TMPS2_MOUSE
ID TMPS2_MOUSE Reviewed; 490 AA.
AC Q9JIQ8; Q7TN04; Q9JKC4; Q9QY82;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Transmembrane protease serine 2;
DE EC=3.4.21.-;
DE AltName: Full=Epitheliasin;
DE AltName: Full=Plasmic transmembrane protein X;
DE Contains:
DE RecName: Full=Transmembrane protease serine 2 non-catalytic chain;
DE Contains:
DE RecName: Full=Transmembrane protease serine 2 catalytic chain;
GN Name=Tmprss2;
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 [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ;
RX PubMed=11169526;
RX DOI=10.1002/1096-9896(2000)9999:9999<::aid-path743>3.0.co;2-t;
RA Vaarala M.H., Porvari K.S., Kellokumpu S., Kyllonen A.P., Vihko P.T.;
RT "Expression of transmembrane serine protease TMPRSS2 in mouse and human
RT tissues.";
RL J. Pathol. 193:134-140(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Han J., Kim S.;
RT "Putative transmembrane protease X.";
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
RX PubMed=10683448; DOI=10.1016/s0014-5793(00)01196-0;
RA Jacquinet E.J., Rao N.V., Rao G.V., Hoidal J.R.;
RT "Cloning, genomic organization, chromosomal assignment and expression of a
RT novel mosaic serine proteinase: epitheliasin.";
RL FEBS Lett. 468:93-100(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=129; TISSUE=Mammary gland;
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 [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=16428450; DOI=10.1128/mcb.26.3.965-975.2006;
RA Kim T.S., Heinlein C., Hackman R.C., Nelson P.S.;
RT "Phenotypic analysis of mice lacking the Tmprss2-encoded protease.";
RL Mol. Cell. Biol. 26:965-975(2006).
RN [6]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=24348248; DOI=10.1371/journal.ppat.1003774;
RA Hatesuer B., Bertram S., Mehnert N., Bahgat M.M., Nelson P.S., Poehlman S.,
RA Schughart K.;
RT "Tmprss2 is essential for influenza H1N1 virus pathogenesis in mice.";
RL PLoS Pathog. 9:E1003774-E1003774(2013).
RN [7]
RP FUNCTION (MICROBIAL INFECTION), AND DISRUPTION PHENOTYPE.
RX PubMed=24600012; DOI=10.1128/jvi.03677-13;
RA Sakai K., Ami Y., Tahara M., Kubota T., Anraku M., Abe M., Nakajima N.,
RA Sekizuka T., Shirato K., Suzaki Y., Ainai A., Nakatsu Y., Kanou K.,
RA Nakamura K., Suzuki T., Komase K., Nobusawa E., Maenaka K., Kuroda M.,
RA Hasegawa H., Kawaoka Y., Tashiro M., Takeda M.;
RT "The host protease TMPRSS2 plays a major role for in vivo replication of
RT emerging H7N9 and seasonal influenza viruses.";
RL J. Virol. 88:5608-5616(2014).
RN [8]
RP FUNCTION (MICROBIAL INFECTION), DISRUPTION PHENOTYPE, AND TISSUE
RP SPECIFICITY.
RX PubMed=24522916; DOI=10.1128/jvi.03799-13;
RA Tarnow C., Engels G., Arendt A., Schwalm F., Sediri H., Preuss A.,
RA Nelson P.S., Garten W., Klenk H.D., Gabriel G.,
RA Boettcher-Friebertshaeuser E.;
RT "TMPRSS2 is a host factor that is essential for pneumotropism and
RT pathogenicity of H7N9 influenza A virus in mice.";
RL J. Virol. 88:4744-4751(2014).
RN [9]
RP FUNCTION.
RX PubMed=25734995; DOI=10.1097/j.pain.0000000000000130;
RA Lam D.K., Dang D., Flynn A.N., Hardt M., Schmidt B.L.;
RT "TMPRSS2, a novel membrane-anchored mediator in cancer pain.";
RL Pain 156:923-930(2015).
