P60033 (CD81_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
CD81 antigen

Alternative name(s):
26 kDa cell surface protein TAPA-1
Target of the antiproliferative antibody 1
Tetraspanin-28
Short name=Tspan-28
CD_antigen=CD81

Gene names

Name:	CD81
Synonyms:	TAPA1, TSPAN28

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	236 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May play an important role in the regulation of lymphoma cell growth. Interacts with a 16-kDa Leu-13 protein to form a complex possibly involved in signal transduction. May act as the viral receptor for HCV.
Subunit structure	Plays a critical role in HCV attachment and/or cell entry by interacting with HCV E1/E2 glycoproteins heterodimer. Interacts directly with IGSF8. Interacts with CD53 and SCIMP. Interacts with IFITM1, IFITM2 and IFITM3. Part of a GPCR-tetraspanin complex consisting at least of GPR56, CD81, eventually CD9, and GNA11 in which CD81 is enhancing the association of GPR56 with GNA11. Ref.6 Ref.8 Ref.9 Ref.10 Ref.11 Ref.14
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Hematolymphoid, neuroectodermal and mesenchymal tumor cell lines.
Post-translational modification	Not glycosylated Probable.
Involvement in disease	Immunodeficiency, common variable, 6 (CVID6) [MIM:613496]: 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12
Sequence similarities	Belongs to the tetraspanin (TM4SF) family.

Ontologies

Keywords
Biological process	Host-virus interaction
Cellular component	Membrane
Domain	Transmembrane Transmembrane helix
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of MAPK activity Inferred from direct assay PubMed 14676841. Source: UniProtKB cell proliferation Traceable author statement Ref.1. Source: ProtInc phosphatidylinositol biosynthetic process Inferred from direct assay PubMed 14676841. Source: UniProtKB phosphatidylinositol metabolic process Inferred from direct assay PubMed 14676841. Source: UniProtKB positive regulation of 1-phosphatidylinositol 4-kinase activity Inferred from direct assay PubMed 14676841. Source: UniProtKB positive regulation of cell proliferation Inferred from direct assay PubMed 14676841. Source: UniProtKB positive regulation of peptidyl-tyrosine phosphorylation Inferred from direct assay PubMed 14676841. Source: UniProtKB protein localization Inferred from direct assay PubMed 14676841. Source: UniProtKB receptor-mediated virion attachment to host cell Traceable author statement PubMed 14676841. Source: UniProtKB regulation of immune response Traceable author statement. Source: Reactome viral entry into host cell Traceable author statement PubMed 14676841. Source: UniProtKB
Cellular_component	extracellular vesicular exosome Inferred from direct assay PubMed 19056867PubMed 19199708. Source: UniProt immunological synapse Inferred from direct assay Ref.14. Source: UniProtKB integral component of plasma membrane Inferred from direct assay PubMed 14676841. Source: UniProtKB plasma membrane Traceable author statement. Source: Reactome
Molecular_function	MHC class II protein complex binding Inferred from direct assay PubMed 20458337. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
	P27958	7	EBI-712921,EBI-6904269	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 236

236

CD81 antigen

PRO_0000219221

Regions

Topological domain

1 – 12

12

Cytoplasmic Potential

Transmembrane

13 – 33

21

Helical; Potential

Topological domain

34 – 63

30

Extracellular Potential

Transmembrane

64 – 84

21

Helical; Potential

Topological domain

85 – 89

5

Cytoplasmic Potential

Transmembrane

90 – 112

23

Helical; Potential

Topological domain

113 – 201

89

Extracellular Potential

Transmembrane

202 – 224

23

Helical; Potential

Topological domain

225 – 236

12

Cytoplasmic Potential

Amino acid modifications

Disulfide bond

156 ↔ 190

Disulfide bond

157 ↔ 175

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

236

Helix Strand Turn

Details...

