Persius/hicric huggingface dataset:
COX6B1
Cytochrome c oxidase subunit 6B1 is an enzyme that in humans is encoded by the COX6B1 gene. Cytochrome c oxidase 6B1 is a subunit of the cytochrome c oxidase complex, also known as Complex IV, the last enzyme in the mitochondrial electron transport chain. Mutations of the COX6B1 gene are associated with severe infantile encephalomyopathy and mitochondrial complex IV deficiency (MT-C4D).

# Structure
The COX6B1 gene, located on the q arm of chromosome 19 in position 13.1, contains 4 exons and is 10,562 base pairs in length. The COX6B1 protein weighs 10 kDa and is composed of 86 amino acids. The protein is a subunit of Complex IV, a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes, and multiple structural subunits encoded by nuclear genes.

# Function
Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. It is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, and the nuclear-encoded subunits may be involved in the regulation and assembly of the complex. This nuclear gene encodes subunit VIb. Three pseudogenes COX6BP-1, COX6BP-2 and COX6BP-3 have been found on chromosomes 7, 17 and 22q13.1-13.2, respectively.
Summary reaction:

# Clinical significance
Mutations affecting the COX6B1 gene are associated with mitochondrial complex IV deficiency (MT-C4D), a disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations, ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Features include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, exercise intolerance, developmental delay, delayed motor development, and mental retardation. Some affected individuals manifest a fatal hypertrophic cardiomyopathy resulting in neonatal death. A subset of patients manifest Leigh's syndrome. A COX6B1 R20C missense mutation has been linked to complex IV deficiency with encephalomyopathy, hydrocephalus, and hypertrophic cardiomyopathy.

# Interactions
COX6B1 has been shown to have 548 binary protein-protein interactions including 547 co-complex interactions.
COX6B2
Cytochrome c oxidase subunit VIb polypeptide 2 is a protein that in humans is encoded by the COX6B2 gene. Cytochrome c oxidase 6B2 is a subunit of the cytochrome c oxidase complex, also known as Complex IV, the last enzyme in the mitochondrial electron transport chain.

# Structure
The COX6B2 gene, located on the q arm of chromosome 19 in position 13.42, contains 5 exons and is 5,113 base pairs in length. The protein encoded by the COX6B2 gene weighs 11 kDa and is composed of 88 amino acids. The protein is a subunit of Complex IV, a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes.

# Function
Cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial respiratory chain. It is a multi-subunit enzyme complex that couples the transfer of electrons from cytochrome c to molecular oxygen and contributes to a proton electrochemical gradient across the inner mitochondrial membrane to drive ATP synthesis via protonmotive force.  The mitochondrially-encoded subunits perform the electron transfer of proton pumping activities. The functions of the nuclear-encoded subunits are unknown but they may play a role in the regulation and assembly of the complex.
Summary reaction:
CPPene

# Overview
CPPene is a potent competitive antagonist at the NMDA receptor. It was originally designed as a potential therapy for excitotoxicity, epilepsy or neuropathic pain. It looked very promising in in vitro trials proving to be a potent competitive antagonist at the NMDA without affecting other receptors. It's promise continued through to in vitro tissue culture studies where it proved to limit damage after occluding the middle cerebral artery leading to ischaemia. It also blocked photosensitive epilepsies in Baboons.
CPPene has a pharmacokinetic profile suitable of progressing to clinical trials as it has no toxic by products, is excreted exclusively via the renal system and remains unchanged in the brain.
However CPPene was removed from clinical trials as it provided no suitable neuronal protection or beneficial treatment for epilepsy. The reasons behind this is the relatively short therapeutic time window following ischaemic damage and a small amount of glutamate helps neuronal survival. It is also believed that some "pro-survival" genes are activated by NMDA receptors.
Possible directions for future development is via specific AMPA, Kainate of mGlu R subunits leading to more specific responses.
-  Dr David Jane
CRABP1
Cellular retinoic acid-binding protein 1 is a protein that in humans is encoded by the CRABP1 gene.
CRABP1 is assumed to play an important role in retinoic acid-mediated differentiation and proliferation processes. It is structurally similar to the cellular retinol-binding proteins, but binds only retinoic acid. CRABP1 is constitutively expressed and is believed to have different functions in the cell than the related CRABP2.

