Persius/hicric huggingface dataset:
CD23
CD23, also known as Fc epsilon RII, or FcRII, is the "low-affinity" receptor for IgE, an antibody isotype involved in allergy and resistance to parasites, and is important in regulation of IgE levels. Unlike many of the antibody receptors, CD23 is a C-type lectin. It is found on mature B cells, activated macrophages, eosinophils, follicular dendritic cells, and platelets.
There are two forms of CD23: CD23a and CD23b.  CD23a is present on follicular B cells, whereas CD23b requires IL-4 to be expressed on T-cells, monocytes, Langerhans cells, eosinophils, and macrophages.

# Function
CD23 is known to have a role of transportation in antibody feedback regulation. Antigens which enter the blood stream can be captured by antigen specific IgE antibodies. The IgE immune complexes that are formed bind to CD23 molecules on B cells, and are transported to the B cell follicles of the spleen. The antigen is then transferred from CD23+ B cells to CD11c+ antigen presenting cells. The CD11c+ cells in turn present the antigen to CD4+ T cells, which can lead to an enhanced antibody response.

# Clinical significance
The allergen responsible in dust mite allergy Der p 1 is known to cleave CD23 from a cells surface. As CD23 is soluble, it can move freely and interact with cells in plasma. Recent studies have shown that increased levels of soluble CD23 cause the recruitment of non-sensitised B-cells in the presentation of antigen peptides to allergen-specific B-cells, therefore increasing the production of allergen specific IgE. IgE, in turn, is known to upregulate the cellular expression of CD23 and Fc epsilon RI (high-affinity IgE receptor).
In flow cytometry, CD23 is helpful in the differentiation of chronic lymphocytic leukemia (CD23-positive) from mantle cell lymphoma (CD23-negative). CD23 can also be demonstrated in germinal centre B-cells using immunohistochemistry, but it is not present in the resting cells of the surrounding mantle zone. Lymphomas arising from the mantle zone are generally negative for CD23, but most B-cell chronic lymphomocytic leukaemias and low-grade B-cell lymphomas are positive, allowing immunohistochemistry to distinguish these conditions, which otherwise have a similar appearance. ReedSternberg cells are usually positive for CD23.
CD27
CD27 is a member of the tumor necrosis factor receptor superfamily. It is currently of interest to immunologists as a co-stimulatory immune checkpoint molecule.

# Function
The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is required for generation and long-term maintenance of T cell immunity. It binds to ligand CD70, and plays a key role in regulating B-cell activation and immunoglobulin synthesis. This receptor transduces signals that lead to the activation of NF-B and MAPK8/JNK. Adaptor proteins TRAF2 and TRAF5 have been shown to mediate the signaling process of this receptor. CD27-binding protein (SIVA), a proapoptotic protein, can bind to this receptor and is thought to play an important role in the apoptosis induced by this receptor.

# Clinical significance

## As a drug target
Varlilumab is an antibody that binds to CD27 and is an experimental cancer treatment.

# Interactions
CD27 has been shown to interact with SIVA1, TRAF2 and TRAF3.
CD30
CD30, also known as TNFRSF8, is a cell membrane protein of  the tumor necrosis factor receptor family and tumor marker.

# Function
This receptor is expressed by activated, but not by resting, T and B cells. TRAF2 and TRAF5 can interact with this receptor, and mediate the signal transduction that leads to the activation of NF-kappaB. It is a positive regulator of apoptosis, and also has been shown to limit the proliferative potential of autoreactive CD8 effector T cells and protect the body against autoimmunity. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported.

# Clinical significance
CD30 is associated with anaplastic large cell lymphoma. It is expressed in embryonal carcinoma but not in seminoma and is thus a useful marker in distinguishing between these germ cell tumors. CD30 and CD15 are also expressed on Reed-Sternberg cells typical for Hodgkin's lymphoma.

# Cancer treatment
CD30 is the target of the FDA approved therapeutic brentuximab vedotin (Adcetris).  It is approved for use in:
- Hodgkin lymphoma (HL) (brentuximab vedotin) after failure of autologous stem cell transplant (ASCT)
- HL in patients who are not ASCT candidates after failure of at least 2 multiagent chemotherapy regimens
- Systemic anaplastic large cell lymphoma (sALCL) after failure of at least 1 multiagent chemotherapy regimen
- Primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy

# Interactions
CD30 has been shown to interact with TRAF5, TRAF1, TRAF2 and TRAF3.
CD33
CD33 or Siglec-3 (sialic acid binding Ig-like lectin 3, SIGLEC3, SIGLEC-3, gp67, p67) is a transmembrane receptor expressed on cells of myeloid lineage. It is usually considered myeloid-specific, but it can also be found on some lymphoid cells.
It binds sialic acids, therefore is a member of the SIGLEC family of lectins.

