Persius/hicric huggingface dataset:
CBFB
Core-binding factor subunit beta is a protein that in humans is encoded by the CBFB gene.
The protein encoded by this gene is the beta subunit of a heterodimeric core-binding transcription factor belonging to the PEBP2/CBF transcription factor family which master-regulates a host of genes specific to hematopoiesis (e.g., RUNX1) and osteogenesis (e.g., RUNX2). The beta subunit is a non-DNA binding regulatory subunit; it allosterically enhances DNA binding by the alpha subunit as the complex binds to the core site of various enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers and GM-CSF promoters. Alternative splicing generates two mRNA variants, each encoding a distinct carboxyl terminus. In some cases, a pericentric inversion of chromosome 16  produces a chimeric transcript consisting of the N terminus of core-binding factor beta in a fusion with the C-terminal portion of the smooth muscle myosin heavy chain 11. This chromosomal rearrangement is associated with acute myeloid leukemia of the M4Eo subtype. Two transcript variants encoding different isoforms have been found for this gene. Mutations in CBFB are implicated in cases of breast cancer.
Core binding factor acute myeloid leukaemia is a cancer related to genetic changes in the CBF gene. It is most commonly caused by an inversion of particular region of chromosome 16; however it can also be caused by translocation between copies of chromosome 16. The rearrangements cause formation of CBF but with impaired function. This prevents proper differentiation of blood cells, leading to the formation of Myeloblast.
CBLC
Signal transduction protein CBL-C is a protein that in humans is encoded by the CBLC gene.
CBL proteins, such as CBLC, are phosphorylated upon activation of a variety of receptors that signal via protein tyrosine kinases. Through interactions with proteins containing SRC (MIM 190090) homology-2 (SH2) and SH3 domains, CBL proteins modulate downstream cell signaling (Keane et al., 1999).

# Interactions
CBLC has been shown to interact with FYN and Epidermal growth factor receptor.
CBX1
Chromobox protein homolog 1 is a protein that in humans is encoded by the CBX1 gene.

# Function
The protein is localized at heterochromatin sites, where it mediates gene silencing.

# Model organisms
Model organisms have been used in the study of CBX1 function. A conditional knockout mouse line, called Cbx1tm1a(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  at the Wellcome Trust Sanger Institute.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty two tests were carried out and two phenotypes were reported. No homozygous mutant animals survived until two weeks of age, therefore the remaining tests were carried out on heterozygous mutant mice. Male heterozygotes showed increased VO2, rate of elimination of carbon dioxide, and energy expenditure as determined by indirect calorimetry.

# Interactions
CBX1 has been shown to interact with:
- C11orf30,
- CBX3 and
- CBX5,  and
- SUV39H1.
CBX3
Chromobox protein homolog 3 is a protein that is encoded by the CBX3 gene in humans.
At the nuclear envelope, the nuclear lamina and heterochromatin are adjacent to the inner nuclear membrane. The protein encoded by this gene binds DNA and is a component of heterochromatin. This protein also can bind lamin B receptor, an integral membrane protein found in the inner nuclear membrane. The dual binding functions of the encoded protein may explain the association of heterochromatin with the inner nuclear membrane. Two transcript variants encoding the same protein but differing in the 5' UTR, have been found for this gene.

# Interactions
CBX3 has been shown to interact with PIM1, Ki-67, Lamin B receptor, CBX5 and CBX1.
CCL3
Chemokine (C-C motif) ligand 3 (CCL3) also known as macrophage inflammatory protein 1-alpha (MIP-1-alpha) is a protein that in humans is encoded by the CCL3 gene.

# Function
CCL3 is a cytokine belonging to the CC chemokine family that is involved in the acute inflammatory state in the recruitment and activation of polymorphonuclear leukocytes through binding to the receptors CCR1, CCR4 and CCR5.
Sherry et al. (1988) demonstrated 2 protein components of MIP1, called by them alpha (CCL3, this protein) and beta (CCL4).
CCL3 produces a monophasic fever of rapid onset whose magnitude is equal to or greater than that of fevers produced with either recombinant human tumor necrosis factor or recombinant human interleukin-1. However, in contrast to these two endogenous pyrogens, the fever induced by MIP-1 is not inhibited by the cyclooxygenase inhibitor ibuprofen and CCL3 may participate in the febrile response that is not mediated through prostaglandin synthesis and clinically cannot be ablated by cyclooxygenase.

