ID TMPS3_HUMAN Reviewed; 454 AA. AC P57727; D3DSJ6; Q5USC7; Q6ZMC3; DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 21-FEB-2001, sequence version 2. DT 27-MAR-2024, entry version 206. DE RecName: Full=Transmembrane protease serine 3; DE EC=3.4.21.-; DE AltName: Full=Serine protease TADG-12; DE AltName: Full=Tumor-associated differentially-expressed gene 12 protein; GN Name=TMPRSS3; Synonyms=ECHOS1, TADG12; ORFNames=UNQ323/PRO382; 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] (ISOFORMS A; E AND T). RC TISSUE=Ovarian carcinoma; RX PubMed=11068177; DOI=10.1016/s0925-4439(00)00058-2; RA Underwood L.J., Shigemasa K., Tanimoto H., Beard J.B., Schneider E.N., RA Wang Y., Parmley T.H., O'Brien T.J.; RT "Ovarian tumor cells express a novel multi-domain cell surface serine RT protease."; RL Biochim. Biophys. Acta 1502:337-350(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND D), AND VARIANT ILE-53. RX PubMed=11137999; DOI=10.1038/83768; RA Scott H.S., Kudoh J., Wattenhofer M., Shibuya K., Berry A., Chrast R., RA Guipponi M., Wang J., Kawasaki K., Asakawa S., Minoshima S., Younus F., RA Mehdi S.Q., Radhakrishna U., Papasavvas M.P., Gehrig C., Rossier C., RA Korostishevsky M., Gal A., Shimizu N., Bonne-Tamir B., Antonarakis S.E.; RT "Insertion of beta-satellite repeats identifies a transmembrane protease RT causing both congenital and childhood onset autosomal recessive deafness."; RL Nat. Genet. 27:59-63(2001). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), AND INVOLVEMENT IN DFNB8. RC TISSUE=Retina; RX PubMed=15447792; DOI=10.1186/1471-2350-5-24; RA Ahmed Z.M., Li X.C., Powell S.D., Riazuddin S., Young T.L., Ramzan K., RA Ahmad Z., Luscombe S., Dhillon K., MacLaren L., Ploplis B., Shotland L.I., RA Ives E., Riazuddin S., Friedman T.B., Morell R.J., Wilcox E.R.; RT "Characterization of a new full length TMPRSS3 isoform and identification RT of mutant alleles responsible for nonsyndromic recessive deafness in RT Newfoundland and Pakistan."; RL BMC Med. Genet. 5:24-24(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM E). 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM E). 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10830953; DOI=10.1038/35012518; RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U., RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.; RT "The DNA sequence of human chromosome 21."; RL Nature 405:311-319(2000). RN [7] 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A AND E). RC TISSUE=Lung; 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 [9] RP SUBCELLULAR LOCATION, AUTOCATALYTIC CLEAVAGE, MUTAGENESIS OF SER-401, RP CHARACTERIZATION OF VARIANTS DFNB8 GLY-103; TRP-109; PHE-194; CYS-251; RP LEU-404 AND ARG-407, AND FUNCTION IN ENAC CLEAVAGE. RX PubMed=12393794; DOI=10.1093/hmg/11.23.2829; RA Guipponi M., Vuagniaux G., Wattenhofer M., Shibuya K., Vazquez M., RA Dougherty L., Scamuffa N., Guida E., Okui M., Rossier C., Hancock M., RA Buchet K., Reymond A., Hummler E., Marzella P.L., Kudoh J., Shimizu N., RA Scott H.S., Antonarakis S.E., Rossier B.C.; RT "The transmembrane serine protease (TMPRSS3) mutated in deafness DFNB8/10 RT activates the epithelial sodium channel (ENaC) in vitro."; RL Hum. Mol. Genet. 