bluuebunny/crossref_metadata_2025 huggingface dataset:
Rab20
Authors: Lutcke Anne , Zerial Marino
Published: November 2023

Like Rab17 and Rab18, the Rab20 cDNA was isolated from an embryonic day 17 mouse kidney cDNA library using a polymerase chain reaction (PCR) fragment identified by Chavrier et al. (1992) as a probe. One ∼1.4-kb full-length clone was identified lacking a minor portion from the 5’ untranslated region of the corresponding mRNA (-1.6 kb). The nucleotide and deduced amino acid sequences are shown in Fig. 1 and can be obtained from the EMBL/GenBank/DDB under the accession number X80332.
Rab24
Authors: Olkkonen Vesa M
Published: November 2023

The sequence was first identified in the PCR study of Chavrier et al. (1992). Here, Rab/Rho-related sequences were amplified from adult mouse kidney cDNA using degenerated oligonucleotides corresponding to two of the conserved sequence stretches of Rab/Rho GTPases as primers. The PCR-Rab16 fragment containing the 5’-end of the open reading frame (ORF) was used for designing gene-specific primers, with which the sequence was extended to the 3’-direction with the 3’-RACE PCR technique (Frohman et al. 1988; Walker et al. 1992).
Rab25
Authors: Goldenring James R
Published: November 2023

The Rab25 nucelotide sequence was identified initially through amplification of carboxy-terminal sequences of rabbit parietal cell small GTP-binding proteins using a 3’-rapid amplification of cDNA ends (3’RACE) protocol based on a degenerate oligonucleotide synthesized for the WDTAGQE motif (Goldenring et al. 1993). The complete Rab25 sequence wasobtained with 5’-RACE (Fig. 1; GenBank accession number L03303).
Rab-GDI2
Authors: Shisheva Assia , Czech Michael P
Published: November 2023

A full-length mouse GDI2 cDNA was isolated by screening a mouse skeletal muscle cDNA library with the full-length rat brain GDI1 cDNA (Shisheva et al. 1994). A cDNA clone found to be the mouse homolog of the previously reported bovine brain smg p25A-GDI (Matsui et al. 1990) and rat brain GDI1 (Shisheva etal. 1994) was also isolated from the mouse skeletal muscle library and is denoted mGDI1 (Shisheva et al. 1994). The DNA sequence of mGDI2 is presented in Fig. 1. The GenBank accession number is UO7951.
Yptlp (Saccharomyces cerevisiae)
Authors: Gallwitz Dieter
Published: November 2023

The YPT1 gene was originally discovered in the course of analyzing the actin gene (ACT1) and its chromosomal surroundings (Gallwitz and Seidel 1980). The gene, provisionally called YP2 (Gallwitz etal. 1983) and later renamed YPT1 (Schmitt et al. 1986), is located on the short arm of chromosome VI between the p-tubulin gene (TUB2) and ACT1. YPT1 and TUB2 are bidirectionally transcribed and separated by an Abf1/Baf1-binding DNA segment (Halfter et al. 1989). The DNA sequence of YPT1 (Gallwitz et al. 1983) is shown in Fig. 1. The GenBank accession number is X00209.
Ypt51p
Authors: Singer-Kruger Birgit
Published: November 2023

S. cerevisiae YPT51 (Fig. 1) was identified by a polymerase chain reaction (PCR) approach in a search for putative yeast homolog(s) of mammalian Rab5 proteins (Singer-Kruger et al. 1994). Two degenerated oligonucleotides were used, corresponding to the sequences GXXXXGKS/T and LAPMYYR. The first sequence resembles a motif of the phosphate-binding loop of all Rab/Ypt proteins (Chavrier etal. 1992), whereas the latter is located within the helix 2 and was found to contribute to the functional specificity of Rab5a (Stenmark et al. 1994).
Sly2p/Sec22p
Authors: Schmitt Hans Dieter , Dascher Christiane , Gallwitz Dieter
Published: November 2023

The SLY2/SEC22 gene of S. cerevisiae was isolated as a fragment of genomic yeast DNA that could suppress the deletion of YPT1 in a dosage-dependent manner (Dascher et al. 1991). The coding sequence is not interrupted by an intron. The EMBL accession number is X54236.
Bos1p
Authors: Ferro-Novick Susan
Published: November 2023

DNA sequence analysis predicts that the BOS1 gene contains a putative 88-bp intron with conserved 5’ and 3’ sequences for RNA splicing (Shim et al. 1991). The Bos1 protein (244 amino acids) is hydrophilic at its amino-termi- nus with a hydrophobic stretch of 18 amino acids near its carboxy-terminus. This hydrophobic domain may serve as a membrane anchor. BOS1 is 27% identical and 52% similar to SNC1, a gene whose product is 40% identical to synap- tobrevin (Gerst etal. 1992). SNC1 is required for post-Golgi secretion in yeast (Protopopov et al. 1993). The GenBank accession number is X57792.
Ryh1
Authors: Hengst Ludger , Gallwitz Dieter
Published: November 2023

ryh1 was identified and cloned using a protein-coding fragment of the S. cerevisiae YPT1 gene (Gallwitz etal. 1983) as hybridization probe (Hengst et al. 1990). The proteincoding part of ryh 1 is interrupted by three short introns. The ryh 1 gene has been mapped to the left arm of chromosome I, approximately 20 cM from ade3. (Miyake et al. 1991).The DNA sequence ofthegene is shown in Fig. I.The GenBank accession number is X52475.
Arf3
Authors: Kahn Richard A
Published: November 2023

ARF3 cDNA (accession number P16587) was cloned from a human cerebellum cDNA library using bovine ARF2 cDNA as probe (Bobak etal. 1989). The message size is about 3.7 kb with a weaker hybridizing signal detected at about 1.2 kb.
Arf5
Authors: Kahn Richard A
Published: November 2023

The ARF5cDNA (accession number P26437) was cloned from a human HL-60 cell lamdba ZAP library by cross-species hybridization with a bovine ARF2 probe. A message size of about 1300 bp is consistently detected in a number of differ- enttissues and species examined (Tsuchiya etal. 1991).
ArL1
Authors: Kahn Richard A
Published: November 2023

