CD81

Domain

Binds cholesterol in a cavity lined by the transmembrane spans.

Function

Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling. Essential for trafficking and compartmentalization of CD19 receptor on the surface of activated B cells (PubMed:20237408, PubMed:27881302, PubMed:16449649). Upon initial encounter with microbial pathogens, enables the assembly of CD19-CR2/CD21 and B cell receptor (BCR) complexes at signaling TERMs, lowering the threshold dose of antigen required to trigger B cell clonal expansion and antibody production (PubMed:15161911, PubMed:20237408). In T cells, facilitates the localization of CD247/CD3 zeta at antigen-induced synapses with B cells, providing for costimulation and polarization toward T helper type 2 phenotype (PubMed:22307619, PubMed:23858057, PubMed:8766544). Present in MHC class II compartments, may also play a role in antigen presentation (PubMed:8409388, PubMed:8766544). Can act both as positive and negative regulator of homotypic or heterotypic cell-cell fusion processes. Positively regulates sperm-egg fusion and may be involved in acrosome reaction (By similarity). In myoblasts, associates with CD9 and PTGFRN and inhibits myotube fusion during muscle regeneration (By similarity). In macrophages, associates with CD9 and beta-1 and beta-2 integrins, and prevents macrophage fusion into multinucleated giant cells specialized in ingesting complement-opsonized large particles (PubMed:12796480). Also prevents the fusion of mononuclear cell progenitors into osteoclasts in charge of bone resorption (By similarity). May regulate the compartmentalization of enzymatic activities. In T cells, defines the subcellular localization of dNTPase SAMHD1 and permits its degradation by the proteasome, thereby controlling intracellular dNTP levels (PubMed:28871089). Also involved in cell adhesion and motility. Positively regulates integrin-mediated adhesion of macrophages, particularly relevant for the inflammatory response in the lung (By similarity).

(Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes. Association with CLDN1 and the CLDN1-CD81 receptor complex is essential for HCV entry into host cell.

(Microbial infection) Involved in SAMHD1-dependent restriction of HIV-1 replication. May support early replication of both R5- and X4-tropic HIV-1 viruses in T cells, likely via proteasome-dependent degradation of SAMHD1.

(Microbial infection) Specifically required for Plasmodium falciparum infectivity of hepatocytes, controlling sporozoite entry into hepatocytes via the parasitophorous vacuole and subsequent parasite differentiation to exoerythrocytic forms.

Involvement in disease

Immunodeficiency, common variable, 6

CVID6

A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Not glycosylated.

Likely constitutively palmitoylated at low levels. Protein palmitoylation is up-regulated upon coligation of BCR and CD9-C2R-CD81 complexes in lipid rafts.

Sequence similarities

Belongs to the tetraspanin (TM4SF) family.

Tissue specificity

Expressed on B cells (at protein level) (PubMed:20237408). Expressed in hepatocytes (at protein level) (PubMed:12483205). Expressed in monocytes/macrophages (at protein level) (PubMed:12796480). Expressed on both naive and memory CD4-positive T cells (at protein level) (PubMed:22307619).

Cellular localization

• Cell membrane
• Multi-pass membrane protein
• Basolateral cell membrane
• Multi-pass membrane protein
• Associates with CLDN1 and the CLDN1-CD81 complex localizes to the basolateral cell membrane.

Alternative names

• CD81 antigen
• 26 kDa cell surface protein TAPA-1
• Target of the antiproliferative antibody 1
• Tetraspanin-28
• Tspan-28
• CD81
• TSPAN28
• TAPA1

Database links

• entrezGene:975
• omim:186845
• swissprot:P60033

Target type

Proteins

Primary research area

Immunology & Infectious Disease

Other research areas

• Oncology

Molecular weight

25809Da