# Interactions
CCL3 has been shown to interact with CCL4.
Attracts macrophages, monocytes and neutrophils.
CCL4
Chemokine (C-C motif) ligand 4, also known as CCL4, is a protein which in humans is encoded by the CCL4 gene.

# Function
CCL4, also known as Macrophage inflammatory protein-1 (MIP-1) is a CC chemokine with specificity for CCR5 receptors. It is a chemoattractant for natural killer cells, monocytes and a variety of other immune cells.
CCL4 is a major HIV-suppressive factor produced by CD8+ T cells.
Perforin-low memory CD8+ T cells that normally synthesize MIP-1-beta.
CCL4 is produced by: monocytes, B cells, T cells, fibroblasts, endothelial cells, and epithelial cells.
Concentration of this chemokine has been shown to be inversely related with MicroRNA-125b. Concentration of CCL4 within the body increases with age, which may cause chronic inflammation and liver damage.

# Interactions
CCL4 has been shown to interact with CCL3.
CCL4 binds to G protein-Coupled Receptors CCR5 and CCR8.
CCL5
Chemokine (C-C motif) ligand 5  (also CCL5) is a protein which in humans is encoded by the CCL5 gene. It is also known as RANTES (regulated on activation, normal T cell expressed and secreted).

# Function
CCL5 is an 8kDa protein classified as a chemotactic cytokine or chemokine. CCL5 is chemotactic for T cells, eosinophils, and basophils, and plays an active role in recruiting leukocytes into inflammatory sites. With the help of particular cytokines (i.e., IL-2 and IFN-) that are released by T cells, CCL5 also induces the proliferation and activation of certain natural-killer (NK) cells to form CHAK (CC-Chemokine-activated killer) cells. It is also an HIV-suppressive factor released from CD8+ T cells.  This chemokine has been localized to chromosome 17 in humans.
RANTES was first identified in a search for genes expressed "late" (35 days) after T cell activation.  It was subsequently determined to be a CC chemokine and expressed in more than 100 human diseases.  RANTES expression is regulated in T lymphocytes by Kruppel like factor 13 (KLF13). RANTES, along with the related chemokines MIP-1alpha and MIP-1beta, has been identified as a natural HIV-suppressive factor secreted by activated CD8+ T cells and other immune cells. Recently, the RANTES protein has been engineered for in vivo production by Lactobacillus bacteria, and this solution is being developed into a possible HIV entry-inhibiting topical microbicide.

# Interactions
CCL5 has been shown to interact with CCR3,   CCR5 and CCR1.
CCL5 also activates the G-protein coupled receptor GPR75.
CCL8
Chemokine (C-C motif) ligand 8 (CCL8), also known as monocyte chemoattractant protein 2 (MCP2), is a protein that in humans is encoded by the CCL8 gene.
CCL8 is a small cytokine belonging to the CC chemokine family.  The CCL8 protein is produced as a precursor containing 109 amino acids, which is cleaved to produce mature CCL8 containing 75 amino acids.  The gene for CCL8 is encoded by 3 exons and is located within a large cluster of CC chemokines on chromosome 17q11.2 in humans. MCP-2 is chemotactic for and activates many different immune cells, including mast cells, eosinophils and basophils, (that are implicated in allergic responses), and monocytes, T cells, and NK cells that are involved in the inflammatory response.  CCL8 elicits its effects by binding to several different cell surface receptors called chemokine receptors.  These receptors include CCR1, CCR2B, CCR3 and CCR5.
CCL8 is a CC chemokine that utilizes multiple cellular receptors to attract and activate human leukocytes. CCL8 is a potent inhibitor of HIV1 by virtue of its high-affinity binding to the receptor CCR5, one of the major co-receptors for HIV1. In addition, CCL8 attributes to the growth of metastasis in breast cancer cells. The manipulation of this chemokine activity influences the histology of tumors promoting steps of metastatic processes. CCL8 is also involved in attracting macrophages to the decidua in labor.
CCM2
The CCM2 gene contains 10 coding exons and an alternatively spliced exon 1B.  This gene is located on chromosome 7p13  and loss of function mutations on CCM2 lead to the onset of Cerebral Cavernous Malformations (CCM) illness.  Cerebral cavernous malformations (CCMs) are vascular malformations in the brain and spinal cord made of dilated capillary vessels.

