN) or TBL1X (TBL1X_HUMAN) (SEQ ID NO:410) corresponding to the P4-P4′ cleavage site SLID(86)/AVMP (SEQ ID NO:411).
FIG. 13. CID spectrum of the SY-labeled N-terminal peptide GGGPGQVVDDGLEHR from HDAC7 (HDAC7_HUMAN) (SEQ ID NO:412) corresponding to the P4-P4′ cleavage site LETD(412)/GGGP (SEQ ID NO:413).
FIG. 14. CID spectrum of the SY-labeled N-terminal peptide SIQEPVVLFHSR from SHARP (MINT_HUMAN) (SEQ ID NO:414) corresponding to P4-P4′ caspase-like cleavage site STTD(1574)/SIQE (SEQ ID NO:415).
FIG. 15. CID spectrum of the SY-labeled N-terminal peptide SDKGEFGGFGSVTGK from RBBP7 (RBBP7_HUMAN) (SEQ ID NO:416) corresponding to P4-P4′ caspase-like cleavage site SHCD(98)/SDKG (SEQ ID NO:417).



DETAILED DESCRIPTION OF THE INVENTION
The present invention provides novel proteolytic apoptotic polypeptide biomarkers. In one embodiment of the invention, the proteolytic apoptotic polypeptide biomarkers are generated in response to an apoptotic stimulus. In certain embodiments, the apoptotic stimulus may be endogenous to the cell, tissue, organ, or organism of interest. In other embodiments, the apoptotic stimulus may be exogenous or induced, such as in tissue culture. In some embodiments, apoptosis may be induced by the treatment of cells, tissues, organs, or organisms with a drug known to cause apoptosis, such as etoposide, camptothecin, anisomycin, and the like. In a specific embodiment, the proteolytic apoptotic polypeptide biomarkers of the present invention comprise N-terminal or C-terminal sequences selected from those found in Table 1.
In certain embodiments of the invention, the proteolytic apoptotic polypeptide biomarkers comprise proteolytic fragments that are generated by cleavage of a full length protein of Table 1 or an intact proteolytic apoptotic cleavage junction of Table 1 by the action of a suitable protease. Suitable proteases will be obvious to the skilled artisan. In one particular embodiment, the protease is an enzyme known to function in the apoptotic pathway of a cell such as a caspase. In one embodiment of the present invention, a proteolytic apoptotic polypeptide biomarker of the present invention will have a sequence selected from those found in Table 1 at its N-terminus or C-terminus. In some embodiments of any of the above the polypeptide biomarker corresponds to a protein having a M value from Table 1 of 1 or greater than 1, 2, 4, or 8. In other embodiments, the biomarker corresponds to a protein of Table 1 or 3 having a plurality of such apoptotic polypeptide biomarkers or cleavage sites. In yet another embodiment, a plurality of biomarkers from Table 1 are used in assessing apoptosis or a particular apoptosis pathway in which the biomarkers correspond to apoptotic cleavages of multiple protein substrates of a single apoptotic protease (e.g., caspase) of interest. In other embodiments, the biomarkers from Table 1 are selected so as to include biomarkers for the activity of a plurality of apoptotic proteases of interest.
In certain embodiments, a proteolytic apoptotic polypeptide biomarker of the invention may further comprise a recombinant sequence N-terminal or C-terminal to a sequence found in Table 1. For example, a biomarker of the invention may further comprise a fusion tag used to facilitate purification, detection, or both purification and detection of the polypeptide. Many fusion tags suitable for use with the present invention are well known in the art and include without limitation, polyhistidine tags, GST tags, biotin, calmodulin binding protein tags, chitin binding protein tags, TAP tags, Strep tags, Myc tags, HA tags, and the like. Other suitable recombinant sequences may further comprise a linker between the fusion tag and the polypeptide. Linker sequences may comprise a protease recognition site, such as a TEV cleavage site.
The present invention also provides proteolytic apoptotic cleavage junctions. In certain embodiments, a cleavage junction of the present invention may comprise an amino acid sequence targeted by a protease in response to an apoptotic stimulus. In a particular embodiment, the cleavage junctions of the present invention comprise sequences selected from those found in Table 3. In one embodiment, a cleavage junction of the invention comprises a full length protein containing a sequence identical to a sequence listed in Table 3. In a second embodiment, a cleavage junction of the present invention may comprise a protein fragment containing a sequence found in Table 3, that is competent for cleavage by a protease involved in apoptosis. In certain embodiments, the protein fragment may comprise about 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 250, 300, 400, 500, 600, 700, 800, 900, 1000, or more amino acids of a protein identified by a Swiss-Prot ID found in Table 3. In some embodiments, the peptide is preferably at least about 6 amino acids long, 7 amino acids long, 8 amino acids long, 10 amino acids long and less than 50 amino acids long and can comprise or consist of an amino acid sequence (previous amino acid or C-terminal amino acid sequence, unmodified or identified amino acid, or N-terminal amino acid sequence, modified identified amino acid sequence, or protein) of Table 1. Preferred peptides for measuring the activity of apoptotic protease include the cleavage junction corresponding to a previous amino acid sequence of Table 1 and its corresponding immediately following identified or unmodified peptide of Table 1. A preferred ranged of peptide lengths is from about 7 to 50 amino acids in length and may include the full sequences of both the previous and identified or unmodified polypeptides of Table 1. Other suitable lengths range from 7 to 25, 7 to 15, 10 to 30, 15 to 35, and 15 to 25.
The apoptotic biomarkers of the present invention find use in the detection and quantification of apoptosis in a biological sample. In certain embodiments, the biomarkers can be used to detect apoptosis in a sample from an organism suffering from a disease characterized by apoptosis. In one embodiment, the biomarkers of the present invention can be used to diagnose or provide a prognosis for a disease characterized by apoptosis in an individual. In other embodiments the biomarkers can be used to determine the extent of apoptosis or the extent of a disease state in an individual or in a sample from an individual. In yet other embodiments, the biomarkers of the present invention are useful for determining the efficacy of a drug or for monitoring treatment in a patient. The biomarkers are particularly useful for determining the efficacy of drugs that induce apoptosis or for monitoring a treatment in a patient that results in apoptosis.
In one embodiment, the present invention provides proteolytic apoptotic signatures or profiles. In a specific embodiment, the apoptotic signatures of the present invention comprise one or more proteolytic polypeptide that is generated in response to an apoptotic stimulus. In another embodiment, an apoptotic signature of the invention comprises the level of at least one proteolytic apoptotic polypeptide biomarker in a biological sample. In one specific embodiment of the invention, an apoptotic signature comprises the level of at least one, preferably at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 250, 300, or more proteolytic apoptotic polypeptides comprising an N-terminus or C-terminus selected from those found in Table 1, in a biological sample. In some embodiments, the N-terminus or C-terminus is that formed by the cleavage of a polypeptide by an apoptotic protease. In another embodiment of the invention, an apoptotic signature or profile comprises a plurality, or the level of a plurality, of proteolytic apoptotic cleavage junctions. In a specific embodiment, an apoptotic signature comprises the level of at least one, preferably at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 250, 300, or more proteolytic apoptotic cleavage junctions, in a biological sample, selected from those found in Table 3. In further embodiments of the present invention, a proteolytic apoptotic signature may comprise a mixture of proteolytic apoptotic polypeptides and proteolytic apoptotic cleavage junctions, or the levels thereof, in a biological sample. In yet another embodiment, a proteolytic apoptotic signature comprises one or more ratio of a proteolytic apoptotic polypeptide to its corresponding intact proteolytic apoptotic cleavage junction in a biological sample. For example, a proteolytic apoptotic signature of the present invention may comprise at least one, preferably at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 250, 300, or more ratios of cut to uncut proteolytic apoptotic cleavage junctions selected from those found in Table 3, or corresponding to the proteins identified by a Swiss-Prot ID found in Table 3, in a biological sample.
In certain embodiments, the present invention provides proteolytic apoptotic signatures that correspond to a specific level or degree of apoptosis in a biological sample, or in an individual. In other embodiments, the proteolytic apoptotic signatures of the present invention correspond to the level of apoptosis in a mammal suffering from a disease characterized by apoptosis. In yet other embodiments of the invention, a proteolytic apoptotic signature may correspond to a specific disease state or to a specific prognosis for a disease in an individual suffering with a disease characterized by apoptosis. In further embodiments, the proteolytic apoptotic signatures of the present invention may correspond to a specific efficacy for a drug administered to an individual or to a predicted response to a drug administered to an individual. The proteolytic apoptotic signatures of the present invention may be derived from a single biological sample from an individual or from a plurality of samples taken a group of individuals suffering from a disease characterized by apoptosis. In certain embodiments, the apoptotic signature may comprise an average of apoptotic signatures determined from a study or disease cohort.
In some embodiments, the present invention provides apoptotic signatures that correspond to healthy subjects, i.e. individuals that are not suffering from a disease, individuals that are suffering from a disease, individuals that have undergone therapy for a specific disease, individuals that have a good prognosis, individuals that have a bad prognosis, individuals with cancer, individuals with a high likelihood of developing metastatic cancer, individuals with a particular disease state, i.e. stage of cancer, severity of disease, benign tumor, and the like. As such, the various apoptotic signatures of the present invention find use in the diagnosis and prognosis of various diseases and disease states, as well as for monitoring the progression of a disease or the progression of a disease treatment regime.
In some embodiments, the invention provides synthetic peptides or polypeptides which are labeled with heavy isotopes of C, N, H, or O. For instance, 13C or 15N labeled peptides can be used as internal standards in the assay methods as known to one of ordinary skill in the art. By adding a known quantity of a heavy isotope-labeled peptide to a sample and then calculating the amount of the labeled polypeptide detected, it is possible to estimate the concentration of an unlabeled endogenous corresponding polypeptide in a sample by use of an analytical technique such as mass spectrometry (see, PCT Patent Publications WO 03026861 and WO 2008/054597), and see also, Carr et al., Clinical Chemistry 54:11 1749-1752 (2008) the contents of each of which are incorporated herein by reference in their entirety with respect to methods of quantitating proteins or polypeptides in a biological sample. Anderson et al., Journal of Proteome Research 2004, 3, 235-244; Carr et al., Nature Biotechnology 24(8):971 (2006); and Addona et al., Nature Biotechnology 27(7): 633 (2009); and McIntosh et al. Nature Biotechnology 27(7):622 (2009) are also each incorporated by reference in their entirety with respect to their disclosures of methods for detecting biomarkers in biological samples by targeted mass spectrometry. For instance, detection methods using selected reaction monitoring (SRM) or multiple reaction monitoring (MRM are contemplated.
An isotopically labeled peptide is preferably at least about 6 amino acids long, 7 amino acids long, 8 amino acids long, 10 amino acids long and less than 50 amino acids long and can comprise an amino acid sequence (previous amino acid or C-terminal amino acid sequence, identified or unmodified amino acid or N-terminal amino acid sequence, or the modified identified amino acid sequence of Table 1. Preferred labeled peptides for measuring the activity of apoptotic protease comprise a previous amino acid sequence of Table 1 with its corresponding immediately following identified or unmodified peptide of Table 1. A preferred ranged of labeled peptide lengths is from about 7 to 50 amino acids in length and may include the full sequences of both the previous and identified or unmodified polypeptides of Table 1.
The method detects and quantifies a target protein in a sample by introducing a known quantity of at least one heavy-isotope labeled peptide standard into a digested biological sample. By comparing to the peptide standard, one may readily determine the quantity of a peptide having the same sequence and protein modification(s) in the biological sample. Briefly, the methodology has two stages: (1) peptide internal standard selection and validation; method development; and (2) implementation using validated peptide internal standards to detect and quantify a target protein in a sample. The method is a powerful technique for detecting and quantifying a given peptide/protein within a complex biological mixture, such as a biological sample, a cell lysate, tissue section, or serum and may be used, e.g., to quantify change in protein as a result of drug treatment, or to quantify a protein in different biological states.
Generally, to develop a suitable internal standard, a particular peptide (or modified peptide) within a target protein sequence is chosen based on its amino acid sequence and a particular protease for digestion. The peptide can then generated by solid-phase peptide synthesis such that one residue is replaced with that same residue containing stable isotopes (e.g., 13C, 15N). The result is a peptide that is chemically identical to its native counterpart formed by proteolysis, but is easily distinguishable by MS via a mass shift. A newly synthesized internal standard peptide is then evaluated by the detection method. This process provides qualitative information about peptide retention by the detection method.
The second stage of the strategy is its implementation to measure the amount of a protein or the modified form of the protein from complex mixtures. A biological sample such as a cell lysate, tissue section lysate, or serum may be extensively digested with a protease such as trypsin. Labeled peptides can then be spiked in to the complex peptide mixture obtained by digestion of the biological sample with a proteolytic enzyme, either before or after an optional affinity purification of a subset of the peptides in the mixture, as described above. The retention time and fragmentation pattern of the native peptide formed by digestion (e.g., trypsinization) is identical to that 25 of the labeled internal standard peptide determined previously; thus, the use of isotopically labeled peptides results in the highly specific and sensitive measurement of both internal standard and analyte directly from extremely complex peptide mixtures. Because an absolute amount of the labeled peptide is added, the ratio of the amount of endogenous peptide detected to the amount of labeled peptide detected can be used to determine the precise levels of a polypeptide, or more specifically, a proteolytic apoptotic polypeptide, in a sample.
In addition, the internal or labeled polypeptide standard when present during digestion and chromatography, such that peptide extraction efficiencies and absolute losses during sample handling (including vacuum centrifugation), and variability during introduction into the detection system do not affect the determined ratio of native and labeled polypeptide abundances.
A peptide sequence within a target protein is selected according to one or more criteria to optimize the use of the peptide as an internal standard. Preferably, the size of the peptide is selected to minimize the chances that the peptide sequence will be repeated elsewhere in other non-target proteins. Thus, a peptide is preferably at least about 6 amino acids. The size of the peptide is also optimized to maximize ionization frequency. Thus, peptides longer than about 20 amino acids are not preferred. The preferred ranged is about 7 to 15 amino acids. A peptide sequence is also selected that is not likely to be chemically reactive during mass spectrometry, thus sequences comprising cysteine, tryptophan, or methionine are avoided.
The peptide is labeled using one or more labeled amino acids (i.e. the label is an actual part of the peptide) or less preferably, labels may be attached after synthesis according to standard methods. Preferably, the label is a mass-altering label selected based on the following considerations: The mass should be unique to shift fragment masses produced by MS analysis to regions of the spectrum with low background; the ion mass signature component is the portion of the labeling moiety that preferably exhibits a unique ion mass signature in MS analysis; the sum of the masses of the constituent atoms of the label is preferably uniquely different than the fragments of all the possible amino acids. As a result, the labeled amino acids and peptides are readily distinguished from unlabeled ones by the ion/mass pattern in the resulting mass spectrum. Preferably, the ion mass signature component imparts a mass to a protein fragment that does not match the residue mass for any of the 20 natural amino acids.
The label should be robust under the fragmentation conditions of MS and not undergo unfavorable fragmentation. Labeling chemistry should be efficient under a range of conditions, particularly denaturing conditions, and the labeled tag preferably remains soluble in the MS buffer system of choice. The label preferably does not suppress the ionization efficiency of the protein and is not chemically reactive. The label may contain a mixture of two or more isotopically distinct species to generate a unique mass spectrometric pattern at each labeled fragment position. Stable isotopes, such as 13C, 15N, 17O, 18O, or 34S, are among preferred labels. Pairs of peptide internal standards that incorporate a different isotope label may also be prepared.
Peptide internal standards are characterized according to their mass-to-charge (m/z) ratio, and preferably, also according to their behavior in chromatographic columns (e.g. an HPLC column). Internal standards that co-elute with unlabeled peptides of identical sequence are selected as optimal internal standards. The internal standard can then analyzed be fragmenting the peptide by any suitable means, for example by collision-induced dissociation (CID) using, e.g., argon or helium as a collision gas. The fragments can then be analyzed, for example, by multi-stage mass spectrometry (MSn) to obtain a fragment ion spectrum, to obtain a peptide fragmentation signature. Preferably, peptide fragments have significant differences in m/z ratios to enable peaks corresponding to each fragment to be well separated, and a signature that is unique for the target peptide is obtained. If a suitable fragment signature is not obtained at the first stage, additional stages of MS are performed until a unique signature is obtained.
Fragment ions in the MS/MS and MS spectra are typically highly specific for the peptide of interest, and, in conjunction with LC methods, allow a highly selective means of detecting and quantifying a target peptide/protein in a complex protein mixture, such as a cell lysate, containing many thousands or tens of thousands of proteins. Any biological sample potentially containing a target protein/peptide of interest may be assayed. Crude or partially purified cell extracts are preferably used. Generally, the sample may have at least 0.01 mg of protein, typically a concentration of 0.1-10 mg/mL, and may be adjusted to a desired buffer concentration and pH.
Accordingly, internal peptide standards (heavy-isotope or light isotope labeled peptides) may be produced, as described above, for any of the novel polypeptides of the invention (see Table 1). These peptides may then be further used in assessing apoptotic enzyme activities in samples as described herein.
Quantitation of Corresponding Peptides Derived from the Neo-Epitopes in Samples.
In one embodiment, the present invention provides reagents for detecting the proteolytic apoptotic polypeptide biomarkers of the invention. In one embodiment, the reagents comprise proteins that bind to the biomarkers with high affinity and specificity. In another embodiment, the invention provides binding reagents for detecting proteolytic apoptotic cleavage junctions. In a particular embodiment, the reagents comprise antibodies, or fragments thereof, generated against the proteolytic apoptotic polypeptides or proteolytic apoptotic cleavage junctions of the present invention. Suitable antibody fragment types include without limitation, F(ab′)2, F(ab), Fv, scFv, and the like. Antibodies can be generated by a number of well known methods including, without limitation, animal immunization, molecular display techniques, including phage display and ribosomal or mRNA display, rational design, and the like. In certain embodiments of the present invention, the binding reagents further comprise a detectable moiety and/or a tag to facilitate purification of the binding reagent or binding reagent-biomarker complex.
In another embodiment, the present invention provides methods for generating binding reagents to one or more apoptotic biomarkers. In certain embodiments the apoptotic biomarkers comprise N-terminal or C-terminal sequences selected form those found in Table 3. In other embodiments, the apoptotic biomarkers comprise cleavage junctions selected from those found in Table 3. In a specific embodiment, the methods of the present invention comprise the steps of: (a) generating a plurality of proteolytic apoptotic polypeptides; (b) generating one or more binding reagents to said plurality of proteolytic apoptotic polypeptides; and (c) purifying at least one of said binding reagents. Pluralities of proteolytic apoptotic polypeptides can be generated, for example, by heterologous gene expression, in vitro translation, synthetic peptide synthesis, purification of proteolytic polypeptides from a biological sample, or in vitro proteolysis of peptides containing a proteolytic apoptosis cleavage junction. In one embodiment, the binding reagents comprise proteins or antibodies that specifically bind to either a proteolytic apoptotic polypeptide or to an intact cleavage junction corresponding to a proteolytic apoptotic polypeptide, but do not substantially bind to both.
In certain embodiments, the methods of the present invention for generating one or more antibodies comprise the steps of (a) simultaneously immunizing a mammal with a plurality of apoptotic proteolytic polypeptides; (b) collecting the immune serum from said mammal; (c) affinity purifying a first antibody to a first proteolytic polypeptide, (d) affinity purifying at least a second antibody to at least a second proteolytic polypeptide from the supernatant of step (c), (e) removing antibodies that bind to the cleavage junction corresponding to said first proteolytic polypeptide by affinity means from said first antibody purification, and (f) removing antibodies that bind to the cleavage junction corresponding to said at least second proteolytic polypeptide by affinity means from said second antibody purification, thereby generating at least two antibodies to proteolytic apoptotic polypeptides. These methods find use in generating a plurality of antibodies that bind to a proteolytic apoptotic polypeptide, but that do not substantially bind to the cleavage junction corresponding to said proteolytic polypeptide. In certain embodiments, the methods can be altered in order to generate a plurality of antibodies that bind to a proteolytic apoptotic cleavage junction, but that do not substantially bind to the corresponding proteolytic polypeptides generated in response to an apoptotic stimulus. In further embodiments, the methods of the present invention can be performed using molecular display techniques.
In yet other embodiments, the present invention provides methods of generating an antibody to the N-terminus or C-terminus of a proteolytic polypeptide, the method comprising the steps of: (a) Generating the N-terminal or C-terminal apoptotic product, by means of heterologous gene expression, in vitro transcription-translation, or synthetic methods, or by producing the full length protein and cleaving it with a protease to generate the N-terminal and C-terminal pieces and purification of the N-terminal proteolytic fragment, C-terminal proteolytic fragment, or any combination thereof; (b) using the N-terminal or C-terminal apoptotic fragment to generate one or more antibodies, either by immunization of animal, or in vitro selection methods such as phage display, ribosome display or other suitable display or selection methods, or to generate other suitable binding protein or proteins, either by in vitro selection methods such as phage display, ribosome display or other suitable display or selection methods
The present invention also provides methods of detecting proteolytic apoptotic biomarkers, including both proteolytic apoptotic polypeptides and proteolytic apoptotic cleavage junctions, in a biological sample. In one embodiment, the method comprises contacting a biological sample with a binding reagent that specifically binds to a proteolytic apoptotic biomarker of the present invention and detecting the binding reagent, thereby detecting the biomarker. In a second embodiment, the present invention provides methods of quantitating the amount of a proteolytic apoptotic biomarker in a biological sample, the method comprising the steps of contacting a biological sample with a binding reagent of the present invention, and determining the amount of biomarker is said sample. Methods of detecting and quantitating the amount of a polypeptide in a sample are well known in the art and include, without limitation, ELISA, immunohistochemical techniques, mass spectrometry, Luminex® xMAP technology, and the like.
In another embodiment, the present invention provides methods of detecting apoptosis in an individual. In one embodiment, the methods comprise detecting at least one proteolytic apoptotic polypeptide in a biological sample from an individual. In another specific embodiment, the methods comprise detecting an increased ratio of the level of at least a first proteolytic apoptotic polypeptide biomarker to the level of at least one first proteolytic apoptotic cleavage junction biomarker that corresponds to said first proteolytic apoptotic polypeptide. In some embodiments, the present methods comprise the detection or quantitation of at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 250, 300, or more proteolytic apoptotic biomarkers of the present invention, or corresponding ratios thereof. In a second embodiment, the methods of the present invention comprise the detection of a proteolytic apoptotic signature in a biological sample from an individual, thereby detecting the presence of apoptosis is said individual. In yet another embodiment, the present invention provides methods of detecting a proteolytic apoptotic signature in a subject, the methods comprising the steps of: (a) determining the level of at least two proteolytic polypeptides in a biological sample from said subject; and (b) comparing said levels of at least two proteolytic polypeptides to a proteolytic apoptotic signature, thereby detecting a proteolytic signature in the subject, wherein said at least two proteolytic polypeptides comprise N-terminal or C-terminal sequences selected from those found in Table 1.
In one embodiment, the present invention provides methods of determining the level of apoptosis in an individual. In a particular embodiment, the methods comprise the steps of: (a) determining the level of at least one proteolytic polypeptide that is generated in response to an apoptotic stimulus in a biological sample from said subject; and (b) comparing said level of at least one proteolytic polypeptide to a biological signature corresponding to no apoptosis, thereby determining the level of apoptosis in the subject, wherein said at least one proteolytic polypeptide comprises an N-terminal or C-terminal sequence selected from those found in Table 1. In a related embodiment, the method further comprises the step of (c) comparing said level of at least one proteolytic polypeptide to at least one biological signature corresponding to a predetermined level of apoptosis. In a second embodiment, the methods comprise the steps of: (a) determining the level of at least one intact proteolytic apoptotic cleavage junction in a biological sample from said subject; (b) determining the level of at least one of the N-terminal or C-terminal proteolytic polypeptides corresponding to said at least one intact proteolytic apoptotic cleavage junction in said biological sample; and (c) determining the ratio of proteolytic polypeptides to intact proteolytic apoptotic cleavage junctions in said biological sample, thereby determining the level of apoptosis in the subject, wherein said proteolytic polypeptides are generated in response to an apoptotic stimulus.
In another embodiment, the invention provides methods of diagnosing or providing a prognosis for a disease characterized by apoptosis in an individual. In a specific embodiment, the methods comprise the steps of: (a) detecting a first proteolytic apoptotic signature in a biological sample from said individual; and (b) comparing said first proteolytic apoptotic signature to at least a second proteolytic apoptotic signature corresponding to a diagnosis or prognosis for a disease characterized by apoptosis, thereby diagnosing or providing a prognosis for a disease characterized by apoptosis in said individual. In other embodiments, the methods further comprise the steps of: (c) comparing said first apoptotic signature to at least a third apoptotic signature corresponding to a diagnosis of no disease or a second prognosis for said disease; and (d) determining which apoptotic signature said first apoptotic most highly correlates to, thereby diagnosing or providing a prognosis for a disease characterized by apoptosis in said individual.
Many correlation methodologies may be employed for the comparison of both individual proteolytic apoptotic biomarker levels and proteolytic apoptotic signatures or profiles in the present invention. Non-limiting examples of these correlation methods include parametric and non-parametric methods as well as methodologies based on mutual information and non-linear approaches. Examples of parametric approaches include without limitation, Pearson correlation (or Pearson r, also referred to as linear or product-moment correlation) and cosine correlation. Non-limiting examples of non-parametric methods include Spearman's R (or rank-order) correlation, Kendall's Tau correlation, and the Gamma statistic. Each correlation methodology can be used to determine the level of correlation between the levels or ratios of individual biomarkers in the data set. The correlation of all biomarkers with all other biomarkers is most readily considered as a matrix. Using Pearson's correlation as a non-limiting example, the correlation coefficient r in the method is used as the indicator of the level of correlation. When other correlation methods are used, the correlation coefficient analogous to r may be used, along with the recognition of equivalent levels of correlation corresponding to r being at or about 0.25 to being at or about 0.5. The correlation coefficient may be selected as desired to reduce the number of correlated biomarkers to various numbers. In particular embodiments of the invention using r, the selected coefficient value may be of about 0.25 or higher, about 0.3 or higher, about 0.35 or higher, about 0.4 or higher, about 0.45 or higher, or about 0.5 or higher.
In another embodiment, the present invention provides methods of monitoring the progression of therapy for a disease in an individual. In certain embodiments, the methods comprise determining the level of a proteolytic apoptotic biomarker or an apoptotic signature at different time points in a sample from an individual undergoing therapy for a disease. In some embodiments, the method will comprise comparing the levels of biomarkers or signatures at different times during the course of a disease treatment. Typically, a disease that is characterized by increased apoptosis, such as auto-imune diseases, will result in a decrease in apoptosis, as measured by the levels of biomarkers or signatures in a biological sample from an individual, during the course of a successful treatment regime. Conversely, a disease that is characterized by decreased apoptosis, such as cancer, will typically result in increased apoptosis, as measured by the levels of biomarkers or signatures in a biological sample from an individual, during the course of a successful treatment regime. In this fashion a biological sample from a patient that is responding favorably to a treatment regime will show a change, either increase or decrease, in the level of apoptosis over time, as measured by the methods of the present invention. In a particular embodiment, the methods of the present invention are useful for monitoring the progression of cancer therapy in an individual. The methods of the invention are compatible with all types of cancer therapy including, without limitation, chemotherapy, hormone therapy, biologic therapy, radiation therapy, surgical therapy, and the like.
In one embodiment, the present invention provides methods of determining the efficacy of a drug. In a specific embodiment, the methods comprise the steps of: (a) determining the level of at least one proteolytic polypeptide generated in response to an apoptotic stimulus in a biological sample from a first subject receiving a dose of said drug; (b) determining the level of at least one proteolytic polypeptide generated in response to an apoptotic stimulus in a biological sample from a second subject not receiving a dose of said drug; and (c) comparing said first and said second levels of said at least one proteolytic polypeptide, thereby determining the efficacy of said drug, wherein said at least one proteolytic polypeptide comprises an N-terminal or C-terminal sequence selected from those found in Table 1. In yet other embodiments of the invention, the method comprises determining a proteolytic apoptotic signature and comparing said signature to a second proteolytic apoptotic signature corresponding to a specific level of apoptosis. Drugs particularly well suited for use with the above methods include both drugs that induce apoptosis and anti-apoptotic drugs.
Many pharmaceuticals are known to cause apoptosis in vivo including, without limitation, nonsteroidal anti-inflammatory drugs (NSAIDs) (Yamazaki et al., Journal of Pharmacology and Experimental Therapeutics 302(1): 18-25 (2002)) and chemotherapeutic drugs. Examples of NSAIDs include, without limitation, Salicylates (including Acetylsalicylic acid (Aspirin), Amoxiprin Benorylate/Benorilate, Choline magnesium salicylate, Diflunisal, Ethenzamide, Faislamine, Methyl salicylate, Magnesium salicylate, Salicyl salicylate, and Salicylamide), Arylalkanoic acids (including Diclofenac, Aceclofenac, Acemetacin, Alclofenac, Bromfenac, Etodolac, Indometacin, Nabumetone, Oxametacin, Proglumetacin, Sulindac, and Tolmetin), 2-Arylpropionic acids (profens) (including Ibuprofen, Alminoprofen, Benoxaprofen, Carprofen, Dexibuprofen, Dexketoprofen, Fenbufen, Fenoprofen, Flunoxaprofen, Flurbiprofen, Ibuproxam, Indoprofen, Ketoprofen, Ketorolac, Loxoprofen, Naproxen, Oxaprozin, Pirprofen, Suprofen, and Tiaprofenic acid), N-Arylanthranilic acids (fenamic acids) (including Mefenamic acid, Flufenamic acid, Meclofenamic acid, and Tolfenamic acid), Pyrazolidine derivatives (including Phenylbutazone, Ampyrone, Azapropazone, Clofezone, Kebuzone, Metamizole, Mofebutazone, Oxyphenbutazone, Phenazone, Phenylbutazone, and Sulfinpyrazone), Oxicams (including Piroxicam, Droxicam, Lornoxicam, Meloxicam, and Tenoxicam), COX-2 inhibitors (including Celecoxib, Etoricoxib, Lumiracoxib, Parecoxib, Rofecoxib, Valdecoxib), Sulphonanilides including Nimesulide, histone deacetylase inhibitors (including Trichostatin A, cyclic tetrapeptides, benzamides, electrophilic ketones, phenylbutyrate, valproic acid, SAHA (approved by the FDA in 2007 for leukemia therapy under the name Vorinostat), Belinostat/PXD101, MS275, LAQ824/LBH589, CI994, MGCD0103 (Beckers et al., Int. J. Cancer 121(5): 1138-48 (2007)) nicotinamide, dihydrocoumarin, naphthopyranone, 2-hydroxynaphaldehydes, and the like). While not all NSAIDs induce apoptosis, one of skill in the art will know which drugs are appropriate for use in the present invention. Drugs that do not induce apoptosis, including some NSAIDs and some chemotherapeutic agents, may be used in combination with other drugs that do induce apoptosis in certain embodiments of the present invention.
Examples of chemotherapeutic anti-cancer drugs include, without limitation, Aminopterin, Methotrexate, Pemetrexed, Raltitrexed, Cladribine, Clofarabine, Fludarabine, Mercaptopurine, Pentostatin, Thioguanine, Cytarabine, Decitabine, Fluorouracil/Capecitabine, Floxuridine, Gemcitabine, Sapacitabine, Chlorambucil, Chlormethine, Cyclophosphamide, Ifosfamide, Melphalan, Bendamustine, Trofosfamide, Uramustine, Carmustine, Fotemustine, Lomustine, Nimustine, Prednimustine, Ranimustine, Semustine, Streptozocin, Carboplatin, Cisplatin, Nedaplatin, Oxaliplatin, Triplatin tetranitrate, Satraplatin, Busulfan, Mannosulfan, Treosulfan, Procarbazine, Dacarbazine, Temozolomide, Carboquone, ThioTEPA, Triaziquone, Triethylenemelamine, Docetaxel, Larotaxel, Ortataxel, Paclitaxel, Tesetaxel, Vinblastine, Vincristine, Vinflunine, Vindesine, Vinorelbine, Ixabepilone, Aclarubicin, Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Amrubicin, Pirarubicin, Mitoxantrone, Pixantrone, Valrubicin, Zorubicin, Actinomycin, Bleomycin, Mitomycin, Plicamycin, Hydroxyurea, Camptothecin, Topotecan, Irinotecan, Rubitecan, Belotecan, Etoposide, Teniposide, Altretamine, Amsacrine, Bexarotene, Estramustine, Irofulven, Trabectedin, Cetuximab, Panitumumab, Trastuzumab, Rituximab, Tositumomab, Alemtuzumab, Bevacizumab, Edrecolomab, Gemtuzumab, Axitinib, Bosutinib, Cediranib, Dasatinib, Erlotinib, Gefitinib, Imatinib, Lapatinib, Lestaurtinib, Nilotinib, Semaxanib, Sorafenib, Sunitinib, Vandetanib, Alvocidib, Seliciclib, Aflibercept, Denileukin diftitox, Aminolevulinic acid, Efaproxiral, Methyl aminolevulinate, Porfimer sodium, Temoporfin, Verteporfin, Alitretinoin, Tretinoin, Anagrelide, Arsenic trioxide, Pegaspargase, Atrasentan, Bortezomib, Carmofur, Celecoxib, Demecolcine, Elesclomol, Elsamitrucin, Etoglucid, Lonidamine, Lucanthone, Masoprocol, Mitobronitol, Mitoguazone, Mitotane, Oblimersen, Omacetaxine, Sitimagene ceradenovec, Testolactone, Tiazofurine, Tipifarnib, and the like. While not all chemotherapeutic drugs induce apoptosis, one of skill in the art will know which drugs are appropriate for use in the present invention.
The invention also provides RNA interference, or RNAi, by use of siRNA or shRNA molecules directed toward a protein of Table 1. An “siRNA” or “shRNA” refers to a nucleic acid that forms a double stranded RNA, which double stranded RNA has the ability to reduce or inhibit expression of a gene or target gene when the siRNA expressed in the same cell as the gene or target gene. “siRNA” or “shRNA” thus refers to the double stranded RNA formed by the complementary strands. The complementary portions of the siRNA that hybridize to form the double stranded molecule typically have substantial or complete identity. In one embodiment, an siRNA refers to a nucleic acid that has substantial or complete identity to a target gene and forms a double stranded siRNA. Typically, the siRNA is at least about 15-50 nucleotides in length (e.g., each complementary sequence of the double stranded siRNA is 15-50 nucleotides in length, and the double stranded siRNA is about 15-50 base pairs in length, preferable about preferably about 20-30 base nucleotides, preferably about 20-25 or about 24-29 nucleotides in length, e.g., 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 nucleotides in length. The siRNA find use in moulating apoptosis, treating cancer by promoting apoptosis, and in treating conditions in which the modulation or promotion of apoptosis would be beneficial, or in treating disease or conditions characterized by apoptosis. The subjects are preferably human.
The design and making of siRNA molecules and vectors are well known to those of ordinary skill in the art. For instance, an efficient process for designing a suitable siRNA is to start at the AUG start codon of the mRNA transcript and scan for AA dinucleotide sequences (see, Elbashir et al. EMBO J. 20: 6877-6888 (2001). Each AA and the 3′ adjacent nucleotides are potential siRNA target sites. The length of the adjacent site sequence will determine the length of the siRNA. For instance, 19 adjacent sites would give a 21 nucleotide long siRNA siRNAs with 3′ overhanging UU dinucleotides are often the most effective. This approach is also compatible with using RNA pol III to transcribe hairpin siRNAs. RNA pol III terminates transcription at 4-6 nucleotide poly(T) tracts to create RNA molecules having a short poly(U) tail. However, siRNAs with other 3′ terminal dinucleotide overhangs can also effectively induce RNAi and the sequence may be empirically selected. For selectivity, target sequences with more than 16-17 contiguous base pairs of homology to other coding sequences can be avoided by conducting a BLAST search (see, www.ncbi.nlm.nih.gov/BLAST).
The siRNA or shRNA can be administered directly or an siRNA or shRNA expression vector can be used to induce RNAi. A vector can have inserted two inverted repeats separated by a short spacer sequence and ending with a string of T's which serve to terminate transcription. The expressed RNA transcript is predicted to fold into a short hairpin shRNA. The selection of shRNA target sequence, the length of the inverted repeats that encode the stem of a putative hairpin, the order of the inverted repeats, the length and composition of the spacer sequence that encodes the loop of the hairpin, and the presence or absence of 5′-overhangs, can vary. A preferred order of the shRNA expression cassette is sense strand, short spacer, and antisense strand. shRNAs with these various stem lengths (e.g., 15 to 30) are suitable. The length of the loops linking sense and antisense strands of the shRNA can have varying lengths (e.g., 3 to 9 nucleotides, or longer). The vectors may contain promoters and expression enhancers or other regulatory elements which are operably linked to the nucleotide sequence encoding the shRNA.
The expression “control sequences” refers to DNA sequences necessary for the expression of an operably linked coding sequence in a particular host organism. The control sequences that are suitable for prokaryotes, for example, include a promoter, optionally an operator sequence, and a ribosome binding site. Eukaryotic cells are known to utilize promoters, polyadenylation signals, and enhancers. These control elements may be designed to allow the clinician to turn of or on the expression of the gene by adding or controlling external factors to which the regulatory elements are responsive.
In yet another embodiment, the present invention provides kits for detecting or quantitating the biomarkers of the present invention. In certain embodiments, these kits comprise binding reagents, such as antibodies or proteins, that specifically bind the biomarkers of the invention. In other embodiments, the kits of the present invention comprise protein binding arrays for the detection or quantitation of the biomarkers of the invention. In one embodiment, the kits of the present invention are useful in the detection or quantitation of apoptosis in a biological sample. In a second embodiment, the kits of the invention are useful for diagnosing or for providing a prognosis for a disease characterized by apoptosis in an individual.
The present invention also provides novel enzymatic approaches for positive selection of protein fragments containing unblocked α-amines, characteristically produced in proteolysis. This approach makes use of an engineered peptide ligase termed subtiligase to selectively biotinylate unblocked protein α-amines in complex samples with great selectivity over ε-amines of lysine side chains. Site-specific biotinylation permits subsequent purification and identification of corresponding N-terminal peptides using tandem mass spectrometry (LC/MS/MS).
The present invention provides a proteomic workflow utilizing subtiligase that enables biotinylation of protein α-amines in complex mixtures and subsequent cataloguing of N-termini in a given sample (FIGS. 1A-1 and 1A-2). Detergent lysates of either normal or apoptotic cells are first prepared in the presence of protease inhibitors to quench all protease activity. Proteins in these lysates are then N-terminally biotinylated by treatment with subtiligase and a peptide glycolate ester substrate specially tailored to the proteomic workflow (FIGS. 1B-1 and 1B-2). Biotinylated samples are then exhaustively digested with trypsin, and N-terminal peptides are captured using avidin affinity media. The peptide ester substrate contains a tobacco etch virus (TEV) protease cleavage site between biotin and the site of ligation to permit facile recovery of captured peptides (Rigaut et al., 1999). An important aspect of the workflow is that all labeled peptides recovered using TEV protease retain an N-terminal SY-dipeptide modification. This modification provides a key hallmark to distinguish ligated peptides from contaminating unligated ones using LC/MS/MS. Identification of recovered SY-peptides permits identification of corresponding proteins, native N-termini, and localization of proteolytic processing sites.
DEFINITIONS
“Subtiligase” refers generally to proteins which have the enzymatic activity of being able to ligate esterified peptides site-specifically onto the N termini of proteins or peptides. An example of such a subtiligase is one derived from the enzyme subtilisin BPN′ by site directed mutagenesis to effect the double substitution Ser221Cys and Pro225Ala, as described herein. Also described herein are additional subtiligases which have been engineered to exhibit other advantageous features, such as enhanced stability.
A “substrate” used in the context of subtiligase refers generally to any chemical moiety that is capable of being utilized during the enzymatic action of subtiligase that results in the specific labeling of the N termini of proteins or peptides by subtiligase. Examples of such substrates include peptide esters as described in greater detail herein.
“A complex mixture” refers generally to any composition that is composed of at least two or more proteins or peptides containing α-amines. A complex mixture can have at least two different proteins encoded by different genes; a complex mixture can be naturally occurring (e.g., a cell extract) or prepared (e.g., a formulation); a complex mixture can have recombinant, synthetic, or naturally occurring proteins or a mixture thereof. In many cases, a complex sample is one which displays a high degree of heterogeneity of proteins or peptides. Examples of complex mixtures include whole cells, cell extracts, partially purified cell extracts, tissues, bodily fluids, and animals, among others. Accordingly, in some embodiments, such complex mixtures comprise the naturally occurring proteins found in cells and tissues encoded by, for instance, different genes as found in the genomes of the source of the complex mixture (e.g., a cell or tissue extract or a bodily fluid such as serum). However, a complex mixture can also contain, as a component thereof, a recombinant protein or a purified protein or polypeptide either as an endogenous component (in the case of a recombinant protein), or as one added exogenously to the composition.
The term “recombinant” when used with reference, e.g., to a cell, or nucleic acid, protein, or vector, indicates that the cell, nucleic acid, protein or vector, has been modified by the introduction of a heterologous nucleic acid or protein or the alteration of a native nucleic acid or protein, or that the cell is derived from a cell so modified. Thus, for example, recombinant cells express genes that are not found within the native (non-recombinant) form of the cell or express native genes that are otherwise abnormally expressed, under expressed or not expressed at all.
The term “heterologous” when used with reference to portions of a nucleic acid indicates that the nucleic acid comprises two or more subsequences that are not found in the same relationship to each other in nature. For instance, the nucleic acid is typically recombinantly produced, having two or more sequences from unrelated genes arranged to make a new functional nucleic acid, e.g., a promoter from one source and a coding region from another source. Similarly, a heterologous protein indicates that the protein comprises two or more subsequences that are not found in the same relationship to each other in nature (e.g., a fusion protein).
A “cleavable linker” when used in the context of a peptide ester of the present invention refers generally to any element contained within the peptide that can serve as a spacer and is labile to cleavage upon suitable manipulation. Accordingly, a cleavable linker may comprise any of a number of chemical entities, including amino acids, nucleic acids, or small molecules, among others. A cleavable linker may be cleaved by, for instance, chemical, enzymatic, or physical means. Non-limiting examples of cleavable linkers include protease cleavage sites and nucleic acid sequences cleaved by nucleases. Further, a nucleic acid sequence may form a cleavable linker between multiple entities in double stranded form by complementary sequence hybridization, with cleavage effected by, for instance, application of a suitable temperature increase to disrupt hybridization of complementary strands. Examples of chemical cleavage sites include the incorporation photolabile, acid-labile, or base-labile functional groups into peptides.
“Proteases” (or “proteinases”, “peptidases”, or “proteolytic” enzymes) generally refer to a class of enzymes that cleave peptide bonds between amino acids of proteins. Because proteases use a molecule of water to effect hydrolysis of peptide bonds, these enzymes can also be classified as hydrolases. Six classes of proteases are presently known: serine proteases, threonine proteases, cysteine proteases, aspartic acid proteases, metalloproteases, and glutamic acid proteases (see, e.g., Barrett A. J. et al. The Handbook of Proteolytic Enzymes, 2nd ed. Academic Press, 2003).
Proteases are involved in a multitude of physiological reactions from simple digestion of food proteins to highly regulated cascades (e.g., the cell cycle, the blood clotting cascade, the complement system, and apoptosis pathways). It is well known to the skilled artisan that proteases can break either specific peptide bonds, depending on the amino acid sequence of a protein, or break down a polypeptide to constituent amino acids.
Among the proteases of this invention are “caspases”, a family of cysteine proteases, which cleave other proteins after an aspartic acid residue. Many of the caspases are held in an inactive form as a zymogen until they are activated by proteolytic cleavage, which converts the inactive caspase into an active conformation, allowing caspase cleavage of downstream targets. Caspases serve an essential role in apoptosis, in which a cascade of sequential caspase activation is responsible executing programmed cell death. See, e.g., Thornberry, N. L. and Lazebnik, Y., Science, 281:1312-1316 (1998); Shi, Y., Cell, 117:855-8 (2004) for reviews. As an example of this regulatory hierarchy, caspase-3 is processed into an active form through its proteolysis by caspases-8, -9, and -10. Upon activation, caspase 3 is then able to activate caspases-6 and -7 via proteolysis. Caspases-3, -6, and -7 are then able to proteolyze cellular substrates such as nuclear lamins. Caspases can also become inappropriately and acutely activated during stroke, myocardial infarction, or Parkinson's disease.
“Apoptosis” refers generally to a process of programmed cell death and involves a series of ordered molecular events leading to characteristic changes in cell morphology and death, as distinguished from general cell death or necrosis that results from exposure of cells to non-specific toxic events such as metabolic poisons or ischemia. Cells undergoing apoptosis show characteristic morphological changes such as chromatin condensation and fragmentation and breakdown of the nuclear envelope. As apoptosis proceeds, the plasma membrane is seen to form blebbings, and the apoptotic cells are either phagocytosed or else break up into smaller vesicles which are then phagocytosed. Typical assays used to detect and measure apoptosis include microscopic examination of cellular morphology, TUNEL assays for DNA fragmentation, caspase activity assays, annexin-V externalization assays, and DNA laddering assays, among others. It is well known to the skilled artisan that the process of apoptosis is controlled by a diversity of cell signals which includes extracellular signals such as hormones, growth factors, cytokines, and nitric oxide, among others. These signals may positively or negatively induce apoptosis. Other effectors of apoptosis include oncogenes (e.g., c-myc) and exposure of cancer cells to chemotherapeutic agents, among other examples.
“Inducing apoptosis” or “inducer of apoptosis” refers to an agent or process which causes a cell to undergo the program of cell death described above for apoptosis.
A “cell signal” refers to any agent which may initiate or stimulate directly or indirectly proteolysis within a cell. Examples of cell signals include agents that cause cells to undergo apoptosis such as those discussed above. In the context of this invention, a cell signal may include introduction of an activated or overexpressed oncogene, such as c-myc, or any other protein that causes a proteolytic event to occur within cells, as well as, externally applied agents (e.g., chemotherapeutic drugs, etc.).
A “peptide ester” refers generally to any peptide in which one carboxyl group of the peptide is esterified, i.e., is of the structure —CO—O—R. In embodiments of this invention, a peptide ester can serve as a substrate for subtiligase such that the peptide is added to the α-amino group of polypeptides to form the structure —CO—NH—R, thus labeling the polypeptide. In some embodiments of this invention, a peptide ester can carry a detectable label and a site for proteolysis or another form of chemical cleavage (e.g., through introduction of photolabile, acid-labile, or base-labile functional groups).
A “label” or “detectable label” or “tag” is a composition detectable by mass spectrometric, spectroscopic, photochemical, biochemical, immunochemical, or chemical means. For example, useful labels include radioactive isotopes (e.g., 3H, 35S, 32P, 51Cr, or 125I), stable isotopes (e.g., 13C or 15N), fluorescent dyes, electron-dense reagents, enzymes (e.g., alkaline phosphatase, horseradish peroxidase, or others commonly used in an ELISA), biotin, digoxigenin, or haptens or epitopes and proteins for which antisera or monoclonal antibodies are available. In general, a label as used in the context of the present invention is any entity that may be used to detect or isolate the product of the subtiligase ligation reaction. Thus, any entity that is capable of binding to another entity maybe used in the practice of this invention, including without limitation, epitopes for antibodies, ligands for receptors, and nucleic acids, which may interact with a second entity through means such as complementary base pair hybridization.
“Biological sample” as used herein is a sample of cells, biological tissue, or fluid that is to be tested for the occurrence of proteolysis or the presence, more generally, of polypeptides of interest in the sample. Among the cells that can be examined are cancer cells, cells stimulated to under apoptosis, and cells at different stages of development, among others. The biological tissues of this invention include any of the tissues that comprise the organs of an organism. The biological sample can be derived from any species including bacteria, yeasts, plants, invertebrates, and vertebrate organisms. The fluid of this invention can be any fluid associated with a cell or tissue. Such fluids may include the media in which cells are cultured as well as the fluid surrounding tissues and organs, as well as the fluid comprising the circulatory system of invertebrates and vertebrates (e.g., body fluids such as whole blood, serum, plasma, cerebrospinal fluid, urine, lymph fluids, and various external secretions of the respiratory, intestinal and genitourinary tracts, tears, saliva, milk, white blood cells, myelomas, and the like). An “extracellular fluid” refers generally to any fluid found exterior to cells. Such fluids may include all of the fluids described above. In certain embodiments, such fluids may further include cellular debri, for example from lysed cells, including membrane-bound and cytosolic proteins. A biological sample used in the present invention may be from a suitable organism, for example a mammal such as a mouse, rat, hamster, guinea pig, rabbit, sheep, goat, pig, monkey, human, and the like.
A “negative control” has the definition recognized by the skilled artisan and generally refers to an experiment in which the desired result is no effect. Conversely, a “positive control” is a control experiment in which the desired outcome is a well-defined or well-known effect. In the context of this invention, a negative control may be a biological sample which is not treated with an agent that provides a cell signal to stimulate proteolysis or may be a sample treated with a placebo.
“Secreted protein” refers generally to any protein that is synthesized by a cell for export to the exterior of the cell membrane, for instance, secretion to the extracellular fluid. A variety of secreted proteins are recognized by the skilled artisan including: hormones, growth factors, antibiotics, antibodies, neuropeptides, toxins, cytokines, apolipoproteins, proteases and protease inhibitors, among others.
“Disease” or “disease state” refers generally to any derangement of normal physiology. Examples of diseases relevant to the practice of this invention include, without limitation: inflammatory diseases such as rheumatoid arthritis, osteoporosis, inflammatory bowel syndrome, asthma; cardiovascular diseases such as ischemia, stroke, myocardial infarction, congestive heart failure, atherosclerosis; type I and II diabetes and diabetes related diseases such as hyperglycemia, diabetic retinopathy, peripheral neuropathy; thrombotic disorders, such as diseases affecting blood clotting or complement fixation; neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, age-related dementia; liver diseases, such as liver infection, fibrosis, cirrhosis; kidney infection, fibrosis, and cirrhosis; muscular dystrophy; multiple sclerosis; lung diseases, such as lung fibrosis; schizophrenia and other mental disorders; and disorders of cell proliferation such as psoriasis and cancer (see below). (See, generally, Harrison's Principles of Internal Medicine, 16th edition, 2004.)
“Cancer” and “cancer cells” refers generally to human and animal cancers and carcinomas, sarcomas, adenocarcinomas, lymphomas, leukemias, etc., including solid and lymphoid cancers, kidney, breast, lung, bladder, colon, ovarian, prostate, pancreas, stomach, brain, head and neck, skin, uterine, testicular, glioma, esophagus, and liver cancer, including hepatocarcinoma, lymphoma, including B-acute lymphoblastic lymphoma, non-Hodgkin's lymphomas (e.g., Burkitt's, Small Cell, and Large Cell lymphomas) and Hodgkin's lymphoma, leukemia (including AML, ALL, and CML), multiple myeloma, mantle cell lymphoma, Waldenstrom's macrogobulinemia, and Philadelphia positive cancers, among others.
“Chemotherapeutic drugs or agents” include conventional chemotherapeutic reagents such as alkylating agents, anti-metabolites, plant alkaloids, antibiotics, and miscellaneous compounds e.g., cis-platinum, CDDP, methotrexate, vincristine, adriamycin, bleomycin, and hydroxyurea, as well as biologics, such as therapeutic antibodies. Chemotherapeutic agents can include other therapeutic approaches known in the art for treating cancer, such as radiation therapy. Chemotherapeutic drugs or agents can be used alone or in combination in the practice of the present invention. The methods of the present invention are useful in combination with adjuvant cancer therapies, including hormone therapy, chemotherapy, biologic therapy (i.e. antibody therapy), radiation therapy, immunotherapy, surgery, and the like.
By “therapeutically effective amount or dose” or “sufficient amount or dose” herein is meant a dose that produces effects for which it is administered. The exact dose will depend on the purpose of the treatment, and will be ascertainable by one skilled in the art using known techniques (see, e.g., Lieberman, Pharmaceutical Dosage Forms (vols. 1-3, 1992); Lloyd, The Art, Science and Technology of Pharmaceutical Compounding (1999); Pickar, Dosage Calculations (1999); and Remington: The Science and Practice of Pharmacy, 20th Edition, 2003, Gennaro, Ed., Lippincott, Williams & Wilkins)
“Metastasis” refers to spread of a cancer from the primary tumor or origin to other tissues and parts of the body, such as the lymph nodes.
“Providing a prognosis” refers to providing a prediction of the likelihood of metastasis, predictions of disease free and overall survival, the probable course and outcome of cancer therapy, or the likelihood of recovery from the cancer, in a subject.
“Diagnosis” refers to identification of a disease state, such as cancer, in a subject. The methods of diagnosis provided by the present invention can be combined with other methods of diagnosis well known in the art. Non-limiting examples of other methods of diagnosis include, detection of previously known disease biomarkers, including protein and nucleic acid biomarkers, radiography, co-axial tomography (CAT) scans, positron emission tomography (PET), radionuclide scanning, and the like.
The terms “cancer-associated antigen”, or “tumor-specific marker”, or “tumor marker”, or “biomarker” interchangeably refer to a molecule (typically nucleic acid, protein, proteolytic fragment, carbohydrate, or lipid) that is present in a biological sample, from a subject with cancer, expressed in a cancer cell, expressed on the surface of a cancer cell, or secreted by a cancer cell differentially in comparison to a biological sample from a subject without cancer or a non-cancer cell, and which is useful for the diagnosis of cancer, for providing a prognosis, or for preferential targeting of a pharmacological agent to the cancer cell. In the context of the present invention, a cancer-associated antigen may be a proteolytic fragment, for example one that is generated in response to an apoptotic stimulus, that is present in a biological sample, such as a blood sample, tumor biopsy, tissue, and the like, from a patient suffering from a disease, such as cancer, at an elevated level, for example, 10% greater level, 20%, 50%, 75%, 100% or greater level, than found in an biological sample from an individual not suffering from the disease. In other cases, the proteolytic fragment may be present at about 1-fold, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 75, 100, 250, 500, or 1000-fold greater level in a sample from a patient suffering from the disease as compared to a sample from an individual not suffering from the disease, or a control sample. In some embodiments, a biomarker of the present invention may be a proteolytic fragment that is present in a biological sample from a patient suffering from a disease, such as cancer, but not present, or present at a minimal level, in a sample from an individual not suffering from the disease. In other embodiments, a cancer-associated antigen is a molecule that is overexpressed in a biological sample from a subject with cancer or a cancer cell in comparison to a biological sample from a subject without cancer or a non-cancer cell, for instance, 1-fold over expression, 2-fold overexpression, 3-fold overexpression or more in comparison. Oftentimes, a cancer-associated antigen is a molecule that is inappropriately synthesized in a cancer cell or present in a biological sample from a subject with cancer, for instance, a molecule that contains deletions, additions or mutations in comparison to the molecule expressed in a biological sample from a subject without cancer or in a non-cancer cell.
The “proteolytic apoptotic polypeptide biomarkers” of the present invention generally relate to proteolytic polypeptides that are generated in response to an apoptotic stimulus. Typically, these fragments are formed by the cleavage of a “pro-apoptotic polypeptide” or “proteolytic apoptotic cleavage junction” by a protease involved in an apoptotic pathway. Typically, two proteolytic apoptotic polypeptide biomarkers are generated by every cleavage. For example, one proteolytic polypeptide may comprise an N-terminal sequence selected from those found in Table 1. I.e., cleavage of Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform, Swiss-Prot accession number Q13362, results in a proteolytic apoptotic polypeptide biomarkers comprising the sequence AANSNGPFQPVVLLHIR (SEQ ID NO:418), wherein AAN are the first three, or N-terminal, residues of the biomarker. A second proteolytic apoptotic polypeptide biomarker formed by a cleavage reaction may comprise a C-terminal sequence also found in Table 1. I.e., cleavage of Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform, Swiss-Prot accession number Q13362, will also result in a proteolytic apoptotic polypeptide biomarkers comprising the sequence AGSRMVVD (SEQ ID NO:419), wherein VVD are the last three, or C-terminal, residues of the biomarkers. In certain embodiments, proteolytic apoptotic polypeptide biomarkers of the invention may further comprise a fusion sequence N-terminal or C-terminal to a sequence found in Table 1, in order to facilitate purification or detection of the biomarker. Proteolytic apoptotic polypeptide biomarkers of the present invention may comprise polypeptides spanning from the cleavage site (P1 or P1′ residue) to the N- or C-terminus of the parent protein. In other embodiments, the proteolytic apoptotic polypeptide biomarkers of the invention may undergo further proteolysis prior to detection or quantitation. As such, a proteolytic apoptotic polypeptide biomarker may comprise at least about 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 80, 90, 100, 125, 150, 175, 200, 250, 300, 400, 500, or more of the parent protein, including the identified N- or C-terminal sequence, for example those found in Table 1.
A “proteolytic apoptotic cleavage junction”, or “cleavage junction”, or “intact cleavage junction”, in the context of the present invention, refers to an amino acid sequence, or polypeptide containing said sequence, that contains a recognition motif that is cleaved by a protease under certain conditions. In one embodiment, a cleavage junction of the invention is cleaved in response to an apoptotic stimulus. In a particular embodiment, the cleavage junctions comprise a sequence selected from those found in Table 3. A cleavage junction is said to correspond to a proteolytic polypeptide or a proteolytic apoptotic polypeptide biomarker if said proteolytic polypeptide is formed or generated by the proteolysis of the cleavage junction. Thus, typically a cleavage junction of the present invention will result in the formation of two proteolytic apoptotic polypeptide biomarkers that correspond to said intact cleavage junction. In one embodiment, a cleavage junction comprising a sequence selected from those found in Table 3, with a given Swiss-Prot accession number, will correspond to two proteolytic polypeptides, one comprising an N-terminal sequence selected from those found in Table 1 and one comprising a C-terminal sequence selected from those found in Table 1, with the same Swiss-Prot accession number. For example, a cleavage junction of Table 3, Swiss-Prot accession number Q13362, would correspond to both a proteolytic polypeptide comprising a N-terminal sequence of the corresponding unmodified polypeptide sequence and a proteolytic polypeptide comprising an C-terminal sequence of the corresponding previous amino acid sequence.
