TSN12_HUMAN
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 03-AUG-2022, entry version 160.
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 activate 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}.
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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. [O95859-1]
DR RefSeq; XP_011514296.1; XM_011515994.1. [O95859-1]
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; O95859; -.
DR PeptideAtlas; O95859; -.
DR PRIDE; O95859; -.
DR ProteomicsDB; 51092; -. [O95859-1]
DR ProteomicsDB; 51093; -. [O95859-2]
DR Antibodypedia; 31686; 201 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 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; GCSRSNK; -.
DR PhylomeDB; O95859; -.
DR TreeFam; TF316345; -.
DR PathwayCommons; O95859; -.
DR SignaLink; O95859; -.
DR SIGNOR; O95859; -.
DR BioGRID-ORCS; 23554; 15 hits in 1072 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 187 other tissues.
DR ExpressionAtlas; O95859; baseline and differential.
DR Genevisible; O95859; HS.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0045765; P:regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:1900746; P:regulation of vascular endothelial growth factor signaling pathway; IBA:GO_Central.
DR GO; GO:0010842; P:retina layer formation; ISS:UniProtKB.
DR Gene3D; 1.10.1450.10; -; 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; PTHR19282; 1.
DR Pfam; PF00335; Tetraspanin; 1.
DR PIRSF; PIRSF002419; Tetraspanin; 1.
DR SUPFAM; SSF48652; SSF48652; 1.
DR PROSITE; PS00421; TM4_1; 1.
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
