Persius/hicric huggingface dataset:
CD120
CD120 (Cluster of Differentiation 120) can refer to two members of the tumor necrosis factor receptor superfamily: tumor necrosis factor receptor 1 (TNFR1) and tumor necrosis factor receptor 2 (TNFR2).

# Receptor subtypes
There are two variants of the receptor, each encoded by a separate gene:
- CD120a - TNFR1 - TNFR superfamily member 1A
- CD120b - TNFR2 - TNFR superfamily member 1B
TNFR1 is the receptor type responsible for mediation of TNF-alpha induced sickness behavior, and is involved in neurotoxic processes. Elevated levels of TNFR1 has been found in severe mental disorders.

# Signaling pathway
CD133
CD133 antigen, also known as prominin-1, is a glycoprotein that in humans is encoded by the PROM1 gene. It is a member of pentaspan transmembrane glycoproteins, which specifically localize to cellular protrusions. When embedded in the cell membrane, the membrane topology of prominin-1 is such that the N-terminus extends into the extracellular space and the C-terminus resides in the intracellular compartment. The protein consists of five transmembrane segments, with the first and second segments and the third and fourth segments connected by intracellular loops while the second and third as well as fourth and fifth transmembrane segments are connected by extracellular loops. While the precise function of CD133 remains unknown, it has been proposed that it acts as an organizer of cell membrane topology.

# Tissue distribution
CD133 is expressed in hematopoietic stem cells, endothelial progenitor cells, glioblastoma, neuronal and glial stem cells, various pediatric brain tumors, as well as adult kidney, mammary glands, trachea, salivary glands, uterus, placenta, digestive tract, testes, and some other cell types.

# Clinical significance
Today CD133 is the most commonly used marker for isolation of cancer stem cell (CSC) population from different tumors, mainly from various gliomas and carcinomas. Initial studies that showed ability of CD133-positive population to efficiently propagate tumor when injected into immune-compromised mice firstly were performed on brain tumors.  However, subsequent studies have indicated the difficulty in isolating pure CSC populations. CD133+ melanoma cells are considered a subpopulation of CSC and play a critical role in recurrence. Moreover, CD133+ melanoma cells are immunogenic and can be used as an antimelanoma vaccination. In mice the vaccination with CD133+ melanoma cells mediated strong anti-tumor activity that resulted in the eradication of parental melanoma cells. In addition, it has also been shown that CD133+ melanoma cells preferentially express the RNA helicase DDX3X . As DDX3X also is an immunogenic protein, the same anti-melanoma vaccination strategy can be employed to give therapeutic antitumor immunity in mice.
CD134
Tumor necrosis factor receptor superfamily, member 4 (TNFRSF4), also known as CD134 and OX40 receptor, is a member of the TNFR-superfamily of receptors which is not constitutively expressed on resting naive T cells, unlike CD28. OX40 is a secondary co-stimulatory immune checkpoint molecule, expressed after 24 to 72 hours following activation; its ligand, OX40L, is also not expressed on resting antigen presenting cells, but is following their activation. Expression of OX40 is dependent on full activation of the T cell; without CD28, expression of OX40 is delayed and of fourfold lower levels.

# Function
OX40 has no effect on the proliferative abilities of CD4+ cells for the first three days, however after this time proliferation begins to slow and cells die at a greater rate, due to an inability to maintain a high level of PKB activity and expression of Bcl-2, Bcl-XL and survivin. OX40L binds to OX40 receptors on T-cells, preventing them from dying and subsequently increasing cytokine production. OX40 has a critical role in the maintenance of an immune response beyond the first few days and onwards to a memory response due to its ability to enhance survival. OX40 also plays a crucial role in both Th1 and Th2 mediated reactions in vivo.
OX40 binds TRAF2, 3 and 5 as well as PI3K by an unknown mechanism. TRAF2 is required for survival via NF-B and memory cell generation whereas TRAF5 seems to have a more negative or modulatory role, as knockouts have higher levels of cytokines and are more susceptible to Th2-mediated inflammation. TRAF3 may play a critical role in OX40-mediated signal transduction. CTLA-4 is down-regulated following OX40 engagement in vivo and the OX40-specific TRAF3 DN defect was partially overcome by CTLA-4 blockade in vivo.  TRAF3 may be linked to OX40-mediated memory T cell expansion and survival, and point to the down-regulation of CTLA-4 as a possible control element to enhance early T cell expansion through OX40 signaling.

# Clinical significance
OX40 has been implicated in the pathologic cytokine storm associated with certain viral infections, including the H5N1 bird flu.