# Function
CRABP1 binds to retinoid acid and helps to transport it into cells (Figure 1). Both CRABP1 and CRABP2 perform this activity. The retinoic acid molecule is then released and further bound to retinoic acid receptor (RAR) and the retinoid X receptor (RXR) as homodimers or heterodimers. This complex then further binds to retinoic acid response elements (RARE) on DNA that regulates transcription of retinoid acid dependent null genes. The domains for the nuclear localization and the retinoic acid binding are shown in Figure 3.
CRABP1 has been found to be involved in multiple cancer proliferation pathways. CRABP1 activates the extracellular signal-regulated kinase, ERK1 and ERK2 kinases, which are involved in the cell cycle. CRABP1 activity can thus extend the cell cycle, e.g. in embryonic and neural stem cells. Knockout mice without CRABP1 showed increased neural stem cell proliferation and thus hippocampus neurogenesis. Furthermore, learning and memory were improved in knockout mice, as measured by the Morris water maze test and an object recognition task.
CRABP1 is also involved in cancer cell apoptosis. trans-retinoic acid was considered a   as a ligand of CRABP1. It was observed that CRABP1 regulated extracellular signal regulated kinase (ERK1/2) which in turn activates the protein phosphatase 2A (PP2A) that induces apoptosis of cancer cells and lengthens the cell cycle of embryonic stem cells. PP2A activity promotes the stem cells renewal ability during the differentiation process. When CRABP1 was knocked down the apoptotic induction  ability was also removed and allowed for cell proliferation. The re-expression of CRABP1 in CRABP1 null cells brought back the induced apoptotic activity. Thus CRABP1 may be used as a therapeutic target along with trans-retinoic acid for apoptotic activity within cancer cells. Figure 2 illustrates both pathways of retinoic acid binding to CRABP for cell proliferation and apoptotic activity.
CRABP2
Cellular retinoic acid-binding protein 2 is a cytoplasmic binding protein that in humans is encoded by the CRABP2 gene.
CRABP2 is structurally similar to CRABP1, but CRABP2 has a lower affinity for retinoic acid (RA). CRABP2 is associated with cells that produce large amounts of retinoic acid and may play a role in mediating the effects of retinoic acid in the cell.

# Function
A number of specific carrier proteins for members of the vitamin A family have been discovered. Retinoic acid is an active metabolite of vitamin A (retinol). Cellular retinoic acid binding proteins (CRABP) are low molecular weight proteins whose precise function remains largely unknown.
The inducibility of the CRABP2 gene suggests that this isoform is important in retinoic acid-mediated regulation of human skin growth, differentiation and development. CRABP2 is involved in the metabolism and transportation of retinoic acid from the cytosol to the RARs (retinoic acid receptors) located in the nucleus. CRABP2 is specifically co-expressed with RAR- and cellular retinol binding protein 1 genes in certain tissues. It has been postulated that the CRABP2 gene is transcriptionally regulated by a newly synthesized regulatory protein.

# Tissue distribution
Tissue distribution of the CRABP2 gene has primarily been studied using mouse models. During embryonic development, CRABP2 is present in tissues throughout the body in a more diffuse pattern than CRABP1. CRABP1 is more isolated to specific regions, though it does appear in higher concentrations. CRABP1 and 2 often overlap in tissues.
CRABP2 gene expression is abundant in the trunk and hindbrain (and to a lesser extent the forebrain), but are present in other areas of the body. Structures such as the limbs, hindbrain and cranial neural crest cells have been shown to be excessively sensitive to high levels of retinoic acid. Rhombomere segmentation in the hindbrain and the development of cranial ganglia V, VII, VIII, IX, and X also appear to be partially dependent on CRABP2 expression. CRABP2 is abundant in the dorsal part of the limb during development.
CRABP2 genes are also expressed in structures that are less sensitive to retinoid levels throughout the body during embryonic development. These structures include the pharyngeal pouches, foregut, midgut, mandibular and frontal mesenchyme, developing muscle, interdigital mesenchyme, the urogenital system, optic vessels, and inner ear sensory epithelium.

