Q969P0 (IGSF8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Immunoglobulin superfamily member 8
Short name=IgSF8

Alternative name(s):
CD81 partner 3
Glu-Trp-Ile EWI motif-containing protein 2
Short name=EWI-2
Keratinocytes-associated transmembrane protein 4
Short name=KCT-4
LIR-D1
Prostaglandin regulatory-like protein
Short name=PGRL
CD_antigen=CD316

Gene names

Name:	IGSF8
Synonyms:	CD81P3, EWI2, KCT4

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 › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	613 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May play a key role in diverse functions ascribed to CD81 and CD9 such as oocytes fertilization or hepatitis C virus function. May regulate proliferation and differentiation of keratinocytes. May be a negative regulator of cell motility: suppresses T-cell mobility coordinately with CD81, associates with CD82 to suppress prostate cancer cell migration, regulates epidermoid cell reaggregation and motility on laminin-5 with CD9 and CD81 as key linkers. May also play a role on integrin-dependent morphology and motility functions. May participate in the regulation of neurite outgrowth and maintenance of the neural network in the adult brain. Ref.1 Ref.3 Ref.8 Ref.9 Ref.10
Subunit structure	Interacts directly with CD82, CD81/tetraspanin-28 and CD9/tetraspanin-29. Also interacts with integrin alpha-3/beta-1 and integrin alpha-4/beta-1. Ref.1 Ref.8 Ref.9 Ref.10
Subcellular location	Cell membrane By similarity; Single-pass membrane protein.
Tissue specificity	Expressed in brain, kidney, testis, liver and placenta with moderate expression in all other tissues. Detected on a majority of B-cells, T-cells, and natural killer cells but not on monocytes, polynuclear cells and platelets. Ref.1 Ref.2 Ref.8
Domain	The Ig-like C2-type domains 3 and 4 are required for interaction with CD81 By similarity. The short cytoplasmic domain is very basic, interacts with membrane PIPs, and mediates plasma membrane localization By similarity.
Sequence similarities	Contains 4 Ig-like C2-type (immunoglobulin-like) domains.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cell proliferation Non-traceable author statement Ref.1. Source: UniProtKB cellular component movement Non-traceable author statement Ref.1. Source: UniProtKB nervous system development Non-traceable author statement Ref.1. Source: UniProtKB single fertilization Non-traceable author statement Ref.1. Source: UniProtKB skeletal muscle tissue development Non-traceable author statement Ref.1. Source: UniProtKB
Cellular_component	integral to membrane Inferred from direct assay Ref.1. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q969P0-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q969P0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-241: Missing.
     242-315: ELRLGKEGTD...AVTVGPGERR → MRGRSWHWAA...GSFVWARKGP

Note: No experimental confirmation available.

Isoform 3 (identifier: Q969P0-3)