In certain embodiments, the cleaved products of the present invention may be further trimmed in vivo or in vitro by exoproteases after capsase-based proteolysis. The present invention, in one embodiment, includes fragments of the biomarkers identified herein that have been further processed by such exoproteases, which may serve as biomarkers of apoptosis equivalent to their predecessor fragments. In other embodiments, the detection of either an N-terminal or C-terminal proteolytic fragment, in the absence of the other, will provide diagnostic or prognostic power for the detection of spoptosis in a biological sample.
An “apoptotic stimulus” generally refers to a signal or condition that causes or induces a cell to undergo apoptosis. Apoptotic signals may originate intracellularly, as per the action of an intrinsic inducer, or extracellularly, as in the action of an extrinsic inducer. Extracellular signals may include, without limitation, toxins, hormones, growth factors, nitric oxide, cytokines, cytotoxic dugs, and the like. Intracellular apoptotic signalling is typically initiated in response to stress. These stimuli include, without limitation, the binding of nuclear receptors by glucocorticoids, heat, radiation, nutrient deprivation, viral infection, hypoxia, and the like. In certain embodiments of the invention, apoptosis may be induced through the use of cytotoxic drugs or by environmental conditioning of the cells.
“Biological sample” includes sections of tissues such as biopsy and autopsy samples, and frozen sections taken for histologic purposes. Such samples include blood and blood fractions or products (e.g., serum, plasma, platelets, red blood cells, and the like), sputum or saliva, lymph and tongue tissue, cultured cells, e.g., primary cultures, explants, and transformed cells, stool, urine, etc. A biological sample is typically obtained from a eukaryotic organism, most preferably a mammal such as a primate e.g., chimpanzee or human; cow; dog; cat; a rodent, e.g., guinea pig, rat, Mouse; rabbit; or a bird; reptile; or fish
A “biopsy” refers to the process of removing a tissue sample for diagnostic or prognostic evaluation, and to the tissue specimen itself. Any biopsy technique known in the art can be applied to the diagnostic and prognostic methods of the present invention. The biopsy technique applied will depend on the tissue type to be evaluated (e.g., tongue, colon, prostate, kidney, bladder, lymph node, liver, bone marrow, blood cell, etc.), the size and type of the tumor (e.g., solid or suspended, blood or ascites), among other factors. Representative biopsy techniques include, but are not limited to, excisional biopsy, incisional biopsy, needle biopsy, surgical biopsy, and bone marrow biopsy. An “excisional biopsy” refers to the removal of an entire tumor mass with a small margin of normal tissue surrounding it. An “incisional biopsy” refers to the removal of a wedge of tissue that includes a cross-sectional diameter of the tumor. A diagnosis or prognosis made by endoscopy or fluoroscopy can require a “core-needle biopsy” of the tumor mass, or a “fine-needle aspiration biopsy” which generally obtains a suspension of cells from within the tumor mass. Biopsy techniques are discussed, for example, in Harrison's Principles of Internal Medicine, Kasper, et al., eds., 16th ed., 2005, Chapter 70, and throughout Part V.
The terms “identical” or percent “identity,” in the context of two or more nucleic acids or polypeptide sequences, refer to two or more sequences or subsequences that are the same or have a specified percentage of amino acid residues or nucleotides that are the same (i.e., about 60% identity, preferably 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or higher identity over a specified region, when compared and aligned for maximum correspondence over a comparison window or designated region) as measured using a BLAST or BLAST 2.0 sequence comparison algorithms with default parameters described below, or by manual alignment and visual inspection (see, e.g., NCBI web site http://www.ncbi.nlm.nih.gov/BLAST/ or the like). Such sequences are then said to be “substantially identical.” This definition also refers to, or may be applied to, the compliment of a test sequence. The definition also includes sequences that have deletions and/or additions, as well as those that have substitutions. As described below, the preferred algorithms can account for gaps and the like. Preferably, identity exists over a region that is at least about 25 amino acids or nucleotides in length, or more preferably over a region that is 50-100 amino acids or nucleotides in length.
For sequence comparison, typically one sequence acts as a reference sequence, to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are entered into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. Preferably, default program parameters can be used, or alternative parameters can be designated. The sequence comparison algorithm then calculates the percent sequence identities for the test sequences relative to the reference sequence, based on the program parameters.
A “comparison window”, as used herein, includes reference to a segment of any one of the number of contiguous positions selected from the group consisting of from 20 to 600, usually about 50 to about 200, more usually about 100 to about 150 in which a sequence may be compared to a reference sequence of the same number of contiguous positions after the two sequences are optimally aligned. Methods of alignment of sequences for comparison are well-known in the art. Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith & Waterman, Adv. Appl. Math. 2:482 (1981), by the homology alignment algorithm of Needleman & Wunsch, J. Mol. Biol. 48:443 (1970), by the search for similarity method of Pearson & Lipman, Proc. Nat'l. Acad. Sci. USA 85:2444 (1988), by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, Wis.), or by manual alignment and visual inspection (see, e.g., Current Protocols in Molecular Biology (Ausubel et al., eds. 1987-2005, Wiley Interscience)).
A preferred example of algorithm that is suitable for determining percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al., Nuc. Acids Res. 25:3389-3402 (1977) and Altschul et al., J. Mol. Biol. 215:403-410 (1990), respectively. BLAST and BLAST 2.0 are used, with the parameters described herein, to determine percent sequence identity for the nucleic acids and proteins of the invention. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov/). This algorithm involves first identifying high scoring sequence pairs (HSPs) by identifying short words of length W in the query sequence, which either match or satisfy some positive-valued threshold score T when aligned with a word of the same length in a database sequence. T is referred to as the neighborhood word score threshold (Altschul et al., supra). These initial neighborhood word hits act as seeds for initiating searches to find longer HSPs containing them. The word hits are extended in both directions along each sequence for as far as the cumulative alignment score can be increased. Cumulative scores are calculated using, for nucleotide sequences, the parameters M (reward score for a pair of matching residues; always >0) and N (penalty score for mismatching residues; always <0). For amino acid sequences, a scoring matrix is used to calculate the cumulative score. Extension of the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity X from its maximum achieved value; the cumulative score goes to zero or below, due to the accumulation of one or more negative-scoring residue alignments; or the end of either sequence is reached. The BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment. The BLASTN program (for nucleotide sequences) uses as defaults a wordlength (W) of 11, an expectation (E) of 10, M=5, N=−4 and a comparison of both strands. For amino acid sequences, the BLASTP program uses as defaults a wordlength of 3, and expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff & Henikoff, Proc. Natl. Acad. Sci. USA 89:10915 (1989)) alignments (B) of 50, expectation (E) of 10, M=5, N=−4, and a comparison of both strands.
“Nucleic acid” refers to deoxyribonucleotides or ribonucleotides and polymers thereof in either single- or double-stranded form, and complements thereof. The term encompasses nucleic acids containing known nucleotide analogs or modified backbone residues or linkages, which are synthetic, naturally occurring, and non-naturally occurring, which have similar binding properties as the reference nucleic acid, and which are metabolized in a manner similar to the reference nucleotides. Examples of such analogs include, without limitation, phosphorothioates, phosphoramidates, methyl phosphonates, chiral-methyl phosphonates, 2-O-methyl ribonucleotides, peptide-nucleic acids (PNAs).
Unless otherwise indicated, a particular nucleic acid sequence also implicitly encompasses conservatively modified variants thereof (e.g., degenerate codon substitutions) and complementary sequences, as well as the sequence explicitly indicated. Specifically, degenerate codon substitutions may be achieved by generating sequences in which the third position of one or more selected (or all) codons is substituted with mixed-base and/or deoxyinosine residues (Batzer et al., Nucleic Acid Res. 19:5081 (1991); Ohtsuka et al., J. Biol. Chem. 260:2605-2608 (1985); Rossolini et al., Mol. Cell. Probes 8:91-98 (1994)). The term nucleic acid is used interchangeably with gene, cDNA, mRNA, oligonucleotide, and polynucleotide.
A particular nucleic acid sequence also implicitly encompasses “splice variants” and nucleic acid sequences encoding truncated forms of cancer antigens. Similarly, a particular protein encoded by a nucleic acid implicitly encompasses any protein encoded by a splice variant or truncated form of that nucleic acid. “Splice variants,” as the name suggests, are products of alternative splicing of a gene. After transcription, an initial nucleic acid transcript may be spliced such that different (alternate) nucleic acid splice products encode different polypeptides. Mechanisms for the production of splice variants vary, but include alternate splicing of exons. Alternate polypeptides derived from the same nucleic acid by read-through transcription are also encompassed by this definition. Any products of a splicing reaction, including recombinant forms of the splice products, are included in this definition. Nucleic acids can be truncated at the 5′ end or at the 3′ end. Polypeptides can be truncated at the N-terminal end or the C-terminal end. Truncated versions of nucleic acid or polypeptide sequences can be naturally occurring or recombinantly created.
The terms “polypeptide,” “peptide” and “protein” are used interchangeably herein to refer to a polymer of amino acid residues. The terms apply to amino acid polymers in which one or more amino acid residue is an artificial chemical mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers and non-naturally occurring amino acid polymer.
The term “amino acid” refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally occurring amino acids. Naturally occurring amino acids are those encoded by the genetic code, as well as those amino acids that are later modified, e.g., hydroxyproline, γ-carboxyglutamate, and O-phosphoserine. Amino acid analogs refers to compounds that have the same basic chemical structure as a naturally occurring amino acid, i.e., an α-carbon that is bound to a hydrogen, a carboxyl group, an amino group, and an R group, e.g., homoserine, norleucine, methionine sulfoxide, methionine methyl sulfonium. Such analogs have modified R groups (e.g., norleucine) or modified peptide backbones, but retain the same basic chemical structure as a naturally occurring amino acid. Amino acid mimetics refers to chemical compounds that have a structure that is different from the general chemical structure of an amino acid, but that functions in a manner similar to a naturally occurring amino acid.
Amino acids may be referred to herein by either their commonly known three letter symbols or by the one-letter symbols recommended by the IUPAC-IUB Biochemical Nomenclature Commission. Nucleotides, likewise, may be referred to by their commonly accepted single-letter codes.
“Conservatively modified variants” applies to both amino acid and nucleic acid sequences. With respect to particular nucleic acid sequences, conservatively modified variants refers to those nucleic acids which encode identical or essentially identical amino acid sequences, or where the nucleic acid does not encode an amino acid sequence, to essentially identical sequences. Because of the degeneracy of the genetic code, a large number of functionally identical nucleic acids encode any given protein. For instance, the codons GCA, GCC, GCG and GCU all encode the amino alanine. Thus, at every position where an alanine is specified by a codon, the codon can be altered to any of the corresponding codons described without altering the encoded polypeptide. Such nucleic acid variations are “silent variations,” which are one species of conservatively modified variations. Every nucleic acid sequence herein which encodes a polypeptide also describes every possible silent variation of the nucleic acid. One of skill will recognize that each codon in a nucleic acid (except AUG, which is ordinarily the only codon for methionine, and TGG, which is ordinarily the only codon for tryptophan) can be modified to yield a functionally identical molecule. Accordingly, each silent variation of a nucleic acid which encodes a polypeptide is implicit in each described sequence with respect to the expression product, but not with respect to actual probe sequences.
As to amino acid sequences, one of skill will recognize that individual substitutions, deletions or additions to a nucleic acid, peptide, polypeptide, or protein sequence which alters, adds or deletes a single amino acid or a small percentage of amino acids in the encoded sequence is a “conservatively modified variant” where the alteration results in the substitution of an amino acid with a chemically similar amino acid. Conservative substitution tables providing functionally similar amino acids are well known in the art. Such conservatively modified variants are in addition to and do not exclude polymorphic variants, interspecies homologs, and alleles of the invention.
The following eight groups each contain amino acids that are conservative substitutions for one another: 1) Alanine (A), Glycine (G); 2) Aspartic acid (D), Glutamic acid (E); 3) Asparagine (N), Glutamine (Q); 4) Arginine (R), Lysine (K); 5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V); 6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W); 7) Serine (S), Threonine (T); and 8) Cysteine (C), Methionine (M) (see, e.g., Creighton, Proteins (1984)).
A “label” or a “detectable moiety” is a composition detectable by spectroscopic, photochemical, biochemical, immunochemical, chemical, or other physical means. For example, useful labels include 32P, fluorescent dyes, electron-dense reagents, enzymes (e.g., as commonly used in an ELISA), biotin, digoxigenin, or haptens and proteins which can be made detectable, e.g., by incorporating a radiolabel into the peptide or used to detect antibodies specifically reactive with the peptide.
The phrase “stringent hybridization conditions” refers to conditions under which a probe will hybridize to its target subsequence, typically in a complex mixture of nucleic acids, but to no other sequences. Stringent conditions are sequence-dependent and will be different in different circumstances. Longer sequences hybridize specifically at higher temperatures. An extensive guide to the hybridization of nucleic acids is found in Tijssen, Techniques in Biochemistry and Molecular Biology—Hybridization with Nucleic Probes, “Overview of principles of hybridization and the strategy of nucleic acid assays” (1993). Generally, stringent conditions are selected to be about 5-10° C. lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength pH. The Tm is the temperature (under defined ionic strength, pH, and nucleic concentration) at which 50% of the probes complementary to the target hybridize to the target sequence at equilibrium (as the target sequences are present in excess, at Tm, 50% of the probes are occupied at equilibrium). Stringent conditions may also be achieved with the addition of destabilizing agents such as formamide. For selective or specific hybridization, a positive signal is at least two times background, preferably 10 times background hybridization. Exemplary stringent hybridization conditions can be as following: 50% formamide, 5×SSC, and 1% SDS, incubating at 42° C., or, 5×SSC, 1% SDS, incubating at 65° C., with wash in 0.2×SSC, and 0.1% SDS at 65° C.
Nucleic acids that do not hybridize to each other under stringent conditions are still substantially identical if the polypeptides which they encode are substantially identical. This occurs, for example, when a copy of a nucleic acid is created using the maximum codon degeneracy permitted by the genetic code. In such cases, the nucleic acids typically hybridize under moderately stringent hybridization conditions. Exemplary “moderately stringent hybridization conditions” include a hybridization in a buffer of 40% formamide, 1 M NaCl, 1% SDS at 37° C., and a wash in 1×SSC at 45° C. A positive hybridization is at least twice background. Those of ordinary skill will readily recognize that alternative hybridization and wash conditions can be utilized to provide conditions of similar stringency. Additional guidelines for determining hybridization parameters are provided in numerous reference, e.g., and Current Protocols in Molecular Biology, ed. Ausubel, et al., supra.
“Antibody” refers to a polypeptide comprising a framework region from an immunoglobulin gene or fragments thereof that specifically binds and recognizes an antigen. The recognized immunoglobulin genes include the kappa, lambda, alpha, gamma, delta, epsilon, and mu constant region genes, as well as the myriad immunoglobulin variable region genes. Light chains are classified as either kappa or lambda. Heavy chains are classified as gamma, mu, alpha, delta, or epsilon, which in turn define the immunoglobulin classes, IgG, IgM, IgA, IgD and IgE, respectively. Typically, the antigen-binding region of an antibody will be most critical in specificity and affinity of binding. Antibodies can be polyclonal or monoclonal, derived from serum, a hybridoma or recombinantly cloned, and can also be chimeric, primatized, or humanized.
An exemplary immunoglobulin (antibody) structural unit comprises a tetramer. Each tetramer is composed of two identical pairs of polypeptide chains, each pair having one “light” (about 25 kD) and one “heavy” chain (about 50-70 kD). The N-terminus of each chain defines a variable region of about 100 to 110 or more amino acids primarily responsible for antigen recognition. The terms variable light chain (VL) and variable heavy chain (VH) refer to these light and heavy chains respectively.
Antibodies exist, e.g., as intact immunoglobulins or as a number of well-characterized fragments produced by digestion with various peptidases. Thus, for example, pepsin digests an antibody below the disulfide linkages in the hinge region to produce F(ab)′2, a dimer of Fab which itself is a light chain joined to VH-CH1 by a disulfide bond. The F(ab)′2 may be reduced under mild conditions to break the disulfide linkage in the hinge region, thereby converting the F(ab)′2 dimer into an Fab′ monomer. The Fab′ monomer is essentially Fab with part of the hinge region (see Fundamental Immunology (Paul ed., 3d ed. 1993). While various antibody fragments are defined in terms of the digestion of an intact antibody, one of skill will appreciate that such fragments may be synthesized de novo either chemically or by using recombinant DNA methodology. Thus, the term antibody, as used herein, also includes antibody fragments either produced by the modification of whole antibodies, or those synthesized de novo using recombinant DNA methodologies (e.g., single chain Fv) or those identified using phage display libraries (see, e.g., McCafferty et al., Nature 348:552-554 (1990))
In one embodiment, the antibody is conjugated to an “effector” moiety. The effector moiety can be any number of molecules, including labeling moieties such as radioactive labels or fluorescent labels, or can be a therapeutic moiety. In one aspect the antibody modulates the activity of a target protein or polypeptide.
The phrase “specifically (or selectively) binds” to or “specifically (or selectively) immunoreactive with” an antibody or binding reagent, when referring to a protein or peptide, refers to a binding reaction that is determinative of the presence of the protein, often in a heterogeneous population of proteins and other biologics. Similarly, an antibody or binding reagent is considered to “substantially bind” to an epitope, when the antibody or binding reagent binds to said epitope in a specific or selective fashion. Thus, under designated immunoassay conditions, the specified antibodies or binding reagents bind to a particular protein at least two times the background and more typically more than 10 to 100 times background. Specific binding to an antibody or binding reagent under such conditions requires an antibody or binding reagent that is selected for its specificity for a particular protein. For example, polyclonal antibodies can be selected to obtain only those polyclonal antibodies that are specifically immunoreactive with the selected antigen and not with other proteins. This selection may be achieved by subtracting out antibodies that cross-react with other molecules. A variety of immunoassay formats may be used to select antibodies or binding reagents specifically immunoreactive with a particular protein. For example, solid-phase ELISA immunoassays are routinely used to select antibodies specifically immunoreactive with a protein (see, e.g., Harlow & Lane, Antibodies, A Laboratory Manual (1988) for a description of immunoassay formats and conditions that can be used to determine specific immunoreactivity).
A binding reagent or antibody that “binds with a lower affinity” to a second polypeptide or to a background polypeptide will generally bind specifically to a first target polypeptide of interest with a greater affinity as compared to the binding affinity to said second polypeptide. In certain embodiments, the binding reagent or antibody will bind to the second polypeptide with at least a two fold lower affinity, or more typically at least about 10-fold, 100-fold, or 1000-fold lower affinity as compared to the binding affinity of the first or target polypeptide. In this fashion, a binding reagent or polypeptide that binds with a lower affinity to a second polypeptide can discriminate between a first target polypeptide and a second polypeptide, even when the second polypeptide is a derivative of the first polypeptide. For example, an antibody specific for a proteolytic polypeptide of the present invention may bind with a lower affinity to the corresponding proteolytic cleavage junction, or a polypeptide containing said cleavage junction, such that the target proteolytic polypeptide, or the level thereof, can be discriminated from said cleavage junction in a biological sample.
In the context of the present invention, a disease is “characterized by apoptosis” if said disease results in altered levels of apoptosis in an individual suffering from the disease. A disease may be considered to be characterized by apoptosis, for example, if levels of apoptosis are reduced or increased in an individual suffering from the disease as compared to levels in individuals not suffering from said disease. In one embodiment of the present invention, apoptosis levels may be reduced or increased by at least about 5%, or at least about 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, or 100% as compared to levels in an individual not suffering from said disease. In other embodiments, the level of apoptosis may be reduced or increased by at least about 1-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold or more as compared to levels in individuals not suffering from the disease. In yet other embodiments, apoptosis may be reduced or increased by at least about 1 order of magnitude, or at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, or more orders of magnitude as compared to levels in an individual not suffering from the disease. Non-limiting examples of diseases that are characterized by apoptosis include, cancer, auto-imune diseases (such as Graves' disease, Lupus erythematosus, Rheumatoid arthritis, Sjögren's syndrome, multiple sclerosis, type-I diabetes mellitus, Hashimoto thyroiditis, and the like), neurodegenerative diseases (such as Parkinson's or Alzheimer's Diseases), preeclampsia, acute and chronic liver diseases, and the like.
Diagnostic Methods
The present invention provides methods of diagnosing a disease characterized by apoptosis, by examining proteolytic apoptotic biomarkers, including proteolytic polypeptides comprising an N-terminal or C-terminal sequence found in Table 1 and proteolytic apoptotic cleavage junctions comprising a sequence found in Table 3, in biological samples, including wild-type, truncated or alternatively spliced forms. Diagnosis involves determining the level of a polypeptide of the invention in a patient and then comparing the level to a baseline or range. Typically, the baseline value is representative of a polypeptide of the invention in a healthy person not suffering from the disease, as measured using biological sample such as blood, serum, saliva, urine, a tissue sample (e.g., tongue or lymph tissue), or a biopsy. Variation of the levels of a polypeptide of the invention from the baseline range (either up or down) indicates that the patient has a disease characterized by apoptosis or is at risk of developing a disease characterized by apoptosis.
Analysis of a protein can be achieved, for example, by high pressure liquid chromatography (HPLC), alone or in combination with mass spectrometry (e.g., MALDI/MS, MALDI-TOF/MS, tandem MS, etc.).
A detectable moiety can be used in the assays described herein. A wide variety of detectable moieties can be used, with the choice of label depending on the sensitivity required, ease of conjugation with the antibody, stability requirements, and available instrumentation and disposal provisions. Suitable detectable moieties include, but are not limited to, radionuclides, fluorescent dyes (e.g., fluorescein, fluorescein isothiocyanate (FITC), Oregon GreenTM, rhodamine, Texas red, tetrarhodimine isothiocynate (TRITC), Cy3, Cy5, etc.), fluorescent markers (e.g., green fluorescent protein (GFP), phycoerythrin, etc.), autoquenched fluorescent compounds that are activated by tumor-associated proteases, enzymes (e.g., luciferase, horseradish peroxidase, alkaline phosphatase, etc.), nanoparticles, biotin, digoxigenin, and the like.
Immunoassay techniques and protocols are generally described in Price and Newman, “Principles and Practice of Immunoassay,” 2nd Edition, Grove's Dictionaries, 1997; and Gosling, “Immunoassays: A Practical Approach,” Oxford University Press, 2000. A variety of immunoassay techniques, including competitive and non-competitive immunoassays, can be used (see, e.g., Self et al., Curr. Opin. Biotechnol., 7:60-65 (1996)). The term immunoassay encompasses techniques including, without limitation, enzyme immunoassays (EIA) such as enzyme multiplied immunoassay technique (EMIT), enzyme-linked immunosorbent assay (ELISA), IgM antibody capture ELISA (MAC ELISA), and microparticle enzyme immunoassay (MEIA); capillary electrophoresis immunoassays (CEIA); radioimmunoassays (RIA); immunoradiometric assays (IRMA); fluorescence polarization immunoassays (FPIA); and chemiluminescence assays (CL). If desired, such immunoassays can be automated. Immunoassays can also be used in conjunction with laser induced fluorescence (see, e.g., Schmalzing et al., Electrophoresis, 18:2184-93 (1997); Bao, J. Chromatogr. B. Biomed. Sci., 699:463-80 (1997)). Liposome immunoassays, such as flow-injection liposome immunoassays and liposome immunosensors, are also suitable for use in the present invention (see, e.g., Rongen et al., J. Immunol. Methods, 204:105-133 (1997)). In addition, nephelometry assays, in which the formation of protein/antibody complexes results in increased light scatter that is converted to a peak rate signal as a function of the marker concentration, are suitable for use in the methods of the present invention. Nephelometry assays are commercially available from Beckman Coulter (Brea, Calif.; Kit #449430) and can be performed using a Behring Nephelometer Analyzer (Fink et al., J. Clin. Chem. Clin. Biochem., 27:261-276 (1989)).
Specific immunological binding of the antibody or binding reagent to a protein can be detected directly or indirectly. Direct labels include fluorescent or luminescent tags, metals, dyes, radionuclides, and the like, attached to the antibody. An antibody labeled with iodine-125 (125I) can be used. A chemiluminescence assay using a chemiluminescent antibody specific for the protein marker is suitable for sensitive, non-radioactive detection of protein levels. An antibody labeled with fluorochrome is also suitable. Examples of fluorochromes include, without limitation, DAPI, fluorescein, Hoechst 33258, R-phycocyanin, B-phycoerythrin, R-phycoerythrin, rhodamine, Texas red, and lissamine. Indirect labels include various enzymes well known in the art, such as horseradish peroxidase (HRP), alkaline phosphatase (AP), β-galactosidase, urease, and the like. A horseradish-peroxidase detection system can be used, for example, with the chromogenic substrate tetramethylbenzidine (TMB), which yields a soluble product in the presence of hydrogen peroxide that is detectable at 450 nm. An alkaline phosphatase detection system can be used with the chromogenic substrate p-nitrophenyl phosphate, for example, which yields a soluble product readily detectable at 405 nm. Similarly, a β-galactosidase detection system can be used with the chromogenic substrate o-nitrophenyl-β-D-galactopyranoside (ONPG), which yields a soluble product detectable at 410 nm. An urease detection system can be used with a substrate such as urea-bromocresol purple (Sigma Immunochemicals; St. Louis, Mo.).
A signal from the direct or indirect label can be analyzed, for example, using a spectrophotometer to detect color from a chromogenic substrate; a radiation counter to detect radiation such as a gamma counter for detection of 125I; or a fluorometer to detect fluorescence in the presence of light of a certain wavelength. For detection of enzyme-linked antibodies, a quantitative analysis can be made using a spectrophotometer such as an EMAX Microplate Reader (Molecular Devices; Menlo Park, Calif.) in accordance with the manufacturer's instructions. If desired, the assays of the present invention can be automated or performed robotically, and the signal from multiple samples can be detected simultaneously.
The antibodies or binding reagents can be immobilized onto a variety of solid supports, such as polystyrene beads, magnetic or chromatographic matrix particles, the surface of an assay plate (e.g., microtiter wells), pieces of a solid substrate material or membrane (e.g., plastic, nylon, paper), and the like. An assay strip can be prepared by coating the antibody or a plurality of antibodies in an array on a solid support. This strip can then be dipped into the test sample and processed quickly through washes and detection steps to generate a measurable signal, such as a colored spot.
Useful physical formats comprise surfaces having a plurality of discrete, addressable locations for the detection of a plurality of different biomarkers. Such formats include protein microarrays, or “protein chips” (see, e.g., Ng et al., J. Cell Mol. Med., 6:329-340 (2002)) and certain capillary devices (see, e.g., U.S. Pat. No. 6,019,944). In these embodiments, each discrete surface location may comprise antibodies to immobilize one or more protein markers for detection at each location. Surfaces may alternatively comprise one or more discrete particles (e.g., microparticles or nanoparticles) immobilized at discrete locations of a surface, where the microparticles comprise antibodies to immobilize one or more protein markers for detection.
The analysis can be carried out in a variety of physical formats. For example, the use of microtiter plates or automation could be used to facilitate the processing of large numbers of test samples. Alternatively, single sample formats could be developed to facilitate diagnosis or prognosis in a timely fashion.
Compositions, Kits and Integrated Systems
The invention provides compositions, kits and integrated systems for practicing the assays described herein using polypeptides of the invention, antibodies or binding reagents specific for polypeptides of the invention, etc.
The invention provides assay compositions for use in solid phase assays; such compositions can include, for example, one or more antibodies or binding reagents specific for the polypeptide biomarkers of the invention immobilized on a solid support, and a labeling reagent. In each case, the assay compositions can also include additional reagents that are desirable for hybridization.
The invention also provides kits for carrying out the diagnostic or prognostic assays of the invention. The kits typically include a probe that comprises an antibody or binding reagent that specifically binds to polypeptides of the invention, and a label for detecting the presence of the probe. The kits may include several antibodies specific for the polypeptides of the invention. In one embodiment, the kits of the invention comprise at least 2, or at least about 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 250, 300 or more antibodies or binding reagents.
Optical images viewed (and, optionally, recorded) by a camera or other recording device (e.g., a photodiode and data storage device) are optionally further processed in any of the embodiments herein, e.g., by digitizing the image and storing and analyzing the image on a computer. A variety of commercially available peripheral equipment and software is available for digitizing, storing and analyzing a digitized video or digitized optical images.
One conventional system carries light from the specimen field to a cooled charge-coupled device (CCD) camera, in common use in the art. A CCD camera includes an array of picture elements (pixels). The light from the specimen is imaged on the CCD. Particular pixels corresponding to regions of the specimen are sampled to obtain light intensity readings for each position. Multiple pixels are processed in parallel to increase speed. The apparatus and methods of the invention are easily used for viewing any sample, e.g., by fluorescent or dark field microscopic techniques.
N-Terminal Labeling of Polypeptides
In general, any method of making an extract from cells or tissues from a biological sample that preserves the ability to label the N-termini of polypeptides with the reagents described below may be used in the practice of this invention. Any of a number of such methods are known in the art and are described in standard sources (see, e.g., Scopes, Protein Purification: Principles and Practice (1982)). In general, cells are disrupted to release and solubilize intracellular contents, followed by centrifugation to remove insoluble material, such as cell membranes and organelles. For tissue culture cells, a lysis buffer which may contain a detergent (e.g., TRITON X-100 detergent, NP-40, among others) may be used. For adherent tissue culture cells, cell disruption can be accomplished by the process of scraping cells in the presence of the lysis buffer from culture plates using, for example, a rubber policeman. Other mechanical means can also be used to effect cell disruption. For example, cells can be lysed using a Dounce homogenizer. As recognized by the skilled artisan, additional mechanical means may be needed to prepare cell extracts from tissues, such as homogenization in a blender or sonication. (See, generally, e.g., Scopes, Protein Purification: Principles and Practice (1982).)
The labeling of polypeptides can be accomplished using any method that labels the N-terminus (i.e., α-amino group) of a polypeptide present in a complex mixture.
In one embodiment of this invention, the labeling is accomplished using the enzyme subtiligase, which is derived from the enzyme subtilisin BPN′ by converting the catalytic residue, Ser-221, to a cysteine residue, and Pro-225 to an alanine residue. The resulting double mutant protein provides the enzymatic activity of ligation of esterified peptides site-specifically onto the N termini of proteins or peptides (see, e.g., Chang, T. K. et al., Proc. Natl. Acad. Sci. U.S.A., 91, 12544-12548 (1994)). Furthermore, additional forms of subtiligase that exhibit increased stability have been generated through the introduction of additional site directed mutations into the sequence (e.g., Met-50 to Phe, Asn-76 to Asp, Asn-109 to Ser, Lys-213 to Arg, and Asn-218 to Ser). Such mutant enzymes have also been termed stabiligases and may also may be used in the practice of the present invention (see, e.g., Chang, T. K. et al., Proc. Natl. Acad. Sci. U.S.A., 91, 12544-12548 (1994)).
All of the earlier work describing the use of subtiligase and its variants disclosed the ligation of peptides and proteins in non-complex samples composed of single purified polypeptides. In this earlier work, two examples of the application of subtiligase to the ligation of proteins that were recombinantly expressed on the surface of phage particles were shown. For example, the work of Chang et al. demonstrated the ligation of phage-displayed human growth hormone variants that were randomized at the first three residues (Chang, T. K. et al., Proc. Natl. Acad. Sci. U.S.A., 91, 12544-12548 (1994)). The work of Atwell et al. demonstrated the autoligation of phage-displayed subtiligase variants that contained an N-terminal extension and were randomized at up to five different residues outside of this N-terminal extension (Atwell S. et al., Proc. Natl. Acad. Sci. U.S.A., 96, 9497-9502 (1999)). In contrast, the present invention represents a major advance, as it applies subtiligase to the ligation of polypeptides in complex mixtures of endogenous proteins as found in a variety of biological samples, not merely to simple formulations of recombinant proteins, as shown by the earlier studies. The modest amount of sample complexity in the earlier reported phage display experiments arises from minor genetic manipulations of either the human growth hormone gene or the subtiligase gene. In contrast, the complexity found in the biological samples of the present invention arises from the fact that the component polypeptides of the complex mixtures of the invention are products of a plurality of endogenous genes, which are subject to transcriptional, translational, and post-translational modulation of expression.
Furthermore, the work of Chang et al. demonstrated that subtiligase is very dependent on the primary and secondary structure of polypeptide substrates. Although subtiligase was found to exhibit broad specificity for peptide substrates, some N-terminal residues in these substrates were found to be exceedingly more preferred than others. Structural occlusion of N-termini in a protein substrate was also found to drastically affect ligation efficiency. This earlier work indicated limitations to this approach for labeling a plurality of polypeptides in complex mixtures and provided no indication of applicability to more complex samples, as the only substrates used in addition to short peptides were recombinant human growth hormone and subtiligase. In fact, those of skill in the art recognized several potential pitfalls in the implementation of subtiligase as a tool for selective labeling of polypeptide α-amines in complex mixtures. First, it was believed that only the most abundant proteins in the sample would be labeled. Second, the previous data indicated the possibility that only the most efficient substrates, based on the identity of N-terminal residues, would be labeled. Third, there existed the possibility of poor labeling of mixtures due to structural occlusion of N-termini. Fourth, there was a strong possibility that complex samples would contain inhibitors of subtiligase. Fifth, there was a prevalent concern that the peptide glycolate ester reagents would not be stable in biological samples because of the action of endogenous esterases and proteases.
However, as demonstrated below, the inventors have surprisingly found that these many pitfalls could be circumvented and have demonstrated that subtiligase may be used to efficiently label the N-termini of a plurality of polypeptides in complex mixtures, such as cell extracts and serum. For example, the inventors show that addition of a cocktail of inhibitors sufficiently blocks endogenous proteases and esterases without inhibiting subtiligase, thus, allowing for sufficient substrate to be available for ligation. Another advantage imparted by the present invention is the nature of the labeled peptide ester reagents used here. The inventors have designed versions of these reagents that are optimized for use in proteomic studies. Among other innovations, they have found that incorporation of a cleavable linker into these reagents greatly facilitates purification of labeled polypeptides from complex mixtures and subsequent analysis by tandem mass spectrometry for identification of the corresponding proteins.
Additional variants of subtiligase enzymes that have enhanced activity have also been selected through the application of phage display methods (see, e.g., Atwell, S. et al., Proc. Natl. Acad. Sci. U.S.A., 96:9497-502 (1999)). Such variants may also be used in the practice of the present invention. Furthermore, other subtilisin-like enzymes and their variants may also be engineered to be used in the practice of this invention.
Subtiligase has been used to incorporate a variety of label moieties into proteins and polypeptides, including affinity handles (e.g., biotin), immunoprobes, isotopic labels, heavy-atom derivatives, PEG moieties, and other non-natural constituents (see, e.g., Chang, T. K. et al., Proc. Natl. Acad. Sci. U.S.A., 91, 12544-12548 (1994)). The skilled artisan will recognize that this is not an exhaustive list, as for instance, any detectable label that can be incorporated into a substrate (e.g., biotin labeled peptide esters) to be used to label a free N-terminus (e.g., α-amino group of a polypeptide generated through proteolysis) may be used. In particular, any of the labels disclosed above may be used in the practice of the present invention.
The reaction by which subtiligase may be used to label a free N-terminus of a polypeptide is illustrated in FIGS. 1A-1, 1A-2, 1B-1, and 1B-2 with a biotin labeled peptide ester as the substrate for the introduction of a biotin label onto a protein. In the first step of this reaction, a free sulhydryl group on subtiligase serves as a nucleophile to effect a nucleophilic attack on the carbonyl carbon atom of the ester moiety of the substrate peptide ester, resulting in the release of an alcohol leaving group. In a second step, the carbonyl carbon of the thioester linkage between the peptide substrate and the subtiligase enzyme is then subject to nucleophilic attack by the α-amino group of a protein or peptide. This reaction results in a covalent adduct comprising the biotin labeled peptide linked to the α-amino group on a protein or peptide via an amide bond. Accordingly, the biotin label then can serve as an affinity handle to allow the identification and isolation of polypeptides that have a free N-terminus or free α-amino group (e.g., protein fragments that have resulted from proteolysis, or native non-acetylated or otherwise N-terminally blocked proteins).
In general, any peptide ester with the following generic elements may be used in the practice of the present invention: label-linker-peptide sequence-esterified carboxyl terminus. The skilled artisan will recognize that the location of the label within this structure may be varied without affecting the operation of the present invention. The generic structure of these elements may optionally contain a protease cleavage site or other cleavable moiety to facilitate the ready removal of the label added to the α-amino group of a protein or polypeptide. Such removal also greatly facilitates downstream mass spectrometric analysis of labeled proteins or polypeptides. FIG. 6 shows a representative peptide ester that may be used in the practice of the invention. In this example, there is a biotin label at the N-terminus of the peptide ester, a site for a protease cleavage (TEV protease), and an esterified carboxyl terminus, which serves as a subtiligase cleavage site (i.e., the site for the nucleophilic attack by a free sulfhydryl group on subtiligase as described above). Among the peptide sequences that may be used in the practice of the invention include, but are not limited to: ENLYFQSY (SEQ ID NO:420), ENLYFQSK (SEQ ID NO:421), ENLYFQSA (SEQ ID NO:422), AAPY (SEQ ID NO:423), AAPK (SEQ ID NO:424), and AAPA (SEQ ID NO:425), among others. Optional protease cleavage sites that may be used in the practice of this invention include, but are not limited to: the site for TEV protease: EXXYXQ(S/G/A) (SEQ ID NO:436), where X corresponds to any amino acid; the site for rhinovirus 3C protease: E(T/V)LFQGP (SEQ ID NO:426); the site for enterokinase: DDDDK (SEQ ID NO:427); the site for Factor Xa: I(D/E)GR; the site for thrombin: LVPR (SEQ ID NO:428); the site for furin: RXXR (SEQ ID NO:437), where X corresponds to any amino acid; and the site for Granzyme B: IEPD (SEQ ID NO:429). Some examples of the many possible moieties that may be used to esterify the carboxyl terminus of the peptide are: HO—CH2-CO—X, where X is any amino acid, in the case of glycolate esters; HO—CHCH3-CO—X, where X is any amino acid, in the case of lactate esters; HO—R, where R is an alkyl or aryl substituent; and HS—R, where R is an alkyl or aryl substituent. A number of label moieties may be used, including radioisotopes, stable isotopes, flurophores, heavy metals, and biotin, among others.
In general, any reaction conditions that favor nucleophilic attack of a carbonyl group at an ester or thioester linkage to result in the release of the relevant leaving group (e.g., an alcohol in step one or the —SH group of subtiligase in step two) may be used in the practice of this invention for the labeling of free α-amino groups. Generally, any conditions under which ester reagents are stable to degradation and hydrolysis in complex samples; conditions under which subtiligase is stable and active; and conditions under which protein and polypeptide N-termini are free and available to react with the thioester linkage formed after the reaction of subtiligase with ester reagents are favored for the practice of this invention.
In some embodiments of this invention, the pre-existing unblocked α-amino groups of polypeptides may be blocked with a suitable N-termini blocking agent before an experimental treatment. Thus, for instance, the free, unblocked N-termini of cellular proteins may be blocked with any reagent that reacts with free α-amino groups prior to exposure of a biological sample to an agent, such as a chemotherapeutic agent, which promotes a physiological response of interest, such as apoptosis. After the experimental treatment, the newly exposed N termini which have resulted from the proteolytic events that accompany apoptosis can then be labeled using subtiligase and the ester substrates of the present invention. Examples of such blocking agents include: amine-reactive reagents such as succinimidyl esters, isothiocyanates, sulfonyl chlorides, and aldehydes, among others, provided these reagents do not contain primary or secondary amine moieties. In one embodiment, the blocking reaction can be accomplished using subtiligase and an acetylated ester.
It will be appreciated by the skilled artisan that a variety of complex samples can be labeled using the methods and compositions of the present invention. Such samples may include, without limitation, whole cells, cell extracts, media from cell cultures, serum from humans or animals, and other bodily fluids, among others. For example, the culture medium of cells stimulated with an agent that causes polypeptide secretion can be labeled using the methods of the present invention to identify polypeptides that have been secreted. As another example, proteins found on the surfaces of intact cells may be labeled to identify cell surface proteins, such as membrane proteins. The comparison of the cell surface proteins labeled in normal versus transformed cells can be used to identify, for example, tumor specific antigens. As a further example, serum or other bodily fluids from normal subjects and patients suffering from various diseases can be labeled to identify proteins that are unique to the serum of a patient population. The proteins so identified can serve as easily detected disease markers to be used in disease diagnostics. U.S. patent application Ser. No. 12/524,557 filed on Jul. 24, 2009, assigned to the same assignee as the present invention, the disclosure of which is incorporated by reference in its entirety and with particularity with reference to its teachings concerning methods for the specific N-terminal labeling and detection of peptides and proteins in complex mixtures.
EXAMPLES
Example 1
This example demonstrates the identification and profiling of N-termini in normal Jurkat cells.
As a validation of a method provided by the present invention, endogenous N-termini in non-apoptotic Jurkat cells were analysed in two small-scale experiments using one-dimensional reversed-phase (1D) LC/MS/MS and two large-scale experiments using two-dimensional strong cation exchange/reversed-phase (2D) LC/MS/MS. Comparison of data obtained in both types of experiments is informative since 1D LC/MS/MS typically results in identification of abundant N-termini, whereas the increased proteomic coverage afforded by 2D LC/MS/MS results in additional identification of lower abundance N-termini. Of the combined 131 unique N-termini identified in small-scale experiments, 72% are either annotated in Swiss-Prot as native protein N-termini, or correspond to cleavages within the first 50 residues of proteins as would be expected for N-terminal signal or transit peptide processing (FIG. 2A). The remaining 28% correspond to cleavages outside the first 50 residues, arising from additional processing or constitutive protein degradation. In support of the latter notion, 51% of the combined 661 unique N-termini identified in large-scale experiments correspond to cleavages outside the first 50 residues (FIG. 2A). The increased frequency of such N-termini in large-scale experiments is consistent with the expected lower abundance for products of constitutive protein degradation.
Example 2
This example provides degradomic analysis of apoptotic Jurkat cells.
For analysis of apoptosis in Jurkat cells, several small-scale (1D) and large-scale (2D) LC/MS/MS experiments were carried out using cells treated with the topoisomerase II poison etoposide. The experiments with untreated cells described above serve as respective controls for the small- and large-scale experiments with apoptotic cells, in which a combined 244 and 733 unique N-termini, respectively, were identified. Caspases are known to exhibit strict substrate specificity for aspartate at P1, and for glycine>serine>alanine at P1′ (Schilling et al., Nat. Biotechnol. 2008; 26(6):685-94; Stennicke et al., Biochem J. 2000; 350 Pt 2:563-8). In small-scale experiments, 43% of N-termini identified in apoptotic cells were derived from P1 aspartate cleavages, in contrast to less than 1% in untreated cells (FIG. 3A). In large-scale experiments, 43% of N-termini identified in apoptotic cells were derived from P1 aspartate cleavages, in contrast to 3% in untreated cells (FIG. 3B). An increased frequency of glycine at the first position of N-termini is also observed in apoptotic cells relative to untreated cells at both experimental scales (FIGS. 3A and 3B). The N-termini uniquely identified in apoptotic Jurkat cells are thus consistent with induction of caspase-like activity.
Of the 3% P1 aspartate N-termini detected in large-scale experiments with untreated cells (FIG. 3B), 55% correspond to reported caspase substrates (Lüthi et al., Cell Death Differ. 2007; 14(4):641-50). Thus, it is likely that these originate from the small number of apoptotic cells typically present in untreated cultures. The detection of 3% P1 aspartate N-termini in large-scale experiments with untreated cells and less than 1% in small-scale experiments is consistent with the low abundance of such N-termini in cultures of normal cells. Additionally, if one considers that N-termini annotated in Swiss-Prot are representative of native N-termini in healthy cells, it is notable that <1% are derived from proteolytic processing following an aspartate residue (FIG. 4). In apoptotic samples, the increased frequency of N-termini located beyond the first 50 residues is solely attributable to P1 aspartate N-termini (FIGS. 2B and 2C). Thus, the vast majority of proteolysis we observe in apoptosis is attributable to caspases or proteases with caspase-like substrate specificity.
Among the total 1099 SY-labeled peptides identified in etoposide-treated Jurkat cells, 418 follow aspartate in corresponding protein sequences. These peptides correspond to 333 P1 aspartate N-termini and caspase-like cleavage sites. In turn, these cleavage sites map to 282 unique substrates and 10 additional others that cannot be distinguished from homologs containing the same identified cleavage site. Approximately 16 of the proteins identified as caspase substrates in these studies have been verified to be cleaved during apoptosis using immunoblotting (representative examples are indicated in FIG. 5A). The proteolysis of a representative set of substrates is also blocked by the broad-spectrum caspase inhibitor Z-VAD(OMe)-fmk, consistent with this proteolysis being caspase-dependent (FIG. 5B). Representative CID spectra for P1 aspartate peptides are included (FIGS. 8-15).
The most frequent residues at the P4, P3, P2, and P1′ positions of the caspase-like cleavage sites identified in apoptotic Jurkat cells are aspartate, glutamate, valine, and glycine, respectively (FIG. 6A). Thus, an averaged composite of these cleavage sites indicates that the most common caspase activity in apoptotic cells exhibits a specificity that is most similar to the substrate specificity of executioner caspases-3 and -7, as determined using peptide substrates (FIG. 6B) (Thornberry et al., J Biol Chem. 1997; 272(29):17907-11). However, there are significant differences between the cellular cleavage sites and the in vitro specificity profiles. Notably, the canonical DEVD (SEQ ID NO:430) cleavage site motif is found in less than 1% of the caspase-like cleavage sites observed in apoptotic Jurkat cells, and the broader DXXD (SEQ ID NO:438) motif is still only found in 22% of the identified cleavage sites (FIG. 6D). A distinct difference in the composite cellular profile is the high frequency of serine and threonine residues at P4, P3, and P2, which is not observed in vitro for any of the caspases (FIG. 7). Interestingly, a composite of all previously reported human and human ortholog of rodent caspase cleavage sites (Lüthi et al., Cell Death Differ. 2007; 14(4):641-50) is very similar to the Jurkat cellular profile reported here (FIG. 6C).
These observations suggest that caspase substrate specificity determined using peptide substrates has limited value as a predictor of physiological caspase cleavage sites. To investigate the predictive value of a large set of known physiological caspase cleavage sites, we constructed three profile hidden Markov models (HMMs) using the cleavage sites identified in our studies, previously reported cleavage sites, and the union of these two datasets. The accuracy of these HMMs was estimated using jackknifing and plotted in a receiver operator characteristic (ROC) plot, showing the true positive rate versus the false positive rate at different HMM score thresholds. While all three HMMs predict caspase cleavage sites relatively accurately, the HMM built from the merged substrate set performed most accurately (FIG. 6E).
Example 5
Cell Culture, Induction of Apoptosis, and Cell Lysate Preparation
Jurkat clone E6-1 (ATCC) cells were grown in RPMI-1640 supplemented with 10% fetal bovine serum, sodium pyruvate, and antibiotics. Normal cells were harvested for experiments at a density of 1×106 cells/ml. For apoptotic samples, cells at a density of 1×106 cells/ml were treated with etoposide (50 μM) for 12 hours prior to harvesting. Harvested cells (0.1 to 1 billion) were pelleted at 2,000×g and 25° C. for 5 minutes, washed twice with phosphate buffered saline, and lysed at a typical concentration of 2×108 cells/ml in 1.0% TRITON X-100 detergent, 100 mM BICINE pH 8.0, 100 μM Z-VAD-FMK, 100 μM E-64, 1 mM PMSF, 1 mM AEBSF, and 5 mM EDTA. Cell lysates were incubated at room temperature for 1 hour to allow complete inhibition of endogenous protease and esterase activity, and centrifuged at 21,000×g and 4° C. for 15 minutes to pellet insoluble material. Clarified supernatant was immediately used in ligation reactions at a protein concentration of approximately 20 mg/ml, as determined by Bradford assay (Bio-Rad).
Example 6
Sample Biotinylation, Denaturation, Reduction, Alkylation, and Gel Filtration
Subtiligase (1 μM), biotinylated peptide ester (1 mM), and DTT (2 mM) were added to either control or apoptotic cell lysate. Ligation reactions were typically left to proceed at room temperature for 60 minutes. Samples were then denatured by direct addition of solid guanidine hydrochloride to a final concentration of 6 M, reduced by addition of neutralized TCEP (2 mM), heated at 95° C. for 15 minutes, cooled to room temperature, and alkylated by addition of iodoacetamide (6 mM) and incubation at room temperature in the dark for 1 hour. The alkylation reaction was quenched by addition of DTT (10 mM), the sample was passed through a 0.8 μm filter, and subjected to gel filtration chromatography using a Superdex 30 16/60 column (GE Healthcare) on an ÄKTA FPLC system (GE Healthcare). The mobile phase was 100 mM BICINE pH 8.0, 200 mM NaCl, and 1 M guanidine hydrochloride. Fractions containing protein (corresponding to polypeptides greater than 5 kDa) were collected and pooled for a final volume of approximately 30 ml.
Example 7
Trypsinization and Recovery of Biotinylated Peptides
The gel-filtered material was supplemented with CaCl2 (20 mM) and digested with sequencing grade modified trypsin (100 μg, Promega) by incubation at 37° C. for 12 hours. Trypsinized samples were clarified by centrifugation, supplemented with benzamidine (500 mM), and NeutrAvidin agarose (250 μl bed volume, Pierce) was added for affinity capture of biotinylated N-terminal peptides. After 12 hours of gentle agitation, NeutrAvidin agarose resin was pelleted and washed with 100 mM BICINE pH 8.0 and AEBSF (1 mM), 100 mM BICINE pH 8.0, 5 M NaCl, and again with a few washes of 100 mM BICINE pH 8.0. More stringent washes using either 1 M or 5 M guanidine hydrochloride were used in some cases. Captured peptides were released from NeutrAvidin agarose resin by treatment with TEV protease (1 μM) in 100 mM BICINE pH 8.0 and DTT (1 mM). Recovered peptides were concentrated and desalted using ZipTipC18 pipette tips, or a C18 Macrotrap (Michrom) trap column on a 2796 HPLC system (Waters). TEV protease was sometimes depleted from samples using an SCX Macrotrap (Michrom) trap column.
Example 9
Expression and Purification of Subtiligase
The expression construct for subtiligase was prepared using the B. subtilis/E. coli shuttle vector pBS42 (ATCC) (Wells et al., Nucleic Acids Res. 1983; 11(22):7911-25). The variant of subtiligase used corresponds to subtilisin BPN′ containing point mutations S221C, P225A, M124L, and S125A for ligase activity (Abrahmsen et al., Biochemistry. 1991; 30(17):4151-9; Atwell et al., Proc Natl Acad Sci USA. 1999; 96(17):9497-502), and point mutations M50F, N76D, N109S, K213R, AND N218S for increased stability (Chang et al., Proc Natl Acad Sci USA. 1994; 91(26):12544-8). Recombinant subtiligase was prepared in B. subtilis strain 168 (ATCC). Subtiligase expression and purification was carried out essentially as described (Abrahmsen et al., Biochemistry. 1991; 30(17):4151-9). The purified enzyme was stored at −80° C. in 100 mM BICINE, pH 8.0 and 10 mM DTT or TCEP.
Example 12
Synthesis of Peptide Ester Substrates
Peptide glycolate ester substrates for subtiligase were prepared by solid-phase peptide synthesis using Fmoc chemistry as previously described (Braisted et al., Methods Enzymol. 1997; 289:298-313). Peptides were purified using 10×50 mm XTerra Prep MS C18 ODB columns on a Parallex Flex HPLC system (Biotage). Purity and identity of peptides was verified by LC/MS analysis using a 4.6×50 mm XTerra MS C18 column on a 2795 HPLC (Waters) system equipped with a ZQ quadrupole MS detector (Waters).
Example 13
Sample Fractionation Using Strong Cation Exchange (SCX) Chromatography
For larger scale experiments, samples were fractionated by SCX chromatography prior to LC/MS/MS analysis using a 2.1×200 mm PolySULFOETHYL Aspartamide column (The Nest Group) at a flow rate of 0.3 ml/min on a 2796 HPLC system (Waters). Buffer A consisted of 25 mM ammonium formate pH 2.8 and 30% acetonitrile, and buffer B consisted of 500 mM ammonium formate pH 2.8 and 30% acetonitrile. Approximately 25 fractions were collected during a 40 minute gradient block from 0% to 75% buffer B. Solvent from fractions was removed using an EZ-2 Plus evaporator (GeneVac), and remaining ammonium formate salt was removed by lyophilization. Some samples were also fractionated using a phosphate buffer and KCl salt system, in which case each fraction was subjected to automated desalting using a C is Microtrap (Michrom) trap column on a 2796 HPLC system (Waters) before solvent removal.
Example 14
Nano-LC-ESI-Qq-TOF MS/MS Analysis
Desalted fractionated or unfractionated samples were separated using a 75 μm×15 cm C18 column (LC Packings) at a flow rate of 350 nl/min, with a 60 minute gradient of 3 to 30% acetonitrile in 0.1% formic acid, on a 1100 series HPLC system (Agilent). The LC eluent was coupled to a microion spray source attached to a QSTAR Pulsar or QSTAR XL mass spectrometer (Applied Biosystems). Peptides were analyzed in positive ion mode. MS spectra were acquired for 1 s. For each MS spectrum, either the single most intense or the two most intense multiply charged peaks were selected for generation of subsequent CID mass spectra, depending on the analysis method used. The CID collision energy was automatically adjusted based upon peptide charge and m/z ratio. A dynamic exclusion window was applied that prevented the same m/z from being selected for 3 min after its initial acquisition. Representative CID spectra are included as FIGS. 11-18. Additional CID figures will be made available upon request.
Example 15
Interpretation of MS/MS Spectra
Data were analyzed using Analyst QS software (version 1.1), and MS/MS centroid peak lists were generated using the Mascot.dll script (version 1.6b16). Data were searched against the Swiss-Prot human database (March 2008 release) using Protein Prospector 5.0 (University of California, San Francisco). Initial peptide tolerances in MS and MS/MS modes were 200 ppm and 300 ppm, respectively. The digest protease specified was trypsin, allowing for non-specific cleavage at N-termini in searches for N-terminally labeled semitryptic peptides, and trypsin allowing for non-specific cleavage at 0 N-termini in searches for unlabeled fully tryptic peptide contaminants. Two missed cleavages were typically allowed in searches. An N-terminal SY modification was specified as a fixed modification in searches for Nterminal peptides, but not in searches for unlabeled peptides. Cysteine carbamidomethylation was specified as a fixed modification and methionine oxidation was specified as a variable modification in all searches. High scoring peptide identifications from individual LC/MS/MS runs were then used to internally recalibrate MS parent ion m/z values within each run. Recalibrated data files were then searched again with an MS peptide tolerance of 100 ppm. Peptides with scores of greater than or equal to 22 and expectation values of less than or equal to 0.05 were considered positively identified. False positive rates for peptide identifications were estimated by conducting searches using a concatenated database containing the original Swiss-Prot human database, as well as a version of each original database entry where the sequence had been randomized. The overall false positive rate for N-terminal peptides identified was found to be 2.09%, while the false positive rate for peptides following aspartic acid in corresponding protein sequences was found to be 0.71%. A representative sampling of SY-labeled peptide identifications, particularly those based on expectation values near 0.05, was also manually validated.
Example 16
Immunoblotting and DNA Fragmentation Analysis
Jurkat cells at a density of 1×106 cells/ml were treated with etoposide (50 μM) for 0, 2, 4, 8, 12, and 24 hours prior to harvesting. Harvested cells were pelleted at 2,000×g and 25° C. for 5 minutes, washed twice with phosphate buffered saline, and lysed at a concentration of 2×107 cells/ml in 1.0% SDS, phosphate buffered saline, 100 μM Z-VAD-FMK, 100 μM E-64, 1 mM PMSF, 1 mM AEBSF, 5 mM EDTA, and 10 mM sodium butyrate. Whole cell lysates were sonicated to shear genomic DNA, normalized to a protein concentration of approximately 2 mg/ml, as determined by BCA assay (Pierce). Cell lysates for each apoptotic timepoint were then analyzed by SDS-PAGE and Western blot. Mouse monoclonal anti-caspase-3 (#9668) and rabbit polyclonal anti-HDAC3 (#2632) antibodies were purchased from Cell Signaling Technology. Mouse monoclonal anti-DFF45 (#611036) antibody was purchased from BD Transduction Laboratories. Goat polyclonal anti-N-Cor (#sc-1611) and rabbit polyclonal anti-HDAC7 (#sc-11412) antibodies were purchased from Santa Cruz Biotechnology. Rabbit polyclonal anti-TBLR1 (#A300-408A), rabbit polyclonal anti-SHARP (#A301-119A), and rabbit polyclonal anti-RBBP7 (#A300-959A) antibodies were purchased from Bethyl Laboratories. Rabbit polyclonal anti-SMRTe (#06-891) antibody was purchased from Millipore. Western blots were imaged using SuperSignal West Femto Substrate (Pierce) with a Fluor Chem SP imager (Alpha Innotech). DNA fragmentation of whole cell DNA was analyzed by agarose gel with the Apoptotic DNA Ladder Kit (Roche).
Example 17
Identification of protein N-termini in serum. Serum and plasma can be labeled by N-terminal protein biotinylation by a process similar to that described in Example 6. For example, two milliliters of human serum (NHS) supplemented with 100 mM BICINE pH 8.0, 1 mM EDTA, 1 mM PMSF, and 10% DMSO are labeled with 1 mM of biotinylated peptide ester using 1 μM subtiligase at room temperature for 15 to 120 minutes. Peptides corresponding to protein N termini of serum or plasma proteins are then recovered and identified as described in the Examples above. As a result of such an analysis, 79 nonredundant peptides can be identified in a single LC/MS/MS run, corresponding to 34 unique proteins. 68% of the peptides corresponded to annotated N termi resulting from signal cleavage or other known functional proteolytic processing. The 32% of N-terminal peptides with unknown origin indicate the potential of this technique to identify previously unknown posttranslational modifications in serum proteins. The abundances of identified proteins can span five orders of magnitude, from the processed N terminus of serum albumin ( ̃20 mg/ml) to insulin-like growth factor II ( ̃500 ng/ml). Low abundance serum proteins can be identified despite no effort being made to deplete highabundance proteins prior to analysis, illustrating the power of this labeling technique to partially neutralize dynamic range problems that confound serum proteomics. These results can be obtained without pre-fractionation of the labeled serum peptides. Significantly improved depth of coverage can be obtained with SCX fractionation.







