Persius/hicric huggingface dataset:
COQ9
Ubiquinone biosynthesis protein COQ9, mitochondrial, also known as coenzyme Q9 homolog (COQ9), is a protein that in humans is encoded by the COQ9 gene.

# Function
This locus represents a mitochondrial ubiquinone biosynthesis gene. The encoded protein is likely necessary for biosynthesis of coenzyme Q10, as mutations at this locus have been associated with autosomal-recessive neonatal-onset primary coenzyme Q10 deficiency.

# Clinical significance
It may be associated with Coenzyme Q10 deficiency.

# Model organisms
Model organisms have been used in the study of COQ9 function. A conditional knockout mouse line, called Coq9tm1a(KOMP)Wtsi was generated as part of the International Knockout Mouse Consortium program  a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty two tests were carried out on homozygous mutant mice and one significant abnormality was observed: females displayed hyperactivity in an open field test.
CPA3
Carboxypeptidase A3 (mast cell carboxypeptidase A), also known as CPA3, is an enzyme which in humans is encoded by the CPA3 gene. The "CPA3" gene expression has only been detected in mast cells and mast-cell-like lines, and CPA3 is located in secretory granules. CPA3 is one of 8-9 members of the A/B subfamily that includes the well-studied pancreatic enzymes carboxypeptidase A1 (CPA1), carboxypeptidase A2 (CPA2), and carboxypeptidase B. This subfamily includes 6 carboxypeptidase A-like enzymes, numbered 1-6. The enzyme now called CPA3 was originally named mast cell carboxypeptidase A, and another protein was initially called CPA3. A gene nomenclature committee renamed mast cell carboxypeptidase A as CPA3, and the original CPA3 reported by Huang et al. became CPA4 to reflect the order of their discovery.

# Structure

## Gene
The "CPA3" gene is a 32kb-gene located at chromosome 3q24, consisting of 11 exons.

## Protein
CPA3 shares significant homology with the CPA subfamily of metalloprecarboxypeptidases and all the residues essential for the coordination of the Zn2+ active site, substrate peptide anchoring, and CP activity are preserved in the putative CPA3 protein. It resembles pancreatic CPA1 in cleaving C-terminal aromatic and aliphatic amino acid residues.CPA3 contains an N-terminal sequence of 16 amino acids and a pro-peptide between the NH2-terminal signial peptide sequence and COOH-terminal CP moiety.

# Function
CPA3 has a pH optimum in the neutral to basic range. CPA3 functions together with endopeptidases secreted from mast cells such as chymases and tryptases to degrade proteins and peptides,including the apolipoprotein B component of LDL particles and  angiotensin I.  Upon mast cell activation and degranulation, CPA3, the chymases, and tryptases are released in complexes with heparin proteoglycan.The parasitic nematode Ascaris produces CPA3 inhibitors, which increase its survival during infection. This finding implies that CPA3 might be involved in host defense against certain parasites. CPA3 is also reported to have an important role in the protection towards snake venom toxins and vasoconstricting peptide endothelin 1(ET1).

# Clinical significance
CPA3 provides protection from ET-1-induced damage, suggesting CPA3 could have a role in regulating sepsis. The involvement of CPA3 in autoimmune disease models makes it a potential diagnostic parameter of related diseases. The significantly increased concentration of CPA3 in drug-induced anaphylaxis also implies that CPA3 could serve as a diagnostic parameter and detection of it could improve the forensic identification. A new mast cell subtype reported to appear in mucosa is implicated in allergic inflammation and these mast cells have high levels of CPA3. The highly upregulated transcript of CPA3 is readily detected in luminal brushings and biopsies, making it a useful biomarker of allergic inflammation.

