ID TSN12_HUMAN Reviewed; 305 AA. AC O95859; A4D0V8; B4DRG6; Q549U9; Q8N5Y0; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1999, sequence version 1. DT 24-JAN-2024, entry version 168. DE RecName: Full=Tetraspanin-12; DE Short=Tspan-12; DE AltName: Full=Tetraspan NET-2; DE AltName: Full=Transmembrane 4 superfamily member 12; GN Name=TSPAN12; Synonyms=NET2, TM4SF12; ORFNames=UNQ774/PRO1568; 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] (ISOFORM 1). RX PubMed=10719184; DOI=10.1016/s0167-4838(00)00022-4; RA Serru V., Dessen P., Boucheix C., Rubinstein E.; RT "Sequence and expression of seven new tetraspans."; RL Biochim. Biophys. Acta 1478:159-163(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Adrenal gland, and Teratocarcinoma; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D., RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., RA Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT SER-57. RC TISSUE=Brain; 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 [7] RP FUNCTION, INTERACTION WITH ADAM10, PALMITOYLATION, AND MUTAGENESIS OF RP CYS-9; CYS-12 AND CYS-83. RX PubMed=19587294; DOI=10.1096/fj.09-133462; RA Xu D., Sharma C., Hemler M.E.; RT "Tetraspanin12 regulates ADAM10-dependent cleavage of amyloid precursor RT protein."; RL FASEB J. 23:3674-3681(2009). RN [8] RP FUNCTION. RX PubMed=19211836; DOI=10.1091/mbc.e08-11-1149; RA Lafleur M.A., Xu D., Hemler M.E.; RT "Tetraspanin proteins regulate membrane type-1 matrix metalloproteinase- RT dependent pericellular proteolysis."; RL Mol. Biol. Cell 20:2030-2040(2009). RN [9] RP VARIANTS EVR5 ARG-188 AND PRO-237. RX PubMed=20159111; DOI=10.1016/j.ajhg.2009.12.016; RA Nikopoulos K., Gilissen C., Hoischen A., van Nouhuys C.E., Boonstra F.N., RA Blokland E.A., Arts P., Wieskamp N., Strom T.M., Ayuso C., Tilanus M.A., RA Bouwhuis S., Mukhopadhyay A., Scheffer H., Hoefsloot L.H., Veltman J.A., RA Cremers F.P., Collin R.W.; RT "Next-generation sequencing of a 40 Mb linkage interval reveals TSPAN12 RT mutations in patients with familial exudative vitreoretinopathy."; RL Am. J. Hum. Genet. 86:240-247(2010). RN [10] RP VARIANTS EVR5 HIS-101 AND ARG-210. RX PubMed=20159112; DOI=10.1016/j.ajhg.2010.01.012; RA Poulter J.A., Ali M., Gilmour D.F., Rice A., Kondo H., Hayashi K., RA Mackey D.A., Kearns L.S., Ruddle J.B., Craig J.E., Pierce E.A., RA Downey L.M., Mohamed M.D., Markham A.F., Inglehearn C.F., Toomes C.; RT "Mutations in TSPAN12 cause autosomal-dominant familial exudative RT vitreoretinopathy."; RL Am. J. Hum. Genet. 86:248-253(2010). RN [11] RP VARIANTS EVR5 MET-49; CYS-138 AND PRO-223. RX PubMed=22427576; DOI=10.1167/iovs.11-8629; RA Poulter J.A., Davidson A.E., Ali M., Gilmour D.F., Parry D.A., RA Mintz-Hittner H.A., Carr I.M., Bottomley H.M., Long V.W., Downey L.M., RA Sergouniotis P.I., Wright G.A., MacLaren R.E., Moore A.T., Webster A.R., RA Inglehearn C.F., Toomes C.; RT "Recessive mutations in TSPAN12 cause retinal dysplasia and severe familial RT exudative vitreoretinopathy (FEVR)."; RL Invest. Ophthalmol. Vis. Sci. 53:2873-2879(2012). CC -!