TABLE 1







Identified caspase-derived peptides. Previous residues indicates the inferred


 P8-P1 residues in the given protein substrate that directly precede the 


sequence of residues corresponding to the identified peptide. Unmodified  


peptide indicates the sequence of residues corresponding to the identified   


peptide. Modified peptide indicates the peptide as identified, sometimes 


containing chemical modifications such as oxidized methionine and 


carbamidomethylated cysteine, and always containing either an N-terminal serinyl-


glycyl dipeptide (SerTyr) modification or an N-terminal 2-aminobutyryl (Abu)  


modification. Start residue(SR) indicates the residue number  in the full-length 


protein sequence of the first residue of the unmodified peptide. 


“M” indicates the number of matches.













SEQ








ID
Swiss-Prot
Swiss-
unmodified





NO.
ID
Prot acc #
peptide
SR
M
protein name

















2A5G_HUMAN
Q13362

15
1
Serine/threonine-protein








phosphatase 2A 56 kDa








regulatory subunit gamma








isoform


 


1
3MG_HUMAN
P29372
AAQAPAEQPHSSS
37
1
DNA-3-methyladenine





DAAQAPCPR


glycosylase



41_HUMAN
P11171

551
1
Protein 4.1



41_HUMAN
P11171

551
1
Protein 4.1



4EBP1_HUMAN
Q13541

26
1
Eukaryotic translation








initiation factor 4E-binding








protein 1



4EBP2_HUMAN
Q13542

27
1
Eukaryotic translation








initiation factor 4E-binding








protein 2



A26CA_HUMAN
Q6S8J3

945
10
ANKRD26-like family C








member 1A



A26CB_HUMAN
A5A3E0

945

ANKRD26-like family C








member 1B



ACTA_HUMAN
P62736

247

Actin, aortic smooth muscle



ACTBL_HUMAN
Q562R1

246

Beta-actin-like protein 2



ACTB_HUMAN
P60709

245

Actin, cytoplasmic 1



ACTC_HUMAN
P68032

247

Actin, alpha cardiac muscle 1



ACTG_HUMAN
P63261

245

Actin, cytoplasmic 2



ACTH_HUMAN
P63267

246

Actin, gamma-enteric








smooth muscle



ACTK_HUMAN
Q9BYX7

245

Kappa-actin



ACTS_HUMAN
P68133

247

Actin, alpha skeletal muscle



A26CA_HUMAN
Q6S8J3

945
10
ANKRD26-like family C








member 1A



A26CB_HUMAN
A5A3E0

945

ANKRD26-like family C








member 1B



ACTA_HUMAN
P62736

247

Actin, aortic smooth muscle



ACTBL_HUMAN
Q562

246

Beta-actin-like protein 2



ACTB_HUMAN
P60709

245

Actin, cytoplasmic 1



ACTC_HUMAN
P68032

247

Actin, alpha cardiac muscle 1



ACTG_HUMAN
P63261

245

Actin, cytoplasmic 2



ACTH_HUMAN
P63267

246

Actin, gamma-enteric








smooth muscle



ACTK_HUMAN
Q9BYX7

245

Kappa-actin



ACTS_HUMAN
P68133

247

Actin, alpha skeletal muscle



A26CA_HUMAN
Q6S8J3

923
3
ANKRD26-like family C








member 1A



ACTB_HUMAN
P60709

223

Actin, cytoplasmic 1



ACTG_HUMAN
P63261

223

Actin, cytoplasmic 2



AASD1_HUMAN
Q9BTE6

81
1
Alanyl-tRNA synthetase








domain-containing protein 1



ABL1_HUMAN
P00519

940
1
Proto-oncogene tyrosine-








protein kinase ABL1



ABLM1_HUMAN
O14639

568
1
Actin-binding LIM protein 1



ACAP3_HUMAN
Q96P50

589
1
ArfGAP with coiled-coil,








ANK repeat and PH domain-








containing protein 3



ACINU_HUMAN
Q9UKV3

664
1
Apoptotic chromatin








condensation inducer in the








nucleus



ACINU_HUMAN
Q9UKV3

512
1
Apoptotic chromatin








condensation inducer in the








nucleus



ACINU_HUMAN
Q9UKV3

69
1
Apoptotic chromatin








condensation inducer in the








nucleus



ACINU_HUMAN
Q9UKV3

664
1
Apoptotic chromatin








condensation inducer in the








nucleus



ACOC_HUMAN
P21399

674
1
Cytoplasmic aconitate








hydratase



ACSL3_HUMAN
O95573

572
2
Long-chain-fatty-acid--CoA




O60488

563

ligase 3



ACSL4_HUMAN




Long-chain-fatty-acid--CoA








ligase 4



ACTA_HUMAN
P62736

54
6
Actin, aortic smooth muscle



ACTB_HUMAN
P60709

52

Actin, cytoplasmic 1



ACTC_HUMAN
P68032

54

Actin, alpha cardiac muscle 1



ACTG_HUMAN
P63261

52

Actin, cytoplasmic 2



ACTH_HUMAN
P63267

53

Actin, gamma-enteric








smooth muscle



ACTS_HUMAN
P68133

54

Actin, alpha skeletal muscle



ACTA_HUMAN
P62736

54
6
Actin, aortic smooth muscle



ACTB_HUMAN
P60709

52

Actin, cytoplasmic 1



ACTC_HUMAN
P68032

54

Actin, alpha cardiac muscle 1



ACTG_HUMAN
P63261

52

Actin, cytoplasmic 2



ACTH_HUMAN
P63267

53

Actin, gamma-enteric








smooth muscle



ACTS_HUMAN
P68133

54

Actin, alpha skeletal muscle



ACTB_HUMAN
P60709

155
2
Actin, cytoplasmic 1



ACTG_HUMAN
P63261

155

Actin, cytoplasmic 2



ACTB_HUMAN
P60709

158
2
Actin, cytoplasmic 1



ACTG_HUMAN
P63261

158

Actin, cytoplasmic 2



ACTN1_HUMAN
P12814

6
1
Alpha-actinin-1



ACTN1_HUMAN
P12814

6
1
Alpha-actinin-1



ACTN1_HUMAN
P12814

23
4
Alpha-actinin-1



ACTN2_HUMAN
P35609

30

Alpha-actinin-2



ACTN3_HUMAN
Q08043

37

Alpha-actinin-3



ACTN4_HUMAN
O43707

42

Alpha-actinin-4



ADDA_HUMAN
P35611

634
1
Alpha-adducin



AEBP2_HUMAN
Q6ZN18

234
1
Zinc finger protein AEBP2



AEDO_HUMAN
Q96SZ5

35
1
2-aminoethanethiol








dioxygenase



AF1L2_HUMAN
Q8N4X5

631
1
Actin filament-associated








protein 1-like 2



AF1L2_HUMAN
Q8N4X5

631
1
Actin filament-associated








protein 1-like 2



AF1L2_HUMAN
Q8N4X5

313
1
Actin filament-associated








protein 1-like 2



AFTIN_HUMAN
Q6ULP2

340
1
Aftiphilin



AGGF1_HUMAN
Q8N302

149
1
Angiogenic factor with G








patch and FHA domains 1



AGGF1_HUMAN
Q8N302

149
1
Angiogenic factor with G








patch and FHA domains 1



AGGF1_HUMAN
Q8N302

149
1
Angiogenic factor with G








patch and FHA domains 1



AHNK_HUMAN
Q09666

3719
1
Neuroblast differentiation-








associated protein AHNAK



AHNK_HUMAN
Q09666

1425
1
Neuroblast differentiation-








associated protein AHNAK



AHNK_HUMAN
Q09666

2712
1
Neuroblast differentiation-








associated protein AHNAK



AHNK_HUMAN
Q09666

3719
1
Neuroblast differentiation-








associated protein AHNAK



AHNK_HUMAN
Q09666

5581
1
Neuroblast differentiation-








associated protein AHNAK



AHNK_HUMAN
Q09666

576
1
Neuroblast differentiation-








associated protein AHNAK



AHNK_HUMAN
Q09666

3494
1
Neuroblast differentiation-








associated protein AHNAK



AHNK_HUMAN
Q09666

738
1
Neuroblast differentiation-








associated protein AHNAK



AHNK_HUMAN
Q09666

866
1
Neuroblast differentiation-








associated protein AHNAK



AHNK_HUMAN
Q09666

1584
1
Neuroblast differentiation-








associated protein AHNAK



AHNK_HUMAN
Q09666

740
1
Neuroblast differentiation-








associated protein AHNAK



AHNK_HUMAN
Q09666

3465
1
Neuroblast differentiation-








associated protein AHNAK



AHNK_HUMAN
Q09666

920
1
Neuroblast differentiation-








associated protein AHNAK



AHNK_HUMAN
Q09666

2883
1
Neuroblast differentiation-








associated protein AHNAK



AHNK_HUMAN
Q09666

4359
1
Neuroblast differentiation-








associated protein AHNAK



AHNK_HUMAN
Q09666

1169
1
Neuroblast differentiation-








associated protein AHNAK



AHSA1_HUMAN
O95433

255
1
Activator of 90 kDa heat








shock protein ATPase








homolog 1



AHSA1_HUMAN
O95433

255
1
Activator of 90 kDa heat








shock protein ATPase








homolog 1



AHSA1_HUMAN
O95433

19
1
Activator of 90 kDa heat








shock protein ATPase








homolog 1



AHTF1_HUMAN
Q8WYP5

1368
1
AT-hook-containing








transcription factor 1



AIM1_HUMAN
Q9Y4K1

68
1
Absent in melanoma 1








protein



AIM1_HUMAN
Q9Y4K1

68
1
Absent in melanoma 1








protein



AKA12_HUMAN
Q02952

452
1
A-kinase anchor protein 12



AKAP2_HUMAN
Q9Y2D5

473
1
A-kinase anchor protein 2



AKAP9_HUMAN
Q99996

1034
1
A-kinase anchor protein 9



AKAP9_HUMAN
Q99996

1034
1
A-kinase anchor protein 9



AKNA_HUMAN
Q7Z591

800
1
AT-hook-containing








transcription factor



AKP13_HUMAN
Q12802

545
1
A-kinase anchor protein 13



AKP13_HUMAN
Q12802

545
1
A-kinase anchor protein 13



AKP13_HUMAN
Q12802

830
1
A-kinase anchor protein 13



AKP13_HUMAN
Q12802

906
1
A-kinase anchor protein 13



AKP13_HUMAN
Q12802

1056
1
A-kinase anchor protein 13



AKP13_HUMAN
Q12802

1540
1
A-kinase anchor protein 13



AKP8L_HUMAN
Q9ULX6

109
1
A-kinase anchor protein 8-








like



ALMS1_HUMAN
Q8TCU4

428
1
Alstrom syndrome protein 1



ALMS1_HUMAN
Q8TCU4

780
1
Alstrom syndrome protein 1



ALMS1_HUMAN
Q8TCU4

591
1
Alstrom syndrome protein 1


 


2
ALO17_HUMAN
Q9HCF4
AVAEPANAVK
274
1
Protein ALO17


 


3
ALO17_HUMAN
Q9HCF4
AVAEPANAVKGA
274
1
Protein ALO17





GK





 


4
ALO17_HUMAN
Q9HCF4
AVAEPANAVKGA
274
1
Protein ALO17





GKEMK






AMPD3_HUMAN
Q01432

37
1
AMP deaminase 3



AMPM1_HUMAN
P53582

13
1
Methionine aminopeptidase 1



ANKH1_HUMAN
Q8IWZ3

1049
1
Ankyrin repeat and KH








domain-containing protein 1



ANKH1_HUMAN
Q8IWZ3

5
1
Ankyrin repeat and KH








domain-containing protein 1



ANKS6_HUMAN
Q68DC2

276
1
Ankyrin repeat and SAM








domain-containing protein 6



ANS1A_HUMAN
Q92625

530
1
Ankyrin repeat and SAM








domain-containing protein








1A



ANXA2_HUMAN
P07355

17
2
Annexin A2



AXA2L_HUMAN
A6NMY6

17

Putative annexin A2-like








protein



AP1G1_HUMAN
O43747

690
1
AP-1 complex subunit








gamma-1



AP1G2_HUMAN
O75843

632
1
AP-1 complex subunit








gamma-like 2



AP2A2_HUMAN
O94973

691
1
AP-2 complex subunit alpha-2



AP3B2_HUMAN
Q13367

844
1
AP-3 complex subunit beta-2



AP3B2_HUMAN
Q13367

844
1
AP-3 complex subunit beta-2



APBB2_HUMAN
Q92870

280
1
Amyloid beta A4 precursor








protein-binding family B








member 2



APC_HUMAN
P25054

1499
1
Adenomatous polyposis coli








protein



APMAP_HUMAN
Q9HDC9

23
1
Adipocyte plasma








membrane-associated protein



APTX_HUMAN
Q7Z2E3

142
1
Aprataxin



AR13B_HUMAN
Q3SXY8

242
1
ADP-ribosylation factor-like








protein 13B



ARBK1_HUMAN
P25098

528
1
Beta-adrenergic receptor








kinase 1



ARBK1_HUMAN
P25098

482
2
Beta-adrenergic receptor








kinase 1



ARBK2_HUMAN
P35626

482

Beta-adrenergic receptor








kinase 2



ARBK1_HUMAN
P25098

482
2
Beta-adrenergic receptor








kinase 1



ARBK2_HUMAN
P35626

482

Beta-adrenergic receptor








kinase 2



ARHG1_HUMAN
Q92888

293
1
Rho guanine nucleotide








exchange factor 1



ARHG2_HUMAN
Q92974

627
1
Rho guanine nucleotide








exchange factor 2



ARHGA_HUMAN
O15013

1247
1
Rho guanine nucleotide








exchange factor 10



ARI1A_HUMAN
O14497

607
1
AT-rich interactive domain-








containing protein 1A



ARI1A_HUMAN
O14497

607
1
AT-rich interactive domain-








containing protein 1A



ARI1A_HUMAN
O14497

76
1
AT-rich interactive domain-








containing protein 1A



ARI4A_HUMAN
P29374

1031
1
AT-rich interactive domain-








containing protein 4A



ARI4B_HUMAN
Q4LE39

1073
1
AT-rich interactive domain-








containing protein 4B



ARID2_HUMAN
Q68CP9

626
1
AT-rich interactive domain-








containing protein 2



ARID2_HUMAN
Q68CP9

630
1
AT-rich interactive domain-








containing protein 2



ARM10_HUMAN
Q8N2F6

87
1
Armadillo repeat-containing








protein 10



ARMC6_HUMAN
Q6NXE6

83
1
Armadillo repeat-containing








protein 6



ARMC6_HUMAN
Q6NXE6

83
1
Armadillo repeat-containing








protein 6



ARNT_HUMAN
P27540

152
1
Aryl hydrocarbon receptor








nuclear translocator



ARP21_HUMAN
Q9UBL0

495
1
cAMP-regulated








phosphoprotein 21



ARP2_HUMAN
P61160

162
1
Actin-related protein 2



ARP3_HUMAN
P61158

60
1
Actin-related protein 3



ARPC5_HUMAN
O15511

30
1
Actin-related protein 2/3








complex subunit 5



ARPC5_HUMAN
O15511

33
1
Actin-related protein 2/3








complex subunit 5



ARS2_HUMAN
Q9BXP5

162
1
Arsenite-resistance protein 2



ASB13_HUMAN
Q8WXK3

52
1
Ankyrin repeat and SOCS








box protein 13



ASCC1_HUMAN
Q8N9N2

35
1
Activating signal








cointegrator 1 complex








subunit 1



ASCC2_HUMAN
Q9H1I8

622
1
Activating signal








cointegrator 1 complex








subunit 2



ASHWN_HUMAN
Q9BVC5

106
1
Ashwin



ASPP2_HUMAN
Q13625

528
1
Apoptosis-stimulating of p53








protein 2



ATAD5_HUMAN
Q96QE3

285
1
ATPase family AAA








domain-containing protein 5



ATD2B_HUMAN
Q9ULI0

78
1
ATPase family AAA








domain-containing protein








2B



ATF1_HUMAN
P18846

47
1
Cyclic AMP-dependent








transcription factor ATF-1


 


5
ATF4_HUMAN
P18848
GLVSPSNNSKEDA
66
1
Cyclic AMP-dependent





FSGTDWMLEK


transcription factor ATF-4



ATF7_HUMAN
P17544

44
1
Cyclic AMP-dependent








transcription factor ATF-7



ATF7_HUMAN
P17544

44
1
Cyclic AMP-dependent








transcription factor ATF-7



ATG3_HUMAN
Q9NT62

105
1
Autophagy-related protein 3



ATG3_HUMAN
Q9NT62

105
1
Autophagy-related protein 3



ATG4B_HUMAN
Q9Y4P1

3
1
Cysteine protease ATG4B



ATRX_HUMAN
P46100

920
1
Transcriptional regulator








ATRX



ATX1L_HUMAN
P0C7T5

309
1
Ataxin-1-like



ATX2L_HUMAN
Q8WWM7

585
1
Ataxin-2-like protein



ATX2L_HUMAN
Q8WWM7

585
1
Ataxin-2-like protein



ATX2_HUMAN
Q99700

843
1
Ataxin-2


 


6
ATX3_HUMAN
P54252
GSGMLDEDEEDL
218
1
Ataxin-3





QR






AZI1_HUMAN
Q9UPN4

549
1
5-azacytidine-induced








protein 1



BA2D1_HUMAN
Q9Y520

889
1
BAT2 domain-containing








protein 1



BA2D1_HUMAN
Q9Y520

2190
1
BAT2 domain-containing








protein 1



BAP1_HUMAN
Q92560

312
1
Ubiquitin carboxyl-terminal








hydrolase BAP1



BAP31_HUMAN
P51572

165
1
B-cell receptor-associated








protein 31



BAP31_HUMAN
P51572

165
1
B-cell receptor-associated








protein 31



BASP_HUMAN
P80723

166
1
Brain acid soluble protein 1



BASP_HUMAN
P80723

172
1
Brain acid soluble protein 1



BAT3_HUMAN
P46379

1002
1
Large proline-rich protein








BAT3



BAT3_HUMAN
P46379

1002
1
Large proline-rich protein








BAT3



BAZ1A_HUMAN
Q9NRL2

500
1
Bromodomain adjacent to








zinc finger domain protein








1A


 


7
BCAP_HUMAN
Q6ZUJ8
SVTDTEPEDEK
149
1
Phosphoinositide 3-kinase








adapter protein 1


 


8
BCAP_HUMAN
Q6ZUJ8
SVTDTEPEDEKVV
149
1
Phosphoinositide 3-kinase





SYSK


adapter protein 1



BCLF1_HUMAN
Q9NYF8

325
1
Bcl-2-associated








transcription factor 1



BCLF1_HUMAN
Q9NYF8

383
1
Bcl-2-associated








transcription factor 1



BCR_HUMAN
P11274

244
1
Breakpoint cluster region








protein



BDP1_HUMAN
A6H8Y1

526
1
Transcription factor TFIIIB








component B′′ homolog



BID_HUMAN
P55957

76
1
BH3-interacting domain








death agonist



BIG3_HUMAN
Q5TH69

293
1
Brefeldin A-inhibited








guanine nucleotide-exchange








protein 3



BIN1_HUMAN
O00499

302
1
Myc box-dependent-








interacting protein 1



BIRC6_HUMAN
Q9NR09

462
1
Baculoviral IAP repeat-








containing protein 6



BL1S3_HUMAN
Q6QNY0

65
1
Biogenesis of lysosome-








related organelles complex 1








subunit 3


 


9
BLNK_HUMAN
Q8WV28
YVVPVEDNDENY
178
1
B-cell linker protein





IHPTESSSPPPEK






BNIP2_HUMAN
Q12982

84
1
BCL2/adenovirus E1B 19 kDa








protein-interacting








protein 2



BPTF_HUMAN
Q12830

1626
1
Nucleosome-remodeling








factor subunit BPTF



BRD1_HUMAN
O95696

922
1
Bromodomain-containing








protein 1



BRD4_HUMAN
O60885

338
1
Bromodomain-containing








protein 4



BRD8_HUMAN
Q9H0E9

561
1
Bromodomain-containing








protein 8



BTB14_HUMAN
Q96RE7

175
1
BTB/POZ domain-








containing protein 14B



BUB1_HUMAN
O43683

396
1
Mitotic checkpoint








serine/threonine-protein








kinase BUB1



BUB1_HUMAN
O43683

396
1
Mitotic checkpoint








serine/threonine-protein








kinase BUB1



BUD13_HUMAN
Q9BRD0

274
1
BUD13 homolog



C170L_HUMAN
Q96L14

51
1
Cep170-like protein



C1QBP_HUMAN
Q07021

186
1
Complement component 1 Q








sub component-binding








protein, mitochondrial



C2C2L_HUMAN
O14523

443
1
C2 domain-containing








protein 2-like



C2D1A_HUMAN
Q6P1N0

31
1
Coiled-coil and C2 domain-








containing protein 1A



C2D1A_HUMAN
Q6P1N0

31
1
Coiled-coil and C2 domain-








containing protein 1A



C2D1B_HUMAN
Q5T0F9

461
1
Coiled-coil and C2 domain-








containing protein 1B



CA059_HUMAN
Q5T8I9

14
1
UPF0486 protein C1orf59



CA059_HUMAN
Q5T8I9

14
1
UPF0486 protein C1orf59



CA103_HUMAN
Q5T3J3

516
1
Uncharacterized protein








C1orf103



CA103_HUMAN
Q5T3J3

516
1
Uncharacterized protein








C1orf103



CA163_HUMAN
Q96BR5

121
1
Hcp beta-lactamase-like








protein C1orf163



CA165_HUMAN
Q7L4P6

104
1
Coiled-coil domain-








containing protein C1orf165



CA170_HUMAN
Q5SV97

43
1
Uncharacterized protein








C1orf170



CA175_HUMAN
Q68CQ1

412
1
Uncharacterized protein








C1orf175



CA1L1_HUMAN
Q08AD1

422
1
Calmodulin-regulated








spectrin-associated protein 1-








like protein 1



CABL2_HUMAN
Q9BTV7

59
1
CDK5 and ABL1 enzyme








substrate 2



CACO1_HUMAN
Q9P1Z2

135
1
Calcium-binding and coiled-








coil domain-containing








protein 1



CADH2_HUMAN
P19022

800
1
Cadherin-2



CADH2_HUMAN
P19022

800
1
Cadherin-2



CAF1A_HUMAN
Q13111

615
1
Chromatin assembly factor 1








subunit A



CAF1A_HUMAN
Q13111

111
1
Chromatin assembly factor 1








subunit A



CAF1A_HUMAN
Q13111

111
1
Chromatin assembly factor 1








subunit A



CALR_HUMAN
P27797

259
1
Calreticulin



CALR_HUMAN
P27797

329
1
Calreticulin


 


10
CALR_HUMAN
P27797
MHGDSEYNIMFG
122
1
Calreticulin





PDICGPGTK






CAMKV_HUMAN
Q8NCB2

408
1
CaM kinase-like vesicle-








associated protein



CAMLG_HUMAN
P49069

10
1
Calcium signal-modulating








cyclophilin ligand



CAMLG_HUMAN
P49069

10
1
Calcium signal-modulating








cyclophilin ligand



CAMLG_HUMAN
P49069

116
1
Calcium signal-modulating








cyclophilin ligand



CAMP1_HUMAN
Q5T5Y3

752
1
Calmodulin-regulated








spectrin-associated protein 1



CAMP1_HUMAN
Q5T5Y3

1255
1
Calmodulin-regulated








spectrin-associated protein 1



CAMP1_HUMAN
Q5T5Y3

1255
1
Calmodulin-regulated








spectrin-associated protein 1



CAPR1_HUMAN
Q14444

95
1
Caprin-1



CAPZB_HUMAN
P47756

150
1
F-actin-capping protein








subunit beta



CASC3_HUMAN
O15234

390
1
Protein CASC3



CASC5_HUMAN
Q8NG31

1195
1
Protein CASC5



CASP3_HUMAN
P42574

29
1
Caspase-3



CASP3_HUMAN
P42574

176
1
Caspase-3



CASP3_HUMAN
P42574

176
1
Caspase-3



CASP7_HUMAN
P55210

199
1
Caspase-7



CASP_HUMAN
Q13948

388
2
Protein CASP



CUX1_HUMAN
P39880

377

Homeobox protein cut-like 1



CATB_HUMAN
P07858

78
1
Cathepsin B



CB044_HUMAN
Q9H6R7

509
1
WD repeat-containing








protein C2orf44



CBL_HUMAN
P22681

807
1
E3 ubiquitin-protein ligase








CBL



CBWD1_HUMAN
Q9BRT8

185
6
COBW domain-containing








protein 1



CBWD2_HUMAN
Q8IUF1

185

COBW domain-containing








protein 2



CBWD3_HUMAN
Q5JTY5

185

COBW domain-containing








protein 3



CBWD5_HUMAN
Q5RIA9

185

COBW domain-containing








protein 5



CBWD6_HUMAN
Q4V339

185

COBW domain-containing








protein 6



CBWD7_HUMAN
A6NM15

37

COBW domain-containing








protein 7



CC104_HUMAN
Q96G28

142
1
Coiled-coil domain-








containing protein 104


 


11
CC104_HUMAN
Q96G28
GSDVVSDLEHEE
142
1
Coiled-coil domain-





MK


containing protein 104



CC104_HUMAN
Q96G28

145
1
Coiled-coil domain-








containing protein 104



CC104_HUMAN
Q96G28

145
1
Coiled-coil domain-








containing protein 104



CC124_HUMAN
Q96CT7

150
1
Coiled-coil domain-








containing protein 124



CC131_HUMAN
O60293

336
1
Coiled-coil domain-








containing protein 131


 


12
CC50A_HUMAN
Q9NV96
GGPPCAPGGTAK
13
1
Cell cycle control protein








50A



CCD43_HUMAN
Q96MW1

17
1
Coiled-coil domain-








containing protein 43



CCD53_HUMAN
Q9Y3C0

5
1
Coiled-coil domain-








containing protein 53



CCD91_HUMAN
Q7Z6B0

100
1
Coiled-coil domain-








containing protein 91



CCD97_HUMAN
Q96F63

53
1
Coiled-coil domain-








containing protein 97



CCDC9_HUMAN
Q9Y3X0

300
1
Coiled-coil domain-








containing protein 9



CCDC9_HUMAN
Q9Y3X0

300
1
Coiled-coil domain-








containing protein 9



CCNT2_HUMAN
O60583

455
1
Cyclin-T2



CCNT2_HUMAN
O60583

455
1
Cyclin-T2



CD2L1_HUMAN
P21127

406
1
PITSLRE serine/threonine-








protein kinase CDC2L1



CD2L1_HUMAN
P21127

406
1
PITSLRE serine/threonine-








protein kinase CDC2L1



CD2L5_HUMAN
Q14004

1354
1
Cell division cycle 2-like








protein kinase 5



CDC27_HUMAN
P30260

237
1
Cell division cycle protein 27








homolog



CDC27_HUMAN
P30260

244
1
Cell division cycle protein 27








homolog



CDC5L_HUMAN
Q99459

392
1
Cell division cycle 5-like








protein



CDCA7_HUMAN
Q9BWT1

40
1
Cell division cycle-








associated protein 7



CDV3_HUMAN
Q9UKY7

123
1
Protein CDV3 homolog


 


13
CDYL1_HUMAN
Q9Y232
GFQSESPEKLDPV
211
1
Chromodomain Y-like





EQGQEDTVAPEV


protein





AAEKPVGALLGP








GAER






CE022_HUMAN
Q49AR2

197
1
UPF0489 protein C5orf22



CE152_HUMAN
O94986

63
1
Centrosomal protein of 152 kDa



CE170_HUMAN
Q5SW79

1325
1
Centrosomal protein of 170 kDa



CE170_HUMAN
Q5SW79

1325
1
Centrosomal protein of 170 kDa



CE170_HUMAN
Q5SW79

937
1
Centrosomal protein of 170 kDa



CEBPZ_HUMAN
Q03701

918
1
CCAAT/enhancer-binding








protein zeta



CEBPZ_HUMAN
Q03701

775
1
CCAAT/enhancer-binding








protein zeta



CEBPZ_HUMAN
Q03701

956
1
CCAAT/enhancer-binding








protein zeta



CH041_HUMAN
Q6NXR4

5
1
Uncharacterized protein








C8orf41



CH082_HUMAN
Q6P1X6

26
1
UPF0598 protein C8orf82



CH60_HUMAN
P10809

505
1
60 kDa heat shock protein,








mitochondrial



CH60_HUMAN
P10809

112
1
60 kDa heat shock protein,








mitochondrial



CH60_HUMAN
P10809

453
1
60 kDa heat shock protein,








mitochondrial



CH60_HUMAN
P10809

453
1
60 kDa heat shock protein,








mitochondrial



CHD3_HUMAN
Q12873

373
3
Chromodomain-helicase-








DNA-binding protein 3



CHD4_HUMAN
Q14839

364

Chromodomain-helicase-








DNA-binding protein 4



CHD5_HUMAN
Q8TDI0

337

Chromodomain-helicase-








DNA-binding protein 5


 


14
CHD4_HUMAN
Q14839
GGGDNKEGEDSS
1234
1
Chromodomain-helicase-





VIHYDDK


DNA-binding protein 4


 


15
CHD4_HUMAN
Q14839
GGGDNKEGEDSS
1234
1
Chromodomain-helicase-





VIHYDDKAIER


DNA-binding protein 4


 


16
CHD7_HUMAN
Q9P2D1
GFYMEDGDPSVA
2286
1
Chromodomain-helicase-





QLLHER


DNA-binding protein 7


 


17
CHM4B_HUMAN
Q9H444
GTLSTIEFQR
84
3
Charged multivesicular body








protein 4b


17
CHM4C_HUMAN
Q96CF2
GTLSTIEFQR
84

Charged multivesicular body








protein 4c



CI080_HUMAN
Q9NRY2

58
1
Uncharacterized protein








C9orf80



CJ018_HUMAN
Q5VWN6

1208
1
Uncharacterized protein








C10orf18



CJ047_HUMAN
Q86WR7

110
1
Uncharacterized protein








C10orf47



CK059_HUMAN
Q6IAA8

73
1
UPF0404 protein C11orf59



CK059_HUMAN
Q6IAA8

73
1
UPF0404 protein C11orf59



CL035_HUMAN
Q9HCM1

360
1
Uncharacterized protein








C12orf35



CL035_HUMAN
Q9HCM1

502
1
Uncharacterized protein








C12orf35



CL043_HUMAN
Q96C57

73
1
Uncharacterized protein








C12orf43



CL043_HUMAN
Q96C57

205
1
Uncharacterized protein








C12orf43



CL043_HUMAN
Q96C57

205
1
Uncharacterized protein








C12orf43



CL043_HUMAN
Q96C57

205
1
Uncharacterized protein








C12orf43



CLAP1_HUMAN
Q7Z460

1219
1
CLIP-associating protein 1



CLAP1_HUMAN
Q7Z460

1219
1
CLIP-associating protein 1



CLCA_HUMAN
P09496

77
1
Clathrin light chain A



CLCA_HUMAN
P09496

77
1
Clathrin light chain A



CLCA_HUMAN
P09496

93
1
Clathrin light chain A



CLIC1_HUMAN
O00299

142
1
Chloride intracellular








channel protein 1



CLIP1_HUMAN
P30622

398
1
CAP-Gly domain-containing








linker protein 1



CLSPN_HUMAN
Q9HAW4

564
1
Claspin



CND2_HUMAN
Q15003

200
1
Condensin complex subunit 2


 


18
CND2_HUMAN
Q15003
GSLGDDFDANDE
367
1
Condensin complex subunit 2





PDHTAVGDHEEFR






CND2_HUMAN
Q15003

381
1
Condensin complex subunit 2



CND2_HUMAN
Q15003

171
1
Condensin complex subunit 2



CND2_HUMAN
Q15003

200
1
Condensin complex subunit 2



CNDH2_HUMAN
Q6IBW4

460
1
Condensin-2 complex








subunit H2



CO6A3_HUMAN
P12111

2616
1
Collagen alpha-3(VI) chain



COBL1_HUMAN
Q53SF7

984
1
Cordon-bleu protein-like 1


 


19
COPA_HUMAN
P53621
GFVEATEGLGDD
857
1
Coatomer subunit alpha





ALGK





 


20
COPA_HUMAN
P53621
LFGTTDAVVK
189
1
Coatomer subunit alpha



COPB2_HUMAN
P35606

855
1
Coatomer subunit beta′



COR1A_HUMAN
P31146

395
2
Coronin-1A



CP088_HUMAN
Q1ED39

183
1
Protein C16orf88



CP110_HUMAN
Q7Z7A1

1396
1
Centriolin



CP110_HUMAN
Q7Z7A1

802
1
Centriolin



CPIN1_HUMAN
Q6FI81

215
1
Anamorsin



CPNE1_HUMAN
Q99829

465
1
Copine-1



CPNE3_HUMAN
O75131

429
1
Copine-3



CPSF6_HUMAN
Q16630

55
1
Cleavage and








polyadenylation specificity








factor subunit 6



CPSF7_HUMAN
Q8N684

325
1
Cleavage and








polyadenylation specificity








factor subunit 7



CPSF7_HUMAN
Q8N684

30
1
Cleavage and








polyadenylation specificity








factor subunit 7



CPSF7_HUMAN
Q8N684

34
1
Cleavage and








polyadenylation specificity








factor subunit 7



CPZIP_HUMAN
Q6JBY9

273
1
Capz-interacting protein



CQ056_HUMAN
Q96N21

381
1
Uncharacterized protein








C17orf56



CQ085_HUMAN
Q53F19

158
1
Uncharacterized protein








C17orf85



CQ085_HUMAN
Q53F19

232
1
Uncharacterized protein








C17orf85



CR025_HUMAN
Q96B23

45
1
Uncharacterized protein








C18orf25



CR025_HUMAN
Q96B23

45
1
Uncharacterized protein








C18orf25



CR025_HUMAN
Q96B23

45
1
Uncharacterized protein








C18orf25


 


21
CR025_HUMAN
Q96B23
GVADSTVISSMPC
45
1
Uncharacterized protein





LLMELR


C18orf25


 


22
CR025_HUMAN
Q96B23
GVADSTVISSMPC
45
1
Uncharacterized protein





LLMELRR


C18orf25



CREB1_HUMAN
P16220

230
1
cAMP response element-








binding protein



CREB1_HUMAN
P16220

117
1
cAMP response element-








binding protein



CREB1_HUMAN
P16220

117
1
cAMP response element-








binding protein



CROCC_HUMAN
Q5TZA2

579
1
Rootletin



CS043_HUMAN
Q9BQ61

63
1
Uncharacterized protein








C19orf43



CS044_HUMAN
Q9H6X5

369
1
Uncharacterized protein








C19orf44



CSN1_HUMAN
Q13098

95
1
COP9 signalosome complex








subunit 1



CSRN2_HUMAN
Q9H175

40
1
Cysteine/serine-rich nuclear








protein 2



CSTF3_HUMAN
Q12996

577
1
Cleavage stimulation factor








77 kDa subunit



CTBL1_HUMAN
Q8WYA6

67
1
Beta-catenin-like protein 1



CTCF_HUMAN
P49711

47
1
Transcriptional repressor








CTCF



CTCF_HUMAN
P49711

47
1
Transcriptional repressor








CTCF



CTCF_HUMAN
P49711

47
1
Transcriptional repressor








CTCF



CTNB1_HUMAN
P35222

116
1
Catenin beta-1



CTND1_HUMAN
O60716

162
1
Catenin delta-1



CTR9_HUMAN
Q6PD62

1121
1
RNA polymerase-associated








protein CTR9 homolog



CUL4B_HUMAN
Q13620

26
1
Cullin-4B



CUTC_HUMAN
Q9NTM9

34
1
Copper homeostasis protein








cutC homolog



CUX1_HUMAN
P39880

1340
1
Homeobox protein cut-like 1


 


23
CYB5B_HUMAN
O43169
GKGQEVETSVTY
11
1
Cytochrome b5 type B





YR






DBPA_HUMAN
P16989

270
1
DNA-binding protein A



DBPA_HUMAN
P16989

162
1
DNA-binding protein A



DBPA_HUMAN
P16989

145
1
DNA-binding protein A



DBPA_HUMAN
P16989

138
3
DNA-binding protein A



YBOX1_HUMAN
P67809

106

Nuclease-sensitive element-








binding protein 1



YBOX2_HUMAN
Q9Y2T7

141

Y-box-binding protein 2



DCNL2_HUMAN
Q6PH85

43
1
DCN1-like protein 2



DCTN1_HUMAN
Q14203

303
1
Dynactin subunit 1



DD19A_HUMAN
Q9NUU7

5
1
ATP-dependent RNA








helicase DDX19A



DDX1_HUMAN
Q92499

440
1
ATP-dependent RNA








helicase DDX1


 


24
DDX24_HUMAN
Q9GZR7
ALPDDTVIESEAL
297
1
ATP-dependent RNA





PSDIAAEAR


helicase DDX24



DDX46_HUMAN
Q7L014

872
1
Probable ATP-dependent








RNA helicase DDX46



DDX46_HUMAN
Q7L014

923
1
Probable ATP-dependent








RNA helicase DDX46



DDX46_HUMAN
Q7L014

872
1
Probable ATP-dependent








RNA helicase DDX46



DDX46_HUMAN
Q7L014

872
1
Probable ATP-dependent








RNA helicase DDX46


 


25
DDX59_HUMAN
Q5T1V6
AVATEAATIDR
44
1
Probable ATP-dependent








RNA helicase DDX59



DESM_HUMAN
P17661

265
1
Desmin



DESM_HUMAN
P17661

265
1
Desmin



DFFA_HUMAN
O00273

7
1
DNA fragmentation factor








subunit alpha



DFFA_HUMAN
O00273

222
1
DNA fragmentation factor








subunit alpha



DFFA_HUMAN
O00273

222
1
DNA fragmentation factor








subunit alpha


 


26
DGCR8_HUMAN
Q8WYQ5
ALLEEGLCAPK
249
1
Protein DGCR8



DGCR8_HUMAN
Q8WYQ5

397
1
Protein DGCR8


 


27
DGCR8_HUMAN
Q8WYQ5
SMGADPGPPDEK
397
1
Protein DGCR8





DPLGAEAAPGAL








GQVK





 


28
DGCR8_HUMAN
Q8WYQ5
SMGADPGPPDEK
397
1
Protein DGCR8





DPLGAEAAPGAL








GQVKAK






DGKH_HUMAN
Q86XP1

583
1
Diacylglycerol kinase eta


 


29
DGKH_HUMAN
Q86XP1
SVPGPAVAASKE
699
1
Diacylglycerol kinase eta





NLPVLNTR






DGLB_HUMAN
Q8NCG7

549
1
Sn1-specific diacylglycerol








lipase beta



DHAK_HUMAN
Q3LXA3

363
1
Dihydroxyacetone kinase



DHAK_HUMAN
Q3LXA3

363
1
Dihydroxyacetone kinase



DHX30_HUMAN
Q7L2E3

207
1
Putative ATP-dependent








RNA helicase DHX30



DHX37_HUMAN
Q8IY37

574
1
Probable ATP-dependent








RNA helicase DHX37



DHX9_HUMAN
Q08211

168
1
ATP-dependent RNA








helicase A



DHX9_HUMAN
Q08211

97
1
ATP-dependent RNA








helicase A



DHX9_HUMAN
Q08211

97
1
ATP-dependent RNA








helicase A



DIAP1_HUMAN
O60610

649
1
Protein diaphanous homolog 1



DIDO1_HUMAN
Q9BTC0

1251
1
Death-inducer obliterator 1



DIDO1_HUMAN
Q9BTC0

1519
1
Death-inducer obliterator 1



DIDO1_HUMAN
Q9BTC0

1353
1
Death-inducer obliterator 1



DIDO1_HUMAN
Q9BTC0

1353
1
Death-inducer obliterator 1



DIDO1_HUMAN
Q9BTC0

988
1
Death-inducer obliterator 1



DLG1_HUMAN
Q12959

413
1
Disks large homolog 1



DNJC7_HUMAN
Q99615

9
1
DnaJ homolog subfamily C








member 7



DNJC7_HUMAN
Q99615

9
1
DnaJ homolog subfamily C








member 7


 


30
DNJC7_HUMAN
Q99615
VVMAATEPELLD
9
1
DnaJ homolog subfamily C





DQEAK


member 7


 


31
DNJC7_HUMAN
Q99615
VVMAATEPELLD
9
1
DnaJ homolog subfamily C





DQEAKR


member 7



DNM1L_HUMAN
O00429

580
1
Dynamin-1-like protein



DNM1L_HUMAN
O00429

504
1
Dynamin-1-like protein



DNM1L_HUMAN
O00429

504
1
Dynamin-1-like protein



DNM1L_HUMAN
O00429

504
1
Dynamin-1-like protein



DNM1L_HUMAN
O00429

504
1
Dynamin-1-like protein


 


32
DNM3A_HUMAN
Q9Y6K1
MWVEPEAAAYAP
439
1
DNA (cytosine-5)-





PPPAKKPR


methyltransferase 3A



DOC10_HUMAN
Q96BY6

328
1
Dedicator of cytokinesis








protein 10


 


33
DOHH_HUMAN
Q9BU89
AIGQTLVDPK
9
1
Deoxyhypusine hydroxylase


 


34
DOHH_HUMAN
Q9BU89
AIGQTLVDPKQPL
9
1
Deoxyhypusine hydroxylase





QAR






DOT1L_HUMAN
Q8TEK3

1334
1
Histone-lysine N-








methyltransferase, H3 lysine-








79 specific


 


35
DP13A_HUMAN
Q9UKG1
SLVAPDTPIQFDII
445
1
DCC-interacting protein 13-





SPVCEDQPGQAK


alpha


 


36
DPOD1_HUMAN
P28340
HYVGPAQPVPGG
103
1
DNA polymerase delta





PPPSR


catalytic subunit


 


37
DPOD1_HUMAN
P28340
HYVGPAQPVPGG
103
1
DNA polymerase delta





PPPSRGSVPVLR


catalytic subunit


 


38
DPOLA_HUMAN
P09884
GIGYVEDGR
84
1
DNA polymerase alpha








catalytic subunit



DPP9_HUMAN
Q86TI2

14
1
Dipeptidyl peptidase 9



DPYL4_HUMAN
O14531

457
1
Dihydropyrimidinase-related








protein 4



DREB_HUMAN
Q16643

341
1
Drebrin



DREB_HUMAN
Q16643

478
1
Drebrin



DSRAD_HUMAN
P55265

215
1
Double-stranded RNA-








specific adenosine deaminase



DTL_HUMAN
Q9NZJ0

579
1
Denticleless protein homolog



DTL_HUMAN
Q9NZJ0

579
1
Denticleless protein homolog



DTX3L_HUMAN
Q8TDB6

218
1
Protein deltex-3-like



DYHC1_HUMAN
Q14204

4368
1
Cytoplasmic dynein 1 heavy








chain 1



DYHC1_HUMAN
Q14204

4221
1
Cytoplasmic dynein 1 heavy








chain 1



E400N_HUMAN
Q6ZTU2

184
2
EP400 N-terminal-like








protein



EP400_HUMAN
Q96L91

195

E1A-binding protein p400



E41L2_HUMAN
O43491

913
1
Band 4.1-like protein 2



EAP1_HUMAN
Q9H1B7

133
1
Enhanced at puberty protein 1



EBP2_HUMAN
Q99848

212
1
Probable rRNA-processing








protein EBP2



ECE1_HUMAN
P42892

34
1
Endothelin-converting








enzyme 1


 


39
ECT2_HUMAN
Q9H8V3
GCPANLLSSHR
629
1
Protein ECT2



EDC4_HUMAN
Q6P2E9

797
1
Enhancer of mRNA-








decapping protein 4



EDC4_HUMAN
Q6P2E9

663
1
Enhancer of mRNA-








decapping protein 4



EDC4_HUMAN
Q6P2E9

663
1
Enhancer of mRNA-








decapping protein 4



EDC4_HUMAN
Q6P2E9

491
1
Enhancer of mRNA-








decapping protein 4



EDC4_HUMAN
Q6P2E9

486
1
Enhancer of mRNA-








decapping protein 4


 


40
EDC4_HUMAN
Q6P2E9
SLGADGTHGAGA
486
1
Enhancer of mRNA-





MESAAGVLIK


decapping protein 4



EDC4_HUMAN
Q6P2E9

58
1
Enhancer of mRNA-








decapping protein 4


 


41
EDRF1_HUMAN
Q3B7T1
SVGNDVDVVSDS
116
1
Erythroid differentiation-





ENIK


related factor 1


 


42
EDRF1_HUMAN
Q3B7T1
SVGNDVDVVSDS
116
1
Erythroid differentiation-





ENIKK


related factor 1


 


43
EEA1_HUMAN
Q15075
SSAELQSLEQQLE
133
1
Early endosome antigen 1





EAQTENFNIK





 


44
EEA1_HUMAN
Q15075
GLVTDSSAELQSL
128
1
Early endosome antigen 1





EQQLEEAQTENF








NIK






EF1A1_HUMAN
P68104

399
2
Elongation factor 1-alpha 1



EF1A3_HUMAN
Q5VTE0

399

Putative elongation factor 1-








alpha-like 3



EF1A1_HUMAN
P68104

404
2
Elongation factor 1-alpha 1



EF1A3_HUMAN
Q5VTE0

404

Putative elongation factor 1-








alpha-like 3



EF1A1_HUMAN
P68104

404
2
Elongation factor 1-alpha 1



EF1A3_HUMAN
Q5VTE0

404

Putative elongation factor 1-








alpha-like 3



EF1A1_HUMAN
P68104

200
2
Elongation factor 1-alpha 1



EF1A3_HUMAN
Q5VTE0

200

Putative elongation factor 1-








alpha-like 3



EF1A1_HUMAN
P68104

234
2
Elongation factor 1-alpha 1



EF1A3_HUMAN
Q5VTE0

234

Putative elongation factor 1-








alpha-like 3



EF1A1_HUMAN
P68104

404
2
Elongation factor 1-alpha 1



EF1A3_HUMAN
Q5VTE0

404

Putative elongation factor 1-








alpha-like 3


 


45
EF1B_HUMAN
P24534
LFGSDDEEESEEA
103
1
Elongation factor 1-beta





KR





 


46
EF1B_HUMAN
P24534
LFGSDDEEESEEAK
103
1
Elongation factor 1-beta



EF1D_HUMAN
P29692

159
1
Elongation factor 1-delta



EF1D_HUMAN
P29692

159
1
Elongation factor 1-delta



EF2_HUMAN
P13639

612
1
Elongation factor 2


 


47
EH1L1_HUMAN
Q8N3D4
SQQPPGGSSPSEE
1330
1
EH domain-binding protein





PPPSPGEEAGLQR


1-like protein 1



EHBP1_HUMAN
Q8NDI1

275
1
EH domain-binding protein 1



EHD1_HUMAN
Q9H4M9

416
1
EH domain-containing








protein 1



EHMT1_HUMAN
Q9H9B1

330
1
Histone-lysine N-








methyltransferase, H3 lysine-








9 specific 5



EHMT1_HUMAN
Q9H9B1

482
1
Histone-lysine N-








methyltransferase, H3 lysine-








9 specific 5



EHMT2_HUMAN
Q96KQ7

454
1
Histone-lysine N-








methyltransferase, H3 lysine-








9 specific 3



EIF3B_HUMAN
P55884

4
1
Eukaryotic translation








initiation factor 3 subunit B



EIF3B_HUMAN
P55884

185
1
Eukaryotic translation








initiation factor 3 subunit B



EIF3G_HUMAN
O75821

8
1
Eukaryotic translation








initiation factor 3 subunit G


 


48
EIF3J_HUMAN
O75822
NWDDDDDEKKE
51
1
Eukaryotic translation





EAEVKPEVK


initiation factor 3 subunit J



ELF1_HUMAN
P32519

146
1
ETS-related transcription








factor Elf-1


 


49
ELF1_HUMAN
P32519
GIPEVMETQQVQ
146
1
ETS-related transcription





EK


factor Elf-1



ENOA_HUMAN
P06733

204
1
Alpha-enolase



ENPL_HUMAN
P14625

60
1
Endoplasmin



ENPL_HUMAN
P14625

29
1
Endoplasmin



ENPL_HUMAN
P14625

29
1
Endoplasmin



EP15R_HUMAN
Q9UBC2

570
1
Epidermal growth factor








receptor substrate 15-like 1



EP15_HUMAN
P42566

619
1
Epidermal growth factor








receptor substrate 15



EPC1_HUMAN
Q9H2F5

28
1
Enhancer of polycomb








homolog 1



EPN1_HUMAN
Q9Y6I3

461
1
Epsin-1



EPN2_HUMAN
O95208

340
1
Epsin-2



ERC6L_HUMAN
Q2NKX8

802
1
DNA excision repair protein








ERCC-6-like



ERCC6_HUMAN
Q03468

53
1
DNA excision repair protein








ERCC-6



ERF3A_HUMAN
P15170

40
1
Eukaryotic peptide chain








release factor GTP-binding








subunit ERF3A



ERF3A_HUMAN
P15170

40
1
Eukaryotic peptide chain








release factor GTP-binding








subunit ERF3A



ERF3A_HUMAN
P15170

40
1
Eukaryotic peptide chain








release factor GTP-binding








subunit ERF3A


 


50
ERF3A_HUMAN
P15170
GRPPEESAHEMM
40
1
Eukaryotic peptide chain





EEEEEIPKPK


release factor GTP-binding








subunit ERF3A


 


51
ERF_HUMAN
P50548
GTSELEEPLGEDPR
192
1
ETS domain-containing








transcription factor ERF



ERIC1_HUMAN
Q86X53

277
1
Glutamate-rich protein 1



ESYT2_HUMAN
A0FGR8

760
1
Extended synaptotagmin-2



ETUD1_HUMAN
Q7Z2Z2

933
1
Elongation factor Tu GTP-








binding domain-containing








protein 1



ETUD1_HUMAN
Q7Z2Z2

933
1
Elongation factor Tu GTP-








binding domain-containing








protein 1



EXDL2_HUMAN
Q9NVH0

199
1
Exonuclease 3′-5′ domain-








like-containing protein 2


 


52
F101B_HUMAN
Q8N5W9
AAAATPAAPSPAS
62
1
Protein FAM101B





LPLAPGCALR






F107B_HUMAN
Q9H098

6
1
Protein FAM107B


 


53
F117B_HUMAN
Q6P1L5
GHRAPPPLVQR
375
1
Protein FAM117B


 


54
F125A_HUMAN
Q96EY5
AASQPSKGGLLER
173
1
Protein FAM125A



F169A_HUMAN
Q9Y6X4

447
1
UPF0611 protein FAM169A



FA13A_HUMAN
O94988

595
1
Protein FAM13A1



FA13A_HUMAN
O94988

595
1
Protein FAM13A1



FA21A_HUMAN
Q641Q2

1135
4
Protein FAM21A



FA21B_HUMAN
Q5SNT6

1047

Protein FAM21B



FA21C_HUMAN
Q9Y4E1

1114

Protein FAM21C



FA21D_HUMAN
Q5SRD0

102

Protein FAM21D



FA29A_HUMAN
Q7Z4H7

569
1
Protein FAM29A


 


55
FA44A_HUMAN
Q8NFC6
GLMATTASGDIT
2045
1
Protein FAM44A





NQNSLAGGKNQGK






FA44A_HUMAN
Q8NFC6

1484
1
Protein FAM44A



FA44A_HUMAN
Q8NFC6

2045
1
Protein FAM44A



FA44A_HUMAN
Q8NFC6

2045
1
Protein FAM44A



FA44A_HUMAN
Q8NFC6

2045
1
Protein FAM44A



FA44A_HUMAN
Q8NFC6

1709
1
Protein FAM44A



FAS_HUMAN
P49327

1166
1
Fatty acid synthase



FETUA_HUMAN
P02765

134
1
Alpha-2-HS-glycoprotein



FIP1_HUMAN
Q6UN15

159
1
Pre-mRNA 3′-end-processing








factor FIP1



FKB15_HUMAN
Q5T1M5

307
1
FK506-binding protein 15



FKB15_HUMAN
Q5T1M5

307
1
FK506-binding protein 15



FLI1_HUMAN
Q01543

21
1
Friend leukemia integration 1








transcription factor


 


56
FLNA_HUMAN
P21333
GSPVPSSPFQVPV
1337
1
Filamin-A





TEGCDPSR





 


57
FLNA_HUMAN
P21333
GSPVPSSPFQVPV
1337
1
Filamin-A





TEGCDPSRVR






FLNA_HUMAN
P21333

2537
1
Filamin-A



FLNA_HUMAN
P21333

26
1
Filamin-A



FLNA_HUMAN
P21333

1505
1
Filamin-A


 


58
FLNA_HUMAN
P21333
GVPVPGSPFPLEA
1049
1
Filamin-A





VAPTKPSK





 


59
FLNA_HUMAN
P21333
GVPVPGSPFPLEA
1049
1
Filamin-A





VAPTKPSKVK





 


60
FLNA_HUMAN
P21333
GVPVPGSPFPLEA
1049
1
Filamin-A





VAPTKPSKVKAF








GPGLQGGSAGSP








AR






FLNA_HUMAN
P21333

35
3
Filamin-A



FLNB_HUMAN
O75369

8

Filamin-B



FLNC_HUMAN
Q14315

28

Filamin-C



FLNB_HUMAN
O75369

479
1
Filamin-B



FLNB_HUMAN
O75369

1022
1
Filamin-B



FLNB_HUMAN
O75369

1477
1
Filamin-B



FLNB_HUMAN
O75369

1477
1
Filamin-B



FNBP1_HUMAN
Q96RU3

520
1
Formin-binding protein 1



FNBP1_HUMAN
Q96RU3

520
1
Formin-binding protein 1



FNBP4_HUMAN
Q8N3X1

154
1
Formin-binding protein 4



FNBP4_HUMAN
Q8N3X1

426
1
Formin-binding protein 4



FNBP4_HUMAN
Q8N3X1

778
1
Formin-binding protein 4



FOXJ2_HUMAN
Q9P0K8

213
1
Forkhead box protein J2


 


61
FOXK1_HUMAN
P85037
SAVAGAAPALVA
81
1
Forkhead box protein K1





AAAASVR






FOXO3_HUMAN
O43524

55
1
Forkhead box protein O3


 


62
FOXP4_HUMAN
Q8IVH2
GLVHPPTSAAAPV
407
1
Forkhead box protein P4





TPLRPPGLGSASL








HGGGPAR






FRAP_HUMAN
P42345

2460
1
FKBP12-rapamycin








complex-associated protein



FRAP_HUMAN
P42345

2460
1
FKBP12-rapamycin








complex-associated protein



FRYL_HUMAN
O94915

1513
1
Protein furry homolog-like



FUBP1_HUMAN
Q96AE4

182
1
Far upstream element-








binding protein 1



FUBP1_HUMAN
Q96AE4

84
1
Far upstream element-








binding protein 1



FUBP1_HUMAN
Q96AE4

140
2
Far upstream element-








binding protein 1



FUBP2_HUMAN
Q92945

184

Far upstream element-








binding protein 2


 


63
FUBP2_HUMAN
Q92945
SISSQLGPIHPPPR
129
1
Far upstream element-








binding protein 2


 


64
FUBP3_HUMAN
Q96I24
SNSTIQEILIPASK
160
1
Far upstream element-








binding protein 3



FUBP3_HUMAN
Q96I24

35
1
Far upstream element-








binding protein 3


 


65
FUS_HUMAN
P35637
GKEFSGNPIKVSF
356
1
RNA-binding protein FUS





ATR





 


66
FUS_HUMAN
P35637
GKEFSGNPIK
356
1
RNA-binding protein FUS



FXR2_HUMAN
P51116

562
1
Fragile X mental retardation








syndrome-related protein 2



FYB_HUMAN
O15117

656
1
FYN-binding protein


 


67
FYB_HUMAN
O15117
GAGNLDEEQDSE
447
1
FYN-binding protein





GETYEDIEASK





 


68
FYB_HUMAN
O15117
GAGNLDEEQDSE
447
1
FYN-binding protein





GETYEDIEASKER






FYN_HUMAN
P06241

20
1
Proto-oncogene tyrosine-








protein kinase Fyn



FYTD1_HUMAN
Q96QD9

327
2
Forty-two-three domain-








containing protein 1



THOC4_HUMAN
Q86V81



THO complex subunit 4



FYV1_HUMAN
Q9Y2I7

1608
1
FYVE finger-containing








phosphoinositide kinase



FYV1_HUMAN
Q9Y2I7

1608
1
FYVE finger-containing








phosphoinositide kinase



FYV1_HUMAN
Q9Y2I7

990
1
FYVE finger-containing








phosphoinositide kinase



G3P_HUMAN
P04406

90
1
Glyceraldehyde-3-phosphate








dehydrogenase



GABP1_HUMAN
Q06547

304
1
GA-binding protein subunit








beta-1



GABP1_HUMAN
Q06547

304
1
GA-binding protein subunit








beta-1



GABP2_HUMAN
Q8TAK5

305
1
GA-binding protein subunit








beta-2



GALT_HUMAN
P07902

19
1
Galactose-1-phosphate








uridylyltransferase


 


69
GAPD1_HUMAN
Q14C86
SASQAAHPQDSA
1103
1
GTPase-activating protein





FSYR


and VPS9 domain-containing








protein 1


 


70
GAPD1_HUMAN
Q14C86
SASQAAHPQDSA
1103
1
GTPase-activating protein





FSYRDAK


and VPS9 domain-containing








protein 1



GATA2_HUMAN
P23769

47
1
Endothelial transcription








factor GATA-2


 


71
GBF1_HUMAN
Q92538
SASVHDMDYVNPR
369
1
Golgi-specific brefeldin A-








resistance guanine nucleotide








exchange factor 1



GBF1_HUMAN
Q92538
SASVHDMDYVNPR
369
1
Golgi-specific brefeldin A-








resistance guanine nucleotide








exchange factor 1



GCFC_HUMAN
Q9Y5B6

222
1
GC-rich sequence DNA-








binding factor homolog



GCP2_HUMAN
Q9BSJ2

773
1
Gamma-tubulin complex








component 2



GCP60_HUMAN
Q9H3P7

16
1
Golgi resident protein








GCP60


 


72
GCP60_HUMAN
Q9H3P7
SSEKELEPEAAEE
344
1
Golgi resident protein





ALENGPK


GCP60



GDIR2_HUMAN
P52566

20
1
Rho GDP-dissociation








inhibitor 2



GDIR2_HUMAN
P52566

20
1
Rho GDP-dissociation








inhibitor 2



GDIR2_HUMAN
P52566

56
1
Rho GDP-dissociation








inhibitor 2



GELS_HUMAN
P06396

640
1
Gelsolin


 


73
GELS_HUMAN
P06396
GLGLSYLSSHIAN
404
1
Gelsolin





VER





 


74
GEMI5_HUMAN
Q8TEQ6
TASTEETDPETSQ
1320
1
Gem-associated protein 5





PEPNRPSELDLR






GEMI8_HUMAN
Q9NWZ8

170
1
Gem-associated protein 8



GEN_HUMAN
Q17RS7

624
1
Flap endonuclease GEN








homolog 1



GFPT1_HUMAN
Q06210

261
1
Glucosamine--fructose-6-








phosphate aminotransferase








[isomerizing] 1



GGA3_HUMAN
Q9NZ52

334
1
ADP-ribosylation factor-








binding protein GGA3



GGA3_HUMAN
Q9NZ52

518
1
ADP-ribosylation factor-








binding protein GGA3



GIT1_HUMAN
Q9Y2X7

633
1
ARF GTPase-activating








protein GIT1



GIT1_HUMAN
Q9Y2X7

419
1
ARF GTPase-activating








protein GIT1



GIT1_HUMAN
Q9Y2X7

419
1
ARF GTPase-activating








protein GIT1



GIT1_HUMAN
Q9Y2X7

633
1
ARF GTPase-activating








protein GIT1



GIT2_HUMAN
Q14161

626
1
ARF GTPase-activating








protein GIT2



GLGB_HUMAN
Q04446

308
1
1,4-alpha-glucan-branching








enzyme



GLRX3_HUMAN
O76003

102
1
Glutaredoxin-3



GLRX3_HUMAN
O76003

102
1
Glutaredoxin-3



GLU2B_HUMAN
P14314

102
1
Glucosidase 2 subunit beta



GLU2B_HUMAN
P14314

102
1
Glucosidase 2 subunit beta



GLU2B_HUMAN
P14314

227
1
Glucosidase 2 subunit beta



GLU2B_HUMAN
P14314

95
1
Glucosidase 2 subunit beta


 


75
GMIP_HUMAN
Q9P107
GGGEVSSQGPEDS
843
1
GEM-interacting protein





LLGTQSR






GMIP_HUMAN
Q9P107

425
1
GEM-interacting protein



GMIP_HUMAN
Q9P107

473
1
GEM-interacting protein


 


76
GNL1_HUMAN
P36915
SAMEPTGPTQER
344
1
Guanine nucleotide-binding








protein-like 1


 


77
GNL1_HUMAN
P36915
SAMEPTGPTQER
344
1
Guanine nucleotide-binding





YKDGVVTIGCVG


protein-like 1





FPNVGK






GNL1_HUMAN
P36915

53
1
Guanine nucleotide-binding








protein-like 1



GNL1_HUMAN
P36915

344
1
Guanine nucleotide-binding








protein-like 1



GNL1_HUMAN
P36915

50
1
Guanine nucleotide-binding








protein-like 1



GOGB1_HUMAN
Q14789

1246
1
Golgin subfamily B member 1



GOGB1_HUMAN
Q14789

1802
1
Golgin subfamily B member 1


 


78
GOGB1_HUMAN
Q14789
SLSMSTRPTCSES
1802
1
Golgin subfamily B member 1





VPSAK






GON4L_HUMAN
Q3T8J9

482
1
GON-4-like protein


 


79
GPKOW_HUMAN
Q92917
GAGPSPEEKDFLK
38
1
G patch domain and KOW








motifs-containing protein


 


80
GPKOW_HUMAN
Q92917
GAGPSPEEK
38
1
G patch domain and KOW








motifs-containing protein


 


81
GPKOW_HUMAN
Q92917
GAGPSPEEKDFLK
38
1
G patch domain and KOW





TVEGR


motifs-containing protein



GPKOW_HUMAN
Q92917

99
1
G patch domain and KOW








motifs-containing protein



GPKOW_HUMAN
Q92917

99
1
G patch domain and KOW








motifs-containing protein



GPN1_HUMAN
Q9HCN4

312
1
GPN-loop GTPase 1



GPTC8_HUMAN
Q9UKJ3

883
1
G patch domain-containing








protein 8



GRDN_HUMAN
Q3V6T2

220
1
Girdin



GRDN_HUMAN
Q3V6T2

485
1
Girdin



GRIN1_HUMAN
Q7Z2K8

307
1
G protein-regulated inducer








of neurite outgrowth 1


 


82
GSDMD_HUMAN
P57764
GQIQGSVELAAPG
88
1
Gasdermin-D





QAK





 


83
GSDMD_HUMAN
P57764
GVPAEGAFTEDF
276
1
Gasdermin-D





QGLR






GSTP1_HUMAN
P09211

92
1
Glutathione S-transferase P



GSTP1_HUMAN
P09211

92
1
Glutathione S-transferase P



GTF2I_HUMAN
P78347

106
1
General transcription factor








II-I



GTF2I_HUMAN
P78347

106
1
General transcription factor








II-I



H2AY_HUMAN
O75367

173
1
Core histone macro-H2A.1



H4_HUMAN
P62805

70
1
Histone H4



H4_HUMAN
P62805

70
1
Histone H4



H4_HUMAN
P62805

70
1
Histone H4


 


84
H4_HUMAN
P62805
NIQGITKPAIR
26
1
Histone H4



HAP28_HUMAN
Q13442

25
1
28 kDa heat- and acid-stable








phosphoprotein



HAP28_HUMAN
Q13442

25
1
28 kDa heat- and acid-stable








phosphoprotein



HBS1L_HUMAN
Q9Y450

30
1
HBS1-like protein


 


85
HCLS1_HUMAN
P14317
FVNDISEKEQR
27
1
Hematopoietic lineage cell-








specific protein


 


86
HCLS1_HUMAN
P14317
FVNDISEK
27
1
Hematopoietic lineage cell-








specific protein



HDAC4_HUMAN
P56524

9
1
Histone deacetylase 4



HDAC4_HUMAN
P56524

290
1
Histone deacetylase 4



HDAC6_HUMAN
Q9UBN7

1089
1
Histone deacetylase 6



HDAC6_HUMAN
Q9UBN7

1089
1
Histone deacetylase 6


 


87
HDAC7_HUMAN
Q8WUI4
GGGPGQVVDDGL
413
1
Histone deacetylase 7





EHR






HDC_HUMAN
Q9UBI9

324
1
Headcase protein homolog



HDGR2_HUMAN
Q7Z4V5

31
1
Hepatoma-derived growth








factor-related protein 2



HDGR2_HUMAN
Q7Z4V5

242
1
Hepatoma-derived growth








factor-related protein 2



HDGR2_HUMAN
Q7Z4V5

242
1
Hepatoma-derived growth








factor-related protein 2



HDGR2_HUMAN
Q7Z4V5

31
1
Hepatoma-derived growth








factor-related protein 2



HECD1_HUMAN
Q9ULT8

1493
1
E3 ubiquitin-protein ligase








HECTD1


 


88
HELLS_HUMAN
Q9NRZ9
TAVITPAMLEEEE
23
1
Lymphoid-specific helicase





QLEAAGLER






HG2A_HUMAN
P04233

23
1
HLA class II








histocompatibility antigen








gamma chain


 


89
HG2A_HUMAN
P04233
LISNNEQLPMLGR
23
1
HLA class II








histocompatibility antigen








gamma chain



HIRP3_HUMAN
Q9BW71

111
1
HIRA-interacting protein 3


 


90
HJURP_HUMAN
Q8NCD3
GSVQAAAWGPEL
92
1
Holliday junction recognition





PSHR


protein


 


91
HMHA1_HUMAN
Q92619
GGAGASAFEQAD
663
1
Minor histocompatibility





LNGMTPELPVAV


protein HA-1





PSGPFRHEGLSK





 


92
HMHA1_HUMAN
Q92619
AGCLPAEEVDVL
263
1
Minor histocompatibility





LQR


protein HA-1


 


93
HMHA1_HUMAN
Q92619
AVFPGPSLEPPAG
40
1
Minor histocompatibility





SSGVK


protein HA-1



HMOX2_HUMAN
P30519

252
1
Heme oxygenase 2



HMOX2_HUMAN
P30519

252
1
Heme oxygenase 2



HMOX2_HUMAN
P30519

252
1
Heme oxygenase 2



HNRH1_HUMAN
P31943

341
1
Heterogeneous nuclear








ribonucleoprotein H



HNRH1_HUMAN
P31943

95
2
Heterogeneous nuclear








ribonucleoprotein H



HNRH2_HUMAN
P55795

95

Heterogeneous nuclear








ribonucleoprotein H2



HNRH1_HUMAN
P31943

95
2
Heterogeneous nuclear








ribonucleoprotein H



HNRH2_HUMAN
P55795

95

Heterogeneous nuclear








ribonucleoprotein H2



HNRH1_HUMAN
P31943

252
2
Heterogeneous nuclear








ribonucleoprotein H



HNRH2_HUMAN
P55795

252

Heterogeneous nuclear








ribonucleoprotein H2



HNRH2_HUMAN
P55795

341
1
Heterogeneous nuclear








ribonucleoprotein H2


 


94
HNRH3_HUMAN
P31942
GGYGGFDDYGGY
145
1
Heterogeneous nuclear





NNYGYGNDGFDDR


ribonucleoprotein H3



HNRL1_HUMAN
Q9BUJ2

97
1
Heterogeneous nuclear








ribonucleoprotein U-like








protein 1


 


95
HNRL1_HUMAN
Q9BUJ2
GHYAMDNITR
97
1
Heterogeneous nuclear








ribonucleoprotein U-like








protein 1


 


96
HNRL2_HUMAN
Q1KMD3
ASEKPAEATAGS
127
1
Heterogeneous nuclear





GGVNGGEEQGLGK


ribonucleoprotein U-like








protein 2


 


97
HNRL2_HUMAN
Q1KMD3
ASEKPAEATAGS
127
1
Heterogeneous nuclear





GGVNGGEEQGLG


ribonucleoprotein U-like








protein 2



HNRLL_HUMAN
Q8WVV9

290
1
Heterogeneous nuclear








ribonucleoprotein L-like



HNRPD_HUMAN
Q14103

70
1
Heterogeneous nuclear








ribonucleoprotein D0



HNRPF_HUMAN
P52597

252
1
Heterogeneous nuclear








ribonucleoprotein F



HNRPG_HUMAN
P38159

284
1
Heterogeneous nuclear








ribonucleoprotein G



HNRPG_HUMAN
P38159

234
1
Heterogeneous nuclear








ribonucleoprotein G


 


98
HNRPK_HUMAN
P61978
AVECLNYQHYK
129
1
Heterogeneous nuclear








ribonucleoprotein K


 


99
HNRPK_HUMAN
P61978
AVECLNYQHYKG
129
1
Heterogeneous nuclear





SDFDCELR


ribonucleoprotein K


 


100
HNRPK_HUMAN
P61978
SAIDTWSPSEWQ
347
1
Heterogeneous nuclear





MAYEPQGGSGYD


ribonucleoprotein K





YSYAGGR





 


101
HNRPK_HUMAN
P61978
YSYAGGR
371
2
Heterogeneous nuclear








ribonucleoprotein K


 


102
HNRPL_HUMAN
P14866
YTNPNLSGQGDP
285
1
Heterogeneous nuclear





GSNPNKR


ribonucleoprotein L



HNRPQ_HUMAN
O60506

469
1
Heterogeneous nuclear








ribonucleoprotein Q



HOOK1_HUMAN
Q9UJC3

234
1
Protein Hook homolog 1



HOOK1_HUMAN
Q9UJC3

234
1
Protein Hook homolog 1


 