11:2829-2836(2002). RN [10] RP VARIANTS DFNB8 CYS-251 AND LEU-404. RX PubMed=11462234; DOI=10.1002/humu.1159; RA Masmoudi S., Antonarakis S.E., Schwede T., Ghorbel A.M., Gratri M., RA Pappasavas M.P., Drira M., Elgaied-Boulila A., Wattenhofer M., Rossier C., RA Scott H.S., Ayadi H., Guipponi M.; RT "Novel missense mutations of TMPRSS3 in two consanguineous Tunisian RT families with non-syndromic autosomal recessive deafness."; RL Hum. Mutat. 18:101-108(2001). RN [11] RP VARIANTS DFNB8 TRP-109; PHE-194 AND ARG-407, AND VARIANTS ILE-53; SER-111 RP AND VAL-253. RX PubMed=11424922; DOI=10.1136/jmg.38.6.396; RA Ben-Yosef T., Wattenhofer M., Riazuddin S., Ahmed Z.M., Scott H.S., RA Kudoh J., Shibuya K., Antonarakis S.E., Bonne-Tamir B., Radhakrishna U., RA Naz S., Ahmed Z., Riazuddin S., Pandya A., Nance W.E., Wilcox E.R., RA Friedman T.B., Morell R.J.; RT "Novel mutations of TMPRSS3 in four DFNB8/B10 families segregating RT congenital autosomal recessive deafness."; RL J. Med. Genet. 38:396-400(2001). RN [12] RP VARIANTS DFNB8 GLY-103 AND THR-426, AND VARIANT ASN-173. RX PubMed=11907649; DOI=10.1007/s00109-001-0310-6; RA Wattenhofer M., Di Iorio V., Rabionet R., Dougherty L., Pampanos A., RA Schwede T., Montserrat-Sentis B., Arbones L., Iliades T., RA Pasquadibisceglie A., D'Amelio M., Alwan S., Rossier C., Dahl H.-H.M., RA Petersen M.B., Estivill X., Gasparini P., Scott H.S., Antonarakis S.E.; RT "Mutations in the TMPRSS3 gene are a rare cause of childhood nonsyndromic RT deafness in Caucasian patients."; RL J. Mol. Med. 80:124-131(2002). RN [13] RP VARIANTS DFNB8 LEU-216 AND LEU-404. RX PubMed=16021470; DOI=10.1007/s00439-005-1332-x; RA Wattenhofer M., Sahin-Calapoglu N., Andreasen D., Kalay E., Caylan R., RA Braillard B., Fowler-Jaeger N., Reymond A., Rossier B.C., Karaguzel A., RA Antonarakis S.E.; RT "A novel TMPRSS3 missense mutation in a DFNB8/10 family prevents RT proteolytic activation of the protein."; RL Hum. Genet. 117:528-535(2005). CC -!- FUNCTION: Probable serine protease that plays a role in hearing. Acts CC as a permissive factor for cochlear hair cell survival and activation CC at the onset of hearing and is required for saccular hair cell survival CC (By similarity). Activates ENaC (in vitro). {ECO:0000250, CC ECO:0000269|PubMed:12393794}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:12393794}; Single-pass type II membrane protein CC {ECO:0000269|PubMed:12393794}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=A; CC IsoId=P57727-1; Sequence=Displayed; CC Name=B; Synonyms=C; CC IsoId=P57727-2; Sequence=VSP_005391; CC Name=D; CC IsoId=P57727-3; Sequence=VSP_005392; CC Name=T; Synonyms=Truncated, TADG-12V; CC IsoId=P57727-4; Sequence=VSP_005393, VSP_005394; CC Name=E; CC IsoId=P57727-5; Sequence=VSP_013184; CC Name=6; Synonyms=TMPRSS3e; CC IsoId=P57727-6; Sequence=VSP_047695; CC -!