# Protein
Malcavernin is a protein that in humans is encoded by the CCM2 gene. The normal function of malcavernin is to act as a scaffold for a variety of signaling complexes including p38 MAP Kinase.  This protein is also involved in regulating the cellular localization of the KRIT1 protein and acts with the Rho Kinase signaling pathway to maintain normal blood vessel structure.

# Advocacy
For more information and support for Cerebral Cavernous Malformations Patients and their families, please visit the Angioma Alliance website: www.angioma.org
CCR1
C-C chemokine receptor type 1 is a protein that in humans is encoded by the CCR1 gene.
CCR1 has also recently been designated CD191 (cluster of differentiation 191).

# Function
This gene encodes a member of the beta chemokine receptor family, which belongs to G protein-coupled receptors. The ligands of this receptor include CCL3 (or MIP-1 alpha), CCL5 (or RANTES), CCL7 (or MCP-3), and CCL23 (or MPIF-1). Chemokines and their receptors, which mediate signal transduction, are critical for the recruitment of effector immune cells to the site of inflammation. Knockout studies of the mouse homolog suggested the roles of this gene in host protection from inflammatory response, and susceptibility to virus and parasite. This gene and other chemokine receptor genes, including CCR2, CCRL2, CCR3, CCR5 and CXCR1, are found to form a gene cluster on chromosome 3p.

# Interactions
CCR1 has been shown to interact with CCL5.
CCR2
C-C chemokine receptor type 2 (CCR2 or CD192 (cluster of differentiation 192) is a protein  that in humans is encoded by the CCR2 gene. CCR2 is a chemokine receptor.

# Gene
This CCR2 gene is located in the chemokine receptor gene cluster region. Two alternatively spliced transcript variants are expressed by the gene.

# Function
This gene encodes two isoforms of a receptor for monocyte chemoattractant protein-1 (CCL2), a chemokine which specifically mediates monocyte chemotaxis. Monocyte chemoattractant protein-1 is involved in monocyte infiltration in inflammatory diseases such as rheumatoid arthritis as well as in the inflammatory response against tumors. The receptors encoded by this gene mediate agonist-dependent calcium mobilization and inhibition of adenylyl cyclase.

# Animal studies

## Alzheimer
CCR2 deficient mice have been shown to develop an accelerated Alzheimer's-like pathology in comparison to wild type mice. This is not the first time that immune function and inflammation have been linked to age-related cognitive decline (i.e. dementia).

## Obesity
Within the fat (adipose) tissue of CCR2 deficient mice, there is an increased number of eosinophils, greater alternative macrophage activation, and a propensity towards type 2 cytokine expression. Furthermore, this effect was exaggerated when the mice became obese from a high fat diet.

## Myocardial Infarct
CCR2 surface expression on blood monocytes changes in a time-of-daydependent manner (being higher at the beginning of the active phase) and affects monocytes recruitment in tissues including the heart. As a consequence when an acute ischemic event happens during the active phase, monocytes are more susceptible to invade the heart . An excessive monocytes infiltration generates higher inflammation and increases the risk of heart failure.

# Clinical significance
In an observational study of gene expression in blood leukocytes in humans, Harries et al. found evidence of a relationship between expression of CCR2 and cognitive function (assessed using the mini-mental state examination, MMSE). Higher CCR2 expression was associated with worse performance on the MMSE assessment of cognitive function. The same study found that CCR2 expression was also associated with cognitive decline over 9-years in a sub-analysis on inflammatory related transcripts only. Harries et al. suggest that CCR2 signaling may have a direct role in human cognition, partly because expression of CCR2 was associated with the ApoE haplotype (previously associated with Alzheimer's disease), but also because CCL2 is expressed at high concentrations in macrophages found in atherosclerotic plaques and in brain microglia. The difference in observations between mice (CCR2 depletion causes cognitive decline) and humans (higher CCR2 associated with lower cognitive function) could be due to increased demand for macrophage activation during cognitive decline, associated with increased -amyloid deposition (a core feature of Alzheimer's disease progression).
CCR4
C-C chemokine receptor type 4 is a protein that in humans is encoded by the CCR4 gene. CCR4 has also recently been designated CD194 (cluster of differentiation 194).
The protein encoded by this gene belongs to the G protein-coupled receptor family. It is a receptor for the following CC chemokines:
- CCL2 (MCP-1)
- CCL4 (MIP-1)
- CCL5 (RANTES)
- CCL17 (TARC)
- CCL22 (Macrophage-derived chemokine)
Chemokines are a group of small structurally related proteins that regulate cell trafficking of various types of leukocytes. The chemokines also play fundamental roles in the development, homeostasis, and function of the immune system, and they have effects on cells of the central nervous system as well as on endothelial cells involved in angiogenesis or angiostasis.

