ID   UROK_RAT                Reviewed;         432 AA.
AC   P29598; Q6LBK5;
DT   01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-1993, sequence version 1.
DT   08-NOV-2023, entry version 176.
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   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Fischer 344;
RX   PubMed=1568219;
RA   Henderson B.R., Tansey W.P., Phillips S.M., Ramshaw I.A., Kefford R.F.;
RT   "Transcriptional and posttranscriptional activation of urokinase
RT   plasminogen activator gene expression in metastatic tumor cells.";
RL   Cancer Res. 52:2489-2496(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Kidney;
RA   Rabbani S.A.;
RL   Submitted (APR-1992) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 31-62, AND IDENTIFICATION OF UROKINASE
RP   PLASMINOGEN ACTIVATOR SURFACE RECEPTOR BINDING DOMAIN.
RX   PubMed=1321734; DOI=10.1016/0014-5793(92)80998-v;
RA   Ragno P., Cassano S., Degen J., Kessler C., Blasi F., Rossi G.;
RT   "The receptor for the plasminogen activator of urokinase type is up-
RT   regulated in transformed rat thyroid cells.";
RL   FEBS Lett. 306:193-198(1992).
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   -!- 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; X63434; CAA45028.1; -; mRNA.
DR   EMBL; X65651; CAA46601.1; -; mRNA.
DR   EMBL; X66907; CAA47356.1; -; Genomic_DNA.
DR   PIR; S24604; S18932.
DR   AlphaFoldDB; P29598; -.
DR   SMR; P29598; -.
DR   STRING; 10116.ENSRNOP00000014273; -.
DR   BindingDB; P29598; -.
DR   ChEMBL; CHEMBL1075245; -.
DR   MEROPS; S01.231; -.
DR   PhosphoSitePlus; P29598; -.
DR   PaxDb; 10116-ENSRNOP00000014273; -.
DR   UCSC; RGD:3343; rat.
DR   AGR; RGD:3343; -.
DR   RGD; 3343; Plau.
DR   eggNOG; ENOG502QRMI; Eukaryota.
DR   InParanoid; P29598; -.
DR   PhylomeDB; P29598; -.
DR   Reactome; R-RNO-6798695; Neutrophil degranulation.
DR   Reactome; R-RNO-75205; Dissolution of Fibrin Clot.
DR   PRO; PR:P29598; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0009986; C:cell surface; ISO:RGD.
DR   GO; GO:0005615; C:extracellular space; IDA:RGD.
DR   GO; GO:0098637; C:protein complex involved in cell-matrix adhesion; ISO:RGD.
DR   GO; GO:0097180; C:serine protease inhibitor complex; ISO:RGD.
DR   GO; GO:1905370; C:serine-type endopeptidase complex; ISO:RGD.
DR   GO; GO:0008233; F:peptidase activity; IDA:RGD.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
DR   GO; GO:0001525; P:angiogenesis; IMP:RGD.
DR   GO; GO:0071498; P:cellular response to fluid shear stress; IEP:RGD.
DR   GO; GO:0071333; P:cellular response to glucose stimulus; IEP:RGD.
DR   GO; GO:0035729; P:cellular response to hepatocyte growth factor stimulus; IEP:RGD.
DR   GO; GO:0071456; P:cellular response to hypoxia; IEP:RGD.
DR   GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:RGD.
DR   GO; GO:0071310; P:cellular response to organic substance; IEP:RGD.
DR   GO; GO:0072734; P:cellular response to staurosporine; IEP:RGD.
DR   GO; GO:0007566; P:embryo implantation; IEP:RGD.
DR   GO; GO:0042730; P:fibrinolysis; ISO:RGD.
DR   GO; GO:0031639; P:plasminogen activation; ISO:RGD.
DR   GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:RGD.
DR   GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IDA:RGD.
DR   GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IMP:RGD.
DR   GO; GO:0030155; P:regulation of cell adhesion; ISO:RGD.
DR   GO; GO:0033628; P:regulation of cell adhesion mediated by integrin; ISO:RGD.
DR   GO; GO:0042127; P:regulation of cell population proliferation; ISO:RGD.
DR   GO; GO:2000345; P:regulation of hepatocyte proliferation; IMP:RGD.
DR   GO; GO:0014910; P:regulation of smooth muscle cell migration; ISO:RGD.