- TISSUE SPECIFICITY: Expressed in many tissues including fetal cochlea. CC Isoform T is found at increased levels in some carcinomas. CC -!- PTM: Undergoes autoproteolytic activation. CC -!- DISEASE: Deafness, autosomal recessive, 8 (DFNB8) [MIM:601072]: A form CC of non-syndromic sensorineural hearing loss. Sensorineural deafness CC results from damage to the neural receptors of the inner ear, the nerve CC pathways to the brain, or the area of the brain that receives sound CC information. {ECO:0000269|PubMed:11424922, ECO:0000269|PubMed:11462234, CC ECO:0000269|PubMed:11907649, ECO:0000269|PubMed:12393794, CC ECO:0000269|PubMed:15447792, ECO:0000269|PubMed:16021470}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: [Isoform 6]: Has a predicted N-terminal signal sequence, CC indicating it may be secreted. Expressed in retina, lung, liver, CC pancreas, placenta and kidney. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE- CC ProRule:PRU00274}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/42593/TMPRSS3"; 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; AF201380; AAG37012.1; -; mRNA. DR EMBL; AB038157; BAB20077.1; -; mRNA. DR EMBL; AB038158; BAB20078.1; -; mRNA. DR EMBL; AB038159; BAB20079.1; -; mRNA. DR EMBL; AB038160; BAB20080.1; -; mRNA. DR EMBL; AY633572; AAT66641.1; -; mRNA. DR EMBL; AY358458; AAQ88823.1; -; mRNA. DR EMBL; AK172842; BAD18806.1; -; mRNA. DR EMBL; AP001623; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471079; EAX09564.1; -; Genomic_DNA. DR EMBL; CH471079; EAX09566.1; -; Genomic_DNA. DR EMBL; BC074846; AAH74846.1; -; mRNA. DR EMBL; BC074847; AAH74847.1; -; mRNA. DR CCDS; CCDS13686.1; -. [P57727-1] DR CCDS; CCDS42939.1; -. [P57727-3] DR CCDS; CCDS58790.1; -. [P57727-5] DR RefSeq; NP_001243246.1; NM_001256317.1. [P57727-5] DR RefSeq; NP_076927.1; NM_024022.2. [P57727-1] DR RefSeq; NP_115780.1; NM_032404.2. [P57727-2] DR RefSeq; NP_115781.1; NM_032405.1. [P57727-3] DR AlphaFoldDB; P57727; -. DR SMR; P57727; -. DR BioGRID; 122236; 48. DR IntAct; P57727; 33. DR STRING; 9606.ENSP00000411013; -. DR MEROPS; S01.079; -. DR TCDB; 8.A.131.1.1; the transmembrane protease serine 3 (tmprss3) family. DR GlyCosmos; P57727; 1 site, No reported glycans. DR GlyGen; P57727; 1 site. DR iPTMnet; P57727; -. DR PhosphoSitePlus; P57727; -. DR BioMuta; TMPRSS3; -. DR DMDM; 13124582; -. DR jPOST; P57727; -. DR MassIVE; P57727; -. DR PaxDb; 9606-ENSP00000291532; -. DR PeptideAtlas; P57727; -. DR Antibodypedia; 23790; 326 antibodies from 34 providers. DR DNASU; 64699; -. DR Ensembl; ENST00000398397.3; ENSP00000381434.3; ENSG00000160183.17. [P57727-3] DR Ensembl; ENST00000433957.7; ENSP00000411013.3; ENSG00000160183.17. [P57727-1] DR Ensembl; ENST00000644384.2; ENSP00000494414.1; ENSG00000160183.17. [P57727-5] DR Ensembl; ENST00000652415.1; ENSP00000498756.1; ENSG00000160183.17. [P57727-5] DR GeneID; 64699; -. DR KEGG; hsa:64699; -. DR MANE-Select; ENST00000644384.2; ENSP00000494414.1; NM_001256317.3; NP_001243246.1. [P57727-5] DR UCSC; uc002zbc.4; human. [P57727-1] DR AGR; HGNC:11877; -. DR CTD; 64699; -. DR DisGeNET; 64699; -. DR GeneCards; TMPRSS3; -. DR