ID UROK_HUMAN Reviewed; 431 AA.
AC P00749; B4DPZ2; Q15844; Q16618; Q53XS3; Q5SWW9; Q969W6;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 3.
DT 27-MAR-2024, entry version 268.
DE RecName: Full=Urokinase-type plasminogen activator;
DE Short=U-plasminogen activator;
DE Short=uPA {ECO:0000303|PubMed:24434139};
DE EC=3.4.21.73;
DE Contains:
DE RecName: Full=Urokinase-type plasminogen activator long chain A {ECO:0000305};
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 {ECO:0000312|HGNC:HGNC:9052};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT PRO-141.
RA Holmes W.E., Pennica D., Blaber M., Rey M.W., Guenzler W.A., Steffens G.J.,
RA Heyneker H.L.;
RT "Cloning and expression of the gene for pro-urokinase in Escherichia
RT coli.";
RL Biotechnology (N.Y.) 3:923-929(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT PRO-141.
RX PubMed=3888571; DOI=10.1089/dna.1985.4.139;
RA Jacobs P., Cravador A., Loriau R., Brockly F., Colau B., Chuchana P.,
RA van Elsen A., Herzog A., Bollen A.;
RT "Molecular cloning, sequencing, and expression in Escherichia coli of human
RT preprourokinase cDNA.";
RL DNA 4:139-146(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT PRO-141.
RX PubMed=2415429; DOI=10.1016/0378-1119(85)90084-8;
RA Nagai M., Hiramatsu R., Kaneda T., Hayasuke N., Arimura H., Nishida M.,
RA Suyama T.;
RT "Molecular cloning of cDNA coding for human preprourokinase.";
RL Gene 36:183-188(1985).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS PRO-141 AND MET-214.
RX PubMed=2987867; DOI=10.1093/nar/13.8.2759;
RA Riccio A., Grimaldi G., Verde P., Sebastio G., Boast S., Blasi F.;
RT "The human urokinase-plasminogen activator gene and its promoter.";
RL Nucleic Acids Res. 13:2759-2771(1985).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-141.
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) System Donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT PRO-141.
RC TISSUE=Mesangial cell;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-15; PRO-141 AND
RP GLN-231.
RG SeattleSNPs variation discovery resource;
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT PRO-141.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-141.
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 21-431.
RX PubMed=8652631; DOI=10.1016/0167-4838(95)00228-6;
RA Yoshimoto M., Ushiyama Y., Sakai M., Tamaki S., Hara H., Takahashi K.,
RA Sawasaki Y., Hanada K.;
RT "Characterization of single chain urokinase-type plasminogen activator with
RT a novel amino-acid substitution in the kringle structure.";
RL Biochim. Biophys. Acta 1293:83-89(1996).
RN [12]
RP PROTEIN SEQUENCE OF 21-43, GLYCOSYLATION AT THR-38, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=2023947; DOI=10.1073/pnas.88.9.3992;
RA Buko A.M., Kentzer E.J., Petros A., Menon G., Zuiderweg E.R., Sarin V.K.;
RT "Characterization of a posttranslational fucosylation in the growth factor
RT domain of urinary plasminogen activator.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:3992-3996(1991).
RN [13]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 66-431, AND VARIANTS PRO-141
RP AND MET-214.
RX PubMed=6589620; DOI=10.1073/pnas.81.15.4727;
RA Verde P., Stoppelli M.P., Galeffi P., di Nocera P., Blasi F.;
RT "Identification and primary sequence of an unspliced human urokinase
RT poly(A)+ RNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 81:4727-4731(1984).
RN [14]
RP PROTEIN SEQUENCE OF 21-177, AND VARIANT PRO-141.
RX PubMed=6754569; DOI=10.1515/bchm2.1982.363.2.1155;
RA Gunzler W.A., Steffens G.J., Otting F., Kim S.-M.A., Frankus E., Flohe L.;
RT "The primary structure of high molecular mass urokinase from human urine.
RT The complete amino acid sequence of the A chain.";
RL Hoppe-Seyler's Z. Physiol. Chem. 363:1155-1165(1982).
RN [15]
RP PROTEIN SEQUENCE OF 156-176 AND 179-224.
RX PubMed=6749491; DOI=10.1111/j.1432-1033.1982.tb06676.x;
RA Schaller J., Nick H., Rickli E.E., Gillessen D., Lergier W., Studer R.O.;
RT "Human low-molecular-weight urinary urokinase. Partial characterization and
RT preliminary sequence data of the two polypeptide chains.";
RL Eur. J. Biochem. 125:251-257(1982).
RN [16]
RP PROTEIN SEQUENCE OF 158-410.
