CD81

CD81 (CD81 Molecule) is a Protein Coding gene. Diseases associated with CD81 include Immunodeficiency, Common Variable, 6 and Common Variable Immunodeficiency. Among its related pathways are Innate Immune System and B cell receptor signaling pathway (KEGG). Gene Ontology (GO) annotations related to this gene include MHC class II protein complex binding. An important paralog of this gene is CD9.

CD81 Molecule

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.

Activation of MAPK activity Source: UniProtKB
CD4-positive, alpha-beta T cell costimulation Source: UniProtKB
Cellular response to low-density lipoprotein particle stimulus Source: UniProtKB
Humoral immune response mediated by circulating immunoglobulin Source: UniProtKB
Immunological synapse formation Source: UniProtKB
Macrophage fusion Source: UniProtKB
Myoblast fusion involved in skeletal muscle regeneration Source: UniProtKB
Osteoclast fusion Source: UniProtKB
Positive regulation of 1-phosphatidylinositol 4-kinase activity Source: UniProtKB
Positive regulation of adaptive immune memory response Source: UniProtKB
Positive regulation of B cell proliferation Source: AgBase
Positive regulation of B cell receptor signaling pathway Source: UniProtKB
Positive regulation of CD4-positive, alpha-beta T cell proliferation Source: UniProtKB
Positive regulation of cell population proliferation Source: UniProtKB
Positive regulation of inflammatory response to antigenic stimulus Source: UniProtKB
Positive regulation of peptidyl-tyrosine phosphorylation Source: UniProtKB
Positive regulation of protein catabolic process in the vacuole Source: BHF-UCL
Positive regulation of protein exit from endoplasmic reticulum Source: UniProtKB
Positive regulation of receptor clustering Source: UniProtKB
Positive regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting Cell Source: UniProtKB
Positive regulation of T cell receptor signaling pathway Source: UniProtKB
Positive regulation of T-helper 2 cell cytokine production Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: BHF-UCL
Protein localization Source: UniProtKB
Protein localization to lysosome Source: BHF-UCL
Protein localization to plasma membrane Source: UniProtKB
Receptor internalization Source: UniProtKB
Receptor-mediated virion attachment to host cell Source: UniProtKB
Regulation of complement activation Source: Reactome
Regulation of immune response Source: Reactome
Regulation of macrophage migration Source: UniProtKB
Regulation of protein stability Source: BHF-UCL
Viral entry into host cell Source: UniProtKB

Cell membrane; Basolateral cell membrane. Associates with CLDN1 and the CLDN1-CD81 complex localizes to the basolateral cell membrane.

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.

Cytoplasmic: 1-12
Helical: 13-33
Extracellular: 34-63
Helical: 64-84
Cytoplasmic: 85-89
Helical: 90-112
Extracellular: 113-201
Helical: 202-224
Cytoplasmic: 225-236

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.