GeneReviews; TMPRSS3; -. DR HGNC; HGNC:11877; TMPRSS3. DR HPA; ENSG00000160183; Tissue enhanced (fallopian tube, stomach). DR MalaCards; TMPRSS3; -. DR MIM; 601072; phenotype. DR MIM; 605511; gene. DR neXtProt; NX_P57727; -. DR OpenTargets; ENSG00000160183; -. DR Orphanet; 90636; Rare autosomal recessive non-syndromic sensorineural deafness type DFNB. DR PharmGKB; PA36578; -. DR VEuPathDB; HostDB:ENSG00000160183; -. DR eggNOG; KOG3627; Eukaryota. DR GeneTree; ENSGT00940000158589; -. DR HOGENOM; CLU_069382_0_0_1; -. DR InParanoid; P57727; -. DR OMA; LIEPICL; -. DR OrthoDB; 4629979at2759; -. DR PhylomeDB; P57727; -. DR TreeFam; TF351678; -. DR PathwayCommons; P57727; -. DR SignaLink; P57727; -. DR BioGRID-ORCS; 64699; 10 hits in 1143 CRISPR screens. DR ChiTaRS; TMPRSS3; human. DR GeneWiki; TMPRSS3; -. DR GenomeRNAi; 64699; -. DR Pharos; P57727; Tbio. DR PRO; PR:P57727; -. DR Proteomes; UP000005640; Chromosome 21. DR RNAct; P57727; Protein. DR Bgee; ENSG00000160183; Expressed in pancreatic ductal cell and 125 other cell types or tissues. DR ExpressionAtlas; P57727; baseline and differential. DR GO; GO:0005783; C:endoplasmic reticulum; HDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; NAS:UniProtKB. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0004252; F:serine-type endopeptidase activity; NAS:UniProtKB. DR GO; GO:0017080; F:sodium channel regulator activity; IDA:MGI. DR GO; GO:0006883; P:intracellular sodium ion homeostasis; IDA:MGI. DR GO; GO:0006508; P:proteolysis; NAS:UniProtKB. DR GO; GO:0007605; P:sensory perception of sound; IEA:Ensembl. DR CDD; cd00112; LDLa; 1. DR CDD; cd00190; Tryp_SPc; 1. DR Gene3D; 4.10.400.10; Low-density Lipoprotein Receptor; 1. DR Gene3D; 3.10.250.10; SRCR-like domain; 1. DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 1. DR InterPro; IPR036055; LDL_receptor-like_sf. DR InterPro; IPR023415; LDLR_class-A_CS. DR InterPro; IPR002172; LDrepeatLR_classA_rpt. DR InterPro; IPR009003; Peptidase_S1_PA. DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin. DR InterPro; IPR001314; Peptidase_S1A. DR InterPro; IPR001190; SRCR. DR InterPro; IPR017448; SRCR-like_dom. DR InterPro; IPR036772; SRCR-like_dom_sf. DR InterPro; IPR001254; Trypsin_dom. DR InterPro; IPR018114; TRYPSIN_HIS. DR InterPro; IPR033116; TRYPSIN_SER. DR PANTHER; PTHR24252; ACROSIN-RELATED; 1. DR PANTHER; PTHR24252:SF14; TRANSMEMBRANE PROTEASE SERINE 3-LIKE; 1. DR Pfam; PF00057; Ldl_recept_a; 1. DR Pfam; PF15494; SRCR_2; 1. DR Pfam; PF00089; Trypsin; 1. DR PRINTS; PR00722; CHYMOTRYPSIN. DR SMART; SM00192; LDLa; 1. DR SMART; SM00202; SR; 1. DR SMART; SM00020; Tryp_SPc; 1. DR SUPFAM; SSF57424; LDL receptor-like module; 1. DR SUPFAM; SSF56487; SRCR-like; 1. DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1. DR PROSITE; PS01209; LDLRA_1; 1. DR PROSITE; PS50068; LDLRA_2; 1. DR PROSITE; PS00420; SRCR_1; 1. DR PROSITE; PS50287; SRCR_2; 1. DR PROSITE; PS50240; TRYPSIN_DOM; 1. DR PROSITE; PS00134; TRYPSIN_HIS; 1. DR PROSITE; PS00135; TRYPSIN_SER; 1. DR Genevisible; P57727; HS. PE 1: Evidence at protein level; KW Alternative