# As a drug or drug target
An artificially created biologic fusion protein, OX40-immunoglobulin (OX40-Ig), prevents OX40 from reaching the T-cell receptors, thus reducing the T-cell response.  Experiments in mice have demonstrated that OX40-Ig can reduce the symptoms associated with the cytokine storm (an immune overreaction) while allowing the immune system to fight off the virus successfully.
An anti-OX40 antibody GSK3174998 has started clinical trials as a cancer treatment.  Research in mice has included the combination of an agonistic OX40 antibody (clone OX86) injected directly into a tumor in combination with an unmethylated CpG oligonucleotide, which as a TLR9 ligand activates expression of OX40 so that it can be affected.

# Interactions
CD134 has been shown to interact with TRAF5 and TRAF2.
CD137
CD137 is a member of the tumor necrosis factor (TNF) receptor family. Its alternative names are tumor necrosis factor receptor superfamily member 9 (TNFRSF9), 4-1BB and induced by lymphocyte activation (ILA). It is currently of interest to immunologists as a co-stimulatory immune checkpoint molecule.

# Expression
CD137 can be expressed by activated T cells, but to a larger extent on CD8 than on CD4 T cells. In addition, CD137 expression is found on dendritic cells, B cells, follicular dendritic cells, natural killer cells, granulocytes and cells of blood vessel walls at sites of inflammation.

# Specific effects on cells
The best characterized activity of CD137 is its costimulatory activity for activated T cells. Crosslinking of CD137 enhances T cell proliferation, IL-2 secretion, survival and cytolytic activity. Further, it can enhance immune activity to eliminate tumors in mice.

# Interactions
CD137 has been shown to interact with TRAF2.

# As a drug target

## Utomilumab
Utomilumab (PF-05082566) targets this receptor to stimulate a more intense immune system attack on cancers. It is a fully human IgG2 monoclonal antibody. It is in early clinical trials. As of  June 2016 5 clinical trials are active.
CD146
CD146 (cluster of differentiation 146) also known as the melanoma cell adhesion molecule (MCAM) or cell surface glycoprotein MUC18, is a 113kDa cell adhesion molecule currently used as a marker for endothelial cell lineage.  In humans, the CD146 protein is encoded by the MCAM gene.

# Function
MCAM functions as a receptor for laminin alpha 4, a matrix molecule that is broadly expressed within the vascular wall.  Accordingly, MCAM is highly expressed by cells that are components of the blood vessel wall, including vascular endothelial cells, smooth muscle cells and pericytes.  Its function is still poorly understood, but evidence points to it being part of the endothelial junction associated with the actin cytoskeleton.  A member of the Immunoglobulin superfamily, it consists of five Ig domains, a transmembrane domain, and a cytoplasmic region.  It is expressed on chicken embryonic spleen and thymus, activated human T cells, endothelial progenitors such as angioblasts and mesenchymal stem cells, and strongly expressed on blood vessel endothelium and smooth muscle.
Two isoforms exist (MCAM long (MCAM-1), and MCAM short, or MCAM-s) which differ in the length of their cytoplasmic domain.  Activation of these isoforms seems to produce functional differences as well.  Natural killer cells transfected with MCAM-1 demonstrate decreased rolling velocity and increased cell adhesion to an endothelial cell monolayer and increased microvilli formation while cells transfected with MCAM-s showed no change in adhesion characteristics.  Since these characteristics are important in leukocyte extravasation, MCAM-1 may be an important part of the inflammatory response.
CD146 has been demonstrated to appear on a small subset of T and B lymphocytes in the peripheral blood of healthy individuals. The CD146+ T cells display an immunophenotype consistent with effector memory cells and have a distinct gene profile from the CD146- T cells. CD146 T cells have been shown by Dagur and colleagues to produce IL-17.
CD146 has been seen as a marker for mesenchymal stem cells isolated from multiple adult and fetal organs, and its expression may be linked to multipotency; mesenchymal stem cells with greater differentiation potential express higher levels of CD146 on the cell surface.

# Clinical significance
MCAM inhibits breast cancer progression.
CD155
CD155 (cluster of differentiation 155) also known as the poliovirus receptor is a protein that in humans is encoded by the PVR gene.

# Function
CD155 is a Type I transmembrane glycoprotein in the immunoglobulin superfamily. Commonly known as Poliovirus Receptor (PVR) due to its involvement in the cellular poliovirus infection in primates, CD155's normal cellular function is in the establishment of intercellular adherens junctions between epithelial cells. The role of CD155 in the immune system is unclear, though it may be involved in intestinal humoral immune responses. Subsequent data has also suggested that CD155 may also be used to positively select MHC-independent T cells in the thymus.
The external domain mediates cell attachment to the extracellular matrix molecule vitronectin, while its intracellular domain interacts with the dynein light chain Tctex-1/DYNLT1. The gene is specific to the primate lineage, and serves as a cellular receptor for poliovirus in the first step of poliovirus replication.

