CD81_SAGOE
ID CD81_SAGOE Reviewed; 236 AA.
AC Q9N0J9;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 91.
DE RecName: Full=CD81 protein;
DE AltName: CD_antigen=CD81;
GN Name=CD81;
OS Saguinus oedipus (Cotton-top tamarin).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Platyrrhini; Cebidae;
OC Callitrichinae; Saguinus.
OX NCBI_TaxID=9490;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=10846074; DOI=10.1128/jvi.74.13.5933-5938.2000;
RA Meola A., Sbardellati A., Bruni E.B., Cerretani M., Pezzanera M.,
RA Ceccacci A., Vitelli A., Levy S., Nicosia A., Traboni C., McKeating J.,
RA Scarselli E.;
RT "Binding of hepatitis C virus E2 glycoprotein to CD81 does not correlate
RT with species permissiveness to infection.";
RL J. Virol. 74:5933-5938(2000).
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; AJ250197; CAB89875.1; -; mRNA.
DR PDB; 7MWS; X-ray; 1.80 A; A/B=112-202.
DR PDB; 7MWX; X-ray; 3.32 A; D/H=113-202.
DR PDBsum; 7MWS; -.
DR PDBsum; 7MWX; -.
DR AlphaFoldDB; Q9N0J9; -.
DR SMR; Q9N0J9; -.
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 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Cell membrane; Disulfide bond; Immunity;
KW Lipid-binding; Membrane; Transmembrane; Transmembrane helix.
FT CHAIN 1..236
FT /note="CD81 protein"
FT /id="PRO_0000219225"
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"
FT HELIX 116..135
FT /evidence="ECO:0007829|PDB:7MWS"
FT STRAND 139..141
FT /evidence="ECO:0007829|PDB:7MWS"
FT HELIX 143..154
FT /evidence="ECO:0007829|PDB:7MWS"
FT HELIX 160..165
FT /evidence="ECO:0007829|PDB:7MWS"
FT HELIX 166..171
FT /evidence="ECO:0007829|PDB:7MWS"
FT HELIX 181..186
FT /evidence="ECO:0007829|PDB:7MWS"
FT HELIX 190..199
FT /evidence="ECO:0007829|PDB:7MWS"
SQ SEQUENCE 236 AA; 25813 MW; 80DC2FAD2824D96E CRC64;
MGVEGCTKCI KYLLFVFNFV FWLAGGVILG VALWLRHDPQ TTNLLYLELG DKPAPNTFYV
GIYILIAVGA VMMFVGFLGC YGAIQESQCL LGTFFTCLVI LFACEVAAGI WGFVNKDQIA
KDVKQFYDQA LQQAVVDDDA NNAKAVVKTF HETLNCCGSS TLSALTTSML KNNLCPSGSS
IISNLFKEDC HQKIDELFSG KLYLIGIAAI VVAVIMIFEM ILSMVLCCGI RNSSVY