103
HOOK2_HUMAN
Q96ED9
SLSPETYGNFDSQ
161
1
Protein Hook homolog 2





SR






HPS4_HUMANM
Q9NQG7

496
1
Hermansky-Pudlak








syndrome 4 protein



HRX_HUMAN
Q03164

2719
1
Histone-lysine N-








methyltransferase HRX



HRX_HUMAN
Q03164

2719
1
Histone-lysine N-








methyltransferase HRX



HRX_HUMAN
Q03164

2385
1
Histone-lysine N-








methyltransferase HRX



HS105_HUMAN
Q92598

548
1
Heat shock protein 105 kDa



HS105_HUMAN
Q92598

548
1
Heat shock protein 105 kDa



HS105_HUMAN
Q92598

548
1
Heat shock protein 105 kDa



HS71L_HUMAN
P34931

228
6
Heat shock 70 kDa protein








1L



HSP71_HUMAN
P08107

226

Heat shock 70 kDa protein 1



HSP72_HUMAN
P54652

229

Heat shock-related 70 kDa








protein 2



HSP76_HUMAN
P17066

228

Heat shock 70 kDa protein 6



HSP77_HUMAN
P48741

228

Putative heat shock 70 kDa








protein 7



HSP7C_HUMAN
P11142

226

Heat shock cognate 71 kDa








protein



HSP74_HUMAN
P34932

728
1
Heat shock 70 kDa protein 4



HSP7C_HUMAN
P11142

81
1
Heat shock cognate 71 kDa








protein



HTF4_HUMAN
Q99081

23
1
Transcription factor 12


 


104
HTSF1_HUMAN
O43719
AGGEPDSLGQQP
34
1
HIV Tat-specific factor 1





TDTPYEWDLDKK





 


105
HTSF1_HUMAN
O43719
AGGEPDSLGQQP
34
1
HIV Tat-specific factor 1





TDTPYEWDLDKK








AWFPK





 


106
HTSF1_HUMAN
O43719
GASSSTANVEDV
81
1
HIV Tat-specific factor 1





HAR






HTSF1_HUMAN
O43719

40
1
HIV Tat-specific factor 1



HUWE1_HUMAN
Q7Z6Z7

2360
1
E3 ubiquitin-protein ligase








HUWE1


 


107
HUWE1_HUMAN
Q7Z6Z7
GLPEEQPQTTK
3665
1
E3 ubiquitin-protein ligase








HUWE1


 


108
HUWE1_HUMAN
Q7Z6Z7
MNASPLVR
2474
1
E3 ubiquitin-protein ligase








HUWE1


 


109
HUWE1_HUMAN
Q7Z6Z7
SAVAISGADSR
2931
1
E3 ubiquitin-protein ligase








HUWE1



HUWE1_HUMAN
Q7Z6Z7

2018
1
E3 ubiquitin-protein ligase








HUWE1


 


110
HUWE1_HUMAN
Q7Z6Z7
SVLAVMPPDIAAE
3080
1
E3 ubiquitin-protein ligase





AQALR


HUWE1



I2BP2_HUMAN
Q7Z5L9

496
1
Interferon regulatory factor








2-binding protein 2



I5P2_HUMAN
P32019

264
1
Type II inositol-1,4,5-








trisphosphate 5-phosphatase



IASPP_HUMAN
Q8WUF5

295
1
RelA-associated inhibitor


 


111
ICAL_HUMAN
P20810
ALSSDFTCGSPTA
234
1
Calpastatin





AGK





 


112
ICAL_HUMAN
P20810
ALSSDFTCGSPTA
234
1
Calpastatin





AGKK






ICAL_HUMAN
P20810

514
1
Calpastatin



ICAL_HUMAN
P20810

349
1
Calpastatin



ICAL_HUMAN
P20810

660
1
Calpastatin



IF2BL_HUMAN
A6NK07

119
2
Eukaryotic translation








initiation factor 2 subunit 2-








like protein



IF2B_HUMAN
P20042

119

Eukaryotic translation








initiation factor 2 subunit 2



IF2P_HUMAN
O60841

21
1
Eukaryotic translation








initiation factor 5B



IF2P_HUMAN
O60841

21
1
Eukaryotic translation








initiation factor 5B



IF2P_HUMAN
O60841

21
1
Eukaryotic translation








initiation factor 5B



IF4A2_HUMAN
Q14240

22
1
Eukaryotic initiation factor








4A-II



IF4A2_HUMAN
Q14240

22
1
Eukaryotic initiation factor








4A-II



IF4B_HUMAN
P23588

60
1
Eukaryotic translation








initiation factor 4B



IF4B_HUMAN
P23588

51
1
Eukaryotic translation








initiation factor 4B



IF4G1_HUMAN
Q04637

533
1
Eukaryotic translation








initiation factor 4 gamma 1



IF4G1_HUMAN
Q04637

666
1
Eukaryotic translation








initiation factor 4 gamma 1



IF4G1_HUMAN
Q04637

415
1
Eukaryotic translation








initiation factor 4 gamma 1


 


113
IF4G2_HUMAN
P78344
SSSAPSKEQLEQEK
793
1
Eukaryotic translation








initiation factor 4 gamma 2


 


114
IF4G2_HUMAN
P78344
SSSAPSKEQLEQE
793
1
Eukaryotic translation





KQLLLSFKPVMQK


initiation factor 4 gamma 2



IF4G3_HUMAN
O43432

479
1
Eukaryotic translation








initiation factor 4 gamma 3



IF4G3_HUMAN
O43432

479
1
Eukaryotic translation








initiation factor 4 gamma 3


 


115
IF4H_HUMAN
Q15056
SLKEALTYDGAL
94
1
Eukaryotic translation





LGDR


initiation factor 4H



IF5A1_HUMAN
P63241

97
1
Eukaryotic translation








initiation factor 5A-1



IF5A1_HUMAN
P63241

12
2
Eukaryotic translation








initiation factor 5A-1



IF5AL_HUMAN
Q6IS14

12

Eukaryotic translation








initiation factor 5A-1-like



IF5A1_HUMAN
P63241

12
2
Eukaryotic translation








initiation factor 5A-1



IF5AL_HUMAN
Q6IS14

12

Eukaryotic translation








initiation factor 5A-1-like



IF5A1_HUMAN
P63241

12
2
Eukaryotic translation








initiation factor 5A-1



IF5AL_HUMAN
Q6IS14

12

Eukaryotic translation








initiation factor 5A-1-like



IF5A1_HUMAN
P63241

7
2
Eukaryotic translation








initiation factor 5A-1



IF5AL_HUMAN
Q6IS14

7

Eukaryotic translation








initiation factor 5A-1-like



IF5A1_HUMAN
P63241

12
2
Eukaryotic translation








initiation factor 5A-1



IF5AL_HUMAN
Q6IS14

12

Eukaryotic translation








initiation factor 5A-1-like



IF5A1_HUMAN
P63241

7
2
Eukaryotic translation








initiation factor 5A-1



IF5AL_HUMAN
Q6IS14

7

Eukaryotic translation








initiation factor 5A-1-like



IF5A1_HUMAN
P63241

7
2
Eukaryotic translation








initiation factor 5A-1



IF5AL_HUMAN
Q6IS14

7

Eukaryotic translation








initiation factor 5A-1-like



IF5A1_HUMAN
P63241

7
2
Eukaryotic translation








initiation factor 5A-1



IF5AL_HUMAN
Q6IS14

7

Eukaryotic translation








initiation factor 5A-1-like



IF5A2_HUMAN
Q9GZV4

7
1
Eukaryotic translation








initiation factor 5A-2



IF5A2_HUMAN
Q9GZV4

7
1
Eukaryotic translation








initiation factor 5A-2



IKBB_HUMAN
Q15653

160
1
NF-kappa-B inhibitor beta


 


116
IKBL2_HUMAN
Q96HA7
GLTPQLEEDEELQ
499
1
NF-kappa-B inhibitor-like





GHLGR


protein 2


 


117
IKBL2_HUMAN
Q96HA7
GLTPQLEEDEELQ
499
1
NF-kappa-B inhibitor-like





GHLGRR


protein 2



IKZF1_HUMAN
Q13422

368
1
DNA-binding protein Ikaros



IKZF2_HUMAN
Q9UKS7

8
1
Zinc finger protein Helios



IKZF5_HUMAN
Q9H5V7

226
1
Zinc finger protein Pegasus


 


118
ILF3_HUMAN
Q12906
GSGIYDPCEKEAT
288
1
interleukin enhancer-binding





DAIGHLDR


factor 3



ILF3_HUMAN
Q12906

440
1
Interleukin enhancer-binding








factor 3



ILF3_HUMAN
Q12906

440
1
Interleukin enhancer-binding








factor 3



ILKAP_HUMAN
Q9H0C8

40
1
Integrin-linked kinase-








associated serine/threonine








phosphatase 2C



IMA1_HUMAN
P52294

65
1
Importin subunit alpha-1



IMA1_HUMAN
P52294

65
1
Importin subunit alpha-1



IMA7_HUMAN
O60684

70
1
Importin subunit alpha-7


 


119
IMDH2_HUMAN
P12268
CFLEEIMTK
173
1
Inosine-5′-monophosphate








dehydrogenase 2



IN80D_HUMAN
Q53TQ3

679
1
INO80 complex subunit D


 


120
INF2_HUMAN
Q27J81
AVTPGPQPTLEQL
1052
1
Inverted formin-2





EEGGPRPLER





 


121
INF2_HUMAN
Q27J81
AVTPGPQPTLEQL
1052
1
Inverted formin-2





EEGGPRPLERR






INF2_HUMAN
Q27J81

1147
1
Inverted formin-2



IPO9_HUMAN
Q96P70

964
1
Importin-9



IQEC1_HUMAN
Q6DN90

235
1
IQ motif and SEC7 domain-








containing protein 1


 


122
IQGA1_HUMAN
P46940
GLGVARPHYGSV
9
1
Ras GTPase-activating-like





LDNER


protein IQGAP1


 


123
IQGA1_HUMAN
P46940
GLGVARPHYGSV
9
1
Ras GTPase-activating-like





LDNERLTAEEMD


protein IQGAP1





ER






IRF2_HUMAN
P14316

238
1
Interferon regulatory factor 2



IRS4_HUMAN
O14654

717
1
Insulin receptor substrate 4


 


124
ISY1_HUMAN
Q9ULR0
GVIVPLEQEYEK
168
1
Pre-mRNA-splicing factor








ISY1 homolog


 


125
ISY1_HUMAN
Q9ULR0
GVIVPLEQEYEKK
168
1
Pre-mRNA-splicing factor








ISY1 homolog



IWS1_HUMAN
Q96ST2

348
1
Protein IWS1 homolog



IWS1_HUMAN
Q96ST2

348
1
Protein IWS1 homolog


 


126
JHD3C_HUMAN
Q9H3R0
GAEVPNPDSVTD
397
1
JmjC domain-containing





DLK


histone demethylation








protein 3C


 


127
JHD3C_HUMAN
Q9H3R0
GAEVPNPDSVTD
397
1
JmjC domain-containing





DLKVSEK


histone demethylation








protein 3C



JIP4_HUMAN
O60271

214
1
C-jun-amino-terminal








kinase-interacting protein 4



JIP4_HUMAN
O60271

6
1
C-jun-amino-terminal








kinase-interacting protein 4



JIP4_HUMAN
O60271

6
1
C-jun-amino-terminal








kinase-interacting protein 4



JIP4_HUMAN
O60271

285
1
C-jun-amino-terminal








kinase-interacting protein 4



JKIP1_HUMAN
Q96N16

18
1
Janus kinase and








microtubule-interacting








protein 1


 


128
JKIP1_HUMAN
Q96N16
AVQMANEELR
18
1
Janus kinase and








microtubule-interacting








protein 1



JMY_HUMAN
Q8N9B5

723
1
Junction-mediating and -








regulatory protein



JMY_HUMAN
Q8N9B5

723
1
Junction-mediating and -








regulatory protein


 


129
JOSD3_HUMAN
Q9H5J8
HVTSDAVELANR
11
1
Protein JOSD3


 


130
JSPR1_HUMAN
Q96MG2
GGLGSCQALEDH
13
1
Junctional sarcoplasmic





SALAETQEDR


reticulum protein 1



K0174_HUMAN
P53990

198
1
Uncharacterized protein








KIAA0174



K0174_HUMAN
P53990

198
1
Uncharacterized protein








KIAA0174



K0232_HUMAN
Q92628

557
1
Uncharacterized protein








KIAA0232



K0515_HUMAN
Q5JSZ5

1083
1
Uncharacterized protein








KIAA0515



K0515_HUMAN
Q5JSZ5

1236
1
Uncharacterized protein








KIAA0515



K0831_HUMAN
Q6ZNE5

29
1
Uncharacterized protein








KIAA0831



K0831_HUMAN
Q6ZNE5

227
1
Uncharacterized protein








KIAA0831



K1462_HUMAN
Q9P266

1180
1
Uncharacterized protein








KIAA1462


 


131
K1543_HUMAN
Q9P1Y5
GSPAGAEDSLEEE
862
1
Uncharacterized protein





ASSEGEPR


KIAA1543


 


132
K1627_HUMAN
Q9HCE5
SIGAVLNSKDEQR
30
1
Methyltransferase-like








protein KIAA1627


 


133
K1627_HUMAN
Q9HCE5
SIGAVLNSKDEQR
30
1
Methyltransferase-like





EIAETR


protein KIAA1627


 


134
K1627_HUMAN
Q9HCE5
SIGAVLNSK
30
1
Methyltransferase-like








protein KIAA1627



K1704_HUMAN
Q8IXQ4

89
1
Uncharacterized protein








KIAA1704


 


135
K1967_HUMAN
Q8N163
AGAEPITADSDPA
293
1
Protein KIAA1967





YSSK






K1967_HUMAN
Q8N163

769
1
Protein KIAA1967



K1967_HUMAN
Q8N163

619
1
Protein KIAA1967


 


136
KHDR1_HUMAN
Q07666
ATVGGPAPTPLLP
76
1
KH domain-containing,





PSATASVK


RNA-binding, signal








transduction-associated








protein 1



KI67_HUMAN
P46013

2148
1
Antigen KI-67



KI67_HUMAN
P46013

411
1
Antigen KI-67



KI67_HUMAN
P46013

174
1
Antigen KI-67



KIF15_HUMAN
Q9NS87

1134
1
Kinesin-like protein KIF15



KKCC1_HUMAN
Q8N5S9

33
1
Calcium/calmodulin-








dependent protein kinase








Kinase 1



KLF12_HUMAN
Q9Y4X4

74
1
Krueppel-like factor 12


 


137
KPYM_HUMAN
P14618
GADCIMLSGETA
355
1
Pyruvate kinase isozymes





KGDYPLEAVR


M1/M2


 


138
KPYM_HUMAN
P14618
GADCIMLSGETAK
355
2
Pyruvate kinase isozymes


 




M1/M2



138
KPYR_HUMAN
P30613
GADCIMLSGETAK
398

Pyruvate kinase isozymes








R/L



KRI1_HUMAN
Q8N9T8

313
1
Protein KRI1 homolog


 


139
KRR1_HUMAN
Q13601
GWKEPAFSK
39
1
KRR1 small subunit








processome component








homolog


 


140
KRR1_HUMAN
Q13601
GWKEPAFSKEDN
39
1
KRR1 small subunit





PR


processome component








homolog



KS6A4_HUMAN
O75676

378
1
Ribosomal protein S6 kinase








alpha-4



KU86_HUMAN
P13010

456
1
ATP-dependent DNA








helicase 2 subunit 2



KU86_HUMAN
P13010

456
1
ATP-dependent DNA








helicase 2 subunit 2



KU86_HUMAN
P13010

557
1
ATP-dependent DNA








helicase 2 subunit 2



LAGE3_HUMAN
Q14657

29
1
L antigen family member 3



LAMB1_HUMAN
P07942

1359
1
Laminin subunit beta-1



LAP2A_HUMAN
P42166

487
1
Lamina-associated








polypeptide 2, isoform alpha



LAP2A_HUMAN
P42166

442
1
Lamina-associated








polypeptide 2, isoform alpha


 


141
LAP4_HUMAN
Q14160
AALEVSPGVIANP
1198
1
Protein LAP4





FAAGIGHR






LAP4_HUMAN
Q14160

502
1
Protein LAP4



LAP4_HUMAN
Q14160

636
1
Protein LAP4


 


142
LARP1_HUMAN
Q6PKG0
AINWPTPGEIAHK
173
1
La-related protein 1


 


143
LARP1_HUMAN
Q6PKG0
FSQLLNCPEFVPR
496
1
La-related protein 1


 


144
LARP4_HUMAN
Q71RC2
GLNQTTIPVSPPST
574
1
La-related protein 4





TKPSR






LARP5_HUMAN
Q92615

136
1
La-related protein 5



LAT_HUMAN
O43561

168
1
Linker for activation of T-








cells family member 1


 


145
LCAP_HUMAN
Q9UIQ6
LAKEPCLHPLEPD
30
1
Leucyl-cystinyl





EVEYEPR


aminopeptidase



LCORL_HUMAN
Q8N3X6

230
2
Ligand-dependent nuclear








receptor corepressor-like








protein



LCOR_HUMAN
Q96JN0

81

Ligand-dependent








corepressor



LIMA1_HUMAN
Q9UHB6

346
1
LIM domain and actin-








binding protein 1



LIN37_HUMAN
Q96GY3

24
1
Protein lin-37 homolog



LIN7C_HUMAN
Q9NUP9

63
1
Lin-7 homolog C


 


146
LIPA1_HUMAN
Q13136
GVLDINHEQENTP
219
1
Liprin-alpha-1





STSGK





 


147
LIPA1_HUMAN
Q13136
GVLDINHEQENTP
219
1
Liprin-alpha-1





STSGKR






LIPB2_HUMAN
Q8ND30

32
1
Liprin-beta-2



LMNB1_HUMAN
P20700

147
1
Lamin-B1



LMO7_HUMAN
Q8WWI1

963
1
LIM domain only protein 7



LMTK2_HUMAN
Q8IWU2

901
1
Serine/threonine-protein








kinase LMTK2



LNP_HUMAN
Q9C0E8

369
1
Protein lunapark



LPP_HUMAN
Q93052

404
1
Lipoma-preferred partner



LPP_HUMAN
Q93052

404
1
Lipoma-preferred partner



LRBA_HUMAN
P50851

1757
1
Lipopolysaccharide-








responsive and beige-like








anchor protein


 


148
LRBA_HUMAN
P50851
SAQASDMGGESP
1757
1
Lipopolysaccharide-





GSR


responsive and beige-like








anchor protein



LRBA_HUMAN
P50851

1785
1
Lipopolysaccharide-








responsive and beige-like








anchor protein



LRBA_HUMAN
P50851

1785
1
Lipopolysaccharide-








responsive and beige-like








anchor protein


 


149
LRC47_HUMAN
Q8N1G4
AVSGQLPDPTTNP
526
1
Leucine-rich repeat-





SAGK


containing protein 47


 


150
LRC47_HUMAN
Q8N1G4
AVSGQLPDPTTNP
526
1
Leucine-rich repeat-





SAGKDGPSLLVV


containing protein 47





EQVR






LRCH1_HUMAN
Q9Y2L9

406
1
Leucine-rich repeat and








calponin homology domain-








containing protein 1



LRCH1_HUMAN
Q9Y2L9

406
1
Leucine-rich repeat and








calponin homology domain-








containing protein 1



LRCH2_HUMAN
Q5VUJ6

604
1
Leucine-rich repeat and








calponin homology domain-








containing protein 2



LRCH3_HUMAN
Q96II8

643
1
Leucine-rich repeat and








calponin homology domain-








containing protein 3



LRCH4_HUMAN
O75427

359
1
Leucine-rich repeat and








calponin homology domain-








containing protein 4


 


151
LRMP_HUMAN
Q12912
SVVSPLPVTTVK
182
1
Lymphoid-restricted








membrane protein



LRRF1_HUMAN
Q32MZ4

416
1
Leucine-rich repeat








flightless-interacting protein 1



LRRF2_HUMAN
Q9Y608

532
1
Leucine-rich repeat








flightless-interacting protein 2



LSM11_HUMAN
P83369

306
1
U7 snRNA-associated Sm-








like protein LSm11



LSM3_HUMAN
P62310

7
1
U6 snRNA-associated Sm-








like protein LSm3



LSP1_HUMAN
P33241

103
1
Lymphocyte-specific protein 1


 


152
LTV1_HUMAN
Q96GA3
SAGLLSDEDCMS
206
1
Protein LTV1 homolog





VPGKTHR






LYRIC_HUMAN
Q86UE4

184
1
Protein LYRIC


 


153
M6PBP_HUMAN
O60664
GFDVASVQQQR
220
1
Mannose-6-phosphate








receptor-binding protein 1



M6PBP_HUMAN
O60664

10
1
Mannose-6-phosphate








receptor-binding protein 1



M6PBP_HUMAN
O60664

223
1
Mannose-6-phosphate








receptor-binding protein 1



MA7D1_HUMAN
Q3KQU3

571
1
MAP7 domain-containing








protein 1


 


154
MA7D1_HUMAN
Q3KQU3
AAVLTSPPAPAPP
571
1
MAP7 domain-containing





VTPSKPMAGTTD


protein 1





REEATR






MACF1_HUMAN
Q9UPN3

1524
1
Microtubule-actin cross-








linking factor 1, isoforms








1/2/3/5



MACF1_HUMAN
Q9UPN3

3021
2
Microtubule-actin cross-








linking factor 1, isoforms








1/2/3/5



MACF4_HUMAN
Q96PK2

3523

Microtubule-actin cross-








linking factor 1, isoform 4



MACF1_HUMAN
Q9UPN3

3021
2
Microtubule-actin cross-








linking factor 1, isoforms








1/2/3/5



MACF4_HUMAN
Q96PK2

3523

Microtubule-actin cross-








linking factor 1, isoform 4


 


155
MACF1_HUMAN
Q9UPN3
GYMGVNQAPEKL
1727
2
Microtubule-actin cross-





DKQCEMMK


linking factor 1, isoforms








1/2/3/5


155
MACF4_HUMAN
Q96PK2
GYMGVNQAPEKL
2229

Microtubule-actin cross-





DKQCEMMK


linking factor 1, isoform 4



MACF1_HUMAN
Q9UPN3

1727
2
Microtubule-actin cross-








linking factor 1, isoforms








1/2/3/5



MACF4_HUMAN
Q96PK2

2229

Microtubule-actin cross-








linking factor 1, isoform 4



MACF1_HUMAN
Q9UPN3

1727
2
Microtubule-actin cross-








linking factor 1, isoforms








1/2/3/5



MACF4_HUMAN
Q96PK2

2229

Microtubule-actin cross-








linking factor 1, isoform 4


 


156
MACF1_HUMAN
Q9UPN3
GYMGVNQAPEKL
1727
2
Microtubule-actin cross-





DK


linking factor 1, isoforms








1/2/3/5


156
MACF4_HUMAN
Q96PK2
GYMGVNQAPEKL
2229

Microtubule-actin cross-





DK


linking factor 1, isoform 4


 


157
MACF1_HUMAN
Q9UPN3
GYMGVNQAPEK
1727
2
Microtubule-actin cross-








linking factor 1, isoforms








1/2/3/5


157
MACF4_HUMAN
Q96PK2
GYMGVNQAPEK
2229

Microtubule-actin cross-








linking factor 1, isoform 4


 


158
MADD_HUMAN
Q8WXG6
SVIGVSPAVMIR
1178
1
MAP kinase-activating death








domain protein



MAGD1_HUMAN
Q9Y5V3

223
1
Melanoma-associated








antigen D1


 


159
MAGG1_HUMAN
Q96MG7
GFAEEAPSTSR
42
1
Melanoma-associated








antigen G1


 


160
MAGG1_HUMAN
Q96MG7
GFAEEAPSTSRGP
42
1
Melanoma-associated





GGSQGSQGPSPQ


antigen G1





GAR






MAOM_HUMAN
P23368

380
1
NAD-dependent malic








enzyme, mitochondrial


 


161
MAP1A_HUMAN
P78559
SVVAAVQEGAAE
1885
1
Microtubule-associated





LEGGPYSPLGK


protein 1A


 


162
MAP1A_HUMAN
P78559
SVVAAVQEGAAE
1885
1
Microtubule-associated





LEGGPYSPLGKD


protein 1A





YR





 


163
MAP1A_HUMAN
P78559
SVVAAVQEGAAE
1885
1
Microtubule-associated





LEGGPYSPLGKD


protein 1A





YRK






MAP4_HUMAN
P27816

9
1
Microtubule-associated








protein 4



MAP4_HUMAN
P27816

9
1
Microtubule-associated








protein 4



MAP4_HUMAN
P27816

250
1
Microtubule-associated








protein 4



MAP4_HUMAN
P27816

152
1
Microtubule-associated








protein 4



MAP4_HUMAN
P27816

328
1
Microtubule-associated








protein 4



MAP4_HUMAN
P27816

47
1
Microtubule-associated








protein 4



MAP9_HUMAN
Q49MG5

120
1
Microtubule-associated








protein 9



MARE1_HUMAN
Q15691

117
1
Microtubule-associated








protein RP/EB family








member 1



MARK1_HUMAN
Q9P0L2

23
1
Serine/threonine-protein








kinase MARK1


 


164
MATR3_HUMAN
P43243
GQSDENKDDYTIP
764
1
Matrin-3





DEYR





 


165
MATR3_HUMAN
P43243
LANLGDVASDGK
681
1
Matrin-3


 


166
MATR3_HUMAN
P43243
LANLGDVASDGKK
681
1
Matrin-3


 


167
MATR3_HUMAN
P43243
SFDDRGPSLNPVL
188
1
Matrin-3





DYDHGSR





 


168
MATR3_HUMAN
P43243
YYTTTPALVFGKP
453
1
Matrin-3





VR






MATR3_HUMAN
P43243

704
1
Matrin-3


 


169
MATR3_HUMAN
P43243
LANLGDVASDGK
681
1
Matrin-3





KEPSDK






MAVS_HUMAN
Q7Z434

491
1
Mitochondrial antiviral-








signaling protein



MAVS_HUMAN
Q7Z434

491
1
Mitochondrial antiviral-








signaling protein



MAX_HUMAN
P61244

49
1
Protein max



MBB1A_HUMAN
Q9BQG0

750
1
Myb-binding protein 1A



MCM2_HUMAN
P49736

89
1
DNA replication licensing








factor MCM2



MCM2_HUMAN
P49736

69
1
DNA replication licensing








factor MCM2


 


170
MCM3_HUMAN
P25205
SYDPYDFSDTEEE
704
1
DNA replication licensing





MPQVHTPK


factor MCM3


 


171
MCM4_HUMAN
P33991
GAAAEDIVASEQS
133
1
DNA replication licensing





LGQK


factor MCM4


 


172
MCM5_HUMAN
P33992
SFGGDAQADEGQ
14
1
DNA replication licensing





ARK


factor MCM5


 


173
MCM5_HUMAN
P33992
SFGGDAQADEGQ
14
1
DNA replication licensing





AR


factor MCM5


 


174
MCM6_HUMAN
Q14566
GYETEGIRGLR
275
1
DNA replication licensing








factor MCM6


 


175
MCM6_HUMAN
Q14566
GYETEGIR
275
1
DNA replication licensing








factor MCM6



MDC1_HUMAN
Q14676

1036
1
Mediator of DNA damage








checkpoint protein 1



MDC1_HUMAN
Q14676

1036
1
Mediator of DNA damage








checkpoint protein 1



MDN1_HUMAN
Q9NU22

5128
1
Midasin



MED14_HUMAN
O60244

995
1
Mediator of RNA








polymerase II transcription








subunit 14



MED1_HUMAN
Q15648

931
1
Mediator of RNA








polymerase II transcription








subunit 1



MED1_HUMAN
Q15648

1485
1
Mediator of RNA








polymerase II transcription








subunit 1



MED26_HUMAN
O95402

408
1
Mediator of RNA








polymerase II transcription








subunit 26



MEF2C_HUMAN
Q06413

106
1
Myocyte-specific enhancer








factor 2C



MEF2C_HUMAN
Q06413

106
1
Myocyte-specific enhancer








factor 2C



METK2_HUMAN
P31153

40
1
S-adenosylmethionine








synthetase isoform type-2



MEX3B_HUMAN
Q6ZN04

355
1
RNA-binding protein








MEX3B



MGAP_HUMAN
Q8IWI9

681
1
MAX gene-associated








protein



MGAP_HUMAN
Q8IWI9

340
1
MAX gene-associated








protein



MGAP_HUMAN
Q8IWI9

340
1
MAX gene-associated








protein



MGAP_HUMAN
Q8IWI9

572
1
MAX gene-associated








protein



MIA3_HUMAN
Q5JRA6

710
1
Melanoma inhibitory activity








protein 3



MIER1_HUMAN
Q8N108

52
1
Mesoderm induction early








response protein 1



MINT_HUMAN
Q96T58

1575
1
Msx2-interacting protein



MINT_HUMAN
Q96T58

2008
1
Msx2-interacting protein



MINT_HUMAN
Q96T58

2860
1
Msx2-interacting protein



MISSL_HUMAN
Q8NDC0

10
1
MAPK-interacting and








spindle-stabilizing protein-








like


 


176
MKL1_HUMAN
Q969V6
ALSPEQPASHESQ
122
1
MKL/myocardin-like protein 1





GSVPSPLEAR






MKL2_HUMAN
Q9ULH7

183
1
MKL/myocardin-like protein 2


 


177
MLL2_HUMAN
O14686
ALYVACQGQPK
387
1
Histone-lysine N-








methyltransferase MLL2



MLL2_HUMAN
O14686

1866
1
Histone-lysine N-








methyltransferase MLL2



MLL3_HUMAN
Q8NEZ4

2189
1
Histone-lysine N-








methyltransferase MLL3



MOBL3_HUMAN
Q9Y3A3

35
1
Mps one binder kinase








activator-like 3



MOES_HUMAN
P26038

115
1
Moesin



MORC3_HUMAN
Q14149

665
1
MORC family CW-type zinc








finger protein 3



MORC3_HUMAN
Q14149

752
1
MORC family CW-type zinc








finger protein 3



MOT1_HUMAN
P53985

470
1
Monocarboxylate transporter 1



MP2K1_HUMAN
Q02750

283
1
Dual specificity mitogen-








activated protein kinase








kinase 1


 


178
MP2K1_HUMAN
Q02750
GSAVNGTSSAET
17
1
Dual specificity mitogen-





NLEALQK


activated protein kinase








kinase 1


 


179
MP2K1_HUMAN
Q02750
GSAVNGTSSAET
17
1
Dual specificity mitogen-





NLEALQKK


activated protein kinase








kinase 1


 


180
MPP10_HUMAN
O00566
AALLAPEEIKEK
546
1
U3 small nucleolar








ribonucleoprotein protein








MPP10


 


181
MPP10_HUMAN
O00566
AALLAPEEIK
546
1
U3 small nucleolar








ribonucleoprotein protein








MPP10



MPP8_HUMAN
Q99549

20
1
M-phase phosphoprotein 8



MPP8_HUMAN
Q99549

502
1
M-phase phosphoprotein 8



MPP8_HUMAN
Q99549

517
1
M-phase phosphoprotein 8


 


182
MRP_HUMAN
P49006
AIEPAPPSQGAEAK
64
1
MARCKS-related protein



MSPD2_HUMAN
Q8NHP6

275
1
Motile sperm domain-








containing protein 2



MTA70_HUMAN
Q86U44

335
1
N6-adenosine-








methyltransferase 70 kDa








subunit



MYH10_HUMAN
P35580

1310
1
Myosin-10


 


183
MYH10_HUMAN
P35580
TTAAQQELR
1161
1
Myosin-10


 


184
MYH11_HUMAN
P35749
STATQQELR
1161
1
Myosin-11



MYH9_HUMAN
P35579

1376
1
Myosin-9


 


185
MYH9_HUMAN
P35579
STAAQQELR
1154
1
Myosin-9


 


186
MYO9B_HUMAN
Q13459
SLTSDKASVPIVL
1704
1
Myosin-IXb





EK






MYPT1_HUMAN
O14974

886
1
Protein phosphatase 1








regulatory subunit 12A



N4BP1_HUMAN
O75113

491
1
NEDD4-binding protein 1



NACA_HUMAN
Q13765

43
1
Nascent polypeptide-








associated complex subunit








alpha



NACA_HUMAN
Q13765

43
1
Nascent polypeptide-








associated complex subunit








alpha



NADAP_HUMAN
Q9BWU0

538
1
Kanadaptin



NADAP_HUMAN
Q9BWU0

538
1
Kanadaptin



NADAP_HUMAN
Q9BWU0

538
1
Kanadaptin



NAG_HUMAN
A2RRP1

637
1
Neuroblastoma-amplified








gene protein



NAG_HUMAN
A2RRP1

637
1
Neuroblastoma-amplified








gene protein



NAIF1_HUMAN
Q69YI7

103
1
Nuclear apoptosis-inducing








factor 1



NARF_HUMAN
Q9UHQ1

292
1
Nuclear prelamin A








recognition factor



NARF_HUMAN
Q9UHQ1

273
1
Nuclear prelamin A








recognition factor


 


187
NASP_HUMAN
P49321
KIEDVPAPSTSAD
20
1
Nuclear autoantigenic sperm





KVESLDVDSEAK


protein



NASP_HUMAN
P49321

33
1
Nuclear autoantigenic sperm








protein



NASP_HUMAN
P49321

33
1
Nuclear autoantigenic sperm








protein


 


188
NCK1_HUMAN
P16333
SASPADDSFVDPG
89
1
Cytoplasmic protein NCK1





ER






NCOA3_HUMAN
Q9Y6Q9

1013
1
Nuclear receptor coactivator 3



NCOA5_HUMAN
Q9HCD5

381
1
Nuclear receptor coactivator 5



NCOA5_HUMAN
Q9HCD5

154
1
Nuclear receptor coactivator 5



NCOA6_HUMAN
Q14686

1462
1
Nuclear receptor coactivator 6



NCOR1_HUMAN
O75376

1827
1
Nuclear receptor corepressor 1



NCOR1_HUMAN
O75376

386
1
Nuclear receptor corepressor 1



NCOR1_HUMAN
O75376

556
1
Nuclear receptor corepressor 1


 


189
NCOR1_HUMAN
O75376
AAASAPQMDVSK
1827
1
Nuclear receptor corepressor 1



NCOR1_HUMAN
O75376

386
1
Nuclear receptor corepressor 1



NCOR1_HUMAN
O75376

556
1
Nuclear receptor corepressor 1



NCOR2_HUMAN
Q9Y618

378
1
Nuclear receptor corepressor 2



NCOR2_HUMAN
Q9Y618

1927
1
Nuclear receptor corepressor 2



NDRG1_HUMAN
Q92597

10
1
Protein NDRG1


 


190
NEB2_HUMAN
Q96SB3
GTSLVGVTQSFA
552
1
Neurabin-2





ASVLR





 


191
NED4L_HUMAN
Q96PU5
AVAEQGHLPPPSA
346
1
E3 ubiquitin-protein ligase





PAGR


NEDD4-like



NEDD1_HUMAN
Q8NHV4

435
1
Protein NEDD1



NEDD4_HUMAN
P46934

280
1
E3 ubiquitin-protein ligase








NEDD4



NEK1_HUMAN
Q96PY6

950
1
Serine/threonine-protein








kinase Nek1



NEK4_HUMAN
P51957

381
1
Serine/threonine-protein








kinase Nek4



NEK9_HUMAN
Q8TD19

842
1
Serine/threonine-protein








kinase Nek9



NELFA_HUMAN
Q9H3P2

300
1
Negative elongation factor A



NFAC1_HUMAN
O95644

111
1
Nuclear factor of activated T-








cells, cytoplasmic 1



NFAC2_HUMAN
Q13469

67
1
Nuclear factor of activated T-








cells, cytoplasmic 2



NFKB2_HUMAN
Q00653

11
1
Nuclear factor NF-kappa-B








p100 subunit



NFRKB_HUMAN
Q6P4R8

497
1
Nuclear factor related to








kappa-B-binding protein



NFRKB_HUMAN
Q6P4R8

6
1
Nuclear factor related to








kappa-B-binding protein



NHERF_HUMAN
O14745

5
1
Ezrin-radixin-moesin-








binding phosphoprotein 50



NIPA_HUMAN
Q86WB0

450
1
Nuclear-interacting partner








of ALK



NIPA_HUMAN
Q86WB0

296
1
Nuclear-interacting partner








of ALK



NIPBL_HUMAN
Q6KC79

473
1
Nipped-B-like protein



NIPBL_HUMAN
Q6KC79

473
1
Nipped-B-like protein



NKTR_HUMAN
P30414

960
1
NK-tumor recognition








protein



NOL1_HUMAN
P46087

231
1
Putative RNA








methyltransferase NOL1



NOL1_HUMAN
P46087

208
1
Putative RNA








methyltransferase NOL1


 


192
NOL1_HUMAN
P46087
GGLQINVDEEPFV
208
1
Putative RNA





LPPAGEMEQDAQ


methyltransferase NOL1





APDLQR





 


193
NOL1_HUMAN
P46087
GGLQINVDEEPFV
208
1
Putative RNA





LPPAGEMEQDAQ


methyltransferase NOL1





APDLQRVHKR





 


194
NOL5_HUMAN
Q9Y2X3
GLIPGVEPR
125
1
Nucleolar protein 5



NOP14_HUMAN
P78316

320
1
Nucleolar protein 14



NOP14_HUMAN
P78316

320
1
Nucleolar protein 14


 


195
NP1L1_HUMAN
P55209
GLVETPTGYIESL
58
1
Nucleosome assembly





PR


protein 1-like 1


 


196
NP1L1_HUMAN
P55209
GLVETPTGYIESL
58
1
Nucleosome assembly





PRVVKR


protein 1-like 1



NP1L1_HUMAN
P55209

184
1
Nucleosome assembly








protein 1-like 1


 


197
NP1L4_HUMAN
Q99733
GVPSDSVEAAK
9
1
Nucleosome assembly








protein 1-like 4


 


198
NP1L4_HUMAN
Q99733
GVPSDSVEAAKN
9
1
Nucleosome assembly





ASNTEK


protein 1-like 4



NP1L4_HUMAN
Q99733

9
1
Nucleosome assembly








protein 1-like 4


 


199
NP1L4_HUMAN
Q99733
GVPSDSVEAAKN
9
1
Nucleosome assembly





ASNTEKLTDQVM


protein 1-like 4





QNPR





 


200
NP1L4_HUMAN
Q99733
NVPHTPSSYIETLPK
47
1
Nucleosome assembly








protein 1-like 4



NP60_HUMAN
Q49A26

256
1
Nuclear protein NP60



NPAT_HUMAN
Q14207

734
1
Protein NPAT



NPM_HUMAN
P06748

7
1
Nucleophosmin



NPM_HUMAN
P06748

4
1
Nucleophosmin



NS1BP_HUMAN
Q9Y6Y0

239
1
Influenza virus NS1A-








binding protein



NSBP1_HUMAN
P82970

58
1
Nucleosome-binding protein 1


 


201
NSUN2_HUMAN
Q08J23
GQKVEVPQPLSW
109
1
tRNA (cytosine-5-)-





YPEELAWHTNLSR


methyltransferase NSUN2


 


202
NSUN2_HUMAN
Q08J23
GQKVEVPQPLSW
109
1
tRNA (cytosine-5-)-





YPEELAWHTNLS


methyltransferase NSUN2





RK






NSUN2_HUMAN
Q08J23

500
1
tRNA (cytosine-5-)-








methyltransferase NSUN2



NSUN2_HUMAN
Q08J23

500
1
tRNA (cytosine-5-)-








methyltransferase NSUN2



NSUN2_HUMAN
Q08J23

665
1
tRNA (cytosine-5-)-








methyltransferase NSUN2



NU153_HUMAN
P49790

359
1
Nuclear pore complex








protein Nup153



NUCB2_HUMAN
P80303

259
1
Nucleobindin-2



NUCB2_HUMAN
P80303

238
1
Nucleobindin-2



NUCKS_HUMAN
Q9H1E3

30
3
Nuclear ubiquitous casein








and cyclin-dependent kinases








substrate



NUCL_HUMAN
P19338

637
1
Nucleolin



NUDC3_HUMAN
Q8IVD9

126
1
NudC domain-containing








protein 3



NUDC3_HUMAN
Q8IVD9

126
1
NudC domain-containing








protein 3



NUDC3_HUMAN
Q8IVD9

120
1
NudC domain-containing








protein 3



NUFP2_HUMAN
Q7Z417

452
1
Nuclear fragile X mental








retardation-interacting








protein 2



NUMA1_HUMAN
Q14980

1748
1
Nuclear mitotic apparatus








protein 1



NUMA1_HUMAN
Q14980

1748
1
Nuclear mitotic apparatus








protein 1



NUMA1_HUMAN
Q14980

1830
1
Nuclear mitotic apparatus








protein 1


 


203
NUP43_HUMAN
Q8NFH3
GGFEGDHQLLCDIR
59
1
Nucleoporin Nup43



NUP50_HUMAN
Q9UKX7

127
1
Nucleoporin 50 kDa


 


204
NUP93_HUMAN
Q8N1F7
FTQESEPSYISDV
158
1
Nuclear pore complex





GPPGR


protein Nup93


 


205
ODPB_HUMAN
P11177
AINQGMDEELER
38
1
Pyruvate dehydrogenase E1





DEK


component subunit beta,








mitochondrial



OFD1_HUMAN
O75665

854
1
Oral-facial-digital syndrome








1 protein



ORAV1_HUMAN
Q8WV07

10
1
Oral cancer overexpressed








protein 1



OSBL8_HUMAN
Q9BZF1

807
1
Oxysterol-binding protein-








related protein 8



OTU6B_HUMAN
Q8N6M0

81
1
OTU domain-containing








protein 6B



OTUD4_HUMAN
Q01804

10
1
OTU domain-containing








protein 4



OXR1_HUMAN
Q8N573

450
1
Oxidation resistance protein 1



OXR1_HUMAN
Q8N573

450
1
Oxidation resistance protein 1



P4R3A_HUMAN
Q6IN85

693
1
Serine/threonine-protein








phosphatase 4 regulatory








subunit 3A



P66B_HUMAN
Q8WXI9

345
1
Transcriptional repressor








p66-beta


 


206
PA24A_HUMAN
P47712
AAVADPDEFER
523
1
Cytosolic phospholipase A2


 


207
PABP2_HUMAN
Q86U42
GAIEDPELEAIK
112
1
Polyadenylate-binding








protein 2


 


208
PABP2_HUMAN
Q86U42
GAIEDPELEAIKAR
112
1
Polyadenylate-binding








protein 2



PAIRB_HUMAN
Q8NC51

338
1
Plasminogen activator








inhibitor 1 RNA-binding








protein



PAK1_HUMAN
Q13153

91
2
Serine/threonine-protein



PAK2_HUMAN
Q13177

90

kinase PAK 1








Serine/threonine-protein








kinase PAK 2



PAK2_HUMAN
Q13177

149
1
Serine/threonine-protein








kinase PAK 2



PALLD_HUMAN
Q8WX93

433
1
Palladin



PARG_HUMAN
Q86W56

257
1
Poly(ADP-ribose)








glycohydrolase



PARP1_HUMAN
P09874

215
1
Poly [ADP-ribose]








polymerase 1



PARP1_HUMAN
P09874

215
1
Poly [ADP-ribose]








polymerase 1



PARP1_HUMAN
P09874

215
1
Poly [ADP-ribose]








polymerase 1



PARP1_HUMAN
P09874

73
1
Poly [ADP-ribose]








polymerase 1



PAWR_HUMAN
Q96IZ0

132
1
PRKC apoptosis WT1








regulator protein



PAXI_HUMAN
P49023

103
1
Paxillin



PAXI_HUMAN
P49023

6
1
Paxillin



PAXI_HUMAN
P49023

336
1
Paxillin



PB1_HUMAN
Q86U86

22
1
Protein polybromo-1



PCBP1_HUMAN
Q15365

204
1
Poly(rC)-binding protein 1


 


209
PCBP1_HUMAN
Q15365
AYSIQGQHTISPL
221
1
Poly(rC)-binding protein 1





DLAK





 


210
PCBP1_HUMAN
Q15365
ASTQTTHELTIPN
276
1
Poly(rC)-binding protein 1





NLIGCIIGR






PCBP2_HUMAN
Q15366

283
1
Poly(rC)-binding protein 2



PCF11_HUMAN
O94913

1289
1
Pre-mRNA cleavage








complex 2 protein Pcf11


 


211
PCM1_HUMAN
Q15154
GRGEPAMESSQIV
194
1
Pericentriolar material 1





SR


protein



PCM1_HUMAN
Q15154

1552
1
Pericentriolar material 1








protein



PCNT_HUMAN
O95613

81
1
Pericentrin


 


212
PDIP3_HUMAN
Q9BY77
AYTAPALPSSIR
235
1
Polymerase delta-interacting








protein 3



PDLI1_HUMAN
O00151

55
1
PDZ and LIM domain








protein 1



PDXD1_HUMAN
Q6P996

585
1
Pyridoxal-dependent








decarboxylase domain-








containing protein 1



PEBB_HUMAN
Q13951

121
1
Core-binding factor subunit








beta



PFTK1_HUMAN
O94921

57
1
Serine/threonine-protein








kinase PFTAIRE-1


 


213
PGK1_HUMAN
P00558
CVGPEVEK
99
1
Phosphoglycerate kinase 1


 


214
PGK1_HUMAN
P00558
CVGPEVEKACAN
99
1
Phosphoglycerate kinase 1





PAAGSVILLENLR






PGK1_HUMAN
P00558

286
1
Phosphoglycerate kinase 1



PGK1_HUMAN
P00558

69
1
Phosphoglycerate kinase 1



PGK1_HUMAN
P00558

160
2
Phosphoglycerate kinase 1



PGK2_HUMAN
P07205

160

Phosphoglycerate kinase 2



PHAR4_HUMAN
Q8IZ21

21
1
Phosphatase and actin








regulator 4



PHF3_HUMAN
Q92576

1627
1
PHD finger protein 3



PHF3_HUMAN
Q92576

1100
1
PHD finger protein 3



PHF3_HUMAN
Q92576

1158
1
PHD finger protein 3



PHF3_HUMAN
Q92576

1398
1
PHD finger protein 3



PHTNS_HUMAN
Q6NYC8

496
1
Phostensin


 


215
PI4KB_HUMAN
Q9UBF8
SITSQESKEPVFIA
489
1
Phosphatidylinositol 4-kinase





AGDIR


beta


 


216
PI4KB_HUMAN
Q9UBF8
SITSQESKEPVFIA
489
1
Phosphatidylinositol 4-kinase





AGDIRR


beta


 


217
PIAS1_HUMAN
O75925
GHPASSPLLPVSL
101
1
E3 SUMO-protein ligase





LGPK


PIAS1



PICAL_HUMAN
Q13492

277
1
Phosphatidylinositol-binding








clathrin assembly protein



PITM1_HUMAN
O00562

379
1
Membrane-associated








phosphatidylinositol transfer








protein 1



PJA2_HUMAN
O43164

87
1
E3 ubiquitin-protein ligase








Praja2



PKHG1_HUMAN
Q9ULL1

436
1
Pleckstrin homology








domain-containing family G








member 1



PKP4_HUMAN
Q99569

804
1
Plakophilin-4



PLCG1_HUMAN
P19174

771
1
1-phosphatidylinositol-4,5-








bisphosphate








phosphodiesterase gamma-1



PLDN_HUMAN
Q9UL45

11
1
Pallidin



POGZ_HUMAN
Q7Z3K3

28
1
Pogo transposable element








with ZNF domain



POMP_HUMAN
Q9Y244

13
1
Proteasome maturation








protein



PP1RA_HUMAN
Q96QC0

377
1
Serine/threonine-protein








phosphatase 1 regulatory








subunit 10



PP1RA_HUMAN
Q96QC0

294
1
Serine/threonine-protein








phosphatase 1 regulatory








subunit 10



PP1RA_HUMAN
Q96QC0

367
1
Serine/threonine-protein








phosphatase 1 regulatory








subunit 10



PP4R1_HUMAN
Q8TF05

445
1
Serine/threonine-protein








phosphatase 4 regulatory








subunit 1



PPIA_HUMAN
P62937

10
1
Peptidyl-prolyl cis-trans








isomerase A


 


218
PPIL4_HUMAN
Q8WUA2
ADIKPPENVLFVCK
233
1
Peptidyl-prolyl cis-trans








isomerase-like 4



PPR3D_HUMAN
O95685

32
1
Protein phosphatase 1








regulatory subunit 3D



PR40A_HUMAN
O75400

134
1
Pre-mRNA-processing factor








40 homolog A



PRD15_HUMAN
P57071

1270
1
PR domain zinc finger








protein 15



PRD15_HUMAN
P57071

1270
1
PR domain zinc finger








protein 15


 


219
PRKDC_HUMAN
P78527
GDPSDRMEVQEQ
3212
1
DNA-dependent protein





EEDISSLIR


kinase catalytic subunit



PROF1_HUMAN
P07737

20
1
Profilin-1



PROF1_HUMAN
P07737

82
1
Profilin-1



PROF1_HUMAN
P07737

82
1
Profilin-1



PROF1_HUMAN
P07737

15
1
Profilin-1



PRP17_HUMAN
O60508

56
1
Pre-mRNA-processing factor








17


 


220
PRP17_HUMAN
O60508
VAKPSEEEQKELD
205
1
Pre-mRNA-processing factor





EITAKR


17



PRP17_HUMAN
O60508

191
1
Pre-mRNA-processing factor








17



PRP17_HUMAN
O60508

205
1
Pre-mRNA-processing factor








17



PRP17_HUMAN
O60508

205
1
Pre-mRNA-processing factor








17



PRP31_HUMAN
Q8WWY3

387
1
U4/U6 small nuclear








ribonucleoprotein Prp31



PRR12_HUMAN
Q9ULL5

116
1
Proline-rich protein 12



PRR3_HUMAN
P79522

32
1
Proline-rich protein 3



PRS10_HUMAN
P62333

266
1
26S protease regulatory








subunit S10B


 


221
PRS6A_HUMAN
P17980
GIGEEVLK
28
1
26S protease regulatory








subunit 6A



PRS6A_HUMAN
P17980

28
1
26S protease regulatory








subunit 6A


 


222
PRS6A_HUMAN
P17980
GIGEEVLKMSTEE
28
1
26S protease regulatory





IIQR


subunit 6A



PRS6A_HUMAN
P17980

319
1
26S protease regulatory








subunit 6A


 


223
PRS6B_HUMAN
P43686
GFDQNVNVK
298
1
26S protease regulatory








subunit 6B


 


224
PRS8_HUMAN
P62195
SIGSSRLEGGSGG
253
1
26S protease regulatory





DSEVQR


subunit 8



PSA5_HUMAN
P28066

72
1
Proteasome subunit alpha








type-5



PSA7L_HUMAN
Q8TAA3

16
2
Proteasome subunit alpha








type-7-like



PSA7_HUMAN
O14818

14

Proteasome subunit alpha








type-7



PSB1_HUMAN
P20618

48
1
Proteasome subunit beta








type-1


 


225
PSB4_HUMAN
P28070
SFMDPASALYR
30
1
Proteasome subunit beta








type-4



PSB7_HUMAN
Q99436

54
1
Proteasome subunit beta








type-7


 


226
PSD12_HUMAN
O00232
YSATVDQR
20
1
26S proteasome non-ATPase








regulatory subunit 12



PSD4_HUMAN
Q8NDX1

83
1
PH and SEC7 domain-








containing protein 4



PSD4_HUMAN
Q8NDX1

536
1
PH and SEC7 domain-








containing protein 4



PSIP1_HUMAN
O75475

31
1
PC4 and SFRS1-interacting








protein



PSIP1_HUMAN
O75475

31
1
PC4 and SFRS1-interacting








protein


 


227
PSIP1_HUMAN
O75475
SVITQVLNK
434
1
PC4 and SFRS1-interacting








protein



PSME3_HUMAN
P61289

78
1
Proteasome activator








complex subunit 3



PTBP1_HUMAN
P26599

3
1
Polypyrimidine tract-binding








protein 1



PTBP1_HUMAN
P26599

3
1
Polypyrimidine tract-binding








protein 1



PTBP1_HUMAN
P26599

173
1
Polypyrimidine tract-binding








protein 1



PTBP1_HUMAN
P26599

173
1
Polypyrimidine tract-binding








protein 1



PTBP1_HUMAN
P26599

173
1
Polypyrimidine tract-binding








protein 1



PTBP1_HUMAN
P26599

173
1
Polypyrimidine tract-binding








protein 1



PTBP1_HUMAN
P26599

140
2
Polypyrimidine tract-binding








protein 1



PTCA_HUMAN
Q14761

121
1
Protein tyrosine phosphatase








receptor type C-associated








protein



PTCA_HUMAN
Q14761

121
1
Protein tyrosine phosphatase








receptor type C-associated








protein



PTCA_HUMAN
Q14761

117
1
Protein tyrosine phosphatase








receptor type C-associated








protein



PTMA_HUMAN
P06454

4
1
Prothymosin alpha



PTMA_HUMAN
P06454

4
1
Prothymosin alpha



PTMA_HUMAN
P06454

8
1
Prothymosin alpha



PTMA_HUMAN
P06454

8
1
Prothymosin alpha


 


228
PTN3_HUMAN
P26045
GVDQQLLDDFHR
472
1
Tyrosine-protein phosphatase








non-receptor type 3


 


229
PUR2_HUMAN
P22102
GGPNTGGMGAYC
226
1
Trifunctional purine





PAPQVSNDLLLK


biosynthetic protein








adenosine-3



PUR2_HUMAN
P22102

206
1
Trifunctional purine








biosynthetic protein








adenosine-3



PUR2_HUMAN
P22102

444
1
Trifunctional purine








biosynthetic protein








adenosine-3



PUR6_HUMAN
P22234

320
1
Multifunctional protein








ADE2



PUR6_HUMAN
P22234

27
1
Multifunctional protein








ADE2


 


230
PUR9_HUMAN
P31939
GIIAPGYEEEALTI
340
1
Bifunctional purine





LSK


biosynthesis protein PURH



PUS7_HUMAN
Q96PZ0

51
1
Pseudouridylate synthase 7








homolog



PUS7_HUMAN
Q96PZ0

23
1
Pseudouridylate synthase 7








homolog


 


231
PWP2A_HUMAN
Q96N64
GQQSAPQADEPPL
56
1
PWWP domain-containing





PPPPPPPGELAR


protein 2A



PYR1_HUMAN
P27708

1139
1
CAD protein



QKI_HUMAN
Q96PU8

75
1
Protein quaking



QN1_HUMAN
Q5TB80

248
1
Protein QN1 homolog



QSER1_HUMAN
Q2KHR3

1322
1
Glutamine and serine-rich








protein 1


 


232
QSK_HUMAN
Q9Y2K2
GTLNLDSDEGEEP
384
1
Serine/threonine-protein





SPEALVR


kinase QSK



R3HD1_HUMAN
Q15032

500
1
R3H domain-containing








protein 1



R3HD1_HUMAN
Q15032

500
1
R3H domain-containing








protein 1



RA1L3_HUMAN
P0C7M2

158
3
Putative heterogeneous








nuclear ribonucleoprotein








A1-like protein 3



ROA1L_HUMAN
Q32P51

158

Heterogeneous nuclear








ribonucleoprotein A1-like








protein



ROA1_HUMAN
P09651

158

Heterogeneous nuclear








ribonucleoprotein A1



RA1L3_HUMAN
P0C7M2

95
3
Putative heterogeneous








nuclear ribonucleoprotein








A1-like protein 3



ROA1L_HUMAN
Q32P51

95

Heterogeneous nuclear








ribonucleoprotein A1-like








protein



ROA1_HUMAN
P09651

95

Heterogeneous nuclear








ribonucleoprotein A1



RA1L3_HUMAN
P0C7M2

70
2
Putative heterogeneous








nuclear ribonucleoprotein








A1-like protein 3



ROA1_HUMAN
P09651

70

Heterogeneous nuclear








ribonucleoprotein A1



RA1L3_HUMAN
P0C7M2

158
2
Putative heterogeneous








nuclear ribonucleoprotein








A1-like protein 3



ROA1_HUMAN
P09651

158

Heterogeneous nuclear








ribonucleoprotein A1



RA1L3_HUMAN
P0C7M2

70
2
Putative heterogeneous








nuclear ribonucleoprotein








A1-like protein 3



ROA1_HUMAN
P09651

70

Heterogeneous nuclear








ribonucleoprotein A1


 


233
RAD21_HUMAN
O60216
SVDPVEPMPTMT
280
1
Double-strand-break repair





DQTTLVPNEEEAF


protein rad21 homolog





ALEPIDITVK






RAD21_HUMAN
O60216

280
1
Double-strand-break repair








protein rad21 homolog


 


234
RAD21_HUMAN
O60216
SVDPVEPMPTMT
280
1
Double-strand-break repair





DQTTLVPNEEEAF


protein rad21 homolog





ALEPIDITVKETK





 


235
RAD21_HUMAN
O60216
VAQQFSLNQSR
129
1
Double-strand-break repair








protein rad21 homolog



RADIL_HUMAN
Q96JH8

842
1
Ras-associating and dilute








domain-containing protein



RADIL_HUMAN
Q96JH8

842
1
Ras-associating and dilute








domain-containing protein



RANG_HUMAN
P43487

128
1
Ran-specific GTPase-








activating protein



RB3GP_HUMAN
Q15042

253
1
Rab3 GTPase-activating








protein catalytic subunit



RBBP4_HUMAN
Q09028

362
2
Histone-binding protein








RBBP4



RBBP7_HUMAN
Q16576

361

Histone-binding protein








RBBP7



RBBP6_HUMAN
Q7Z6E9

973
1
Retinoblastoma-binding








protein 6



RBBP6_HUMAN
Q7Z6E9

1679
1
Retinoblastoma-binding








protein 6



RBBP6_HUMAN
Q7Z6E9

1268
1
Retinoblastoma-binding








protein 6



RBBP6_HUMAN
Q7Z6E9

1268
1
Retinoblastoma-binding








protein 6


 


236
RBBP7_HUMAN
Q16576
SDKGEFGGFGSVT
99
1
Histone-binding protein





GK


RBBP7



RBBP7_HUMAN
Q16576

94
1
Histone-binding protein








RBBP7



RBBP8_HUMAN
Q99708

743
1
Retinoblastoma-binding








protein 8



RBM15_HUMAN
Q96T37

751
1
Putative RNA-binding








protein 15


 


237
RBM16_HUMAN
Q9UPN6
GVEEEVFEQEAK
381
1
Putative RNA-binding








protein 16



RBM16_HUMAN
Q9UPN6

776
1
Putative RNA-binding








protein 16



RBM25_HUMAN
P49756

634
1
Probable RNA-binding








protein 25



RBM26_HUMAN
Q5T8P6

432
1
RNA-binding protein 26


 


238
RBM26_HUMAN
Q5T8P6
GYNPEAPSITNTS
432
1
RNA-binding protein 26





RPMYR






RBM26_HUMAN
Q5T8P6

281
1
RNA-binding protein 26



RBM26_HUMAN
Q5T8P6

281
1
RNA-binding protein 26



RBM27_HUMAN
Q9P2N5

488
1
RNA-binding protein 27



RBM28_HUMAN
Q9NW13

245
1
RNA-binding protein 28



RBM33_HUMAN
Q96EV2

999
1
RNA-binding protein 33


 


239
RBM39_HUMAN
Q14498
ASSASSFLDSDEL
332
1
RNA-binding protein 39





ER





 


240
RBM39_HUMAN
Q14498
ASSASSFLDSDEL
332
1
RNA-binding protein 39





ERTGIDLGTTGR






RBM8A_HUMAN
Q9Y5S9

7
1
RNA-binding protein 8A



RBM8A_HUMAN
Q9Y5S9

7
1
RNA-binding protein 8A



RBM8A_HUMAN
Q9Y5S9

7
1
RNA-binding protein 8A



RBM8A_HUMAN
Q9Y5S9

7
1
RNA-binding protein 8A



RBM8A_HUMAN
Q9Y5S9

7
1
RNA-binding protein 8A


 


241
RBM8A_HUMAN
Q9Y5S9
SVEQDGDEPGPQR
56
1
RNA-binding protein 8A



RBM9_HUMAN
O43251

103
1
RNA-binding protein 9



RBP2_HUMAN
P49792

2491
1
E3 SUMO-protein ligase








RanBP2


 


242
RBP2_HUMAN
P49792
GGSAHGDDDDDG
1158
1
E3 SUMO-protein ligase





PHFEPVVPLPDKI


RanBP2





EVK





 


243
RBP2_HUMAN
P49792
GTGGQSIYGDKFE
3132
1
E3 SUMO-protein ligase





DENFDVK


RanBP2



RBP2_HUMAN
P49792

2861
1
E3 SUMO-protein ligase








RanBP2



RBP2_HUMAN
P49792

1158
1
E3 SUMO-protein ligase








RanBP2



RBP2_HUMAN
P49792

2307
7
E3 SUMO-protein ligase








RanBP2



RGPD1_HUMAN
Q68DN6

1316

RANBP2-like and GRIP








domain-containing protein 1



RGPD3_HUMAN
A6NKT7

1332

RANBP2-like and GRIP








domain-containing protein 3



RGPD4_HUMAN
Q7Z3J3

1332

RANBP2-like and GRIP








domain-containing protein 4



RGPD5_HUMAN
Q99666

1331

RANBP2-like and GRIP








domain-containing protein 5



RGPD6_HUMAN
Q53T03

1331

RANBP2-like and GRIP








domain-containing protein 6



RGPD8_HUMAN
O14715

321

RANBP2-like and GRIP








domain-containing protein 8








(Fragment)



RBP2_HUMAN
P49792

2237
6
E3 SUMO-protein ligase








RanBP2



RGPD3_HUMAN
A6NKT7

1262

RANBP2-like and GRIP








domain-containing protein 3



RGPD4_HUMAN
Q7Z3J3

1262

RANBP2-like and GRIP








domain-containing protein 4



RGPD5_HUMAN
Q99666

1261

RANBP2-like and GRIP








domain-containing protein 5



RGPD6_HUMAN
Q53T03

1261

RANBP2-like and GRIP








domain-containing protein 6



RGPD8_HUMAN
O14715

251

RANBP2-like and GRIP








domain-containing protein 8








(Fragment)



RBP56_HUMAN
Q92804

141
1
TATA-binding protein-








associated factor 2N



RBTN1_HUMAN
P25800

9
1
Rhombotin-1



RBY1B_HUMAN
A6NDE4

467
3
RNA-binding motif protein,








Y chromosome, family 1








member B



RBY1F_HUMAN
Q15415

467

RNA-binding motif protein,








Y chromosome, family 1








member F/J



RBY1H_HUMAN
Q15378

327

Putative RNA-binding motif








protein, Y chromosome,








family 1 member H


 


