ID TSN8_HUMAN Reviewed; 237 AA. AC P19075; B2R7T7; Q9BS78; DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1990, sequence version 1. DT 02-SEP-2026, entry version 195. DE RecName: Full=Tetraspanin-8; DE Short=Tspan-8; DE AltName: Full=Transmembrane 4 superfamily member 3; DE AltName: Full=Tumor-associated antigen CO-029; GN Name=TSPAN8; Synonyms=TM4SF3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Colon carcinoma; RX PubMed=2395876; DOI=10.1073/pnas.87.17.6833; RA Szala S., Kasai Y., Steplewski Z., Rodeck U., Koprowski H., RA Linnenbach A.J.; RT "Molecular cloning of cDNA for the human tumor-associated antigen CO-029 RT and identification of related transmembrane antigens."; RL Proc. Natl. Acad. Sci. U.S.A. 87:6833-6837(1990). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Colon; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ILE-35 AND ALA-73. RC TISSUE=Liver; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-118. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [6] RP FUNCTION, AND INTERACTION WITH RICTOR AND INTEGRIN ALPHA3. RX PubMed=25761241; DOI=10.3390/ijms16035363; RA Pan S.J., Zhan S.K., Pan Y.X., Liu W., Bian L.G., Sun B., Sun Q.F.; RT "Tetraspanin 8-rictor-integrin alpha3 complex is required for glioma cell RT migration."; RL Int. J. Mol. Sci. 16:5363-5374(2015). RN [7] RP FUNCTION, INTERACTION WITH MEP1B, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP GLU-133 AND GLU-135. RX PubMed=27180357; DOI=10.1515/hsz-20-2016-0126; RA Schmidt F., Mueller M., Prox J., Arnold P., Schoenherr C., Tredup C., RA Minder P., Ebsen H., Janssen O., Annaert W., Pietrzik C., Schmidt-Arras D., RA Sterchi E.E., Becker-Pauly C.; RT "Tetraspanin 8 is an interactor of the metalloprotease meprin beta within RT tetraspanin-enriched microdomains."; RL Biol. Chem. 0:0-0(2016). RN [8] RP SUBCELLULAR LOCATION, AND SUBUNIT. RX PubMed=34524408; DOI=10.1042/bcj20210459; RA Wirth D., Oezdemir E., King C., Ahlswede L., Schneider D., Hristova K.; RT "Quantitative characterization of tetraspanin 8 homointeractions in the RT plasma membrane."; RL Biochem. J. 478:3643-3654(2021). RN [9] RP FUNCTION, AND INTERACTION WITH RICTOR AND MTOR. RX PubMed=35904232; DOI=10.1002/cbin.11870; RA Zhuang L., Jin G., Hu X., Yang Q., Pei X., Zhao W.; RT "TSPAN8 alleviates high glucose-induced apoptosis and autophagy via RT targeting mTORC2."; RL Cell Biol. Int. 46:1693-1703(2022). RN [10] RP FUNCTION, INTERACTION WITH ADAM17, AND SUBCELLULAR LOCATION. RX PubMed=36078095; DOI=10.3390/cells11172683; RA Mueller M., Saunders C., Senftleben A., Heidbuechel J.P.W., Halwachs B., RA Bolik J., Hedemann N., Roeder C., Bauerschlag D., Rose-John S., RA Schmidt-Arras D.; RT "Tetraspanin 8 Subfamily Members Regulate Substrate-Specificity of a RT Disintegrin and Metalloprotease 17."; RL Cells 11:0-0(2022). RN [11] RP FUNCTION, INTERACTION WITH ECE1, AND SUBCELLULAR LOCATION. RX PubMed=37835445; DOI=10.3390/cancers15194751; RA Zhu Y., Saint-Pol J., Nguyen V., Rubinstein E., Boucheix C., Greco C.; RT "The Tetraspanin Tspan8 Associates with Endothelin Converting Enzyme ECE1 RT and Regulates Its Activity."; RL Cancers 15:0-0(2023). RN [12] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=37204469; DOI=10.1007/s00018-023-04803-x; RA Min J., Yang S., Cai Y., Vanderwall D.R., Wu Z., Li S., Liu S., Liu B., RA Wang J., Ding Y., Chen J., Jiang C., Wren J.D., Csiszar A., Ungvari Z., RA Greco C., Kanie T., Peng J., Zhang X.A.; RT "Tetraspanin Tspan8 restrains interferon signaling to stabilize intestinal RT epithelium by directing endocytosis of interferon receptor."; RL Cell. Mol. Life Sci. 80:154-154(2023). 