RX PubMed=6754572; DOI=10.1515/bchm2.1982.363.2.1043;
RA Steffens G.J., Gunzler W.A., Otting F., Frankus E., Flohe L.;
RT "The complete amino acid sequence of low molecular mass urokinase from
RT human urine.";
RL Hoppe-Seyler's Z. Physiol. Chem. 363:1043-1058(1982).
RN [17]
RP ACTIVITY REGULATION, AND HETERODIMER WITH SERPINA5.
RX PubMed=3501295; DOI=10.1515/bchm3.1987.368.2.1427;
RA Stief T.W., Radtke K.P., Heimburger N.;
RT "Inhibition of urokinase by protein C-inhibitor (PCI). Evidence for
RT identity of PCI and plasminogen activator inhibitor 3.";
RL Biol. Chem. Hoppe-Seyler 368:1427-1433(1987).
RN [18]
RP PHOSPHORYLATION AT SER-158 AND SER-323, AND MUTAGENESIS OF SER-158 AND
RP SER-323.
RX PubMed=9151681; DOI=10.1083/jcb.137.3.779;
RA Franco P., Iaccarino C., Chiaradonna F., Brandazza A., Iavarone C.,
RA Mastronicola M.R., Nolli M.L., Stoppelli M.P.;
RT "Phosphorylation of human pro-urokinase on Ser138/303 impairs its receptor-
RT dependent ability to promote myelomonocytic adherence and motility.";
RL J. Cell Biol. 137:779-791(1997).
RN [19]
RP HETERODIMER WITH SERPINA5.
RX PubMed=10340997; DOI=10.1093/molehr/5.6.513;
RA He S., Lin Y.L., Liu Y.X.;
RT "Functionally inactive protein C inhibitor in seminal plasma may be
RT associated with infertility.";
RL Mol. Hum. Reprod. 5:513-519(1999).
RN [20]
RP INTERACTION WITH MRC2.
RX PubMed=10636902; DOI=10.1074/jbc.275.3.1993;
RA Behrendt N., Jensen O.N., Engelholm L.H., Moertz E., Mann M., Danoe K.;
RT "A urokinase receptor-associated protein with specific collagen binding
RT properties.";
RL J. Biol. Chem. 275:1993-2002(2000).
RN [21]
RP INTERACTION WITH LRP1B.
RX PubMed=11384978; DOI=10.1074/jbc.m102727200;
RA Liu C.-X., Li Y., Obermoeller-McCormick L.M., Schwartz A.L., Bu G.;
RT "The putative tumor suppressor LRP1B, a novel member of the low density
RT lipoprotein (LDL) receptor family, exhibits both overlapping and distinct
RT properties with the LDL receptor-related protein.";
RL J. Biol. Chem. 276:28889-28896(2001).
RN [22]
RP INTERACTION WITH LRP1; PLAUR; SERPINE1 AND SORL1.
RX PubMed=15053742; DOI=10.1042/bj20040149;
RA Gliemann J., Hermey G., Nykjaer A., Petersen C.M., Jacobsen C.,
RA Andreasen P.A.;
RT "The mosaic receptor sorLA/LR11 binds components of the plasminogen-
RT activating system and platelet-derived growth factor-BB similarly to LRP1
RT (low-density lipoprotein receptor-related protein), but mediates slow
RT internalization of bound ligand.";
RL Biochem. J. 381:203-212(2004).
RN [23]
RP ACTIVITY REGULATION, AND HETERODIMER WITH SERPINA5.
RX PubMed=14696115; DOI=10.1002/ijc.11594;
RA Wakita T., Hayashi T., Nishioka J., Tamaru H., Akita N., Asanuma K.,
RA Kamada H., Gabazza E.C., Ido M., Kawamura J., Suzuki K.;
RT "Regulation of carcinoma cell invasion by protein C inhibitor whose
RT expression is decreased in renal cell carcinoma.";
RL Int. J. Cancer 108:516-523(2004).
RN [24]
RP TISSUE SPECIFICITY.
RX PubMed=15988036; DOI=10.1128/mcb.25.14.6279-6288.2005;
RA Ustach C.V., Kim H.-R.C.;
RT "Platelet-derived growth factor D is activated by urokinase plasminogen
RT activator in prostate carcinoma cells.";
RL Mol. Cell. Biol. 25:6279-6288(2005).
RN [25]
RP INVOLVEMENT IN QPD.
RX PubMed=20007542; DOI=10.1182/blood-2009-07-233965;
RA Paterson A.D., Rommens J.M., Bharaj B., Blavignac J., Wong I.,
RA Diamandis M., Waye J.S., Rivard G.E., Hayward C.P.;
RT "Persons with Quebec platelet disorder have a tandem duplication of PLAU,
RT the urokinase plasminogen activator gene.";
RL Blood 115:1264-1266(2010).
