UROK_MOUSE
ID UROK_MOUSE Reviewed; 433 AA.
AC P06869;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=Urokinase-type plasminogen activator;
DE Short=U-plasminogen activator;
DE Short=uPA;
DE EC=3.4.21.73;
DE Contains:
DE RecName: Full=Urokinase-type plasminogen activator long chain A;
DE Contains:
DE RecName: Full=Urokinase-type plasminogen activator short chain A;
DE Contains:
DE RecName: Full=Urokinase-type plasminogen activator chain B;
DE Flags: Precursor;
GN Name=Plau;
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].
RX PubMed=2985383; DOI=10.1111/j.1432-1033.1985.tb08829.x;
RA Belin D., Vassalli J.-D., Combepine C., Godeau F., Nagamine Y., Reich E.,
RA Kocher H.P., Duvoisin R.M.;
RT "Cloning, nucleotide sequencing and expression of cDNAs encoding mouse
RT urokinase-type plasminogen activator.";
RL Eur. J. Biochem. 148:225-232(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2831940; DOI=10.1021/bi00399a038;
RA Degen S.J.F., Heckel J.L., Reich E., Degen J.L.;
RT "The murine urokinase-type plasminogen activator gene.";
RL Biochemistry 26:8270-8279(1987).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 21-154 IN COMPLEX WITH PLAUR, AND
RP DISULFIDE BONDS.
RX PubMed=20133942; DOI=10.1074/jbc.m109.093492;
RA Lin L., Gardsvoll H., Huai Q., Huang M., Ploug M.;
RT "Structure-based engineering of species selectivity in the interaction
RT between urokinase and its receptor: implication for preclinical cancer
RT therapy.";
RL J. Biol. Chem. 285:10982-10992(2010).
CC -!- FUNCTION: Specifically cleaves the zymogen plasminogen to form the
CC active enzyme plasmin. {ECO:0000250|UniProtKB:P00749}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Specific cleavage of Arg-|-Val bond in plasminogen to form
CC plasmin.; EC=3.4.21.73;
CC -!- ACTIVITY REGULATION: Inhibited by SERPINA5.
CC {ECO:0000250|UniProtKB:P00749}.
CC -!- SUBUNIT: Found in high and low molecular mass forms. Each consists of
CC two chains, A and B. The high molecular mass form contains a long chain
CC A which is cleaved to yield a short chain A. Forms heterodimer with
CC SERPINA5. Binds LRP1B; binding is followed by internalization and
CC degradation. Interacts with MRC2. Interacts with PLAUR. In complex with
CC SERPINE1, interacts with PLAUR/uPAR. Interacts with SORL1 and LRP1,
CC either alone or in complex with SERPINE1; these interactions are
CC abolished in the presence of LRPAP1/RAP. The ternary complex composed
CC of PLAUR-PLAU-PAI1 also interacts with SORLA.
CC {ECO:0000250|UniProtKB:P00749}.
CC -!- INTERACTION:
CC P06869; Q9Z0K7: Slurp1; NbExp=4; IntAct=EBI-8365661, EBI-14060702;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P00749}.
CC -!- PTM: Produced as an inactive single-chain protein (pro-uPA or sc-uPA),
CC is processed into the active disulfide-linked two-chain form of
CC PLAU/uPA by a proteolytic event mediated, at least, by TMPRSS4.
CC {ECO:0000250|UniProtKB:P00749}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
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DR EMBL; X02389; CAA26231.1; -; mRNA.
DR EMBL; M17922; AAA40539.1; -; Genomic_DNA.
DR CCDS; CCDS26858.1; -.
DR PIR; A29420; UKMS.
DR RefSeq; NP_032899.1; NM_008873.3.
DR RefSeq; XP_017171408.1; XM_017315919.1.
DR PDB; 3LAQ; X-ray; 3.20 A; A/B=21-154.
DR PDB; 5LHN; X-ray; 2.55 A; A=180-426.
DR PDB; 5LHP; X-ray; 2.63 A; A=180-426.
DR PDB; 5LHQ; X-ray; 2.60 A; A=180-426.
DR PDB; 5LHR; X-ray; 2.30 A; A=180-426.
DR PDB; 5LHS; X-ray; 3.05 A; A/B/C/D=180-426.
