ID PLA_YERPE Reviewed; 312 AA. AC P17811; DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1990, sequence version 1. DT 27-MAR-2024, entry version 161. DE RecName: Full=Plasminogen activator {ECO:0000303|PubMed:2651310}; DE Short=Pla {ECO:0000303|PubMed:2526282}; DE EC=3.4.23.48 {ECO:0000269|PubMed:22645135}; DE AltName: Full=Coagulase/fibrinolysin; DE Flags: Precursor; GN Name=pla {ECO:0000303|PubMed:2526282}; GN OrderedLocusNames=YPPCP1.07, YP_pPCP08; OS Yersinia pestis. OG Plasmid pPCP1, and Plasmid pKYP1. OC Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales; OC Yersiniaceae; Yersinia. OX NCBI_TaxID=632; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND SUBCELLULAR LOCATION. RC STRAIN=EV76-6; PLASMID=pKYP1; RX PubMed=2526282; DOI=10.1111/j.1365-2958.1989.tb00225.x; RA McDonough K.A., Falkow S.; RT "A Yersinia pestis-specific DNA fragment encodes temperature-dependent RT coagulase and fibrinolysin-associated phenotypes."; RL Mol. Microbiol. 3:767-775(1989). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION. RC STRAIN=KIM5 / Biovar Mediaevalis; PLASMID=pPCP1; RX PubMed=2651310; DOI=10.1128/iai.57.5.1517-1523.1989; RA Sodeinde O.A., Goguen J.D.; RT "Nucleotide sequence of the plasminogen activator gene of Yersinia pestis: RT relationship to ompT of Escherichia coli and gene E of Salmonella RT typhimurium."; RL Infect. Immun. 57:1517-1523(1989). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=KIM5 / Biovar Mediaevalis; PLASMID=pPCP1; RX PubMed=9748454; DOI=10.1128/jb.180.19.5192-5202.1998; RA Hu P., Elliott J., McCready P., Skowronski E., Garnes J., Kobayashi A., RA Brubaker R.R., Garcia E.; RT "Structural organization of virulence-associated plasmids of Yersinia RT pestis."; RL J. Bacteriol. 180:5192-5202(1998). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=CO-92 / Biovar Orientalis; PLASMID=pPCP1; RX PubMed=11586360; DOI=10.1038/35097083; RA Parkhill J., Wren B.W., Thomson N.R., Titball R.W., Holden M.T.G., RA Prentice M.B., Sebaihia M., James K.D., Churcher C.M., Mungall K.L., RA Baker S., Basham D., Bentley S.D., Brooks K., Cerdeno-Tarraga A.-M., RA Chillingworth T., Cronin A., Davies R.M., Davis P., Dougan G., Feltwell T., RA Hamlin N., Holroyd S., Jagels K., Karlyshev A.V., Leather S., Moule S., RA Oyston P.C.F., Quail M.A., Rutherford K.M., Simmonds M., Skelton J., RA Stevens K., Whitehead S., Barrell B.G.; RT "Genome sequence of Yersinia pestis, the causative agent of plague."; RL Nature 413:523-527(2001). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=91001 / Biovar Mediaevalis; PLASMID=pPCP1; RX PubMed=15368893; DOI=10.1093/dnares/11.3.179; RA Song Y., Tong Z., Wang J., Wang L., Guo Z., Han Y., Zhang J., Pei D., RA Zhou D., Qin H., Pang X., Han Y., Zhai J., Li M., Cui B., Qi Z., Jin L., RA Dai R., Chen F., Li S., Ye C., Du Z., Lin W., Wang J., Yu J., Yang H., RA Wang J., Huang P., Yang R.; RT "Complete genome sequence of Yersinia pestis strain 91001, an isolate RT avirulent to humans."; RL DNA Res. 11:179-197(2004). RN [6] RP DISRUPTION PHENOTYPE, REVIEW, AND MUTAGENESIS OF ASP-104. RX PubMed=17635705; DOI=10.1111/j.1538-7836.2007.02519.x; RA Degen J.L., Bugge T.H., Goguen J.D.; RT "Fibrin and fibrinolysis in infection and host defense."; RL J. Thromb. Haemost. 