The arflike gene was cloned from Drosophila melanogaster as a 1.05-kb transcription unit proximal to the developmental gene, brahma (Tamkun, et al. 1991). The arflike locus is on chromosome III, in salivary gland polytene chromosome region 72AB (accession number M61127). Polymerase chain reaction (PCR) screening of a human cDNA library indentified a cDNA fragment that encoded a peptide that was highly homologous to the fly protein, but the entire open reading frame has not yet been cloned (Clark eta/. 1993).
ArL2
Authors: Kahn Richard A
Published: November 2023

Human ARL2 was cloned from a fibroblast cDNA library (accession number L13687) using a specific probe obtained from analysis of PCR products using degenerate oligonucleotides from highly conserved regions of Arf proteins (Clark etal. 1993). A gene encoding a homolog was cloned from D. melanogaster genomic and cDNA libraries using the same probe (accession number L14923). Messages of the human and fly ARL2 were estimated at 0.88 and 0.8 kb, respectively, with no specificity for tissue or developmental stage observed.
Sec23p
Authors: Yoshihisa Tohru , Barlowe Charles , Schekman Randy
Published: November 2023

The SEC23 gene (GenBank accession number X15474) was isolated by temperature-sensitive complementation of a sec23 mutant strain (Hicke and Schekman, 1989). SEC23 encodes a predicted 768 amino acid protein with a molecular weight of 85.4 kDa. The sequence has no apparent homology to any known GAPs, including p120Ras-GAP, K- Rev-GAP or Rac-GAP. Sec23 homologues have been reported recently from mouse (Wadhwa et al. 1993) and Caenorhabditis elegans (Waterston et al. 1992), although these remain to be tested as functional homologues. Sec23p may belong to a novel family of GAPs that have conserved structure and function in vesicular transport.
TC4/Ran (JDictostelium discoideum
Authors: Bush John , Cardelli James
Published: November 2023

The apparent Dictyostelium homologue to the TC4/ran and spi genes was cloned (Bush and Cardelli 1993) by screening a cDNA library using an oligonucleotide coding for the sequence DTAGQE which is a conserved amino acid domain found in all GTPases. The TC4/ran cDNA insert of 804 nt was sequenced on both strands and this sequence is shown in Fig. 1, the GenBank accession number is L09720.
An Introduction to Cytokine Receptors
Authors: Hilton D J
Published: November 2023

It is well-established that polypeptide hormones elicit their biological effects by binding to receptors expressed on the surface of responsive cells. The characterization of cell surface receptors has proceeded in two distinct phases. Initially, the majority of receptors were described on the basis of their ability to bind radiolabelled derivatives of a particular hormone. These studies allowed the specificity of receptors to be determined and the equilibrium and kinetic characteristics of binding to be investigated. In some cases, through the additional use of chemical cross-linking reagents, an estimate of the apparent molecular weight of receptors was also possible. In general, however, the low abundance of receptors and their integral membrane location hindered their detailed biochemical characterization. Only with the advent and application of appropriate molecular genetic techniques has the predicted primary structure of many receptors been determined. The aim of the following review is to summarize the important structural features that unite receptors of a given family and to highlight themes common to the function of receptors from different families.
Interleukin-4 Receptors
Authors: Park L S
Published: November 2023

Both the murine (Mosley et al. 1989) and human (ldzerda et al. 1990) IL-4 receptors have been molecularly cloned. The murine IL-4 receptor, which was cloned first (Mosley et al. 1989), is produced as an 810-amino-acid precursor with a predicted 25-amino-acid signal peptide (GenBank accession number M27959). It contains a single transmembrane domain of 24 amino acids, an extracellular domain of 208 amino acids and a cytoplasmic domain of 553 amino acids. The extracellular domain contains seven cysteine residues and five potential N-linked glycosylation sites. A cDNA clone for the human IL-4 receptor was isolated utilizing cross-species hybridization and found to encode an 825-amino-acid protein (ldzerda et al. 1990). The predicted protein sequence exhibited 53 per cent sequence identity with the murine IL-4 receptor and contained a 25-aminoacid signal peptide, 207-amino-acid extracellular domain, 24-amino-acid transmembrane domain, and a 569-aminoacid cytoplasmic domain. Five of the seven cysteine residues, and three of the six potential N-linked glycosylation sites in the extracellular domain have been conserved between mouse and human receptors.
Interleukin-5 (IL-5)
Authors: Sanderson C J
Published: November 2023

The cDNA sequence for human and mouse (GenBank accession numbers X04688 and X06270) predict proteins of 134 and 133 amino acids, respectively. Sequence information is available for both the human and mouse genomic genes (GenBank accession numbers J02971 and XO6271).The coding sequence of the IL-5 gene forms four exons. The introns show areas of similarity between the mouse and human sequences, although the mouse has a considerable amount of sequence (including repeat sequences) which are not present in the human gene. The mouse gene includes a 738 bp segment in the 3’ untranslated region which is not present in the human gene, giving a transcript of 1.6 kb compared to 0.9 kb in man. The gross gene structure are also shared by IL-3, IL-4, and GM-CSF (Sanderson 1994).
Interleukin-7 (IL-7)
Authors: Namen A E
Published: November 2023

The nucleotide sequence of murine IL-7 was derived from a cDNA isolated from a bone marrow stromal cell line and predicted a protein composed of 129 amino acids (Namen et al. 1988) (GenBank accession number X07962). The human cDNA was isolated by cross-hybridization from a human hepatoma cell line (Goodwin et al. 1989). The cDNA sequence predicted a protein containing 152 amino acids (GenBank accession number J04156). Comparison of the murine and human cDNAs shows a high homology in the coding region (81 per cent) and a lesser homology in the 5’ noncoding (73 per cent) and 3’ non-coding region (63 per cent).
Interleukin-7 Receptor
Authors: Goodwin R G , Park L S
Published: November 2023