DR PDB; 6A8G; X-ray; 2.53 A; A/B=180-426.
DR PDB; 6A8N; X-ray; 2.49 A; A/B=180-426.
DR PDBsum; 3LAQ; -.
DR PDBsum; 5LHN; -.
DR PDBsum; 5LHP; -.
DR PDBsum; 5LHQ; -.
DR PDBsum; 5LHR; -.
DR PDBsum; 5LHS; -.
DR PDBsum; 6A8G; -.
DR PDBsum; 6A8N; -.
DR AlphaFoldDB; P06869; -.
DR SMR; P06869; -.
DR BioGRID; 202230; 1.
DR ComplexPortal; CPX-495; uPA-PAI-1 complex.
DR ComplexPortal; CPX-510; uPA-uPAR complex.
DR ComplexPortal; CPX-526; uPA-uPAR-vitronectin complex.
DR CORUM; P06869; -.
DR IntAct; P06869; 1.
DR STRING; 10090.ENSMUSP00000022368; -.
DR BindingDB; P06869; -.
DR ChEMBL; CHEMBL1075311; -.
DR MEROPS; S01.231; -.
DR PhosphoSitePlus; P06869; -.
DR PaxDb; P06869; -.
DR PeptideAtlas; P06869; -.
DR PRIDE; P06869; -.
DR ProteomicsDB; 275390; -.
DR ABCD; P06869; 2 sequenced antibodies.
DR Antibodypedia; 1899; 1048 antibodies from 44 providers.
DR DNASU; 18792; -.
DR Ensembl; ENSMUST00000022368; ENSMUSP00000022368; ENSMUSG00000021822.
DR GeneID; 18792; -.
DR KEGG; mmu:18792; -.
DR UCSC; uc007skx.2; mouse.
DR CTD; 5328; -.
DR MGI; MGI:97611; Plau.
DR VEuPathDB; HostDB:ENSMUSG00000021822; -.
DR eggNOG; ENOG502QRMI; Eukaryota.
DR GeneTree; ENSGT01050000244971; -.
DR HOGENOM; CLU_006842_18_4_1; -.
DR InParanoid; P06869; -.
DR OMA; WIAGIFQ; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; P06869; -.
DR TreeFam; TF329901; -.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR Reactome; R-MMU-75205; Dissolution of Fibrin Clot.
DR BioGRID-ORCS; 18792; 2 hits in 74 CRISPR screens.
DR EvolutionaryTrace; P06869; -.
DR PRO; PR:P06869; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; P06869; protein.
DR Bgee; ENSMUSG00000021822; Expressed in ectoplacental cone and 109 other tissues.
DR ExpressionAtlas; P06869; baseline and differential.
DR Genevisible; P06869; MM.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IC:ComplexPortal.
DR GO; GO:0098637; C:protein complex involved in cell-matrix adhesion; ISO:MGI.
DR GO; GO:0097180; C:serine protease inhibitor complex; ISO:MGI.
DR GO; GO:1905370; C:serine-type endopeptidase complex; IPI:ComplexPortal.
DR GO; GO:0008233; F:peptidase activity; ISO:MGI.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; ISO:MGI.
DR GO; GO:0042730; P:fibrinolysis; IMP:MGI.
DR GO; GO:0051918; P:negative regulation of fibrinolysis; IC:ComplexPortal.
DR GO; GO:0010757; P:negative regulation of plasminogen activation; IC:ComplexPortal.
DR GO; GO:0070997; P:neuron death; ISO:MGI.
DR GO; GO:0031639; P:plasminogen activation; ISO:MGI.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0060279; P:positive regulation of ovulation; ISO:MGI.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; ISO:MGI.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; ISO:MGI.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR GO; GO:0030155; P:regulation of cell adhesion; ISO:MGI.
DR GO; GO:0033628; P:regulation of cell adhesion mediated by integrin; ISO:MGI.
DR GO; GO:0042127; P:regulation of cell population proliferation; IGI:MGI.
DR GO; GO:0051917; P:regulation of fibrinolysis; IC:ComplexPortal.
DR GO; GO:2000345; P:regulation of hepatocyte proliferation; ISO:MGI.
DR GO; GO:0010755; P:regulation of plasminogen activation; IC:ComplexPortal.
DR GO; GO:0010469; P:regulation of signaling receptor activity; ISO:MGI.