244
RB_HUMAN
P06400
SIDSFETQR
347
1
Retinoblastoma-associated








protein



RCAN1_HUMAN
P53805

4
1
Calcipressin-1



RCC2_HUMAN
Q9P258

61
1
Protein RCC2



RCC2_HUMAN
Q9P258

61
1
Protein RCC2



RCN2_HUMAN
Q14257

204
1
Reticulocalbin-2



RCOR2_HUMAN
Q8IZ40

392
1
REST corepressor 2



RCOR2_HUMAN
Q8IZ40

392
1
REST corepressor 2



RCOR2_HUMAN
Q8IZ40

392
1
REST corepressor 2



RCOR2_HUMAN
Q8IZ40

392
1
REST corepressor 2



RD23B_HUMAN
P54727

166
1
UV excision repair protein








RAD23 homolog B


 


245
RED_HUMAN
Q13123
GVNKDYEETELIS
109
1
Protein Red





TTANYR





 


246
RED_HUMAN
Q13123
YVPSTTK
325
2
Protein Red


 


247
RED_HUMAN
Q13123
YVPSTTKTPR
325
1
Protein Red


 


248
REL_HUMAN
Q04864
GYYEAEFGQER
87
1
C-Rel proto-oncogene








protein



RENT1_HUMAN
Q92900

76
1
Regulator of nonsense








transcripts 1


 


249
REPS1_HUMAN
Q96D71
SFTSDPEQIGSNV
466
1
RalBP1-associated Eps





TR


domain-containing protein 1


 


250
REPS1_HUMAN
Q96D71
SNIAPADPDTAIV
387
1
RalBP1-associated Eps





HPVPIR


domain-containing protein 1


 


251
REPS1_HUMAN
Q96D71
GYSSSDSFTSDPE
460
1
RalBP1-associated Eps





QIGSNVTR


domain-containing protein 1



REQU_HUMAN
Q92785

244
1
Zinc finger protein ubi-d4


 


252
REQU_HUMAN
Q92785
GSSLEALLR
116
1
Zinc finger protein ubi-d4



REST_HUMAN
Q13127

942
1
RE1-silencing transcription








factor



RFC1_HUMAN
P35251

724
1
Replication factor C subunit 1


 


253
RFC1_HUMAN
P35251
GMAGNEDR
724
1
Replication factor C subunit 1


 


254
RFC1_HUMAN
P35251
GMAGNEDRGGIQ
724
1
Replication factor C subunit 1





ELIGLIK






RFC1_HUMAN
P35251

168
1
Replication factor C subunit 1



RFX7_HUMAN
Q2KHR2

480
1
DNA-binding protein RFX7



RGAP1_HUMAN
Q9H0H5

274
1
Rac GTPase-activating








protein 1



RGAP1_HUMAN
Q9H0H5

274
1
Rac GTPase-activating








protein 1



RGPD1_HUMAN
Q68DN6

1500
7
RANBP2-like and GRIP








domain-containing protein 1



RGPD2_HUMAN
P0C839

765

RANBP2-like and GRIP








domain-containing protein 2



RGPD3_HUMAN
A6NKT7

1516

RANBP2-like and GRIP








domain-containing protein 3



RGPD4_HUMAN
Q7Z3J3

1516

RANBP2-like and GRIP








domain-containing protein 4



RGPD5_HUMAN
Q99666

1515

RANBP2-like and GRIP








domain-containing protein 5



RGPD6_HUMAN
Q53T03

1515

RANBP2-like and GRIP








domain-containing protein 6



RGPD8_HUMAN
O14715

505

RANBP2-like and GRIP








domain-containing protein 8








(Fragment)



RGS10_HUMAN
O43665

15
1
Regulator of G-protein








signaling 10



RGS10_HUMAN
O43665

13
1
Regulator of G-protein








signaling 10



RHG04_HUMAN
P98171

404
1
Rho GTPase-activating








protein 4



RHG04_HUMAN
P98171

404
1
Rho GTPase-activating








protein 4


 


255
RHG25_HUMAN
P42331
SFSSMTSDSDTTS
388
1
Rho GTPase-activating





PTGQQPSDAFPED


protein 25





SSKVPR






RHG25_HUMAN
P42331

398
1
Rho GTPase-activating








protein 25


 


256
RHG30_HUMAN
Q7Z6I6
GCLCPCSLGLGG
908
1
Rho GTPase-activating





VGMR


protein 30



RHG30_HUMAN
Q7Z6I6

593
1
Rho GTPase-activating








protein 30


 


257
RHG30_HUMAN
Q7Z6I6
SIEAAEGEQEPEA
364
1
Rho GTPase-activating





EALGGTNSEPGTPR


protein 30



RHGBA_HUMAN
Q6P4F7

257
1
Rho GTPase-activating








protein 11A


 


258
RHOA_HUMAN
P61586
SLENIPEKWTPEVK
91
2
Transforming protein RhoA


258
RHOC_HUMAN
P08134
SLENIPEKWTPEVK
91

Rho-related GTP-binding








protein RhoC



RIF1_HUMAN
Q5UIP0

1810
1
Telomere-associated protein








RIF1



RIF1_HUMAN
Q5UIP0

2001
1
Telomere-associated protein








RIF1



RIMB1_HUMAN
O95153

1808
1
Peripheral-type








benzodiazepine receptor-








associated protein 1



RIMB1_HUMAN
O95153

45
1
Peripheral-type








benzodiazepine receptor-








associated protein 1


 


259
RING1_HUMAN
Q06587
GTEIAVSPR
32
1
E3 ubiquitin-protein ligase








RING1



RIOK1_HUMAN
Q9BRS2

130
1
Serine/threonine-protein








kinase RIO1



RIOK1_HUMAN
Q9BRS2

130
1
Serine/threonine-protein








kinase RIO1



RIPK1_HUMAN
Q13546

559
1
Receptor-interacting








serine/threonine-protein








kinase 1



RIR2_HUMAN
P31350

30
1
Ribonucleoside-diphosphate








reductase subunit M2



RL17_HUMAN
P18621

111
1
60S ribosomal protein L17


 


260
RL5_HUMAN
P46777
GQPGAFTCYLDA
137
1
60S ribosomal protein L5





GLAR






RL5_HUMAN
P46777

169
1
60S ribosomal protein L5



RN168_HUMAN
Q8IYW5

251
1
RING finger protein 168


 


261
RN213_HUMAN
Q63HN8
GVREEDLAPFSLR
356
1
RING finger protein 213



RN219_HUMAN
Q5W0B1

434
1
RING finger protein 219



RN220_HUMAN
Q5VTB9

414
1
RING finger protein 220



RNF5_HUMAN
Q99942

9
1
E3 ubiquitin-protein ligase








RNF5



RNZ1_HUMAN
Q9H777

280
1
Zinc phosphodiesterase








ELAC protein 1



ROA0_HUMAN
Q13151

63
1
Heterogeneous nuclear








ribonucleoprotein A0



ROA0_HUMAN
Q13151

74
1
Heterogeneous nuclear








ribonucleoprotein A0



ROA0_HUMAN
Q13151

63
1
Heterogeneous nuclear








ribonucleoprotein A0



ROA0_HUMAN
Q13151

63
1
Heterogeneous nuclear








ribonucleoprotein A0



ROA2_HUMAN
P22626

77
1
Heterogeneous nuclear








ribonucleoproteins A2/B1



ROA2_HUMAN
P22626

77
1
Heterogeneous nuclear








ribonucleoproteins A2/B1



ROA2_HUMAN
P22626

77
1
Heterogeneous nuclear








ribonucleoproteins A2/B1



ROA2_HUMAN
P22626

131
1
Heterogeneous nuclear








ribonucleoproteins A2/B1



ROA3_HUMAN
P51991

91
1
Heterogeneous nuclear








ribonucleoprotein A3


 


262
ROA3_HUMAN
P51991
SVKPGAHLTVKK
116
1
Heterogeneous nuclear








ribonucleoprotein A3



ROA3_HUMAN
P51991

179
1
Heterogeneous nuclear








ribonucleoprotein A3



ROA3_HUMAN
P51991

91
1
Heterogeneous nuclear








ribonucleoprotein A3



ROA3_HUMAN
P51991

116
1
Heterogeneous nuclear








ribonucleoprotein A3



ROCK1_HUMAN
Q13464

1114
1
Rho-associated protein








kinase 1



RPAP3_HUMAN
Q9H6T3

125
1
RNA polymerase II-








associated protein 3



RPAP3_HUMAN
Q9H6T3

452
1
RNA polymerase II-








associated protein 3



RPAP3_HUMAN
Q9H6T3

452
1
RNA polymerase II-








associated protein 3



RPB9_HUMAN
P36954

5
1
DNA-directed RNA








polymerase II subunit RPB9



RPC4_HUMAN
P05423

132
1
DNA-directed RNA








polymerase III subunit RPC4


 


263
RPC5_HUMAN
Q9NVU0
SFNGHPPQGCAST
544
1
DNA-directed RNA





PVAR


polymerase III subunit RPC5



RPGF6_HUMAN
Q8TEU7

1283
1
Rap guanine nucleotide








exchange factor 6


 


264
RPGF6_HUMAN
Q8TEU7
SMSAALQDER
1283
1
Rap guanine nucleotide








exchange factor 6



RREB1_HUMAN
Q92766

1174
1
RAS-responsive element-








binding protein 1


 


265
RRMJ3_HUMAN
Q8IY81
STAGTTKQPSKEE
347
1
Putative rRNA





EEEEEEEQLNQTL


methyltransferase 3





AEMK






RRP12_HUMAN
Q5JTH9

1162
1
RRP12-like protein



RRP12_HUMAN
Q5JTH9

1162
1
RRP12-like protein



RRP12_HUMAN
Q5JTH9

1162
1
RRP12-like protein


 


266
RRP12_HUMAN
Q5JTH9
GNKMEEEEGAKG
1162
1
RRP12-like protein





EDEEMADPMEDV








IIR






RRP12_HUMAN
Q5JTH9

557
1
RRP12-like protein



RRP1B_HUMAN
Q14684

276
1
Ribosomal RNA processing








protein 1 homolog B



RS20_HUMAN
P60866

6
1
40S ribosomal protein S20



RS23_HUMAN
P62266

89
1
40S ribosomal protein S23



RS23_HUMAN
P62266

89
1
40S ribosomal protein S23



RS28_HUMAN
P62857

55
1
40S ribosomal protein S28



RS3_HUMAN
P23396

33
1
40S ribosomal protein S3


 


267
RSRC1_HUMAN
Q96IZ7
SFVQQTFR
239
1
Arginine/serine-rich coiled-








coil protein 1



RTF1_HUMAN
Q92541

141
1
RNA polymerase-associated








protein RTF1 homolog


 


268
RTF1_HUMAN
Q92541
GYGEDLMGDEEDR
141
1
RNA polymerase-associated








protein RTF1 homolog


 


269
RTF1_HUMAN
Q92541
GYGEDLMGDEED
141
1
RNA polymerase-associated





RAR


protein RTF1 homolog



RTN4_HUMAN
Q9NQC3

85
1
Reticulon-4



RTN4_HUMAN
Q9NQC3

906
1
Reticulon-4


 


270
RU1C_HUMAN
P09234
TYLTHDSPSVRK
11
1
U1 small nuclear








ribonucleoprotein C


 


271
RU1C_HUMAN
P09234
TYLTHDSPSVR
11
1
U1 small nuclear








ribonucleoprotein C


 


272
RU2A_HUMAN
P09661
AIDFSDNEIR
46
1
U2 small nuclear








ribonucleoprotein A′


 


273
RUSD2_HUMAN
Q8IZ73
STAPSSELGKDDL
442
1
RNA pseudouridylate





EELAAAAQK


synthase domain-containing








protein 2



RUXF_HUMAN
P62306

53
1
Small nuclear








ribonucleoprotein F



S11IP_HUMAN
Q8N1F8

373
1
Serine/threonine kinase 11-








interacting protein



S12A2_HUMAN
P55011

67
1
Solute carrier family 12








member 2



S2546_HUMAN
Q96AG3

11
1
Solute carrier family 25








member 46


 


274
S30BP_HUMAN
Q9UHR5
AYGEDDFSR
45
1
SAP30-binding protein



SAFB1_HUMAN
Q15424

147
1
Scaffold attachment factor








B1



SAFB1_HUMAN
Q15424

797
2
Scaffold attachment factor








B1



SAFB2_HUMAN
Q14151

821

Scaffold attachment factor








B2



SAFB1_HUMAN
Q15424

263
2
Scaffold attachment factor








B



SAFB2_HUMAN
Q14151

262

Scaffold attachment factor








B2



SAFB1_HUMAN
Q15424

263
2
Scaffold attachment factor








B1



SAFB2_HUMAN
Q14151

262

Scaffold attachment factor








B2



SAFB1_HUMAN
Q15424

263
2
Scaffold attachment factor








B1



SAFB2_HUMAN
Q14151

262

Scaffold attachment factor








B2



SAFB1_HUMAN
Q15424

361
2
Scaffold attachment factor








B1



SAFB2_HUMAN
Q14151

360

Scaffold attachment factor








B2



SAFB1_HUMAN
Q15424

797
2
Scaffold attachment factor








B1



SAFB2_HUMAN
Q14151

821

Scaffold attachment factor








B2



SAFB2_HUMAN
Q14151

184
1
Scaffold attachment factor








B2



SAFB2_HUMAN
Q14151

154
1
Scaffold attachment factor








B2



SAFB2_HUMAN
Q14151

154
1
Scaffold attachment factor








B2



SAHH2_HUMAN
O43865

6
1
Putative








adenosylhomocysteinase 2


 


275
SAHH2_HUMAN
O43865
SYSSAASYTDSSD
74
1
Putative





DEVSPR


adenosylhomocysteinase 2


 


276
SAHH2_HUMAN
O43865
SYSSAASYTDSSD
74
1
Putative





DEVSPREK


adenosylhomocysteinase 2



SAHH2_HUMAN
O43865

6
1
Putative








adenosylhomocysteinase 2



SAHH2_HUMAN
O43865

6
1
Putative








adenosylhomocysteinase 2



SAHH2_HUMAN
O43865

6
1
Putative








adenosylhomocysteinase 2



SAHH2_HUMAN
O43865

84
1
Putative








adenosylhomocysteinase 2



SAHH3_HUMAN
Q96HN2

110
1
Putative








adenosylhomocysteinase 3



SAM4B_HUMAN
Q5PRF9

413
1
Sterile alpha motif domain-








containing protein 4B



SAPS1_HUMAN
Q9UPN7

359
1
Serine/threonine-protein








phosphatase 6 regulatory








subunit 1


 


277
SAP_HUMAN
P07602
VYCEVCEFLVK
313
1
Proactivator polypeptide


 


278
SAP_HUMAN
P07602
VYCEVCEFLVKE
313
1
Proactivator polypeptide





VTK






SAP_HUMAN
P07602

406
1
Proactivator polypeptide


 


279
SASH3_HUMAN
O75995
YSLDSPGPEK
116
1
SAM and SH3 domain-








containing protein 3



SASH3_HUMAN
O75995

56
1
SAM and SH3 domain-








containing protein 3



SATB1_HUMAN
Q01826

255
1
DNA-binding protein








SATB1



SATT_HUMAN
P43007

13
1
Neutral amino acid








transporter A



SC16A_HUMAN
O15027

838
1
Protein transport protein








Sec16A



SC16A_HUMAN
O15027

342
1
Protein transport protein








Sec16A



SC24B_HUMAN
O95487

296
1
Protein transport protein








Sec24B



SCAM3_HUMAN
O14828

40
1
Secretory carrier-associated








membrane protein 3



SCMH1_HUMAN
Q96GD3

512
1
Polycomb protein SCMH1



SCO1_HUMAN
O75880

189
1
Protein SCO1 homolog,








mitochondrial



SCO1_HUMAN
O75880

189
1
Protein SCO1 homolog,








mitochondrial



SCOC_HUMAN
Q9UIL1

88
1
Short coiled-coil protein



SCOC_HUMAN
Q9UIL1

88
1
Short coiled-coil protein



SDCG1_HUMAN
O60524

780
1
Serologically defined colon








cancer antigen 1



SEC13_HUMAN
P55735

15
1
Protein SEC13 homolog



SEC20_HUMAN
Q12981

33
1
Vesicle transport protein








SEC20



SENP6_HUMAN
Q9GZR1

50
1
Sentrin-specific protease 6



SEPT9_HUMAN
Q9UHD8

283
1
Septin-9



SETD2_HUMAN
Q9BYW2

648
1
Histone-lysine N-








methyltransferase SETD2



SETD2_HUMAN
Q9BYW2

1170
1
Histone-lysine N-








methyltransferase SETD2



SETD2_HUMAN
Q9BYW2

1170
1
Histone-lysine N-








methyltransferase SETD2


 


280
SETX_HUMAN
Q7Z333
SVSRPQLESLSGTK
1535
1
Probable helicase senataxin



SF01_HUMAN
Q15637

449
1
Splicing factor 1



SF3A1_HUMAN
Q15459

504
1
Splicing factor 3 subunit 1



SF3A1_HUMAN
Q15459

504
1
Splicing factor 3 subunit 1



SF3A1_HUMAN
Q15459

33
1
Splicing factor 3 subunit 1


 


281
SF3B1_HUMAN
O75533
STGYYDQEIYGGS
35
1
Splicing factor 3B subunit 1





DSR






SF3B2_HUMAN
Q13435

292
1
Splicing factor 3B subunit 2


 


282
SF3B2_HUMAN
Q13435
GSETPQLFTVLPEK
754
1
Splicing factor 3B subunit 2


 


283
SF3B2_HUMAN
Q13435
GSETPQLFTVLPE
754
1
Splicing factor 3B subunit 2





KR






SF3B4_HUMAN
Q15427

13
1
Splicing factor 3B subunit 4



SFPQ_HUMAN
P23246

526
1
Splicing factor, proline- and








glutamine-rich



SFR14_HUMAN
Q8IX01

733
1
Putative splicing factor,








arginine/serine-rich 14



SFR14_HUMAN
Q8IX01

902
1
Putative splicing factor,








arginine/serine-rich 14


 


284
SFR14_HUMAN
Q8IX01
GLPGEAAEDDLA
923
1
Putative splicing factor,





GAPALSQASSGTC


arginine/serine-rich 14





FPR





 


285
SFRIP_HUMAN
Q99590
SFCSDQNESEVEP
408
1
SFRS2-interacting protein





SVNADLK






SFRS2_HUMAN
Q01130

71
1
Splicing factor,








arginine/serine-rich 2



SFRS2_HUMAN
Q01130

71
1
Splicing factor,








arginine/serine-rich 2



SFRS2_HUMAN
Q01130

74
1
Splicing factor,








arginine/serine-rich 2



SFRS2_HUMAN
Q01130

74
1
Splicing factor,








arginine/serine-rich 2



SFRS3_HUMAN
P84103

5
1
Splicing factor,








arginine/serine-rich 3



SFRS5_HUMAN
Q13243

53
1
Splicing factor,








arginine/serine-rich 5



SFRS6_HUMAN
Q13247

168
1
Splicing factor,








arginine/serine-rich 6



SGOL1_HUMAN
Q5FBB7

207
1
Shugoshin-like 1



SH2D3_HUMAN
Q8N5H7

376
1
SH2 domain-containing








protein 3C



SHOT1_HUMAN
A0MZ66

130
1
Shootin-1


 


286
SIPA1_HUMAN
Q96FS4
GGSPPGPGDLAEER
815
1
Signal-induced proliferation-








associated protein 1



SIX4_HUMAN
Q9UIU6

297
1
Homeobox protein SIX4


 


287
SKI_HUMAN
P12755
AAAPADAPSGLE
528
1
Ski oncogene





AELEHLR






SKT_HUMAN
Q5T5P2

610
1
Sickle tail protein homolog



SLD5_HUMAN
Q9BRT9

7
1
DNA replication complex








GINS protein SLD5



SLK_HUMAN
Q9H2G2

404
1
STE20-like serine/threonine-








protein kinase



SLMAP_HUMAN
Q14BN4

465
1
Sarcolemmal membrane-








associated protein



SLU7_HUMAN
O95391

8
1
Pre-mRNA-splicing factor








SLU7



SLU7_HUMAN
O95391

8
1
Pre-mRNA-splicing factor








SLU7



SLU7_HUMAN
O95391

8
1
Pre-mRNA-splicing factor








SLU7



SLU7_HUMAN
O95391

8
1
Pre-mRNA-splicing factor








SLU7



SMC2_HUMAN
O95347

1117
1
Structural maintenance of








chromosomes protein 2



SMCA4_HUMAN
P51532

1382
1
Probable global transcription








activator SNF2L4



SMCE1_HUMAN
Q969G3

265
1
SWI/SNF-related matrix-








associated actin-dependent








regulator of chromatin








subfamily E member 1



SMHD1_HUMAN
A6NHR9

6
1
Structural maintenance of








chromosomes flexible hinge








domain-containing protein 1



SMRC2_HUMAN
Q8TAQ2

815
1
SWI/SNF complex subunit








SMARCC2



SMRD2_HUMAN
Q92925

136
1
SWI/SNF-related matrix-








associated actin-dependent








regulator of chromatin








subfamily D member 2



SNPC4_HUMAN
Q5SXM2

1169
1
snRNA-activating protein








complex subunit 4



SNX12_HUMAN
Q9UMY4

22
1
Sorting nexin-12


 


288
SNX29_HUMAN
Q8TEQ0
GEVTVAEQKPGEI
183
1
Sorting nexin-29





AEELASSYER






SNX2_HUMAN
O60749

85
1
Sorting nexin-2



SNX3_HUMAN
O60493

33
1
Sorting nexin-3



SNX6_HUMAN
Q9UNH7

11
1
Sorting nexin-6



SNX6_HUMAN
Q9UNH7

11
1
Sorting nexin-6



SOBP_HUMAN
A7XYQ1

299
1
Sine oculis-binding protein








homolog


 


289
SODC_HUMAN
P00441
GVADVSIEDSVIS
94
1
Superoxide dismutase [Cu—Zn]





LSGDHCIIGR





 


290
SODC_HUMAN
P00441
SVISLSGDHCIIGR
103
1
Superoxide dismutase [Cu—Zn]



SON_HUMAN
P18583

1641
1
SON protein


 


291
SON_HUMAN
P18583
SFLKFDSEPSAVA
154
1
SON protein





LELPTR






SON_HUMAN
P18583

1719
1
SON protein



SON_HUMAN
P18583

1641
1
SON protein



SON_HUMAN
P18583

353
1
SON protein



SP110_HUMAN
Q9HB58

354
1
Sp110 nuclear body protein



SP110_HUMAN
Q9HB58

354
1
Sp110 nuclear body protein



SP1_HUMAN
P08047

200
1
Transcription factor Sp1



SP3_HUMAN
Q02447

276
1
Transcription factor Sp3


 


292
SP3_HUMAN
Q02447
SAGIQLHPGENAD
531
1
Transcription factor Sp3





SPADIR






SPAS2_HUMAN
Q86XZ4

146
1
Spermatogenesis-associated








serine-rich protein 2



SPAST_HUMAN
Q9UBP0

471
1
Spastin



SPD2B_HUMAN
A1X283

683
1
SH3 and PX domain-








containing protein 2B



SPEC1_HUMAN
Q5M775

214
1
Sperm antigen with calponin








homology and coiled-coil








domains 1



SPEE_HUMAN
P19623

7
1
Spermidine synthase



SPF27_HUMAN
O75934

15
1
Pre-mRNA-splicing factor








SPF27


 


293
SPF30_HUMAN
O75940
SFASTQPTHSWK
63
1
Survival of motor neuron-








related-splicing factor 30



SPG20_HUMAN
Q8N0X7

497
1
Spartin



SPG20_HUMAN
Q8N0X7

497
1
Spartin



SPG20_HUMAN
Q8N0X7

497
1
Spartin



SPS2L_HUMAN
Q9NUQ6

120
1
SPATS2-like protein


 


294
SPT6H_HUMAN
Q7KZ85
SYIEVLDGSR
1048
1
Transcription elongation








factor SPT6



SPTA2_HUMAN
Q13813

1479
1
Spectrin alpha chain, brain



SPTA2_HUMAN
Q13813

501
1
Spectrin alpha chain, brain



SPTN2_HUMAN
O15020

1753
1
Spectrin beta chain, brain 2


 


295
SR140_HUMAN
O15042
GAPLEDVDGIPID
705
1
U2-associated protein SR140





ATPIDDLDGVPIK






SR140_HUMAN
O15042

713
1
U2-associated protein SR140


 


296
SR140_HUMAN
O15042
GVPIKSLDDDLDG
726
1
U2-associated protein SR140





VPLDATEDSK





 


297
SR140_HUMAN
O15042
GVPIKSLDDDLDG
726
1
U2-associated protein SR140





VPLDATEDSKK





 


298
SR140_HUMAN
O15042
GVPLDATEDSK
738
1
U2-associated protein SR140


 


299
SR140_HUMAN
O15042
GVPLDATEDSKK
738
1
U2-associated protein SR140


 


300
SR140_HUMAN
O15042
GVPLDATEDSKK
738
1
U2-associated protein SR140





NEPIFK





 


301
SRCAP_HUMAN
Q6ZRS2
GFPAGEGEEAGRP
2276
1
Helicase SRCAP





GAEDEEMSR





 


302
SRCAP_HUMAN
Q6ZRS2
GFPAGEGEEAGRP
2276
1
Helicase SRCAP





GAEDEEMSR






SRC_HUMAN
P12931

46
1
Proto-oncogene tyrosine-








protein kinase Src


 


303
SRFB1_HUMAN
Q8NEF9
SVVSLESQK
212
1
Serum response factor-








binding protein 1


 


304
SRFB1_HUMAN
Q8NEF9
SVVSLESQKTPAD
212
1
Serum response factor-





PKLK


binding protein 1


 


305
SRP68_HUMAN
Q9UHB9
AHQTETSSSQVK
538
1
Signal recognition particle 68 kDa





DNKPLVER


protein


 


306
SRP68_HUMAN
Q9UHB9
AHQTETSSSQVK
538
1
Signal recognition particle 68 kDa








protein



SRPK1_HUMAN
Q96SB4

413
1
Serine/threonine-protein








kinase SRPK1



SRRM2_HUMAN
Q9UQ35

148
1
Serine/arginine repetitive








matrix protein 2


 


307
SRRM2_HUMAN
Q9UQ35
SNSLLGQSR
1150
1
Serine/arginine repetitive








matrix protein 2



SRRM2_HUMAN
Q9UQ35

148
1
Serine/arginine repetitive








matrix protein 2



SSA27_HUMAN
O60232

82
1
Sjoegren








syndrome/scleroderma








autoantigen 1



SSBP3_HUMAN
Q9BWW4

287
1
Single-stranded DNA-








binding protein 3



SSF1_HUMAN
Q9NQ55

246
1
Suppressor of SWI4 1








homolog



SSFA2_HUMAN
P28290

628
1
Sperm-specific antigen 2



SSH2_HUMAN
Q76I76

964
1
Protein phosphatase








Slingshot homolog 2



SSRP1_HUMAN
Q08945

174
1
FACT complex subunit








SSRP1



STAP1_HUMAN
Q9ULZ2

171
1
Signal-transducing adaptor








protein 1


 


308
STAP1_HUMAN
Q9ULZ2
VLNPMPACFYTV
171
1
Signal-transducing adaptor





SR


protein 1



STK10_HUMAN
O94804

333
1
Serine/threonine-protein








kinase 10



STK24_HUMAN
Q9Y6E0

326
1
Serine/threonine-protein








kinase 24



STK24_HUMAN
Q9Y6E0

326
1
Serine/threonine-protein








kinase 24



STK39_HUMAN
Q9UEW8

436
1
STE20/SPS1-related proline-








alanine-rich protein kinase


 


309
STK4_HUMAN
Q13043
GANTMIEHDDTL
350
1
Serine/threonine-protein





PSQLGTMVINAED


kinase 4





EEEEGTMK





 


310
STK4_HUMAN
Q13043
GANTMIEHDDTL
350
1
Serine/threonine-protein





PSQLGTMVINAED


kinase 4





EEEEGTMKR





 


311
STK4_HUMAN
Q13043
GANTMIEHDDTL
350
1
Serine/threonine-protein





PSQLGTMVINAED


kinase 4





EEEEGTMKRR






STRN_HUMAN
O43815

36
1
Striatin


 


312
STRN_HUMAN
O43815
SLTYDIANNK
437
1
Striatin


 


313
STRN_HUMAN
O43815
SLTYDIANNKDALR
437
1
Striatin


 


314
STRN_HUMAN
O43815
SLTYDIANNKDAL
437
1
Striatin





RK






STX10_HUMAN
O60499

197
1
Syntaxin-10



STX10_HUMAN
O60499

139
1
Syntaxin-10


 


315
STX12_HUMAN
Q86Y82
SIEANVESSEVHV
218
1
Syntaxin-12





ER






STX17_HUMAN
P56962

202
1
Syntaxin-17



STX17_HUMAN
P56962

202
1
Syntaxin-17


 


316
STX7_HUMAN
O15400
SIEANVENAEVHV
205
1
Syntaxin-7





QQANQQLSR





 


317
SUGT1_HUMAN
Q9Y2Z0
ALIDEDPQAALEE
21
1
Suppressor of G2 allele of





LTK


SKP1 homolog



SYAP1_HUMAN
Q96A49

282
1
Synapse-associated protein 1



SYEP_HUMAN
P07814

930
1
Bifunctional aminoacyl-








tRNA synthetase


 


318
SYF2_HUMAN
O95926
SAEEGSLAAAAEL
13
1
Pre-mRNA-splicing factor





AAQK


SYF2


 


319
SYF2_HUMAN
O95926
SAEEGSLAAAAEL
13
1
Pre-mRNA-splicing factor





AAQKR


SYF2



SYG_HUMAN
P41250

57
1
Glycyl-tRNA synthetase



SYMPK_HUMAN
Q92797

29
1
Symplekin



SYNC_HUMAN
O43776

410
1
Asparaginyl-tRNA








synthetase, cytoplasmic



SYNE1_HUMAN
Q8NF91

8280
1
Nesprin-1



SYNE2_HUMAN
Q8WXH0

4216
1
Nesprin-2


 


320
SYWC_HUMAN
P23381
FVDPWTVQTSSAK
84
1
Tryptophanyl-tRNA








synthetase, cytoplasmic



T106B_HUMAN
Q9NUM4

20
1
Transmembrane protein








106B



T106B_HUMAN
Q9NUM4

20
1
Transmembrane protein








106B



T106C_HUMAN
Q9BVX2

24
1
Transmembrane protein








106C



T2EA_HUMAN
P29083

304
1
General transcription factor








IIE subunit 1


 


321
T2EA_HUMAN
P29083
AFQEREEGHAGP
304
1
General transcription factor





DDNEEVMR


IIE subunit 1



T2FA_HUMAN
P35269

273
1
General transcription factor








IIF subunit 1



T2FA_HUMAN
P35269

273
1
General transcription factor








IIF subunit 1



TACC1_HUMAN
O75410

324
1
Transforming acidic coiled-








coil-containing protein 1


 


322
TACC1_HUMAN
O75410
GHATDEEKLASTS
501
1
Transforming acidic coiled-





CGQK


coil-containing protein 1


 


323
TACC1_HUMAN
O75410
GHATDEEK
501
1
Transforming acidic coiled-








coil-containing protein 1



TACC2_HUMAN
O95359

372
1
Transforming acidic coiled-








coil-containing protein 2



TACC3_HUMAN
Q9Y6A5

287
1
Transforming acidic coiled-








coil-containing protein 3



TACC3_HUMAN
Q9Y6A5

22
1
Transforming acidic coiled-








coil-containing protein 3



TAD1L_HUMAN
Q96BN2

79
1
Transcriptional adapter 1-








like protein


 


324
TAF11_HUMAN
Q15544
GIPEETDGDADVD
35
1
Transcription initiation factor





LK


TFIID subunit 11



TAF7_HUMAN
Q15545

101
1
Transcription initiation factor








TFIID subunit 7



TBA1A_HUMAN
Q71U36

34
5
Tubulin alpha-1A chain



TBA1B_HUMAN
P68363

34

Tubulin alpha-1B chain



TBA1C_HUMAN
Q9BQE3

34

Tubulin alpha-1C chain



TBA3C_HUMAN
Q13748

34

Tubulin alpha-3C/D chain



TBA3E_HUMAN
Q6PEY2

34

Tubulin alpha-3E chain



TBA1A_HUMAN
Q71U36

34
5
Tubulin alpha-1A chain



TBA1B_HUMAN
P68363

34

Tubulin alpha-1B chain



TBA1C_HUMAN
Q9BQE3

34

Tubulin alpha-1C chain



TBA3C_HUMAN
Q13748

34

Tubulin alpha-3C/D chain



TBA3E_HUMAN
Q6PEY2

34

Tubulin alpha-3E chain



TBA1A_HUMAN
Q71U36

34
5
Tubulin alpha-1A chain



TBA1B_HUMAN
P68363

34

Tubulin alpha-1B chain



TBA1C_HUMAN
Q9BQE3

34

Tubulin alpha-1C chain



TBA3C_HUMAN
Q13748

34

Tubulin alpha-3C/D chain



TBA3E_HUMAN
Q6PEY2

34

Tubulin alpha-3E chain



TBA1A_HUMAN
Q71U36

48
5
Tubulin alpha-1A chain



TBA1B_HUMAN
P68363

48

Tubulin alpha-1B chain



TBA1C_HUMAN
Q9BQE3

48

Tubulin alpha-1C chain



TBA3C_HUMAN
Q13748

48

Tubulin alpha-3C/D chain



TBA3E_HUMAN
Q6PEY2

48

Tubulin alpha-3E chain



TBA1A_HUMAN
Q71U36

34
6
Tubulin alpha-1A chain



TBA1B_HUMAN
P68363

34

Tubulin alpha-1B chain



TBA1C_HUMAN
Q9BQE3

34

Tubulin alpha-1C chain



TBA3C_HUMAN
Q13748

34

Tubulin alpha-3C/D chain



TBA3E_HUMAN
Q6PEY2

34

Tubulin alpha-3E chain



TBA4A_HUMAN
P68366

34

Tubulin alpha-4A chain



TBA1A_HUMAN
Q71U36

200
7
Tubulin alpha-1A chain



TBA1B_HUMAN
P68363

200

Tubulin alpha-1B chain



TBA1C_HUMAN
Q9BQE3

200

Tubulin alpha-1C chain



TBA3C_HUMAN
Q13748

200

Tubulin alpha-3C/D chain



TBA3E_HUMAN
Q6PEY2

200

Tubulin alpha-3E chain



TBA4A_HUMAN
P68366

200

Tubulin alpha-4A chain



TBA8_HUMAN
Q9NY65

200

Tubulin alpha-8 chain



TBA1A_HUMAN
Q71U36

246
7
Tubulin alpha-1A chain



TBA1B_HUMAN
P68363

246

Tubulin alpha-1B chain



TBA1C_HUMAN
Q9BQE3

246

Tubulin alpha-1C chain



TBA3C_HUMAN
Q13748

246

Tubulin alpha-3C/D chain



TBA3E_HUMAN
Q6PEY2

246

Tubulin alpha-3E chain



TBA4A_HUMAN
P68366

246

Tubulin alpha-4A chain



TBA8_HUMAN
Q9NY65

246

Tubulin alpha-8 chain



TBB2A_HUMAN
Q13885

115
5
Tubulin beta-2A chain



TBB2B_HUMAN
Q9BVA1

115

Tubulin beta-2B chain



TBB2C_HUMAN
P68371

115

Tubulin beta-2C chain



TBB3_HUMAN
Q13509

115

Tubulin beta-3 chain



TBB5_HUMAN
P07437

115

Tubulin beta chain



TBB2A_HUMAN
Q13885

115
5
Tubulin beta-2A chain



TBB2B_HUMAN
Q9BVA1

115

Tubulin beta-2B chain



TBB2C_HUMAN
P68371

115

Tubulin beta-2C chain



TBB3_HUMAN
Q13509

115

Tubulin beta-3 chain



TBB5_HUMAN
P07437

115

Tubulin beta chain



TBB2C_HUMAN
P68371

115
2
Tubulin beta-2C chain



TBB5_HUMAN
P07437

115

Tubulin beta chain



TBCC_HUMAN
Q15814

154
1
Tubulin-specific chaperone C



TBCD4_HUMAN
O60343

273
1
TBC1 domain family








member 4



TBCD4_HUMAN
O60343

276
1
TBC1 domain family








member 4



TBL1R_HUMAN
Q9BZK7

153
1
F-box-like/WD repeat-








containing protein TBL1XR1


 


325
TBL1R_HUMAN
Q9BZK7
AVMPDVVQTR
86
2
F-box-like/WD repeat-








containing protein TBL1XR1


325
TBL1X_HUMAN
O60907
AVMPDVVQTR
86

F-box-like/WD repeat-








containing protein TBL1X



TBL1R_HUMAN
Q9BZK7

153
2
F-box-like/WD repeat-








containing protein TBL1XR1



TBL1Y_HUMAN
Q9BQ87

163

F-box-like/WD repeat-








containing protein TBL1Y



TBL1X_HUMAN
O60907

165
1
F-box-like/WD repeat-








containing protein TBL1X



TCEA1_HUMAN
P23193

125
1
Transcription elongation








factor A protein 1



TCF20_HUMAN
Q9UGU0

1220
1
Transcription factor 20



TCF20_HUMAN
Q9UGU0

1220
1
Transcription factor 20



TCF20_HUMAN
Q9UGU0

1220
1
Transcription factor 20



TCOF_HUMAN
Q13428

1243
1
Treacle protein


 


326
TCOF_HUMAN
Q13428
GKQEAKPQQAAG
1243
1
Treacle protein





MLSPK






TCOF_HUMAN
Q13428

1102
1
Treacle protein



TCPD_HUMAN
P50991

457
1
T-complex protein 1 subunit








delta



TCPD_HUMAN
P50991

269
2
T-complex protein 1 subunit








delta



TCPD_HUMAN
P50991

269
2
T-complex protein 1 subunit








delta



TCPE_HUMAN
P48643

66
1
T-complex protein 1 subunit








epsilon



TCPE_HUMAN
P48643

154
1
T-complex protein 1 subunit








epsilon



TCPZ_HUMAN
P40227

405
1
T-complex protein 1 subunit








zeta



TCTP_HUMAN
P13693

26
1
Translationally-controlled








tumor protein



TDRD6_HUMAN
O60522

1919
1
Tudor domain-containing








protein 6



TEX2_HUMAN
Q8IWB9

357
1
Testis-expressed sequence 2








protein


 


327
TEX2_HUMAN
Q8IWB9
GLSVSQAPAILPV
97
1
Testis-expressed sequence 2





SK


protein



TF2B_HUMAN
Q00403

208
1
Transcription initiation factor








IIB



TF2B_HUMAN
Q00403

208
1
Transcription initiation factor








IIB



TF2L1_HUMAN
Q9NZI6

23
3
Transcription factor CP2-like








protein 1



TFCP2_HUMAN
Q12800

43

Alpha-globin transcription








factor CP2



UBIP1_HUMAN
Q9NZI7

40

Upstream-binding protein 1


 


328
TF3A_HUMAN
Q92664
AFIAAGESSAPTPP
19
1
Transcription factor IIIA





RPALPR






TF65_HUMAN
Q04206

98
1
Transcription factor p65



TGS1_HUMAN
Q96RS0

344
1
Trimethylguanosine synthase








homolog



TGS1_HUMAN
Q96RS0

344
1
Trimethylguanosine synthase








homolog



TGS1_HUMAN
Q96RS0

338
1
Trimethylguanosine synthase








homolog



THOC4_HUMAN
Q86V81

94
1
THO complex subunit 4



THOC5_HUMAN
Q13769

18
1
THO complex subunit 5








homolog



THOP1_HUMAN
P52888

14
1
Thimet oligopeptidase



TIF1A_HUMAN
O15164

785
1
Transcription intermediary








factor 1-alpha


 


329
TIF1B_HUMAN
Q13263
ANQCCTSCEDNA
149
1
Transcription intermediary





PATSYCVECSEPL


factor 1-beta





CETCVEAHQR






TIF1B_HUMAN
Q13263

106
1
Transcription intermediary








factor 1-beta


 


330
TIF1B_HUMAN
Q13263
STFSLDQPGGTLD
727
1
Transcription intermediary





LTLIR


factor 1-beta



TIF1B_HUMAN
Q13263

686
1
Transcription intermediary








factor 1-beta



TIF1B_HUMAN
Q13263

689
1
Transcription intermediary








factor 1-beta


 


331
TIM_HUMAN
Q9UNS1
SVVPFDAASEVPV
580
1
Protein timeless homolog





EEQR






TINF2_HUMAN
Q9BSI4

208
1
TERF1-interacting nuclear








factor 2


 


332
TINF2_HUMAN
Q9BSI4
SVNLAEPMEQNP
208
1
TERF1-interacting nuclear





PQQQR


factor 2



TLK2_HUMAN
Q86UE8

133
1
Serine/threonine-protein








kinase tousled-like 2



TM168_HUMAN
Q9H0V1

427
1
Transmembrane protein 168



TM1L2_HUMAN
Q6ZVM7

158
1
TOM1-like protein 2



TMUB1_HUMAN
Q9BVT8

61
1
Transmembrane and








ubiquitin-like domain-








containing protein 1


 


333
TMUB1_HUMAN
Q9BVT8
SMRGEAPGAETPS
61
1
Transmembrane and





LR


ubiquitin-like domain-








containing protein 1



TNIP2_HUMAN
Q8NFZ5

195
1
TNFAIP3-interacting protein 2



TNR6A_HUMAN
Q8NDV7

1543
1
Trinucleotide repeat-








containing gene 6A protein



TNR6A_HUMAN
Q8NDV7

1543
1
Trinucleotide repeat-








containing gene 6A protein


 


334
TOE1_HUMAN
Q96GM8
SIKPEETEQEVAA
374
1
Target of EGR1 protein 1





DETR






TOE1_HUMAN
Q96GM8

8
1
Target of EGR1 protein 1


 


335
TOIP1_HUMAN
Q5JTV8
SILKSELGNQSPST
305
1
Torsin-1A-interacting protein 1





SSR






TOIP1_HUMAN
Q5JTV8

227
1
Torsin-1A-interacting protein 1



TOIP1_HUMAN
Q5JTV8

227
1
Torsin-1A-interacting protein 1



TOLIP_HUMAN
Q9H0E2

37
1
Toll-interacting protein



TOM1_HUMAN
O60784

394
1
Target of Myb protein 1



TOM1_HUMAN
O60784

185
1
Target of Myb protein 1



TOM1_HUMAN
O60784

180
1
Target of Myb protein 1



TOM1_HUMAN
O60784

158
1
Target of Myb protein 1


 


336
TOM1_HUMAN
O60784
MLSPIHTPQR
158
1
Target of Myb protein 1



TOP2B_HUMAN
Q02880

1471
1
DNA topoisomerase 2-beta



TP53B_HUMAN
Q12888

212
1
Tumor suppressor p53-








binding protein 1


 


337
TP53B_HUMAN
Q12888
GCSTPSREEGGCS
318
1
Tumor suppressor p53-





LASTPATTLHLLQ


binding protein 1





LSGQR






TP53B_HUMAN
Q12888

1479
1
Tumor suppressor p53-








binding protein 1



TP53B_HUMAN
Q12888

318
1
Tumor suppressor p53-








binding protein 1


 


338
TP53B_HUMAN
Q12888
SSQPSLPLVR
830
1
Tumor suppressor p53-








binding protein 1



TPD54_HUMAN
O43399

3
1
Tumor protein D54


 


339
TPRGL_HUMAN
Q5T0D9
SAGTSPTAVLAA
10
1
Tumor protein p63-regulated





GEEVGAGGGPGG


gene 1-like protein





GRPGAGTPLR





 


340
TPRGL_HUMAN
Q5T0D9
SAGTSPTAVLAA
10
1
Tumor protein p63-regulated





GEEVGAGGGPGG


gene 1-like protein





GRPGAGTPLRQTL








WPLSIHDPTR






TPR_HUMAN
P12270

1838
1
Nucleoprotein TPR



TPR_HUMAN
P12270

2148
1
Nucleoprotein TPR


 


341
TR150_HUMAN
Q9Y2W1
SFDEDLARPSGLL
575
1
Thyroid hormone receptor-





AQER


associated protein 3



TRBP2_HUMAN
Q15633

235
1
TAR RNA-binding protein 2


 


342
TREF1_HUMAN
Q96PN7
GSNVTVTPGPGE
761
1
Transcriptional-regulating





QTVDVEPR


factor 1



TRI33_HUMAN
Q9UPN9

830
1
E3 ubiquitin-protein ligase








TRIM33



TRI33_HUMAN
Q9UPN9

830
1
E3 ubiquitin-protein ligase








TRIM33



TRI33_HUMAN
Q9UPN9

830
1
E3 ubiquitin-protein ligase








TRIM33



TRIP4_HUMAN
Q15650

123
1
Activating signal








cointegrator 1



TRIP4_HUMAN
Q15650

289
1
Activating signal








cointegrator 1



TRM1L_HUMAN
Q7Z2T5

45
1
TRM1-like protein



TRS85_HUMAN
Q9Y2L5

854
1
Protein TRS85 homolog



TSC1_HUMAN
Q92574

639
1
Hamartin


 


343
TSC1_HUMAN
Q92574
GVPSTSPMEVLDR
639
1
Hamartin





LIQQGADAHSK





 


344
TSC1_HUMAN
Q92574
GVPSTSPMEVLDR
639
1
Hamartin



TSR1_HUMAN
Q2NL82

333
1
Pre-rRNA-processing protein








TSR1 homolog



TSR1_HUMAN
Q2NL82

333
1
Pre-rRNA-processing protein








TSR1 homolog


 


345
TSR1_HUMAN
Q2NL82
AVDDMEEGLK
333
1
Pre-rRNA-processing protein








TSR1 homolog



TSR1_HUMAN
Q2NL82

333
1
Pre-rRNA-processing protein








TSR1 homolog


 


346
TSR1_HUMAN
Q2NL82
AVDDMEEGLKVL
333
1
Pre-rRNA-processing protein





MK


TSR1 homolog



TTC1_HUMAN
Q99614

66
1
Tetratricopeptide repeat








protein 1



TTC4_HUMAN
O95801

255
1
Tetratricopeptide repeat








protein 4


 


347
TTF2_HUMAN
Q9UNY4
STGRPLVILPQR
827
1
Transcription termination








factor 2


 


348
TTF2_HUMAN
Q9UNY4
STGRPLVILPQRK
827
1
Transcription termination








factor 2



TYB10_HUMAN
P63313

7
1
Thymosin beta-10



TYSY_HUMAN
P04818

120
1
Thymidylate synthase



TYY1_HUMAN
P25490

120
1
Transcriptional repressor








protein YY1



U119A_HUMAN
Q13432

45
1
Protein unc-119 homolog A



U119B_HUMAN
A6NIH7

52
1
Protein unc-119 homolog B



U2AF2_HUMAN
P26368

129
1
Splicing factor U2AF 65 kDa








subunit


 


349
U2AF2_HUMAN
P26368
GLAVTPTPVPVV
129
1
Splicing factor U2AF 65 kDa





GSQMTR


subunit


 


350
UAP1L_HUMAN
Q3KQV9
GVPQVVEYSEISP
300
1
UDP-N-acetylhexosamine





ETAQLR


pyrophosphorylase-like








protein 1



UAP56_HUMAN
Q13838

26
1
Spliceosome RNA helicase








BAT1


 


351
UBA1_HUMAN
P22314
ALECLPEDKEVLT
428
1
Ubiquitin-like modifier-





EDK


activating enzyme 1



UBA3_HUMAN
Q8TBC4

26
1
NEDD8-activating enzyme








E1 catalytic subunit



UBA3_HUMAN
Q8TBC4

26
1
NEDD8-activating enzyme








E1 catalytic subunit



UBAP2_HUMAN
Q5T6F2

855
1
Ubiquitin-associated protein 2



UBAP2_HUMAN
Q5T6F2

202
1
Ubiquitin-associated protein 2



UBAP2_HUMAN
Q5T6F2

263
1
Ubiquitin-associated protein 2



UBE2O_HUMAN
Q9C0C9

438
1
Ubiquitin-conjugating








enzyme E2 O


 


352
UBE2O_HUMAN
Q9C0C9
GSASPVEMQDEG
438
1
Ubiquitin-conjugating





AEEPHEAGEQLPP


enzyme E2 O





FLLK





 


353
UBE2O_HUMAN
Q9C0C9
GSASPVEMQDEG
438
1
Ubiquitin-conjugating





AEEPHEAGEQLPP


enzyme E2 O





FLLKEGR





 


354
UBE2O_HUMAN
Q9C0C9
GSASPVEMQDEG
438
1
Ubiquitin-conjugating





AEEPHEAGEQLPP


enzyme E2 O





FLLKEGRDDR






UBE2O_HUMAN
Q9C0C9

1226
1
Ubiquitin-conjugating








enzyme E2 O



UBFD1_HUMAN
O14562

233
1
Ubiquitin domain-containing








protein UBFD1


 


355
UBN1_HUMAN
Q9NPG3
SFIDNSEAYDELV
137
1
Ubinuclein





PASLTTK






UBP10_HUMAN
Q14694

126
1
Ubiquitin carboxyl-terminal








hydrolase 10



UBP10_HUMAN
Q14694

139
1
Ubiquitin carboxyl-terminal








hydrolase 10



UBP10_HUMAN
Q14694

218
1
Ubiquitin carboxyl-terminal








hydrolase 10



UBP14_HUMAN
P54578

77
1
Ubiquitin carboxyl-terminal








hydrolase 14



UBP14_HUMAN
P54578

228
1
Ubiquitin carboxyl-terminal








hydrolase 14


 


356
UBP19_HUMAN
O94966
GRPDEVVAEEAW
620
1
Ubiquitin carboxyl-terminal





QR


hydrolase 19



UBP2L_HUMAN
Q14157

412
1
Ubiquitin-associated protein








2-like



UBP2L_HUMAN
Q14157

299
1
Ubiquitin-associated protein








2-like


 


357
UBP2L_HUMAN
Q14157
GSLASNPYSGDLTK
851
1
Ubiquitin-associated protein








2-like



UBP34_HUMAN
Q70CQ2

3367
1
Ubiquitin carboxyl-terminal








hydrolase 34



UBP34_HUMAN
Q70CQ2

3367
1
Ubiquitin carboxyl-terminal








hydrolase 34



UBP36_HUMAN
Q9P275

577
1
Ubiquitin carboxyl-terminal








hydrolase 36



UBP42_HUMAN
Q9H9J4

765
1
Ubiquitin carboxyl-terminal








hydrolase 42



UBP5_HUMAN
P45974

768
1
Ubiquitin carboxyl-terminal








hydrolase 5



UBP5_HUMAN
P45974

768
1
Ubiquitin carboxyl-terminal








hydrolase 5



UBP5_HUMAN
P45974

783
1
Ubiquitin carboxyl-terminal








hydrolase 5



UBP5_HUMAN
P45974

135
1
Ubiquitin carboxyl-terminal








hydrolase 5



UBP5_HUMAN
P45974

783
1
Ubiquitin carboxyl-terminal








hydrolase 5



UBP7_HUMAN
Q93009

51
1
Ubiquitin carboxyl-terminal








hydrolase 7


 


358
UBP7_HUMAN
Q93009
GHNTAEEDMEDD
51
1
Ubiquitin carboxyl-terminal





TSWR


hydrolase 7



UBQL1_HUMAN
Q9UMX0

16
1
Ubiquilin-1


 


359
UBR4_HUMAN
Q5T4S7
SVAGEHSVSGR
2904
1
E3 ubiquitin-protein ligase








UBR4


 


360
UBXN7_HUMAN
O94888
GFRDFQTETIR
110
1
UBX domain-containing








protein 7


 


361
UBXN7_HUMAN
O94888
GFRDFQTETIRQE
110
1
UBX domain-containing





QELR


protein 7



UBXN7_HUMAN
O94888

401
1
UBX domain-containing








protein 7



UGPA_HUMAN
Q16851

16
1
UTP--glucose-1-phosphate








uridylyltransferase



UH1BL_HUMAN
A0JNW5

1174
1
UHRF1-binding protein 1-








like


 


362
UHRF1_HUMAN
Q96T88
SRPADEDMWDET
119
1
E3 ubiquitin-protein ligase





ELGLYK


UHRF1


 


363
UHRF1_HUMAN
Q96T88
SRPADEDMWDET
119
1
E3 ubiquitin-protein ligase





ELGLYKVNEYVD


UHRF1





AR





 


364
URP2_HUMAN
Q86UX7
SLTTIPELK
345
1
Fermitin family homolog 3


 


365
URP2_HUMAN
Q86UX7
SLTTIPELKDHLR
345
1
Fermitin family homolog 3



USE1_HUMAN
Q9NZ43

130
1
Vesicle transport protein








USE1



USF2_HUMAN
Q15853

121
1
Upstream stimulatory factor 2



USO1_HUMAN
O60763

758
1
General vesicular transport








factor p115



UTRO_HUMAN
P46939

262
1
Utrophin



VAMP2_HUMAN
P63027

69
2
Vesicle-associated








membrane protein 2



VAMP3_HUMAN
Q15836

52

Vesicle-associated








membrane protein 3



VATD_HUMAN
Q9Y5K8

118
1
V-type proton ATPase








subunit D


 


366
VIME_HUMAN
P08670
AINTEFK
91
1
Vimentin


 


367
VIME_HUMAN
P08670
AINTEFKNTR
91
1
Vimentin


 


368
VIME_HUMAN
P08670
ALKGTNESLER
332
1
Vimentin


 


369
VIME_HUMAN
P08670
FSLADAINTEFK
86
1
Vimentin


 


370
VIME_HUMAN
P08670
FSLADAINTEFKN
86
1
Vimentin





TR






VIME_HUMAN
P08670

83
1
Vimentin



VIME_HUMAN
P08670

430
1
Vimentin


 


371
VIME_HUMAN
P08670
VDVSKPDLTAALR
258
1
Vimentin


 


372
VIME_HUMAN
P08670
VDVSKPDLTAAL
258
1
Vimentin





RDVR





 


373
VIME_HUMAN
P08670
VSKPDLTAALR
260
1
Vimentin


 


374
VIME_HUMAN
P08670
VSKPDLTAALRD
260
1
Vimentin





VR





 


375
VP13D_HUMAN
Q5THJ4
SVGTYLPGASR
2611
1
Vacuolar protein sorting-








associated protein 13D


 


376
VPS4A_HUMAN
Q9UN37
SLCGSRNENESEA
231
1
Vacuolar protein sorting-





AR


associating protein 4A


 


377
VPS4A_HUMAN
Q9UN37
SLCGSRNENESEA
231
1
Vacuolar protein sorting-





ARR


associating protein 4A



VRK1_HUMAN
Q99986

232
1
Serine/threonine-protein








kinase VRK1



WAPL_HUMAN
Q7Z5K2

155
1
Wings apart-like protein








homolog



WASF1_HUMAN
Q92558

248
1
Wiskott-Aldrich syndrome








protein family member 1



WASF2_HUMAN
Q9Y6W5

243
1
Wiskott-Aldrich syndrome








protein family member 2



WASF2_HUMAN
Q9Y6W5

412
1
Wiskott-Aldrich syndrome








protein family member 2



WASH1_HUMAN
A8K0Z3

299
1
WAS protein family








homolog 1



WDR33_HUMAN
Q9C0J8

1184
1
WD repeat-containing








protein 33



WDR44_HUMAN
Q5JSH3

84
1
WD repeat-containing








protein 44



WDR55_HUMAN
Q9H6Y2

21
1
WD repeat-containing








protein 55



WDR62_HUMAN
O43379

1302
1
WD repeat-containing








protein 62


 


378
WDR92_HUMAN
Q96MX6
GIGGLGIGEGAPEI
119
1
WD repeat-containing





VTGSR


protein 92



WFS1_HUMAN
O76024

212
1
Wolframin



WFS1_HUMAN
O76024

76
1
Wolframin



WIPF1_HUMAN
O43516

182
1
WAS/WASL-interacting








protein family member 1



WNK1_HUMAN
Q9H4A3

1070
1
Serine/threonine-protein








kinase WNK1



WNK1_HUMAN
Q9H4A3

1070
1
Serine/threonine-protein








kinase WNK1



WNK1_HUMAN
Q9H4A3

1070
1
Serine/threonine-protein








kinase WNK1



WNK1_HUMAN
Q9H4A3

2026
1
Serine/threonine-protein








kinase WNK1



WNK1_HUMAN
Q9H4A3

653
1
Serine/threonine-protein








kinase WNK1



WNK1_HUMAN
Q9H4A3

1070
1
Serine/threonine-protein








kinase WNK1



WRIP1_HUMAN
Q96S55

193
1
ATPase WRNIP1



WWC2_HUMAN
Q6AWC2

856
1
Protein WWC2



XPA_HUMAN
P23025

6
1
DNA repair protein








complementing XP-A cells



YAP1_HUMAN
P46937

112
1
65 kDa Yes-associated








protein



YBOX1_HUMAN
P67809

25
1
Nuclease-sensitive element-








binding protein 1



YBOX1_HUMAN
P67809

25
1
Nuclease-sensitive element-








binding protein 1



YBOX1_HUMAN
P67809

113
1
Nuclease-sensitive element-








binding protein 1



YIPF3_HUMAN
Q9GZM5

69
1
Protein YIPF3



YJ005_HUMAN
Q6ZSR9

118
1
Uncharacterized protein








FLJ45252



YJ005_HUMAN
Q6ZSR9

124
1
Uncharacterized protein








FLJ45252



YM017_HUMAN
A8MX80

224
1
Putative UPF0607 protein








ENSP00000383144


 


379
YTDC2_HUMAN
Q9H6S0
GIPNDSSDSEMEDK
325
1
YTH domain-containing








protein 2



YTHD1_HUMAN
Q9BYJ9

165
1
YTH domain family protein 1



YTHD1_HUMAN
Q9BYJ9

165
1
YTH domain family protein 1



YTHD1_HUMAN
Q9BYJ9

165
1
YTH domain family protein 1


 


380
YTHD2_HUMAN
Q9Y5A9
GNGVGQSQAGSG
368
1
YTH domain family protein 2





STPSEPHPVLEKLR





 


381
YTHD2_HUMAN
Q9Y5A9
GQSAFANETLNK
167
1
YTH domain family protein 2


 


382
YTHD2_HUMAN
Q9Y5A9
GQSAFANETLNK
167
1
YTH domain family protein 2





APGMNTIDQGMA








ALK





 


383
YTHD2_HUMAN
Q9Y5A9
GQSAFANETLNK
167
1
YTH domain family protein 2





APGMNTIDQGMA








ALKLGSTEVASN








VPK






YTHD2_HUMAN
Q9Y5A9

368
1
YTH domain family protein 2



YTHD3_HUMAN
Q7Z739

169
1
YTH domain family protein 3



YTHD3_HUMAN
Q7Z739

169
1
YTH domain family protein 3



ZAP70_HUMAN
P43403

291
1
Tyrosine-protein kinase








ZAP-70



ZBT34_HUMAN
Q8NCN2

140
1
Zinc finger and BTB








domain-containing protein








34


 


384
ZBT44_HUMAN
Q8NCP5
GSISPVSSECSVVER
158
1
Zinc finger and BTB








domain-containing protein








44



ZC11A_HUMAN
O75152

349
1
Zinc finger CCCH domain-








containing protein 11A



ZC11A_HUMAN
O75152

531
1
Zinc finger CCCH domain-








containing protein 11A



ZC3H4_HUMAN
Q9UPT8

68
1
Zinc finger CCCH domain-








containing protein 4



ZC3H4_HUMAN
Q9UPT8

742
1
Zinc finger CCCH domain-








containing protein 4



ZC3HD_HUMAN
Q5T200

160
1
Zinc finger CCCH domain-








containing protein 13



ZC3HD_HUMAN
Q5T200

160
1
Zinc finger CCCH domain-








containing protein 13


 


385
ZC3HE_HUMAN
Q6PJT7
GVPSPPGYMSDQ
524
1
Zinc finger CCCH domain-





EEDMCFEGMKPV


containing protein 14





NQTAASNKGLR





 


386
ZCCHV_HUMAN
Q7Z2W4
GVATDITSTR
434
1
Zinc finger CCCH-type








antiviral protein 1


 


387
ZCCHV_HUMAN
Q7Z2W4
SLSDVTSTTSSR
492
1
Zinc finger CCCH-type








antiviral protein 1


 


388
ZCH18_HUMAN
Q86VM9
TVLEPYADPYYD
362
1
Zinc finger CCCH domain-





YEIER


containing protein 18



ZCHC2_HUMAN
Q9C0B9

235
1
Zinc finger CCHC domain-








containing protein 2


 


389
ZCHC8_HUMAN
Q6NZY4
GETEVGEIQQNK
344
1
Zinc finger CCHC domain-








containing protein 8


 


390
ZEB1_HUMAN
P37275
AADCEGVPEDDL
50
1
Zinc finger E-box-binding





PTDQTVLPGR


homeobox 1



ZF161_HUMAN
O43829

244
1
Zinc finger protein 161








homolog



ZF161_HUMAN
O43829

244
1
Zinc finger protein 161








homolog



ZFAN6_HUMAN
Q6FIF0

107
1
AN1-type zinc finger protein 6



ZFAN6_HUMAN
Q6FIF0

127
1
AN1-type zinc finger protein 6



ZFPL1_HUMAN
O95159

172
1
Zinc finger protein-like 1


 


391
ZFX_HUMAN
P17010
GTCPEVIK
245
1
Zinc finger X-chromosomal








protein


 


392
ZFX_HUMAN
P17010
GTCPEVIKVYIFK
245
1
Zinc finger X-chromosomal








protein



ZFY16_HUMAN
Q7Z3T8

535
1
Zinc finger FYVE domain-








containing protein 16



ZFY16_HUMAN
Q7Z3T8

108
1
Zinc finger FYVE domain-








containing protein 16



ZFY16_HUMAN
Q7Z3T8

284
1
Zinc finger FYVE domain-








containing protein 16


 


393
ZMYM3_HUMAN
Q14202
STESIPVSDEDSD
256
1
Zinc finger MYM-type





AMVDDPNDEDFV


protein 3





PFRPR






ZMYM4_HUMAN
Q5VZL5

929
1
Zinc finger MYM-type








protein 4



ZN143_HUMAN
P52747

183
1
Zinc finger protein 143



ZN143_HUMAN
P52747

152
1
Zinc finger protein 143



ZN200_HUMAN
P98182

189
1
Zinc finger protein 200



ZN264_HUMAN
O43296

160
1
Zinc finger protein 264



ZN277_HUMAN
Q9NRM2

7
1
Zinc finger protein 277



ZN346_HUMAN
Q9UL40

14
1
Zinc finger protein 346


 


394
ZN644_HUMAN
Q9H582
SFGSPLGLDKR
616
1
Zinc finger protein 644


 


395
ZN644_HUMAN
Q9H582
SFGSPLGLDKRK
616
1
Zinc finger protein 644



ZN646_HUMAN
O15015

1006
1
Zinc finger protein 646



ZN787_HUMAN
Q6DD87

231
1
Zinc finger protein 787


 


396
ZN828_HUMAN
Q96JM3
AIDDQKCDILVQE
586
1
Zinc finger protein 828





ELLASPK





 


397
ZN828_HUMAN
Q96JM3
AIDDQKCDILVQE
586
1
Zinc finger protein 828





ELLASPKK





 


398
ZNF24_HUMAN
P17028
SILIIPTPDEEEKILR
10
1
Zinc finger protein 24


 


399
ZNF24_HUMAN
P17028
SILIIPTPDEEEK
10
1
Zinc finger protein 24



ZNF76_HUMAN
P36508

14
1
Zinc finger protein 76



ZNHI2_HUMAN
Q9UHR6

145
1
Zinc finger HIT domain-








containing protein 2



ZNHI2_HUMAN
Q9UHR6

145
1
Zinc finger HIT domain-








containing protein 2



ZYX_HUMAN
Q15942

150
1
Zyxin


 


400
ZYX_HUMAN
Q15942
SLSSLLDDMTK
150
1
Zyxin


 


401
ZYX_HUMAN
Q15942
SLSSLLDDMTKN
150
1
Zyxin





DPFKAR
















TABLE 2







Mass spectrometry statistics for identified caspase-derived peptides.