The human IL-7 receptor is produced as a 459-amino-acid precursor with a predicted 20-amino-acid signal peptide (GenBank accession number M29696) (Fig. 1). It contains a single transmembrane domain of 25 amino acids, an extracellular domain of 219 amino acids, and a cytoplasmic domain of 195 amino acids. The mature protein has a predicted molecular weight of 49 500 but an observed molecular weight by SOS-PAGE analysis of about 75 000, presumably due to post-translational modification of one or more of the six potential N-linked glycosylation sites (Goodwin et al. 1990). The extracellular domain of the IL-7 receptor shows significant homology to a number of other cytokine receptors, forming what is often referred to as the haemopoietin receptor superfamily.
Interleukin-11 (IL-11)
Authors: Clark S C
Published: November 2023

The nucleotide sequences of IL-11 cDNAs cloned from mouse and man (mouse sequence submitted to GenBank, human sequence GenBank accession number M37006) encode proteins with 199 amino acids (Fig. 1) (Paul eta/. 1990). At the amino acid level, the mouse and human proteins are highly conserved (88 per cent identity). The human protein has been shown to include a 21-amino-acid signal sequence which is likely to be identical given the conservation of amino acids around the processing site. That the human and murine proteins are very similar is also supported by the observation that both molecules are active with target cells from the alternate species (C. Wood, unpublished results). Careful analysis of the amino acid sequences and gene structures has revealed that IL-11, IL-6, granulocyte colonystimulating factor (G-CSF), OSM, LIF, CNTF, and growth hormone are all distantly related in evolution (Bruce et al. 1992). However, IL-11 and IL-6 do not directly compete in receptor binding (Yin et al. 1992a,b).
Human B Cell Growth Factor-12kDa (BCGF-12kDa)
Authors: Sharma S
Published: November 2023

The BCGF-12 kDa cDNA was first cloned using size fractionated poly (A+) mRNA from mitogen activated T cells (Sharma et al. 1987). BCGF-12 kDa mRNA was selected on the basis of its ability to encode B cell growth factor activityafter expression in Xenopus oocytes. The open reading frame in the BCGF-12 kDa cDNA predicts a protein of 120 amino acids (Fig. 1). The hydrophobicity analysis suggests a 13-amino-acid putative leader sequence. An unusual feature of the cDNA is the presence of an Alu repeat unit at the 3’ end. Even more intriguing, this Alu repeat unit contributes 40 amino acids to the carboxy terminus of the BCGF-12 kDa protein.
The Interferon-y Receptor
Authors: Schreiber R D , Ague! M
Published: November 2023

The a subunit of the human IFNy receptor (CDw119} is produced as a 489-amino-acid precursor that contains a 17-amino-acid signal sequence (GenBank accession number J03143} (Aguet et al. 1988) (Fig. 1). Although the mature, nonglycosylated 472 amino acid polypeptide has a predicted molecular mass of 50.5 kDa, it displays an Mr of 65 kDa when analysed by SDS-PAGE (Farrar and Schreiber 1993). The molecule is symmetrically oriented around a single 23-amino-acid transmembrane domain. The extracellulardomainconsists of 228 amino acids and includes ten cysteine residues and five potential N-linked glycosylation sites.
Leukaemia Inhibitory Factor (LIF)
Authors: Hilton D J
Published: November 2023

Differentiation inducing factor (DIF), differentiation stimulating factor (D-factor), differentiation inhibitory activity (DIA), differentiation retarding factor (ORF), cholinergic neuronal differentiating factor (CNDF), human interleukin for DA cells (HILDA), hepatocyte stimulating factor-Ill (HSF-111), melanocyte derived lipoprotein lipase inhibitor (MLPLI).
The Ciliary Neurotrophic Factor (CNTF) Receptor Complex
Authors: Yancopoulos G D
Published: November 2023

cDNAs encoding CNTFRa have been cloned from both human (GenBank accession number M73238) (Davis et al. 1991) and rat (GenBank accession number 554212) (Ip et al. 1993). The cDNAs for human and rat CNTFRa both predict protein precursors of 372 amino acids with putative leader sequences of approximately 20 amino acids and four conserved glycosylation sites.
The Nerve Growth Factor Family— Neurotrophins
Authors: Barde Y -A
Published: November 2023

Nucleotide sequences are available for several species, including rat and human for all of them (GenBank accession numbers of the human neurotrophins are: NGF VOl 511; BDNF:M61176; NT-3:M61180; and NT-4/5 M86528). About 50 per cent of the amino acids are common to all neurotrophins, including the six cysteine residues (Fig. 1). With the exception of NT-4/5, neurotrophins are highly conserved proteins between species. In all mammals analysed so far, no amino acid replacements have been found in the mature sequence of BDNF and NT-3.
The Neurotrophin Receptors
Authors: Barker P A
Published: November 2023

Trk receptors are ligand-regulated transmembrane tyrosine kinase receptors that bind specific members of the neurotrophin family (Barbacid 1993). The first trk to be discovered, trkA, was originally observed as a transforming oncogene in colon carcinoma (Martin-Zanca et al. 1986). Its transforming potential was due to the replacement of its normal extracellular sequence with portions of a nonmuscle tropomyosin gene. The trk family members are highly related, particularly within their tyrosine kinase domains. Numerous N-linked glycosylation sites are present extracellularly, which, in part, accounts for the fact that although the proteins have a predicted molecular weight of about 80 kDa, they run on SDS-PAGE at an apparent molecular weight of 140-145 kDa. The preferred ligand for trkA (GenBank accession number X03541, M85214) is nerve growth factor (NGF), for trkB (GenBank accession number X17647, M55291, M55292, M55293) is brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4), and for trkC (GenBank accession number M80800, L03813) is neurotrophin-3 (NT-3) (Ip et al. 1993).
Stem Cell Factor (SCF)
Authors: McNiece I , Shieh J -H
Published: November 2023

