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Database: UniProt
Entry: TMPS3_HUMAN
LinkDB: TMPS3_HUMAN
Original site: 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
//
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