- FUNCTION: Regulator of cell surface receptor signal transduction. Plays CC a central role in retinal vascularization by regulating norrin (NDP) CC signal transduction. Acts in concert with norrin (NDP) to promote FZD4 CC multimerization and subsequent activation of FZD4, leading to promote CC accumulation of beta-catenin (CTNNB1) and stimulate LEF/TCF-mediated CC transcriptional programs. Suprisingly, it only activates the norrin CC (NDP)-dependent activation of FZD4, while it does not activate the Wnt- CC dependent activation of FZD4, suggesting the existence of a Wnt- CC independent signaling that also promote accumulation the beta-catenin CC (CTNNB1) (By similarity). Acts as a regulator of membrane proteinases CC such as ADAM10 and MMP14/MT1-MMP. Activates ADAM10-dependent cleavage CC activity of amyloid precursor protein (APP). Activates MMP14/MT1-MMP- CC dependent cleavage activity. {ECO:0000250, ECO:0000269|PubMed:19211836, CC ECO:0000269|PubMed:19587294}. CC -!- SUBUNIT: Component of a complex, at least composed of TSPAN12, FZD4 and CC norrin (NDP) (By similarity). Interacts (when palmitoylated) with CC ADAM10. Interacts with MMP14/MT1-MMP. {ECO:0000250, CC ECO:0000269|PubMed:19587294}. CC -!- INTERACTION: CC O95859; O14672: ADAM10; NbExp=2; IntAct=EBI-2466403, EBI-1536151; CC O95859; PRO_0000029067 [O14672]: ADAM10; NbExp=2; IntAct=EBI-2466403, EBI-21222747; CC O95859; O95674: CDS2; NbExp=3; IntAct=EBI-2466403, EBI-3913685; CC O95859; Q4LDR2: CTXN3; NbExp=3; IntAct=EBI-2466403, EBI-12019274; CC O95859; Q9BQA9: CYBC1; NbExp=3; IntAct=EBI-2466403, EBI-2680384; CC O95859; P54852: EMP3; NbExp=3; IntAct=EBI-2466403, EBI-3907816; CC O95859; O00155: GPR25; NbExp=3; IntAct=EBI-2466403, EBI-10178951; CC O95859; O60883: GPR37L1; NbExp=3; IntAct=EBI-2466403, EBI-2927498; CC O95859; P24593: IGFBP5; NbExp=3; IntAct=EBI-2466403, EBI-720480; CC O95859; Q9P0N8: MARCHF2; NbExp=3; IntAct=EBI-2466403, EBI-10317612; CC O95859; O14880: MGST3; NbExp=3; IntAct=EBI-2466403, EBI-724754; CC O95859; Q9NZG7: NINJ2; NbExp=3; IntAct=EBI-2466403, EBI-10317425; CC O95859; Q01453: PMP22; NbExp=3; IntAct=EBI-2466403, EBI-2845982; CC O95859; Q96AA3: RFT1; NbExp=3; IntAct=EBI-2466403, EBI-6269616; CC O95859; Q8N8N0: RNF152; NbExp=3; IntAct=EBI-2466403, EBI-2129725; CC O95859; Q9UNK0: STX8; NbExp=3; IntAct=EBI-2466403, EBI-727240; CC O95859; Q9Y6I9: TEX264; NbExp=3; IntAct=EBI-2466403, EBI-10329860; CC O95859; Q12800: TFCP2; NbExp=3; IntAct=EBI-2466403, EBI-717422; CC O95859; Q9NV12: TMEM140; NbExp=3; IntAct=EBI-2466403, EBI-2844246; CC O95859; Q9BVK8: TMEM147; NbExp=3; IntAct=EBI-2466403, EBI-348587; CC O95859; Q6ZP80: TMEM182; NbExp=3; IntAct=EBI-2466403, EBI-10255122; CC O95859; A2RU14: TMEM218; NbExp=3; IntAct=EBI-2466403, EBI-10173151; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane CC protein {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O95859-1; Sequence=Displayed; CC Name=2; CC IsoId=O95859-2; Sequence=VSP_038525; CC -!- PTM: Palmitoylated; required for interaction with ADAM10. The precise CC position of palmitoylated residues is unclear and occurs either on Cys- CC 9, Cys-12 and/or Cys-83. {ECO:0000269|PubMed:19587294}. CC -!- DISEASE: Vitreoretinopathy, exudative 5 (EVR5) [MIM:613310]: A disorder CC of the retinal vasculature characterized by an abrupt cessation of CC growth of peripheral capillaries, leading to an avascular peripheral CC retina. This may lead to compensatory retinal neovascularization, which CC is thought to be induced by hypoxia from the initial avascular insult. CC New vessels are prone to leakage and rupture causing exudates and CC bleeding, followed by scarring, retinal detachment and blindness. CC Clinical features can be highly variable, even within the same family. CC Patients with mild forms of the disease are asymptomatic, and their CC only disease related abnormality