ID   CD81_CHLAE              Reviewed;         236 AA.
AC   O97703;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   03-AUG-2022, entry version 93.
DE   RecName: Full=CD81 antigen;
DE   AltName: CD_antigen=CD81;
GN   Name=CD81;
OS   Chlorocebus aethiops (Green monkey) (Cercopithecus aethiops).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC   Cercopithecidae; Cercopithecinae; Chlorocebus.
OX   NCBI_TaxID=9534;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Levy S., Kuo C.C.;
RT   "African green monkey CD81 cDNA.";
RL   Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Structural component of specialized membrane microdomains
CC       known as tetraspanin-enriched microdomains (TERMs), which act as
CC       platforms for receptor clustering and signaling. Essential for
CC       trafficking and compartmentalization of CD19 receptor on the surface of
CC       activated B cells. Upon initial encounter with microbial pathogens,
CC       enables the assembly of CD19-CR2/CD21 and B cell receptor (BCR)
CC       complexes at signaling TERMs, lowering the threshold dose of antigen
CC       required to trigger B cell clonal expansion and antibody production. In
CC       T cells, facilitates the localization of CD247/CD3 zeta at antigen-
CC       induced synapses with B cells, providing for costimulation and
CC       polarization toward T helper type 2 phenotype. Present in MHC class II
CC       compartments, may also play a role in antigen presentation (By
CC       similarity). Can act both as positive and negative regulator of
CC       homotypic or heterotypic cell-cell fusion processes. Positively
CC       regulates sperm-egg fusion and may be involved in acrosome reaction. In
CC       myoblasts, associates with CD9 and PTGFRN and inhibits myotube fusion
CC       during muscle regeneration (By similarity). In macrophages, associates
CC       with CD9 and beta-1 and beta-2 integrins, and prevents macrophage
CC       fusion into multinucleated giant cells specialized in ingesting
CC       complement-opsonized large particles (By similarity). Also prevents the
CC       fusion of mononuclear cell progenitors into osteoclasts in charge of
CC       bone resorption (By similarity). May regulate the compartmentalization
CC       of enzymatic activities. In T cells, defines the subcellular
CC       localization of dNTPase SAMHD1 and permits its degradation by the
CC       proteasome, thereby controlling intracellular dNTP levels (By
CC       similarity). Also involved in cell adhesion and motility. Positively
CC       regulates integrin-mediated adhesion of macrophages, particularly
CC       relevant for the inflammatory response in the lung (By similarity).
CC       {ECO:0000250|UniProtKB:P35762, ECO:0000250|UniProtKB:P60033}.
CC   -!- SUBUNIT: Homodimer. Part of a complex composed of CD19, CR2/CD21, CD81
CC       and IFITM1/CD225 in the membrane of mature B cells. Interacts (via the
CC       second extracellular domain) with CD19; this interaction is initiated
CC       early during biosynthesis in the ER and enables trafficking of only
CC       properly folded CD19. Part of a complex that includes MHC class II/HLA-
CC       DR molecules and IFITM1. Interacts with IFITM1 (By similarity).
CC       Interacts with IFITM2 and IFITM3 (By similarity). Part of integrin-
CC       tetraspanin complex composed of CD9, CD81, beta-1 and beta-2 integrins
CC       in the membrane of monocyte/macrophages. Interacts (via the second
CC       extracellular domain) with integrin ITGAV:ITGB3. Interacts with
CC       CD247/CD3 zeta, ICAM1 and CD9 at the immune synapse on T cell membrane
CC       (By similarity). Part of a GPCR-tetraspanin complex consisting at least
CC       of ADGRG1, CD81, possibly CD9, and GNA11 in which CD81 enhances the
CC       association of ADGRG1 with GNA11. Part of a complex composed of CD9,
CC       CD81, PTGFRN and IGSF8 (By similarity). Interacts directly with IGSF8.
CC       Interacts with CD53 and SCIMP. Interacts with SAMHD1 (via its C-
CC       terminus) (By similarity). Interacts with glypican GPC3 and with the
CC       transcriptional repressor HHEX; binding to GPC3 decreases the
CC       availability of free CD81 for binding to HHEX, resulting in nuclear
CC       translocation of HHEX and transcriptional repression (By similarity).
CC       Interacts with CLDN1. Interacts with CLDN6 and CLDN9 (By similarity).
CC       {ECO:0000250|UniProtKB:P35762, ECO:0000250|UniProtKB:P60033}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P35762};
CC       Multi-pass membrane protein {ECO:0000255}. Basolateral cell membrane
CC       {ECO:0000250|UniProtKB:P60033}; Multi-pass membrane protein
CC       {ECO:0000255}. Note=Associates with CLDN1 and the CLDN1-CD81 complex
CC       localizes to the basolateral cell membrane.
CC       {ECO:0000250|UniProtKB:P60033}.
CC   -!- DOMAIN: Binds cholesterol in a cavity lined by the transmembrane spans.
CC       {ECO:0000250|UniProtKB:P60033}.
CC   -!- PTM: Not glycosylated. {ECO:0000305}.
CC   -!- PTM: Likely constitutively palmitoylated at low levels. Protein
CC       palmitoylation is up-regulated upon coligation of BCR and CD9-C2R-CD81
CC       complexes in lipid rafts. {ECO:0000250|UniProtKB:P60033}.
CC   -!- SIMILARITY: Belongs to the tetraspanin (TM4SF) family. {ECO:0000305}.