CC -!- FUNCTION: Plasma membrane-anchored serine protease that participates in
CC proteolytic cascades of relevance for the normal physiologic function
CC of the prostate. Androgen-induced TMPRSS2 activates several substrates
CC that include pro-hepatocyte growth factor/HGF, the protease activated
CC receptor-2/F2RL1 or matriptase/ST14 leading to extracellular matrix
CC disruption (By similarity). In addition, activates trigeminal neurons
CC and contribute to both spontaneous pain and mechanical allodynia
CC (PubMed:25734995). {ECO:0000250|UniProtKB:O15393,
CC ECO:0000269|PubMed:25734995}.
CC -!- FUNCTION: (Microbial infection) Essential for spread and pathogenesis
CC of influenza A virus (strains H1N1, H3N2 and H7N9) and is involved in
CC proteolytic cleavage and activation of hemagglutinin (HA) protein which
CC is essential for viral infectivity. {ECO:0000269|PubMed:24348248,
CC ECO:0000269|PubMed:24522916, ECO:0000269|PubMed:24600012}.
CC -!- SUBUNIT: The catalytically active form interacts with ACE2.
CC {ECO:0000250|UniProtKB:O15393}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O15393};
CC Single-pass type II membrane protein {ECO:0000250|UniProtKB:O15393}.
CC -!- SUBCELLULAR LOCATION: [Transmembrane protease serine 2 catalytic
CC chain]: Secreted {ECO:0000250|UniProtKB:O15393}. Note=Activated by
CC cleavage and secreted. {ECO:0000250|UniProtKB:O15393}.
CC -!- TISSUE SPECIFICITY: Larynx, trachea and bronchi, lung, prostate and
CC kidney. {ECO:0000269|PubMed:11169526, ECO:0000269|PubMed:24522916}.
CC -!- PTM: Proteolytically processed; by an autocatalytic mechanism.
CC {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice show normal growth and reach normal
CC adulthood without having abnormalities in organ histology and
CC alteration in protein levels of prostatic secretions (PubMed:16428450).
CC Abrogation of viral spread and protection of mice from severe pathology
CC and death are observed after infection with influenza A virus strains
CC H1N1 and H7N9. {ECO:0000269|PubMed:16428450,
CC ECO:0000269|PubMed:24522916, ECO:0000269|PubMed:24600012}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
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DR EMBL; AF199362; AAF97867.1; -; mRNA.
DR EMBL; AF243500; AAF64186.1; -; mRNA.
DR EMBL; AF113596; AAF21308.1; -; mRNA.
DR EMBL; BC038393; AAH38393.1; -; mRNA.
DR EMBL; BC054348; AAH54348.1; -; mRNA.
DR CCDS; CCDS37417.1; -.
DR RefSeq; NP_056590.2; NM_015775.2.
DR RefSeq; XP_006523127.1; XM_006523064.3.
DR RefSeq; XP_006523128.1; XM_006523065.2.
DR AlphaFoldDB; Q9JIQ8; -.
DR SMR; Q9JIQ8; -.
DR STRING; 10090.ENSMUSP00000000395; -.
DR MEROPS; S01.247; -.
DR GlyGen; Q9JIQ8; 3 sites.
DR iPTMnet; Q9JIQ8; -.
DR PhosphoSitePlus; Q9JIQ8; -.
DR MaxQB; Q9JIQ8; -.
DR PaxDb; Q9JIQ8; -.
DR PRIDE; Q9JIQ8; -.
DR ProteomicsDB; 259042; -.
DR Antibodypedia; 2685; 294 antibodies from 35 providers.
DR DNASU; 50528; -.
DR Ensembl; ENSMUST00000000395; ENSMUSP00000000395; ENSMUSG00000000385.
DR GeneID; 50528; -.
DR KEGG; mmu:50528; -.
DR UCSC; uc008adl.1; mouse.
DR CTD; 7113; -.
DR MGI; MGI:1354381; Tmprss2.
DR VEuPathDB; HostDB:ENSMUSG00000000385; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000155207; -.
DR HOGENOM; CLU_006842_19_2_1; -.
DR InParanoid; Q9JIQ8; -.
DR OMA; AQRKSWH; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; Q9JIQ8; -.
DR TreeFam; TF351678; -.
DR BRENDA; 3.4.21.B60; 3474.
DR BioGRID-ORCS; 50528; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Tmprss2; mouse.
DR PRO; PR:Q9JIQ8; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q9JIQ8; protein.
DR Bgee; ENSMUSG00000000385; Expressed in paneth cell and 157 other tissues.