splicing; Autocatalytic cleavage; Deafness; Disease variant; KW Disulfide bond; Endoplasmic reticulum; Glycoprotein; Hydrolase; Membrane; KW Non-syndromic deafness; Protease; Reference proteome; Serine protease; KW Signal-anchor; Transmembrane; Transmembrane helix; Zymogen. FT CHAIN 1..454 FT /note="Transmembrane protease serine 3" FT /id="PRO_0000088690" FT TOPO_DOM 1..48 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 49..69 FT /note="Helical; Signal-anchor for type II membrane protein" FT /evidence="ECO:0000255" FT TOPO_DOM 70..454 FT /note="Extracellular" FT /evidence="ECO:0000255" FT DOMAIN 72..108 FT /note="LDL-receptor class A" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 109..205 FT /note="SRCR" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196" FT DOMAIN 217..449 FT /note="Peptidase S1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT ACT_SITE 257 FT /note="Charge relay system" FT /evidence="ECO:0000250" FT ACT_SITE 304 FT /note="Charge relay system" FT /evidence="ECO:0000250" FT ACT_SITE 401 FT /note="Charge relay system" FT /evidence="ECO:0000305" FT SITE 216..217 FT /note="Cleavage" FT /evidence="ECO:0000255" FT CARBOHYD 221 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 73..85 FT /evidence="ECO:0000250" FT DISULFID 79..98 FT /evidence="ECO:0000250" FT DISULFID 92..107 FT /evidence="ECO:0000250" FT DISULFID 129..194 FT /evidence="ECO:0000250" FT DISULFID 142..204 FT /evidence="ECO:0000250" FT DISULFID 207..324 FT /evidence="ECO:0000250" FT DISULFID 242..258 FT /evidence="ECO:0000250" FT DISULFID 338..407 FT /evidence="ECO:0000250" FT DISULFID 370..386 FT /evidence="ECO:0000250" FT DISULFID 397..425 FT /evidence="ECO:0000250" FT VAR_SEQ 1..127 FT /note="Missing (in isoform B)" FT /evidence="ECO:0000303|PubMed:11137999" FT /id="VSP_005391" FT VAR_SEQ 1 FT /note="M -> MQAVGPKPLPTLLCGGRTGHRTARVLSFLIRSCPCEPGKGCVYGKPV FT TLWPTISSVVPSTFLGLGNYEVEVEAEPDVRGPEIVTM (in isoform 6)" FT /evidence="ECO:0000303|PubMed:15447792" FT /id="VSP_047695" FT VAR_SEQ 261..293 FT /note="DLYLPKSWTIQVGLVSLLDNPAPSHLVEKIVYH -> EIVAPRERADRRGRK FT LLCWRKPTKMKGPRPSHS (in isoform T)" FT /evidence="ECO:0000303|PubMed:11068177" FT /id="VSP_005393" FT VAR_SEQ 294..454 FT /note="Missing (in isoform T)" FT /evidence="ECO:0000303|PubMed:11068177" FT /id="VSP_005394" FT VAR_SEQ 318..454 FT /note="EMIQPVCLPNSEENFPDGKVCWTSGWGATEDGAGDASPVLNHAAVPLISNKI FT CNHRDVYGGIISPSMLCAGYLTGGVDSCQGDSGGPLVCQERRLWKLVGATSFGIGCAEV FT NKPGVYTRVTSFLDWIHEQMERDLKT -> GTSGSLCGSAALPLFQEDLQLLIEAFL FT (in isoform D)" FT /evidence="ECO:0000303|PubMed:11137999" FT /id="VSP_005392" FT VAR_SEQ 350 FT /note="Missing (in isoform E)" FT /evidence="ECO:0000303|PubMed:11068177, FT ECO:0000303|PubMed:12975309, ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_013184" FT VARIANT 53 FT /note="V -> I (in dbSNP:rs928302)" FT /evidence="ECO:0000269|PubMed:11137999, FT ECO:0000269|PubMed:11424922" FT /id="VAR_010781" FT VARIANT 103 FT /note="D -> G (in DFNB8; fails to undergo proteolytic FT cleavage and is unable to activate ENaC; FT dbSNP:rs387906915)" FT /evidence="ECO:0000269|PubMed:11907649, FT ECO:0000269|PubMed:12393794" FT /id="VAR_013490" FT VARIANT 109 FT /note="R -> W (in DFNB8; fails to undergo proteolytic FT cleavage and is unable to activate ENaC; FT dbSNP:rs201632198)" FT /evidence="ECO:0000269|PubMed:11424922, FT ECO:0000269|PubMed:12393794" FT /id="VAR_013491" FT VARIANT 111 FT /note="G -> S (in dbSNP:rs35227181)" FT /evidence="ECO:0000269|PubMed:11424922" FT /id="VAR_013492" FT VARIANT 173 FT /note="D -> N (in dbSNP:rs766000719)" FT /evidence="ECO:0000269|PubMed:11907649" FT /id="VAR_013493" FT VARIANT 194 FT /note="C -> F (in DFNB8; fails to undergo proteolytic FT cleavage and is unable to activate ENaC; FT dbSNP:rs1333651774)" FT /evidence="ECO:0000269|PubMed:11424922, FT ECO:0000269|PubMed:12393794" FT /id="VAR_013494" FT VARIANT 216 FT /note="R -> L (in DFNB8; fails to undergo proteolytic FT cleavage and is unable to activate ENaC; FT dbSNP:rs137853000)" FT /evidence="ECO:0000269|PubMed:16021470" FT /id="VAR_025354" FT VARIANT 251 FT /note="W -> C (in DFNB8; fails to undergo proteolytic FT cleavage and is unable to activate ENaC; FT dbSNP:rs137852999)" FT /evidence="ECO:0000269|PubMed:11462234, FT ECO:0000269|PubMed:12393794" FT /id="VAR_011678" FT VARIANT 253 FT /note="I -> V (in dbSNP:rs2839500)" FT /evidence="ECO:0000269|PubMed:11424922" FT /id="VAR_013101" FT VARIANT 404 FT /note="P -> L (in DFNB8; fails to undergo proteolytic FT cleavage and is unable to activate ENaC; dbSNP:rs28939084)" FT /evidence="ECO:0000269|PubMed:11462234, FT ECO:0000269|PubMed:12393794, ECO:0000269|PubMed:16021470" FT /id="VAR_011679" FT VARIANT 407 FT /note="C -> R (in DFNB8; fails to undergo proteolytic FT cleavage and is unable to activate ENaC; FT dbSNP:rs773780151)" FT /evidence="ECO:0000269|PubMed:11424922, FT ECO:0000269|PubMed:12393794" FT /id="VAR_013495" FT VARIANT 426 FT /note="A -> T (in DFNB8; dbSNP:rs56264519)" FT /evidence="ECO:0000269|PubMed:11907649" FT /id="VAR_013496" FT MUTAGEN 401 FT /note="S->A: Fails to undergo proteolytic cleavage and is FT unable to activate ENaC." FT /evidence="ECO:0000269|PubMed:12393794" FT CONFLICT 46..54 FT /note="LKFFPIIVI -> FEVFSQSSSL (in Ref. 1; AAG37012)" FT /evidence="ECO:0000305" FT CONFLICT 90 FT /note="A -> T (in Ref. 1; AAG37012)" FT /evidence="ECO:0000305" FT CONFLICT 369..395 FT /note="ICNHRDVYGGIISPSMLCAGYLTGGVD -> DLQPQGRVRWHHLPLHALRGL FT PDGWRWN (in Ref. 1; AAG37012)" FT /evidence="ECO:0000305" FT CONFLICT 427 FT /note="E -> D (in Ref. 1; AAG37012)" FT /evidence="ECO:0000305" SQ SEQUENCE 454 AA; 49405 MW; 57ECC3678F7D6AFF CRC64; MGENDPPAVE APFSFRSLFG LDDLKISPVA PDADAVAAQI LSLLPLKFFP IIVIGIIALI LALAIGLGIH FDCSGKYRCR SSFKCIELIA RCDGVSDCKD GEDEYRCVRV GGQNAVLQVF TAASWKTMCS DDWKGHYANV ACAQLGFPSY VSSDNLRVSS LEGQFREEFV SIDHLLPDDK VTALHHSVYV REGCASGHVV TLQCTACGHR RGYSSRIVGG NMSLLSQWPW QASLQFQGYH LCGGSVITPL WIITAAHCVY DLYLPKSWTI QVGLVSLLDN PAPSHLVEKI VYHSKYKPKR LGNDIALMKL AGPLTFNEMI QPVCLPNSEE NFPDGKVCWT SGWGATEDGA GDASPVLNHA AVPLISNKIC NHRDVYGGII SPSMLCAGYL TGGVDSCQGD SGGPLVCQER RLWKLVGATS FGIGCAEVNK PGVYTRVTSF LDWIHEQMER DLKT //