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 27-MAR-2024, entry version 213. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 10090-ENSMUSP00000022368; -. DR PeptideAtlas; P06869; -. DR ProteomicsDB; 275390; -. DR Pumba; P06869; -. DR ABCD; P06869; 2 sequenced antibodies. DR Antibodypedia; 1899; 1126 antibodies from 45 providers. DR DNASU; 18792; -. DR Ensembl; ENSMUST00000022368.4; ENSMUSP00000022368.3; ENSMUSG00000021822.4. DR GeneID; 18792; -. DR KEGG; mmu:18792; -. DR UCSC; uc007skx.2; mouse. DR AGR; MGI:97611; -. 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; WPWCYVQ; -. DR OrthoDB; 4629979at2759; -. 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 79 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 110 other cell types or tissues. DR ExpressionAtlas; P06869; baseline and differential. DR GO; GO:0009986; C:cell surface; ISO:MGI. DR GO; GO:0009897; C:external side of plasma membrane; NAS:ComplexPortal. DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB. 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; NAS:ComplexPortal. DR GO; GO:0010757; P:negative regulation of plasminogen activation; NAS:ComplexPortal. 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: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: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; NAS:ComplexPortal. DR GO; GO:2000345; P:regulation of hepatocyte proliferation; ISO:MGI. DR GO; GO:0010755; P:regulation of plasminogen activation; NAS:ComplexPortal. 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; NAS:ComplexPortal. DR CDD; cd00108; KR; 1. DR CDD; cd00190; Tryp_SPc; 1. DR Gene3D; 2.10.25.10; Laminin; 1. DR Gene3D; 2.40.20.10; Plasminogen Kringle 4; 1. DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 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 PANTHER; PTHR24264; TRYPSIN-RELATED; 1. DR PANTHER; PTHR24264:SF38; UROKINASE-TYPE PLASMINOGEN ACTIVATOR; 1. DR Pfam; PF00051; Kringle; 1. DR Pfam; PF00089; Trypsin; 1. DR PRINTS; PR00722; CHYMOTRYPSIN. DR PRINTS; PR00018; KRINGLE. DR SMART; SM00130; KR; 1. DR SMART; SM00020; Tryp_SPc; 1. DR SUPFAM; SSF57440; Kringle-like; 1. DR SUPFAM; SSF50494; Trypsin-like serine proteases; 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. DR Genevisible; P06869; MM. 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 //