is an arc of avascular retina in the CC extreme temporal periphery. {ECO:0000269|PubMed:20159111, CC ECO:0000269|PubMed:20159112, ECO:0000269|PubMed:22427576}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. TSPAN12 dominant and recessive mutations have been identified in CC patients with exudative vitreoretinopathy. Patients with mutations in CC both alleles of TSPAN12 have severe exudative vitreoretinopathy or CC retinal dysplasia. These mutations appear to result in a milder CC phenotype in heterozygous mutation carriers (PubMed:22427576). CC {ECO:0000269|PubMed:22427576}. CC -!- SIMILARITY: Belongs to the tetraspanin (TM4SF) family. {ECO:0000305}. 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; AF124522; AAD17317.1; -; mRNA. DR EMBL; AY358703; AAQ89066.1; -; mRNA. DR EMBL; AK299247; BAG61278.1; -; mRNA. DR EMBL; AK312239; BAG35172.1; -; mRNA. DR EMBL; AC004456; AAQ96879.1; -; Genomic_DNA. DR EMBL; CH236947; EAL24349.1; -; Genomic_DNA. DR EMBL; BC031265; AAH31265.1; -; mRNA. DR CCDS; CCDS5777.1; -. [O95859-1] DR RefSeq; NP_036470.1; NM_012338.3. [O95859-1] DR RefSeq; XP_005250296.1; XM_005250239.2. [O95859-1] DR RefSeq; XP_011514295.1; XM_011515993.1. DR RefSeq; XP_011514296.1; XM_011515994.1. DR RefSeq; XP_016867401.1; XM_017011912.1. DR AlphaFoldDB; O95859; -. DR BioGRID; 117098; 21. DR CORUM; O95859; -. DR IntAct; O95859; 37. DR STRING; 9606.ENSP00000222747; -. DR TCDB; 8.A.40.1.20; the tetraspanin (tetraspanin) family. DR iPTMnet; O95859; -. DR PhosphoSitePlus; O95859; -. DR SwissPalm; O95859; -. DR BioMuta; TSPAN12; -. DR MassIVE; O95859; -. DR MaxQB; O95859; -. DR PaxDb; 9606-ENSP00000222747; -. DR PeptideAtlas; O95859; -. DR ProteomicsDB; 51092; -. [O95859-1] DR ProteomicsDB; 51093; -. [O95859-2] DR Antibodypedia; 31686; 221 antibodies from 29 providers. DR DNASU; 23554; -. DR Ensembl; ENST00000222747.8; ENSP00000222747.3; ENSG00000106025.9. [O95859-1] DR Ensembl; ENST00000415871.5; ENSP00000397699.1; ENSG00000106025.9. [O95859-1] DR GeneID; 23554; -. DR KEGG; hsa:23554; -. DR MANE-Select; ENST00000222747.8; ENSP00000222747.3; NM_012338.4; NP_036470.1. DR UCSC; uc003vjk.4; human. [O95859-1] DR AGR; HGNC:21641; -. DR CTD; 23554; -. DR DisGeNET; 23554; -. DR GeneCards; TSPAN12; -. DR HGNC; HGNC:21641; TSPAN12. DR HPA; ENSG00000106025; Tissue enhanced (kidney). DR MalaCards; TSPAN12; -. DR MIM; 613138; gene. DR MIM; 613310; phenotype. DR neXtProt; NX_O95859; -. DR OpenTargets; ENSG00000106025; -. DR Orphanet; 891; Familial exudative vitreoretinopathy. DR PharmGKB; PA134954047; -. DR VEuPathDB; HostDB:ENSG00000106025; -. DR eggNOG; KOG3882; Eukaryota. DR GeneTree; ENSGT00510000047764; -. DR HOGENOM; CLU_055524_1_0_1; -. DR InParanoid; O95859; -. DR OMA; CARHAHF; -. DR OrthoDB; 5341686at2759; -. DR PhylomeDB; O95859; -. DR TreeFam; TF316345; -. DR PathwayCommons; O95859; -. DR SignaLink; O95859; -. DR SIGNOR; O95859; -. DR BioGRID-ORCS; 23554; 15 hits in 1150 CRISPR screens. DR ChiTaRS; TSPAN12; human. DR GeneWiki; TSPAN12; -. DR GenomeRNAi; 23554; -. DR Pharos; O95859; Tbio. DR PRO; PR:O95859; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; O95859; Protein. DR Bgee; ENSG00000106025; Expressed in oocyte and 189 other cell types or tissues. DR ExpressionAtlas; O95859; baseline and differential. DR GO; GO:0016020; C:membrane; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW. DR GO; GO:0007166; P:cell surface receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0035633; P:maintenance