# Structure
The extracellular portion of this receptor contains two immunoglobulin domains (one IgV and one IgC2 domain), placing CD33 within the immunoglobulin superfamily.  The intracellular portion of CD33 contains immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that are implicated in inhibition of cellular activity.

# Clinical significance
CD33 is the target of gemtuzumab ozogamicin (trade name: Mylotarg; Pfizer/Wyeth-Ayerst Laboratories),  an Antibody-drug conjugate for the treatment of patients with acute myeloid leukemia. The drug is a recombinant, humanized anti-CD33 monoclonal antibody (IgG4  antibody hP67.6) covalently attached to the cytotoxic antitumor antibiotic calicheamicin (N-acetyl--calicheamicin) via a bifunctional linker (4-(4-acetylphenoxy)butanoic acid). 
On September 1, 2017, the FDA approved Pfizer's Mylotarg. 
Gemtuzumab ozogamicin was initially approved by the U.S. Food and Drug Administration in 2000.  However, during post marketing clinical trials researchers noticed a greater number of deaths in the group of patients who received gemtuzumab ozogamicin compared with those receiving chemotherapy alone.  Based on these results, Pfizer voluntarily withdrew gemtuzumab ozogamicin from the market in mid-2010, but was reintroduced to the market in 2017.   
CD33 is also the target in Vadastuximab talirine (SGN-CD33A), a novel antibody-drug conjugate being developed by Seattle Genetics, utilizing this company's ADC technology.
CD38
CD38 (cluster of differentiation 38), also known as cyclic ADP ribose hydrolase is a  glycoprotein found on the surface of many immune cells (white blood cells), including CD4+, CD8+, B lymphocytes and natural killer cells. CD38 also functions in cell adhesion, signal transduction and calcium signaling.
In humans, the CD38 protein is encoded by the CD38 gene which is located on chromosome 4.

# Function
CD38 is a multifunctional ectoenzyme that catalyzes the synthesis and hydrolysis of cyclic ADP-ribose (cADPR) from NAD+ to ADP-ribose in addition to synthesis of NAADP from NADP+. These reaction products are essential for the regulation of intracellular Ca2+.

# Clinical significance
The loss of CD38 function is associated with impaired immune responses, metabolic disturbances, and behavioral modifications including social amnesia possibly related to autism.
The CD38 protein is a marker of cell activation. It has been connected to HIV infection, leukemias, myelomas, solid tumors, type II diabetes mellitus and bone metabolism, as well as some genetically determined conditions.
CD38 produces an enzyme which regulates the release of oxytocin within the central nervous system.
Daratumumab which targets CD38 has been used in treating multiple myeloma.
Increased expression of CD 38 is an unfavourable diagnostic marker in chronic lymphocytic leukemia and is associated with increased disease progression.

# Application
CD38 has been used as a prognostic marker in leukemia. CD38 is also used as a target for daratumumab (Darzalex), a medicine that has been approved for the treatment of multiple myeloma.
The use of Daratumumab can interfere with pre-Blood transfusion tests, as CD38 is weakly expressed on the surface of erythrocytes. Thus, a screening assay for irregular antibodies against red blood cell antigens or a direct immunoglobulin test can produce false-positive results. This can be sidelined by either pretreatment of the erythrocytes with dithiothreitol (DTT) or by using an anti-CD38 antibody neutralizing agent, e.g. DaraEx.

# Animal studies
A gradual increase in CD38 has been implicated in the decline of NAD+ with age. Treatment of old mice with a specific CD38 inhibitor, 78c, prevents age-related NAD+ decline.
CD46
CD46 complement regulatory protein also known as CD46 (cluster of differentiation 46) and Membrane Cofactor Protein is a protein which in humans is encoded by the CD46 gene. CD46 is an inhibitory complement receptor.

# Gene
This gene is found in a cluster on chromosome 1q32 with other genes encoding structural components of the complement system. At least fourteen different transcript variants encoding fourteen different isoforms have been found for this gene.