The cDNA sequence for human SCF predicts a protein with a 25-amino-acid signal peptide, a 185-amino-acid extracellular domain, a 27-amino-acid transmembrane segment, and a 36-amino-acid intracellular domain (Martin et al. 1990). Secreted and membrane-bound forms of SCF have been identified and are due to alternative splicing of exon 6 resulting in a 248-amino-acid protein and a 220-amino-acid protein (Flanagan et al. 1991). The 248 residue form of SCF is thought to contain a proteolytic cleavage site which results in the secreted 164-amino-acid protein. Due to the lack of this proteolytic site in the 220-amino-acid form, the protein remains membrane associated.
The Growth Hormone/Prolactin Family
Authors: Clackson T
Published: November 2023

The cDNA sequence of human pituitary GH (hGH; GenBank accession number V00519), human PL, and GHs from most other species code for a 191-amino-acid (aa) protein preceded by a signal sequence of 26 aa (Wallis 1992). Human PL (hPL) is encoded identically from two non-allelic genes, hPL-3/hCS-B (V00573) and hPL-4/hCS-A (J00118). Thehuman pituitary PRL (hPRL) cDNA sequence (J00299) predicts a leader of 28 aa and a mature protein of 199 aa. In primates GH is highly homologous to PL (85 per cent identity in humans), whereas GH and PRL are more distantly related (23 per cent in humans: see Fig. 1).
Receptors and Binding Proteins for Insulin-like Growth Factors
Authors: LeRoith D , Roberts C T
Published: November 2023

The IGF-I receptor is initially synthesized as a precursor composed of a signal peptide and contiguous u and Bsubunits. Processing includes cleavage of the a andB subunits atan Arg-Lys-Arg-Arg tetrapeptide sequence, and the formation of disulphide bonds to generate a mature heterotetramic (a.2/32) receptor (Ullrich et al. 1986). The two 11subunits of the mature receptor lie entirely extracellularly, are N-glycosylated, and are involved in ligand binding.
Saccharomyces cerevisiae Ss1
Authors: Davis J , Miao B , Craig E A
Published: November 2023

The Ssc1 protein (Ssdp) is an abundant protein of the matrix of mitochondria (Craig et al., 1987, 1989). The nucleotide sequence of the SSC1 gene (GenBank accession number M27229) encodes a 654 amino acid polypeptide that includes a leader sequence of 23 amino acids, which is removed upon import into mitochondria.
Saccharomyces cerevisiae Ssh1p
Authors: Craig E A
Published: November 2023

The Ssh1 protein is encoded by an open reading frame on chromosome 12 (GenBank YSCL8039, accession number U19103) predicted to encode a 657 amino acid protein. The predicted sequence includes an N-terminal sequence with similarity to mitochondrial presequences. Sshlp is imported into the mitochondrial matrix, is cleaved in the process. Sshlp shares most identity (53%) with Ssdp. It is 46, 43% identical to Ssalp, Kar2p of the cytosol, ER lumen, respectively (Schilke et al., 1996).
Mammalian HSP100
Authors: Glover J R
Published: November 2023

To date only a single representative of the HSP100 family has been cloned from a mammalian source. The gene (SKD3) was cloned as a suppressor of a potassium transport defect in yeast, suggesting a potential function for HSP100 proteins in solute transport. In addition to the gene from mouse, the human genome sequencing project has thus far contributed a number of partial cDNA sequences corresponding to HSPIOOs of at least two subfamilies. The prevalence of HSPIOOs in prokaryotes, in multiple subcellular compartments of eukaryotes suggests that many more mammalian HSPIOOs will be identified.
Mammalian Hsp27
Authors: Landry J
Published: November 2023

Hsp25, Hsp28, mammalian small or low-molecular-weight heat shock protein (Arrigo, Landry, 1994). The nucleotide sequences of mammalian hsp27 genes encode proteins with highly conserved sequences. Hsp27.
Saccharomyces cerevisiae Ssi1p
Authors: Baxter A K , Craig E A
Published: November 2023

SSI1 was sequenced as part of the yeast genome sequencing project,, identified by its homology of its deduced gene product to known HSP70 proteins (Rasmussen, 1994; Craven etal., 1996; Baxter etal., 1996).

The SSI1 gene (GenBank accession number Z28073) has an open reading frame of 2643 nucleotides, potentially encoding a protein of 881 amino acids with a predicted size of 99.6 kDa.
Calnexin, calreticulin proteins — an overview
Authors: Williams D B
Published: November 2023

cDNA sequences have been determined for calnexin, calreticulin from a variety of species including diverse mammals (see calreticulin, calnexin entries, pp. 299, 304), invertebrates (e.g. GenBank accession numbers L08641 for Schistosoma mansoni calnexin, Hawn et al., 1993; X59589 for Caenorhabditis elegans calreticulin. Smith, 1992; M20565 for Onchocerca volvulus calreticulin, Rokeach et al., 1994),, plants (e.g. Arabidopsis thaliana calnexin Z18242, Huang et al., 1993; N. tabacum calreticulin X85382, Denecke et al., 1995.
Escherichia coli DsbA
Authors: Bardwell J C A
Published: November 2023

The structure of oxidized Escherichia coli DsbA has been determined by X-ray crystallography, originally at a resolution of 2.0 A (Martin et al., 1993), more recently to 1.7 Å (Guddat et al., 1977). The structure consists of two domains, a thioredoxin domain, a helical domain (Fig. 1a). Although the classical thioredoxin fold incorporates a four-stranded β sheet flanked by three helices (Martin, 1995), the thioredoxin domain of DsbA (comprising residues 1-61, 140-189) has an additional N-terminal str,that extends the central β sheet to five strands.
Structure of DsbA
Authors: Guddat L W , Martin J L
Published: November 2023

dsbB null mutants in E. coli have a severe, general defect in disulfide bond formation within the periplasm. The pleiotropic phenotypes associated with this defect are very similar to those of dsbA mutants (see entry p. 318). dsbB mutants have been isolated based on these phenotypes (Bardwell et al., 1993; Belin, Boquet, 1993; Dailey, Berg, 1993; Alksne et al., 1995), by The dsbB gene is located at 26.5 minutes on the E. coli chromosome (Bardwell etal., 1993; Missiakas et a/., 1993). Its sequence (GenBank accession number L03721) predicts a 20.3 kDa protein with inner membrane localization (Jander et al., 1994).
Escherichia coli DsbC
Authors: Missiakis D , Zapun A , Creighton T E , Raina S
Published: November 2023