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 (PubMed:27180357, CC PubMed:36078095). Participates thereby in diverse biological functions CC such as cell signal transduction, migration and protein trafficking CC (PubMed:25761241). Promotes ADAM17-mediated TNF processing through CC recruitment of ADAM17 to tetraspanin-enriched micro-domains (TEMs) CC (PubMed:36078095). Forms a complex with RICTOR and integrin CC alpha3/ITGA3 to mediate mTORC2 activation and AKT1 phosphorylation CC leading to cell migration (PubMed:25761241). Reduces apoptosis and CC autophagy induced by high glucose levels through forming a complex with CC mTOR and RICTOR (PubMed:35904232). Contributes to the maintenance of CC intestinal epithelial barrier and plays a role in the regulation of CC intestine inflammation by switching interferon gamma receptor 1/IFNGR1 CC from clathrin-dependent to lipid raft-dependent endocytosis route to CC limit STAT1 activation magnitude and duration (PubMed:37204469). Acts CC as a modulator of the endothelin axis by associating with endothelin CC converting enzyme ECE1 and regulating its activity of conversion of the CC endothelin-1 precursor to endothelin (PubMed:37835445). CC {ECO:0000269|PubMed:25761241, ECO:0000269|PubMed:27180357, CC ECO:0000269|PubMed:35904232, ECO:0000269|PubMed:36078095, CC ECO:0000269|PubMed:37204469, ECO:0000269|PubMed:37835445}. CC -!- SUBUNIT: Forms homooligomers (PubMed:34524408). Interacts with MEP1B CC (PubMed:27180357). Interacts with integrin alpha3/ITGA3 CC (PubMed:25761241). Interacts with RICTOR and MTOR (PubMed:25761241, CC PubMed:35904232). Interacts with ADAM17 (PubMed:36078095). Interacts CC with ECE1 (PubMed:37835445). {ECO:0000269|PubMed:25761241, CC ECO:0000269|PubMed:27180357, ECO:0000269|PubMed:34524408, CC ECO:0000269|PubMed:35904232, ECO:0000269|PubMed:36078095, CC ECO:0000269|PubMed:37835445}. CC -!- INTERACTION: CC P19075; Q16820: MEP1B; NbExp=4; IntAct=EBI-4289938, EBI-968418; CC P19075; P54315: PNLIPRP1; NbExp=3; IntAct=EBI-4289938, EBI-8652812; CC P19075; Q9NVC3: SLC38A7; NbExp=3; IntAct=EBI-4289938, EBI-10314552; CC P19075; P32856-2: STX2; NbExp=3; IntAct=EBI-4289938, EBI-11956649; CC P19075; O14925: TIMM23; NbExp=3; IntAct=EBI-4289938, EBI-1047996; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:27180357, CC ECO:0000269|PubMed:34524408, ECO:0000269|PubMed:37204469, CC ECO:0000269|PubMed:37835445}; Multi-pass membrane protein. CC -!- TISSUE SPECIFICITY: Gastric, colon, rectal, and pancreatic carcinomas. CC -!- SIMILARITY: Belongs to the tetraspanin (TM4SF) family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/42585/TSPAN8"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M35252; AAA35709.1; -; mRNA. DR EMBL; AK313112; BAG35934.1; -; mRNA. DR EMBL; CH471054; EAW97257.1; -; Genomic_DNA. DR EMBL; BC005246; AAH05246.1; -; mRNA. DR CCDS; CCDS8999.1; -. DR PIR; A36056; A36056. DR RefSeq; NP_001356689.1; NM_001369760.1. DR RefSeq; NP_004607.1; NM_004616.3. DR RefSeq; XP_054229089.1; XM_054373114.1. DR AlphaFoldDB; P19075; -. DR SMR; P19075; -. DR BioGRID; 112958; 81. DR FunCoup; P19075; 46. DR IntAct; P19075; 74. DR NDEx; IQUERY-CP-TSPAN8; 3 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000377003; -. DR GlyCosmos; P19075; 1 site, No reported glycans. DR GlyGen; P19075; 2 sites, 6 N-linked glycans (1 site), 1 O-linked glycan (1 site). DR iPTMnet; P19075; -. DR PhosphoSitePlus; P19075; -. DR SwissPalm; P19075; -. DR BioMuta; TSPAN8; -. DR DMDM; 116589; -. DR jPOST; P19075; -. DR MassIVE; P19075; -. DR PaxDb; 9606-ENSP00000377003; -. DR PeptideAtlas; P19075; -. DR ProteomicsDB; 53629; -. DR Pumba; P19075; -. DR Antibodypedia; 29509; 324 antibodies from 39 providers. DR DNASU; 7103; -. DR Ensembl; ENST00000247829.8; ENSP00000247829.3; ENSG00000127324.10. DR Ensembl; ENST00000393330.6; ENSP00000377003.2; ENSG00000127324.10. DR Ensembl; ENST00000546561.2; ENSP00000447160.1; ENSG00000127324.10. DR Ensembl; ENST00000861089.1; ENSP00000531148.1; ENSG00000127324.10. DR Ensembl; ENST00000861090.1; ENSP00000531149.1; ENSG00000127324.10. DR Ensembl; ENST00000861091.1; ENSP00000531150.1; ENSG00000127324.10. DR