# Function
The protein encoded by this gene is a type I membrane protein and is a regulatory part of the complement system.
The encoded protein has cofactor activity for inactivation (through cleavage) of complement components C3b and C4b by serum factor I, which protects the host cell from damage by complement.
The protein encoded by this gene may be involved in the fusion of the spermatozoa with the oocyte during fertilization.

# Clinical significance
The encoded protein can act as a receptor for the Edmonston strain of measles virus, human herpesvirus-6 (HHV-6), and type IV pili of pathogenic Neisseria.
The extracellular region of CD46 contains four short consensus repeats (SCR) of about 60 amino acids that fold into a compact beta-barrel domain surrounded by flexible loops. As has been demonstrated for CD46 with other ligands, the CD46 protein structure is believed to linearize upon binding HHV-6. While their precise interaction has not yet been determined, the second and third SCR domains have been demonstrated to be required for HHV-6 receptor binding and cellular entry. The heterotetramer gH/gL/gQ1/gQ2 complex of HHV-6 has been identified as a CD46 ligand.
Established medulloblastoma (a malignant brain tumor common in childhood) specimens express CD46, and that medulloblastoma specimens removed from patients had a high level of CD46 expression. Therefore, a vaccine made of the Edmonston strain of measles virus could treat the medulloblastoma. Such a vaccine has already been tested in a number of trials involving other tumor types which have a high expression of CD46, including one type of adult brain tumor.

# Interactions
CD46 has been shown to interact with CD9, CD151 and CD29.
CD48
CD48 antigen (Cluster of Differentiation 48) also known as B-lymphocyte activation marker (BLAST-1) or signaling lymphocytic activation molecule 2 (SLAMF2) is a protein that in humans is encoded by the CD48 gene.
CD48 is a member of the CD2 subfamily of the immunoglobulin superfamily (IgSF) which includes SLAM (signaling lymphocyte activation molecules) proteins, such as CD84, CD150, CD229 and CD244. CD48 is found on the surface of lymphocytes and other immune cells, dendritic cells and endothelial cells, and participates in activation and differentiation pathways in these cells.
CD48 was the first B-cell-specific cellular differentiation antigen identified in transformed B lymphoblasts.

# Structure
The gene for CD48 is located in chromosome 1q23 and contains 4 exons, each exon encoding one of the 4 domains of CD48: signal peptide, variable (V) domain, constant 2 (C2) domain and the glycophosphatidylinositol anchor (GPI anchor).  The cDNA sequence of 1137 nucleotides encodes a 243 amino acid polypeptide of about 45 kDa. It consists of a 26 amino acid signal peptide, 194 amino acids of mature CD48 (V and C2 domains) and the C-terminal 23 amino acid segment comprising the GPI anchor. The GPI linkage of CD48 to the cell surface is through serine residue 220. CD48 does not have a transmembrane domain, however, but is held at the cell surface by a GPI anchor via a C-terminal domain which can be cleaved to yield a soluble form of the receptor.  The CD48 protein is heavily glycosylated, with five possible asparagine-linked glycosylation sites at positions 40, 44, 104, 162 and 189, respectively. Approximately 35-40% of the total molecular weight is attributed to the carbohydrate side chains.

# Interactions
CD48 was found to have a very low affinity for CD2 with dissociation constant (K_{D}) K_{D} = 8 M which is about 5 - 10 times stronger than for CD2.

# Function

## Cell distribution
CD48 is expressed on all peripheral blood lymphocytes (PBL) including T cells, B cells, NK cells and thymocytes. It is also found on the surface of activated T cells, mast cells, monocytes and granulocytes. Like all other GPI anchor protein (GPI-AP), CD48 is deficient in erythrocytes (red blood cells).

## T cell activation
CD48 and CD2 molecular coupling together with other interaction pairs of CD28 and CD80, TCR and peptide-MHC and LFA-1 and ICAM-1 contribute to the formation of an immunological synapse between a T cell and an antigen presenting cell.  CD48 interaction with CD2 has been shown to promote lipid raft formation, T cell activation and the formation of caveolae for macrophages through cell signal transductionthe via GPI moieties.