# Defects
Vitamin A deficiency in mice has been shown to cause problems with spermatogenesis, irregular estrous cycles, changes in the uterine epithelium and reproductive failure ending with fetal death and reabsorption.
Tissues with CRABP2 can be sensitive to high levels of retinoic acid which may cause defects in the development of those tissues.
CRABP2 gene knockout studies should be performed to determine any specific defects caused by loss of this gene.

# Interactions
CRABP2 has been shown to interact with Cyclin D3.
CRYBB2
Beta-crystallin B2 is a protein that in humans is encoded by the CRYBB2 gene.

# Function
Crystallins are separated into two classes: taxon-specific, or enzyme, and ubiquitous. The latter class constitutes the major proteins of vertebrate eye lens and maintains the transparency and refractive index of the lens. Since lens central fiber cells lose their nuclei during development, these crystallins are made and then retained throughout life, making them extremely stable proteins. Mammalian lens crystallins are divided into alpha, beta, and gamma families; beta and gamma crystallins are also considered as a superfamily. Alpha and beta families are further divided into acidic and basic groups. Seven protein regions exist in crystallins: four homologous motifs, a connecting peptide, and N-terminal and C-terminal extensions. Beta-crystallins, the most heterogeneous, differ by the presence of the C-terminal extension (present in the basic group, none in the acidic group). Beta-crystallins form aggregates of different sizes and are able to self-associate to form dimers or to form heterodimers with other beta-crystallins. This gene, a beta basic group member, is part of a gene cluster with beta-A4, beta-B1, and beta-B3. A chain-terminating mutation was found to cause type 2 cerulean cataracts.

# Interactions
CRYBB2 has been shown to interact with Hsp27, CRYGC, CRYAA and CRYAB.
CSNK1D
The CSNK1D gene encodes the casein kinase I isoform delta enzyme in humans.
This gene is a member of the casein kinase I (CKI) gene family whose members have been implicated in the control of cytoplasmic and nuclear processes, including DNA replication and repair. The encoded protein is highly similar to the mouse and rat CK1 delta homologs. Two transcript variants encoding different isoforms have been found for this gene.

# Interactions
CSNK1D has been shown to interact with Gap junction protein, alpha 1.
CSNK2B
Casein kinase II subunit beta is a protein that in humans is encoded by the CSNK2B gene.
This gene encodes the beta subunit of casein kinase II, a ubiquitous protein kinase which regulates metabolic pathways, signal transduction, transcription, translation, and replication. The enzyme localizes to the endoplasmic reticulum and the Golgi apparatus.
Casein kinase, a ubiquitous, well-conserved protein kinase involved in cell metabolism and differentiation, is characterised by its preference for Serine or Threonine in acidic stretches of amino acids. The enzyme is a tetramer of 2 alpha- and 2 beta-subunits. However, some species (e.g., mammals) possess 2 related forms of the alpha-subunit (alpha and alpha'), while others (e.g., fungi) possess 2 related beta-subunits (beta and beta'). The alpha-subunit is the catalytic unit and contains regions characteristic of serine/threonine protein kinases. The beta-subunit is believed to be regulatory, possessing an N-terminal auto-phosphorylation site, an internal acidic domain, and a potential metal-binding motif. The beta subunit is a highly conserved protein of about 25kDa that contains, in its central section, a cysteine-rich motif, CX(n)C, that could be involved in binding a metal such as zinc. The mammalian beta-subunit gene promoter shares common features with those of other mammalian protein kinases and is closely related to the promoter of the regulatory subunit of cAMP-dependent protein kinase.

# Interactions
CSNK2B has been shown to interact with CD163, CSNK2A2, Casein kinase 2, alpha 1, FGF1, TRIB3, CDC34, Ribosomal protein L5, BTF3, BRCA1, RNF7, P70-S6 Kinase 1 and APC.
CX3CL1
Fractalkine also known as chemokine (C-X3-C motif) ligand 1 is a protein that in humans is encoded by the CX3CL1 gene.