DR   GO; GO:2000097; P:regulation of smooth muscle cell-matrix adhesion; ISO:RGD.
DR   GO; GO:0014823; P:response to activity; IEP:RGD.
DR   GO; GO:0035728; P:response to hepatocyte growth factor; IEP:RGD.
DR   GO; GO:0055093; P:response to hyperoxia; IEP:RGD.
DR   GO; GO:0001666; P:response to hypoxia; ISO:RGD.
DR   GO; GO:0043403; P:skeletal muscle tissue regeneration; IMP:RGD.
DR   GO; GO:0014909; P:smooth muscle cell migration; ISO:RGD.
DR   GO; GO:0007283; P:spermatogenesis; IEP:RGD.
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; 2.
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.
PE   1: Evidence at protein level;
KW   Disulfide bond; EGF-like domain; Hydrolase; Kringle; Phosphoprotein;
KW   Plasminogen activation; Protease; Reference proteome; Secreted;
KW   Serine protease; Signal; Zymogen.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000255"
FT   CHAIN           20..432
FT                   /note="Urokinase-type plasminogen activator"
FT                   /id="PRO_0000028333"
FT   CHAIN           20..177
FT                   /note="Urokinase-type plasminogen activator long chain A"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000028334"
FT   CHAIN           156..177
FT                   /note="Urokinase-type plasminogen activator short chain A"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000028335"
FT   CHAIN           179..432
FT                   /note="Urokinase-type plasminogen activator chain B"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000028336"
FT   DOMAIN          27..63
FT                   /note="EGF-like"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          70..151
FT                   /note="Kringle"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT   DOMAIN          179..425
FT                   /note="Peptidase S1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT   REGION          34..57
FT                   /note="Binds urokinase plasminogen activator surface
FT                   receptor"
FT   REGION          152..178
FT                   /note="Connecting peptide"
FT   ACT_SITE        225
FT                   /note="Charge relay system"
FT   ACT_SITE        276
FT                   /note="Charge relay system"
FT   ACT_SITE        377
FT                   /note="Charge relay system"
FT   MOD_RES         158
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P00749"
FT   DISULFID        31..39
FT                   /evidence="ECO:0000250"
FT   DISULFID        33..51
FT                   /evidence="ECO:0000250"
FT   DISULFID        53..62
FT                   /evidence="ECO:0000250"
FT   DISULFID        70..151
FT                   /evidence="ECO:0000250"
FT   DISULFID        91..133
FT                   /evidence="ECO:0000250"
FT   DISULFID        122..146
FT                   /evidence="ECO:0000250"
FT   DISULFID        168..300
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        210..226
FT                   /evidence="ECO:0000250"
FT   DISULFID        218..289
FT                   /evidence="ECO:0000250"
FT   DISULFID        314..383
FT                   /evidence="ECO:0000250"
FT   DISULFID        346..362
FT                   /evidence="ECO:0000250"
FT   DISULFID        373..401
FT                   /evidence="ECO:0000250"
FT   CONFLICT        16
FT                   /note="N -> H (in Ref. 2; CAA46601)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        24
FT                   /note="E -> G (in Ref. 2; CAA46601)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        332
FT                   /note="D -> N (in Ref. 2; CAA46601)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   432 AA;  47957 MW;  4EB1B96C716244C8 CRC64;
     MRVWLASLFL CALVANSEGG SELEASDESN CGCQNGGVCV SYKYFSSIRR CSCPKKFKGE
     HCEIDTSKTC YHGNGQSYRG KANTDTKGRP CLAWNSPAVL QQTYNAHRSD ALSLGLGKHN
     YCRNPDNQRR PWCYVQIGLK QFVQECMVQD CSLSKKPSST VDQQGFQCGQ KALRPRFKIV
     GGEFTVVENQ PWFAAIYLKN KGGSPPSFKC GGSLISPCWV ASATHCFVNQ PKKEEYVVYL
     GQSKRNSYNP GEMKFEVEQL ILHEDFSDET LAFHNDIALL KIRTSTGQCA QPSRTIQTIC
     LPPRFGDAPF GSDCEITGFG QESATDYFYP KDLKMSVVKI ISHEQCKQPH YYGSEINYKM
     LCAADPEWKT DSCSGDSGGP LICNIDGRPT LSGIVSWGSG CAEKNKPGVY TRVSYFLNWI
     QSHIGEENGL AF
//