The sequence of the dsbC gene (Swiss-Prot accession number P21892) predicts a 25 kDa protein (Missiakas et al., 1994). The amino acid sequence homology between DsbC, other members of the thioredoxin superfamily is restricted to around the active site, with the following conserved motif, FXXXXCXXC. Except for this, the amino acid sequence of DsbC does not show any strong homology with other thiol—disulfide oxidoreductases from Escherichia coli, such as thioredoxin or DsbA, nor with the eukaryotic protein disulfide isomerase (PDI) proteins. Escherichia coli DsbC shares limited sequence homology with TcpG, the Vibrio cholerae DsbA homologue (Missiakas et al., 1994). A DsbC homologue has been described in Erwinia chrysanthemi (66% identical to E. coli DsbC; Shevchik etal., 1994.
Saccharomyces cerevisiae Eug1
Authors: Stevens T H
Published: November 2023

EUG1 (ER protein unnecessary for growth under standard laboratory conditions) was named for its observed mutant phenotype (Tachibana, Stevens, 1992). Overproduction or deletion of the EUG1 gene appears to have no effect on cell viability or function. Yeast cells deleted for EUG1 grow with wild-type rates on rich or minimal media at temperatures from 18 to 40°C, can grow anaerobically. Sporulation is not affected in homozygous eug1& cells, nor is the transport of vacuolar, secreted proteins through the secretory pathway.
Trypanosoma brucei BiP
Authors: Craig E A
Published: November 2023

African trypanosomes of the T. brucei species (Order Kinetoplastida) are parasitic protozoa that are the causative agents of African Sleeping Sickness in humans, Nagana in cattle (Vickerman et al., 1993). Analyses of 18S rRNA sequence homologies indicate that these organisms comprise one of the most ancient of all eukaryotic lineages, being as distant phylogenetically from yeast as they are from humans (Sogin et al., 1989). They are digenetic parasites living alternately in the bloodstream of the mammalian host, the midgut, mouthparts of the insect vector, the tsetse fly. Complex differentiation processes occur at each stage of the life cycle, survival in the mammalian host is dependent on the sequential expression of different variant surface glycoproteins (VSG) in a process called antigenic variation. VSG is the major cell surface secretory product of bloodstream trypanosomes comprising 10-20% of total cell protein.
Drosophila melanogaster ninaA
Authors: Zuker C S , Rutherford S L
Published: November 2023

ninaA mutants were originally isolated based on their visual defect by William Pak and co-workers (Pak 1979). Mutant flies can have as much as a 100-fold reduction in Rh1 rhodopsin levels, leading to a dramatic loss of light sensitivity and loss of the prolonged depolarizing after potential (nina = neither inactivation nor after potential) (Larivee etal. 1981; Stephenson etal. 1983); this is a physiological assay that is sensitive to relative rhodopsin levels.
Mammalian cydophilin D
Authors: Livi G P , Bergsma DJ
Published: November 2023

For human cyclophilin D: hCyP3 (Bergsma et al., 1991), Cyp-D (Schneider etal., 1994). Human cyclophilin D is encoded by a cDNA (GenBank accession number M80254) cloned from a Jurkat T cell cDNA library using the cyclophilin A-coding sequence as the probe (Bergsma et al., 1991). The 841 bp nucleotide sequence contains a 621 bp open reading frame predicting a protein of 207 amino acids. Southern blot analysis of human genomic DNA probed with the cyclophilin D cDNA reveals a band pattern consistent with the existence of a single copy gene (Bergsma et al., 1991).
Saccharomyces cerevisiae FKBP12
Authors: Dolinski K , Heitman J
Published: November 2023

The yeast FKBP12 protein was purified by FK506-affinity chromatography and sequenced (Heitman et al., 1991a; Koltin et al., 1991; Wiederrecht et al., 1991). The gene encoding FKBP12, FPR1 (Genbank accession number M60877), was cloned by screening yeast genomic libraries with a PCR product obtained with degenerate oligonucleotide primers based on protein sequence (Heitman et al., 1991a; Wiederrecht et al., 1991). The FPR1 gene was also isolated by complementation of an fpr1 mutation (Koltin et al., 1991). The FPR1 gene encodes a 114 residue protein with a molecular weight of 12 kDa. The protein sequences of yeast and human FKBP12 are 54% identical (Heitman etal., 1991a).
Mammalian FKBP13
Authors: Nigam S K , Burakoff S J
Published: November 2023

FKBP13 was originally isolated from bovine thymus by use of a rapamycin affinity matrix (Jin etal., 1991).

A cDNA clone isolated from a human colon carcinoma cell library (GenBank accession number M65128) encodes a protein of 141 amino acids and a molecular weight of 13 200 Da in agreement with the molecular mass estimated by SDS-PAGE (Jin et al., 1991). Sequence analysis revealed 51% nucleotide homology and 43% amino acid homology to FKBP12 (Jin et al., 1991; see entry p. 420). There is a particuarly strong homology with the PPIase active and drug-binding site of FKBP12, suggesting both similarity of higher structure and molecular mechanism. However, the binding affinity of FK506 for FKBP13 (£,=55 nM) is roughly 50-fold less than for FKBP12, suggesting that it may not be an in vivo target of the drug (Bram et al., 1993). The gene for a yeast homlolog, FKB2, is 57% identical to its human counterpart (Partaledis etal., 1992; Partaledis and Berlin 1993; see entry p. 411).
Drosophila melanogaster dodo
Authors: Maleszka R , Miklos G L Gabor
Published: November 2023

The dodo gene (dod) was identified in the functional analysis of the flightless (fli) region at the base of the X chromosome in Drosophila (Maleszka et al., 1996; see Fig. 1). The genomic analysis was followed by the sequencing of a number of dodo cDNAs from larval and pupal libraries that revealed the existence of two classes of dodo transcripts differing in the lengths of their 3’-untranslated regions. The longer transcript is 1013 bp in length.
The hsp70 genes of mice, men
Authors: Tavaria M , Kola I , Anderson R L
Published: November 2023