of blood-brain barrier; IEA:Ensembl. DR GO; GO:0110135; P:Norrin signaling pathway; IEA:Ensembl. DR GO; GO:0045765; P:regulation of angiogenesis; ISS:UniProtKB. DR GO; GO:0010842; P:retina layer formation; ISS:UniProtKB. DR CDD; cd03157; TM4SF12_like_LEL; 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:SF462; TETRASPANIN-12; 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. DR Genevisible; O95859; HS. PE 1: Evidence at protein level; KW Alternative splicing; Angiogenesis; Cell membrane; Disease variant; KW Lipoprotein; Membrane; Palmitate; Reference proteome; Transmembrane; KW Transmembrane helix. FT CHAIN 1..305 FT /note="Tetraspanin-12" FT /id="PRO_0000219257" FT TOPO_DOM 1..12 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 13..33 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 34..59 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 60..80 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 81..89 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 90..110 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 111..224 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 225..245 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 246..305 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT LIPID 9 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250" FT LIPID 12 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250" FT LIPID 83 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250" FT VAR_SEQ 1..120 FT /note="MAREDSVKCLRCLLYALNLLFWLMSISVLAVSAWMRDYLNNVLTLTAETRVE FT EAVILTYFPVVHPVMIAVCCFLIIVGMLGYCGTVKRNLLLLAWYFGSLLVIFCVELACG FT VWTYEQELM -> MAHKLLL (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_038525" FT VARIANT 49 FT /note="T -> M (in EVR5; dbSNP:rs538591733)" FT /evidence="ECO:0000269|PubMed:22427576" FT /id="VAR_068899" FT VARIANT 57 FT /note="L -> S (in dbSNP:rs17852934)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_062253" FT VARIANT 101 FT /note="L -> H (in EVR5; dbSNP:rs267607152)" FT /evidence="ECO:0000269|PubMed:20159112" FT /id="VAR_063576" FT VARIANT 138 FT /note="Y -> C (in EVR5; dbSNP:rs587777283)" FT /evidence="ECO:0000269|PubMed:22427576" FT /id="VAR_068900" FT VARIANT 188 FT /note="G -> R (in EVR5; dbSNP:rs267607151)" FT /evidence="ECO:0000269|PubMed:20159111" FT /id="VAR_063577" FT VARIANT 210 FT /note="M -> R (in EVR5)" FT /evidence="ECO:0000269|PubMed:20159112" FT /id="VAR_063578" FT VARIANT 223 FT /note="L -> P (in EVR5)" FT /evidence="ECO:0000269|PubMed:22427576" FT /id="VAR_068901" FT VARIANT 237 FT /note="A -> P (in EVR5; dbSNP:rs267607154)" FT /evidence="ECO:0000269|PubMed:20159111" FT /id="VAR_063579" FT MUTAGEN 9 FT /note="C->S: Impairs interaction with ADAM10; when FT associated with S-12 and S-83." FT /evidence="ECO:0000269|PubMed:19587294" FT MUTAGEN 12 FT /note="C->S: Impairs interaction with ADAM10; when FT associated with S-9 and S-83." FT /evidence="ECO:0000269|PubMed:19587294" FT MUTAGEN 83 FT /note="C->S: Impairs interaction with ADAM10; when FT associated with S-9 and S-12." FT /evidence="ECO:0000269|PubMed:19587294" SQ SEQUENCE 305 AA; 35383 MW; EBF4D5E1371E92DC CRC64; MAREDSVKCL RCLLYALNLL FWLMSISVLA VSAWMRDYLN NVLTLTAETR VEEAVILTYF PVVHPVMIAV CCFLIIVGML GYCGTVKRNL LLLAWYFGSL LVIFCVELAC GVWTYEQELM VPVQWSDMVT LKARMTNYGL PRYRWLTHAW NFFQREFKCC GVVYFTDWLE MTEMDWPPDS CCVREFPGCS KQAHQEDLSD LYQEGCGKKM YSFLRGTKQL QVLRFLGISI GVTQILAMIL TITLLWALYY DRREPGTDQM MSLKNDNSQH LSCPSVELLK PSLSRIFEHT SMANSFNTHF EMEEL //