# Structure
CD155 is a transmembrane protein with 3 extracellular immunoglobulin-like domains, D1-D3, where D1 is recognized by the virus.
Low resolution structures of CD155 complexed with poliovirus have been obtained using electron microscopy while a high resolution structures of the ectodomain D1 and D2 of CD155 were solved by x-ray crystallography.
CD160
CD160 antigen is a protein that in humans is encoded by the CD160 gene.
CD160 is a 27 kDa glycoprotein which was initially identified with the monoclonal antibody BY55. Its expression is tightly associated with peripheral blood NK cells and CD8 T lymphocytes with cytolytic effector activity. The cDNA sequence of CD160 predicts a cysteine-rich, glycosylphosphatidylinositol-anchored protein of 181 amino acids with a single Ig-like domain weakly homologous to KIR2DL4 molecule. CD160 is expressed at the cell surface as a tightly disulfide-linked multimer. RNA blot analysis revealed CD160 mRNAs of 1.5 and 1.6 kb whose expression was highly restricted to circulating NK and T cells, spleen and small intestine. Within NK cells CD160 is expressed by CD56dimCD16+ cells whereas among circulating T cells its expression is mainly restricted to TCRgd bearing cells and to TCRab+CD8brightCD95+CD56+CD28-CD27-cells. In tissues, CD160 is expressed on all intestinal intraepithelial lymphocytes. CD160 shows a broad specificity for binding to both classical and nonclassical MHC class I molecules.

# Clinical significance
CD160 is a ligand for HVEM, and considered a proposed immune checkpoint inhibitor with anti-cancer activity alongside with anti- PD-1 antibodies. CD160 has also been proposed as a potential new target in cases of human pathological ocular and tumor neoangiogenesis that do not respond or become resistant to existing antiangiogenic drugs.

# Related gene problems
- TAR syndrome
- 1q21.1 deletion syndrome
- 1q21.1 duplication syndrome
CD163
CD163 (Cluster of Differentiation 163) is a protein that in humans is encoded by the CD163 gene. CD163 is the high affinity scavenger receptor for the hemoglobin-haptoglobin complex and in the absence of haptoglobin - with lower affinity - for hemoglobin alone. It also is a marker of cells from the monocyte/macrophage lineage. CD163 functions as innate immune sensor for gram-positive and gram-negative bacteria. The receptor was discovered in 1987.

# Structure
The molecular size is 130 kDa. The receptor belongs to the scavenger receptor cysteine rich family type B and consists of a 1048 amino acid residues extracellular domain, a single transmembrane segment and a cytoplasmic tail with several splice variants.

# Clinical significance
A soluble form of the receptor exists in plasma, and cerebrospinal fluid., commonly denoted sCD163. It is generated by ectodomain shedding of the membrane bound receptor, which may represent a form of modulation of CD163 function. sCD163 shedding occurs as a result of enzymatic cleavage by ADAM17. sCD163 is upregulated in a large range of inflammatory diseases including liver cirrhosis, type 2 diabetes, macrophage activation syndrome, Gaucher's disease, sepsis, HIV infection, rheumatoid arthritis and Hodgkin Lymphoma. sCD163 is also upregulated in cerebrospinal fluid after subarachnoid haemorrhage.

# Differences between mouse and human
Differences between mice and humans in CD163 biology are important to note since preclinical studies are frequently conducted in mice. sCD163 shedding occurs in humans but not mice, due to the emergence of an Arg-Ser-Ser-Arg sequence in humans, essential for enzymatic cleavage by ADAM17. Human CD163, but mouse CD163, exhibits a strikingly higher affinity to hemoglobin-haptoglobin complex compared to hemoglobin alone.

# Animal studies
Pigs with a section of the CD163 gene removed showed complete resistance to the virus that causes Porcine Reproductive and Respiratory Syndrome.

# Interactions
CD163 has been shown to interact with CSNK2B.
CD226
CD226 (Cluster of Differentiation 226), PTA1 (outdated term, 'platelet and T cell activation antigen 1') or DNAM-1 (DNAX Accessory Molecule-1) is a protein that in humans is encoded by the CD226 gene which is located on chromosome 18q22.3.

