CD81

CD81 molecule, also known as CD81 (Cluster of Differentiation 81), is a is_associated_with::protein which in humans is encoded by the CD81 is_associated_with::gene. It is also known as 26 kDa cell surface protein, Target of the antiproliferative antibody 1 (TAPA-1) and Tetraspanin-28 (Tspan-28).

Gene
The gene is located on the Watson (plus) strand of the short arm of is_associated_with::chromosome 11 (11p15.5). It is 20,103 bases in length and encodes a protein of 236 is_associated_with::amino acids (predicted molecular weight 25.809 kDa).

The protein does not appear to be post translationally modified and has four transmembrane domains. Both the is_associated_with::N-terminus and is_associated_with::C-terminus lie on the intracellular side of the membrane.

The gene is expressed in is_associated_with::hemopoietic, is_associated_with::endothelial and is_associated_with::epithelial cells. It is absent from is_associated_with::erythrocytes, is_associated_with::platelets and is_associated_with::neutrophils.

Function
The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the is_associated_with::tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four is_associated_with::hydrophobic domains. The proteins mediate is_associated_with::signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface is_associated_with::glycoprotein that is known to complex with integrins. This protein appears to promote muscle cell fusion and support is_associated_with::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.

The tetraspanin family includes is_associated_with::CD9, is_associated_with::CD37, is_associated_with::CD53, is_associated_with::CD63, CD81 (this protein), is_associated_with::CD82 and is_associated_with::CD151.

CD81 interacts directly with immunoglobulin superfamily member 8 (is_associated_with::IGSF8, is_associated_with::CD316) and is_associated_with::CD36. It forms a signal transduction complex with is_associated_with::CD19, is_associated_with::CD21 and Leu-13 (CD225) on the surface of the is_associated_with::B cell. On is_associated_with::T cells CD81 associates with is_associated_with::CD4 and is_associated_with::CD8 and provides a costimulatory signal with CD3.

Clinical significance
This protein plays a critical role in is_associated_with::Hepatitis C attachment and/or cell entry by interacting with virus' E1/E2 glycoproteins heterodimer. The large extracellular loop(LEL) 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.

It also appears to play a role in is_associated_with::liver invasion by is_associated_with::Plasmodium species. CD81 is required for is_associated_with::Plasmodium vivax sporozoite entry into human hepatocytes and for is_associated_with::Plasmodium yoelii sporozoite entry into murine hepatocytes.

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. Engagement of CD81 lowers the signaling threshold required to trigger T-Cell\CD3 mediated proviral DNA in CD4+ T cells.

CD81 appears to play a role in the pathogeneis of influenza.

Interactions
CD81 has been shown to interact with is_associated_with::TSPAN4, is_associated_with::CD19,  is_associated_with::CD9, is_associated_with::PTGFRN,  is_associated_with::CD117 and is_associated_with::CD29.

Ligands
is_associated_with::Benzyl salicylate and is_associated_with::terfenadine have been shown to bind to CD81.