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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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 acts a 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. Ref.7 Ref.8 Ref.9
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	Defects in CD81 are the cause of immunodeficiency common variable type 6 (CVID6) [MIM:613496]; also called antibody deficiency due to CD81 defect. CVID6 is 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. Ref.10
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. Source: UniProtKB cell proliferation Traceable author statement. Source: ProtInc phosphatidylinositol biosynthetic process Inferred from direct assay. Source: UniProtKB positive regulation of 1-phosphatidylinositol 4-kinase activity Inferred from direct assay. Source: UniProtKB positive regulation of cell proliferation Inferred from direct assay. Source: UniProtKB positive regulation of peptidyl-tyrosine phosphorylation Inferred from direct assay. Source: UniProtKB protein localization Inferred from direct assay. Source: UniProtKB regulation of immune response Traceable author statement. Source: Reactome virion attachment, binding of host cell surface receptor Traceable author statement. Source: UniProtKB
Cellular component	integral to plasma membrane Inferred from direct assay. Source: UniProtKB
Molecular function	protein binding Inferred from physical interaction Ref.12. Source: UniProtKB
Complete GO annotation...

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

Helix

163 – 165

3

Helix

166 – 171

6

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: 1695320] [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: 16554811] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[6]	"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: 1860863] [Abstract] Cited for: TOPOLOGY.
[7]	"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: 11504738] [Abstract] Cited for: INTERACTION WITH IGSF8.
[8]	"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: 12970454] [Abstract] Cited for: INTERACTION WITH HCV E1/E2 ENVELOPE HETERODIMER.
[9]	"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: 12913001] [Abstract] Cited for: INTERACTION WITH HCV E1/E2 ENVELOPE HETERODIMER.
[10]	"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: 20237408] [Abstract] Cited for: INVOLVEMENT IN CVID6.
[11]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]	"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: 21930792] [Abstract] Cited for: INTERACTION WITH CD53 AND SCIMP.
[13]	"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: 11226150] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 113-202.
[14]	"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: 12437138] [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.

IPI

IPI00000190.

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...

Protein-protein interaction databases

IntAct

P60033. 6 interactions.

MINT

MINT-5001104.

STRING

P60033.

PTM databases

PhosphoSite

P60033.

Polymorphism databases

DMDM

38503376.

Proteomic databases

PRIDE

P60033.

Protocols and materials databases

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.

H-InvDB

HIX0009363.

HGNC

HGNC:1701. CD81.

HPA

CAB002507.
HPA007234.

MIM

186845. gene.
613496. phenotype.

neXtProt

NX_P60033.

Orphanet

77303. Common variable immunodeficiency due to an intrinsic B cell defect.

PharmGKB

PA26240.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG11124.

GeneTree

ENSGT00590000082836.

HOVERGEN

HBG002324.

OrthoDB

EOG4X97J1.

PhylomeDB

P60033.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P60033.

Bgee

P60033.

CleanEx

HS_CD81.

Genevestigator

P60033.

GermOnline

ENSG00000110651. Homo sapiens.

Family and domain databases

InterPro

IPR023396. CD81_extracellular.
IPR018499. Tetraspanin.
IPR018503. Tetraspanin_CS.
IPR008952. Tetraspanin_EC2.
IPR000301. Tetraspanin_subgr.
[Graphical view]

Gene3D

G3DSA:1.10.1450.10. G3DSA:1.10.1450.10. 1 hit.

KO

K06508.

Pfam

PF00335. Tetraspannin. 1 hit.
[Graphical view]

PRINTS

PR00259. TMFOUR.

SUPFAM

SSF48652. Tetraspanin. 1 hit.

PROSITE

PS00421. TM4_1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

4090.

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:	January 25, 2012
This is version 83 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.