DR GO; GO:0014910; P:regulation of smooth muscle cell migration; ISO:MGI.
DR GO; GO:2000097; P:regulation of smooth muscle cell-matrix adhesion; ISO:MGI.
DR GO; GO:0001666; P:response to hypoxia; IMP:MGI.
DR GO; GO:0043403; P:skeletal muscle tissue regeneration; ISO:MGI.
DR GO; GO:0014909; P:smooth muscle cell migration; IMP:MGI.
DR GO; GO:0038195; P:urokinase plasminogen activator signaling pathway; IC:ComplexPortal.
DR GO; GO:0042060; P:wound healing; ISO:MGI.
DR CDD; cd00108; KR; 1.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 1.
DR Gene3D; 2.40.20.10; -; 1.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000001; Kringle.
DR InterPro; IPR013806; Kringle-like.
DR InterPro; IPR018056; Kringle_CS.
DR InterPro; IPR038178; Kringle_sf.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR033116; TRYPSIN_SER.
DR InterPro; IPR034814; Urokinase.
DR PANTHER; PTHR24264:SF38; PTHR24264:SF38; 1.
DR Pfam; PF00051; Kringle; 1.
DR Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00130; KR; 1.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF57440; SSF57440; 1.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS50026; EGF_3; 1.
DR PROSITE; PS00021; KRINGLE_1; 1.
DR PROSITE; PS50070; KRINGLE_2; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; EGF-like domain; Hydrolase; Kringle;
KW Phosphoprotein; Plasminogen activation; Protease; Reference proteome;
KW Secreted; Serine protease; Signal; Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..433
FT /note="Urokinase-type plasminogen activator"
FT /id="PRO_0000028322"
FT CHAIN 21..178
FT /note="Urokinase-type plasminogen activator long chain A"
FT /evidence="ECO:0000250"
FT /id="PRO_0000028323"
FT CHAIN 157..178
FT /note="Urokinase-type plasminogen activator short chain A"
FT /evidence="ECO:0000250"
FT /id="PRO_0000028324"
FT CHAIN 180..433
FT /note="Urokinase-type plasminogen activator chain B"
FT /evidence="ECO:0000250"
FT /id="PRO_0000028325"
FT DOMAIN 28..64
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 71..152
FT /note="Kringle"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 180..426
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT REGION 35..58
FT /note="Binds urokinase plasminogen activator surface
FT receptor"
FT /evidence="ECO:0000250"
FT REGION 153..179
FT /note="Connecting peptide"
FT ACT_SITE 226
FT /note="Charge relay system"
FT ACT_SITE 277
FT /note="Charge relay system"
FT ACT_SITE 378
FT /note="Charge relay system"
FT MOD_RES 159
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P00749"
FT DISULFID 32..40
FT /evidence="ECO:0000269|PubMed:20133942"
FT DISULFID 34..52
FT /evidence="ECO:0000269|PubMed:20133942"
FT DISULFID 54..63
FT /evidence="ECO:0000269|PubMed:20133942"
FT DISULFID 71..152
FT /evidence="ECO:0000269|PubMed:20133942"
FT DISULFID 92..134
FT /evidence="ECO:0000269|PubMed:20133942"
FT DISULFID 123..147
FT /evidence="ECO:0000269|PubMed:20133942"
FT DISULFID 169..301