# Clinical significance
CCR4 is often expressed on leukemic cells in cutaneous T-cell lymphoma (CTCL).

## As a drug target
Mogamulizumab is a humanised monoclonal antibody targeted at CCR4 and is an investigational drug for CTCL.
CCR9
C-C chemokine receptor type 9 is a protein that in humans is encoded by the CCR9 gene.
CCR9 has also recently been designated CDw199 (cluster of differentiation w199).
The protein encoded by this gene is a member of the beta chemokine receptor family. It is predicted to be a seven transmembrane protein similar to G protein-coupled receptors. Chemokines and their receptors are key regulators of thymocyte migration and maturation in normal and inflammatory conditions. The specific ligand of this receptor is CCL25. It has been found that this gene is differentially expressed by T lymphocytes of small intestine and colon, suggested a role in thymocyte recruitment and development that may permit functional specialization of immune responses in different segments of the gastrointestinal tract. This gene is mapped to the chemokine receptor gene cluster region. Two alternatively spliced transcript variants have been described.
CD31
Platelet endothelial cell adhesion molecule (PECAM-1) also known as cluster of differentiation 31 (CD31)  is a protein that in humans is encoded by the PECAM1 gene found on chromosome 17. PECAM-1 plays a key role in removing aged neutrophils from the body.

# Function
PECAM-1 is found on the surface of platelets, monocytes, neutrophils, and some types of T-cells, and makes up a large portion of endothelial cell intercellular junctions. The encoded protein is a member of the immunoglobulin superfamily and is likely involved in leukocyte transmigration, angiogenesis, and integrin activation.

# Tissue distribution
CD31 is normally found on endothelial cells, platelets, macrophages and Kupffer cells, granulocytes, lymphocytes (T cells, B cells, and NK cells), megakaryocytes, and osteoclasts.
CD31 is also expressed in certain tumors, including epithelioid hemangioendothelioma, epithelioid sarcoma-like hemangioendothelioma, other vascular tumors, histiocytic malignancies, and plasmacytomas.  It is rarely found in some sarcomas, such as Kaposi's sarcoma, and carcinomas.

## Immunohistochemistry
In immunohistochemistry, CD31 is used primarily to demonstrate the presence of endothelial cells in histological tissue sections. This can help to evaluate the degree of tumor angiogenesis, which can imply a rapidly growing tumor. Malignant endothelial cells also commonly retain the antigen, so that CD31 immunohistochemistry can also be used to demonstrate both angiomas and angiosarcomas. It can also be demonstrated in small lymphocytic and lymphoblastic lymphomas, although more specific markers are available for these conditions.
CD14
CD14 (cluster of differentiation 14) is a human gene.
The protein encoded by this gene is a component of the innate immune system. CD14 exists in two forms, one anchored to the membrane by a glycosylphosphatidylinositol tail (mCD14), the other a soluble form (sCD14). Soluble CD14 either appears after shedding of mCD14 (48 kDa) or is directly secreted from intracellular vesicles (56 kDa).
The x-ray crystal structure of human CD14 (4GLP.pdb) reveals a monomeric, bent solenoid structure containing a hydrophobic amino-terminal pocket.
CD14 was the first described pattern recognition receptor.

# Function
CD14 acts as a co-receptor (along with the Toll-like receptor TLR 4 and MD-2) for the detection of bacterial lipopolysaccharide (LPS). CD14 can bind LPS only in the presence of lipopolysaccharide-binding protein (LBP).
Although LPS is considered its main ligand, CD14 also recognizes other pathogen-associated molecular patterns such as lipoteichoic acid.

# Tissue distribution
CD14 is expressed mainly by macrophages and (at 10-times lesser extent) by neutrophils. It is also expressed by dendritic cells. The soluble form of the receptor (sCD14) is secreted by the liver and monocytes and is sufficient in low concentrations to confer LPS-responsiveness to cells not expressing CD14. mCD14 and sCD14 are also present on enterocytes. sCD14 is also present in human milk, where it is believed to regulate microbial growth in the infant gut.