Helix

116 – 136

21

Helix

141 – 154

14

Beta strand

158 – 160

3

Helix

163 – 165

3

Helix

166 – 171

6

Helix

172 – 174

3

Helix

181 – 185

5

Helix

190 – 199

10

Sequences

	Sequence		Length	Mass (Da)
	P60033 [UniParc]. Last modified November 21, 2003. Version 1. Checksum: EB9BD7671AC91B4A	FASTA	236	25,809
	10 20 30 40 50 60 MGVEGCTKCI KYLLFVFNFV FWLAGGVILG VALWLRHDPQ TTNLLYLELG DKPAPNTFYV 70 80 90 100 110 120 GIYILIAVGA VMMFVGFLGC YGAIQESQCL LGTFFTCLVI LFACEVAAGI WGFVNKDQIA 130 140 150 160 170 180 KDVKQFYDQA LQQAVVDDDA NNAKAVVKTF HETLDCCGSS TLTALTTSVL KNNLCPSGSN 190 200 210 220 230 IISNLFKEDC HQKIDDLFSG KLYLIGIAAI VVAVIMIFEM ILSMVLCCGI RNSSVY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"TAPA-1, the target of an antiproliferative antibody, defines a new family of transmembrane proteins." Oren R., Takahashi S., Doss C., Levy R., Levy S. Mol. Cell. Biol. 10:4007-4015(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B., Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O., Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I., Nickerson D.A. Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[6]	"TAPA-1, the target of an antiproliferative antibody, is associated on the cell surface with the Leu-13 antigen." Takahashi S., Doss C., Levy S., Levy R. J. Immunol. 145:2207-2213(1990) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH IFITM1.
[7]	"Structure and membrane topology of TAPA-1." Levy S., Nguyen V.Q., Andria M.L., Takahashi S. J. Biol. Chem. 266:14597-14602(1991) [PubMed] [Europe PMC] [Abstract] Cited for: TOPOLOGY.
[8]	"EWI-2 is a major CD9 and CD81 partner and member of a novel Ig protein subfamily." Stipp C.S., Kolesnikova T.V., Hemler M.E. J. Biol. Chem. 276:40545-40554(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH IGSF8.
[9]	"CD81-dependent binding of hepatitis C virus E1E2 heterodimers." Cocquerel L., Kuo C.-C., Dubuisson J., Levy S. J. Virol. 77:10677-10683(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HCV E1/E2 ENVELOPE HETERODIMER.
[10]	"Cell entry of hepatitis C virus requires a set of co-receptors that include the CD81 tetraspanin and the SR-B1 scavenger receptor." Bartosch B., Vitelli A., Granier C., Goujon C., Dubuisson J., Pascale S., Scarselli E., Cortese R., Nicosia A., Cosset F.-L. J. Biol. Chem. 278:41624-41630(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HCV E1/E2 ENVELOPE HETERODIMER.
[11]	"Dynamic regulation of a GPCR-tetraspanin-G protein complex on intact cells: central role of CD81 in facilitating GPR56-Galpha q/11 association." Little K.D., Hemler M.E., Stipp C.S. Mol. Biol. Cell 15:2375-2387(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GRP56 AND GNA11.
[12]	"CD81 gene defect in humans disrupts CD19 complex formation and leads to antibody deficiency." van Zelm M.C., Smet J., Adams B., Mascart F., Schandene L., Janssen F., Ferster A., Kuo C.-C., Levy S., van Dongen J.J.M., van der Burg M. J. Clin. Invest. 120:1265-1274(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN CVID6.
[13]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]	"SCIMP, a transmembrane adapter protein involved in major histocompatibility complex class II signaling." Draber P., Vonkova I., Stepanek O., Hrdinka M., Kucova M., Skopcova T., Otahal P., Angelisova P., Horejsi V., Yeung M., Weiss A., Brdicka T. Mol. Cell. Biol. 31:4550-4562(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CD53 AND SCIMP.
[15]	"CD81 extracellular domain 3D structure: insight into the tetraspanin superfamily structural motifs." Kitadokoro K., Bordo D., Galli G., Petracca R., Falugi F., Abrignani S., Grandi G., Bolognesi M. EMBO J. 20:12-18(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 113-202.
[16]	"Subunit association and conformational flexibility in the head subdomain of human CD81 large extracellular loop." Kitadokoro K., Ponassi M., Galli G., Petracca R., Falugi F., Grandi G., Bolognesi M. Biol. Chem. 383:1447-1452(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 113-201.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M33680 mRNA. Translation: AAA36663.1.
BT019507 mRNA. Translation: AAV38314.1.
BT019508 mRNA. Translation: AAV38315.1.
EF064749 Genomic DNA. Translation: ABK41932.1.
AC129929 Genomic DNA. No translation available.
AC124057 Genomic DNA. No translation available.
BC002978 mRNA. Translation: AAH02978.1.
BC093047 mRNA. Translation: AAH93047.1.