# Structure and function
CD226 is a ~65 kDa glycoprotein expressed on the surface of natural killer cells, platelets, monocytes and a subset of T cells. It is a member of the immunoglobulin superfamily containing 2 Ig-like domains of the V-set.
CD226 mediates cellular adhesion to other cells bearing its ligands, CD112 and CD155, and cross-linking CD226 with antibodies causes cellular activation.
CD244
CD244 (Cluster of Differentiation 244) is a human protein encoded by the CD244 gene. It is also known as Natural Killer Cell Receptor 2B4
This gene encodes a cell surface receptor expressed on natural killer cells (NK cells) (and some T cells) mediating non-major histocompatibility complex (MHC) restricted killing. The interaction between NK-cell and target cells via this receptor is thought to modulate NK-cell cytolytic activity. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.
CD244 can also be expressed on non-lymphocytes such as eosinophils, mast cells and dendritic cells.
CD247
T-cell surface glycoprotein CD3 zeta chain also known as T-cell receptor T3 zeta chain or CD247 (Cluster of Differentiation 247) is a protein that in humans is encoded by the CD247 gene.

# Genomics
The gene is located on the long arm of chromosome 1  at location 1q22-q25 on the Crick (negative) strand. The gene is 87,896 bases in length. The encoded protein is 164 amino acids long with a predicted weight of 18.696 kiloDaltons.

# Function
T-cell receptor zeta (), together with T-cell receptor alpha/beta and gamma/delta heterodimers and CD3-gamma, -delta, and -epsilon, forms the T-cell receptor-CD3 complex. The zeta chain plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. Low expression of the antigen results in impaired immune response. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

# Interactions
CD247 has been shown to interact with Janus kinase 3 and Protein unc-119 homolog.
CD248
Endosialin is a protein that in humans is encoded by the CD248 gene.
Endosialin is a member of the Group XIV, a novel family of C-type lectin transmembrane receptors which play a role not only in cellcell adhesion processes but also in host defence. This family comprise two other members, CD93 and Thrombomodulin which are better characterized.
The function of endosialin remains elusive, but its expression has been associated with angiogenesis in the embryo and uterus and in tumor development and growth.
CD276
CD276 (Cluster of Differentiation 276) is a human protein encoded by the CD276 gene.

# Function
Costimulatory B7 molecules (e.g., B7-1, or CD80; MIM 112203) signal through CD28 (MIM 186760) family molecules such as CD28, CTLA4 (MIM 123890), and ICOS (MIM 604558).
CD276 (aka B7-H3), an immune checkpoint molecule, is expressed by some solid tumours and is the target of anticancer candidates such as MGA271.
CD278
Inducible T-cell costimulator is an immune checkpoint protein that in humans is encoded by the ICOS gene.
CD278 or ICOS (Inducible T-cell COStimulator) is a CD28-superfamily costimulatory molecule that is expressed on activated T cells. It is thought to be important for Th2 cells in particular.

# Function
The protein encoded by this gene belongs to the CD28 and CTLA-4 cell-surface receptor family. It forms homodimers and plays an important role in cell-cell signaling, immune responses and regulation of cell proliferation.

# Knockout phenotype
Compared to wild-type naive T cells, ICOS-/- T cells activated with plate-bound anti-CD3 have reduced proliferation and IL-2 secretion. The defect in proliferation can be rescued by addition of IL-2 to the culture, suggesting the proliferative defect is due either to ICOS-mediated IL-2 secretion or the activation of similar signaling pathways between ICOS and IL-2. In terms of Th1 and Th2 cytokine secretion, ICOS-/- CD4+ T cell activated in vitro reduced IL-4 secretion, while maintaining similar IFN-g secretion. Similarly, CD4+ T cells purified from ICOS-/- mice immunized with the protein keyhole limpet hemocyanin (KLH) in alum or complete Freund's Adjuvant have attenuated IL-4 secretion, but similar IFN-g and IL-5 secretion when recalled with KLH.
These data are similar to an airway hypersensitivity model showing similar IL-5 secretion, but reduced IL-4 secretion in response to sensitization with Ova protein, indicating a defect in Th2 cytokine secretion, but not a defect in Th1 differentiation as both IL-4 and IL-5 are Th2-associated cytokines. In agreement with reduced Th2 responses, ICOS-/- mice expressed reduced germinal center formation and IgG1 and IgE antibody titers in response to immunization.