RN [26]
RP PROTEALITICAL CLEAVAGE, AND SUBCELLULAR LOCATION.
RX PubMed=24434139; DOI=10.1016/j.bbrc.2014.01.013;
RA Min H.J., Lee M.K., Lee J.W., Kim S.;
RT "TMPRSS4 induces cancer cell invasion through pro-uPA processing.";
RL Biochem. Biophys. Res. Commun. 446:1-7(2014).
RN [27]
RP STRUCTURE BY NMR.
RX PubMed=2536903; DOI=10.1038/337579a0;
RA Oswald R.E., Bogusky M.J., Bamberger M., Smith R.A.G., Dobson C.M.;
RT "Dynamics of the multidomain fibrinolytic protein urokinase from two-
RT dimensional NMR.";
RL Nature 337:579-582(1989).
RN [28]
RP STRUCTURE BY NMR OF 67-155.
RX PubMed=1327118; DOI=10.1021/bi00155a008;
RA Li X., Smith R.A.G., Dobson C.M.;
RT "Sequential 1H NMR assignments and secondary structure of the kringle
RT domain from urokinase.";
RL Biochemistry 31:9562-9571(1992).
RN [29]
RP STRUCTURE BY NMR OF 67-155.
RX PubMed=8107091; DOI=10.1006/jmbi.1994.1106;
RA Li X., Bokman A.M., Llinas M., Smith R.A.G., Dobson C.M.;
RT "Solution structure of the kringle domain from urokinase-type plasminogen
RT activator.";
RL J. Mol. Biol. 235:1548-1559(1994).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
RX PubMed=8591045; DOI=10.1016/s0969-2126(01)00203-9;
RA Spraggon G., Phillips C., Nowak U.K., Ponting C.P., Saunders D.,
RA Dobson C.M., Stuart D.I., Jones E.Y.;
RT "The crystal structure of the catalytic domain of human urokinase-type
RT plasminogen activator.";
RL Structure 3:681-691(1995).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 159-411.
RX PubMed=10805774; DOI=10.1073/pnas.97.10.5113;
RA Sperl S., Jacob U., Arroyo de Prada N., Sturzebecher J., Wilhelm O.G.,
RA Bode W., Magdolen V., Huber R., Moroder L.;
RT "(4-aminomethyl)phenylguanidine derivatives as nonpeptidic highly selective
RT inhibitors of human urokinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:5113-5118(2000).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 31-152 IN COMPLEX WITH PLAUR.
RX PubMed=16456079; DOI=10.1126/science.1121143;
RA Huai Q., Mazar A.P., Kuo A., Parry G.C., Shaw D.E., Callahan J., Li Y.,
RA Yuan C., Bian C., Chen L., Furie B., Furie B.C., Cines D.B., Huang M.;
RT "Structure of human urokinase plasminogen activator in complex with its
RT receptor.";
RL Science 311:656-659(2006).
RN [33]
RP VARIANT PRO-141.
RX PubMed=9065988;
RA Conne B., Berczy M., Belin D.;
RT "Detection of polymorphisms in the human urokinase-type plasminogen
RT activator gene.";
RL Thromb. Haemost. 77:434-435(1997).
RN [34]
RP ERRATUM OF PUBMED:9065988.
RA Conne B., Berczy M., Belin D.;
RL Thromb. Haemost. 78:973-973(1997).
RN [35]
RP VARIANT PRO-141.
RX PubMed=9194591; DOI=10.1002/elps.1150180505;
RA Turkmen B., Schmitt M., Schmalfeldt B., Trommler P., Hell W.,
RA Creutzburg S., Graeff H., Magdolen V.;
RT "Mutational analysis of the genes encoding urokinase-type plasminogen
RT activator (uPA) and its inhibitor PAI-1 in advanced ovarian cancer.";
RL Electrophoresis 18:686-689(1997).
RN [36]
RP VARIANT [LARGE SCALE ANALYSIS] PRO-141.
RX PubMed=18987736; DOI=10.1038/nature07485;
RA Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K.,
RA Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L.,
RA Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A.,
RA Abbott S., Locke D., Hillier L.W., Miner T., Fulton L., Magrini V.,
RA Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R.,
RA Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E.,
RA Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S.,
RA Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A.,
RA DiPersio J.F., Wilson R.K.;
RT "DNA sequencing of a cytogenetically normal acute myeloid leukaemia
RT genome.";
RL Nature 456:66-72(2008).
CC -!- FUNCTION: Specifically cleaves the zymogen plasminogen to form the
CC active enzyme plasmin.
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:0000269|PubMed:14696115, ECO:0000269|PubMed:3501295}.