Swiss-Prot







acc #
m/z
z
Error ppm
score
E value















Q13362
695.0352
3
−8.3
60.6
2.80E−06


P29372
833.0408
3
−3.3
44.3
6.30E−05


P11171
756.4105
4
21
51.9
4.30E−08


P11171
663.9429
5
−2.3
62.5
2.50E−09


Q13541
938.7966
3
6.1
55.9
2.30E−07


Q13542
952.7778
3
−2.4
55
1.80E−08


Q6S8J3
737.909
2
−1.2
24.9
0.0013


A5A3E0


P62736


Q562R1


P60709


P68032


P63261


P63267


Q9BYX7


P68133


Q6S8J3
586.3246
2
−0.82
30.7
2.60E−04


A5A3E0


P62736


Q562


P60709


P68032


P63261


P63267


Q9BYX7


P68133


Q6S8J3
600.9496
3
1.2
43.4
9.70E−06


P60709


P63261


Q9BTE6
682.349
3
−6.1
48.5
4.10E−04


P00519
640.3181
3
−5.7
56
1.70E−05


O14639
657.989
3
5.1
45.6
8.30E−06


Q96P50
836.3983
2
−14
42.9
5.50E−07


Q9UKV3
1144.8881
3
0.63
24.3
0.092


Q9UKV3
541.5953
3
3.6
39.8
2.20E−05


Q9UKV3
378.2309
3
27
28.4
0.0014


Q9UKV3
627.2832
2
4.8
34.5
0.009


P21399
812.425
2
−1.4
23.4
4.10E−04


O95573
612.8007
2
−8.2
39.5
0.014


O60488


P62736
662.8276
2
−0.9
34.1
3.00E−06


P60709


P68032


P63261


P63267


P68133


P62736
584.7781
2
0.66
38.2
5.90E−06


P60709


P68032


P63261


P63267


P68133


P60709
638.5862
4
−2.9
42.2
1.80E−06


P63261


P60709
615.0721
4
−11
40.9
4.10E−07


P63261


P12814
1108.499
3
0.83
30.6
2.10E−04


P12814
1103.1478
3
−17
22.4
0.011


P12814
667.8556
2
3.7
41.5
0.096


P35609


Q08043


O43707


P35611
996.1574
3
−18
33.4
4.90E−05


Q6ZN18
396.7168
2
6.6
28.8
0.023


Q96SZ5
1006.9929
2
1.9
22.8
0.0013


Q8N4X5
770.9177
2
−5.7
42.4
2.80E−04


Q8N4X5
604.6598
3
−0.055
39.4
0.019


Q8N4X5
415.2028
3
−1.2
28.2
0.02


Q6ULP2
401.8817
3
19
29.6
0.085


Q8N302
432.7184
2
9.9
28
0.0053


Q8N302
439.4802
4
9.6
32.2
3.70E−04


Q8N302
534.2534
3
−9.1
32.4
0.0061


Q09666
794.9363
2
−2.5
23.4
9.00E−04


Q09666
514.2765
2
3.8
31.7
0.0041


Q09666
416.5694
3
−4.7
31.8
0.005


Q09666
598.7812
2
−20
38.5
0.068


Q09666
463.9146
3
−5.8
44.8
0.013


Q09666
481.7599
2
−19
29.6
0.052


Q09666
496.2643
2
−25
24.4
0.058


Q09666
388.9439
4
−0.37
39.1
3.00E−04


Q09666
519.9274
3
−1.2
48.4
5.60E−04


Q09666
397.2338
3
−5.9
29.2
0.0027


Q09666
446.888
3
−7
30.8
0.025


Q09666
439.2175
3
−3.9
32
0.0024


Q09666
596.7931
2
−4.6
39.1
0.055


Q09666
514.9217
3
−13
40.8
0.0015


Q09666
583.2912
2
1.3
40.7
0.041


Q09666
583.2881
2
−4
37.2
0.048


O95433
788.8887
2
−9.6
37.5
6.50E−05


O95433
547.0416
4
5.6
30.2
2.80E−04


O95433
593.2786
3
9.7
43.6
8.50E−05


Q8WYP5
960.9803
2
−0.86
36.5
5.00E−06


Q9Y4K1
571.6341
3
3.7
57.2
3.60E−06


Q9Y4K1
904.4601
3
−1.9
26.4
0.026


Q02952
596.9709
3
−1.9
35.8
0.02


Q9Y2D5
530.78
2
−9.9
22.1
0.027


Q99996
476.256
2
12
34.5
4.80E−04


Q99996
468.2558
2
6.9
35.5
0.0067


Q7Z591
438.5817
3
10
42.8
2.70E−05


Q12802
737.6817
3
−4.9
46.5
1.60E−04


Q12802
772.363
4
−3.1
44.8
4.50E−05


Q12802
562.265
3
−4.8
35.9
3.00E−04


Q12802
474.2589
2
6.4
34.5
0.0039


Q12802
917.9474
2
−7
52.6
1.00E−05


Q12802
848.4239
2
2
29.9
0.052


Q9ULX6
707.3197
2
5.1
40.1
3.20E−05


Q8TCU4
716.8455
2
−0.84
39.6
6.80E−05


Q8TCU4
530.2837
4
−2.8
30
0.005


Q8TCU4
556.8022
2
2.3
25.9
3.30E−04


Q9HCF4
527.7967
2
−2.9
36.4
4.40E−04


Q9HCF4
684.3854
2
−0.51
23.9
0.0017


Q9HCF4
878.4746
2
−0.13
30.8
6.10E−06


Q01432
1012.9898
2
−14
42
6.50E−05


P53582
608.6207
3
1.5
49.8
7.80E−07


Q8IWZ3
632.3286
5
14
26.7
0.007


Q8IWZ3
933.4111
2
−19
22
2.60E−04


Q68DC2
518.28
3
−7.5
43
0.0026


Q92625
440.5292
3
−5.1
36
7.90E−04


P07355
494.2418
3
2.7
38.9
1.10E−04


A6NMY6


O43747
867.4424
3
−4.5
51.8
5.70E−08


O75843
833.4361
5
−5.6
34.6
0.0022


O94973
679.9964
3
−6.4
49.5
3.40E−06


Q13367
608.3474
4
−6.1
22.8
0.041


Q13367
910.0015
2
−0.16
39.4
7.10E−05


Q92870
792.7011
3
−1.8
43
2.10E−04


P25054
957.4693
3
−11
52.5
4.50E−09


Q9HDC9
475.7311
2
−2.9
33
0.084


Q7Z2E3
891.0972
3
−8.3
50
3.20E−06


Q3SXY8
1169.6076
3
2
31.7
0.0066


P25098
491.9294
3
5.4
36
0.0013


P25098
619.6332
3
−3.3
31.5
1.70E−04


P35626


P25098
779.8454
2
−4.6
32.2
8.90E−07


P35626


Q92888
398.8444
3
−47
26.6
0.0068


Q92974
711.8592
2
4.6
32.7
1.10E−04


O15013
1053.8212
3
−24
23.4
2.10E−04


O14497
830.8775
2
−0.32
22.6
3.00E−05


O14497
822.8813
2
1.2
29.3
1.50E−06


O14497
774.0026
3
−6.1
65.8
1.40E−07


P29374
796.8669
2
2.8
36.1
2.90E−06


Q4LE39
1357.619
3
2.2
28.9
2.60E−05


Q68CP9
710.3607
4
−2.5
34.7
2.40E−05


Q68CP9
652.071
4
−11
23.6
0.0054


Q8N2F6
915.4348
2
3.9
49.2
2.40E−04


Q6NXE6
969.2285
4
−0.03
23.1
0.046


Q6NXE6
965.2247
4
−5.3
42.8
1.40E−06


P27540
621.6545
3
17
41.6
4.50E−04


Q9UBL0
663.9974
3
−13
43
3.50E−06


P61160
567.7937
4
−2.9
25.9
0.0085


P61158
694.0126
3
−2
34.8
1.00E−03


O15511
952.3894
2
−20
61.5
3.00E−08


O15511
837.8722
2
−0.95
43.1
3.90E−08


Q9BXP5
406.8858
3
8.5
32.4
4.10E−04


Q8WXK3
817.952
2
−0.3
26.3
6.10E−04


Q8N9N2
1067.091
3
−15
36.1
8.00E−07


Q9H1I8
709.3174
3
5.1
64.5
6.50E−08


Q9BVC5
476.7547
2
7.9
27.4
0.016


Q13625
884.4693
3
−0.001
28.5
0.0026


Q96QE3
990.488
2
1.2
22
0.003


Q9ULI0
761.9025
2
0.34
27.9
2.30E−04


P18846
378.2114
4
−17
28.1
0.0012


P18848
866.4062
3
−5.7
45.6
2.90E−06


P17544
742.397
2
−17
42
0.0031


P17544
624.6849
3
−10
27.6
0.01


Q9NT62
706.7647
5
0.57
29.7
0.0033


Q9NT62
790.3876
3
3.1
58.8
1.30E−06


Q9Y4P1
687.847
2
−2.3
43.1
0.0069


P46100
689.0362
3
0.84
34
5.70E−04


P0C7T5
631.8268
2
−1.9
27
7.30E−04


Q8WWM7
878.4225
2
−5.3
55.1
2.70E−07


Q8WWM7
870.4253
2
−5
50.7
3.20E−05


Q99700
1189.2343
3
4.8
26.6
0.0068


P54252
839.8587
2
−7.4
40.4
3.10E−04


Q9UPN4
971.4637
3
−11
30.2
6.50E−06


Q9Y520
832.8634
2
−8.3
40.2
2.20E−06


Q9Y520
716.0153
3
0.7
49.7
5.50E−06


Q92560
759.3601
3
−2.9
31.8
0.0062


P51572
479.5827
3
−3.1
42
6.90E−05


P51572
552.5266
4
−4.3
52.9
2.30E−08


P80723
660.9797
3
5.1
49.9
1.20E−05


P80723
494.9073
3
0.21
43.6
3.50E−04


P46379
1087.21
3
−7
37.4
3.70E−05


P46379
1129.9151
3
−0.73
37.4
6.60E−06


Q9NRL2
678.316
3
−11
24.9
0.0029


Q6ZUJ8
750.3245
2
2.2
57.3
4.20E−04


Q6ZUJ8
721.6722
3
2.1
49.5
1.40E−05


Q9NYF8
528.2364
2
1.5
29.8
0.021


Q9NYF8
437.5387
3
9
32.9
3.40E−04


P11274
682.3057
2
−6.1
24.6
6.20E−04


A6H8Y1
803.4489
2
−3.3
29.3
2.90E−04


P55957
581.2888
2
−3.7
39.6
0.0038


Q5TH69
385.5289
3
15
28.2
0.0034


O00499
542.2935
2
0.33
31.9
8.20E−04


Q9NR09
398.861
3
−5.4
26.8
0.025


Q6QNY0
878.9029
2
−2.2
40.9
0.0018


Q8WV28
1031.4701
3
−1.6
34.3
4.70E−05


Q12982
933.0836
3
−4
37.9
6.20E−05


Q12830
613.3208
2
2.6
44.1
0.027


O95696
624.8586
2
21
25
0.0048


O60885
424.5384
3
−0.75
32.9
0.0026


Q9H0E9
597.9905
3
4.6
52
8.20E−05


Q96RE7
420.8942
3
10
29.4
0.037


O43683
463.2503
2
13
28.4
0.0023


Q43683
835.4028
2
−3.2
28.7
4.70E−06


Q9BRD0
740.8795
2
−19
46
0.0071


Q96L14
832.4292
2
0.79
24.5
3.60E−04


Q07021
904.0546
3
−3
48.5
4.20E−09


O14523
567.6593
3
−1.2
49.4
7.10E−06


Q6P1N0
1118.5371
3
−15
52.9
4.20E−08


Q6P1N0
1113.2059
3
−14
52
2.70E−08


Q5T0F9
550.814
2
−9.3
39.7
0.0015


Q5T8I9
516.7592
2
0.29
28.6
0.031


Q5T8I9
619.8312
4
1.9
30.4
0.0013


Q5T3J3
741.8712
2
−1.3
22.9
7.10E−05


Q5T3J3
1040.5147
2
4.5
26.6
1.70E−04


Q96BR5
721.3472
2
−3.2
27.7
1.10E−04


Q7L4P6
579.2901
3
3.5
31.4
2.90E−04


Q5SV97
881.8479
5
−5.2
23
0.028


Q68CQ1
552.8186
2
−10
34.7
0.071


Q08AD1
578.2992
2
6.8
36.9
0.016


Q9BTV7
579.3169
4
22
36.9
1.50E−04


Q9P1Z2
674.3779
2
−2.5
47.5
2.10E−05


P19022
547.86
2
−2.8
22.4
0.0049


P19022
368.5621
3
13
24.2
0.0094


Q13111
661.5167
5
16
51
9.80E−09


Q13111
449.2444
2
3
25.6
0.021


Q13111
919.9718
2
0.46
35.5
1.30E−06


P27797
631.8193
4
−2.6
51.1
1.10E−06


P27797
911.7541
3
−7.3
34.9
5.90E−04


P27797
870.0258
3
−6.1
54.5
1.90E−07


Q8NCB2
865.9321
2
0.86
25.9
2.90E−05


P49069
642.0082
3
−0.29
26
0.0051


P49069
644.9868
3
−3.2
62.1
2.40E−06


P49069
747.6898
3
−14
48.1
1.50E−05


Q5T5Y3
487.9148
3
−0.65
28.9
5.30E−04


Q5T5Y3
686.1413
5
2.1
27.1
9.90E−04


Q5T5Y3
779.045
3
−1.6
52.6
1.10E−05


Q14444
642.6701
3
−0.51
51.8
2.30E−07


P47756
418.2392
3
11
33.5
5.90E−04


O15234
513.2743
3
4.9
30.6
6.70E−05


Q8NG31
810.8847
2
−4
32.6
1.20E−06


P42574
667.3261
2
13
41
0.0012


P42574
500.8599
3
−5.2
39.2
1.30E−05


P42574
495.5289
3
−3.9
30.9
1.00E−04


P55210
671.3188
2
−6.7
54.1
3.20E−05


Q13948
525.3142
3
5.1
29.9
4.40E−04


P39880


P07858
456.5788
3
−7.3
36.9
0.036


Q9H6R7
954.0162
2
0.98
46.1
5.70E−07


P22681
689.8437
4
−4
37
3.20E−06


Q9BRT8
479.7709
2
3
32.6
0.072


Q8IUF1


Q5JTY5


Q5RIA9


Q4V339


A6NM15


Q96G28
559.2568
3
4.8
27.2
0.0029


Q96G28
553.9217
3
−1.5
29.9
4.00E−04


Q96G28
467.5685
3
13
24.4
0.0025


Q96G28
527.9086
3
0.77
40.9
3.70E−05


Q96CT7
546.7925
4
20
27.8
0.0032


O60293
563.6239
3
0.51
42.9
2.20E−05


Q9NV96
577.7865
2
2.9
52.4
2.10E−04


Q96MW1
736.8328
2
2
51.9
5.60E−05


Q9Y3C0
776.4054
2
−3.3
47.6
0.007


Q7Z6B0
791.9203
2
−1.9
38.8
0.005


Q96F63
734.3549
3
−5.2
26.5
0.0023


Q9Y3X0
616.3044
3
−1.6
38.3
6.50E−06


Q9Y3X0
507.7253
4
−30
33
8.60E−05


O60583
768.8993
2
−0.24
34.5
4.40E−05


O60583
1060.8711
3
−1.4
31.1
0.0011


P21127
807.4354
2
−9.3
54.5
1.70E−07


P21127
737.069
3
−8.6
47.5
1.10E−07


Q14004
628.3353
2
−0.65
30.1
5.10E−05


P30260
1014.5668
2
2
29.5
1.10E−04


P30260
762.4204
2
1.3
51.1
0.001


Q99459
571.2824
2
−5.4
37.5
0.0019


Q9BWT1
657.8024
2
−7.4
37.5
5.80E−05


Q9UKY7
725.3042
2
−3.5
33.7
9.40E−05


Q9Y232
1439.7215
3
−0.52
42.5
3.20E−06


Q49AR2
586.9478
3
8.5
41.8
2.40E−05


O94986
626.0437
4
−6.9
36
1.90E−04


Q5SW79
870.4244
3
−12
50.5
2.10E−06


Q5SW79
1117.558
3
1.1
26.3
0.0077


Q5SW79
559.9728
3
1.3
24.6
0.015


Q03701
869.0709
3
0.25
24.2
0.001


Q03701
445.2475
2
7.5
22.2
0.023


Q03701
608.79
2
−1.6
40
0.0048


Q6NXR4
1017.8124
3
1.6
25
0.016


Q6P1X6
774.3731
2
−3.8
29.5
2.90E−06


P10809
698.8351
2
2.1
38
5.30E−04


P10809
538.3097
2
1.4
33.2
0.0055


P10809
594.2953
2
−5.8
39.6
0.0068


P10809
528.3024
4
0.58
23.6
0.02


Q12873
1130.1293
3
−7.1
40.5
5.50E−07


Q14839


Q8TDI0


Q14839
568.7467
4
0.63
38.4
3.10E−06


Q14839
686.0461
4
−24
34.5
3.20E−05


Q9P2D1
777.361
3
12
51
1.80E−06


Q9BY43
618.8337
2
1.5
34.6
0.0014


Q9H444


Q96CF2


Q9NRY2
546.9371
3
−0.91
40.1
3.80E−04


Q5VWN6
526.2781
2
11
40.6
3.00E−04


Q86WR7
931.142
3
7.8
55.6
3.50E−09


Q6IAA8
598.2323
3
−4.3
29.2
0.0064


Q6IAA8
592.907
3
6.4
23.6
0.041


Q9HCM1
701.8622
2
−0.14
27.8
5.00E−05


Q9HCM1
741.8753
2
−2.8
43.8
0.064


Q96C57
688.8449
2
1.5
26.1
3.70E−04


Q96C57
832.9297
2
−0.19
27.4
7.50E−04


Q96C57
824.9339
2
1.8
31.3
8.30E−06


Q96C57
953.0076
2
−1.6
23.2
3.70E−04


Q7Z460
612.289
2
4.7
39.3
0.0017


Q7Z460
684.6447
3
−8.9
39.5
7.40E−05


P09496
1039.7784
3
−5.5
63.1
4.30E−10


P09496
1034.4414
3
−11
59.2
1.40E−10


P09496
680.3305
2
−0.11
40.2
6.10E−04


O00299
917.4094
3
−18
29.1
2.90E−04


P30622
487.59
3
4.3
24
0.038


Q9HAW4
940.0497
2
1.2
32.6
5.20E−06


Q15003
534.2601
2
8.6
40.5
8.00E−04


Q15003
708.3025
4
2.1
29.7
1.50E−05


Q15003
461.5532
3
0.11
36.7
7.50E−06


Q15003
394.2029
3
17
25.1
0.02


Q15003
624.776
2
2.7
34.2
2.60E−05


Q6IBW4
578.9792
3
1.3
35.7
6.90E−04


P12111
1063.8161
3
−21
30.7
0.0079


Q53SF7
889.4591
2
3.8
44
6.80E−04


P53621
914.9333
2
−0.38
53.3
5.70E−07


P53621
650.848
2
8
29.3
0.0038


P35606
603.5815
4
20
35
0.0012


P31146
455.7318
2
−12
23.2
0.033


Q1ED39
484.2491
4
5.1
25.1
0.02


Q7Z7A1
838.9225
2
−2
29.1
4.20E−05


Q7Z7A1
482.9271
3
−2.3
30.2
0.017


Q6FI81
556.5493
4
11
29.9
2.10E−04


Q99829
494.2491
2
−9.9
31.4
0.011


O75131
602.3151
2
1.1
23.1
6.90E−04


Q16630
724.8665
2
−0.77
47.3
0.027


Q8N684
721.3527
3
0.039
26.5
8.10E−04


Q8N684
682.6449
3
−4.8
44.1
2.70E−06


Q8N684
770.3681
2
0.24
42.4
0.0031


Q6JBY9
908.7383
3
−4.8
61.4
1.10E−08


Q96N21
1176.6536
2
3.3
24.7
2.30E−04


Q53F19
666.9666
3
−2.1
24.7
0.096


Q53F19
744.8885
2
−14
46.5
1.80E−04


Q96B23
779.3919
3
−6.8
31.3
5.20E−04


Q96B23
727.367
3
4.8
38.3
1.30E−04


Q96B23
779.3968
3
−0.56
28.3
0.0065


Q96B23
722.0345
3
3.7
40.8
8.90E−05


Q96B23
774.055
3
−14
40.5
3.00E−04


P16220
961.8356
3
−14
49.5
4.30E−07


P16220
425.2108
2
−20
32.1
0.084


P16220
503.2726
2
5.5
32.5
0.06


Q5TZA2
493.88
3
−1.8
30.5
8.70E−04


Q9BQ61
595.811
2
4.6
31.2
0.014


Q9H6X5
782.024
3
−14
32.4
2.60E−05


Q13098
820.4062
3
−2
61.5
1.10E−08


Q9H175
672.7048
3
−6.2
37.6
1.30E−05


Q12996
652.331
4
−6.2
39.9
2.20E−04


Q8WYA6
781.3392
3
−0.45
53.5
1.30E−07


P49711
1069.8452
3
−6.1
38.2
1.20E−07


P49711
1069.8381
3
−13
44.6
2.10E−07


P49711
1064.5039
3
−15
50.7
7.00E−09


P35222
415.2119
3
2.6
29
0.0089


O60716
747.7031
3
−8.9
56.8
3.80E−06


Q6PD62
498.719
4
−7.4
40.8
5.00E−05


Q13620
706.335
2
−5.1
42.6
3.60E−05


Q9NTM9
573.7935
2
4.2
40
8.60E−04


P39880
962.4311
2
4.9
44.1
1.30E−05


O43169
622.9469
3
−32
33.8
7.10E−05


P16989
510.6162
3
10
46.8
1.10E−06


P16989
443.2429
2
−0.47
27.6
0.0021


P16989
892.1155
3
14
51.2
8.10E−06


P16989
761.8609
2
−8.2
27.4
0.0011


P67809


Q9Y2T7


Q6PH85
533.2533
3
3.8
43.5
7.00E−05


Q14203
607.9659
3
6.1
45.5
3.10E−05


Q9NUU7
801.4011
2
−14
26.5
0.014


Q92499
705.915
2
0.84
31.6
2.50E−06


Q9GZR7
1184.5992
2
1.4
34.7
2.00E−05


Q7L014
809.1259
3
1.5
36.2
1.10E−04


Q7L014
424.872
3
3.7
29.6
0.063


Q7L014
755.8863
2
−2
53.1
2.50E−05


Q7L014
747.891
2
1
39.1
2.00E−04


Q5T1V6
601.8233
2
1.4
40.5
0.0018


P17661
490.2534
3
−0.52
23.6
0.0019


P17661
484.9203
3
−3.5
29.6
0.011


O00273
550.2886
2
−3.9
28.9
0.022


O00273
452.2561
2
17
36
0.037


O00273
667.8635
4
2.2
22
0.041


Q8WYQ5
643.3443
2
−0.52
23.3
0.0055


Q8WYQ5
926.1158
3
−4.6
49.6
5.40E−09


Q8WYQ5
920.7767
3
−13
53
2.90E−09


Q8WYQ5
987.1671
3
1.2
24
0.063


Q86XP1
1012.8194
3
−1.8
31.6
2.40E−04


Q86XP1
702.3881
3
−10
53.1
3.80E−09


Q8NCG7
802.0843
3
1.3
63
1.10E−07


Q3LXA3
543.7521
2
−8.5
31.8
0.0026


Q3LXA3
414.8688
3
−12
35.1
3.30E−04


Q7L2E3
519.2635
4
8.9
24.4
2.10E−04


Q8IY37
996.1776
3
−11
34
0.001


Q08211
629.989
3
9.3
39.7
0.0011


Q08211
890.1142
3
−0.28
56.1
2.20E−09


Q08211
884.7845
3
1.9
57.3
1.60E−09


O60610
918.5204
4
11
35.9
9.30E−04


Q9BTC0
865.1213
3
−16
35.4
6.10E−05


Q9BTC0
553.7901
2
16
33.1
8.20E−04


Q9BTC0
796.7609
3
3.5
60.2
2.70E−08


Q9BTC0
877.7758
3
−26
45.1
5.70E−07


Q9BTC0
399.519
3
4.9
24
0.012


Q12959
1189.5762
3
−0.17
25.8
0.0075


Q99615
709.0066
3
2.2
34.6
5.40E−05


Q99615
761.0354
3
−4.4
40.5
1.00E−05


Q99615
703.6769
3
5.1
66
1.10E−06


Q99615
755.7119
3
6.4
55.9
1.10E−06


O00429
665.3303
2
−0.93
29.1
8.40E−05


O00429
605.5967
3
−2.2
51
1.50E−05


O00429
657.6226
3
−14
34.5
1.40E−04


O00429
600.2747
3
14
49.7
1.40E−05


O00429
652.2982
3
−2.9
47.1
1.40E−04


Q9Y6K1
573.5599
4
7.5
38.5
1.10E−04


Q96BY6
709.3342
2
−6.7
30.3
3.40E−06


Q9BU89
563.8221
2
−8.6
29
0.0021


Q9BU89
607.3488
3
−3.8
59.6
1.70E−07


Q8TEK3
826.1048
3
2.2
30.7
0.0027


Q9UKG1
1025.8137
3
−23
53.4
1.20E−07


P28340
599.9963
3
19
43.9
5.90E−07


P28340
627.3408
4
−11
36
1.80E−05


P09884
525.7645
2
0.34
36.6
0.0066


Q86TI2
604.7786
2
−3.6
43.1
0.0049


O14531
407.887
3
4.7
23.4
0.067


Q16643
780.8959
2
−1.2
23.7
0.0024


Q16643
1009.9798
2
−2.1
47.6
2.60E−05


P55265
659.9648
3
−5
39.8
4.40E−06


Q9NZJ0
824.8967
4
−7.2
41.2
3.10E−06


Q9NZJ0
720.5584
5
4.3
44.5
1.80E−06


Q8TDB6
660.31
2
−1.6
24.5
0.0062


Q14204
510.5649
3
0.026
28.9
0.0014


Q14204
600.2835
2
1.4
35.5
0.072


Q6ZTU2
936.4917
3
−6.9
43
7.70E−05


Q96L91


O43491
1026.8482
3
−4.4
24.5
0.027


Q9H1B7
812.954
2
−0.63
34
1.70E−06


Q99848
551.2859
3
−0.34
44
4.20E−04


P42892
813.3829
3
−1.2
46.7
1.30E−04


Q9H8V3
648.8259
2
−2.4
22.2
0.013


Q6P2E9
1036.5319
4
25
32.1
6.80E−04


Q6P2E9
833.9083
2
1.7
36
1.10E−06


Q6P2E9
825.9041
2
−6.5
35.5
8.70E−07


Q6P2E9
557.6229
3
0.72
27.7
0.036


Q6P2E9
700.021
3
−5.3
51.3
1.70E−07


Q6P2E9
760.3679
3
−3.6
55.8
6.80E−07


Q6P2E9
428.8875
3
−4.9
29.4
0.0077


Q3B7T1
881.4229
2
−6.5
39
1.50E−05


Q3B7T1
945.4758
2
−0.38
34.9
2.10E−07


Q15075
907.7752
3
−3.8
22.9
0.009


Q15075
1124.5314
3
−9.8
48.8
1.30E−07


P68104
941.1216
3
−7.7
44.6
1.40E−05


Q5VTE0


P68104
790.0424
3
−0.28
29.8
0.0025


Q5VTE0


P68104
784.7067
3
−5.5
43.6
2.90E−07


Q5VTE0


P68104
674.3309
3
0.44
22.5
0.076


Q5VTE0


P68104
479.2559
4
−13
25.3
0.018


Q5VTE0


P68104
850.3883
3
−0.24
43.8
3.20E−06


Q5VTE0


P24534
609.2763
3
3.1
45.2
4.80E−07


P24534
917.8751
2
−3.9
43.7
2.30E−05


P29692
613.2911
4
−0.12
33.8
1.70E−06


P29692
734.3377
3
−0.37
43.6
2.50E−05


P13639
515.6041
3
4.1
63
3.40E−05


Q8N3D4
951.4455
3
8.8
52.1
6.90E−08


Q8NDI1
843.3957
3
−2.4
45.2
1.10E−05


Q9H4M9
1034.4543
3
−3.1
52.4
3.10E−08


Q9H9B1
576.9345
3
−2.7
40.8
9.40E−05


Q9H9B1
702.3415
2
−0.92
28.2
1.10E−04


Q96KQ7
491.9357
3
5.6
44
1.20E−04


P55884
735.3623
2
−3.9
42.1
0.0024


P55884
683.7148
3
−2
44
1.80E−04


O75821
741.8482
4
−2.3
38.9
1.10E−05


O75822
667.7986
4
−6.4
39.9
6.20E−06


P32519
858.9174
2
−12
60.5
2.40E−06


P32519
850.9296
2
−0.21
44.1
3.40E−06


P06733
905.1272
3
−14
34.6
4.50E−04


P14625
554.7924
2
2.6
32.2
0.085


P14625
599.2788
2
−11
32.4
0.004


P14625
480.912
3
17
30.3
1.90E−04


Q9UBC2
806.7389
3
5.3
57.4
1.20E−06


P42566
843.0613
3
9.5
29.7
0.0043


Q9H2F5
594.3092
2
−4.7
24
8.10E−05


Q9Y6I3
538.6288
3
4.5
37.7
0.0043


O95208
638.8329
2
4.2
32.2
5.10E−04


Q2NKX8
551.6196
3
−2.8
22.4
0.056


Q03468
745.3792
2
5.7
23.2
0.0012


P15170
674.8093
4
−0.88
28.4
0.0016


P15170
533.6556
5
7.9
35.3
1.30E−05


P15170
569.8814
5
39
25
0.0013


P15170
712.066
4
−8.1
48.1
5.00E−06


P50548
807.3873
2
1.2
27.3
0.0017


Q86X53
531.277
2
−0.54
26.6
0.0036


A0FGR8
745.9169
2
3.5
43
0.022


Q7Z2Z2
390.1911
3
15
31.6
3.60E−04


Q7Z2Z2
589.2464
2
2.2
40.2
0.005


Q9NVH0
440.2091
3
13
25.1
0.0051


Q8N5W9
739.3938
3
−8.5
42.5
1.00E−06


Q9H098
660.663
3
1.7
31.1
7.20E−04


Q6P1L5
438.2587
3
1.5
32.9
5.20E−04


Q96EY5
466.9291
3
2
45.8
4.70E−04


Q9Y6X4
667.8344
2
−5.3
23.7
9.90E−04


O94988
507.2676
3
3.8
31.8
0.0025


O94988
567.6108
3
−1.3
55.4
2.50E−06


Q641Q2
809.892
2
3.7
49.8
2.60E−05


Q5SNT6


Q9Y4E1


Q5SRD0


Q7Z4H7
671.3426
2
−1.4
41.6
0.077


Q8NFC6
840.4196
3
−3
53.2
5.30E−08


Q8NFC6
513.9373
3
6.4
40.2
3.50E−06


Q8NFC6
758.3617
3
−0.36
56.7
9.50E−08


Q8NFC6
900.7601
3
−8.8
65.1
3.60E−11


Q8NFC6
753.034
3
4.8
67.6
1.20E−08


Q8NFC6
581.7388
2
7.5
26.8
0.0022


P49327
592.9841
3
1.5
46.1
2.00E−04


P02765
480.8913
3
−0.56
30.6
0.0083


Q6UN15
438.8746
3
−1.5
25.1
0.017


Q5T1M5
1176.6186
3
0.9
32.4
1.60E−04


Q5T1M5
994.8491
3
7.8
49
1.40E−06


Q01543
445.8907
3
−8.7
29.2
0.0027


P21333
1143.0476
2
0.52
42.5
1.10E−08


P21333
847.4108
3
−15
30.1
6.30E−04


P21333
768.7155
3
−3.5
39.7
2.50E−05


P21333
571.7673
2
21
33
0.0063


P21333
736.361
2
−1.9
41.3
4.70E−05


P21333
775.7592
3
6.1
56.5
4.50E−08


P21333
638.8862
4
43
50.2
7.30E−10


P21333
793.4324
5
5.1
33.9
5.30E−06


P21333
590.2847
2
−5
38.7
0.048


O75369


Q14315


O75369
484.2596
3
5
23.2
0.0062


O75369
794.721
3
−5.4
35.1
6.40E−04


O75369
816.7023
3
−19
62.4
1.10E−08


O75369
811.3807
3
−6.7
35.3
1.90E−05


Q96RU3
949.8877
2
4.4
50.8
7.00E−09


Q96RU3
941.8855
2
−0.55
58.5
1.90E−07


Q8N3X1
867.4791
3
1.3
39.8
1.60E−06


Q8N3X1
459.7417
2
13
34.1
0.0046


Q8N3X1
535.2756
2
6.3
35.1
5.30E−05


Q9P0K8
479.7612
2
9
40.5
0.0011


P85037
625.3471
3
7.3
60.1
9.10E−09


O43524
1040.3843
2
−15
43.7
5.70E−07


Q8IVH2
636.952
5
−2.6
42
1.70E−06


P42345
429.552
3
3
42.5
0.0038


P42345
472.2454
3
−7.7
44.6
0.012


O94915
508.5913
3
−0.42
37
0.001


Q96AE4
881.4463
2
0.8
48
9.20E−06


Q96AE4
664.6509
3
−0.6
35.5
0.001


Q96AE4
483.2372
2
−1.7
24
0.049


Q92945


Q92945
579.3093
3
0.37
50.4
4.30E−06


Q96I24
793.4292
2
−18
42.7
3.90E−05


Q96I24
912.4542
3
−7.1
58.7
6.70E−07


P35637
911.9938
2
−0.33
39
5.90E−07


P35637
442.8908
3
−8.2
29.8
6.60E−04


P51116
728.3358
4
10
32.3
7.10E−05


O15117
1037.9759
2
2.9
26.4
2.70E−05


O15117
912.7125
3
−1.8
46
1.90E−07


O15117
1007.7678
3
5.8
72.4
1.30E−09


P06241
577.2888
2
9.2
41.4
1.50E−04


Q96QD9
600.7898
2
−7.8
41.3
0.016


Q86V81


Q9Y2I7
663.8579
2
5.5
27.2
2.20E−05


Q9Y2I7
792.423
2
−0.051
41.6
9.10E−07


Q9Y2I7
801.415
3
−6.1
49.2
8.30E−07


P04406
668.6631
3
5.8
33.8
4.90E−06


Q06547
903.133
3
−7.1
22.6
0.0016


Q06547
955.1564
3
−18
39.6
2.10E−04


Q8TAK5
591.8463
2
1.1
33.2
5.50E−04


P07902
479.244
2
2
29.4
0.047


Q14C86
603.2872
3
6.2
52.3
6.50E−08


Q14C86
531.257
4
5.4
37
5.80E−05


P23769
667.8206
4
10
34.6
4.80E−05


Q92538
788.3685
2
4.9
29.6
8.00E−06


Q92538
586.2578
3
−0.41
43.9
2.20E−07


Q9Y5B6
369.5298
3
0.6
28.4
0.0087


Q9BSJ2
857.7569
3
−4.9
50.5
3.70E−04


Q9H3P7
901.5111
4
48
33.2
2.80E−05


Q9H3P7
803.0445
3
1.7
56
7.40E−08


P52566
692.8988
2
−3.2
23.3
4.80E−04


P52566
429.0122
4
12
31.5
1.90E−04


P52566
531.7784
2
2.7
35.2
0.014


P06396
607.7944
2
−2.1
41.5
0.0065


P06396
656.0097
3
6
55.1
1.10E−05


Q8TEQ6
962.1116
3
−8.3
38.8
7.50E−05


Q9NWZ8
659.951
3
−0.54
42
1.70E−06


Q17RS7
940.4229
2
−5.6
23.4
0.0081


Q06210
698.3406
2
−6.1
37.1
3.20E−05


Q9NZ52
1129.5866
3
−26
37.9
1.10E−04


Q9NZ52
690.3595
2
4.6
48.7
0.0065


Q9Y2X7
814.0902
3
−11
29.1
0.0062


Q9Y2X7
807.43
2
6.6
49.5
4.00E−04


Q9Y2X7
581.3222
3
8.6
42
8.70E−05


Q9Y2X7
959.9743
2
−12
39.5
1.60E−04


Q14161
789.7401
3
9.8
53.7
1.20E−04


Q04446
454.1991
3
6.4
30
6.20E−04


O76003
391.8701
3
5
31.2
0.0041


O76003
434.562
3
−10
33.6
0.0058


P14314
966.4078
2
−1.3
33.4
1.20E−06


P14314
730.3231
3
2.8
56.6
7.40E−08


P14314
1200.0392
4
−16
25.1
3.00E−05


P14314
1019.0646
3
−1.6
38.7
3.90E−07


Q9P107
1023.4906
2
0.26
35.9
8.30E−07


Q9P107
460.7289
2
8
38.5
0.0034


Q9P107
713.3512
2
−4
35.2
9.90E−05


P36915
694.827
2
−0.48
36.4
6.90E−05


P36915
820.6503
4
−10
32.4
5.60E−04


P36915
429.2062
3
−19
32.8
0.03


P36915
785.3473
2
1.5
37.5
1.10E−05


P36915
530.2459
3
−7.5
31.4
0.0016


Q14789
907.4273
3
−15
46.6
1.20E−06


Q14789
670.6572
3
−3
29.8
0.0048


Q14789
730.9991
3
−8.1
49.8
2.80E−06


Q3T8J9
806.3869
2
−11
33.4
7.90E−04


Q92917
487.2541
3
3.5
40.5
1.70E−05


Q92917
561.2759
2
30
31.5
0.018


Q92917
542.5193
4
−5.1
40.6
1.00E−07


Q92917
519.2812
2
−7.2
28.6
0.0096


Q92917
603.3236
3
−13
43
1.10E−04


Q9HCN4
578.3334
3
−5.7
33.2
1.40E−04


Q9UKJ3
892.4116
3
−21
43.8
8.80E−06


Q3V6T2
626.54
4
−4.4
51.6
4.20E−06


Q3V6T2
521.2493
2
6.4
34.8
0.061


Q7Z2K8
715.8928
2
−4.6
23
0.0017


P57764
819.9452
2
1.3
36.9
4.10E−06


P57764
889.9305
2
−9.6
40
4.90E−06


P09211
624.7982
2
0.18
30.9
0.0026


P09211
616.7935
2
−12
41
5.70E−04


P78347
590.8117
2
−4
41.8
0.042


P78347
436.9094
3
−1.5
38
0.044


O75367
898.9377
2
−13
44.9
2.30E−05


P62805
552.7883
2
0.87
22.5
0.0064


P62805
420.9007
3
14
36.2
8.00E−04


P62805
463.5985
3
12
37.5
4.60E−04


P62805
432.605
3
16
39.8
2.10E−04


Q13442
376.8892
3
14
23.9
0.017


Q13442
452.5993
3
5.9
28.8
0.0026


Q9Y450
1007.4704
2
−2
40.9
7.90E−05


P14317
483.9191
3
6.6
46.6
3.10E−04


P14317
601.2884
2
−3.3
35
0.048


P56524
603.0072
3
14
38
9.30E−05


P56524
1383.3258
3
1.1
33.9
6.30E−05


Q9UBN7
596.2706
2
17
34.3
0.0016


Q9UBN7
580.2673
2
3.3
39
0.014


Q8WUI4
581.6054
3
−4.4
45.4
3.20E−06


Q9UBI9
440.8914
3
−7.4
35.5
0.0021


Q7Z4V5
737.1483
4
0.079
22.1
0.035


Q7Z4V5
464.9002
3
−5.8
38.6
5.40E−05


Q7Z4V5
459.5666
3
−10
23.2
0.012


Q7Z4V5
386.5469
3
−4.4
31.6
0.0041


Q9ULT8
897.4596
3
−2.3
28.6
0.0036


Q9NRZ9
829.0873
3
−0.68
35.6
3.60E−04


P04233
875.9403
2
−3.4
48
9.20E−05


P04233
867.9434
2
−2.7
47.9
3.30E−04


Q9BW71
515.2498
2
−11
24.4
0.0058


Q8NCD3
583.3096
3
15
44
9.40E−07


Q92619
920.6968
4
−14
26.5
1.20E−04


Q92619
960.4808
2
0.58
43.9
1.20E−05


Q92619
973.9817
2
−15
38.1
1.10E−05


P30519
369.5154
3
4.6
29.4
0.001


P30519
527.8961
3
−24
35.5
3.60E−06


P30519
392.1869
4
6
22.9
0.0017


P31943
871.9425
2
−0.65
34.4
9.70E−05


P31943
513.8811
5
17
32.1
2.10E−04


P55795


P31943
766.0473
3
−8.5
44.4
7.00E−06


P55795


P31943
554.7388
2
0.87
33.5
2.90E−04


P55795


P55795
581.6278
3
−5.7
24.8
0.037


P31942
934.0253
3
−7.3
40.1
3.20E−08


Q9BUJ2
481.8748
3
−15
42.2
1.70E−05


Q9BUJ2
476.5497
3
−1.9
45.5
6.20E−05


Q1KMD3
851.0696
3
1.4
62.6
7.50E−09


Q1KMD3
677.5804
4
3
53.3
7.20E−07


Q8WVV9
567.6299
3
−0.24
37.5
0.0035


Q14103
499.2117
4
−12
41
7.40E−07


P52597
742.3466
2
0.49
43.3
4.60E−04


P38159
574.2536
2
−1.3
36.1
1.50E−05


P38159
495.25
3
1.8
31.5
0.0024


P61978
755.3641
2
3.7
30.5
2.80E−05


P61978
648.0446
4
2.7
55.5
2.80E−10


P61978
1167.8252
3
−10
22.2
7.80E−05


P61978
512.2341
2
7.6
26.4
0.0056


P14866
756.0158
3
−6.8
34.1
1.90E−04


O60506
555.2274
3
−8.2
37
8.20E−05


Q9UJC3
750.3508
2
−4.7
47.6
5.80E−04


Q9UJC3
543.2718
3
2.9
35.7
7.70E−04


Q96ED9
886.8975
2
−12
48.5
2.10E−04


Q9NQG7
1106.7951
3
−14
55.7
8.90E−10


Q03164
898.9001
2
−12
52.9
4.30E−07


Q03164
642.3179
3
15
53.2
1.90E−06


Q03164
972.9138
2
−5.2
46.5
2.70E−06


Q92598
770.0305
3
8.3
53.5
1.90E−07


Q92598
983.132
3
0.38
44
3.50E−06


Q92598
848.1935
4
45
49
2.60E−07


P34931
449.2161
3
15
31.2
0.0019


P08107


P54652


P17066


P48741


P11142


P34932
451.7001
2
0.47
25.9
0.013


P11142
481.7543
2
3.9
29.1
0.011


Q99081
727.3534
2
−10
28.4
0.0028


O43719
911.4252
3
−2.8
42
4.90E−06


O43719
1121.2057
3
0.38
23.7
0.092


O43719
529.2607
3
6.9
39.2
3.90E−07


O43719
736.0272
3
0.37
55.5
1.70E−08


Q7Z6Z7
616.8288
2
−7.3
26.6
0.0025


Q7Z6Z7
656.8401
2
−1.1
24.5
1.50E−04


Q7Z6Z7
486.7675
2
−1.8
31.8
7.00E−04


Q7Z6Z7
559.7913
2
−4.1
31.5
1.40E−04


Q7Z6Z7
826.3566
3
0.28
57.6
1.20E−08


Q7Z6Z7
701.367
3
−4.1
59.6
1.10E−07


Q7Z5L9
683.3163
3
−0.65
57
9.60E−08


P32019
496.2696
2
0.067
31.9
0.07


Q8WUF5
581.6511
3
−0.51
44.7
3.60E−06


P20810
827.8799
2
−13
56.2
1.50E−07


P20810
594.9629
3
2.8
54.1
4.20E−08


P20810
950.9444
2
−5.7
50.5
1.40E−05


P20810
492.0218
4
−7.7
39
6.40E−07


P20810
881.3723
2
−13
52.4
1.20E−06


A6NK07
471.2361
2
−12
28.9
0.063


P20042


O60841
628.8424
2
−5.6
48.6
6.20E−05


O60841
666.0137
3
−3.9
58.6
7.80E−06


O60841
553.5485
4
4.7
48.4
1.60E−06


Q14240
873.395
3
−0.38
56.2
2.40E−06


Q14240
1067.4832
3
−27
48
8.40E−08


P23588
522.9046
3
−35
23.3
0.051


P23588
648.9545
3
6.7
41.1
1.00E−04


Q04637
1290.1025
4
0.97
22.1
0.028


Q04637
680.3351
2
−4.5
43.7
9.10E−04


Q04637
782.3865
2
7.7
49.6
0.01


P78344
544.9423
3
3
49
8.90E−06


P78344
1015.8857
3
4.5
27.8
0.0033


O43432
596.9612
3
−1.8
44.8
3.30E−06


O43432
648.9964
3
0.65
38.5
0.0019


Q15056
903.9804
2
−3.3
40.4
4.10E−06


P63241
761.391
2
−10
39
3.30E−04


P63241
834.8914
2
−4.6
30.1
1.10E−05


Q6IS14


P63241
594.304
3
7.9
47.1
1.80E−05


Q6IS14


P63241
826.8934
2
−5.3
42.9
1.90E−05


Q6IS14


P63241
782.6949
3
−6.5
54.8
2.50E−10


Q6IS14


P63241
654.6412
3
−6
35
3.20E−04


Q6IS14


P63241
795.0175
3
2.1
57.1
1.90E−06


Q6IS14


P63241
832.3709
3
−14
60.6
2.50E−09


Q6IS14


P63241
789.6877
3
4.4
59.2
4.20E−07


Q6IS14


Q9GZV4
778.6994
3
−0.68
54.2
1.50E−07


Q9GZV4
839.0477
3
2.3
35.9
4.20E−05


Q15653
635.8092
2
3.8
43.4
0.0031


Q96HA7
702.685
3
−2.8
47.6
7.60E−08


Q96HA7
566.2926
4
0.63
41.3
9.40E−06


Q13422
718.8969
2
−9.1
57.1
0.002


Q9UKS7
819.8802
2
6.3
38
1.50E−05


Q9H5V7
541.2358
2
13
27.3
0.0031


Q12906
598.0347
4
3.4
39.8
2.50E−08


Q12906
665.7981
2
−1.5
47.2
5.40E−05


Q12906
486.9006
3
0.88
30.9
7.80E−05


Q9H0C8
1055.1788
3
−7.7
33.7
2.00E−05


P52294
671.91
5
−7.6
23.1
0.011


P52294
1168.8793
3
8.3
56.1
1.40E−07


O60684
868.9194
2
−1.2
48.8
1.80E−05


P12268
628.3016
2
−8.2
27.5
0.0019


Q53TQ3
592.8169
2
−0.42
31.4
0.0017


Q27J81
852.7746
3
−13
28.6
4.10E−04


Q27J81
678.866
4
−0.28
32.1
9.10E−05


Q27J81
491.5756
3
10
32.8
6.10E−06


Q96P70
868.9808
2
6.6
46.8
1.90E−04


Q6DN90
668.841
2
0.35
37.6
3.80E−06


P46940
523.2617
4
−7.9
43
1.20E−06


P46940
791.8718
4
−13
48.2
9.70E−10


P14316
481.7287
4
−0.69
37.4
6.40E−07


O14654
569.2558
3
−1.8
56.2
4.30E−05


Q9ULR0
744.8934
2
−10
35
0.002


Q9ULR0
594.651
3
3.6
35.8
0.0022


Q96ST2
495.5329
3
−1.1
40.8
3.40E−06


Q96ST2
367.9039
4
1.8
27.4
0.0015


Q9H3R0
821.4007
2
−1.5
37.8
1.40E−06


Q9H3R0
695.6855
3
3.5
47
1.90E−06


O60271
596.8115
2
−4.4
42.8
0.047


O60271
706.6559
3
4.1
46.4
3.10E−08


O60271
701.3263
3
7
64.2
2.30E−08


O60271
780.0608
3
−5.7
35.4
0.035


Q96N16
623.3181
2
2.7
36.2
0.0012


Q96N16
713.8268
2
−12
34.1
1.30E−04


Q8N9B5
657.3692
2
−0.032
35.9
1.10E−04


Q8N9B5
724.3729
3
−6.9
55.5
8.50E−09


Q9H5J8
466.25
3
13
31.1
0.0022


Q96MG2
865.3917
3
7
52.6
1.80E−05


P53990
565.7727
2
1.5
25.2
0.04


P53990
420.2057
3
−23
29.6
0.097


Q92628
502.7451
2
−0.04
23.9
0.035


Q5JSZ5
825.9764
2
−0.66
25.7
3.50E−04


Q5JSZ5
416.8733
3
−5.2
29.4
0.0034


Q6ZNE5
804.3995
2
0.31
29.9
7.30E−05


Q6ZNE5
632.7896
2
−0.53
57.2
8.80E−04


Q9P266
772.3801
3
−1.3
43.4
1.10E−05


Q9P1Y5
1094.9782
2
0.65
37.3
1.80E−07


Q9HCE5
501.2751
3
9.2
57.5
1.90E−04


Q9HCE5
551.0467
4
6
50.3
2.00E−07


Q9HCE5
569.8155
2
12
34.1
0.009


Q8IXQ4
742.8841
2
2.5
49.2
1.00E−04


Q8N163
965.44
2
0.78
51.8
9.40E−06


Q8N163
771.413
3
3
42.2
3.30E−04


Q8N163
544.0272
4
−12
24.2
0.0032


Q07666
1009.0557
2
−14
51
2.30E−08


P46013
456.7362
4
−3.1
45.5
3.00E−06


P46013
471.2396
3
−1.6
39.3
4.40E−04


P46013
497.7349
4
−2
33.8
5.00E−04


Q9NS87
640.3066
2
20
36.9
0.0064


Q8N5S9
482.235
2
10
25.9
0.037


Q9Y4X4
669.6589
3
−9.8
48.2
8.50E−05


P14618
813.389
3
−6.8
33.9
5.90E−04


P14618
719.3419
2
3.7
24.7
5.20E−04


P30613


Q8N9T8
365.2104
3
15
22.8
0.0065


Q13601
433.882
3
−4.2
36.2
0.0065


Q13601
478.4787
4
−5.2
41.7
3.70E−06


O75676
446.5743
3
12
37.8
4.00E−04


P13010
567.3097
2
−10
36.9
0.0011


P13010
657.839
2
7.5
33.5
2.40E−05


P13010
406.8455
3
−14
31.1
1.00E−03


Q14657
625.3109
3
−6.5
53.5
5.80E−07


P07942
603.2805
3
−4.7
27.7
0.074


P42166
563.9676
3
2.1
27.5
0.0043


P42166
763.7119
3
−0.39
28.9
7.80E−04


Q14160
711.3793
3
−18
43.8
5.20E−06


Q14160
462.2459
3
12
34.1
0.022


Q14160
600.0339
4
−5.6
44.1
7.30E−09


Q6PKG0
561.9504
3
−7.3
49.7
3.50E−04


Q6PKG0
619.6416
3
5.6
53.1
3.60E−05


Q71RC2
744.3937
3
−0.062
49.5
1.40E−06


Q92615
1019.1531
3
−0.13
24.9
0.029


O43561
1020.0438
2
1.7
22.7
4.00E−04


Q9UIQ6
627.3172
4
7.4
40.6
6.90E−06


Q8N3X6
541.7993
2
17
27
0.011


Q96JN0


Q9UHB6
810.1002
3
−3.4
40.6
3.00E−06


Q96GY3
662.349
2
−5.2
40.5
0.05


Q9NUP9
562.7991
2
29
28.8
0.066


Q13136
1005.9911
2
1.1
38.3
2.30E−07


Q13136
1084.037
2
−3.2
39.1
1.10E−06


Q8ND30
1023.8431
3
−0.77
26.9
0.0098


P20700
572.3392
2
−1.8
26
3.60E−05


Q8WWI1
728.8589
2
−12
52.3
0.0013


Q8IWU2
622.8452
2
−1.1
39.6
3.30E−04


Q9C0E8
617.0009
3
9.8
35.9
4.70E−04


Q93052
763.8397
2
9.2
22.5
1.40E−04


Q93052
755.8336
2
−2.1
27.4
8.00E−05


P50851
761.3326
2
−1.3
31.9
9.80E−07


P50851
851.8504
2
−2.2
51.5
9.90E−09


P50851
639.3044
3
15
61
4.10E−05


P50851
633.9662
3
4.5
49.5
9.80E−05


Q8N1G4
945.4597
2
−6.2
46.9
2.80E−06


Q8N1G4
796.4119
4
−2.2
59
2.90E−10


Q9Y2L9
655.8126
2
−1.4
26.2
8.30E−05


Q9Y2L9
513.2605
3
5.9
29.5
6.80E−04


Q5VUJ6
395.7015
4
−11
39.7
7.80E−05


Q96II8
474.2556
2
14
36.1
0.013


O75427
413.8601
3
4.7
27.9
0.0014


Q12912
738.9125
2
−8.9
48.2
0.0057


Q32MZ4
1070.7324
4
0.24
32.4
4.30E−04


Q9Y608
1281.3087
3
−2.3
30.6
0.0028


P83369
520.261
2
−1.8
22.6
7.10E−04


P62310
985.5148
2
1.7
26.1
7.90E−04


P33241
590.7599
2
6.2
35.6
0.025


Q96GA3
537.006
4
−2
22.3
0.035


Q86UE4
717.348
2
−1.4
38
9.00E−06


O60664
742.8439
2
−22
44.9
9.60E−06


O60664
769.0493
3
1.2
60
1.60E−08


O60664
583.3055
2
6.7
47.7
0.063


Q3KQU3
1073.2181
3
−3.9
30.4
0.0011


Q3KQU3
1067.8871
3
−3.3
28.9
0.005


Q9UPN3
829.739
3
−8
46.7
1.70E−06


Q9UPN3
699.8616
4
−1
30.7
7.80E−04


Q96PK2


Q9UPN3
838.0933
3
−1
33
8.60E−05


Q96PK2


Q9UPN3
611.2847
4
−4.7
50.5
1.10E−08


Q96PK2


Q9UPN3
817.9101
2
−4.8
34.2
2.90E−05


Q96PK2


Q9UPN3
639.8107
2
−0.49
37.5
1.90E−06


Q96PK2


Q9UPN3
605.9573
3
−0.38
49.3
1.50E−06


Q96PK2


Q9UPN3
730.334
2
5.9
41
6.30E−04


Q96PK2


Q8WXG6
657.3757
2
−13
34.7
0.0096


Q9Y5V3
714.665
3
5.1
59.6
1.10E−06


Q96MG7
701.316
2
−2.3
48.5
2.70E−04


Q96MG7
969.7688
3
−12
52.3
1.20E−07


P23368
608.0444
3
15
33.6
2.00E−04


P78559
1157.6109
2
9.5
38.8
1.40E−06


P78559
916.7866
3
−14
53.3
1.60E−06


P78559
719.8776
4
3.4
52.3
6.50E−08


P27816
792.4116
2
−0.25
28.1
4.50E−04


P27816
580.6472
3
5.6
51.1
7.80E−06


P27816
497.9203
3
−5.6
25.8
0.028


P27816
843.7541
3
−1.2
47.2
4.40E−05


P27816
730.7259
3
−0.99
45
8.80E−05


P27816
727.8715
2
−3.9
42
0.0061


Q49MG5
502.7553
2
−4.7
30.1
0.041


Q15691
547.2662
3
7.8
26.6
0.0011


Q9P0L2
507.587
3
5.5
38.4
1.60E−04


P43243
1065.4672
2
0.62
38.4
7.70E−09


P43243
622.8264
2
−2.2
36.2
1.30E−06


P43243
686.8753
2
0.15
36.4
3.30E−06


P43243
583.7786
4
−1.2
39.6
2.10E−05


P43243
600.0053
3
6.5
41.5
1.20E−05


P43243
456.7237
2
−2.3
25.6
0.018


P43243
524.2863
4
42
54.5
3.80E−07


Q7Z434
401.8584
3
−22
30.1
0.0099


Q7Z434
333.6772
4
4.1
28.2
0.031


P61244
515.2815
2
−1.7
27.2
0.072


Q9BQG0
726.3666
3
−7.6
44.5
6.80E−06


P49736
837.0505
3
−8.2
35.4
2.70E−05


P49736
645.802
2
−2.1
28.9
0.014


P25205
927.726
3
4.5
45.9
9.50E−08


P33991
586.9691
3
3.3
48
3.90E−07


P33992
541.2561
3
−1.6
53
6.00E−07


P33992
829.8377
2
−22
48.5
2.30E−07


Q14566
445.9049
3
−0.98
38.8
0.0012


Q14566
587.765
2
−13
32
0.0024


Q14676
1192.6804
4
5.2
25.9
3.50E−04


Q14676
935.8055
3
−7.9
30.8
0.0041


Q9NU22
939.4534
3
7.9
45.5
7.80E−07


O60244
728.3893
3
1.7
49.9
1.40E−04


Q15648
586.3193
2
−3.7
39
0.038


Q15648
547.283
3
1.2
36.1
4.80E−04


O95402
487.5985
3
−3.2
51.1
3.20E−04


Q06413
474.5466
3
5.2
32.5
8.80E−04


Q06413
435.9476
4
−7.9
33.2
3.70E−06


P31153
803.4165
2
1.7
25.7
0.001


Q6ZN04
1048.8488
3
−9.3
26.4
3.70E−04


Q8IWI9
1088.4852
2
−0.27
31.4
1.00E−06


Q8IWI9
578.8284
2
−6.6
36.8
0.018


Q8IWI9
1041.8352
3
−7.7
33
2.50E−04


Q8IWI9
502.26
3
3.5
57
2.80E−05


Q5JRA6
525.2844
2
−1.1
33.7
3.90E−04


Q8N108
454.5474
3
9.1
31.6
9.90E−05


Q96T58
499.6148
3
5.4
40.8
9.70E−05


Q96T58
668.6869
3
3.2
51.5
3.20E−05


Q96T58
626.3152
2
1.3
44
8.50E−04


Q8NDC0
400.5423
3
5.7
27.1