The sequence of this isoform differs from the canonical sequence as follows:
     475-561: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 27	27	Ref.7
	Chain	28 – 613	586	Immunoglobulin superfamily member 8		PRO_0000226247
Regions
	Topological domain	28 – 579	552	Extracellular Potential
	Transmembrane	580 – 600	21	Helical; Potential
	Topological domain	601 – 613	13	Cytoplasmic Potential
	Domain	28 – 149	122	Ig-like C2-type 1
	Domain	162 – 286	125	Ig-like C2-type 2
	Domain	303 – 424	122	Ig-like C2-type 3
	Domain	431 – 560	130	Ig-like C2-type 4
	Motif	274 – 276	3	EWI motif
Amino acid modifications
	Modified residue	12	1	Phosphoserine By similarity
	Lipidation	604	1	S-palmitoyl cysteine By similarity
	Lipidation	605	1	S-palmitoyl cysteine By similarity
	Glycosylation	50	1	N-linked (GlcNAc...) Potential
	Glycosylation	327	1	N-linked (GlcNAc...) Ref.11
	Glycosylation	463	1	N-linked (GlcNAc...) Ref.11
	Disulfide bond	49 ↔ 127		By similarity
	Disulfide bond	186 ↔ 270		By similarity
	Disulfide bond	326 ↔ 406		By similarity
	Disulfide bond	462 ↔ 544		By similarity
Natural variations
	Alternative sequence	1 – 241	241	Missing in isoform 2.		VSP_017429
	Alternative sequence	242 – 315	74	ELRLG…PGERR → MRGRSWHWAAWRGQAHRSTH TWQCPLGDLCPRHQLGGQLC RKWWESGQTWPWRLELPMLS DWLQGSFVWARKGP in isoform 2.		VSP_017430
	Alternative sequence	475 – 561	87	Missing in isoform 3.		VSP_017431
Experimental info
	Sequence conflict	303	1	S → R in AAM94901. Ref.4
	Sequence conflict	306	1	A → P in AAM94901. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: A7255D54D42EFB88	FASTA	613	65,034
	10 20 30 40 50 60 MGALRPTLLP PSLPLLLLLM LGMGCWAREV LVPEGPLYRV AGTAVSISCN VTGYEGPAQQ 70 80 90 100 110 120 NFEWFLYRPE APDTALGIVS TKDTQFSYAV FKSRVVAGEV QVQRLQGDAV VLKIARLQAQ 130 140 150 160 170 180 DAGIYECHTP STDTRYLGSY SGKVELRVLP DVLQVSAAPP GPRGRQAPTS PPRMTVHEGQ 190 200 210 220 230 240 ELALGCLART STQKHTHLAV SFGRSVPEAP VGRSTLQEVV GIRSDLAVEA GAPYAERLAA 250 260 270 280 290 300 GELRLGKEGT DRYRMVVGGA QAGDAGTYHC TAAEWIQDPD GSWAQIAEKR AVLAHVDVQT 310 320 330 340 350 360 LSSQLAVTVG PGERRIGPGE PLELLCNVSG ALPPAGRHAA YSVGWEMAPA GAPGPGRLVA 370 380 390 400 410 420 QLDTEGVGSL GPGYEGRHIA MEKVASRTYR LRLEAARPGD AGTYRCLAKA YVRGSGTRLR 430 440 450 460 470 480 EAASARSRPL PVHVREEGVV LEAVAWLAGG TVYRGETASL LCNISVRGGP PGLRLAASWW 490 500 510 520 530 540 VERPEDGELS SVPAQLVGGV GQDGVAELGV RPGGGPVSVE LVGPRSHRLR LHSLGPEDEG 550 560 570 580 590 600 VYHCAPSAWV QHADYSWYQA GSARSGPVTV YPYMHALDTL FVPLLVGTGV ALVTGATVLG 610 TITCCFMKRL RKR
	Isoform 2 [UniParc]. Checksum: 4872C8D6CC303638	FASTA	372	40,191
	10 20 30 40 50 60 MRGRSWHWAA WRGQAHRSTH TWQCPLGDLC PRHQLGGQLC RKWWESGQTW PWRLELPMLS 70 80 90 100 110 120 DWLQGSFVWA RKGPIGPGEP LELLCNVSGA LPPAGRHAAY SVGWEMAPAG APGPGRLVAQ 130 140 150 160 170 180 LDTEGVGSLG PGYEGRHIAM EKVASRTYRL RLEAARPGDA GTYRCLAKAY VRGSGTRLRE 190 200 210 220 230 240 AASARSRPLP VHVREEGVVL EAVAWLAGGT VYRGETASLL CNISVRGGPP GLRLAASWWV 250 260 270 280 290 300 ERPEDGELSS VPAQLVGGVG QDGVAELGVR PGGGPVSVEL VGPRSHRLRL HSLGPEDEGV 310 320 330 340 350 360 YHCAPSAWVQ HADYSWYQAG SARSGPVTVY PYMHALDTLF VPLLVGTGVA LVTGATVLGT 370 ITCCFMKRLR KR
	Isoform 3 [UniParc]. Checksum: C2A88D773A4F4802	FASTA	526	55,808
	10 20 30 40 50 60 MGALRPTLLP PSLPLLLLLM LGMGCWAREV LVPEGPLYRV AGTAVSISCN VTGYEGPAQQ 70 80 90 100 110 120 NFEWFLYRPE APDTALGIVS TKDTQFSYAV FKSRVVAGEV QVQRLQGDAV VLKIARLQAQ 130 140 150 160 170 180 DAGIYECHTP STDTRYLGSY SGKVELRVLP DVLQVSAAPP GPRGRQAPTS PPRMTVHEGQ 190 200 210 220 230 240 ELALGCLART STQKHTHLAV SFGRSVPEAP VGRSTLQEVV GIRSDLAVEA GAPYAERLAA 250 260 270 280 290 300 GELRLGKEGT DRYRMVVGGA QAGDAGTYHC TAAEWIQDPD GSWAQIAEKR AVLAHVDVQT 310 320 330 340 350 360 LSSQLAVTVG PGERRIGPGE PLELLCNVSG ALPPAGRHAA YSVGWEMAPA GAPGPGRLVA 370 380 390 400 410 420 QLDTEGVGSL GPGYEGRHIA MEKVASRTYR LRLEAARPGD AGTYRCLAKA YVRGSGTRLR 430 440 450 460 470 480 EAASARSRPL PVHVREEGVV LEAVAWLAGG TVYRGETASL LCNISVRGGP PGLRSARSGP 490 500 510 520 VTVYPYMHAL DTLFVPLLVG TGVALVTGAT VLGTITCCFM KRLRKR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH CD81 AND CD9.