# Interactions
CPA3 has been known to interact with:
- Heparin
- PCI
- SR48692
- Tissue carboxypeptidase inhibitor
- Neurotensin
CPN1
Carboxypeptidase N catalytic chain is an enzyme that in humans is encoded by the CPN1 gene.
Carboxypeptidase N is a plasma metallo-protease that cleaves basic amino acids from the C terminal of peptides and proteins. The enzyme is important in the regulation of peptides like kinins and anaphylatoxins, and has also been known as kininase-1 and anaphylatoxin inactivator. This enzyme is a tetramer composed of two identical regulatory subunits and two identical catalytic subunits; this gene encodes the catalytic subunit. Mutations in this gene can be associated with angioedema or chronic urticaria resulting from carboxypeptidase N deficiency.
In melanocytic cells CPN1 gene expression may be regulated by MITF.
CPVL
Probable serine carboxypeptidase CPVL is an enzyme that in humans is encoded by the CPVL gene. The "CPVL" gene is expressed mainly in monocytes and macrophages, and it is located in the endoplasmatic reticulum and in the endosomal/lysosomal compartment. The distribution of CPVL suggests that the enzyme may be involved in antigen processing and the secretory pathway. Besides those macrophages-rich tissues, the heart and kidney also express high levels of CPVL mRNA.The enzyme is similar to the carboxypeptidases CATHA and SCPEP1, but no direct confirmation of the enzymatic activity was obtained so far.  The exact function of this protein, however, has not been determined.

# Structure

## Gene
"CPVL" gene is located at chromosome 7p15.1, consisting of 14 exons.At least two alternatively spliced transcripts which encode the same protein have been observed.

## Protein
The designation of CPVL is a true serine carboxypeptidase. Although the primary sequence displays the expected serine carboxypeptidase active site, the enzymatic activity remains to be demonstrated. The primary sequence of CPVL contains a putative signal sequence, four potential N-linked glycosylation sites and four myristoylation sites, but no transmembrane domain, suggesting that it may be luminal in an organelle and/or involved in the secretory pathway.

# Function
Although the primary sequence of CPVL bears every hallmarks of a serine carboxypeptidase, the enzymatic function of CPVL has not been confirmed. On the basis of its localization, CPVL is postulated to play a role in the biosynthesis of secretory molecules or in the processing and transport of peptides for loading onto MHC I molecules, or in MHC II-dependent APC functions. The high-level expression of CPVL mRNA in heart and kidney implies that CPVL may also have extraimmune functions, such as regulation of cardiovascular homeostasis.

# Clinical significance
The deletion of this gene has been reported associated with Wilms tumor. GWAS show that genetic variations of the CPVL gene are associated with susceptibility to diabetic nephropathy in European Americans, Japanese and Chinese. CPVL is also reported to be one of the four down-regulated proteins which is related to severity of inflammation, and it may be a potential biomarker for identification of infection and prediction of outcome.
CRKL
Crk-like protein is a protein that in humans is encoded by the CRKL gene.

# Function
v-CRK avian sarcoma virus CT10-homolog-like contains one SH2 domain and two SH3 domains.  CRKL has been shown to activate the RAS and JUN kinase signaling pathways and transform fibroblasts in a RAS-dependent fashion.  It is a substrate of the BCR-ABL tyrosine kinase and plays a role in fibroblast transformation by BCR-ABL.  In addition, CRKL has oncogenic potential.
CrkL together with Crk participates in the Reelin signaling cascade downstream of DAB1.

# Interactions
CRKL has been shown to interact with:
- Abl gene,
- BCAR1,
- BCR gene,
- CBLB,
- CD117,
- CD34,
- Cbl gene,
- Dock2,
- EPOR,
- GAB1,
- GAB2,
- INPP5D,
- MAP4K1,
- MAP4K5,
- NEDD9,
- PIK3R2,
- Paxillin
- RAPGEF1,
- RICS,
- STAT5A,
- Syk,  and
- WAS.
CRYM
Mu-crystallin homolog also known as NADP-regulated thyroid-hormone-binding protein (THBP) is a protein that in humans is encoded by the CRYM gene. Multiple alternatively spliced transcript variants have been found for this gene.