FT /note="Interchain (between A and B chains)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000255|PROSITE-ProRule:PRU00121, ECO:0000255|PROSITE-
FT ProRule:PRU00274"
FT DISULFID 211..227
FT /evidence="ECO:0000250"
FT DISULFID 219..290
FT /evidence="ECO:0000250"
FT DISULFID 315..384
FT /evidence="ECO:0000250"
FT DISULFID 347..363
FT /evidence="ECO:0000250"
FT DISULFID 374..402
FT /evidence="ECO:0000250"
FT STRAND 40..42
FT /evidence="ECO:0007829|PDB:3LAQ"
FT HELIX 44..46
FT /evidence="ECO:0007829|PDB:3LAQ"
FT STRAND 50..52
FT /evidence="ECO:0007829|PDB:3LAQ"
FT TURN 60..63
FT /evidence="ECO:0007829|PDB:3LAQ"
FT STRAND 65..68
FT /evidence="ECO:0007829|PDB:3LAQ"
FT HELIX 100..102
FT /evidence="ECO:0007829|PDB:3LAQ"
FT STRAND 103..106
FT /evidence="ECO:0007829|PDB:3LAQ"
FT TURN 110..116
FT /evidence="ECO:0007829|PDB:3LAQ"
FT STRAND 118..120
FT /evidence="ECO:0007829|PDB:3LAQ"
FT STRAND 133..138
FT /evidence="ECO:0007829|PDB:3LAQ"
FT STRAND 141..147
FT /evidence="ECO:0007829|PDB:3LAQ"
FT STRAND 181..185
FT /evidence="ECO:0007829|PDB:5LHR"
FT HELIX 188..190
FT /evidence="ECO:0007829|PDB:5LHR"
FT STRAND 194..199
FT /evidence="ECO:0007829|PDB:5LHR"
FT STRAND 202..204
FT /evidence="ECO:0007829|PDB:5LHQ"
FT STRAND 208..217
FT /evidence="ECO:0007829|PDB:5LHR"
FT STRAND 220..223
FT /evidence="ECO:0007829|PDB:5LHR"
FT HELIX 225..227
FT /evidence="ECO:0007829|PDB:5LHR"
FT STRAND 229..231
FT /evidence="ECO:0007829|PDB:5LHR"
FT HELIX 234..236
FT /evidence="ECO:0007829|PDB:5LHR"
FT STRAND 237..242
FT /evidence="ECO:0007829|PDB:5LHR"
FT STRAND 254..263
FT /evidence="ECO:0007829|PDB:5LHR"
FT STRAND 268..270
FT /evidence="ECO:0007829|PDB:5LHR"
FT STRAND 273..276
FT /evidence="ECO:0007829|PDB:5LHR"
FT STRAND 279..284
FT /evidence="ECO:0007829|PDB:5LHR"
FT STRAND 314..320
FT /evidence="ECO:0007829|PDB:5LHR"
FT STRAND 323..326
FT /evidence="ECO:0007829|PDB:5LHQ"
FT STRAND 335..342
FT /evidence="ECO:0007829|PDB:5LHR"
FT HELIX 344..347
FT /evidence="ECO:0007829|PDB:5LHR"
FT TURN 350..353
FT /evidence="ECO:0007829|PDB:5LHR"
FT HELIX 354..356
FT /evidence="ECO:0007829|PDB:5LHR"
FT STRAND 361..365
FT /evidence="ECO:0007829|PDB:5LHR"
FT STRAND 381..386
FT /evidence="ECO:0007829|PDB:5LHR"
FT STRAND 389..398
FT /evidence="ECO:0007829|PDB:5LHR"
FT STRAND 400..404
FT /evidence="ECO:0007829|PDB:5LHR"
FT STRAND 405..407
FT /evidence="ECO:0007829|PDB:5LHS"
FT STRAND 409..413
FT /evidence="ECO:0007829|PDB:5LHR"
FT HELIX 414..416
FT /evidence="ECO:0007829|PDB:5LHR"
FT HELIX 418..422
FT /evidence="ECO:0007829|PDB:5LHR"
SQ SEQUENCE 433 AA; 48268 MW; A99C35F6250443F9 CRC64;
MKVWLASLFL CALVVKNSEG GSVLGAPDES NCGCQNGGVC VSYKYFSRIR RCSCPRKFQG
EHCEIDASKT CYHGNGDSYR GKANTDTKGR PCLAWNAPAV LQKPYNAHRP DAISLGLGKH
NYCRNPDNQK RPWCYVQIGL RQFVQECMVH DCSLSKKPSS SVDQQGFQCG QKALRPRFKI
VGGEFTEVEN QPWFAAIYQK NKGGSPPSFK CGGSLISPCW VASAAHCFIQ LPKKENYVVY
LGQSKESSYN PGEMKFEVEQ LILHEYYRED SLAYHNDIAL LKIRTSTGQC AQPSRSIQTI
CLPPRFTDAP FGSDCEITGF GKESESDYLY PKNLKMSVVK LVSHEQCMQP HYYGSEINYK
MLCAADPEWK TDSCKGDSGG PLICNIEGRP TLSGIVSWGR GCAEKNKPGV YTRVSHFLDW
IQSHIGEEKG LAF