# Function
Fractalkine is a large cytokine protein of 373 amino acids, it contains multiple domains and is the only known member of the CX3C chemokine family.  It is also commonly known under the names fractalkine (in humans) and neurotactin (in mice).  The polypeptide structure of CX3CL1 differs from the typical structure of other chemokines.  For example, the spacing of the characteristic N-terminal cysteines differs; there are three amino acids separating the initial pair of cysteines in CX3CL1, with none in CC chemokines and only one intervening amino acid in CXC chemokines.  CX3CL1 is produced as a long protein (with 373-amino acid in humans) with an extended mucin-like stalk and a chemokine domain on top. The mucin-like stalk permits it to bind to the surface of certain cells.  However a soluble (90 kD) version of this chemokine has also been observed. Soluble CX3CL1 potently chemoattracts T cells and monocytes, while the cell-bound chemokine promotes strong adhesion of leukocytes to activated endothelial cells, where it is primarily expressed. CX3CL1 elicits its adhesive and migratory functions by interacting with the chemokine receptor CX3CR1.  Its gene is located on human chromosome 16 along with some CC chemokines known as CCL17 and CCL22.
Fractalkine is found commonly throughout the brain, particularly in neural cells, and its receptor is known to be present on microglial cells. It has also been found to be essential for microglial cell migration. CX3CL1 is also up-regulated in the hippocampus during a brief temporal window following spatial learning, the purpose of which may be to regulate glutamate-mediated neurotransmission tone. This indicates a possible role for the chemokine in the protective plasticity process of synaptic scaling.
CX3CR1
CX3C chemokine receptor 1 (CX3CR1) also known as the fractalkine receptor or G-protein coupled receptor 13 (GPR13) is a protein that in humans is encoded by the CX3CR1 gene.  As the name suggests, this receptor binds the chemokine CX3CL1 (also called neurotactin or fractalkine).

# Function
The fractalkine ligand CX3CL1 is a transmembrane protein and chemokine involved in the adhesion and migration of leukocytes. The protein encoded by the CX3CR1 gene is a receptor for the fractalkine ligand.
Expression of this receptor appears to be associated with lymphocytes. CX3CR1 is also expressed by monocytes and plays a major role in the survival of monocytes.
Fractalkine signaling has also recently been discovered to play a developmental role in the migration of microglia in the central nervous system to their synaptic targets, where phagocytosis and synaptic refinement occur. CX3CR1 knockout mice had more synapses on cortical neurons than wild-type mice.

# Clinical significance
CX3CR1 also is a coreceptor for HIV-1, and some variations in this gene lead to increased susceptibility to HIV-1 infection and rapid progression to AIDS.
CX3CR1 variants have been described to modify the survival time and the progression rate of patients with amyotrophic lateral sclerosis.
Mutations in CX3CR1 are associated to                 dysplasia of the hip            .
CXCL10
C-X-C motif chemokine 10 (CXCL10) also known as Interferon gamma-induced protein 10 (IP-10) or small-inducible cytokine B10 is an 8.7 kDa protein that in humans is encoded by the CXCL10 gene. C-X-C motif chemokine 10 is a small cytokine belonging to the CXC chemokine family.

# Gene
The gene for CXCL10 is located on human chromosome 4 in a cluster among several other CXC chemokines.

# Function
CXCL10 is secreted by several cell types in response to IFN-. These cell types include monocytes, endothelial cells and fibroblasts. CXCL10 has been attributed to several roles, such as chemoattraction for monocytes/macrophages, T cells, NK cells, and dendritic cells,  promotion of T cell adhesion to endothelial cells, antitumor activity, and inhibition of bone marrow colony formation and angiogenesis.
This chemokine elicits its effects by binding to the cell surface chemokine receptor CXCR3.

# Structure
The three-dimensional crystal structure of this chemokine has been determined under 3 different conditions to a resolution of up to 1.92 A. The Protein Data Bank accession codes for the structures of CXCL10 are 1lv9, 1o7y, and 1o80.

# Biomarkers
CXCL9, CXCL10 and CXCL11 have proven to be valid biomarkers for the development of heart failure and left ventricular dysfunction, suggesting an underlining pathophysiological relation between levels of these chemokines and the development of adverse cardiac remodeling.