# Function
Crystallins are separated into two classes: taxon-specific and ubiquitous. The former class is also called phylogenetically-restricted crystallins. The latter class constitutes the major proteins of vertebrate eye lens and maintains the transparency and refractive index of the lens. This gene encodes a taxon-specific crystallin protein that binds NADPH and has sequence similarity to bacterial ornithine cyclodeaminases. The encoded protein does not perform a structural role in lens tissue, and instead it binds thyroid hormone for possible regulatory or developmental roles.
Its enzyme function has been determined as a ketimine reductase, reducing cyclic ketimines to their reduced forms. Either NADH or NADPH can be used as cofactor. The most active substrate at pH 5.0 is aminoethylcysteine ketimine (AECK), however at neutral pH (pH 7.2) the most active substrate is 1-piperideine-2-carboxylate which is an important part of the pipecolic acid pathway. The active form of thyroxine, T3, has been found to be a potent inhibitor at nanomolar concentrations.
Besides its role in lens biology, CRYM seems also to be involved in thyroid hormone signalling in other tissues. It could be demonstrated that CRYM mutations may cause deafness through thyroid hormone binding effects on the fibrocytes of the cochlea. Disruption of the CRYM gene leads to decreased T3 concentrations in both tissues and serum without alteration of peripheral T3 action in vivo.
The existence of intracellular thyroid hormone binding proteins has been postulated from mathematical modelling of pituitary-thyroid homeostasis. Binding properties have been assumed to be similar to those of extracellular binding proteins, however it is not clear, if THBP is the only intracellular thyroid hormone binding protein.
CST1
Cystatin-SN is a protein that in humans is encoded by the CST1 gene.
"The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and the kininogens. The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions, where they appear to provide protective functions. The cystatin locus on chromosome 20 contains the majority of the type 2 cystatin genes and pseudogenes. This gene is located in the cystatin locus and encodes a cysteine proteinase inhibitor found in saliva, tears, urine, and seminal fluid."

# Gene

## Transcriptions
The "four cystatin genes  contain the ATA-box sequence (ATAAA) in their 5'-flanking regions; however, the CAT-box sequence (CAT), a binding site of the transcription factor, CTF, is found only in the 5'-flanking region of the S-type cystatin genes."
CST2
Cystatin-SA is a protein that in humans is encoded by the CST2 gene.
"The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and the kininogens. The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions, where they appear to provide protective functions. The cystatin locus on chromosome 20 contains the majority of the type 2 cystatin genes and pseudogenes. This gene is located in the cystatin locus and encodes a secreted thiol protease inhibitor found at high levels in saliva, tears and seminal plasma."

# Gene

## Transcriptions
The "four cystatin genes  contain the ATA-box sequence (ATAAA) in their 5'-flanking regions; however, the CAT-box sequence (CAT), a binding site of the transcription factor, CTF, is found only in the 5'-flanking region of the S-type cystatin genes."
CST4
Cystatin-S is a protein that in humans is encoded by the CST4 gene.
The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and the kininogens. The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions. The cystatin locus on chromosome 20 contains the majority of the type 2 cystatin genes and pseudogenes. This gene is located in the cystatin locus and encodes a type 2 salivary cysteine peptidase inhibitor. The protein is an S-type cystatin, based on its high level of expression in saliva, tears and seminal plasma. The specific role in these fluids is unclear but antibacterial and antiviral activity is present, consistent with a protective function.

# Gene

## Transcriptions
The "four cystatin genes  contain the ATA-box sequence (ATAAA) in their 5'-flanking regions; however, the CAT-box sequence (CAT), a binding site of the transcription factor, CTF, is found only in the 5'-flanking region of the S-type cystatin genes."
CTGF
CTGF, also known as CCN2 or connective tissue growth factor, is a matricellular protein of the CCN family of extracellular matrix-associated heparin-binding proteins (see also CCN intercellular signaling protein). CTGF has important roles in many biological processes, including cell adhesion, migration, proliferation, angiogenesis, skeletal development, and tissue wound repair, and is critically involved in fibrotic disease and several forms of cancers.

# Structure and binding partners
Members of the CCN protein family, including CTGF, are structurally characterized by having four conserved, cysteine-rich domains. These domains are, from N- to C-termini, the insulin-like growth factor binding protein (IGFBP) domain, the von Willebrand type C repeats (vWC) domain, the thrombospondin type 1 repeat (TSR) domain, and a C-terminal domain (CT) with a cysteine knot motif. CTGF exerts its functions by binding to various cell surface receptors in a context-dependent manner, including integrin receptors, cell surface  heparan sulfate proteoglycans (HSPGs), LRPs, and TrkA. In addition, CTGF also binds growth factors and extracellular matrix proteins. The N-terminal half of CTGF interacts with aggrecan, the TSR domain interacts with VEGF, and the CT domain interacts with members of the TGF- superfamily, fibronectin, perlecan, fibulin-1, slit, and mucins.