# Combination therapy
Ipilimumab patients expressed increased ICOS+ T cells in tumor tissues and blood. The increase served as a pharmacodynamic biomarker of anti-CTLA-4 treatment. In wild-type C57BL/6 mice, anti-CTLA-4 treatment resulted in tumor rejection in 80 to 90% of subjects, but in gene-targeted mice that were deficient for either ICOS or its ligand (ICOSLG), the efficacy was less than 50%. An agonistic stimulus for the ICOS pathway during anti-CTLA-4 therapy resulted in an increase in efficacy that was about four to five times as large as that of control treatments. As of 2015 antibodies for ICOS were not available for clinical testing.
CD49b
Integrin alpha-2 or CD49b (cluster of differentiation 49b) is a protein which in humans is encoded by the CD49b gene.
The CD49b protein is an integrin alpha subunit. It makes up half of the 21 integrin duplex. Integrins are heterodimeric integral membrane glycoproteins composed of a distinct alpha chain and a common beta chain. They are found on a wide variety of cell types including, T cells (the NKT cells), NK cells, fibroblasts and platelets. Integrins are involved in cell adhesion and also participate in cell-surface mediated signalling.
Expression of CD49b in conjunction with LAG-3 has been used to identify type 1 regulatory (Tr1) cells.
DX5 is a monoclonal antibody which binds to CD49b.

# Interactions
CD49b has been shown to interact with MMP1.
CD49c
Integrin alpha-3 is a protein that in humans is encoded by the ITGA3 gene.
ITGA3 is an integrin alpha subunit. Together with beta-1 subunit, it makes up half of the 31 integrin duplex that plays a role in neural migration and corticogenesis, acted upon by such factors as netrin-1 and reelin.
ITGA3 encodes the integrin alpha 3 chain. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. Alpha chain 3 undergoes post-translational cleavage in the extracellular domain to yield disulfide-linked light and heavy chains that join with beta 1 to form an integrin that interacts with many extracellular matrix proteins.

# Alternative names
The alpha 3 beta 1 integrin is known variously as: very late (activation) antigen 3 ('VLA-3'), very common antigen 2 ('VCA-2'), extracellular matrix receptor 1 ('ECMR1'), and galactoprotein b3 ('GAPB3').

# Interactions
CD49c has been shown to interact with:
- CD9
- FHL2,
- LGALS8,  and
- TSPAN4.
CDC34
CDC34 is a gene encoding a protein product that has ubiquitin conjugating activity. CDC34 was originally discovered by work in baker's yeast as a gene that has a role in the cell division cycle. Cdc34 in yeast targets numerous substrates (Sic1, Far1, Cln1, Cln2)  for ubiquitin mediated degradation.
Ubiquitin-conjugating enzyme E2 R1 is a protein that in humans is encoded by the CDC34 gene.
The protein encoded by this gene is a member of the ubiquitin-conjugating enzyme family. Ubiquitin-conjugating enzyme catalyzes the covalent attachment of ubiquitin to other proteins. This protein is a part of the large multiprotein complex, which is required for ubiquitin-mediated degradation of cell cycle G1 regulators, and for the initiation of DNA replication.

# Interactions
CDC34 has been shown to interact with CSNK2B, BTRC and CDK9.
CDC37
Hsp90 co-chaperone Cdc37 is a protein that in humans is encoded by the CDC37 gene.
The protein encoded by this gene is highly similar to Cdc 37, a cell division cycle control protein of Saccharomyces cerevisiae. This protein is a molecular chaperone with specific function in cell signal transduction. It has been shown to form complex with Hsp90 and a variety of protein kinases including CDK4, CDK6, SRC, RAF1, MOK, as well as eIF-2 alpha kinases. It is thought to play a critical role in directing Hsp90 to its target kinases.

# Interactions
CDC37 has been shown to interact with:
- CDK4,
- HSP90AA1
- IKBKG,
- IKK2,  and
- STK11.

# Domain architecture
CDC37 consists of three structural domains. The N-terminal domain binds to protein kinases.  The central domain is the Hsp90 chaperone (heat shock protein 90) binding domain. The function of the C-terminal domain is unclear.
CDC73
Cell division cycle 73, Paf1/RNA polymerase II complex component, homolog (S. cerevisiae), also known as CDC73 and parafibromin, is a protein which in humans is encoded by the CDC73 gene.

# Function
Parafibromin, LEO1, PAF1, and CTR9 form the PAF protein complex, which associates with the RNA polymerase II subunit POLR2A and with a histone methyltransferase complex.

# Clinical significance
Mutations in the CDC73 gene are associated with hyperparathyroidism-jaw tumor syndrome (HPT-JT) and parathyroid carcinomas.
CDCA5
Sororin is a protein that in humans is encoded by the CDCA5 gene.

# Function
Sororin is required for stable binding of cohesin to chromatin and for sister chromatid cohesion in interphase.

# Clinical significance
Transactivation of Sororin and its phosphorylation at Ser209 by ERK play an important role in lung cancer proliferation.