TMPS3_HUMAN
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 03-AUG-2022, entry version 197.
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="http://atlasgeneticsoncology.org/Genes/TMPRSS3ID42593ch21q22.html";
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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.ENSP00000291532; -.
DR MEROPS; S01.079; -.
DR TCDB; 8.A.131.1.1; the transmembrane protease serine 3 (tmprss3) family.
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; P57727; -.
DR PeptideAtlas; P57727; -.
DR PRIDE; P57727; -.
DR Antibodypedia; 23790; 295 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 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; 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; ITPLWVV; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; P57727; -.
DR TreeFam; TF351678; -.
DR PathwayCommons; P57727; -.
DR SignaLink; P57727; -.
DR BioGRID-ORCS; 64699; 10 hits in 1065 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 tissues.
DR ExpressionAtlas; P57727; baseline and differential.
DR Genevisible; P57727; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; HDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005044; F:scavenger receptor activity; IEA:InterPro.
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:cellular 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; 2.40.10.10; -; 1.
DR Gene3D; 3.10.250.10; -; 1.
DR Gene3D; 4.10.400.10; -; 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 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; SSF50494; SSF50494; 1.
DR SUPFAM; SSF56487; SSF56487; 1.
DR SUPFAM; SSF57424; SSF57424; 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.
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