# Role in development
Knockout mice with the Ctgf gene disrupted die at birth due to respiratory stress as a result of severe chondrodysplasia. Ctgf-null mice also show defects in angiogenesis, with impaired interaction between endothelial cells and pericytes and collagen IV deficiency in the endothelial basement membrane. CTGF is also important for pancreatic beta cell development, and is critical for normal ovarian follicle development and ovulation.

# Clinical significance
CTGF is associated with wound healing and virtually all fibrotic pathology. It is thought that CTGF can cooperate with TGF- to induce sustained fibrosis and to exacerbate extracellular matrix production in association other fibrosis-inducing conditions. Overexpression of CTGF in fibroblasts promotes fibrosis in the dermis, kidney, and lung, and deletion of Ctgf in fibroblasts and smooth muscle cells greatly reduces bleomycin-induced skin fibrosis.
In addition to fibrosis, aberrant CTGF expression is also associated with many types of malignancies, diabetic nephropathy and retinopathy, arthritis, and cardiovascular diseases. Several clinical trials are now ongoing that investigate the therapeutic value of targeting CTGF in fibrosis, diabetic nephropathy, and pancreatic cancer.
CUL5
Cullin-5 is a protein that in humans is encoded by the CUL5 gene.

# Discovery
The mammalian gene product was originally discovered by expression cloning, due to the protein's ability to mobilize intracellular calcium in response to the peptide hormone arginine vasopressin.  It was first titled VACM-1, for vasopressin-activated, calcium-mobilizing receptor.  Since then, VACM-1 has been shown to be homologous to the Cullin family of proteins, and was subsequently dubbed cul5.

# Tissue distribution
Studies have shown that the cul5 protein is expressed at its highest levels in heart and skeletal tissue, and is specifically expressed in vascular endothelium and renal collecting tubules.

# Function
Cul5 inhibits cellular proliferation, potentially through its involvement in the SOCS/ BC-box/ eloBC/ cul5/ RING E3 ligase complex, which functions as part of the ubiquitin system for protein degradation.
One study have shown that Cul5 plays a role in Reelin signaling cascade, participating in the DAB1 degradation and thus ensuring the negative feedback mechanism of Reelin signaling during corticogenesis.

# Interactions
CUL5 has been shown to interact with RBX1.
CYC1
Cytochrome c1, heme protein, mitochondrial (CYC1), also known as UQCR4, MC3DN6, Complex III subunit 4, Cytochrome b-c1 complex subunit 4, or Ubiquinol-cytochrome-c reductase complex cytochrome c1 subunit is a protein that in humans is encoded by the CYC1 gene. CYC1 is a respiratory subunit of Ubiquinol Cytochrome c Reductase (complex III), which is located in the inner mitochondrial membrane and is part of the electron transport chain. Mutations in this gene may cause mitochondrial complex III deficiency, nuclear, type 6.

# Structure
CYC1 is located on the q arm of chromosome 8 in position 24.3 and has 8 exons. The CYC1 gene produces a 13.5 kDa protein composed of 130 amino acids. CYC1 belongs to the cytochrome c family. CYC1 is a phosphoprotein and subunit of Ubiquinol Cytochrome c Reductase that binds heme groups. It has helix, transit peptide, and transmembrane domains and contains 9 alpha helixes, 5 beta strands, and 3 turns. The transmembrane protein passes through the inner mitochondrial membrane once and the majority of the protein is found on the intermembrane side. CYC1 contains covalent heme bindings sites at positions 121 and 124 and heme axial ligand iron-metal binding sites at positions 125 and 244.

# Function
CYC1 encodes a protein that is located in the inner mitochondrial membrane and is part of Ubiquinol Cytochrome c Reductase (complex III). The encoded protein, CYC1, is a respiratory subunit of the cytochrome bc1 complex, which plays an important role in the mitochondrial respiratory chain by transferring electrons from the Rieske iron-sulfur protein to cytochrome c.

# Species
CYC1 is a human gene that is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, zebrafish, fruit fly, mosquito, C. elegans, S. cerevisiae, K. lactis, E. gossypii, S. pombe, N. crassa, A. thaliana, rice, and frog. There are orthologs of CYC1 in 137 known organisms.