1:24-31(2007). RN [7] {ECO:0007744|PDB:2X4M, ECO:0007744|PDB:2X55, ECO:0007744|PDB:2X56} RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 21-312 WITH AND WITHOUT LPS RP ANALOG, FUNCTION, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, RP SUBCELLULAR LOCATION, DOMAIN, TOPOLOGY, AND MUTAGENESIS OF ASP-104; RP ASP-106; HIS-228 AND ARG-231. RX PubMed=20637417; DOI=10.1016/j.str.2010.03.013; RA Eren E., Murphy M., Goguen J., van den Berg B.; RT "An active site water network in the plasminogen activator pla from RT Yersinia pestis."; RL Structure 18:809-818(2010). RN [8] {ECO:0007744|PDB:4DCB} RP X-RAY CRYSTALLOGRAPHY (2.03 ANGSTROMS) OF 25-312 IN COMPLEX WITH SUBSTRATE RP PEPTIDE, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND DOMAIN. RX PubMed=22645135; DOI=10.1074/jbc.M112.376418; RA Eren E., van den Berg B.; RT "Structural basis for activation of an integral membrane protease by RT lipopolysaccharide."; RL J. Biol. Chem. 287:23971-23976(2012). CC -!- FUNCTION: In the mammalian host activates (cleaves) plasminogen to CC generate the serine protease plasmin. Plasmin degrades fibrin clots CC (fibrinolysis) and facilitates bacterial cell migration, enabling rapid CC dissemination of bacteria from the initial site of infection CC (Probable). Cleaves host plasminogen to generate plasmin and probably CC also has autocatalytic activity (PubMed:20637417, PubMed:22645135). CC Fibrinolytic activity prevails at 37 degrees Celsius whereas coagulase CC expression predominates at lower temperatures (28 degrees Celsius) CC (PubMed:2526282). Cleaves plasminogen; plasminogen cleavage is much CC higher than coagulase activity (PubMed:2651310, PubMed:2526282, CC PubMed:20637417, PubMed:22645135). {ECO:0000269|PubMed:20637417, CC ECO:0000269|PubMed:22645135, ECO:0000269|PubMed:2526282, CC ECO:0000269|PubMed:2651310, ECO:0000305|PubMed:17635705}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Converts human Glu-plasminogen to plasmin by cleaving the 560- CC Arg-|-Val-561 peptide bond that is also hydrolyzed by the mammalian CC u-plasminogen activator and t-plasminogen activator. Also cleaves CC arginyl bonds in other proteins.; EC=3.4.23.48; CC Evidence={ECO:0000269|PubMed:22645135}; CC -!- ACTIVITY REGULATION: Requires bacterial lipopolysaccharide (LPS) for CC activation; addition of LPS to inactive protein reactivates it CC (PubMed:20637417). In the absence of LPS the active site groove is CC slightly narrower, and peptide substrate binds deep within the active CC site groove, displacing the nucleophilic water molecule CC (PubMed:22645135). {ECO:0000269|PubMed:20637417, CC ECO:0000269|PubMed:22645135}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC pH dependence: CC Optimum pH is 6-7 for plasminogen cleavage (PubMed:20637417). CC {ECO:0000269|PubMed:20637417}; CC -!- SUBCELLULAR LOCATION: Cell outer membrane {ECO:0000305|PubMed:20637417, CC ECO:0000305|PubMed:2526282}; Multi-pass membrane protein CC {ECO:0000269|PubMed:20637417, ECO:0000269|PubMed:22645135}. CC -!- DOMAIN: Forms a narrow, elliptical 10-stranded beta barrel with the CC active site pairs on the extracellular surface (PubMed:20637417, CC PubMed:22645135). {ECO:0000269|PubMed:20637417, CC ECO:0000269|PubMed:22645135}. CC -!- DISRUPTION PHENOTYPE: 90% survival of infected mice, mice develop a CC robust immune defense (PubMed:17635705). {ECO:0000269|PubMed:17635705}. CC -!- SIMILARITY: Belongs to the peptidase A26 family. {ECO:0000305}. 