# Clinical Significance
CD48 is being investigated amongst other markers in research on inflammation markers and therapies for HIV/AIDS.
CD52
CAMPATH-1 antigen, also known as cluster of differentiation 52 (CD52),  is a glycoprotein that in humans is encoded by the CD52 gene.
CD52 is present on the surface of mature lymphocytes, but not on the stem cells from which these lymphocytes were derived. It also is found on monocytes and dendritic cells. Further, it is found within the male genital tract and is present on the surface of mature sperm cells.
CD52 is a peptide of 12 amino acids, anchored to glycosylphosphatidylinositol (GPI). Since it is highly negatively charged and present on sperm cells and lymphocytes, it has been conjectured that its function is anti-adhesion, allowing cells to freely move around.
CD52 binds the ITIM (immunoreceptor tyrosine-based inhibitory motif)-bearing sialic acid-binding lectin SIGLEC10.

# Clinical significance
It is associated with certain types of lymphoma.
It is the protein targeted by alemtuzumab, a monoclonal antibody used for the treatment of chronic lymphocytic leukemia. A phase III trial into treatment of relapsing-remitting multiple sclerosis showed a reduction in relapse rate, but no statistically significant reduction in accumulated disability, when used as a first-line therapy. However, a sister study looking at patients in whom relapses had occurred despite treatment with interferon beta or glatiramer demonstrated reduction in both relapse rate and accumulated disability. 20% patients randomised to interferon beta 1a had "sustained accumulation of disability" compared with 13% in the alemtuzumab group. .
CD58
CD58, or lymphocyte function-associated antigen 3 (LFA-3), is a cell adhesion molecule expressed on Antigen Presenting Cells (APC), particularly macrophages.
It binds to CD2 (LFA-2)  on T cells and is important in strengthening the adhesion between the T cells and Professional Antigen Presenting Cells. This adhesion occurs as part of the transitory initial encounters between T cells and Antigen Presenting Cells before T cell activation, when  T cells are roaming the lymph nodes looking at the surface of APCs for peptide:MHC complexes the T-cell receptors are reactive to.
Polymorphisms in the CD58 gene are associated with increased risk for multiple sclerosis.. Genomic region containing the single-nucleotide polymorphism rs1335532, associated with high risk of multiple sclerosis, has enhancer properties and can significantly boost the CD58 promoter activity in lymphoblast cells. The protective (C) rs1335532 allele creates functional binding site for ASCL2 transcription factor, a target of the Wnt signaling pathway
CD59
CD59 glycoprotein, also known as MAC-inhibitory protein (MAC-IP), membrane inhibitor of reactive lysis (MIRL), or protectin,  is a protein that in humans is encoded by the CD59 gene. It belongs to the LY6/uPAR/alpha-neurotoxin protein family.
CD59 attaches to host cells via a glycophosphatidylinositol (GPI) anchor.  When complement activation leads to deposition of C5b678 on host cells, CD59 can prevent C9 from polymerizing and forming the complement membrane attack complex. It may also signal the cell to perform active measures such as endocytosis of the CD59-CD9 complex.
Mutations affecting GPI that reduce expression of CD59 and decay-accelerating factor on red blood cells result in paroxysmal nocturnal hemoglobinuria.
Viruses such as HIV, human cytomegalovirus and vaccinia incorporate host cell CD59 into their own viral envelope to prevent lysis by complement.
CD61
Integrin beta-3 (3) or CD61 is a protein that in humans is encoded by the ITGB3 gene.  CD61 is a cluster of differentiation found on thrombocytes.

# Structure and function
The ITGB3 protein product is the integrin beta chain beta 3. 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. Integrin beta 3 is found along with the alpha IIb chain in platelets. Integrins are known to participate in cell adhesion as well as cell-surface-mediated signaling.

# Role in endometriosis
Defectively expressed 3 integrin subunit has been correlated with presence of endometriosis, and has been suggested as a putative marker of this condition.

# Interactions
CD61 has been shown to interact with PTK2, ITGB3BP, TLN1 and CIB1.
CD63
CD63 antigen is a protein that in humans is encoded by the CD63 gene. CD63 is mainly associated with membranes of intracellular vesicles, although cell surface expression may be induced.

# Function
The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth, and motility.
This encoded protein is a cell surface glycoprotein that is known to complex with integrins. It may function as a blood platelet activation marker. Deficiency of this protein is associated with  Hermansky-Pudlak Syndrome . Also this gene has been associated with tumor progression. The use of alternate polyadenylation sites has been found for this gene. Alternative splicing results in multiple transcript variants encoding different proteins.

