CD81 molecule, also known as CD81 (Cluster of Differentiation 81), is a protein which in humans is encoded by the CD81 gene. [5] [6] It is also known as 26 kDa cell surface protein, TAPA-1 (Target of the Antiproliferative Antibody 1), and Tetraspanin-28 (Tspan-28).
The gene is located on the plus strand of the short arm of chromosome 11 (11p15.5). It is 20,103 bases in length and encodes a protein of 236 amino acids (predicted molecular weight 25.809 kDa). [6]
The protein does not appear to be post translationally modified and has four transmembrane domains. Both the N-terminus and C-terminus lie on the intracellular side of the membrane.
The gene is expressed in hemopoietic, endothelial, and epithelial cells. It is absent from erythrocytes, platelets, and neutrophils.
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. This protein appears to promote muscle cell fusion and support myotube maintenance. Also it may be involved in signal transduction. This gene is localized in the tumor-suppressor gene region and thus it is a candidate gene for malignancies. [5]
The tetraspanin family includes CD9, CD37, CD53, CD63, CD81 (this protein), CD82 and CD151.
CD81 interacts directly with immunoglobulin superfamily member 8 (IGSF8, [7] CD316) and CD36. It forms a signal transduction complex with CD19, CD21 and Leu-13 (CD225) on the surface of the B cell. [8] On T cells CD81 associates with CD4 and CD8 and provides a costimulatory signal with CD3. [8]
This protein plays a critical role in Hepatitis C attachment and/or cell entry by interacting with virus' E1/E2 glycoproteins heterodimer. [9] The large extracellular loop of CD81 binds the hepatitis E2 glycoprotein dimer. HCV-E2 and CD81 binding Kd is 1.8 nM. HCV-E2 engaged CD81 is only 30% internalized after 12hr, suggesting CD81 may be primarily an attachment receptor for HCV. [10]
It also appears to play a role in liver invasion by Plasmodium species. [11] CD81 is required for Plasmodium vivax sporozoite entry into human hepatocytes and for Plasmodium yoelii sporozoite entry into murine hepatocytes. [12]
HIV gag proteins use tetraspanin enriched microdomains (containing minimally CD81, CD82, CD63) as a platform for virion assembly and release. Purified HIV produced by MOLT\HIV cells contains CD81. Anti-CD81 antibodies downregulate HIV production 3 fold, however the CD81 protein free virus is more infectious. [13] Engagement of CD81 lowers the signaling threshold required to trigger T-Cell\CD3 mediated proviral DNA in CD4+ T cells. [14]
CD81 appears to play a role in the pathogenesis of influenza. [15]
CD81 has been shown to interact with TSPAN4, [16] CD19, [17] [18] [19] CD9, [19] [20] PTGFRN, [21] [22] CD117 [23] and CD29. [24] [25]
Benzyl salicylate [26] and terfenadine [27] have been shown to bind to CD81.
Tetraspanins are a family of membrane proteins found in all multicellular eukaryotes also referred to as the transmembrane 4 superfamily (TM4SF) proteins. These proteins have four transmembrane alpha-helices and two extracellular domains, one short and one longer, typically 100 amino acid residues. Although several protein families have four transmembrane alpha-helices, tetraspanins are defined by conserved amino acid sequences including four or more cysteine residues in the EC2 domain, with two in a highly conserved 'CCG' motif. Tetraspanins are often thought to act as scaffolding proteins, anchoring multiple proteins to one area of the cell membrane.
Complement receptor type 2 (CR2), also known as complement C3d receptor, Epstein-Barr virus receptor, and CD21, is a protein that in humans is encoded by the CR2 gene.
B-lymphocyte antigen CD19, also known as CD19 molecule, B-Lymphocyte Surface Antigen B4, T-Cell Surface Antigen Leu-12 and CVID3 is a transmembrane protein that in humans is encoded by the gene CD19. In humans, CD19 is expressed in all B lineage cells. Contrary to some early doubts, human plasma cells do express CD19, as confirmed by others. CD19 plays two major roles in human B cells: on the one hand, it acts as an adaptor protein to recruit cytoplasmic signaling proteins to the membrane; on the other, it works within the CD19/CD21 complex to decrease the threshold for B cell receptor signaling pathways. Due to its presence on all B cells, it is a biomarker for B lymphocyte development, lymphoma diagnosis and can be utilized as a target for leukemia immunotherapies.
Integrin beta-1 (ITGB1), also known as CD29, is a cell surface receptor that in humans is encoded by the ITGB1 gene. This integrin associates with integrin alpha 1 and integrin alpha 2 to form integrin complexes which function as collagen receptors. It also forms dimers with integrin alpha 3 to form integrin receptors for netrin 1 and reelin. These and other integrin beta 1 complexes have been historically known as very late activation (VLA) antigens.
CD49d is an integrin alpha subunit. It makes up half of the α4β1 lymphocyte homing receptor.
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 α3β1 integrin duplex that plays a role in neural migration and corticogenesis, acted upon by such factors as netrin-1 and reelin.
CD9 is a gene encoding a protein that is a member of the transmembrane 4 superfamily also known as the tetraspanin family. It is a cell surface glycoprotein that consists of four transmembrane regions and has two extracellular loops that contain disulfide bonds which are conserved throughout the tetraspanin family. Also containing distinct palmitoylation sites that allows CD9 to interact with lipids and other proteins.
Leukocyte antigen CD37 is a protein that in humans is encoded by the CD37 gene.
Leukocyte surface antigen CD53 is a protein that in humans is encoded by the CD53 gene.
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.
CD151 molecule, also known as CD151, is a human gene.
CD82, or KAI1, is a human protein encoded by the CD82 gene.
Junctional adhesion molecule C is a protein that in humans is encoded by the JAM3 gene.
Tetraspanin-7 is a protein that in humans is encoded by the TSPAN7 gene.
Uroplakin-1a (UP1a) is a protein that in humans is encoded by the UPK1A gene.
Tetraspanin-4 is a protein that in humans is encoded by the TSPAN4 gene.
Prostaglandin F2 receptor negative regulator is a protein that in humans is encoded by the PTGFRN gene. PTGFRN has also been designated as CD315.
Immunoglobulin superfamily member 8 is a protein that in humans is encoded by the IGSF8 gene. IGSF8 has also been designated as CD316.
Tetraspanin-8 is a protein that in humans is encoded by the TSPAN8 gene.
Tetraspanin-6 is a protein that in humans is encoded by the TSPAN6 gene.
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.