Genes encoding proteins of the HSP70 family have been identified, cloned from numerous species, ranging from bacteria to humans. Phylogenetic analysis reveals that these genes have been highly conserved during evolution (Rensing, Maier, 1994). Despite being first identified as stress-inducible proteins, many of these isoforms are expressed in the absence of stress. The constitutively expressed isoforms are expressed throughout the cell, are concentrated at sites of protein synthesis, translocation. These HSP70 proteins act as molecular chaperones which, in association with other molecular chaperones, oversee the folding process of newly synthesized, transported proteins (see reviews by Gething, Sambrook, 1992; Hartl, Martin 1995; this volume, overview of HSP70, p. 3). The role of the stressinducible HSP70 isoforms is less well understood, although increasing evidence supports the long-held belief that these isoforms are involved in the protection and/or repair of stress-induced protein damage.
Vertebrate p23
Authors: Johnson J L
Published: November 2023

p23 is a Hsp90-binding protein that is a component of mature steroid receptor complexes. p23 forms a complex with Hsp90 and immunophilins that is disrupted by the Hsp90-binding agent geldanamycin. p23, or the p23 complex, is necessary for the formation of mature steroid receptor complexes, and may be involved in several diverse signal transduction pathways.

p23 was found to coimmunoprecipitate with inactive chick progesterone receptor complexes, along with Hsp90, p60, and the immunophilins FKBP52, FKBP54 and Cyp40 (Smith et al., 1990; Smith and Toft, 1993; for review see p. 518). Monoclonal and peptide-directed polyclonal antibodies were used to isolate a chicken cDNA from an expression library (Johnson etal., 1994).
The role of molecular chaperones in DNA replication
Authors: ów A Wawrzyn , ícz M Zyl
Published: November 2023

The role of the DnaK/DnaJ/GrpE molecular chaperones has been described in detail for a few DNA replication systems, namely, A, mini-F, mini-P1 and oriC plasmid DNA replication. Only in the case of the A DNA replication system has it been shown that the DnaK/DnaJ/GrpE chaperone machine is directly involved in the initiation process. In all other cases, the DnaK/DnaJ/GrpE chaperones activate the initiation proteins but do not participate during the final DNA replication initiation event. Recently, studies on the bacteriophage Mu DNA replication have suggested that this system could be another example of the direct involvement of molecular chaperones (in this case Clp ATPase) in the initiation process (Levchenko etal., 1995; Kruklitis etal., 1996).
Functions of molecular chaperone proteins in the biogenesis of mitochondria
Authors: Langer T , Neupert W , Schwarz E
Published: November 2023

Molecular chaperone proteins bind non-native protein structures and stabilize them against aggregation. By this means, they affect multiple cellular processes, ranging from folding of newly synthesized polypeptides emerging from ribosomes, cellular protein trafficking, translocation across intracellular membranes, the reactivation of heat- denatured proteins and proteolytic breakdown. This is exemplified by mitochondria whose biogenesis depends on the activity of various chaperone systems. In the cytosol, molecular chaperone proteins maintain nuclear-encoded preproteins in a conformation allowing subsequent membrane translocation. The mitochondrial Hsp70 machinery mediates the vectorial translocation of nuclear encoded preproteins across the mitochondrial membranes. In the mitochondrial matrix space, the Hsp70 and Hsp60 chaperone systems ensure proper folding of newly imported proteins and the proteolytic breakdown of misfolded polypeptides. In addition to these ‘housekeeping’ functions, chaperone activity is required to maintain mitochondrial functions during heat stress. Thus, studying mitochondrial biogenesis, a wide range of chaperone functions have been identified and their modes of action were subsequently characterized at the molecular level. This review will focus on the multiple roles of cytosolic and mitochondrial chaperones in various processes of mitochondrial biogenesis.
Protein translocation into the endoplasmic reticulum
Authors: Lyman S K , Schekman R
Published: November 2023

Translocation of precursors into the endoplasmic reticulum (ER) may occur either cotranslationally, where the polypeptide is threaded through a proteinaceous pore as it spools off the ribosome; or post-translationally, where synthesis is completed before the polypeptide engages the pore. Recent advances have begun to form a coherent picture of the means by which proteins cross a lipid bilayer. In this review we examine progress towards defining the mechanism of protein translocation into the ER, with particular emphasis on the involvement of HSP70 proteins and their DnaJ-retated partners in translocation in Saccharomyces cerevisiae.
The pathway of assembly of the progesterone receptor
Authors: Smith D F
Published: November 2023

The PR assembly pathway minimally involves the following chaperone components: Hsp90, Hsc70, Hip, Hop (p60), p23, FKBP52, FKBP51, and Cyp40 (Smith etal., 1995 and references therein; also see the individual entries in this volume for these and other chaperones mentioned in this review). There is also genetic evidence from steroid receptor expression in yeast cells that Ydj1, a cytosolic DnaJ homolog, is required for proper function of steroid receptors (Caplan et al., 1995; Kimura et al., 1995).
Mammalian Prp73
Authors: Dice J F
Published: November 2023

Prp73 was identified as a cytosolic protein able to bind specifically to RNase S-peptide (residues 1-20 of RNase A), a known substrate for a selective pathway of lysosomal proteolysis (Chiang et al., 1989; Dice, 1990). Prp73 binds to RNase S-peptide-Sepharose with a Kd of approximately 5 /iM (Terlecky et al., 1992), was able to stimulate uptake, degradation of RNase S-peptide, RNase A by lysosomes (Chiang et al., 1989; Terlecky et al., 1992).
Mammalian Pbp74
Authors: Pierce S K , Dahlseid J
Published: November 2023

Grp75 (Mizzen et al., 1989); P71 (Leustek et al., 1989); C3H strain-specific antigen (CSA) (Michikawa etal., 1993); mortalin (Wadhwa et al., 1993a); mtHsp70 (Webster etal., 1994); mthsp75 (Bhattacharyya etal., 1995).
STCH
Authors: Kaye FJ , Otterson G A , Flynn G C
Published: November 2023