DR ExpressionAtlas; Q9JIQ8; baseline and differential.
DR Genevisible; Q9JIQ8; MM.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISS: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:0046598; P:positive regulation of viral entry into host cell; ISS:UniProtKB.
DR GO; GO:0016540; P:protein autoprocessing; ISS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IDA: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 2: Evidence at transcript level;
KW Autocatalytic cleavage; Cell membrane; Disulfide bond; Glycoprotein;
KW Hydrolase; Membrane; Protease; Reference proteome; Secreted;
KW Serine protease; Signal-anchor; Transmembrane; Transmembrane helix;
KW Zymogen.
FT CHAIN 1..253
FT /note="Transmembrane protease serine 2 non-catalytic chain"
FT /id="PRO_0000027857"
FT CHAIN 254..490
FT /note="Transmembrane protease serine 2 catalytic chain"
FT /id="PRO_0000027858"
FT TOPO_DOM 1..83
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 84..104
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 105..490
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 111..149
FT /note="LDL-receptor class A"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 150..242
FT /note="SRCR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00196"
FT DOMAIN 254..487
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 294
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 343
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 439
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT SITE 253..254
FT /note="Cleavage"
FT /evidence="ECO:0000255"
FT CARBOHYD 111
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 212
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 474
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 112..125
FT /evidence="ECO:0000250"
FT DISULFID 119..138
FT /evidence="ECO:0000250"
FT DISULFID 132..147
FT /evidence="ECO:0000250"
FT DISULFID 171..230
FT /evidence="ECO:0000250"
FT DISULFID 184..240
FT /evidence="ECO:0000250"
FT DISULFID 243..363
FT /note="Interchain (between non-catalytic and catalytic
FT chains)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124,
FT ECO:0000255|PROSITE-ProRule:PRU00196, ECO:0000255|PROSITE-
FT ProRule:PRU00274"
FT DISULFID 279..295
FT /evidence="ECO:0000250"
FT DISULFID 408..424
FT /evidence="ECO:0000250"
FT DISULFID 435..463
FT /evidence="ECO:0000250"
FT CONFLICT 75
FT /note="L -> P (in Ref. 1; AAF97867, 2; AAF64186, 3;
FT AAF21308 and 4; AAH38393)"
FT /evidence="ECO:0000305"
FT CONFLICT 122
FT /note="S -> L (in Ref. 3; AAF21308)"
FT /evidence="ECO:0000305"
FT CONFLICT 178
FT /note="S -> N (in Ref. 3; AAF21308)"
FT /evidence="ECO:0000305"
FT CONFLICT 302
FT /note="S -> G (in Ref. 1; AAF97867, 2; AAF64186, 3;
FT AAF21308 and 4; AAH38393)"
FT /evidence="ECO:0000305"
FT CONFLICT 320
FT /note="Y -> H (in Ref. 1; AAF97867)"
FT /evidence="ECO:0000305"
FT CONFLICT 474
FT /note="N -> D (in Ref. 1; AAF97867)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 490 AA; 53526 MW; 54650B028417665A CRC64;
MALNSGSPPG IGPCYENHGY QSEHICPPRP PVAPNGYNLY PAQYYPSPVP QYAPRITTQA
STSVIHTHPK SSGALCTSKS KKSLCLALAL GTVLTGAAVA AVLLWRFWDS NCSTSEMECG
SSGTCISSSL WCDGVAHCPN GEDENRCVRL YGQSFILQVY SSQRKAWYPV CQDDWSESYG
RAACKDMGYK NNFYSSQGIP DQSGATSFMK LNVSSGNVDL YKKLYHSDSC SSRMVVSLRC
IECGVRSVKR QSRIVGGLNA SPGDWPWQVS LHVQGVHVCG GSIITPEWIV TAAHCVEEPL
SSPRYWTAFA GILRQSLMFY GSRHQVEKVI SHPNYDSKTK NNDIALMKLQ TPLAFNDLVK
PVCLPNPGMM LDLDQECWIS GWGATYEKGK TSDVLNAAMV PLIEPSKCNS KYIYNNLITP
AMICAGFLQG SVDSCQGDSG GPLVTLKNGI WWLIGDTSWG SGCAKALRPG VYGNVTVFTD
WIYQQMRANS