[2]	"EWI-2 is a new component of the tetraspanin web in hepatocytes and lymphoid cells." Charrin S., Le Naour F., Labas V., Billard M., Le Caer J.-P., Emile J.-F., Petit M.-A., Boucheix C., Rubinstein E. Biochem. J. 373:409-421(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), IDENTIFICATION BY MASS SPECTROMETRY, TISSUE SPECIFICITY.
[3]	"Identification of novel genes for secreted and membrane-anchored proteins in human keratinocytes." Bonkobara M., Das A., Takao J., Cruz P.D. Jr., Ariizumi K. Br. J. Dermatol. 148:654-664(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION.
[4]	"Identification of novel membrane proteins." Zhang W., Li N., Wan T., Cao X. Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Kidney.
[6]	"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] (ISOFORM 1). Tissue: Lymph.
[7]	"Global profiling of protease cleavage sites by chemoselective labeling of protein N-termini." Xu G., Shin S.B., Jaffrey S.R. Proc. Natl. Acad. Sci. U.S.A. 106:19310-19315(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE [LARGE SCALE ANALYSIS] OF 28-40. Tissue: Leukemic T-cell.
[8]	"EWI2/PGRL associates with the metastasis suppressor KAI1/CD82 and inhibits the migration of prostate cancer cells." Zhang X.A., Lane W.S., Charrin S., Rubinstein E., Liu L. Cancer Res. 63:2665-2674(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CD82, IDENTIFICATION BY MASS SPECTROMETRY, TISSUE SPECIFICITY.
[9]	"EWI-2 regulates alpha3beta1 integrin-dependent cell functions on laminin-5." Stipp C.S., Kolesnikova T.V., Hemler M.E. J. Cell Biol. 163:1167-1177(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH INTEGRIN ALPHA-3 BETA-1.
[10]	"EWI-2 modulates lymphocyte integrin alpha4beta1 functions." Kolesnikova T.V., Stipp C.S., Rao R.M., Lane W.S., Luscinskas F.W., Hemler M.E. Blood 103:3013-3019(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH INTEGRIN ALPHA-4 BETA-1.
[11]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-327 AND ASN-463, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF407274 mRNA. Translation: AAL01052.1. AY044845 mRNA. Translation: AAK92220.1. AY157579 mRNA. Translation: AAO13163.1. AF311906 mRNA. Translation: AAM94901.1. AK055843 mRNA. Translation: BAB71027.1. BC004108 mRNA. Translation: AAH04108.2. BC053881 mRNA. Translation: AAH53881.1.
IPI	IPI00056478. IPI00186736. IPI00386532.
RefSeq	NP_001193594.1. NM_001206665.2. NP_443100.1. NM_052868.4.
UniGene	Hs.332012.
3D structure databases
ProteinModelPortal	Q969P0.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000316664.
PTM databases
PhosphoSite	Q969P0.
Polymorphism databases
DMDM	74762642.
2D gel databases
UCD-2DPAGE	Q969P0.
Proteomic databases
PaxDb	Q969P0.
PRIDE	Q969P0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000314485; ENSP00000316664; ENSG00000162729. ENST00000368086; ENSP00000357065; ENSG00000162729.
GeneID	93185.
KEGG	hsa:93185.
UCSC	uc001fuz.3. human.
Organism-specific databases
CTD	93185.
GeneCards	GC01M160061.
HGNC	HGNC:17813. IGSF8.
HPA	HPA011917.
MIM	606644. gene.
neXtProt	NX_Q969P0.
PharmGKB	PA29767.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG28691.
HOGENOM	HOG000113020.
HOVERGEN	HBG073047.
InParanoid	Q969P0.
KO	K06730.
OMA	VTCCFMK.
OrthoDB	EOG4D52XK.
PhylomeDB	Q969P0.
Gene expression databases
ArrayExpress	Q969P0.
Bgee	Q969P0.
CleanEx	HS_IGSF8.
Genevestigator	Q969P0.
GermOnline	ENSG00000162729. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.10. 4 hits.
InterPro	IPR007110. Ig-like_dom. IPR013783. Ig-like_fold. IPR003599. Ig_sub. IPR013106. Ig_V-set. [Graphical view]
Pfam	PF07686. V-set. 1 hit. [Graphical view]
SMART	SM00409. IG. 4 hits. [Graphical view]
PROSITE	PS50835. IG_LIKE. 2 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	IGSF8. human.
GenomeRNAi	93185.
NextBio	78023.
SOURCE	Search...

Entry information

Entry name

IGSF8_HUMAN

Accession

Primary (citable) accession number: Q969P0
Secondary accession number(s): Q8NG09, Q96DP4, Q9BTG9

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 7, 2006
Last sequence update:	December 1, 2001
Last modified:	May 1, 2013
This is version 94 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.