Stch was isolated from a human cDNA library derived from the K562 erythroleukemia cell line, its sequence (GenBank/EMBL accession number U04735) predicts a peptide of 471 amino acids (Otterson et al., 1994). The STCH product contains a unique hydrophobic leader sequence, shares homology within the N-terminal domains of the HSP70 gene family (33% identity, 43% homology to both human Hsp70, BiP ATPase domains).
Mammalian Hsp110
Authors: Easton D P , Subjeck J R
Published: November 2023

Although the Hsp110 designation is now highly prevalent, the protein has also been referred to as Hsp107 (Landry et al., 1982), Hsp112 (Tomasovic et al., 1983), Hsp105 (Hatayama etal., 1994).
Escherichia coli CbpA
Authors: Mizuno T , Ueguchi C
Published: November 2023

CbpA was first identified, purified as an E. coli DNA- binding protein that could preferentially bind to a synthetic curved DNA sequence by means of a DNA-binding gel shift assay in the presence of an excess amount of a non-curved competitor sequence (Ueguchi et al., 1994). The curved DNA sequence, used as the probe, contains (dA)5 stretches which were designed so as to be phased at 10 bp intervals in the DNA helix (c. 200 bp).
Saccharomyces cerevisiae Ydjl
Authors: Cyr D M , Caplan AJ
Published: November 2023

Ydj1 was identified independently by two laboratories. Caplan, Douglas (1991) identified Ydj1 as a component of a protein extract generated from the nuclear matrix of Saccharomyces cerevisiae. Atencio, Yaffe (1992) identified a protein identical to Ydj1, Mas5p, in a search for proteins that facilitate the transport of proteins into mitochondria.
Saccharomyces cerevisiae Sec63p
Authors: Brodsky J L
Published: November 2023

The SEC63 gene was isolated initially in genetic selections for temperature-sensitive mutants in yeast that accumulate an untranslocated hybrid protein when shifted to the non-permissive temperature (Toyn et al., 1988; Rothblatt et al., 1989). The gene was also obtained in a selection for temperature-sensitive mutants that mislocalize a nuclear-targeted fusion protein at the non-permissive temperature (Sadler et al., 1989; Bossie et al., 1992). Disruption of SEC63 indicates that the gene product is essential for spore germination (Sadler etal., 1989).
Drosophila melanogaster Tid56
Authors: Kurzik-Dumke U , Debes A , Gundacker D
Published: November 2023

The starting material for the identification of the Drosophila melangaster tumour suppressor gene lethal(2) tumorous imaginal discs [l(2)tid] was a mutant, l(2)tid1, generated via EMS mutagenesis, characterized by neoplastic growth of imaginal discs (Kurzik-Dumke etal., 1992) . The l(2)tid gene was mapped genetically to the position 104 ± 1 cM on the right arm of the second chromosome (Kurzik-Dumke et al., 1992). The cytogenetic locus was further determined by deletion mapping, an extensive chromosome walk encompassing the bands 59D-60A (Kurzik-Dumke et al.,
Auxillin
Authors: Eisenberg A , Greene L E
Published: November 2023

Auxilin was first isolated from bovine brain clathrin- coated vesicles by Ahle, Ungewickell (1990). It was purified from a Tris extract of clathrin-coated vesicles by first separating the assembly protein fraction from clathrin by gel chromatography, then purifying the auxilin by hydroxyapatite chromatography followed by Superose 6 gel chromatography. Clathrin-coated vesicles, formed during receptor-mediated endocytosis, are composed primarily of clathrin, assembly proteins (or adaptins). The latter proteins promote the assembly of clathrin into clathrin coats. Auxilin was originally identified as a minor assembly protein (Ahle, Ungewickell, 1990; Lindner, Ungewickell, 1992), but more recently it has been identified as a cofactor necessary for the Hsc70-dependent dissociation of clathrin from clathrin cages (Ungewickell etal., 1995).
Mammalian Mtj
Authors: Lassie M W , Zetter B R , Brightman S E , Blatch G L
Published: November 2023

The cDNA encoding Mtj1 was isolated from an M27 Lewis lung carcinoma expression library (Brightman et al., 1995). Antibodies used for the screen were prepared against 50-60 kDa proteins that were retained on a hydrophobic peptide affinity column (YVGVAPG).
Saccharomyces cerevisiae Mge1
Authors: Laloraya S , Craig E A
Published: November 2023

Yge1 (yeast GrpE, Ikeda et al., 1994; Nakai et al., 1994), GrpEp (Bolliger etal., 1994), mitochondrial GrpE (mt-GrpE).

MGE1 was found in the GenBank database based on its similarity to E. coli grpE (Bolliger et al., 1994; Laloraya et al., 1994). It was also found as a gene (YGE1) that, when present in multiple copies, conferred resistance to staurosporine, a protein kinase C inhibitor (Ikeda etal., 1994).
Mammalian mitochondrial GrpE
Authors: Naylor D J , Hoogenraad N J , Hoj P B
Published: November 2023

The amino acid sequence deduced from the cDNA sequence of rat liver mt-GrpE (GenBank accession number U62940; Naylor et al. 1996) reveals a precursor protein of 217 amino acids (c. 24.3 kDa) with a 27 residue N-terminal targeting sequence, which upon mitochondrial protein import is proteolytically removed to generate the mature protein of 190 amino acids (c. 21.3 kDa). The nucleotide sequences of two partial cDNA clones from human white blood cells (TIGR EST#121800), normal foreskin melanocyctes (Genbank accession number N28384), together encode a precursor protein of 217 amino acids. A partial mouse cDNA clone (GenBank accession number W08216) has also been isolated.
Mammalian Hsp90
Authors: Jakob U , Buchner J
Published: November 2023

The alternative names of members of the Hsp90 family correspond to their apparent molecular weight on SDS-PAGE, depend on the context in which they have been identified: Hsp84/Hsp86 (mouse; Moore et al., 1989), Hsp85 (L929-cells; Lanks, 1989), Hsp89/Hsp90 (HeLa cells; Welch, Feramisco, 1982).
Saccharomyces cerevisiae Hsp10
Authors: Hohfeld J
Published: November 2023

