UROK_RABIT
ID UROK_RABIT Reviewed; 433 AA.
AC Q8MHY7; Q8MIL0;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 125.
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 Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=12204121; DOI=10.1093/oxfordjournals.jbchem.a003248;
RA Sugiki M., Omura S., Yoshida E., Itoh H., Kataoka H., Maruyama M.;
RT "Downregulation of urokinase-type and tissue-type plasminogen activators in
RT a rabbit model of renal ischemia/reperfusion.";
RL J. Biochem. 132:501-508(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=12149463; DOI=10.1073/pnas.162236599;
RA Falkenberg M., Tom C., DeYoung M.B., Wen S., Linnemann R., Dichek D.A.;
RT "Increased expression of urokinase during atherosclerotic lesion
RT development causes arterial constriction and lumen loss, and accelerates
RT lesion growth.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:10665-10670(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Yano W., Watanabe M.;
RT "Oryctolagus cuniculus urokinase-type plasminogen activator, mRNA, complete
RT cds.";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Graf S.K., Wen S., Dichek D.A.;
RT "Rabbit urokinase plasminogen activator (genomic DNA).";
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
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: Phosphorylation of Ser-325 abolishes proadhesive ability but does
CC not interfere with receptor binding. {ECO:0000250}.
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; AY029517; AAK40239.1; -; mRNA.
DR EMBL; AY122285; AAM83187.1; -; mRNA.
DR EMBL; AB087224; BAC02685.1; -; mRNA.
DR EMBL; AY453856; AAR21232.1; -; Genomic_DNA.
DR RefSeq; NP_001075480.1; NM_001082011.1.
DR RefSeq; XP_008268125.1; XM_008269903.2.
DR AlphaFoldDB; Q8MHY7; -.
DR SMR; Q8MHY7; -.
DR STRING; 9986.ENSOCUP00000023296; -.
DR MEROPS; S01.231; -.
DR ABCD; Q8MHY7; 1 sequenced antibody.
DR Ensembl; ENSOCUT00000029709; ENSOCUP00000023296; ENSOCUG00000003155.
DR GeneID; 100008633; -.
DR KEGG; ocu:100008633; -.
DR CTD; 5328; -.
DR eggNOG; ENOG502QRMI; Eukaryota.
DR GeneTree; ENSGT01050000244971; -.
DR HOGENOM; CLU_006842_18_4_1; -.
DR InParanoid; Q8MHY7; -.
DR OMA; WIAGIFQ; -.
DR OrthoDB; 1314811at2759; -.
DR TreeFam; TF329901; -.
DR Proteomes; UP000001811; Chromosome 18.
DR Bgee; ENSOCUG00000003155; Expressed in adult mammalian kidney and 15 other tissues.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0098637; C:protein complex involved in cell-matrix adhesion; IEA:Ensembl.
DR GO; GO:0097180; C:serine protease inhibitor complex; IEA:Ensembl.
DR GO; GO:1905370; C:serine-type endopeptidase complex; IEA:Ensembl.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0042730; P:fibrinolysis; IEA:Ensembl.
DR GO; GO:0031639; P:plasminogen activation; IEA:Ensembl.
DR GO; GO:0030335; P:positive regulation of cell migration; IEA:Ensembl.
DR GO; GO:0033628; P:regulation of cell adhesion mediated by integrin; IEA:Ensembl.
DR GO; GO:0042127; P:regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0010469; P:regulation of signaling receptor activity; IEA:Ensembl.
DR GO; GO:0014910; P:regulation of smooth muscle cell migration; IEA:Ensembl.
DR GO; GO:2000097; P:regulation of smooth muscle cell-matrix adhesion; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0014909; P:smooth muscle cell migration; IEA:Ensembl.
DR CDD; cd00108; KR; 1.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
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; IPR018114; TRYPSIN_HIS.
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; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 2: Evidence at transcript level;
KW Disulfide bond; EGF-like domain; Glycoprotein; Hydrolase; Kringle;
KW Phosphoprotein; Plasminogen activation; Protease; Reference proteome;
KW Secreted; Serine protease; Signal; Zymogen.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..433
FT /note="Urokinase-type plasminogen activator"
FT /id="PRO_0000285901"
FT CHAIN 21..179
FT /note="Urokinase-type plasminogen activator long chain A"
FT /evidence="ECO:0000250"
FT /id="PRO_0000285902"
FT CHAIN 157..179
FT /note="Urokinase-type plasminogen activator short chain A"
FT /evidence="ECO:0000250"
FT /id="PRO_0000285903"
FT CHAIN 181..433
FT /note="Urokinase-type plasminogen activator chain B"
FT /evidence="ECO:0000250"
FT /id="PRO_0000285904"
FT DOMAIN 29..65
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 71..153
FT /note="Kringle"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 181..426
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT REGION 36..59
FT /note="Binds urokinase plasminogen activator surface
FT receptor"
FT /evidence="ECO:0000250"
FT REGION 154..180
FT /note="Connecting peptide"
FT /evidence="ECO:0000250"
FT ACT_SITE 226
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 277
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 378
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT MOD_RES 325
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P00749"
FT CARBOHYD 324
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 33..41
FT /evidence="ECO:0000250"
FT DISULFID 35..53
FT /evidence="ECO:0000250"
FT DISULFID 55..64
FT /evidence="ECO:0000250"
FT DISULFID 72..153
FT /evidence="ECO:0000250"
FT DISULFID 93..135
FT /evidence="ECO:0000250"
FT DISULFID 124..148
FT /evidence="ECO:0000250"
FT DISULFID 170..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 CONFLICT 268
FT /note="R -> S (in Ref. 2; AAM83187)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 433 AA; 48444 MW; 6DD35A371010A6EE CRC64;
MRVLLVCLLL CALVVSDSEG SHELHGVSDA SNCGCLNGGT CVTYKYFSNI WRCNCPKKFQ
GEHCEIDTLK TCYHGDGHSY RGKANTDIMD RPCLAWNSAN VLTKTYHAHR PDALQLGLGK
HNYCRNPDHQ RRPWCYVQVG LKQLIQECKV HDCSSGKKPA LPPGKLEFQC GQKALRPRFK
IIGGEFTIIE NQPWFAAIYR RHRGGSVTYV CGGSLISPCW VVSATHCFIN HQKKEDYIVY
LGRSRLNSMT PGEMKFEVEQ LILHEGYRAD TLAHHNDIAL LKILSNNGQC AQPSRSIQTI
CLPPWNADPN FGTSCEITGF GKENSTDYLY PEQLKMTVVK LVSYQECQQP HYYGSEVTTK
MLCAADPQWE TDSCQGDSGG PLVCSVQGRM TLTGIVSWGR GCALKNKPGV YTRVSRFLPW
IRSHIGEENG LAL