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DR   EMBL; AF116599; AAD11439.1; -; mRNA.
DR   AlphaFoldDB; O97703; -.
DR   SMR; O97703; -.
DR   GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0001772; C:immunological synapse; ISS:UniProtKB.
DR   GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR   GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0097197; C:tetraspanin-enriched microdomain; ISS:UniProtKB.
DR   GO; GO:0015485; F:cholesterol binding; ISS:UniProtKB.
DR   GO; GO:0005178; F:integrin binding; ISS:UniProtKB.
DR   GO; GO:0035783; P:CD4-positive, alpha-beta T cell costimulation; ISS:UniProtKB.
DR   GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; ISS:UniProtKB.
DR   GO; GO:0002455; P:humoral immune response mediated by circulating immunoglobulin; ISS:UniProtKB.
DR   GO; GO:0001771; P:immunological synapse formation; ISS:UniProtKB.
DR   GO; GO:0034238; P:macrophage fusion; ISS:UniProtKB.
DR   GO; GO:0014905; P:myoblast fusion involved in skeletal muscle regeneration; ISS:UniProtKB.
DR   GO; GO:0072675; P:osteoclast fusion; ISS:UniProtKB.
DR   GO; GO:0043128; P:positive regulation of 1-phosphatidylinositol 4-kinase activity; ISS:UniProtKB.
DR   GO; GO:0050871; P:positive regulation of B cell activation; ISS:UniProtKB.
DR   GO; GO:0050861; P:positive regulation of B cell receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:2000563; P:positive regulation of CD4-positive, alpha-beta T cell proliferation; ISS:UniProtKB.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR   GO; GO:0002863; P:positive regulation of inflammatory response to antigenic stimulus; ISS:UniProtKB.
DR   GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR   GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR   GO; GO:0070863; P:positive regulation of protein exit from endoplasmic reticulum; ISS:UniProtKB.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; ISS:UniProtKB.
DR   GO; GO:2001190; P:positive regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell; ISS:UniProtKB.
DR   GO; GO:0050862; P:positive regulation of T cell receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:2000553; P:positive regulation of T-helper 2 cell cytokine production; ISS:UniProtKB.
DR   GO; GO:0008104; P:protein localization; ISS:UniProtKB.
DR   GO; GO:0072659; P:protein localization to plasma membrane; ISS:UniProtKB.
DR   GO; GO:0031623; P:receptor internalization; ISS:UniProtKB.
DR   GO; GO:1905521; P:regulation of macrophage migration; ISS:UniProtKB.
DR   Gene3D; 1.10.1450.10; -; 1.
DR   InterPro; IPR018499; Tetraspanin/Peripherin.
DR   InterPro; IPR000301; Tetraspanin_animals.
DR   InterPro; IPR018503; Tetraspanin_CS.
DR   InterPro; IPR008952; Tetraspanin_EC2_sf.
DR   PANTHER; PTHR19282; PTHR19282; 1.
DR   Pfam; PF00335; Tetraspanin; 1.
DR   PIRSF; PIRSF002419; Tetraspanin; 1.
DR   SUPFAM; SSF48652; SSF48652; 1.
DR   PROSITE; PS00421; TM4_1; 1.
PE   2: Evidence at transcript level;
KW   Adaptive immunity; Cell membrane; Disulfide bond; Immunity; Lipid-binding;
KW   Membrane; Transmembrane; Transmembrane helix.
FT   CHAIN           1..236
FT                   /note="CD81 antigen"
FT                   /id="PRO_0000219220"
FT   TOPO_DOM        1..12
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        13..33
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:P60033"
FT   TOPO_DOM        34..63
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        64..84
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:P60033"
FT   TOPO_DOM        85..89
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        90..112
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:P60033"
FT   TOPO_DOM        113..201
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        202..224
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:P60033"
FT   TOPO_DOM        225..236
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   BINDING         219
FT                   /ligand="cholesterol"
FT                   /ligand_id="ChEBI:CHEBI:16113"
FT                   /evidence="ECO:0000250|UniProtKB:P60033"
FT   SITE            116
FT                   /note="Important for interaction with integrin"
FT                   /evidence="ECO:0000250|UniProtKB:P60033"
FT   SITE            144
FT                   /note="Important for interaction with integrin"
FT                   /evidence="ECO:0000250|UniProtKB:P60033"
FT   SITE            148
FT                   /note="Important for interaction with integrin"
FT                   /evidence="ECO:0000250|UniProtKB:P60033"
FT   DISULFID        156..190
FT                   /evidence="ECO:0000250|UniProtKB:P60033"
FT   DISULFID        157..175
FT                   /evidence="ECO:0000250|UniProtKB:P60033"
SQ   SEQUENCE   236 AA;  25758 MW;  E07A8EC2C7637A4A CRC64;
     MGVEGCTKCI KYLLFVFNFV FWLAGGVILG VALWLRHDPQ TTNLLYLELG DKPAPNTFYV
     GIYILIAVGA VMMFVGFLGC YGAIQESQCL LGTFFTCLVI LFACEVAAGI WGFVNKDQIA
     KDVKQFYDQA LQQAVVDDDA NNAKAVVKTF HETLDCCGSS TLAALTTSVL KNNLCPSGSN
     IISNLLKKDC HQKIDELFSG KLYLIGIAAI VVAVIMIFEM ILSMVLCCGI RNSSVY