0.0033


Q969V6
1230.1066
2
−4.2
24.9
1.30E−05


Q9ULH7
840.3932
3
4.7
51.4
1.70E−07


O14686
660.3398
2
−4.1
34.5
1.40E−04


O14686
820.7642
3
−1.1
36.3
1.00E−04


Q8NEZ4
712.8812
2
1.3
46.4
0.019


Q9Y3A3
638.0062
3
6.2
53.9
5.60E−06


P26038
732.3907
3
7.2
25.9
0.0026


Q14149
736.3953
2
0.61
24.1
0.0051


Q14149
720.8905
2
0.28
41.8
0.0015


P53985
431.5621
3
−9.8
26.8
0.0017


Q02750
415.5408
3
−24
28.8
0.0062


Q02750
709.685
3
9.6
47.9
7.20E−07


Q02750
752.3787
3
2.9
46.7
2.00E−06


O00566
466.2746
3
3.3
34.2
6.70E−04


O00566
652.8626
2
6.3
41.4
0.022


Q99549
844.3957
3
−0.76
35.4
1.40E−05


Q99549
1028.7731
3
−14
23.6
3.10E−04


Q99549
794.3193
2
−1.6
55.5
3.40E−05


P49006
725.8746
2
−8.1
40.6
4.00E−04


Q8NHP6
602.8095
4
−16
37.8
9.40E−06


Q86U44
709.7824
2
0.83
53.3
6.20E−06


P35580
792.055
3
−9.6
25
0.018


P35580
634.3247
2
11
29.9
0.054


P35749
642.3197
2
7.4
27.1
0.043


P35579
521.604
3
8.5
45.1
2.10E−04


P35579
627.3053
2
−6.9
36.9
0.0022


Q13459
557.99
3
1.5
34
0.0017


O14974
627.3053
4
−6.9
42.9
2.90E−06


O75113
688.861
2
6.6
36.9
2.00E−04


Q13765
858.0908
3
−6.1
49.1
2.10E−06


Q13765
924.4515
3
−24
31.4
0.0042


Q9BWU0
472.7181
2
7.8
26.2
2.10E−04


Q9BWU0
464.7216
2
10
28.1
0.0046


Q9BWU0
563.2347
2
2.6
41.1
0.0018


A2RRP1
938.4413
2
−5.6
36.5
5.80E−05


A2RRP1
569.2801
4
−12
39.5
5.10E−06


Q69YI7
863.7732
3
−5.9
50.7
1.30E−04


Q9UHQ1
726.8673
2
−4.8
23.9
0.001


Q9UHQ1
591.296
3
−0.82
40.2
4.80E−04


P49321
679.5959
4
1.8
38.5
3.00E−06


P49321
523.927
3
1.4
47.7
0.0015


P49321
425.2185
4
−4.2
39.9
6.30E−05


P16333
817.8674
2
−1
41.4
3.50E−07


Q9Y6Q9
560.5436
4
4.2
35.2
4.00E−05


Q9HCD5
456.2735
2
9.8
25.8
0.018


Q9HCD5
492.2351
3
−8.6
42.4
6.70E−05


Q14686
663.6483
3
−13
34.3
0.0096


O75376
630.8125
2
−6
44.6
1.20E−04


O75376
549.9297
3
−0.67
53
5.80E−05


O75376
596.9484
3
−2.8
54.4
1.60E−05


O75376
721.3387
2
5
30.6
2.60E−04


O75376
699.316
2
4.8
35.5
0.015


O75376
636.2653
2
−12
32.1
0.0085


Q9Y618
616.3077
2
−6.8
39.8
0.0015


Q9Y618
903.9988
2
11
42.7
1.70E−05


Q92597
459.2619
3
−8.7
43.3
0.0064


Q96SB3
889.4941
2
0.17
30.7
8.60E−06


Q96PU5
635.6574
3
−1.9
45.6
2.10E−04


Q8NHV4
832.9363
2
−8.5
38.2
0.0049


P46934
848.4097
3
1.9
26.7
0.016


Q96PY6
684.826
4
−9.1
33.7
0.0076


P51957
580.2952
2
−2
33.9
7.50E−04


Q8TD19
770.9013
2
3.9
44.2
0.045


Q9H3P2
561.8099
2
−2.6
24.4
7.20E−05


O95644
491.7674
2
−4.2
37.3
0.0064


Q13469
747.0483
3
−4
48.9
1.00E−05


Q00653
675.3181
2
2.1
25.5
0.0063


Q6P4R8
413.7458
2
7.4
25.7
0.038


Q6P4R8
537.7532
4
−2.4
47.4
3.00E−07


O14745
454.7748
2
12
39.5
0.0026


Q86WB0
549.7813
2
−2.3
33.1
0.0039


Q86WB0
741.0469
3
0.66
46.8
1.20E−05


Q6KC79
428.9177
3
9
39.1
0.012


Q6KC79
493.2756
4
7
24.9
0.004


P30414
530.8812
3
13
24.9
0.002


P46087
492.2631
2
−8.1
26.2
0.045


P46087
1155.5475
3
−10
52.3
5.30E−08


P46087
1150.2057
3
−19
48.5
7.50E−08


P46087
794.62
5
20
38
1.60E−05


Q9Y2X3
594.3311
2
11
29.8
0.02


P78316
435.8993
3
−5.7
33.9
0.011


P78316
438.8914
3
21
30.9
0.019


P55209
858.9613
2
−0.83
44.8
3.60E−07


P55209
550.5661
4
−3.2
31.1
3.30E−04


P55209
475.2504
3
8.3
22.8
0.0092


Q99733
572.7957
2
−0.29
37.8
4.10E−06


Q99733
630.3146
3
2.4
56.1
1.00E−08


Q99733
813.918
4
33
32
1.10E−04


Q99733
809.8793
4
−16
53.4
2.20E−09


Q99733
644.9927
3
−3.5
46.4
1.80E−06


Q49A26
556.9489
3
−7
35.5
0.0015


Q14207
458.7825
2
13
25.1
0.046


P06748
762.0246
3
−15
35.4
2.40E−05


P06748
873.0628
3
−6.9
28.7
0.004


Q9Y6Y0
702.3287
3
−10
43.8
9.70E−07


P82970
628.3083
2
−5.7
46.2
7.40E−04


Q08J23
763.1407
4
−4
36.7
1.40E−05


Q08J23
636.3339
5
−2.5
27.9
0.002


Q08J23
492.2567
2
8.5
24.8
0.0075


Q08J23
371.2087
3
17
24.1
0.013


Q08J23
1021.5092
2
8.1
22.2
3.20E−04


P49790
530.278
2
−9
25.6
0.033


P80303
862.9316
2
−11
32.8
6.60E−04


P80303
684.3105
2
1.7
26.6
0.013


Q9H1E3
418.7163
2
12
23.2
0.08


P19338
721.4094
2
−3.3
25.2
3.20E−04


Q8IVD9
456.2354
2
5.9
26.6
0.034


Q8IVD9
857.4669
2
−0.98
39.5
3.10E−06


Q8IVD9
519.9218
3
7.6
40
2.80E−05


Q7Z417
635.6724
3
1.5
32.9
1.80E−04


Q14980
784.3966
2
−14
40.5
0.0049


Q14980
927.2416
4
−11
29.4
0.001


Q14980
602.7781
2
−8.6
41.7
5.10E−05


Q8NFH3
567.9402
3
2.8
38
8.00E−05


Q9UKX7
639.3153
4
0.62
43.6
5.20E−06


Q8N1F7
739.3486
3
7.6
38.8
1.10E−05


P11177
621.2949
3
5.7
33.6
0.0033


O75665
701.6811
3
−10
36.1
0.011


Q8WV07
495.2563
2
−3.1
27.2
0.028


Q9BZF1
557.611
3
12
33.7
0.0014


Q8N6M0
700.7099
3
3.3
57.1
8.30E−06


Q01804
740.3386
3
−6.1
28.2
4.80E−04


Q8N573
698.8929
2
−0.63
28.6
0.001


Q8N573
435.566
3
−0.84
33.3
6.20E−04


Q6IN85
619.801
2
3.8
40.8
0.0034


Q8WXI9
541.2675
2
0.45
42.8
0.0029


P47712
652.8033
2
−9.5
35.2
5.30E−05


Q86U42
685.3593
2
−7
39.5
0.0063


Q86U42
532.9647
3
13
55
3.60E−05


Q8NC51
432.2047
3
28
22.1
0.044


Q13153
882.9118
2
−12
49.2
1.60E−05


Q13177


Q13177
622.8325
2
−4.6
39.4
4.70E−06


Q8WX93
840.421
2
1.8
34.5
0.01


Q86W56
740.3677
3
7.7
28.4
5.70E−04


P09874
401.7048
2
−35
25.7
0.035


P09874
465.7711
2
10
33.5
0.017


P09874
353.5514
3
18
24.1
0.0076


P09874
586.9405
3
−0.65
28.2
0.044


Q96IZ0
361.2023
4
8
28.4
0.0021


P49023
467.7274
2
6.9
31.8
0.012


P49023
612.6551
3
6.6
46.8
6.20E−06


P49023
771.8785
2
1.9
42.3
8.30E−04


Q86U86
490.2353
3
−0.87
26.6
0.045


Q15365
1223.6101
3
−5.1
30.1
0.0016


Q15365
643.0097
3
−7.1
53.5
4.40E−08


Q15365
887.1171
3
−5.2
49.4
2.30E−06


Q15366
906.4588
3
2.1
49.9
3.90E−06


O94913
1111.7555
4
−7.2
22.1
0.0019


Q15154
563.6162
3
−2.6
46.3
3.40E−05


Q15154
764.7111
3
3.7
44
4.90E−06


O95613
1011.4802
3
8.1
34.6
0.0018


Q9BY77
748.8864
2
−5.9
45.5
8.00E−04


O00151
893.912
2
1.7
29.3
3.20E−04


Q6P996
700.8916
2
1.1
41.4
6.70E−04


Q13951
714.2997
2
−0.56
33.9
3.80E−07


O94921
568.9773
3
7.1
43.1
6.10E−04


P00558
501.7499
2
0.087
24.7
0.018


P00558
918.1347
3
−8.1
28.2
9.60E−04


P00558
490.5819
3
2.8
44.4
8.50E−06


P00558
686.3663
3
−7.1
40.4
2.80E−05


P00558
478.9172
3
17
24.9
0.0089


P07205


Q8IZ21
726.8483
2
2.8
32.1
5.70E−04


Q92576
838.9101
2
6.4
27.5
1.60E−04


Q92576
454.8939
3
18
39.9
1.50E−06


Q92576
941.1218
3
3.4
41.1
1.20E−04


Q92576
530.9376
3
1.9
43.8
1.40E−04


Q6NYC8
442.2755
2
8.7
28.1
0.012


Q9UBF8
766.7201
3
−6.7
53.9
2.10E−07


Q9UBF8
614.3193
4
−2.9
24.9
0.0093


O75925
585.6803
3
5.7
45.4
2.20E−06


Q13492
515.9336
3
−2.8
44
4.50E−04


O00562
1007.4763
2
−15
52.1
3.40E−06


O43164
659.8461
2
−3
29.6
0.0021


Q9ULL1
921.9333
2
0.13
25.2
0.0011


Q99569
505.3024
2
−6.4
32.2
3.60E−05


P19174
589.7828
2
9.1
32.8
0.039


Q9UL45
1347.968
3
−15
29.9
1.50E−04


Q7Z3K3
670.3166
2
−8.7
30.9
5.30E−04


Q9Y244
747.3844
3
−7.6
48.5
5.30E−07


Q96QC0
620.3147
3
0.11
48.1
1.80E−05


Q96QC0
658.8625
2
−2.5
46.5
0.015


Q96QC0
938.4655
3
−4.8
41.7
1.10E−04


Q8TF05
704.3491
3
−0.9
24.2
0.0029


P62937
556.3095
2
1
22.2
0.0042


Q8WUA2
857.9648
2
1.6
29.7
1.50E−04


O95685
442.2522
2
−2.9
31
0.033


O75400
541.7818
2
8.1
46.6
0.011


P57071
1206.6293
2
0.34
25
0.0053


P57071
684.3572
4
−6.9
44.8
4.20E−06


P78527
840.0617
3
−0.86
25
5.70E−04


P07737
667.6942
3
−6.2
28.8
0.0037


P07737
528.2513
2
12
26
0.025


P07737
520.2524
2
9.5
34.9
9.30E−04


P07737
854.7551
3
−5.8
36.1
1.00E−04


O60508
443.2527
2
−6.7
22.9
0.0035


O60508
572.0596
4
8.1
39
5.20E−05


O60508
563.2973
2
13
23.6
0.0096


O60508
465.5632
3
−3.3
36.4
0.0026


O60508
574.2879
4
−4.3
47.2
1.20E−07


Q8WWY3
573.9644
3
5
35.1
5.40E−06


Q9ULL5
537.7743
2
−1.3
23.6
0.016


P79522
849.7758
3
8.5
33.3
0.0019


P62333
365.8465
3
2.9
25.1
0.0038


P17980
465.2692
2
0.96
29.6
0.017


P17980
678.3531
3
−6.7
52
9.60E−07


P17980
673.0301
3
6.2
53.9
2.30E−06


P17980
634.8181
2
1.5
22.6
0.04


P43686
635.799
2
−12
53.2
6.90E−04


P62195
654.986
3
−2
46.3
5.70E−06


P28066
533.939
3
2.7
34
7.20E−04


Q8TAA3
623.6471
3
4.8
49.9
4.00E−04


O14818


P20618
532.788
2
−4.5
25.5
9.40E−04


P28070
754.3484
2
0.66
45.6
0.0018


Q99436
493.7846
2
−1
22.2
0.0037


O00232
595.2774
2
−0.74
38.2
0.0087


Q8NDX1
651.809
2
0.028
41.6
0.003


Q8NDX1
418.2104
4
−5.7
39.9
8.30E−06


O75475
580.7258
5
4.6
43.8
5.00E−07


O75475
387.8818
3
3.9
31.4
0.0051


O75475
626.3578
2
11
49.6
0.037


P61289
468.2449
2
−0.75
28.2
0.03


P26599
577.8366
2
−10
41.2
5.60E−04


P26599
437.604
3
14
39.6
9.10E−06


P26599
785.8742
2
3.8
47.7
1.20E−06


P26599
777.8724
2
−1.8
44
0.0012


P26599
777.8709
2
−3.7
45.2
9.70E−05


P26599
769.871
2
−6.9
49.1
3.10E−05


P26599
505.2334
2
−10
24.6
0.034


Q14761
923.0806
3
−11
37.9
1.10E−05


Q14761
1108.5143
3
2.7
35.1
5.60E−05


Q14761
1063.8215
3
−0.022
37.9
6.80E−06


P06454
654.3372
2
−1.4
41
2.30E−07


P06454
832.4412
2
0.093
35.2
5.90E−05


P06454
476.2544
2
2.2
29.9
0.006


P06454
782.9235
2
−2
27.6
0.0033


P26045
564.9375
3
0.22
47.9
6.10E−05


P22102
834.7403
3
−2
57.7
1.80E−06


P22102
430.2471
4
29
24.1
0.0091


P22102
591.8156
2
4.3
46
0.0065


P22234
636.3664
2
−17
29.6
0.0031


P22234
436.2483
3
−4.7
24.9
0.066


P31939
945.0053
2
−12
29.8
0.041


Q96PZ0
765.7245
3
3.7
43.9
3.50E−04


Q96PZ0
441.9001
3
5.1
39.5
9.40E−04


Q96N64
876.7814
3
−4.6
47.6
5.80E−06


P27708
974.7468
4
−9.9
27.6
0.013


Q96PU8
716.3922
2
−4.9
53.5
0.0016


Q5TB80
531.7871
4
−1.5
53.9
1.80E−07


Q2KHR3
524.2761
2
−2
25.2
0.023


Q9Y2K2
1107.0348
2
2.5
34.5
2.90E−06


Q15032
679.3418
3
9.9
38.5
1.60E−06


Q15032
673.9918
3
−17
37.4
2.70E−05


P0C7M2
557.8447
2
−0.74
23.6
0.0054


Q32P51


P09651


P0C7M2
481.9217
3
−14
29.8
0.032


Q32P51


P09651


P0C7M2
503.2672
3
−2.6
29.9
0.0038


P09651


P0C7M2
646.0898
4
2.7
28.8
0.0037


P09651


P0C7M2
422.9679
4
12
31.8
7.60E−05


P09651


O60216
1319.9436
3
−27
24.4
4.60E−04


O60216
1439.373
3
−0.97
28.2
0.0025


O60216
1434.0475
3
3.3
28
0.0022


O60216
681.8575
2
−3.5
24.1
5.80E−04


Q96JH8
745.3844
2
2.4
30.1
2.90E−06


Q96JH8
539.2765
4
−1.5
36.6
5.10E−05


P43487
636.9929
3
6.2
39
4.60E−05


Q15042
791.9123
2
3.9
47.8
6.20E−04


Q09028
456.7423
4
1.9
25.9
0.0013


Q16576


Q7Z6E9
1041.1916
3
2.9
28.1
9.90E−04


Q7Z6E9
593.3615
2
18
30.4
0.004


Q7Z6E9
692.8444
2
8.1
28.4
6.30E−06


Q7Z6E9
559.9359
3
−8.7
34.1
8.10E−05


Q16576
779.3788
2
−2.5
29.2
8.90E−06


Q16576
573.9941
4
−12
29.6
9.80E−05


Q99708
964.4301
2
−12
28.1
3.80E−05


Q96T37
583.2963
2
13
45.6
5.30E−05


Q9UPN6
739.8526
2
−2
30.8
5.50E−05


Q9UPN6
460.2171
3
1.5
32.4
0.0019


P49756
716.9792
3
−5.8
59.2
5.80E−07


Q5T8P6
719.011
3
−2.4
33.5
4.00E−04


Q5T8P6
713.675
3
−8.5
38.4
4.90E−05


Q5T8P6
713.8652
2
−2.1
22.3
7.60E−04


Q5T8P6
705.869
2
−0.17
22.7
2.80E−04


Q9P2N5
760.8699
2
−0.91
35.9
2.70E−07


Q9NW13
984.907
2
−6.3
50.6
3.80E−07


Q96EV2
517.2424
3
−3.6
38.6
2.90E−04


Q14498
849.8904
2
−4.9
43.8
5.00E−07


Q14498
890.7576
3
−10
45.9
2.00E−06


Q9Y5S9
601.5095
4
5.1
43.7
4.50E−08


Q9Y5S9
726.0813
4
−5.9
28.1
0.0057


Q9Y5S9
597.5048
4
−4.9
47.7
3.70E−10


Q9Y5S9
526.4485
5
9.6
30.6
9.60E−04


Q9Y5S9
962.4462
3
−0.58
40.9
5.80E−06


Q9Y5S9
749.8414
2
−0.93
28.1
4.30E−04


O43251
937.9043
2
0.75
46.3
3.90E−05


P49792
869.4243
2
1.4
43
4.10E−07


P49792
606.2963
5
6.3
39.5
1.30E−04


P49792
764.3483
3
−6.9
27.7
0.006


P49792
453.7201
2
−3
23.4
0.017


P49792
681.5493
4
−3.7
34
1.70E−05


P49792
1157.9086
3
−9.2
26.7
0.0099


Q68DN6


A6NKT7


Q7Z3J3


Q99666


Q53T03


O14715


P49792
984.5243
2
−4.8
33.2
2.80E−06


A6NKT7


Q7Z3J3


Q99666


Q53T03


O14715


Q92804
566.5941
3
3
47.2
1.90E−06


P25800
661.3486
2
5.9
24.1
0.016


A6NDE4
758.0301
3
−3.6
22.7
0.032


Q15415


Q15378


P06400
666.792
2
−23
35.8
9.80E−04


P53805
632.3271
3
2.6
43.1
8.80E−06


Q9P258
397.1981
2
6.2
22.4
0.013


Q9P258
317.1538
3
−40
30.6
0.014


Q14257
808.9093
2
9.8
34.2
1.30E−06


Q8IZ40
508.2666
3
3.8
39.4
0.0019


Q8IZ40
774.3639
2
3
55.4
5.30E−07


Q8IZ40
568.6037
3
−12
28.5
0.0019


Q8IZ40
766.3689
2
6.2
40.2
3.10E−05


P54727
523.7205
2
−4.6
28.4
8.70E−04


Q13123
818.3831
3
−4.8
50.8
1.70E−06


Q13123
523.2591
2
−8.7
22.9
0.011


Q13123
467.2408
3
−9.9
36.2
7.00E−04


Q04864
717.3198
2
−0.66
35.5
3.10E−06


Q92900
740.0423
3
6.1
62.6
3.80E−07


Q96D71
861.908
2
−12
51.2
6.10E−07


Q96D71
690.0421
3
−3.3
48.9
3.90E−07


Q96D71
828.6982
3
0.13
59
8.00E−08


Q92785
591.3139
2
−5.7
33.4
0.0012


Q92785
598.317
2
−4.2
35.6
0.0012


Q13127
476.2368
2
2.6
25.4
0.037


P35251
691.3596
3
−7.9
39.5
2.00E−06


P35251
467.708
2
4.3
35.5
0.003


P35251
686.0367
3
4.9
47.4
4.90E−05


P35251
632.7869
2
−23
37.7
0.036


Q2KHR2
556.6503
3
2.2
29.9
0.0067


Q9H0H5
638.3082
2
−1.5
48.5
3.30E−04


Q9H0H5
728.8242
2
−5
33.2
6.60E−04


Q68DN6
856.4174
2
2.5
40.1
1.30E−07


P0C839


A6NKT7


Q7Z3J3


Q99666


Q53T03


O14715


O43665
452.2108
3
−4.1
29.8
0.0036


O43665
519.5628
3
−5.4
44.2
4.60E−05


P98171
698.8462
2
−7.4
37
4.00E−04


P98171
1136.0371
2
−2.9
33.7
1.40E−06


P42331
1154.517
3
2.3
30.6
1.50E−05


P42331
744.0015
3
5.2
44.6
1.90E−04


Q7Z6I6
889.9152
2
3.5
27.4
3.60E−04


Q7Z6I6
1013.5108
4
−3
34
0.001


Q7Z6I6
992.7758
3
−7.1
49.4
4.70E−08


Q6P4F7
935.4164
3
−13
29
0.0057


P61586
640.6616
3
−2.5
42.4
8.10E−04


P08134


Q5UIP0
481.2801
2
−3.7
33.1
0.012


Q5UIP0
680.6394
3
12
46.5
1.30E−05


O95153
838.6621
4
−3.7
23.1
0.049


O95153
529.6074
3
−29
28.4
0.011


Q06587
507.7835
2
1.9
29.4
0.022


Q9BRS2
551.8251
2
−3.4
26.2
0.0026


Q9BRS2
673.3936
2
0.097
25.7
0.0016


Q13546
507.9304
3
15
41.1
1.30E−06


P31350
507.5879
3
−14
38.8
6.40E−05


P18621
830.9908
2
−0.077
36.8
7.20E−07


P46777
891.4249
2
−12
50.6
9.60E−07


P46777
416.2192
3
0.43
31.9
4.20E−04


Q8IYW5
431.8839
3
7
35
3.40E−04


Q63HN8
525.2821
3
−0.97
32.2
0.0011


Q5W0B1
608.942
3
−5.1
22.5
0.031


Q5VTB9
586.2893
3
−0.1
47.2
5.30E−06


Q99942
517.239
2
0.95
24.2
0.017


Q9H777
651.0489
4
−17
23.2
0.008


Q13151
506.5176
4
4.8
47
3.70E−06


Q13151
501.2954
2
9.6
38.6
0.011


Q13151
683.329
3
−1.4
44.2
1.80E−06


Q13151
551.7779
4
6
36.5
1.20E−05


P22626
664.025
3
−2.4
31.1
0.0099


P22626
405.4502
4
2.1
34.1
6.60E−06


P22626
401.447
4
−9
27.1
1.20E−04


P22626
593.2562
2
−4.1
27.7
0.0076


P51991
518.5953
3
−4.8
28.8
0.0016


P51991
675.4156
2
−1.8
26.1
4.70E−04


P51991
557.8444
2
−1.3
27.9
5.20E−04


P51991
434.4605
4
2.3
30.2
2.30E−04


P51991
462.9331
3
7.9
33.6
7.70E−04


Q13464
429.2267
2
−1.7
30.1
0.049


Q9H6T3
378.523
3
−3.6
23.8
0.012


Q9H6T3
926.4674
3
−2.7
55.1
9.90E−08


Q9H6T3
969.1674
3
−0.9
47.6
2.60E−06


P36954
640.8309
2
−6.9
34.8
2.00E−04


P05423
459.2409
3
3
29.9
0.015


Q9NVU0
678.3157
3
1.6
45.8
1.20E−06


Q8TEU7
604.7821
2
−0.54
36
4.80E−05


Q8TEU7
596.7848
2
−0.25
28.9
8.60E−04


Q92766
570.2785
2
−7.2
29.4
0.004


Q8IY81
877.8995
4
−10
33.8
9.60E−06


Q5JTH9
788.8457
4
−3
41.8
8.20E−06


Q5JTH9
788.8351
4
−16
40.1
9.90E−06


Q5JTH9
788.8461
4
−2.4
36.9
1.60E−05


Q5JTH9
1046.1287
3
−1.2
39.1
1.80E−05


Q5JTH9
618.2945
2
−6.8
29.1
3.60E−04


Q14684
769.8537
4
−0.7
25.8
0.004


P60866
446.7393
4
0.93
34.2
2.70E−05


P62266
742.0295
3
1.6
29.7
0.0016


P62266
784.7221
3
−5.8
25.6
0.0015


P62857
655.3537
2
0.21
45.2
0.086


P23396
476.2526
2
8.9
31.4
0.0036


Q96IZ7
549.2897
2
−1.6
35.8
6.80E−04


Q92541
605.2661
3
10
49
4.20E−08


Q92541
785.8209
2
1.2
40.5
3.90E−06


Q92541
599.9287
3
0.35
53
3.20E−08


Q9NQC3
517.2857
2
17
23.3
0.0032


Q9NQC3
682.331
3
−11
47.5
2.20E−05


P09234
744.8917
2
−3
25
7.60E−04


P09234
509.2383
3
−18
38.6
2.00E−05


P09661
632.8091
2
−4.6
34.1
0.0041


Q8IZ73
827.7338
3
−4.9
49.9
1.00E−05


P62306
524.6212
3
−3.1
36.4
0.0019


Q8N1F8
536.6424
3
0.61
24.6
0.029


P55011
558.2956
3
−2.6
34
0.0074


Q96AG3
598.0486
4
12
24.9
0.013


Q9UHR5
572.7506
2
3
36.2
2.10E−05


Q15424
718.303
3
0.43
39.1
2.70E−05


Q15424
389.8636
3
19
28.6
0.002


Q14151


Q15424
876.9452
4
0.7
28.5
0.0017


Q14151


Q15424
670.5357
5
−1.7
50
5.80E−07


Q14151


Q15424
613.7926
4
11
58.9
7.50E−10


Q14151


Q15424
666.8127
2
−5.4
44.1
4.80E−04


Q14151


Q15424
588.7517
2
0.48
45.1
0.0033


Q14151


Q14151
928.9761
2
3.2
38.1
6.10E−06


Q14151
613.7917
2
3.2
40.8
0.0013


Q14151
719.6928
3
−0.31
49
3.40E−06


O43865
551.6385
3
−1.8
51.6
1.20E−06


O43865
1054.9309
2
−16
45.8
3.20E−09


O43865
789.3434
3
−4.7
32.1
1.00E−05


O43865
753.8749
2
−5.6
31.1
0.0013


O43865
611.9803
3
−8.2
44.8
3.90E−06


O43865
745.8807
2
−1.2
42.4
0.006


O43865
621.2629
2
−7.7
30.5
0.012


Q96HN2
458.2483
2
−0.03
31.2
0.052


Q5PRF9
785.7272
3
2.4
41.1
3.70E−04


Q9UPN7
756.6575
4
−6.3
47.1
3.20E−08


P07602
765.863
2
−9.4
40.9
9.10E−06


P07602
663.3343
3
0.84
41.8
2.50E−06


P07602
603.7409
2
−14
38.4
0.0013


O75995
589.2881
2
−3.9
37.5
8.30E−05


O75995
711.7937
2
−41
25.8
0.084


Q01826
1516.7479
3
0.93
42.1
1.70E−07


P43007
605.6328
3
3.2
54.9
2.70E−05


O15027
726.8801
2
−1.7
35.8
1.40E−05


O15027
522.7519
2
0.83
40.2
3.00E−04


O95487
1144.919
3
9.5
24.5
0.023


O14828
638.2995
2
−6.9
28.6
0.027


Q96GD3
773.8944
2
−0.26
29
4.60E−05


O75880
1107.1123
2
4.9
24.4
0.0014


O75880
853.1275
3
−3.2
35.1
1.60E−04


Q9UIL1
637.3021
2
−24
32.7
0.0016


Q9UIL1
510.9325
3
4.6
33.6
0.0063


O60524
553.6177
3
−6.7
36.5
0.0019


P55735
562.584
3
−2.2
32.6
2.10E−04


Q12981
580.9564
3
4.3
26.8
0.046


Q9GZR1
703.6621
3
−5.3
44.2
6.30E−07


Q9UHD8
571.7677
2
−20
27.9
0.018


Q9BYW2
402.236
3
13
30.6
0.0032


Q9BYW2
817.3996
3
1.9
34.7
8.20E−05


Q9BYW2
883.7687
3
−7.5
25.4
0.026


Q7Z333
787.4313
2
0.53
26.6
3.90E−04


Q15637
784.8964
2
−13
47.5
8.40E−06


Q15459
356.8125
3
−28
24.5
9.50E−05


Q15459
351.4769
3
−40
25
1.40E−04


Q15459
719.3953
3
−1.7
40.2
1.30E−04


O75533
941.8958
2
−13
46.5
1.10E−07


Q13435
364.2256
3
14
26.9
0.055


Q13435
898.4512
2
−9
46.4
1.00E−04


Q13435
651.3396
3
−4.1
48.5
5.60E−06


Q15427
618.8253
2
−3
38.6
5.10E−04


P23246
401.2014
4
1.1
30.7
0.0017


Q8IX01
1310.8661
4
1.6
25.4
0.0011


Q8IX01
674.3126
2
0.24
45.5
0.0011


Q8IX01
999.1261
3
−3.4
60.5
3.30E−10


Q99590
835.6921
3
−4.1
58.8
4.90E−07


Q01130
719.8186
2
−0.12
28.1
1.90E−05


Q01130
703.8222
2
−2.2
38.3
1.90E−04


Q01130
545.2738
2
4.2
34.6
0.0051


Q01130
635.7889
2
−2.2
47.8
3.50E−04


P84103
482.7164
2
3
22.2
0.019


Q13243
585.2827
3
−5.1
49.2
9.40E−07


Q13247
498.745
2
8.2
28.6
0.076


Q5FBB7
557.2639
3
4.1
31.6
0.0014


Q8N5H7
526.9266
3
−2.5
40.4
0.0014


A0MZ66
761.8523
2
−0.94
43.8
7.40E−07


Q96FS4
712.3373
2
−9.7
51.2
1.70E−06


Q9UIU6
928.7876
3
5.4
61.4
5.70E−09


P12755
668.3472
3
3.9
44.9
1.10E−05


Q5T5P2
416.5381
3
−1.4
29.2
0.016


Q9BRT9
849.4166
3
−10
49.2
1.20E−05


Q9H2G2
500.2528
3
7.9
28.1
2.90E−04


Q14BN4
843.8928
2
−13
46.8
2.00E−05


O95391
550.3146
2
10
30.9
5.00E−05


O95391
681.6812
3
−6.7
50.8
4.40E−07


O95391
543.5403
4
0.81
35.3
3.30E−05


O95391
742.0353
3
5.1
48.6
2.80E−05


O95347
618.331
3
4.6
44.6
1.30E−06


P51532
609.3476
2
−0.79
22.4
0.01


Q969G3
419.8795
3
1.3
32.5
0.046


A6NHR9
632.291
3
−2.9
53.2
5.80E−10


Q8TAQ2
492.9114
3
−1.3
34.4
0.0015


Q92925
797.8757
2
6.1
42.5
3.40E−04


Q5SXM2
736.887
2
−13
27.7
0.057


Q9UMY4
914.4595
3
2.6
45.9
9.70E−08


Q8TEQ0
859.7477
3
−15
26.2
0.0094


O60749
1009.8868
3
3.2
26.1
0.0095


O60493
599.8294
2
−1.9
27.8
2.20E−04


Q9UNH7
490.7423
2
9.1
28.1
0.0089


Q9UNH7
426.897
3
5.8
35.2
0.031


A7XYQ1
711.8476
2
−9.3
42.9
0.015


P00441
828.7504
3
−1.3
29
0.011


P00441
533.6151
3
−0.76
55
1.10E−05


P18583
1296.6627
3
1
28.2
0.0013


P18583
1096.5876
2
3.7
44.5
8.70E−09


P18583
754.3801
4
−8.9
43
1.10E−06


P18583
803.7332
3
15
34
6.70E−05


P18583
626.9766
3
−6.1
41.9
0.0011


Q9HB58
398.5299
3
14
30
0.0044


Q9HB58
458.8638
3
−13
28.9
0.0014


P08047
1047.0821
2
5.1
44.3
2.80E−06


Q02447
1236.5731
3
4.8
22.3
0.026


Q02447
733.3483
3
−7.7
58.9
3.20E−08


Q86XZ4
788.4009
2
−18
37.1
3.30E−04


Q9UBP0
577.758
2
1.3
39
0.023


A1X283
830.4031
2
−5.8
35.4
1.60E−06


Q5M775
766.3726
2
−2.7
38
9.80E−04


P19623
609.3094
2
−13
44.2
0.0013


O75934
644.9756
3
−0.17
51.8
6.80E−07


O75940
731.3598
2
0.17
33.9
4.90E−06


Q8N0X7
625.3093
2
6.9
22.1
8.50E−04


Q8N0X7
506.7756
4
19
26.3
0.0069


Q8N0X7
538.7899
4
0.5
29.9
0.0016


Q9NUQ6
482.5808
3
−32
27.4
0.059


Q7KZ85
612.3149
2
−3.4
33.8
0.0015


Q13813
872.4677
2
0.34
31.4
1.10E−04


Q13813
486.8061
2
−4.1
23
0.011


O15020
605.312
3
−4.8
45.7
1.50E−04


O15042
910.7951
3
−14
26.2
0.091


O15042
967.4972
2
−32
46.4
1.30E−05


O15042
828.7499
3
0.01
38
2.70E−05


O15042
653.8394
4
2.1
38
1.30E−04


O15042
608.8057
2
−1.1
35.2
1.80E−07


O15042
448.9081
3
6.8
41.1
2.60E−07


O15042
519.029
4
3.9
48.2
7.40E−08


Q6ZRS2
788.3406
3
−5.5
45.7
2.60E−06


Q6ZRS2
848.6655
3
−30
41.6
4.20E−08


P12931
860.4475
2
−2.8
26.5
1.70E−04


Q8NEF9
531.2961
2
1.1
27.9
0.0016


Q8NEF9
478.7739
4
−0.65
22.5
0.085


Q9UHB9
585.5641
4
17
49.3
1.30E−07


Q9UHB9
518.2524
3
12
38.7
0.004


Q96SB4
1439.3376
3
5.3
28
2.60E−04


Q9UQ35
489.739
2
7
28.9
0.0047


Q9UQ35
523.7805
2
−5
36.5
0.0018


Q9UQ35
433.8676
3
−15
22.8
0.078


O60232
639.9947
3
−4.3
55.7
6.90E−06


Q9BWW4
1146.555
2
4.5
22.9
0.0016


Q9NQ55
831.9291
2
−2.9
41
8.60E−08


P28290
769.4176
2
1.3
41.8
0.0041


Q76I76
792.3868
3
−0.59
30.4
0.0021


Q08945
912.4597
2
−2.8
49.6
8.00E−06


Q9ULZ2
640.9686
3
−3.6
55.6
1.60E−05


Q9ULZ2
635.637
3
−3.7
57.2
3.90E−05


O94804
1440.6692
4
1.1
25.8
2.10E−04


Q9Y6E0
919.9206
2
−18
54.6
3.10E−08


Q9Y6E0
609.8011
4
1.4
32.3
0.0096


Q9UEW8
799.3599
2
16
55.5
4.90E−04


Q13043
1230.8882
3
1.3
33.7
2.40E−04


Q13043
962.4368
4
−5.5
22.6
0.025


Q13043
801.4111
5
45
35
8.50E−05


O43815
483.2445
2
1.9
32.5
0.0058


O43815
694.8362
2
−2.9
48.2
9.90E−04


O43815
615.3103
3
−1.1
43.5
4.70E−04


O43815
493.7484
4
−21
28.1
0.0056


O60499
562.9101
3
−1.1
23.4
3.30E−04


O60499
550.2824
2
18
32.8
0.019


Q86Y82
645.6447
3
5.4
62.6
2.30E−06


P56962
585.3108
4
9.3
30.6
1.00E−04


P56962
697.6675
3
−5.2
53.4
8.10E−05


O15400
905.4229
3
−22
66.6
1.80E−08


Q9Y2Z0
920.9676
2
−14
26.6
0.0026


Q96A49
537.5916
3
0.68
43.1
2.60E−04


P07814
702.9106
2
3.1
52.2
0.0046


O95926
567.9626
3
4.7
25.8
0.0053


O95926
619.9912
3
−4.1
51.6
2.40E−07


P41250
716.8691
2
−8.5
52.1
6.30E−05


Q92797
524.2259
2
3.2
31.3
0.0031


O43776
971.4463
2
−0.63
31
8.20E−05


Q8NF91
610.962
3
3.1
50.1
5.70E−07


Q8WXH0
601.2927
2
−2.1
44.7
2.40E−04


P23381
775.8948
2
−1.7
48.5
1.10E−05


Q9NUM4
580.2535
2
−4.4
37.4
3.10E−04


Q9NUM4
572.2618
2
5.6
33.8
0.0046


Q9BVX2
913.4464
3
−20
31.1
0.0016


P29083
605.0193
4
5.4
35.1
1.90E−04


P29083
601.0209
4
5.9
44.9
1.80E−06


P35269
1007.3983
2
1.3
55.5
1.30E−08


P35269
999.4013
2
1.8
52.8
2.30E−07


O75410
669.3194
2
−1.3
24.8
3.40E−05


O75410
635.2991
3
0.77
34.2
3.00E−05


O75410
379.4883
3
−31
22.4
0.0045


O95359
459.5494
3
−2.8
24.8
0.021


Q9Y6A5
921.7929
3
5.9
31.8
3.90E−04


Q9Y6A5
750.3785
2
−2.1
34.1
0.0043


Q96BN2
504.0201
4
1.7
31.8
3.90E−04


Q15544
829.8834
2
−9.7
39.6
3.50E−05


Q15545
1032.492
2
−2
30.2
0.0038


Q71U36
669.1185
5
4.2
56.2
1.60E−08


P68363


Q9BQE3


Q13748


Q6PEY2


Q71U36
665.9205
5
5.7
62.1
1.10E−09


P68363


Q9BQE3


Q13748


Q6PEY2


Q71U36
946.0852
3
−11
51.1
1.30E−08


P68363


Q9BQE3


Q13748


Q6PEY2


Q71U36
492.5025
4
5.7
42.9
6.80E−06


P68363


Q9BQE3


Q13748


Q6PEY2


Q71U36
514.7216
2
0.51
34.3
0.035


P68363


Q9BQE3


Q13748


Q6PEY2


P68366


Q71U36
706.6535
3
−5
27.8
0.0062


P68363


Q9BQE3


Q13748


Q6PEY2


P68366


Q9NY65


Q71U36
744.7286
3
2.4
36.4
9.50E−06


P68363


Q9BQE3


Q13748


Q6PEY2


P68366


Q9NY65


Q13885
334.2091
3
−2.1
22
0.071


Q9BVA1


P68371


Q13509


P07437


Q13885
436.7664
2
6.4
30.8
0.087


Q9BVA1


P68371


Q13509


P07437


P68371
859.4191
5
−15
41.1
1.90E−05


P07437


Q15814
658.03
3
0.2
39.1
4.50E−07


O60343
763.0459
3
−3.5
55.2
3.30E−05


O60343
672.0145
3
−3.1
50.5
4.90E−05


Q9BZK7
586.3129
3
−20
32.1
0.0085


Q9BZK7
691.336
2
−9.6
43.6
0.016


O60907


Q9BZK7
609.805
2
2.2
40.9
0.0013


Q9BQ87


O60907
598.2951
2
−1
39.3
0.032


P23193
603.7908
2
−3.8
27.3
0.0051


Q9UGU0
1006.0216
2
−1.5
48.2
3.60E−09


Q9UGU0
954.2312
4
−2.5
22.6
0.02


Q9UGU0
548.7724
4
−4
32.2
0.0013


Q13428
935.4953
2
−0.91
37
3.50E−07


Q13428
927.4999
2
1.3
37.6
1.50E−07


Q13428
958.0103
2
0.16
32.3
1.80E−06


P50991
904.4691
3
−13
38.6
6.50E−05


P50991
525.2248
2
6.3
34.3
0.002


P50991
517.2261
2
4
31.5
0.017


P48643
872.7516
3
−9.3
36
4.90E−04


P48643
652.3692
3
−6.7
48.5
7.30E−07


P40227
676.3702
3
15
31.4
3.40E−04


P13693
545.2834
2
−1.3
29.7
0.0049


O60522
686.3245
4
7.1
24.2
0.079


Q8IWB9
575.7741
2
−6.8
30.8
0.0014


Q8IWB9
858.9738
2
−7.4
24.2
4.90E−04


Q00403
703.8401
2
7.7
31.8
0.0032


Q00403
695.8365
2
−0.95
37.1
0.029


Q9NZI6
575.849
2
3.2
36.2
0.073


Q12800


Q9NZI7


Q92664
697.7161
3
−0.33
44.4
6.10E−05


Q04206
721.3227
2
−2.5
35.6
4.20E−06


Q96RS0
428.8935
3
9
27.2
0.0093


Q96RS0
720.8799
2
−2
30.9
4.60E−05


Q96RS0
709.9974
3
−2.8
24.1
0.012


Q86V81
715.8326
2
2.3
46.5
4.30E−07


Q13769
440.2166
2
6.1
25.8
0.05


P52888
687.3451
2
−0.95
35.6
3.60E−05


O15164
664.6242
3
−5.5
36.4
1.30E−04


Q13263
1426.8933
3
1.10E−04
38.5
3.70E−08


Q13263
824.3788
2
2.4
42.8
4.30E−09


Q13263
1010.0201
2
−21
37.5
4.00E−04


Q13263
577.788
2
0.019
43.1
0.002


Q13263
456.2436
2
−3.8
23.4
0.061


Q9UNS1
972.4909
2
1.9
35.7
9.10E−06


Q9BSI4
1033.9965
2
−3.2
25.8
1.80E−04


Q9BSI4
1026.0031
2
0.72
41.1
1.30E−05


Q86UE8
934.4821
3
−7.8
22.9
0.044


Q9H0V1
731.0532
3
−2.6
29.4
0.012


Q6ZVM7
402.2346
3
7.9
22.8
0.0059


Q9BVT8
608.9508
3
−9.2
36.5
4.60E−04


Q9BVT8
603.6198
3
−8.2
44
4.50E−04


Q8NFZ5
478.9161
3
7.9
44.1
9.40E−04


Q8NDV7
782.8917
2
−3.4
27.9
7.00E−04


Q8NDV7
620.07
4
8.1
23.2
0.0096


Q96GM8
1008.9917
2
2
42.9
1.30E−07


Q96GM8
762.3608
2
−13
32.7
6.70E−05


Q5JTV8
938.495
2
3.1
37.6
3.00E−07


Q5JTV8
448.9175
3
11
35.3
4.20E−05


Q5JTV8
428.2089
3
−12
34.5
8.60E−04


Q9H0E2
620.6697
3
12
44.5
4.60E−07


O60784
464.7612
2
−6.4
38.2
0.08


O60784
1207.2751
3
−3.6
26
0.0021


O60784
1360.34
3
−3.7
28.4
6.00E−05


O60784
482.5728
3
−12
38.5
6.80E−04


O60784
477.2509
3
8.7
34.5
0.0015


Q02880
738.8719
2
−0.28
41.4
0.0032


Q12888
656.8251
4
−0.49
46
1.30E−06


Q12888
839.9387
4
30
34.3
3.70E−04


Q12888
721.3541
2
−4.2
52.6
0.023


Q12888
507.7201
2
1.9
23.5
0.024


Q12888
667.3603
2
1.7
30.1
0.0082


O43399
721.8639
2
−2
26.3
2.70E−04


Q5T0D9
1006.5086
3
−9.5
32.5
3.30E−04


Q5T0D9
913.2612
5
−16
22
0.07


P12270
1124.0409
2
2.1
33.2
1.30E−05


P12270
629.3242
3
1.3
60.4
5.40E−08


Q9Y2W1
663.6706
3
−3.2
53
4.60E−08


Q15633
672.3055
3
−4.1
48.2
1.30E−07


Q96PN7
763.6944
3
−13
32.8
1.80E−05


Q9UPN9
583.8284
2
−2.8
28.9
4.30E−04


Q9UPN9
815.7195
3
2.2
28.2
0.0058


Q9UPN9
810.3852
3
−1.1
34.6
2.90E−04


Q15650
557.6242
3
−3.3
39.4
6.60E−04


Q15650
848.3895
2
4
45.1
2.00E−04


Q7Z2T5
1096.5593
3
−4.9
54.4
3.00E−10


Q9Y2L5
473.2404
3
12
43.7
0.0099


Q92574
736.869
2
−7.2
42.8
4.60E−04


Q92574
656.089
4
−0.31
26
0.0095


Q92574
827.393
2
−0.13
50
1.50E−04


Q2NL82
604.2764
2
−4.5
39.1
1.10E−06


Q2NL82
560.285
3
0.83
48
3.30E−08


Q2NL82
596.2769
2
−8.1
39.6
3.20E−05


Q2NL82
560.2876
3
5.6
37
1.10E−06


Q2NL82
609.9619
3
−8.5
42.7
8.30E−05


Q99614
661.2932
3
−8
41.5
2.00E−06


O95801
612.3082
2
−3
29.2
1.00E−04


Q9UNY4
711.4294
2
−5
22.4
0.0033


Q9UNY4
517.3247
3
3.9
29
0.0014


P63313
624.2846
2
0.51
41
0.0033


P04818
426.731
2
−3.2
23
0.0056


P25490
1025.0097
4
−13
33.5
3.20E−05


Q13432
429.9161
3
4.5
42.9
2.20E−04


A6NIH7
668.8739
4
0.24
40
2.50E−06


P26368
692.6958
3
−3.2
49.2
1.10E−07


P26368
687.3638
3
−3.7
58.5
4.20E−08


Q3KQV9
1094.0704
2
1.9
43.5
2.00E−08


Q13838
511.2687
2
−1.2
32.2
0.049


P22314
658.6626
3
−0.22
36.1
9.70E−05


Q8TBC4
715.3295
3
0.66
28.7
0.0019


Q8TBC4
758.7929
2
1.8
48.6
7.10E−07


Q5T6F2
759.3829
2
−0.63
22.5
3.60E−04


Q5T6F2
570.7653
2
2.8
30.8
4.90E−06


Q5T6F2
597.2897
2
3
33
0.0015


Q9C0C9
1065.1611
3
−9.6
28.9
7.90E−04


Q9C0C9
1059.8263
3
−13
38.6
1.60E−04


Q9C0C9
880.6616
4
−13
26.6
0.0033


Q9C0C9
1302.6199
3
5.3
30.6
0.0012


Q9C0C9
420.5742
3
7
24.5
7.50E−04


O14562
1090.4749
4
−15
42.2
4.40E−08


Q9NPG3
1143.0427
2
−18
44.7
3.20E−07


Q14694
753.6938
3
−8
31.3
2.60E−04


Q14694
458.2583
2
9.5
38
0.021


Q14694
701.3464
3
−7.4
39.1
3.10E−05


P54578
513.7778
2
1.6
32
0.018


P54578
622.2935
2
−0.35
43.6
3.30E−05


O94966
576.2896
3
2
28.2
0.0018


Q14157
607.8398
2
6.9
22
0.0015


Q14157
791.3962
3
−15
48.8
7.20E−07


Q14157
830.3892
2
−9
31.8
2.80E−04


Q70CQ2
463.2114
2
4
26.1
0.028


Q70CQ2
706.8328
2
5.3
27.7
4.20E−04


Q9P275
540.8051
2
8.6
27.9
0.016


Q9H9J4
445.7561
2
12
37.4
8.80E−04


P45974
625.7867
2
−1.7
45
2.30E−06


P45974
617.7907
2
0.68
30
3.50E−05


P45974
480.615
3
6.2
32.1
1.80E−04


P45974
623.837
2
−9.9
36
0.033


P45974
675.3514
2
0.65
33.6
9.00E−05


Q93009
659.9335
3
−0.98
45.6
2.80E−07


Q93009
720.2814
3
2
50.9
7.00E−07


Q9UMX0
870.4346
2
3.5
29.1
1.30E−04


Q5T4S7
390.8701
3
8.1
35.6
1.60E−05


O94888
540.5906
3
−15
42.6
3.90E−04


O94888
601.534
4
−23
30
6.90E−04


O94888
717.3751
2
11
34.3
1.10E−05


Q16851
692.8494
2
4.3
54.5
0.063


A0JNW5
859.4135
3
−1.4
26.5
0.0025


Q96T88
747.3409
3
−4.2
42
2.50E−06


Q96T88
797.411
4
48
60.3
1.00E−08


Q86UX7
626.3471
2
3.1
42.8
0.011


Q86UX7
443.9826
4
−26
38.1
4.10E−04


Q9NZ43
650.2803
2
0.97
33.5
6.70E−04


Q15853
1464.7474
3
−4.7
35.2
2.50E−05


O60763
567.7412
2
−4.8
25.5
0.0023


P46939
634.8724
2
4.3
25.6
0.0021


P63027
577.2989
3
25
30.6
4.10E−04


Q15836


Q9Y5K8
630.3138
2
−5
31.2
0.0048


P08670
454.2513
2
7.7
27.6
0.019


P08670
639.8444
2
1.1
23.8
2.50E−04


P08670
651.8523
2
−2.9
30.6
1.00E−04


P08670
720.8728
2
0.96
41.1
1.10E−05


P08670
604.6469
3
−1.4
65
9.00E−08


P08670
705.0226
3
−1.3
52.9
4.50E−07


P08670
376.4564
4
5.1
31.5
3.40E−04


P08670
545.6313
3
2.9
37.2
2.90E−05


P08670
502.0231
4
−0.35
27.4
0.0011


P08670
474.2526
3
−25
44
3.20E−04


P08670
448.502
4
5.7
27.1
0.0059


Q5THJ4
679.3378
2
−4.6
31.2
0.018


Q9UN37
588.9353
3
−0.85
47.2
5.10E−04


Q9UN37
640.9725
3
4.7
27.1
0.0062


Q99986
386.86
3
0.44
33.9
0.0011


Q7Z5K2
476.2366
2
10
24.1
0.0055


Q92558
779.7277
3
11
54
1.30E−05


Q9Y6W5
1083.515
4
16
41.1
5.20E−06


Q9Y6W5
633.0053
3
−2.7
45.2
4.30E−05


A8K0Z3
984.5248
4
−17
52.7
2.40E−07


Q9C0J8
435.7081
4
6.3
24.8
0.0035


Q5JSH3
972.0395
2
8.3
37.9
8.50E−06


Q9H6Y2
438.7174
2
3.7
27.6
0.027


O43379
1109.2663
3
−6
37.5
1.50E−05


Q96MX6
912.9972
2
3.2
33
1.10E−06


O76024
496.7763
2
−7.2
31.2
0.0013


O76024
730.6953
3
−1.5
35.3
8.80E−04


O43516
608.3255
4
−3.5
45.9
1.80E−08


Q9H4A3
707.815
4
4.7
34.3
2.70E−05


Q9H4A3
1167.0025
2
−3.4
50.4
3.30E−11


Q9H4A3
563.2531
5
2.4
41
7.00E−07


Q9H4A3
414.6975
4
−5.4
37
3.30E−06


Q9H4A3
932.4238
2
2.5
58
2.30E−06


Q9H4A3
838.7054
3
23
56.8
1.00E−07


Q96S55
622.6505
3
0.23
29.8
0.0039


Q6AWC2
443.279
2
−0.92
25
0.011


P23025
747.3813
3
−12
60
1.40E−07


P46937
682.3796
2
5.7
23.4
6.30E−04


P67809
855.4151
3
3.3
44.5
1.10E−06


P67809
673.8279
4
−10
47.1
1.30E−08


P67809
863.0819
3
−27
48.6
7.20E−08


Q9GZM5
826.8774
2
0.15
32.9
6.80E−05


Q6ZSR9
802.416
2
−14
31.1
4.50E−04


Q6ZSR9
585.8135
2
−9.4
30
0.0073


A8MX80
652.3391
3
0.68
22.5
0.028


Q9H6S0
895.3569
2
−0.24
53.6
4.40E−07


Q9BYJ9
679.841
2
3.5
26.3
9.90E−05


Q9BYJ9
726.6064
4
0.45
22.8
0.024


Q9BYJ9
718.6071
4
−2.2
39.8
9.40E−06


Q9Y5A9
669.3386
4
−8.1
46.5
3.20E−07


Q9Y5A9
682.8468
2
4.3
30
7.20E−05


Q9Y5A9
955.1275
3
−14
62.1
4.20E−09


Q9Y5A9
1012.2638
4
0.3
28.2
0.0086


Q9Y5A9
857.4025
3
−7.4
69.2
6.50E−09


Q7Z739
926.4589
3
−19
48
9.90E−07


Q7Z739
722.8388
2
−0.035
33.7
0.0014


P43403
488.2466
2
−3.6
33.3
7.70E−04


Q8NCN2
730.3552
2
0.59
30.5
2.40E−04


Q8NCP5
839.407
2
−2.6
22.4
1.60E−04


O75152
668.407
2
−2.9
27.7
5.00E−05


O75152
620.8188
4
2.3
40.1
2.20E−06


Q9UPT8
759.8306
2
−8.4
51
2.40E−05


Q9UPT8
674.1222
4
32
35.5
6.20E−05


Q5T200
497.2648
3
−2.2
24.9
0.016


Q5T200
505.5844
3
13
28.2
0.0013


Q6PJT7
1304.925
3
−1.4
27.4
3.80E−04


Q7Z2W4
553.298
2
3.6
30.3
9.60E−05


Q7Z2W4
663.3275
2
−5
45.2
2.00E−04


Q86VM9
741.0172
3
1.5
24.5
0.022


Q9C0B9
620.3225
2
4
46.2
2.10E−05


Q6NZY4
708.8519
2
−0.04
36.9
6.20E−04


P37275
869.06
3
−2.6
44.5
5.20E−07


O43829
785.3593
3
−0.25
51.6
1.90E−07


O43829
851.0337
3
−3.8
57.4
4.40E−08


Q6FIF0
1121.534
3
4.7
28.7
0.0043


Q6FIF0
741.8363
2
−3.6
48.5
4.00E−04


O95159
1104.0579
4
0.9
22.8
0.035


P17010
494.7613
2
2.1
26.2
0.043


P17010
546.9704
3
2.5
26.4
0.003


Q7Z3T8
877.9525
2
−20
47
2.30E−05


Q7Z3T8
804.889
2
1.3
26.5
3.00E−04


Q7Z3T8
568.3072
3
1.5
40.9
4.00E−05


Q14202
1161.5114
3
0.59
28.4
0.0011


Q5VZL5
485.2796
3
5.6
31.4
2.50E−04


P52747
679.3239
3
−1.5
59.9
1.20E−07


P52747
934.1298
3
−9
47.4
1.30E−06


P98182
963.9767
2
−2.9
23.5
0.0016


O43296
589.2808
2
−7.4
38.2
5.50E−05


Q9NRM2
758.3427
2
2.5
25.8
4.70E−05


Q9UL40
741.8506
4
−9.4
31.6
5.30E−04


Q9H582
421.2414
3
16
22.1
0.01


Q9H582
463.9373
3
9.1
39.6
4.60E−05


O15015
930.9646
2
1.8
35.8
4.00E−07


Q6DD87
1035.1812
3
−26
56
5.80E−09


Q96JM3
1185.6155
2
0.71
35.7
1.20E−05


Q96JM3
625.3273
4
−12
44.8
7.50E−05


P17028
651.0446
3
4.2
49.2
1.80E−05


P17028
867.4384
2
−8.6
41.9
0.0017


P36508
782.9207
2
0.71
27.4
1.80E−04


Q9UHR6
833.909
2
−17
45.4
6.50E−04


Q9UHR6
1177.5831
3
−0.27
28.7
0.0058


Q15942
738.3417
2
−12
29.9
9.80E−05


Q15942
730.359
2
8.3
30.9
0.0068


Q15942
572.7885
4
4.1
43.3
1.40E−06





“E value” is the expectation value.













TABLE 3







Caspase-like cleavage sites. P4-P4′ indicates the eight amino acid


residues spanning the cleavage site, which is located between the


fourth and fifth residues of the sequence. P1 residue indicates the


residue directly preceding the cleavage site. P1′ indicates the


residue directly following the cleavage site. P1 residue # indicates


the residue number in the full-length protein sequence


corresponding to the P1 residue. Entries separated by vertical


bars indicate cleavage sites found in more than one


homologous protein.