Chaperonin 10, cpn10 (Rospert et al., 1993a). Since this entry focuses on mitochondrial cpn10 which cooperates with Hsp60 in the matrix compartment, the term Hsp10 will be used throughout the text. The nuclear HSP10 gene of S. cerevisiae (GenBank accession number X75754) encodes a polypeptide of 106 amino acids with a deduced molecular mass of 11 374 Da (Rospert et al., 1993a; Hohfeld, Hartl, 1994). Hsp10 displays a native mass of about 80 kDa reflecting the assembly of seven subunits to a homo-oligomeric ring structure characteristic of GroES, its homologues (Mande et al., 1996; Hunt etal., 1996).
Mammalian Cpn10
Authors: Viitanen P V
Published: November 2023

Mammalian mt-cpn1O (Lubben et al., 1990); heat shock protein 10 (HSP10), (Hartman et al., 1992); early pregnancy factor (EPF) (Cavanagh, Morton, 1994). The nucleotide sequences of mammalian CPN10 cDNAs cloned from rat (Ryan et al., 1994), cow (Pilkington, Walker, 1993), mouse (Dickson et al., 1994), human (Monzini et al., 1994) (GenBank accession numbers X71429, X69556, U09659, X75821, respectively) predict proteins of 102 amino acid residues (calculated molecular mass of c.10.8 kDa).
CCTδ
Authors: Kubota H , Willison K
Published: November 2023

The yeast homologue of CCT3 is also called Anc2p (Vinh, Drubin, 1994) or Cct4p (Kubota etal., 1995a).

A temperature-sensitive mutant called anc2-1 shows abnormal actin organization in budding yeast, a null allele of the gene is a recessive lethal (Vinh, Drubin, 1994).
CCTζ
Authors: Kubota H , Willison K
Published: November 2023

The human homologue of CCT£ is also called TCP20 (Li et al., 1994). The yeast homologue of CCT£ is also called Tcp20p (Li etal., 1994) or Cct6p (Kubota etal., 1995a). A null allele of the yeast homologue of Cctlj gene is a recessive lethal (Li etal., 1994).
Alpha-Actin in
Authors: Celio Marco R
Published: November 2023

Alpha-actinin was first isolated from muscle cells (Ebashi and Ebashi 1965). It is present at the Z-discs where it is proposed to crosslink ends of both parallel and antiparallel arrays of actin filaments (Endo and Masaki 1982; Meyer and Aebi 1990). In non-muscle cells it is located in cell-cell and cell-extracellular matrix junctions, and along actin filaments in fibroblasts. It belongs to a family of F-actin binding proteins that includes spectrin, dystrophin, gelation factor, filamin and fimbrin and is defined by similar and functionally homologous actin binding domains (Hemmings etal. 1992). Alpha-actinin is an elongated molecule consisting of two identical subunits with a molecular mass of approximately 100 kDa. In the homodimer the subunits have an antiparallel arrangement (Wallraff et al. 1986; Imamura et al. 1988). Each subunit contains an N-terminal F-actin binding site which is followed by a central rod domain formed by four spectrin-like alpha-helical repeats. Two EF-hands at the C-terminus are responsible for the Ca2+ regulation of nonmuscle alpha-actinin. In an incomplete form they are also present in skeletal muscle alpha-actinins which exhibit a Ca2+-independent crosslinking activity. Mutational analyses of the two EF-hands of Dictyostelium alpha-actinin, a typical non-muscle alpha-actinin, indicate that they have a different impact on the activity of the molecule (Witke et al. 1993). The more N-terminal EF-hand is the low affinity Ca2+-binding site and regulates the crosslinking activity, the C-terminal EF-hand represents the high affinity binding site for Ca2+.
Calbindin D-28k
Authors: Celio Marco R
Published: November 2023

Calbindin D-28k from various species was found to consist of 261 (mammalian) or 262 (avian) amino acids as deduced from the corresponding cDNA sequences. The molecular weight and IEP of the human protein are 30,025 and 4.54, respectively. Calbindin D-28k (similar to most other EF-hand proteins) has a rather rigid structure and readily renatures after heat-or chemical denaturaton. Vitamin D-dependent Ca2+-binding protein (Wassermann and Taylor 1966), CaBP. Calbindin D-28k was first observed in the chicken duodenal mucosa as a protein which is induced by vitamin D (Wassermann and Taylor 1966). Since vitamin D was also found to induce the absorption of Ca2+ from the intestinal lumen, the possibility of a link was obvious. Indeed, Breddermann and Wasserman (1974) found that calbindin D-28k binds with high affinity 3-4 moles of Ca2+ per mole of protein. The original purification procedure included a heat denaturation step. More recent procedures take advantage of the differing properties of the protein in the presence or absence of Ca2+, e.g. a Ca2+-mediated elution from cation exchange chromatography (Friedlander and Norman 1980). Calbindin D-28k can easily be produced in an active conformation in E. coli (Gross etal. 1988).
Calcineurin
Authors: Celio Marco R
Published: November 2023

Calcineurin (Cn) is a Ca2+/calmodulin-dependent protein phosphatase, composed of a catalytic and a regulatory subunit. It has been found in the brain, where it is one of the most abundant calmodulin-binding proteins.

Recently it was demonstrated that calcineurin is the target of immunosuppressant drugs (cyc/osporin, FK-506). This observation indicated that calcineurin is a necessary component in the activation of T cells.
CaIcy phosine
Authors: Celio Marco R
Published: November 2023

Calcyphosine (p24) is a Ca2+-binding protein located in the cytosol and is present in numerous tissues. p24 was initially identified as being a major phosphorylated substrate for cyclic AMP-dependent protein kinase following stimulation of dog thyroid cells by thyrotropin (Lecocq et al. 1979). The role of p24 is as yet unknown. All cells where p24 has been found are epithelial and of the secretory type, which leads us to propose the hypothesis that calcyphosine may play a role in the regulation of ionic transport.