# Differentiation
CD14+ monocytes  can differentiate into a host of different cells, including dendritic cells, a differentiation pathway encouraged by cytokines, including GM-CSF and IL-4.

# Interactions
CD14 has been shown to interact with lipopolysaccharide-binding protein.
CD18
Integrin beta-2 (CD18) is a protein that in humans is encoded by the ITGB2 gene.
It is the beta subunit of four different structures:
- LFA-1 (paired with CD11a)
- Macrophage-1 antigen (paired with CD11b)
- Integrin alphaXbeta2 (paired with CD11c)
- Integrin alphaDbeta2 (paired with CD11d)

# Function
The ITGB2 protein product is the integrin beta chain beta 2. Integrins are integral cell-surface proteins composed of an alpha chain and a beta chain.  A given chain may combine with multiple partners resulting in different integrins.  For example, beta 2 combines with the alpha L chain to form the integrin LFA-1, and combines with the alpha M chain to form the integrin Mac-1. Integrins are known to participate in cell adhesion as well as cell-surface mediated signalling.

# Clinical significance
In humans lack of CD18 causes Leukocyte Adhesion Deficiency, a disease defined by a lack of leukocyte extravasation from blood into tissues. The beta 2 integrins have also been found in a soluble form. The soluble beta 2 integrins are ligand binding and plasma levels are inversely associated with disease activity in the autoimmune disease spondyloarthritis.

# Interactions
CD18 has been shown to interact with:
- FHL2,
- GNB2L1,
- ICAM-1,  and
- PSCD1.
CD1D
CD1D is the human gene that encodes the protein CD1d, a member of the CD1 (cluster of differentiation 1) family of glycoproteins expressed on the surface of various human antigen-presenting cells. They are non-classical MHC proteins, related to the class I MHC proteins, and are involved in the presentation of lipid antigens to T cells. CD1d is the only member of the group 2 CD1 molecules.

# Biological significance
CD1d-presented lipid antigens activate a special class of T cells, known as natural killer T (NKT) cells, through the interaction with the T-cell receptor present on NKT membranes. When activated, NKT cells rapidly produce Th1 and Th2 cytokines, typically represented by interferon-gamma and interleukin 4 production.

# Nomenclature
CD1d is also known as R3G1

# Ligands
Some of the known ligands for CD1d are:
- -galactosylceramide (-GalCer), a compound originally derived from the marine sponge Agelas mauritanius  with no physiological role but great research utility.
- -glucuronyl- and -galacturonyl- ceramides, a family of compounds of microbial origin which can be found, for example, on the cell wall of Sphingomonas, a ubiquitous Gram-negative  bacterium. The related -D-glucopyranosylceramide is accumulated in antigen-presenting cells after infection, where it serves to activate invariant NKTs (iNKTs), a special kind of NKT.
- iGb3, a self antigen which has been implied in iNKT selection.
- HS44, a synthetic amino cyclitolic ceramide analogue which has less contact with the TCR, activating iNKTs in a more constrained way than -GalCer (specially in relation to Th2 cytokines production) and thus being more interesting for therapeutic use.

# CD1d tetramers
CD1d tetramers are protein constructs composed of four CD1d molecules joined together and usually fluorescently labelled, used to identify NKT cells or other CD1d-reactive cells. In particular, type I NKT cells and some type II NKT cells are stained by them. A differentiation of these two types can be obtained in human by using an antibody against the TCR V24 chain, which is specific of type I NKT cells.
Although they are the most widely used of CD1d oligomers, sometimes CD1d dimers (two units) or pentamers (five units) are used instead.
CD22
CD22, or cluster of differentiation-22, is a molecule belonging to the SIGLEC family of lectins.  It is found on the surface of mature B cells and to a lesser extent on some immature B cells. Generally speaking, CD22 is a regulatory molecule that prevents the overactivation of the immune system and the development of autoimmune diseases.
CD22 is a sugar binding transmembrane protein, which specifically binds sialic acid with an immunoglobulin (Ig) domain located at its N-terminus. The presence of Ig domains makes CD22 a member of the immunoglobulin superfamily.  CD22 functions as an inhibitory receptor for B cell receptor (BCR) signaling. It is also involved in the B cell trafficking to Peyer's patches in mice.
An immunotoxin, BL22, that targets this receptor is being tested at the NIH.

# Interactions
CD22 has been shown to interact with Grb2, PTPN6, LYN, SHC1 and INPP5D.