# Clinical significance
Baseline pre-treatment plasma levels of CXCL10 are elevated in patients chronically infected with hepatitis C virus (HCV) of genotypes 1 or 4 who do not achieve a sustained viral response (SVR) after completion of antiviral therapy. CXCL10 in plasma is mirrored by intrahepatic  CXCL10 mRNA, and both strikingly predict the first days of elimination of HCV RNA  (first phase decline) during interferon/ribavirin therapy for all HCV genotypes. This also applies for patients co-infected with HIV, where pre-treatment IP-10 levels below 150 pg/mL are predictive of a favorable response, and may thus be useful in encouraging these otherwise difficult-to-treat patients to initiate therapy.
CXCL11
C-X-C motif chemokine 11 (CXCL11) is a protein that in humans is encoded by the CXCL11 gene.
C-X-C motif chemokine 11 is a small cytokine belonging to the CXC chemokine family that is also called Interferon-inducible T-cell alpha chemoattractant (I-TAC) and Interferon-gamma-inducible protein 9 (IP-9).  It is highly expressed in peripheral blood leukocytes, pancreas and liver, with moderate levels in thymus, spleen and lung and low expression levels were in small intestine, placenta and prostate.
Gene expression of CXCL11 is strongly induced by IFN- and IFN-, and weakly induced by IFN-. This chemokine elicits its effects on its target cells by interacting with the cell surface chemokine receptor CXCR3, with a higher affinity than do the other ligands for this receptor, CXCL9 and CXCL10. CXCL11 is chemotactic for activated T cells.  Its gene is located on human chromosome 4 along with many other members of the CXC chemokine family.

# Biomarkers
CXCL9, -10, -11 have proven to be valid biomarkers for the development of heart failure and left ventricular dysfunction, suggesting an underlining pathophysiological relation between levels of these chemokines and the development of adverse cardiac remodeling.
CXCL13
chemokine (C-X-C motif) ligand 13 (CXCL13), also known as B lymphocyte chemoattractant (BLC) or  B cell-attracting chemokine 1 (BCA-1), is a protein ligand that in humans is encoded by the CXCL13 gene.

# Function
CXCL13 is a small chemokine belonging to the CXC chemokine family.  As its name suggests, this chemokine is selectively chemotactic for B cells belonging to both the B-1 and B-2 subsets, and elicits its effects by interacting with chemokine receptor CXCR5.  CXCL13 and its receptor CXCR5 control the organization of B cells within follicles of lymphoid tissues. and is expressed highly in the liver, spleen, lymph nodes, and gut of humans.  The gene for CXCL13 is located on human chromosome 4 in a cluster of other CXC chemokines.
In T lymphocytes, CXCL13 expression is thought to reflect a germinal center origin of the T cell, particularly a subset of T cells called follicular B helper T cells (or TFH cells). Hence, expression of CXCL13 in T-cell lymphomas, such as Angioimmunoblastic T-cell Lymphoma, is thought to reflect a germinal center origin of the neoplastic T-cells.
CXCL17
Chemokine (C-X-C motif) ligand 17 (CXCL17) is a small cytokine belonging to the CXC chemokine family that has been identified in humans and mice. CXCL17 attracts dendritic cells and monocytes and is regulated in tumors.  It is also known as VEGF co-regulated chemokine 1 (VCC-1) and dendritic cell- and monocyte-attracting chemokine-like protein (DMC). This chemokine is constitutively expressed in the lung. The gene for human CXCL17 is located on chromosome 19.
CXCL17 is an orphan chemokine with no known receptor.

# Receptor
The receptor for CXCL17 is likely to be a G protein-coupled receptor (GPCR).
The GPCR GPR35 was thought to be a receptor of CXCL17. Subsequent research has suggested that GPR35 is not a receptor for CXCL17.
CYB561
Cytochrome b561 is a protein that in humans is encoded by the CYB561 gene.

# Model organisms
Model organisms have been used in the study of CYB561 function. A conditional knockout mouse line, called Cyb561tm1a(EUCOMM)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 three tests were carried out on mutant mice and one significant abnormality was observed: female homozygotes displayed a decreased circulating glucose level after a glucose tolerance test.