# Allergy diagnosis
CD63 is a good marker for flow cytometric quantification of in vitro activated basophils for diagnosis of IgE-mediated allergy. The test is commonly designated as basophil activation test (BAT).

# Research
Initially, deletion and point mutants were used to investigate the role of the C-terminus, which contains a putative lysosomal-targeting/internalisation motif (GYEVM). C-terminal mutants showed increased surface expression and decreased intracellular localisation relative to CD63Wt. Antibody induced internalisation was reduced in C-terminal deletion mutants and abolished in GA and YA mutants, showing the crucial role of these residues in internalisation.
CD63 is extensively and variably glycosylated and the EC2 region contain three potential N-linked glycosylation sites (N130, N150, and N172). Mutants N130A and N150A were similar to hCD63Wt with respect to intracellular localisation and internalisation. However, the hCD63N172A mutant showed a mainly cell surface localisation and low internalisation. Expression of a mutant lacking all three glycosylation sites was very unstable. It was speculated that the reduced internalisation of CD63N172A might be due to changes in its interaction with cell surface molecules. Immunoprecipitation experiments showed some evidence of a protein (100kDa) associating with CD63N172A, but this was not consistent. However, an association between CD63Wt and 2 integrin (CD18) was shown by co-internalisation of these proteins. Interactions with CD63 may therefore affect the trafficking and function of 2 integrins.
A recent investigation showed that expression of CD63 positively correlates with the invasiveness of ovarian cancer.
In cell biology, CD63 is often used as a marker for multivesicular bodies, which are enriched with CD63.

# Interactions
CD63 has been shown to interact with CD117 and CD82.
CD70
CD70 (Cluster of Differentiation 70) is a ligand for CD27.

# Clinical significance
The CD70 protein is expressed on highly activated lymphocytes (like in T- and B-cell lymphomas). It is therefore suggested that anti-CD70 antibodies might be a possible treatment for CD70 positive lymphomas as normal lymphocytes have low CD70 expression.

# Drug development
ARGX-110 is a CD70-specific antibody that is currently under investigation for the treatment of hematological malignancies. It is being developed by the Belgian company arGEN-X. In December 2013 a first part of a phase 1b trial was completed. In January 2014 a safety and efficacy phase of the study started.
Vorsetuzumab mafodotin is a CD70-targeted antibody-drug conjugate that started clinical trials for renal cell carcinoma.
CD74
HLA class II histocompatibility antigen gamma chain also known as HLA-DR antigens-associated invariant chain or  CD74 (Cluster of Differentiation 74), is a protein that in humans is encoded by the CD74 gene. The invariant chain (Abbreviated Ii) is a polypeptide involved in the formation and transport of MHC class II protein. The cell surface form of the invariant chain is known as CD74.

# Function
The nascent MHC class II protein in the rough ER binds a segment of the invariant chain (Ii; a trimer) in order to shape the peptide binding groove and prevent formation of a closed conformation.
The invariant chain also facilitates MHC class II's export from the ER in a vesicle. The signal for endosomal targeting resides in the cytoplasmic tail of the invariant chain. This fuses with a late endosome containing the endocytosed antigen proteins (from the exogenous pathway). Binding to Ii ensures that no antigen peptides from the endogenous pathway meant for MHC class I molecules  accidentally bind to the groove of MHC class II molecules. The Ii is then cleaved by cathepsin S (cathepsin L in cortical thymic epithelial cells), leaving only a small fragment called CLIP remaining bound to the groove of MHC class II molecules. The rest of the Ii is degraded. CLIP blocks peptide binding until HLA-DM interacts with MHC II, releasing CLIP and allowing other peptides to bind. In some cases, CLIP dissociates without any further molecular interactions, but in other cases the binding to the MHC is more stable.
The stable MHC class-II with antigen complex is then presented on the cell surface. Without CLIP, MHC class II aggregates, disassemble, and/or denature in the endosomes, and proper antigen presentation is impaired

# Clinical significance

## Cancer
Found on a number of cancer cell types. Possible cancer therapy target. See Milatuzumab#CD74

## Axial Spondyloarthritis
Autoantibodies against CD74 have been identified as a promising biomarkers in the early diagnosis of the autoimmune disease called axial spondyloarthritis (non-radiographic axial Spondyloarthritis and radiographic axial Spondyloarthritis / Ankylosing spondylitis). 

# Interactions
CD74 receptor interacts with the cytokine Macrophage migration inhibitory factor to mediate its proinflammatory functions.