Ensembl; ENST00000861093.1; ENSP00000531152.1; ENSG00000127324.10. DR Ensembl; ENST00000861094.1; ENSP00000531153.1; ENSG00000127324.10. DR Ensembl; ENST00000861097.1; ENSP00000531156.1; ENSG00000127324.10. DR Ensembl; ENST00000861100.1; ENSP00000531159.1; ENSG00000127324.10. DR Ensembl; ENST00000861102.1; ENSP00000531161.1; ENSG00000127324.10. DR Ensembl; ENST00000963071.1; ENSP00000633130.1; ENSG00000127324.10. DR GeneID; 7103; -. DR KEGG; hsa:7103; -. DR MANE-Select; ENST00000247829.8; ENSP00000247829.3; NM_004616.3; NP_004607.1. DR UCSC; uc001swj.2; human. DR AGR; HGNC:11855; -. DR ClinPGx; PA36556; -. DR CTD; 7103; -. DR DisGeNET; 7103; -. DR GeneCards; TSPAN8; -. DR HGNC; HGNC:11855; TSPAN8. DR HPA; ENSG00000127324; Tissue enhanced (intestine, stomach). DR MIM; 600769; gene. DR OpenTargets; ENSG00000127324; -. DR VEuPathDB; HostDB:ENSG00000127324; -. DR eggNOG; KOG3882; Eukaryota. DR GeneTree; ENSGT00940000158153; -. DR HOGENOM; CLU_055524_4_2_1; -. DR InParanoid; P19075; -. DR OMA; IAIWIRV; -. DR OrthoDB; 5982705at2759; -. DR PAN-GO; P19075; 1 GO annotation based on evolutionary models. DR PhylomeDB; P19075; -. DR PathwayCommons; P19075; -. DR SignaLink; P19075; -. DR Agora; ENSG00000127324; -. DR BioGRID-ORCS; 7103; 7 hits in 1085 CRISPR screens. DR ChiTaRS; TSPAN8; human. DR GeneWiki; TSPAN8; -. DR GenomeRNAi; 7103; -. DR Pharos; P19075; Tbio. DR PRO; PR:P19075; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; P19075; protein. DR Bgee; ENSG00000127324; Expressed in colonic mucosa and 178 other cell types or tissues. DR GO; GO:0009986; C:cell surface; IEA:Ensembl. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; EXP:UniProtKB. DR GO; GO:0005178; F:integrin binding; IEA:Ensembl. DR GO; GO:0030195; P:negative regulation of blood coagulation; IEA:Ensembl. DR CDD; cd03154; TM4SF3_like_LEL; 1. DR FunFam; 1.10.1450.10:FF:000031; Tetraspanin; 1. DR Gene3D; 1.10.1450.10; Tetraspanin; 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; TETRASPANIN; 1. DR PANTHER; PTHR19282:SF380; TETRASPANIN-8; 1. DR Pfam; PF00335; Tetraspanin; 1. DR PIRSF; PIRSF002419; Tetraspanin; 1. DR PRINTS; PR00259; TMFOUR. DR SUPFAM; SSF48652; Tetraspanin; 1. DR PROSITE; PS00421; TM4_1; 1. PE 1: Evidence at protein level; KW Cell membrane; Glycoprotein; Membrane; Proteomics identification; KW Reference proteome; Transmembrane; Transmembrane helix. FT CHAIN 1..237 FT /note="Tetraspanin-8" FT /id="PRO_0000219252" FT TOPO_DOM 1..9 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 10..33 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 34..57 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 58..72 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 73..83 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 84..109 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 110..205 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 206..230 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 231..237 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT CARBOHYD 118 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT VARIANT 35 FT /note="V -> I (in dbSNP:rs17849952)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_061848" FT VARIANT 73 FT /note="G -> A (in dbSNP:rs3763978)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_020093" FT VARIANT 213 FT /note="S -> A (in dbSNP:rs1051334)" FT /id="VAR_012054" FT MUTAGEN 133 FT /note="E->A: No difference in TSPAN8-mediated MEP1B FT activity." FT /evidence="ECO:0000269|PubMed:27180357" FT MUTAGEN 135 FT /note="E->A: No difference in TSPAN8-mediated MEP1B FT activity." FT /evidence="ECO:0000269|PubMed:27180357" SQ SEQUENCE 237 AA; 26044 MW; D1058F054EE8C14E CRC64; MAGVSACIKY SMFTFNFLFW LCGILILALA IWVRVSNDSQ AIFGSEDVGS SSYVAVDILI AVGAIIMILG FLGCCGAIKE SRCMLLLFFI GLLLILLLQV ATGILGAVFK SKSDRIVNET LYENTKLLSA TGESEKQFQE AIIVFQEEFK CCGLVNGAAD WGNNFQHYPE LCACLDKQRP CQSYNGKQVY KETCISFIKD FLAKNLIIVI GISFGLAVIE ILGLVFSMVL YCQIGNK //