TMPS3_MOUSE
ID TMPS3_MOUSE Reviewed; 453 AA.
AC Q8K1T0; Q812A6; Q8VDE0;
DT 30-MAY-2003, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Transmembrane protease serine 3;
DE EC=3.4.21.-;
GN Name=Tmprss3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], SUBCELLULAR LOCATION, AND
RP 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 [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Rao N.V., Rao G.N., Hoidal J.R.;
RT "Genomic organization of murine transmembrane proteinases.";
RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND ALTERNATIVE
RP SPLICING (ISOFORM 2).
RX PubMed=21454591; DOI=10.1074/jbc.m110.190652;
RA Fasquelle L., Scott H.S., Lenoir M., Wang J., Rebillard G., Gaboyard S.,
RA Venteo S., Francois F., Mausset-Bonnefont A.L., Antonarakis S.E.,
RA Neidhart E., Chabbert C., Puel J.L., Guipponi M., Delprat B.;
RT "Tmprss3, a transmembrane serine protease deficient in human DFNB8/10
RT deafness, is critical for cochlear hair cell survival at the onset of
RT hearing.";
RL J. Biol. Chem. 286:17383-17397(2011).
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
CC survival. Activates ENaC (in vitro). {ECO:0000269|PubMed:12393794,
CC ECO:0000269|PubMed:21454591}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:12393794, ECO:0000269|PubMed:21454591}; Single-pass
CC type II membrane protein {ECO:0000269|PubMed:12393794,
CC ECO:0000269|PubMed:21454591}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8K1T0-1; Sequence=Displayed;
CC Name=2; Synonyms=F;
CC IsoId=Q8K1T0-2; Sequence=VSP_041581;
CC -!- TISSUE SPECIFICITY: Strongly expressed in liver, cochlea, brain,
CC cerebellum, spleen, lung, and muscle and at a lower degree in retina,
CC kidney, and heart. Expressed in the spiral ganglion, the cells
CC supporting the organ of Corti and the stria vascularis. Isoform 2 is
CC strongly expressed only in the cochlea with very faint expression in
CC the cerebellum, spleen and muscle. {ECO:0000269|PubMed:21454591}.
CC -!- PTM: Undergoes autoproteolytic activation.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
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DR EMBL; AJ429216; CAD22137.1; -; Genomic_DNA.
DR EMBL; AJ300738; CAC83350.1; -; mRNA.
DR EMBL; AY261383; AAO33581.1; -; Genomic_DNA.
DR CCDS; CCDS37547.1; -. [Q8K1T0-1]
DR CCDS; CCDS50053.1; -. [Q8K1T0-2]
DR RefSeq; NP_542765.2; NM_080727.2. [Q8K1T0-1]
DR AlphaFoldDB; Q8K1T0; -.
DR SMR; Q8K1T0; -.
DR STRING; 10090.ENSMUSP00000110196; -.
DR MEROPS; S01.079; -.
DR GlyGen; Q8K1T0; 1 site.
DR PhosphoSitePlus; Q8K1T0; -.
DR PaxDb; Q8K1T0; -.
DR PRIDE; Q8K1T0; -.
DR Antibodypedia; 23790; 295 antibodies from 34 providers.
DR DNASU; 140765; -.
DR Ensembl; ENSMUST00000024833; ENSMUSP00000024833; ENSMUSG00000024034. [Q8K1T0-1]
DR Ensembl; ENSMUST00000114549; ENSMUSP00000110196; ENSMUSG00000024034. [Q8K1T0-2]
DR Ensembl; ENSMUST00000236793; ENSMUSP00000158048; ENSMUSG00000024034. [Q8K1T0-1]
DR GeneID; 140765; -.
DR KEGG; mmu:140765; -.
DR UCSC; uc008bup.2; mouse. [Q8K1T0-1]
DR CTD; 64699; -.
DR MGI; MGI:2155445; Tmprss3.
DR VEuPathDB; HostDB:ENSMUSG00000024034; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000158589; -.
DR HOGENOM; CLU_006842_19_2_1; -.
DR InParanoid; Q8K1T0; -.
DR OMA; ITPLWVV; -.
DR TreeFam; TF351678; -.
DR BioGRID-ORCS; 140765; 0 hits in 74 CRISPR screens.
DR PRO; PR:Q8K1T0; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q8K1T0; protein.
DR Bgee; ENSMUSG00000024034; Expressed in epithelium of cochlear duct and 40 other tissues.
DR ExpressionAtlas; Q8K1T0; baseline and differential.
DR Genevisible; Q8K1T0; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043025; C:neuronal cell body; IDA:UniProtKB.
DR GO; GO:0005044; F:scavenger receptor activity; IEA:InterPro.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0017080; F:sodium channel regulator activity; ISO:MGI.
DR GO; GO:0006883; P:cellular sodium ion homeostasis; ISO:MGI.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0007605; P:sensory perception of sound; IMP:UniProtKB.
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; 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; Disulfide bond; Endoplasmic reticulum; Glycoprotein;
KW Hydrolase; Membrane; Protease; Reference proteome; Serine protease;
KW Signal-anchor; Transmembrane; Transmembrane helix; Zymogen.
FT CHAIN 1..453
FT /note="Transmembrane protease serine 3"
FT /id="PRO_0000088691"
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..453
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 104..205
FT /note="SRCR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 217..448
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 400
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..406
FT /evidence="ECO:0000250"
FT DISULFID 369..385
FT /evidence="ECO:0000250"
FT DISULFID 396..424
FT /evidence="ECO:0000250"
FT VAR_SEQ 1
FT /note="M -> MAASEMVEVEPEPNIRGPEIVTM (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_041581"
FT CONFLICT 117
FT /note="L -> H (in Ref. 1; CAC83350)"
FT /evidence="ECO:0000305"
FT CONFLICT 246
FT /note="I -> V (in Ref. 1; CAD22137)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 453 AA; 49506 MW; 1EE7ECD6CB3DD894 CRC64;
MGENDPPAAE APFSFRSLFG LDDLKISPVA PDGDAVAAQI LSLLPLKFFP IIVIGIIALI
LALAIGLGIH FDCSGKYRCH SSFKCIELTA RCDGVSDCKN AEDEYRCVRV SGQRAALQVF
TAAAWRTMCS DDWKSHYAKI ACAQLGFPSY VSSDHLRVDA LEEQFQGDFV SINHLLSDDK
VTALHHSVYM REGCTSGHVV TLKCSACGTR TGYSPRIVGG NMSSLTQWPW QVSLQFQGYH
LCGGSIITPL WIVTAAHCVY DLYHPKSWTV QVGLVSLMDS PVPSHLVEKI IYHSKYKPKR
LGNDIALMKL SEPLTFDETI QPICLPNSEE NFPDGKLCWT SGWGATEDGG DASPVLNHAA
VPLISNKICN HRDVYGGIIS PSMLCAGYLK GGVDSCQGDS GGPLVCQERR LWKLVGATSF
GIGCAEVNKP GVYTRITSFL DWIHEQLERD LKT