PIR

A35649.

RefSeq

NP_004347.1. NM_004356.3.

UniGene

Hs.54457.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1G8Q	X-ray	1.60	A/B	113-201	[»]
1IV5	X-ray	2.60	A/B	113-201	[»]
2AVZ	model	-	A	1-236	[»]

ProteinModelPortal

P60033.

SMR

P60033. Positions 113-201.

ModBase

Search...

MobiDB

Search...

Protein-protein interaction databases

BioGrid

107413. 198 interactions.

IntAct

P60033. 10 interactions.

MINT

MINT-5001104.

STRING

9606.ENSP00000263645.

Chemistry

ChEMBL

CHEMBL1075180.

Protein family/group databases

TCDB

8.A.40.1.1. the tetraspanin (tetraspanin) family.

PTM databases

PhosphoSite

P60033.

Polymorphism databases

DMDM

38503376.

Proteomic databases

PaxDb

P60033.

PRIDE

P60033.

Protocols and materials databases

DNASU

975.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000263645; ENSP00000263645; ENSG00000110651.

GeneID

975.

KEGG

hsa:975.

UCSC

uc001lwf.1. human.

Organism-specific databases

CTD

975.

GeneCards

GC11P002397.

HGNC

HGNC:1701. CD81.

HPA

CAB002507.
HPA007234.

MIM

186845. gene.
613496. phenotype.

neXtProt

NX_P60033.

Orphanet

1572. Common variable immunodeficiency.

PharmGKB

PA26240.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG305712.

HOGENOM

HOG000230651.

HOVERGEN

HBG002324.

KO

K06508.

PhylomeDB

P60033.

TreeFam

TF352895.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

SignaLink

P60033.

Gene expression databases

ArrayExpress

P60033.

Bgee

P60033.

CleanEx

HS_CD81.

Genevestigator

P60033.

Family and domain databases

InterPro

IPR000301. Tetraspanin.
IPR018499. Tetraspanin/Peripherin.
IPR018503. Tetraspanin_CS.
IPR008952. Tetraspanin_EC2.
[Graphical view]

Pfam

PF00335. Tetraspannin. 1 hit.
[Graphical view]

PIRSF

PIRSF002419. Tetraspanin. 1 hit.

PRINTS

PR00259. TMFOUR.

SUPFAM

SSF48652. SSF48652. 1 hit.

PROSITE

PS00421. TM4_1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

CD81. human.

EvolutionaryTrace

P60033.

GeneWiki

CD81.

GenomeRNAi

975.

NextBio

4090.

PRO

P60033.

SOURCE

Search...

Entry information

Entry name

CD81_HUMAN

Accession

Primary (citable) accession number: P60033
Secondary accession number(s): P18582, Q5U0J6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 21, 2003
Last sequence update:	November 21, 2003
Last modified:	April 16, 2014
This is version 107 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.