P1



Swiss-Prot ID
Swiss-Prot acc #
residue #















2A5G_HUMAN
Q13362
14



3MG_HUMAN
P29372
36



41_HUMAN
P11171
550



4EBP1_HUMAN
Q13541
25



4EBP2_HUMAN
Q13542
26



AASD1_HUMAN
Q9BTE6
80



ABL1_HUMAN
P00519
939



ABLM1_HUMAN
O14639
567



ACAP3_HUMAN
Q96P50
588



ACINU_HUMAN
Q9UKV3
68



ACINU_HUMAN
Q9UKV3
511



ACINU_HUMAN
Q9UKV3
663



ACOC_HUMAN
P21399
673



ACSL3_HUMAN
O95573
571



ACSL4_HUMAN
O60488
562



ACTB_HUMAN
P60709
157



ACTG_HUMAN
P63261



ACTN1_HUMAN
P12814
5



ACTN1_HUMAN
P12814
22



ACTN2_HUMAN
P35609
29



ACTN3_HUMAN
Q08043
36



ACTN4_HUMAN
O43707
41



ADDA_HUMAN
P35611
633



AEBP2_HUMAN
Q6ZN18
233



AEDO_HUMAN
Q96SZ5
34



AF1L2_HUMAN
Q8N4X5
312



AF1L2_HUMAN
Q8N4X5
630



AFTIN_HUMAN
Q6ULP2
339



AGGF1_HUMAN
Q8N302
148



AHNK_HUMAN
Q09666
575



AHNK_HUMAN
Q09666
737



AHNK_HUMAN
Q09666
739



AHNK_HUMAN
Q09666
865



AHNK_HUMAN
Q09666
919



AHNK_HUMAN
Q09666
1168



AHNK_HUMAN
Q09666
1424



AHNK_HUMAN
Q09666
1583



AHNK_HUMAN
Q09666
2711



AHNK_HUMAN
Q09666
2882



AHNK_HUMAN
Q09666
3464



AHNK_HUMAN
Q09666
3493



AHNK_HUMAN
Q09666
3718



AHNK_HUMAN
Q09666
4358



AHNK_HUMAN
Q09666
5580



AHSA1_HUMAN
O95433
18



AHSA1_HUMAN
O95433
254



AHTF1_HUMAN
Q8WYP5
1367



AIM1_HUMAN
Q9Y4K1
67



AKA12_HUMAN
Q02952
451



AKAP2_HUMAN
Q9Y2D5
472



AKAP9_HUMAN
Q99996
1033



AKNA_HUMAN
Q7Z591
799



AKP13_HUMAN
Q12802
544



AKP13_HUMAN
Q12802
829



AKP13_HUMAN
Q12802
905



AKP13_HUMAN
Q12802
1055



AKP13_HUMAN
Q12802
1539



AKP8L_HUMAN
Q9ULX6
108



ALMS1_HUMAN
Q8TCU4
427



ALMS1_HUMAN
Q8TCU4
590



ALMS1_HUMAN
Q8TCU4
779



ALO17_HUMAN
Q9HCF4
273



AMPD3_HUMAN
Q01432
36



AMPM1_HUMAN
P53582
12



ANKH1_HUMAN
Q8IWZ3
4



ANKH1_HUMAN
Q8IWZ3
1048



ANKS6_HUMAN
Q68DC2
275



ANS1A_HUMAN
Q92625
529



ANXA2_HUMAN
P07355
16



AXA2L_HUMAN
A6NMY6



AP1G1_HUMAN
O43747
689



AP1G2_HUMAN
O75843
631



AP2A2_HUMAN
O94973
690



AP3B2_HUMAN
Q13367
843



APBB2_HUMAN
Q92870
279



APC_HUMAN
P25054
1498



APMAP_HUMAN
Q9HDC9
22



APTX_HUMAN
Q7Z2E3
141



AR13B_HUMAN
Q3SXY8
241



ARBK1_HUMAN
P25098
527



ARBK1_HUMAN
P25098
481



ARBK2_HUMAN
P35626



ARHG1_HUMAN
Q92888
292



ARHG2_HUMAN
Q92974
626



ARHGA_HUMAN
O15013
1246



ARI1A_HUMAN
O14497
75



ARI1A_HUMAN
O14497
606



ARI4A_HUMAN
P29374
1030



ARI4B_HUMAN
Q4LE39
1072



ARID2_HUMAN
Q68CP9
625



ARID2_HUMAN
Q68CP9
629



ARM10_HUMAN
Q8N2F6
86



ARMC6_HUMAN
Q6NXE6
82



ARNT_HUMAN
P27540
151



ARP2_HUMAN
P61160
161



ARP21_HUMAN
Q9UBL0
494



ARP3_HUMAN
P61158
59



ARPC5_HUMAN
O15511
29



ARPC5_HUMAN
O15511
32



ARS2_HUMAN
Q9BXP5
161



ASB13_HUMAN
Q8WXK3
51



ASCC1_HUMAN
Q8N9N2
34



ASCC2_HUMAN
Q9H1I8
621



ASHWN_HUMAN
Q9BVC5
105



ASPP2_HUMAN
Q13625
527



ATAD5_HUMAN
Q96QE3
284



ATD2B_HUMAN
Q9ULI0
77



ATF1_HUMAN
P18846
46



ATF4_HUMAN
P18848
65



ATF7_HUMAN
P17544
43



ATG3_HUMAN
Q9NT62
104



ATRX_HUMAN
P46100
919



ATX1L_HUMAN
P0C7T5
308



ATX2_HUMAN
Q99700
842



ATX2L_HUMAN
Q8WWM7
584



ATX3_HUMAN
P54252
217



AZI1_HUMAN
Q9UPN4
548



BA2D1_HUMAN
Q9Y520
888



BA2D1_HUMAN
Q9Y520
2189



BAP1_HUMAN
Q92560
311



BAP31_HUMAN
P51572
164



BASP_HUMAN
P80723
165



BASP_HUMAN
P80723
171



BAT3_HUMAN
P46379
1001



BAZ1A_HUMAN
Q9NRL2
499



BCAP_HUMAN
Q6ZUJ8
148



BCLF1_HUMAN
Q9NYF8
324



BCLF1_HUMAN
Q9NYF8
382



BCR_HUMAN
P11274
243



BDP1_HUMAN
A6H8Y1
525



BID_HUMAN
P55957
75



BIG3_HUMAN
Q5TH69
292



BIN1_HUMAN
O00499
301



BIRC6_HUMAN
Q9NR09
461



BL1S3_HUMAN
Q6QNY0
64



BLNK_HUMAN
Q8WV28
177



BNIP2_HUMAN
Q12982
83



BPTF_HUMAN
Q12830
1625



BRD1_HUMAN
O95696
921



BRD4_HUMAN
O60885
337



BRD8_HUMAN
Q9H0E9
560



BTB14_HUMAN
Q96RE7
174



BUB1_HUMAN
O43683
395



BUD13_HUMAN
Q9BRD0
273



C170L_HUMAN
Q96L14
50



C1QBP_HUMAN
Q07021
185



C2C2L_HUMAN
O14523
442



C2D1A_HUMAN
Q6P1N0
30



C2D1B_HUMAN
Q5T0F9
460



CA059_HUMAN
Q5T8I9
13



CA103_HUMAN
Q5T3J3
515



CA163_HUMAN
Q96BR5
120



CA165_HUMAN
Q7L4P6
103



CA170_HUMAN
Q5SV97
42



CA175_HUMAN
Q68CQ1
411



CA1L1_HUMAN
Q08AD1
421



CABL2_HUMAN
Q9BTV7
58



CACO1_HUMAN
Q9P1Z2
134



CADH2_HUMAN
P19022
799



CAF1A_HUMAN
Q13111
110



CAF1A_HUMAN
Q13111
614



CALR_HUMAN
P27797
121



CALR_HUMAN
P27797
258



CALR_HUMAN
P27797
328



CAMKV_HUMAN
Q8NCB2
407



CAMLG_HUMAN
P49069
9



CAMLG_HUMAN
P49069
115



CAMP1_HUMAN
Q5T5Y3
751



CAMP1_HUMAN
Q5T5Y3
1254



CAPR1_HUMAN
Q14444
94



CAPZB_HUMAN
P47756
149



CASC3_HUMAN
O15234
389



CASC5_HUMAN
Q8NG31
1194



CASP_HUMAN
Q13948
387



CUX1_HUMAN
P39880
376



CASP3_HUMAN
P42574
28



CASP3_HUMAN
P42574
175



CASP7_HUMAN
P55210
198



CATB_HUMAN
P07858
77



CB044_HUMAN
Q9H6R7
508



CBL_HUMAN
P22681
806



CBWD1_HUMAN
Q9BRT8
184



CBWD2_HUMAN
Q8IUF1
184



CBWD3_HUMAN
Q5JTY5
184



CBWD5_HUMAN
Q5RIA9
184



CBWD6_HUMAN
Q4V339
184



CBWD7_HUMAN
A6NM15
36



CC104_HUMAN
Q96G28
141



CC104_HUMAN
Q96G28
144



CC124_HUMAN
Q96CT7
149



CC131_HUMAN
O60293
335



CC50A_HUMAN
Q9NV96
12



CCD43_HUMAN
Q96MW1
16



CCD53_HUMAN
Q9Y3C0
4



CCD91_HUMAN
Q7Z6B0
99



CCD97_HUMAN
Q96F63
52



CCDC9_HUMAN
Q9Y3X0
299



CCNT2_HUMAN
O60583
454



CD2L1_HUMAN
P21127
405



CD2L5_HUMAN
Q14004
1353



CDC27_HUMAN
P30260
236



CDC27_HUMAN
P30260
243



CDC5L_HUMAN
Q99459
391



CDCA7_HUMAN
Q9BWT1
39



CDV3_HUMAN
Q9UKY7
122



CDYL1_HUMAN
Q9Y232
210



CE022_HUMAN
Q49AR2
196



CE152_HUMAN
O94986
62



CE170_HUMAN
Q5SW79
936



CE170_HUMAN
Q5SW79
1324



CEBPZ_HUMAN
Q03701
774



CEBPZ_HUMAN
Q03701
917



CEBPZ_HUMAN
Q03701
955



CH041_HUMAN
Q6NXR4
4



CH082_HUMAN
Q6P1X6
25



CH60_HUMAN
P10809
111



CH60_HUMAN
P10809
452



CH60_HUMAN
P10809
504



CHD3_HUMAN
Q12873
372



CHD4_HUMAN
Q14839
363



CHD5_HUMAN
Q8TDI0
336



CHD4_HUMAN
Q14839
1233



CHD7_HUMAN
Q9P2D1
2285



CHM4A_HUMAN
Q9BY43
80



CHM4B_HUMAN
Q9H444
83



CHM4C_HUMAN
Q96CF2
83



CI080_HUMAN
Q9NRY2
57



CJ018_HUMAN
Q5VWN6
1207



CJ047_HUMAN
Q86WR7
109



CK059_HUMAN
Q6IAA8
72



CL035_HUMAN
Q9HCM1
359



CL035_HUMAN
Q9HCM1
501



CL043_HUMAN
Q96C57
72



CL043_HUMAN
Q96C57
204



CLAP1_HUMAN
Q7Z460
1218



CLCA_HUMAN
P09496
76



CLCA_HUMAN
P09496
92



CLIC1_HUMAN
O00299
141



CLIP1_HUMAN
P30622
397



CLSPN_HUMAN
Q9HAW4
563



CND2_HUMAN
Q15003
170



CND2_HUMAN
Q15003
199



CND2_HUMAN
Q15003
366



CND2_HUMAN
Q15003
380



CNDH2_HUMAN
Q6IBW4
459



CO6A3_HUMAN
P12111
2615



COBL1_HUMAN
Q53SF7
983



COPA_HUMAN
P53621
188



COPA_HUMAN
P53621
856



COPB2_HUMAN
P35606
854



COR1A_HUMAN
P31146
394



CP088_HUMAN
Q1ED39
182



CP110_HUMAN
Q7Z7A1
801



CP110_HUMAN
Q7Z7A1
1395



CPIN1_HUMAN
Q6FI81
214



CPNE1_HUMAN
Q99829
464



CPNE3_HUMAN
O75131
428



CPSF6_HUMAN
Q16630
54



CPSF7_HUMAN
Q8N684
29



CPSF7_HUMAN
Q8N684
33



CPSF7_HUMAN
Q8N684
324



CPZIP_HUMAN
Q6JBY9
272



CQ056_HUMAN
Q96N21
380



CQ085_HUMAN
Q53F19
157



CQ085_HUMAN
Q53F19
231



CR025_HUMAN
Q96B23
44



CREB1_HUMAN
P16220
116



CREB1_HUMAN
P16220
229



CROCC_HUMAN
Q5TZA2
578



CS043_HUMAN
Q9BQ61
62



CS044_HUMAN
Q9H6X5
368



CSN1_HUMAN
Q13098
94



CSRN2_HUMAN
Q9H175
39



CSTF3_HUMAN
Q12996
576



CTBL1_HUMAN
Q8WYA6
66



CTCF_HUMAN
P49711
46



CTNB1_HUMAN
P35222
115



CTND1_HUMAN
O60716
161



CTR9_HUMAN
Q6PD62
1120



CUL4B_HUMAN
Q13620
25



CUTC_HUMAN
Q9NTM9
33



CUX1_HUMAN
P39880
1339



CYB5B_HUMAN
O43169
10



DBPA_HUMAN
P16989
144



DBPA_HUMAN
P16989
161



DBPA_HUMAN
P16989
269



DBPA_HUMAN
P16989
137



YBOX1_HUMAN
P67809
105



YBOX2_HUMAN
Q9Y2T7
140



DCNL2_HUMAN
Q6PH85
42



DCTN1_HUMAN
Q14203
302



DD19A_HUMAN
Q9NUU7
4



DDX1_HUMAN
Q92499
439



DDX24_HUMAN
Q9GZR7
296



DDX46_HUMAN
Q7L014
871



DDX46_HUMAN
Q7L014
922



DDX59_HUMAN
Q5T1V6
43



DESM_HUMAN
P17661
264



DFFA_HUMAN
O00273
6



DFFA_HUMAN
O00273
221



DGCR8_HUMAN
Q8WYQ5
248



DGCR8_HUMAN
Q8WYQ5
396



DGKH_HUMAN
Q86XP1
582



DGKH_HUMAN
Q86XP1
698



DGLB_HUMAN
Q8NCG7
548



DHAK_HUMAN
Q3LXA3
362



DHX30_HUMAN
Q7L2E3
206



DHX37_HUMAN
Q8IY37
573



DHX9_HUMAN
Q08211
96



DHX9_HUMAN
Q08211
167



DIAP1_HUMAN
O60610
648



DIDO1_HUMAN
Q9BTC0
987



DIDO1_HUMAN
Q9BTC0
1250



DIDO1_HUMAN
Q9BTC0
1352



DIDO1_HUMAN
Q9BTC0
1518



DLG1_HUMAN
Q12959
412



DNJC7_HUMAN
Q99615
8



DNM1L_HUMAN
O00429
503



DNM1L_HUMAN
O00429
579



DNM3A_HUMAN
Q9Y6K1
438



DOC10_HUMAN
Q96BY6
327



DOHH_HUMAN
Q9BU89
8



DOT1L_HUMAN
Q8TEK3
1333



DP13A_HUMAN
Q9UKG1
444



DPOD1_HUMAN
P28340
102



DPOLA_HUMAN
P09884
83



DPP9_HUMAN
Q86TI2
13



DPYL4_HUMAN
O14531
456



DREB_HUMAN
Q16643
340



DREB_HUMAN
Q16643
477



DSRAD_HUMAN
P55265
214



DTL_HUMAN
Q9NZJ0
578



DTX3L_HUMAN
Q8TDB6
217



DYHC1_HUMAN
Q14204
4220



DYHC1_HUMAN
Q14204
4367



E400N_HUMAN
Q6ZTU2
183



EP400_HUMAN
Q96L91
194



E41L2_HUMAN
O43491
912



EAP1_HUMAN
Q9H1B7
132



EBP2_HUMAN
Q99848
211



ECE1_HUMAN
P42892
33



ECT2_HUMAN
Q9H8V3
628



EDC4_HUMAN
Q6P2E9
57



EDC4_HUMAN
Q6P2E9
485



EDC4_HUMAN
Q6P2E9
490



EDC4_HUMAN
Q6P2E9
662



EDC4_HUMAN
Q6P2E9
796



EDRF1_HUMAN
Q3B7T1
115



EEA1_HUMAN
Q15075
127



EEA1_HUMAN
Q15075
132



EF1A1_HUMAN
P68104
403



EF1A3_HUMAN
Q5VTE0



EF1B_HUMAN
P24534
102



EF1D_HUMAN
P29692
158



EF2_HUMAN
P13639
611



EH1L1_HUMAN
Q8N3D4
1329



EHBP1_HUMAN
Q8NDI1
274



EHD1_HUMAN
Q9H4M9
415



EHMT1_HUMAN
Q9H9B1
329



EHMT1_HUMAN
Q9H9B1
481



EHMT2_HUMAN
Q96KQ7
453



EIF3B_HUMAN
P55884
184



EIF3G_HUMAN
O75821
7



EIF3J_HUMAN
O75822
50



ELF1_HUMAN
P32519
145



ENOA_HUMAN
P06733
203



ENPL_HUMAN
P14625
28



ENPL_HUMAN
P14625
59



EP15_HUMAN
P42566
618



EP15R_HUMAN
Q9UBC2
569



EPC1_HUMAN
Q9H2F5
27



EPN1_HUMAN
Q9Y6I3
460



EPN2_HUMAN
O95208
339



ERC6L_HUMAN
Q2NKX8
801



ERCC6_HUMAN
Q03468
52



ERF_HUMAN
P50548
191



ERF3A_HUMAN
P15170
39



ERIC1_HUMAN
Q86X53
276



ESYT2_HUMAN
A0FGR8
759



ETUD1_HUMAN
Q7Z2Z2
932



EXDL2_HUMAN
Q9NVH0
198



F101B_HUMAN
Q8N5W9
61



F107B_HUMAN
Q9H098
5



F117B_HUMAN
Q6P1L5
374



F125A_HUMAN
Q96EY5
172



F169A_HUMAN
Q9Y6X4
446



FA13A_HUMAN
O94988
594



FA21A_HUMAN
Q641Q2
1134



FA21B_HUMAN
Q5SNT6
1046



FA21C_HUMAN
Q9Y4E1
1113



FA21D_HUMAN
Q5SRD0
101



FA29A_HUMAN
Q7Z4H7
568



FA44A_HUMAN
Q8NFC6
1483



FA44A_HUMAN
Q8NFC6
1708



FA44A_HUMAN
Q8NFC6
2044



FAS_HUMAN
P49327
1165



FETUA_HUMAN
P02765
133



FIP1_HUMAN
Q6UN15
158



FKB15_HUMAN
Q5T1M5
306



FLI1_HUMAN
Q01543
20



FLNA_HUMAN
P21333
25



FLNA_HUMAN
P21333
1048



FLNA_HUMAN
P21333
1336



FLNA_HUMAN
P21333
1504



FLNA_HUMAN
P21333
2536



FLNA_HUMAN
P21333
34



FLNB_HUMAN
O75369
7



FLNC_HUMAN
Q14315
27



FLNB_HUMAN
O75369
478



FLNB_HUMAN
O75369
1021



FLNB_HUMAN
O75369
1476



FNBP1_HUMAN
Q96RU3
519



FNBP4_HUMAN
Q8N3X1
153



FNBP4_HUMAN
Q8N3X1
425



FNBP4_HUMAN
Q8N3X1
777



FOXJ2_HUMAN
Q9P0K8
212



FOXK1_HUMAN
P85037
80



FOXO3_HUMAN
O43524
54



FOXP4_HUMAN
Q8IVH2
406



FRAP_HUMAN
P42345
2459



FRYL_HUMAN
O94915
1512



FUBP1_HUMAN
Q96AE4
83



FUBP1_HUMAN
Q96AE4
181



FUBP1_HUMAN
Q96AE4
139



FUBP2_HUMAN
Q92945
183



FUBP2_HUMAN
Q92945
128



FUBP3_HUMAN
Q96I24
34



FUBP3_HUMAN
Q96I24
159



FUS_HUMAN
P35637
355



FXR2_HUMAN
P51116
561



FYB_HUMAN
O15117
446



FYB_HUMAN
O15117
655



FYN_HUMAN
P06241
19



FYTD1_HUMAN
Q96QD9
31



THOC4_HUMAN
Q86V81
6



FYV1_HUMAN
Q9Y2I7
989



FYV1_HUMAN
Q9Y2I7
1607



G3P_HUMAN
P04406
89



GABP1_HUMAN
Q06547
303



GABP2_HUMAN
Q8TAK5
304



GALT_HUMAN
P07902
18



GAPD1_HUMAN
Q14C86
1102



GATA2_HUMAN
P23769
46



GBF1_HUMAN
Q92538
368



GCFC_HUMAN
Q9Y5B6
221



GCP2_HUMAN
Q9BSJ2
772



GCP60_HUMAN
Q9H3P7
15



GCP60_HUMAN
Q9H3P7
343



GDIR2_HUMAN
P52566
19



GDIR2_HUMAN
P52566
55



GELS_HUMAN
P06396
403



GELS_HUMAN
P06396
639



GEMI5_HUMAN
Q8TEQ6
1319



GEMI8_HUMAN
Q9NWZ8
169



GEN_HUMAN
Q17RS7
623



GFPT1_HUMAN
Q06210
260



GGA3_HUMAN
Q9NZ52
333



GGA3_HUMAN
Q9NZ52
517



GIT1_HUMAN
Q9Y2X7
418



GIT1_HUMAN
Q9Y2X7
632



GIT2_HUMAN
Q14161
625



GLGB_HUMAN
Q04446
307



GLRX3_HUMAN
O76003
101



GLU2B_HUMAN
P14314
94



GLU2B_HUMAN
P14314
101



GLU2B_HUMAN
P14314
226



GMIP_HUMAN
Q9P107
424



GMIP_HUMAN
Q9P107
472



GMIP_HUMAN
Q9P107
842



GNL1_HUMAN
P36915
49



GNL1_HUMAN
P36915
52



GNL1_HUMAN
P36915
343



GOGB1_HUMAN
Q14789
1245



GOGB1_HUMAN
Q14789
1801



GON4L_HUMAN
Q3T8J9
481



GPKOW_HUMAN
Q92917
37



GPKOW_HUMAN
Q92917
98



GPN1_HUMAN
Q9HCN4
311



GPTC8_HUMAN
Q9UKJ3
882



GRDN_HUMAN
Q3V6T2
219



GRDN_HUMAN
Q3V6T2
484



GRIN1_HUMAN
Q7Z2K8
306



GSDMD_HUMAN
P57764
87



GSDMD_HUMAN
P57764
275



GSTP1_HUMAN
P09211
91



GTF2I_HUMAN
P78347
105



H2AY_HUMAN
O75367
172



H4_HUMAN
P62805
25



H4_HUMAN
P62805
69



HAP28_HUMAN
Q13442
24



HBS1L_HUMAN
Q9Y450
29



HCLS1_HUMAN
P14317
26



HDAC4_HUMAN
P56524
8



HDAC4_HUMAN
P56524
289



HDAC6_HUMAN
Q9UBN7
1088



HDAC7_HUMAN
Q8WUI4
412



HDC_HUMAN
Q9UBI9
323



HDGR2_HUMAN
Q7Z4V5
30



HDGR2_HUMAN
Q7Z4V5
241



HECD1_HUMAN
Q9ULT8
1492



HELLS_HUMAN
Q9NRZ9
22



HG2A_HUMAN
P04233
22



HIRP3_HUMAN
Q9BW71
110



HJURP_HUMAN
Q8NCD3
91



HMHA1_HUMAN
Q92619
39



HMHA1_HUMAN
Q92619
262



HMHA1_HUMAN
Q92619
662



HMOX2_HUMAN
P30519
251



HNRH1_HUMAN
P31943
340



HNRH2_HUMAN
P55795
340



HNRH3_HUMAN
P31942
144



HNRL1_HUMAN
Q9BUJ2
96



HNRL2_HUMAN
Q1KMD3
126



HNRLL_HUMAN
Q8WVV9
289



HNRPD_HUMAN
Q14103
69



HNRPF_HUMAN
P52597
251



HNRPG_HUMAN
P38159
233



HNRPG_HUMAN
P38159
283



HNRPK_HUMAN
P61978
128



HNRPK_HUMAN
P61978
346



HNRPK_HUMAN
P61978
370



HNRPL_HUMAN
P14866
284



HNRPQ_HUMAN
O60506
468



HOOK1_HUMAN
Q9UJC3
233



HOOK2_HUMAN
Q96ED9
160



HPS4_HUMAN
Q9NQG7
495



HRX_HUMAN
Q03164
2384



HRX_HUMAN
Q03164
2718



HS105_HUMAN
Q92598
547



HSP74_HUMAN
P34932
727



HSP7C_HUMAN
P11142
80



HTF4_HUMAN
Q99081
22



HTSF1_HUMAN
O43719
33



HTSF1_HUMAN
O43719
39



HTSF1_HUMAN
O43719
80



HUWE1_HUMAN
Q7Z6Z7
2017



HUWE1_HUMAN
Q7Z6Z7
2359



HUWE1_HUMAN
Q7Z6Z7
2473



HUWE1_HUMAN
Q7Z6Z7
2930



HUWE1_HUMAN
Q7Z6Z7
3079



HUWE1_HUMAN
Q7Z6Z7
3664



I2BP2_HUMAN
Q7Z5L9
495



I5P2_HUMAN
P32019
263



IASPP_HUMAN
Q8WUF5
294



ICAL_HUMAN
P20810
233



ICAL_HUMAN
P20810
348



ICAL_HUMAN
P20810
513



ICAL_HUMAN
P20810
659



IF2BL_HUMAN
A6NK07
118



IF2B_HUMAN
P20042



IF2P_HUMAN
O60841
20



IF4A2_HUMAN
Q14240
21



IF4B_HUMAN
P23588
50



IF4B_HUMAN
P23588
59



IF4G1_HUMAN
Q04637
414



IF4G1_HUMAN
Q04637
532



IF4G1_HUMAN
Q04637
665



IF4G2_HUMAN
P78344
792



IF4G3_HUMAN
O43432
478



IF4H_HUMAN
Q15056
93



IF5A1_HUMAN
P63241
96



IF5A1_HUMAN
P63241
6



IF5AL_HUMAN
Q6IS14



IF5A2_HUMAN
Q9GZV4
6



IKBB_HUMAN
Q15653
159



IKBL2_HUMAN
Q96HA7
498



IKZF1_HUMAN
Q13422
367



IKZF2_HUMAN
Q9UKS7
7



IKZF5_HUMAN
Q9H5V7
225



ILF3_HUMAN
Q12906
287



ILF3_HUMAN
Q12906
439



ILKAP_HUMAN
Q9H0C8
39



IMA1_HUMAN
P52294
64



IMA7_HUMAN
O60684
69



IMDH2_HUMAN
P12268
172



IN80D_HUMAN
Q53TQ3
678



INF2_HUMAN
Q27J81
1051



INF2_HUMAN
Q27J81
1146



IPO9_HUMAN
Q96P70
963



IQEC1_HUMAN
Q6DN90
234



IQGA1_HUMAN
P46940
8



IRF2_HUMAN
P14316
237



IRS4_HUMAN
O14654
716



ISY1_HUMAN
Q9ULR0
167



IWS1_HUMAN
Q96ST2
347



JHD3C_HUMAN
Q9H3R0
396



JIP4_HUMAN
O60271
5



JIP4_HUMAN
O60271
213



JIP4_HUMAN
O60271
284



JKIP1_HUMAN
Q96N16
17



JMY_HUMAN
Q8N9B5
722



JOSD3_HUMAN
Q9H5J8
10



JSPR1_HUMAN
Q96MG2
12



K0174_HUMAN
P53990
197



K0232_HUMAN
Q92628
556



K0515_HUMAN
Q5JSZ5
1082



K0515_HUMAN
Q5JSZ5
1235



K0831_HUMAN
Q6ZNE5
28



K0831_HUMAN
Q6ZNE5
226



K1462_HUMAN
Q9P266
1179



K1543_HUMAN
Q9P1Y5
861



K1627_HUMAN
Q9HCE5
29



K1704_HUMAN
Q8IXQ4
88



K1967_HUMAN
Q8N163
292



K1967_HUMAN
Q8N163
618



K1967_HUMAN
Q8N163
768



KHDR1_HUMAN
Q07666
75



KI67_HUMAN
P46013
173



KI67_HUMAN
P46013
410



KI67_HUMAN
P46013
2147



KIF15_HUMAN
Q9NS87
1133



KKCC1_HUMAN
Q8N5S9
32



KLF12_HUMAN
Q9Y4X4
73



KPYM_HUMAN
P14618
354



KRI1_HUMAN
Q8N9T8
312



KRR1_HUMAN
Q13601
38



KS6A4_HUMAN
O75676
377



KU86_HUMAN
P13010
455



KU86_HUMAN
P13010
556



LAGE3_HUMAN
Q14657
28



LAMB1_HUMAN
P07942
1358



LAP2A_HUMAN
P42166
441



LAP2A_HUMAN
P42166
486



LAP4_HUMAN
Q14160
501



LAP4_HUMAN
Q14160
635



LAP4_HUMAN
Q14160
1197



LARP1_HUMAN
Q6PKG0
172



LARP1_HUMAN
Q6PKG0
495



LARP4_HUMAN
Q71RC2
573



LARP5_HUMAN
Q92615
135



LAT_HUMAN
O43561
167



LCAP_HUMAN
Q9UIQ6
29



LCORL_HUMAN
Q8N3X6
229



LCOR_HUMAN
Q96JN0
80



LIMA1_HUMAN
Q9UHB6
345



LIN37_HUMAN
Q96GY3
23



LIN7C_HUMAN
Q9NUP9
62



LIPA1_HUMAN
Q13136
218



LIPB2_HUMAN
Q8ND30
31



LMNB1_HUMAN
P20700
146



LMO7_HUMAN
Q8WWI1
962



LMTK2_HUMAN
Q8IWU2
900



LNP_HUMAN
Q9C0E8
368



LPP_HUMAN
Q93052
403



LRBA_HUMAN
P50851
1756



LRBA_HUMAN
P50851
1784



LRC47_HUMAN
Q8N1G4
525



LRCH1_HUMAN
Q9Y2L9
405



LRCH2_HUMAN
Q5VUJ6
603



LRCH3_HUMAN
Q96II8
642



LRCH4_HUMAN
O75427
358



LRMP_HUMAN
Q12912
181



LRRF1_HUMAN
Q32MZ4
415



LRRF2_HUMAN
Q9Y608
531



LSM11_HUMAN
P83369
305



LSM3_HUMAN
P62310
6



LSP1_HUMAN
P33241
102



LTV1_HUMAN
Q96GA3
205



LYRIC_HUMAN
Q86UE4
183



M6PBP_HUMAN
O60664
9



M6PBP_HUMAN
O60664
219



M6PBP_HUMAN
O60664
222



MA7D1_HUMAN
Q3KQU3
570



MACF1_HUMAN
Q9UPN3
1523



MACF1_HUMAN
Q9UPN3
1726



MACF4_HUMAN
Q96PK2
2228



MACF1_HUMAN
Q9UPN3
3020



MACF4_HUMAN
Q96PK2
3522



MADD_HUMAN
Q8WXG6
1177



MAGD1_HUMAN
Q9Y5V3
222



MAGG1_HUMAN
Q96MG7
41



MAOM_HUMAN
P23368
379



MAP1A_HUMAN
P78559
1884



MAP4_HUMAN
P27816
8



MAP4_HUMAN
P27816
46



MAP4_HUMAN
P27816
151



MAP4_HUMAN
P27816
249



MAP4_HUMAN
P27816
327



MAP9_HUMAN
Q49MG5
119



MARE1_HUMAN
Q15691
116



MARK1_HUMAN
Q9P0L2
22



MATR3_HUMAN
P43243
187



MATR3_HUMAN
P43243
452



MATR3_HUMAN
P43243
680



MATR3_HUMAN
P43243
703



MATR3_HUMAN
P43243
763



MAVS_HUMAN
Q7Z434
490



MAX_HUMAN
P61244
48



MBB1A_HUMAN
Q9BQG0
749



MCM2_HUMAN
P49736
68



MCM2_HUMAN
P49736
88



MCM3_HUMAN
P25205
703



MCM4_HUMAN
P33991
132



MCM5_HUMAN
P33992
13



MCM6_HUMAN
Q14566
274



MDC1_HUMAN
Q14676
1035



MDN1_HUMAN
Q9NU22
5127



MED1_HUMAN
Q15648
930



MED1_HUMAN
Q15648
1484



MED14_HUMAN
O60244
994



MED26_HUMAN
O95402
407



MEF2C_HUMAN
Q06413
105



METK2_HUMAN
P31153
39



MEX3B_HUMAN
Q6ZN04
354



MGAP_HUMAN
Q8IWI9
339



MGAP_HUMAN
Q8IWI9
571



MGAP_HUMAN
Q8IWI9
680



MIA3_HUMAN
Q5JRA6
709



MIER1_HUMAN
Q8N108
51



MINT_HUMAN
Q96T58
1574



MINT_HUMAN
Q96T58
2007



MINT_HUMAN
Q96T58
2859



MISSL_HUMAN
Q8NDC0
9



MKL1_HUMAN
Q969V6
121



MKL2_HUMAN
Q9ULH7
182



MLL2_HUMAN
O14686
386



MLL2_HUMAN
O14686
1865



MLL3_HUMAN
Q8NEZ4
2188



MOBL3_HUMAN
Q9Y3A3
34



MOES_HUMAN
P26038
114



MORC3_HUMAN
Q14149
664



MORC3_HUMAN
Q14149
751



MOT1_HUMAN
P53985
469



MP2K1_HUMAN
Q02750
16



MP2K1_HUMAN
Q02750
282



MPP10_HUMAN
O00566
545



MPP8_HUMAN
Q99549
19



MPP8_HUMAN
Q99549
501



MPP8_HUMAN
Q99549
516



MRP_HUMAN
P49006
63



MSPD2_HUMAN
Q8NHP6
274



MTA70_HUMAN
Q86U44
334



MYH10_HUMAN
P35580
1160



MYH10_HUMAN
P35580
1309



MYH11_HUMAN
P35749
1160



MYH9_HUMAN
P35579
1153



MYH9_HUMAN
P35579
1375



MYO9B_HUMAN
Q13459
1703



MYPT1_HUMAN
O14974
885



N4BP1_HUMAN
O75113
490



NACA_HUMAN
Q13765
42



NADAP_HUMAN
Q9BWU0
537



NAG_HUMAN
A2RRP1
636



NAIF1_HUMAN
Q69YI7
102



NARF_HUMAN
Q9UHQ1
272



NARF_HUMAN
Q9UHQ1
291



NASP_HUMAN
P49321
19



NASP_HUMAN
P49321
32



NCK1_HUMAN
P16333
88



NCOA3_HUMAN
Q9Y6Q9
1012



NCOA5_HUMAN
Q9HCD5
153



NCOA5_HUMAN
Q9HCD5
380



NCOA6_HUMAN
Q14686
1461



NCOR1_HUMAN
O75376
385



NCOR1_HUMAN
O75376
555



NCOR1_HUMAN
O75376
1826



NCOR2_HUMAN
Q9Y618
377



NCOR2_HUMAN
Q9Y618
1926



NDRG1_HUMAN
Q92597
9



NEB2_HUMAN
Q96SB3
551



NED4L_HUMAN
Q96PU5
345



NEDD1_HUMAN
Q8NHV4
434



NEDD4_HUMAN
P46934
279



NEK1_HUMAN
Q96PY6
949



NEK4_HUMAN
P51957
380



NEK9_HUMAN
Q8TD19
841



NELFA_HUMAN
Q9H3P2
299



NFAC1_HUMAN
O95644
110



NFAC2_HUMAN
Q13469
66



NFKB2_HUMAN
Q00653
10



NFRKB_HUMAN
Q6P4R8
5



NFRKB_HUMAN
Q6P4R8
496



NHERF_HUMAN
O14745
4



NIPA_HUMAN
Q86WB0
295



NIPA_HUMAN
Q86WB0
449



NIPBL_HUMAN
Q6KC79
472



NKTR_HUMAN
P30414
959



NOL1_HUMAN
P46087
207



NOL1_HUMAN
P46087
230



NOL5_HUMAN
Q9Y2X3
124



NOP14_HUMAN
P78316
319



NP1L1_HUMAN
P55209
57



NP1L1_HUMAN
P55209
183



NP1L4_HUMAN
Q99733
8



NP1L4_HUMAN
Q99733
46



NP60_HUMAN
Q49A26
255



NPAT_HUMAN
Q14207
733



NPM_HUMAN
P06748
6



NS1BP_HUMAN
Q9Y6Y0
238



NSBP1_HUMAN
P82970
57



NSUN2_HUMAN
Q08J23
108



NSUN2_HUMAN
Q08J23
499



NSUN2_HUMAN
Q08J23
664



NU153_HUMAN
P49790
358



NUCB2_HUMAN
P80303
237



NUCB2_HUMAN
P80303
258



NUCKS_HUMAN
Q9H1E3
29



NUCL_HUMAN
P19338
636



NUDC3_HUMAN
Q8IVD9
119



NUDC3_HUMAN
Q8IVD9
125



NUFP2_HUMAN
Q7Z417
451



NUMA1_HUMAN
Q14980
1747



NUMA1_HUMAN
Q14980
1829



NUP43_HUMAN
Q8NFH3
58



NUP50_HUMAN
Q9UKX7
126



NUP93_HUMAN
Q8N1F7
157



ODPB_HUMAN
P11177
37



OFD1_HUMAN
O75665
853



ORAV1_HUMAN
Q8WV07
9



OSBL8_HUMAN
Q9BZF1
806



OTU6B_HUMAN
Q8N6M0
80



OTUD4_HUMAN
Q01804
9



OXR1_HUMAN
Q8N573
449



P4R3A_HUMAN
Q6IN85
692



P66B_HUMAN
Q8WXI9
344



PA24A_HUMAN
P47712
522



PABP2_HUMAN
Q86U42
111



PAIRB_HUMAN
Q8NC51
337



PAK1_HUMAN
Q13153
90



PAK2_HUMAN
Q13177
89



PAK2_HUMAN
Q13177
148



PALLD_HUMAN
Q8WX93
432



PARG_HUMAN
Q86W56
256



PARP1_HUMAN
P09874
72



PARP1_HUMAN
P09874
214



PAWR_HUMAN
Q96IZ0
131



PAXI_HUMAN
P49023
5



PAXI_HUMAN
P49023
102



PAXI_HUMAN
P49023
335



PB1_HUMAN
Q86U86
21



PCBP1_HUMAN
Q15365
203



PCBP1_HUMAN
Q15365
220



PCBP1_HUMAN
Q15365
275



PCBP2_HUMAN
Q15366
282



PCF11_HUMAN
O94913
1288



PCM1_HUMAN
Q15154
193



PCM1_HUMAN
Q15154
1551



PCNT_HUMAN
O95613
80



PDIP3_HUMAN
Q9BY77
234



PDLI1_HUMAN
O00151
54



PDXD1_HUMAN
Q6P996
584



PEBB_HUMAN
Q13951
120



PFTK1_HUMAN
O94921
56



PGK1_HUMAN
P00558
68



PGK1_HUMAN
P00558
98



PGK1_HUMAN
P00558
285



PGK1_HUMAN
P00558
159



PGK2_HUMAN
P07205



PHAR4_HUMAN
Q8IZ21
20



PHF3_HUMAN
Q92576
1099



PHF3_HUMAN
Q92576
1157



PHF3_HUMAN
Q92576
1397



PHF3_HUMAN
Q92576
1626



PHTNS_HUMAN
Q6NYC8
495



PI4KB_HUMAN
Q9UBF8
488



PIAS1_HUMAN
O75925
100



PICAL_HUMAN
Q13492
276



PITM1_HUMAN
O00562
378



PJA2_HUMAN
O43164
86



PKHG1_HUMAN
Q9ULL1
435



PKP4_HUMAN
Q99569
803



PLCG1_HUMAN
P19174
770



PLDN_HUMAN
Q9UL45
10



POGZ_HUMAN
Q7Z3K3
27



POMP_HUMAN
Q9Y244
12



PP1RA_HUMAN
Q96QC0
293



PP1RA_HUMAN
Q96QC0
366



PP1RA_HUMAN
Q96QC0
376



PP4R1_HUMAN
Q8TF05
444



PPIA_HUMAN
P62937
9



PPIL4_HUMAN
Q8WUA2
232



PPR3D_HUMAN
O95685
31



PR40A_HUMAN
O75400
133



PRD15_HUMAN
P57071
1269



PRKDC_HUMAN
P78527
3211



PROF1_HUMAN
P07737
14



PROF1_HUMAN
P07737
19



PROF1_HUMAN
P07737
81



PRP17_HUMAN
O60508
55



PRP17_HUMAN
O60508
190



PRP17_HUMAN
O60508
204



PRP31_HUMAN
Q8WWY3
386



PRR12_HUMAN
Q9ULL5
115



PRR3_HUMAN
P79522
31



PRS10_HUMAN
P62333
265



PRS6A_HUMAN
P17980
27



PRS6A_HUMAN
P17980
318



PRS6B_HUMAN
P43686
297



PRS8_HUMAN
P62195
252



PSA5_HUMAN
P28066
71



PSA7L_HUMAN
Q8TAA3
15



PSA7_HUMAN
O14818
13



PSB1_HUMAN
P20618
47



PSB4_HUMAN
P28070
29



PSB7_HUMAN
Q99436
53



PSD12_HUMAN
O00232
19



PSD4_HUMAN
Q8NDX1
82



PSD4_HUMAN
Q8NDX1
535



PSIP1_HUMAN
O75475
30



PSIP1_HUMAN
O75475
433



PSME3_HUMAN
P61289
77



PTBP1_HUMAN
P26599
139



PTBP1_HUMAN
P26599
172



PTCA_HUMAN
Q14761
116



PTCA_HUMAN
Q14761
120



PTMA_HUMAN
P06454
7



PTN3_HUMAN
P26045
471



PUR2_HUMAN
P22102
205



PUR2_HUMAN
P22102
225



PUR2_HUMAN
P22102
443



PUR6_HUMAN
P22234
26



PUR6_HUMAN
P22234
319



PUR9_HUMAN
P31939
339



PUS7_HUMAN
Q96PZ0
22



PUS7_HUMAN
Q96PZ0
50



PWP2A_HUMAN
Q96N64
55



PYR1_HUMAN
P27708
1138



QKI_HUMAN
Q96PU8
74



QN1_HUMAN
Q5TB80
247



QSER1_HUMAN
Q2KHR3
1321



QSK_HUMAN
Q9Y2K2
383



R3HD1_HUMAN
Q15032
499



RA1L3_HUMAN
P0C7M2
69



ROA1_HUMAN
P09651



RA1L3_HUMAN
P0C7M2
157



ROA1_HUMAN
P09651



RAD21_HUMAN
O60216
128



RAD21_HUMAN
O60216
279



RADIL_HUMAN
Q96JH8
841



RANG_HUMAN
P43487
127



RB_HUMAN
P06400
346



RB3GP_HUMAN
Q15042
252



RBBP4_HUMAN
Q09028
361



RBBP7_HUMAN
Q16576
360



RBBP6_HUMAN
Q7Z6E9
972



RBBP6_HUMAN
Q7Z6E9
1267



RBBP6_HUMAN
Q7Z6E9
1678



RBBP7_HUMAN
Q16576
93



RBBP7_HUMAN
Q16576
98



RBBP8_HUMAN
Q99708
742



RBM15_HUMAN
Q96T37
750



RBM16_HUMAN
Q9UPN6
380



RBM16_HUMAN
Q9UPN6
775



RBM25_HUMAN
P49756
633



RBM26_HUMAN
Q5T8P6
280



RBM26_HUMAN
Q5T8P6
431



RBM27_HUMAN
Q9P2N5
487



RBM28_HUMAN
Q9NW13
244



RBM33_HUMAN
Q96EV2
998



RBM39_HUMAN
Q14498
331



RBM8A_HUMAN
Q9Y5S9
6



RBM8A_HUMAN
Q9Y5S9
55



RBM9_HUMAN
O43251
102



RBP2_HUMAN
P49792
1157



RBP2_HUMAN
P49792
2490



RBP2_HUMAN
P49792
2860



RBP2_HUMAN
P49792
3131



RBP2_HUMAN
P49792
2306



RGPD1_HUMAN
Q68DN6
1315



RGPD3_HUMAN
A6NKT7
1331



RGPD4_HUMAN
Q7Z3J3
1331



RGPD5_HUMAN
Q99666
1330



RGPD6_HUMAN
Q53T03
1330



RGPD8_HUMAN
O14715
320



RBP2_HUMAN
P49792
2236



RGPD3_HUMAN
A6NKT7
1261



RGPD4_HUMAN
Q7Z3J3
1261



RGPD5_HUMAN
Q99666
1260



RGPD6_HUMAN
Q53T03
1260



RGPD8_HUMAN
O14715
250



RBP56_HUMAN
Q92804
140



RBTN1_HUMAN
P25800
8



RBY1B_HUMAN
A6NDE4
466



RBY1F_HUMAN
Q15415
466



RBY1H_HUMAN
Q15378
326



RCC2_HUMAN
Q9P258
60



RCN2_HUMAN
Q14257
203



RCOR2_HUMAN
Q8IZ40
391



RD23B_HUMAN
P54727
165



RED_HUMAN
Q13123
108



RED_HUMAN
Q13123
324



REL_HUMAN
Q04864
86



RENT1_HUMAN
Q92900
75



REPS1_HUMAN
Q96D71
386



REPS1_HUMAN
Q96D71
459



REPS1_HUMAN
Q96D71
465



REQU_HUMAN
Q92785
115



REQU_HUMAN
Q92785
243



REST_HUMAN
Q13127
941



RFC1_HUMAN
P35251
167



RFC1_HUMAN
P35251
723



RFX7_HUMAN
Q2KHR2
479



RGAP1_HUMAN
Q9H0H5
273



RGPD1_HUMAN
Q68DN6
1499



RGPD2_HUMAN
P0C839
764



RGPD3_HUMAN
A6NKT7
1515



RGPD4_HUMAN
Q7Z3J3
1515



RGPD5_HUMAN
Q99666
1514



RGPD6_HUMAN
Q53T03
1514



RGPD8_HUMAN
O14715
504



RGS10_HUMAN
O43665
12



RGS10_HUMAN
O43665
14



RHG04_HUMAN
P98171
403



RHG25_HUMAN
P42331
387



RHG25_HUMAN
P42331
397



RHG30_HUMAN
Q7Z6I6
363



RHG30_HUMAN
Q7Z6I6
592



RHG30_HUMAN
Q7Z6I6
907



RHGBA_HUMAN
Q6P4F7
256



RHOA_HUMAN
P61586
90



RHOC_HUMAN
P08134



RIF1_HUMAN
Q5UIP0
1809



RIF1_HUMAN
Q5UIP0
2000



RIMB1_HUMAN
O95153
44



RIMB1_HUMAN
O95153
1807



RING1_HUMAN
Q06587
31



RIOK1_HUMAN
Q9BRS2
129



RIPK1_HUMAN
Q13546
558



RIR2_HUMAN
P31350
29



RL17_HUMAN
P18621
110



RL5_HUMAN
P46777
136



RL5_HUMAN
P46777
168



RN168_HUMAN
Q8IYW5
250



RN213_HUMAN
Q63HN8
355



RN219_HUMAN
Q5W0B1
433



RN220_HUMAN
Q5VTB9
413



RNF5_HUMAN
Q99942
8



RNZ1_HUMAN
Q9H777
279



ROA0_HUMAN
Q13151
62



ROA0_HUMAN
Q13151
73



ROA2_HUMAN
P22626
76



ROA2_HUMAN
P22626
130



ROA3_HUMAN
P51991
90



ROA3_HUMAN
P51991
115



ROA3_HUMAN
P51991
178



ROCK1_HUMAN
Q13464
1113



RPAP3_HUMAN
Q9H6T3
124



RPAP3_HUMAN
Q9H6T3
451



RPB9_HUMAN
P36954
4



RPC4_HUMAN
P05423
131



RPC5_HUMAN
Q9NVU0
543



RPGF6_HUMAN
Q8TEU7
1282



RREB1_HUMAN
Q92766
1173



RRMJ3_HUMAN
Q8IY81
346



RRP12_HUMAN
Q5JTH9
556



RRP12_HUMAN
Q5JTH9
1161



RRP1B_HUMAN
Q14684
275



RS20_HUMAN
P60866
5



RS23_HUMAN
P62266
88



RS28_HUMAN
P62857
54



RS3_HUMAN
P23396
32



RSRC1_HUMAN
Q96IZ7
238



RTF1_HUMAN
Q92541
140



RTN4_HUMAN
Q9NQC3
84



RTN4_HUMAN
Q9NQC3
905



RU1C_HUMAN
P09234
10



RU2A_HUMAN
P09661
45



RUSD2_HUMAN
Q8IZ73
441



RUXF_HUMAN
P62306
52



S11IP_HUMAN
Q8N1F8
372



S12A2_HUMAN
P55011
66



S2546_HUMAN
Q96AG3
10



S30BP_HUMAN
Q9UHR5
44



SAFB1_HUMAN
Q15424
146



SAFB1_HUMAN
Q15424
262



SAFB2_HUMAN
Q14151
261



SAFB1_HUMAN
Q15424
360



SAFB2_HUMAN
Q14151
359



SAFB1_HUMAN
Q15424
796



SAFB2_HUMAN
Q14151
820



SAFB2_HUMAN
Q14151
153



SAFB2_HUMAN
Q14151
183



SAHH2_HUMAN
O43865
5



SAHH2_HUMAN
O43865
73



SAHH2_HUMAN
O43865
83



SAHH3_HUMAN
Q96HN2
109



SAM4B_HUMAN
Q5PRF9
412



SAP_HUMAN
P07602
312



SAP_HUMAN
P07602
405



SAPS1_HUMAN
Q9UPN7
358



SASH3_HUMAN
O75995
55



SASH3_HUMAN
O75995
115



SATB1_HUMAN
Q01826
254



SATT_HUMAN
P43007
12



SC16A_HUMAN
O15027
341



SC16A_HUMAN
O15027
837



SC24B_HUMAN
O95487
295



SCAM3_HUMAN
O14828
39



SCMH1_HUMAN
Q96GD3
511



SCO1_HUMAN
O75880
188



SCOC_HUMAN
Q9UIL1
87



SDCG1_HUMAN
O60524
779



SEC13_HUMAN
P55735
14



SEC20_HUMAN
Q12981
32



SENP6_HUMAN
Q9GZR1
49



SEPT9_HUMAN
Q9UHD8
282



SETD2_HUMAN
Q9BYW2
647



SETD2_HUMAN
Q9BYW2
1169



SETX_HUMAN
Q7Z333
1534



SF01_HUMAN
Q15637
448



SF3A1_HUMAN
Q15459
32



SF3A1_HUMAN
Q15459
503



SF3B1_HUMAN
O75533
34



SF3B2_HUMAN
Q13435
291



SF3B2_HUMAN
Q13435
753



SF3B4_HUMAN
Q15427
12



SFPQ_HUMAN
P23246
525



SFR14_HUMAN
Q8IX01
732



SFR14_HUMAN
Q8IX01
901



SFR14_HUMAN
Q8IX01
922



SFRIP_HUMAN
Q99590
407



SFRS2_HUMAN
Q01130
70



SFRS2_HUMAN
Q01130
73



SFRS3_HUMAN
P84103
4



SFRS5_HUMAN
Q13243
52



SFRS6_HUMAN
Q13247
167



SGOL1_HUMAN
Q5FBB7
206



SH2D3_HUMAN
Q8N5H7
375



SHOT1_HUMAN
A0MZ66
129



SIPA1_HUMAN
Q96FS4
814



SIX4_HUMAN
Q9UIU6
296



SKI_HUMAN
P12755
527



SKT_HUMAN
Q5T5P2
609



SLD5_HUMAN
Q9BRT9
6



SLK_HUMAN
Q9H2G2
403



SLMAP_HUMAN
Q14BN4
464



SLU7_HUMAN
O95391
7



SMC2_HUMAN
O95347
1116



SMCA4_HUMAN
P51532
1381



SMCE1_HUMAN
Q969G3
264



SMHD1_HUMAN
A6NHR9
5



SMRC2_HUMAN
Q8TAQ2
814



SMRD2_HUMAN
Q92925
135



SNPC4_HUMAN
Q5SXM2
1168



SNX12_HUMAN
Q9UMY4
21



SNX2_HUMAN
O60749
84



SNX29_HUMAN
Q8TEQ0
182



SNX3_HUMAN
O60493
32



SNX6_HUMAN
Q9UNH7
10



SOBP_HUMAN
A7XYQ1
298



SODC_HUMAN
P00441
93



SODC_HUMAN
P00441
102



SON_HUMAN
P18583
153



SON_HUMAN
P18583
352



SON_HUMAN
P18583
1640



SON_HUMAN
P18583
1718



SP1_HUMAN
P08047
199



SP110_HUMAN
Q9HB58
353



SP3_HUMAN
Q02447
275



SP3_HUMAN
Q02447
530



SPAS2_HUMAN
Q86XZ4
145



SPAST_HUMAN
Q9UBP0
470



SPD2B_HUMAN
A1X283
682



SPEC1_HUMAN
Q5M775
213



SPEE_HUMAN
P19623
6



SPF27_HUMAN
O75934
14



SPF30_HUMAN
O75940
62



SPG20_HUMAN
Q8N0X7
496



SPS2L_HUMAN
Q9NUQ6
119



SPT6H_HUMAN
Q7KZ85
1047



SPTA2_HUMAN
Q13813
500



SPTA2_HUMAN
Q13813
1478



SPTN2_HUMAN
O15020
1752



SR140_HUMAN
O15042
704



SR140_HUMAN
O15042
712



SR140_HUMAN
O15042
725



SR140_HUMAN
O15042
737



SRC_HUMAN
P12931
45



SRCAP_HUMAN
Q6ZRS2
2275



SRFB1_HUMAN
Q8NEF9
211



SRP68_HUMAN
Q9UHB9
537



SRPK1_HUMAN
Q96SB4
412



SRRM2_HUMAN
Q9UQ35
147



SRRM2_HUMAN
Q9UQ35
1149



SSA27_HUMAN
O60232
81



SSBP3_HUMAN
Q9BWW4
286



SSF1_HUMAN
Q9NQ55
245



SSFA2_HUMAN
P28290
627



SSH2_HUMAN
Q76I76
963



SSRP1_HUMAN
Q08945
173



STAP1_HUMAN
Q9ULZ2
170



STK10_HUMAN
O94804
332



STK24_HUMAN
Q9Y6E0
325



STK39_HUMAN
Q9UEW8
435



STK4_HUMAN
Q13043
349



STRN_HUMAN
O43815
35



STRN_HUMAN
O43815
436



STX10_HUMAN
O60499
138



STX10_HUMAN
O60499
196



STX12_HUMAN
Q86Y82
217



STX17_HUMAN
P56962
201



STX7_HUMAN
O15400
204



SUGT1_HUMAN
Q9Y2Z0
20



SYAP1_HUMAN
Q96A49
281



SYEP_HUMAN
P07814
929



SYF2_HUMAN
O95926
12



SYG_HUMAN
P41250
56



SYMPK_HUMAN
Q92797
28



SYNC_HUMAN
O43776
409



SYNE1_HUMAN
Q8NF91
8279



SYNE2_HUMAN
Q8WXH0
4215



SYWC_HUMAN
P23381
83



T106B_HUMAN
Q9NUM4
19



T106C_HUMAN
Q9BVX2
23



T2EA_HUMAN
P29083
303



T2FA_HUMAN
P35269
272



TACC1_HUMAN
O75410
323



TACC1_HUMAN
O75410
500



TACC2_HUMAN
O95359
371



TACC3_HUMAN
Q9Y6A5
21



TACC3_HUMAN
Q9Y6A5
286



TAD1L_HUMAN
Q96BN2
78



TAF11_HUMAN
Q15544
34



TAF7_HUMAN
Q15545
100



TBA1A_HUMAN
Q71U36
33



TBA1B_HUMAN
P68363



TBA1C_HUMAN
Q9BQE3



TBA3C_HUMAN
Q13748



TBA3E_HUMAN
Q6PEY2



TBA1A_HUMAN
Q71U36
245



TBA1B_HUMAN
P68363



TBA1C_HUMAN
Q9BQE3



TBA3C_HUMAN
Q13748



TBA3E_HUMAN
Q6PEY2



TBA4A_HUMAN
P68366



TBA8_HUMAN
Q9NY65



TBB2A_HUMAN
Q13885
114



TBB2B_HUMAN
Q9BVA1



TBB2C_HUMAN
P68371



TBB3_HUMAN
Q13509



TBB5_HUMAN
P07437



TBB2C_HUMAN
P68371
114



TBB5_HUMAN
P07437



TBCC_HUMAN
Q15814
153



TBCD4_HUMAN
O60343
272



TBCD4_HUMAN
O60343
275



TBL1R_HUMAN
Q9BZK7
152



TBL1R_HUMAN
Q9BZK7
85



TBL1X_HUMAN
O60907



TBL1R_HUMAN
Q9BZK7
152



TBL1Y_HUMAN
Q9BQ87
162



TBL1X_HUMAN
O60907
164



TCEA1_HUMAN
P23193
124



TCF20_HUMAN
Q9UGU0
1219



TCOF_HUMAN
Q13428
1101



TCOF_HUMAN
Q13428
1242



TCPD_HUMAN
P50991
268



TCPD_HUMAN
P50991
456



TCPE_HUMAN
P48643
65



TCPE_HUMAN
P48643
153



TCPZ_HUMAN
P40227
404



TCTP_HUMAN
P13693
25



TDRD6_HUMAN
O60522
1918



TEX2_HUMAN
Q8IWB9
96



TEX2_HUMAN
Q8IWB9
356



TF2B_HUMAN
Q00403
207



TF2L1_HUMAN
Q9NZI6
22



TFCP2_HUMAN
Q12800
42



UBIP1_HUMAN
Q9NZI7
39



TF3A_HUMAN
Q92664
18



TF65_HUMAN
Q04206
97



TGS1_HUMAN
Q96RS0
337



TGS1_HUMAN
Q96RS0
343



THOC4_HUMAN
Q86V81
93



THOC5_HUMAN
Q13769
17



THOP1_HUMAN
P52888
13



TIF1A_HUMAN
O15164
784



TIF1B_HUMAN
Q13263
105



TIF1B_HUMAN
Q13263
148



TIF1B_HUMAN
Q13263
685



TIF1B_HUMAN
Q13263
688



TIF1B_HUMAN
Q13263
726



TIM_HUMAN
Q9UNS1
579



TINF2_HUMAN
Q9BSI4
207



TLK2_HUMAN
Q86UE8
132



TM168_HUMAN
Q9H0V1
426



TM1L2_HUMAN
Q6ZVM7
157



TMUB1_HUMAN
Q9BVT8
60



TNIP2_HUMAN
Q8NFZ5
194



TNR6A_HUMAN
Q8NDV7
1542



TOE1_HUMAN
Q96GM8
7



TOE1_HUMAN
Q96GM8
373



TOIP1_HUMAN
Q5JTV8
226



TOIP1_HUMAN
Q5JTV8
304



TOLIP_HUMAN
Q9H0E2
36



TOM1_HUMAN
O60784
157



TOM1_HUMAN
O60784
179



TOM1_HUMAN
O60784
184



TOM1_HUMAN
O60784
393



TOP2B_HUMAN
Q02880
1470



TP53B_HUMAN
Q12888
211



TP53B_HUMAN
Q12888
317



TP53B_HUMAN
Q12888
829



TP53B_HUMAN
Q12888
1478



TPR_HUMAN
P12270
1837



TPR_HUMAN
P12270
2147



TPRGL_HUMAN
Q5T0D9
9



TR150_HUMAN
Q9Y2W1
574



TRBP2_HUMAN
Q15633
234



TREF1_HUMAN
Q96PN7
760



TRI33_HUMAN
Q9UPN9
829



TRIP4_HUMAN
Q15650
122



TRIP4_HUMAN
Q15650
288



TRM1L_HUMAN
Q7Z2T5
44



TRS85_HUMAN
Q9Y2L5
853



TSC1_HUMAN
Q92574
638



TSR1_HUMAN
Q2NL82
332



TTC1_HUMAN
Q99614
65



TTC4_HUMAN
O95801
254



TTF2_HUMAN
Q9UNY4
826



TYB10_HUMAN
P63313
6



TYSY_HUMAN
P04818
119



TYY1_HUMAN
P25490
119



U119A_HUMAN
Q13432
44



U119B_HUMAN
A6NIH7
51



U2AF2_HUMAN
P26368
128



UAP1L_HUMAN
Q3KQV9
299



UAP56_HUMAN
Q13838
25



UBA1_HUMAN
P22314
427



UBA3_HUMAN
Q8TBC4
25



UBAP2_HUMAN
Q5T6F2
201



UBAP2_HUMAN
Q5T6F2
262



UBAP2_HUMAN
Q5T6F2
854



UBE2O_HUMAN
Q9C0C9
437



UBE2O_HUMAN
Q9C0C9
1225



UBFD1_HUMAN
O14562
232



UBN1_HUMAN
Q9NPG3
136



UBP10_HUMAN
Q14694
125



UBP10_HUMAN
Q14694
138



UBP10_HUMAN
Q14694
217



UBP14_HUMAN
P54578
76



UBP14_HUMAN
P54578
227



UBP19_HUMAN
O94966
619



UBP2L_HUMAN
Q14157
298



UBP2L_HUMAN
Q14157
411



UBP2L_HUMAN
Q14157
850



UBP34_HUMAN
Q70CQ2
3366



UBP36_HUMAN
Q9P275
576



UBP42_HUMAN
Q9H9J4
764



UBP5_HUMAN
P45974
134



UBP5_HUMAN
P45974
767



UBP5_HUMAN
P45974
782



UBP7_HUMAN
Q93009
50



UBQL1_HUMAN
Q9UMX0
15



UBR4_HUMAN
Q5T4S7
2903



UBXN7_HUMAN
O94888
109



UBXN7_HUMAN
O94888
400



UGPA_HUMAN
Q16851
15



UH1BL_HUMAN
A0JNW5
1173



UHRF1_HUMAN
Q96T88
118



URP2_HUMAN
Q86UX7
344



USE1_HUMAN
Q9NZ43
129



USF2_HUMAN
Q15853
120



USO1_HUMAN
O60763
757



UTRO_HUMAN
P46939
261



VAMP2_HUMAN
P63027
68



VAMP3_HUMAN
Q15836
51



VATD_HUMAN
Q9Y5K8
117



VIME_HUMAN
P08670
82



VIME_HUMAN
P08670
85



VIME_HUMAN
P08670
90



VIME_HUMAN
P08670
257



VIME_HUMAN
P08670
259



VIME_HUMAN
P08670
331



VIME_HUMAN
P08670
429



VP13D_HUMAN
Q5THJ4
2610



VPS4A_HUMAN
Q9UN37
230



VRK1_HUMAN
Q99986
231



WAPL_HUMAN
Q7Z5K2
154



WASF1_HUMAN
Q92558
247



WASF2_HUMAN
Q9Y6W5
242



WASF2_HUMAN
Q9Y6W5
411



WASH1_HUMAN
A8K0Z3
298



WDR33_HUMAN
Q9C0J8
1183



WDR44_HUMAN
Q5JSH3
83



WDR55_HUMAN
Q9H6Y2
20



WDR62_HUMAN
O43379
1301



WDR92_HUMAN
Q96MX6
118



WFS1_HUMAN
O76024
75



WFS1_HUMAN
O76024
211



WIPF1_HUMAN
O43516
181



WNK1_HUMAN
Q9H4A3
652



WNK1_HUMAN
Q9H4A3
1069



WNK1_HUMAN
Q9H4A3
2025



WRIP1_HUMAN
Q96S55
192



WWC2_HUMAN
Q6AWC2
855



XPA_HUMAN
P23025
5



YAP1_HUMAN
P46937
111



YBOX1_HUMAN
P67809
24



YBOX1_HUMAN
P67809
112



YIPF3_HUMAN
Q9GZM5
68



YJ005_HUMAN
Q6ZSR9
117



YJ005_HUMAN
Q6ZSR9
123



YM017_HUMAN
A8MX80
223



YTDC2_HUMAN
Q9H6S0
324



YTHD1_HUMAN
Q9BYJ9
164



YTHD2_HUMAN
Q9Y5A9
166



YTHD2_HUMAN
Q9Y5A9
367



YTHD3_HUMAN
Q7Z739
168



ZAP70_HUMAN
P43403
290



ZBT34_HUMAN
Q8NCN2
139



ZBT44_HUMAN
Q8NCP5
157



ZC11A_HUMAN
O75152
348



ZC11A_HUMAN
O75152
530



ZC3H4_HUMAN
Q9UPT8
67



ZC3H4_HUMAN
Q9UPT8
741



ZC3HD_HUMAN
Q5T200
159



ZC3HE_HUMAN
Q6PJT7
523



ZCCHV_HUMAN
Q7Z2W4
433



ZCCHV_HUMAN
Q7Z2W4
491



ZCH18_HUMAN
Q86VM9
361



ZCHC2_HUMAN
Q9C0B9
234



ZCHC8_HUMAN
Q6NZY4
343



ZEB1_HUMAN
P37275
49



ZF161_HUMAN
O43829
243



ZFAN6_HUMAN
Q6FIF0
106



ZFAN6_HUMAN
Q6FIF0
126



ZFPL1_HUMAN
O95159
171



ZFX_HUMAN
P17010
244



ZFY16_HUMAN
Q7Z3T8
107



ZFY16_HUMAN
Q7Z3T8
283



ZFY16_HUMAN
Q7Z3T8
534



ZMYM3_HUMAN
Q14202
255



ZMYM4_HUMAN
Q5VZL5
928



ZN143_HUMAN
P52747
151



ZN143_HUMAN
P52747
182



ZN200_HUMAN
P98182
188



ZN264_HUMAN
O43296
159



ZN277_HUMAN
Q9NRM2
6



ZN346_HUMAN
Q9UL40
13



ZN644_HUMAN
Q9H582
615



ZN646_HUMAN
O15015
1005



ZN787_HUMAN
Q6DD87
230



ZN828_HUMAN
Q96JM3
585



ZNF24_HUMAN
P17028
9



ZNF76_HUMAN
P36508
13



ZNHI2_HUMAN
Q9UHR6
144



ZYX_HUMAN
Q15942
149










It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and scope of the appended claims. All publications, accession numbers, patents, and patent applications cited herein are hereby incorporated by reference in their entirety for all purposes.

## Claims

1. A method of detecting a proteolytic polypeptide in a subject, the method comprising the steps of:
(a) obtaining a sample from a subject;
(b) contacting a proteolytic polypeptide with an antibody in said sample, wherein said antibody specifically binds said proteolytic polypeptide relative to a corresponding proteolytic cleavage junction of said proteolytic polypeptide; and
(c) detecting binding between said proteolytic polypeptide and said antibody;
wherein said proteolytic polypeptide is a sequence selected from the group consisting of SEQ ID NO:1 through SEQ ID NO:401.

2. The method of claim 1, wherein
step (b) comprises contacting a plurality of different proteolytic polypeptides with a plurality of different antibodies in said biological sample;
wherein said plurality of different proteolytic polypeptides are sequences selected from the group consisting of SEQ ID NO:1 through SEQ ID NO:401.

3. The method of claim 1, wherein said proteolytic polypeptide is selected from the group consisting of:
SISSQLGPIHPPPR (SEQ ID NO:63),
SFGGDAQADEGQAR (SEQ ID NOs:172 and 173),
GVPSDSVEAAKNASNTEK (SEQ ID NOs:198 and 199),
GVPLDATEDSKKNEPIFK (SEQ ID NO:300),
GSETPQLFTVLPEKR (SEQ ID NO:283),
GLPEEQPQTTK (SEQ ID NO:107),
GLGVARPHYGSVLDNER (SEQ ID NO:122 and 123),
GGGPGQVVDDGLEHR (SEQ ID NOs:87 and 412),
AYEPQGGSGYDYSYAGGR (SEQ ID NO:100),
ASSASSFLDSDELER (SEQ ID NOs:239 and 240),
ALYVACQGQPK (SEQ ID NO:177),
GFDVASVQQQR (SEQ ID NO:153),
GLAVTPTPVPVVGSQMTR (SEQ ID NO:349),
GQSDENKDDYTIPDEYR (SEQ ID NO:164),
GLVETPTGYIESLPR (SEQ ID NOs:195 and 196),
GVPSDSVEAAK (SEQ ID NOs:197, 198 and 199),
AINTEFK (SEQ ID NOs:366, 367, 369 and 370),
SLADAINTEFKNTR (SEQ ID NO:370),
GFDQNVNVK (SEQ ID NO:223),
GLGLSYLSSHIANVER (SEQ ID NO:73),
AINTEFKNTR (SEQ ID NOs:367 and 370),
ALKGTNESLER (SEQ ID NO:368),
AVTPGPQPTLEQLEEGGPRPLER (SEQ ID NOs:120 and 121),
AVSGQLPDPTTNPSAGKDGPSLLVVEQVR (SEQ ID NO:150),
GVPVPGSPFPLEAVAPTKPSK (SEQ ID NOs:58, 59 and 60),
GVPSDSVEAAKNASNTEKLTDQVMQNPR (SEQ ID NO:199), and
ATVGGPAPTPLLPPSATASVK (SEQ ID NO:136).