Alt. symbols: TAPA1 | TAPA-1 | TSPAN28

Approved name: CD81 molecule
Alt. names: CD81 antigen (target of antiproliferative antibody 1)

Location: 11p15.5: 2376177 - 2397802 (+)
Gene type: protein_coding, 17 transcripts.

Scores: LoFtool: 0.219000 | pLI: 0.95052160 | LOEUF: 0.381

HGNC: 1701

NCBI: 975, RefSeq: NG_023386.1

Ensembl: ENSG00000110651.13

LRG_142 | Status: public

OMIM: 186845

Expression | ProteinAtlas

CD81 (also known as TAPA-1) is a member of the transmembrane 4 superfamily, which is known as the tetraspanin family. CD81 is a cell surface glycoprotein that complexes with integrins and mediates signal transduction events important for the regulation of cell development, activation, growth and motility. CD81 is a structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signalling. It is 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 signalling 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). As it is present in MHC class II compartments, it may also play a role in antigen presentation (PubMed:8409388, PubMed:8766544). 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). In T cells, defines the subcellular localization of dNTPase SAMHD1 and permits its degradation by the proteasome, thereby controlling intracellular dNTP levels (PubMed:28871089). CD81 is required for Plasmodium vivax sporozoite entry into human hepatocytes and it appears to play a role in the pathogenesis of influenza. It can act both as positive and negative regulator of homotypic or heterotypic cell-cell fusion processes (Sources: UniProtKB, RefSeq).

To date, only one familial case with mutations in this gene has been reported in the literature (van Zelm M. et al., JCI 2010). The authors reported a 6-year-old girl with an antibody deficiency syndrome and glomerulonephritis, born to consanguineous parents of Moroccan descent. She suffered from recurrent respiratory tract infections since the age of 2 and developed an acute glomerulonephritis along with gross hematuria and a pruritic rash at the age of 3.5 years. She also presented leukocytocl astic IgA vasculitis, recurrent episodes of thrombocytopenia associated with antiplatelet antibodies, low IgG levels, but normal number of B-, T- and NK-cells. She was initially diagnosed with Henoch-Schönlein purpura. The patient had a homozygous EX6+1G>A mutation in CD81. The authors observed that the mutation completely disrupts the splice donor site of exon 6, and the mutated allele only produced alternative splice products, which resulted in complete lack of CD81 expression on blood leukocytes. This rare form of immunodeficiency is known as common variable immunodeficiency 6 [MIM:613496]. [Load More]