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; X15136; CAA33235.1; -; Genomic_DNA. DR EMBL; M27820; AAA27667.1; -; Genomic_DNA. DR EMBL; AF053945; AAC62545.1; -; Genomic_DNA. DR EMBL; AL109969; CAB53170.1; -; Genomic_DNA. DR EMBL; AE017046; AAS58765.1; -; Genomic_DNA. DR PIR; A42928; A42928. DR PIR; S06979; A30916. DR RefSeq; NP_395233.1; NC_003132.1. DR RefSeq; NP_857784.1; NC_004837.1. DR RefSeq; WP_002218234.1; NZ_WUCM01000123.1. DR RefSeq; YP_006960975.1; NC_019235.1. DR PDB; 2X4M; X-ray; 2.55 A; A/B/C/D=21-312. DR PDB; 2X55; X-ray; 1.85 A; A=21-312. DR PDB; 2X56; X-ray; 2.30 A; A=21-312. DR PDB; 4DCB; X-ray; 2.03 A; A=25-312. DR PDBsum; 2X4M; -. DR PDBsum; 2X55; -. DR PDBsum; 2X56; -. DR PDBsum; 4DCB; -. DR AlphaFoldDB; P17811; -. DR SMR; P17811; -. DR IntAct; P17811; 1. DR MINT; P17811; -. DR ChEMBL; CHEMBL1075037; -. DR MEROPS; A26.003; -. DR DNASU; 1149148; -. DR EnsemblBacteria; AAS58765; AAS58765; YP_pPCP08. DR GeneID; 57977666; -. DR KEGG; ype:YPPCP1.07; -. DR KEGG; ypm:YP_pPCP08; -. DR PATRIC; fig|214092.21.peg.114; -. DR HOGENOM; CLU_063041_1_0_6; -. DR OMA; YNYDNGA; -. DR OrthoDB; 2112810at2; -. DR BRENDA; 3.4.23.48; 4559. DR BRENDA; 3.4.23.49; 4559. DR EvolutionaryTrace; P17811; -. DR PRO; PR:P17811; -. DR Proteomes; UP000000815; Plasmid pPCP1. DR Proteomes; UP000001019; Plasmid pPCP1. DR GO; GO:0009279; C:cell outer membrane; IEA:UniProtKB-SubCell. DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IEA:UniProtKB-KW. DR GO; GO:0042730; P:fibrinolysis; IEA:UniProtKB-KW. DR GO; GO:0007599; P:hemostasis; IEA:UniProtKB-KW. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR Gene3D; 2.40.128.90; OMPT-like; 1. DR InterPro; IPR020080; OM_adhesin/peptidase_omptin. DR InterPro; IPR020079; Peptidase_A26_CS. DR InterPro; IPR000036; Peptidase_A26_omptin. DR Pfam; PF01278; Omptin; 1. DR PIRSF; PIRSF001522; Peptidase_A26; 1. DR PRINTS; PR00482; OMPTIN. DR SUPFAM; SSF69917; OMPT-like; 1. DR PROSITE; PS00834; OMPTIN_1; 1. DR PROSITE; PS00835; OMPTIN_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Aspartyl protease; Cell outer membrane; Hydrolase; Membrane; KW Plasmid; Protease; Reference proteome; Signal; Transmembrane; KW Transmembrane beta strand; Virulence. FT SIGNAL 1..20 FT /evidence="ECO:0000305|PubMed:20637417" FT CHAIN 21..312 FT /note="Plasminogen activator" FT /id="PRO_0000025819" FT TOPO_DOM 21..31 FT /note="Periplasmic" FT /evidence="ECO:0000269|PubMed:20637417" FT TRANSMEM 32..40 FT /note="Beta stranded; Name=1" FT /evidence="ECO:0000269|PubMed:20637417" FT TOPO_DOM 41..70 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:20637417" FT TRANSMEM 71..80 FT /note="Beta stranded; Name=2" FT /evidence="ECO:0000269|PubMed:20637417" FT TOPO_DOM 81..84 FT /note="Periplasmic" FT /evidence="ECO:0000269|PubMed:20637417" FT TRANSMEM 85..94 FT /note="Beta stranded; Name=3" FT /evidence="ECO:0000269|PubMed:20637417" FT TOPO_DOM 95..131 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:20637417" FT TRANSMEM 132..140 FT /note="Beta stranded; Name=4" FT /evidence="ECO:0000269|PubMed:20637417" FT TOPO_DOM 141..145 FT /note="Periplasmic" FT /evidence="ECO:0000269|PubMed:20637417" FT TRANSMEM 146..154 FT /note="Beta stranded; Name=5" FT /evidence="ECO:0000269|PubMed:20637417" FT TOPO_DOM 155..194 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:20637417" FT TRANSMEM 195..204 FT /note="Beta stranded; Name=6" FT /evidence="ECO:0000269|PubMed:20637417" FT TOPO_DOM 205..207 FT /note="Periplasmic" FT /evidence="ECO:0000269|PubMed:20637417" FT TRANSMEM 208..216 FT /note="Beta stranded; Name=7" FT /evidence="ECO:0000269|PubMed:20637417" FT TOPO_DOM 217..244 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:20637417" FT TRANSMEM 245..255 FT /note="Beta stranded; Name=8" FT /evidence="ECO:0000269|PubMed:20637417" FT TOPO_DOM 256..258 FT /note="Periplasmic" FT /evidence="ECO:0000269|PubMed:20637417" FT TRANSMEM 259..267 FT /note="Beta stranded; Name=9" FT /evidence="ECO:0000269|PubMed:20637417" FT TOPO_DOM 268..301 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:20637417" FT TRANSMEM 302..312 FT /note="Beta stranded; Name=10" FT /evidence="ECO:0000269|PubMed:20637417" FT ACT_SITE 104 FT /evidence="ECO:0000305|PubMed:17635705, FT ECO:0000305|PubMed:20637417" FT ACT_SITE 106 FT /evidence="ECO:0000305|PubMed:20637417" FT ACT_SITE 226 FT /evidence="ECO:0000305|PubMed:20637417" FT ACT_SITE 228 FT /evidence="ECO:0000305|PubMed:20637417" FT MUTAGEN 104 FT /note="D->A: No plasminogen cleavage." FT /evidence="ECO:0000269|PubMed:20637417" FT MUTAGEN 104 FT /note="D->E: A high percentage of mice survive Y.pestis FT infection." FT /evidence="ECO:0000269|PubMed:17635705" FT MUTAGEN 104 FT /note="D->N: About 15% plasminogen cleavage." FT /evidence="ECO:0000269|PubMed:20637417" FT MUTAGEN 106 FT /note="D->A: Extremely low plasminogen cleavage, no FT autocleavage." FT /evidence="ECO:0000269|PubMed:20637417" FT MUTAGEN 106 FT /note="D->N: Extremely low plasminogen cleavage." FT /evidence="ECO:0000269|PubMed:20637417" FT MUTAGEN 228 FT /note="H->N: No plasminogen cleavage." FT /evidence="ECO:0000269|PubMed:20637417" FT MUTAGEN 231 FT /note="R->A,K: Very low plasminogen cleavage." FT /evidence="ECO:0000269|PubMed:20637417" FT CONFLICT 279 FT /note="T -> I (in Ref. 5; AAS58765)" FT /evidence="ECO:0000305" FT HELIX 31..33 FT /evidence="ECO:0007829|PDB:4DCB" FT STRAND 34..52 FT /evidence="ECO:0007829|PDB:2X55" FT TURN 54..56 FT /evidence="ECO:0007829|PDB:2X55" FT STRAND 59..82 FT /evidence="ECO:0007829|PDB:2X55" FT STRAND 85..96 FT /evidence="ECO:0007829|PDB:2X55" FT STRAND 98..106 FT /evidence="ECO:0007829|PDB:2X55" FT STRAND 116..142 FT /evidence="ECO:0007829|PDB:2X55" FT STRAND 144..165 FT /evidence="ECO:0007829|PDB:2X55" FT STRAND 167..170 FT /evidence="ECO:0007829|PDB:2X55" FT TURN 171..174 FT /evidence="ECO:0007829|PDB:2X55" FT STRAND 175..178 FT /evidence="ECO:0007829|PDB:2X55" FT STRAND 184..205 FT /evidence="ECO:0007829|PDB:2X55" FT STRAND 208..228 FT /evidence="ECO:0007829|PDB:2X55" FT HELIX 229..231 FT /evidence="ECO:0007829|PDB:2X55" FT STRAND 233..256 FT /evidence="ECO:0007829|PDB:2X55" FT STRAND 259..270 FT /evidence="ECO:0007829|PDB:2X55" FT STRAND 275..280 FT /evidence="ECO:0007829|PDB:4DCB" FT TURN 282..284 FT /evidence="ECO:0007829|PDB:2X4M" FT HELIX 292..294 FT /evidence="ECO:0007829|PDB:2X55" FT STRAND 295..312 FT /evidence="ECO:0007829|PDB:2X55" SQ SEQUENCE 312 AA; 34611 MW; 52B7CB4F32E8FBE9 CRC64; MKKSSIVATI ITILSGSANA ASSQLIPNIS PDSFTVAAST GMLSGKSHEM LYDAETGRKI SQLDWKIKNV AILKGDISWD PYSFLTLNAR GWTSLASGSG NMDDYDWMNE NQSEWTDHSS HPATNVNHAN EYDLNVKGWL LQDENYKAGI TAGYQETRFS WTATGGSYSY NNGAYTGNFP KGVRVIGYNQ RFSMPYIGLA GQYRINDFEL NALFKFSDWV RAHDNDEHYM RDLTFREKTS GSRYYGTVIN AGYYVTPNAK VFAEFTYSKY DEGKGGTQTI DKNSGDSVSI GGDAAGISNK NYTVTAGLQY RF //