# Clinical Significance
Variants of CYC1 have been associated with mitochondrial complex III deficiency, nuclear, type 6. Mitochondrial complex III deficiency, nuclear, type 6 is an autosomal recessive disorder of the mitochondrial respiratory chain resulting from a defect in Ubiquinol Cytochrome c Reductase (complex III) that leads to reduced complex III activity. Clinical features tend to emerge in early childhood and include episodic acute lactic acidosis, ketoacidosis, insulin-responsive hyperglycemia, liver dysfunction, encephalopathy, and associated infection, although psychomotor development may remain normal. Pathogenic mutations have included c.288G>T, p.Trp96Cys and c.643C>T p.Leu215Phe.

# Interactions
CYC1 has 78 protein-protein interactions with 72 of them being co-complex interactions. CYC1 is one of 11 subunits of Ubiquinol Cytochrome c Reductase (b1-c complex) that includes the respiratory subunits cytochrome b, cytochrome c1 (CYC1), UQCRFS1, the core proteins UQCRC1 and UQCRC2, and the low-molecular weight proteins UQCRH, UQCRB, UQCRQ, UQCR10, UQCR11, as well as an additional cleavage product of UQCRFS1. Additionally, CCP1, CDKA-1, and CDKB1-1 have also been found to interact with CYC1.
ClpX
ATP-dependent Clp protease ATP-binding subunit clpX-like, mitochondrial is an enzyme that in humans is encoded by the CLPX gene. This protein is a member of the family of AAA Proteins (AAA+ ATPase) and is to form the protein complex of Clp protease (Endopeptidase Clp).

# Structure

## Protein Structure
The knowledge of human ClpX protein are majorly based on the investigations on E. Coli protein.  The monomer of ClpX protein in E. Coli contains a N-terminal domain and a AAA+ module which consists of a large and a small AAA+ domain.

## Complex Assembly
During protease Clp complex assembly, the ClpX subunits form a hexameric ring structure. According to the orientation of ClpX subunits within the ring structure, these subunits can be categorized into two classes: "loadable" subunit (L subunit) and "unloadable" subunit (U subunit). In L subunit, the large and small AAA+ domain form a cleft for nucleotide ATP or ADP binding. However, the large and small AAA+ domains in U subunit rotate ~ 80, which prevents nucleotide binding. The L and U subunits form a "L-L-U-L-L-U" pattern when they assemble into a hexameric ring, which has the maximum capacity to bind four ATP or ADP.   Electro-microscopy (EM) studies showed that ClpX ring structures stack coaxially on either one side or both side of ClpP tetradecamer complex to form ClpXP protease complexes. ATP binding can stabilize the association between ClpX and ClpP ring structures.

# Function
ClpX is an ATP-dependent chaperone that can recognize protein substrates by binding to protein degradation tags. These tags can be short unstructured peptide sequences (e.g., ssrA-tag in E coli). As an essential component of ClpP protease complex, ClpX recruits degradable substrates and unfolds their tertiary structure, which requires energy provided by ATP hydrolysis. Subsequently, these ClpX Chaperons transfer protein substrates into the proteolytic chamber formed by ClpP tetradecamer.

# Clinical Significance
In mammals, ClpXP protease is a pivotal contributor to mitochondrial protein quality control. A compromised ClpXP function usually leads to the accumulation of damaged proteins and mitochondrial dysfunctions, which believes to be potential causes for neurodegenerative diseases and aging.
Cmax

# Overview
Cmax is a term used in pharmacokinetics refers to the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and prior to the administration of a second dose.  Cmax is the opposite of Cmin, which is the minimum (or trough) concentration that a drug achieves after dosing.
Tmax is the term used in pharmacokinetics to describe the time at which the Cmax is observed.
After an intravenous administration, Cmax and Tmax are closely dependent on the experimental protocol, since the concentrations are always decreasing after the dose. But after oral administration,Cmax and Tmax are dependent on the extent, and the rate of drug absorption and the disposition profile of the drug. They could be used to characterize the properties of different formulations in the same subject.
Short term drug side effects are most likely to occur at or near the Cmax whereas the therapeutic effect of drug with sustained duration of action usually occurs at concentrations slightly above the Cmin.
The Cmax is often measured in an effort to show bioequivalence between a generic and innovator drug product. According to FDA, drug quality BA (bioavailability) and BE (bioequivalence) rely on pharmacokinetic measures such as AUC and Cmax that are reflective of systemic exposure.