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 (PubMed:15053742). Interacts with
CC SORL1 and LRP1, either alone or in complex with SERPINE1; these
CC interactions are abolished in the presence of LRPAP1/RAP
CC (PubMed:15053742). The ternary complex composed of PLAUR-PLAU-PAI1 also
CC interacts with SORLA (PubMed:15053742). {ECO:0000269|PubMed:10636902,
CC ECO:0000269|PubMed:11384978, ECO:0000269|PubMed:15053742,
CC ECO:0000269|PubMed:16456079}.
CC -!- INTERACTION:
CC P00749; Q9UKQ2: ADAM28; NbExp=3; IntAct=EBI-3905042, EBI-1384181;
CC P00749; P05067: APP; NbExp=3; IntAct=EBI-3905042, EBI-77613;
CC P00749; Q03405-1: PLAUR; NbExp=2; IntAct=EBI-3905042, EBI-15695188;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:24434139}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P00749-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P00749-2; Sequence=VSP_038368;
CC -!- TISSUE SPECIFICITY: Expressed in the prostate gland and prostate
CC cancers. {ECO:0000269|PubMed:15988036}.
CC -!- PTM: Phosphorylation of Ser-158 and Ser-323 abolishes proadhesive
CC ability but does not interfere with receptor binding.
CC {ECO:0000269|PubMed:9151681}.
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:0000269|PubMed:24434139}.
CC -!- DISEASE: Quebec platelet disorder (QPD) [MIM:601709]: An autosomal
CC dominant bleeding disorder due to a gain-of-function defect in
CC fibrinolysis. Although affected individuals do not exhibit systemic
CC fibrinolysis, they show delayed onset bleeding after challenge, such as
CC surgery. The hallmark of the disorder is markedly increased PLAU levels
CC within platelets, which causes intraplatelet plasmin generation and
CC secondary degradation of alpha-granule proteins.
CC {ECO:0000269|PubMed:20007542}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- PHARMACEUTICAL: Available under the name Abbokinase (Abbott). Used in
CC Pulmonary Embolism (PE) to initiate fibrinolysis. Clinically used for
CC therapy of thrombolytic disorders.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Urokinase entry;
CC URL="https://en.wikipedia.org/wiki/Urokinase";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/plau/";
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DR EMBL; M15476; AAA61253.1; -; mRNA.
DR EMBL; X02760; CAA26535.1; -; mRNA.
DR EMBL; D00244; BAA00175.1; -; mRNA.
DR EMBL; K03226; AAC97138.1; -; mRNA.
DR EMBL; X02419; CAA26268.1; -; Genomic_DNA.
DR EMBL; AF377330; AAK53822.1; -; Genomic_DNA.
DR EMBL; BT007391; AAP36055.1; -; mRNA.
DR EMBL; AK298560; BAG60754.1; -; mRNA.
DR EMBL; AL596247; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471083; EAW54544.1; -; Genomic_DNA.
DR EMBL; BC013575; AAH13575.1; -; mRNA.
DR EMBL; D11143; BAA01919.1; -; mRNA.
DR EMBL; K02286; AAA61252.1; -; Genomic_DNA.
DR CCDS; CCDS44442.1; -. [P00749-2]
DR CCDS; CCDS7339.1; -. [P00749-1]
DR PIR; A00931; UKHU.
DR RefSeq; NP_001138503.1; NM_001145031.2. [P00749-2]
DR RefSeq; NP_001306120.1; NM_001319191.1.
DR RefSeq; NP_002649.1; NM_002658.4. [P00749-1]
DR RefSeq; XP_011538168.1; XM_011539866.2. [P00749-1]
DR PDB; 1C5W; X-ray; 1.94 A; A=156-178, B=179-431.
DR PDB; 1C5X; X-ray; 1.75 A; A=156-178, B=179-431.
DR PDB; 1C5Y; X-ray; 1.65 A; A=156-178, B=179-431.
DR PDB; 1C5Z; X-ray; 1.85 A; A=156-178, B=179-431.
DR PDB; 1EJN; X-ray; 1.80 A; A=179-431.
DR PDB; 1F5K; X-ray; 1.80 A; U=179-431.
DR PDB; 1F5L; X-ray; 2.10 A; A=179-431.
DR PDB; 1F92; X-ray; 2.60 A; A=179-431.
DR PDB; 1FV9; X-ray; 3.00 A; A=179-423.
DR PDB; 1GI7; X-ray; 1.79 A; A=156-178, B=179-423.
DR PDB; 1GI8; X-ray; 1.75 A; A=156-178, B=179-423.
DR PDB; 1GI9; X-ray; 1.80 A; A=156-178, B=179-423.
DR PDB; 1GJ7; X-ray; 1.50 A; A=156-178, B=179-431.
DR PDB; 1GJ8; X-ray; 1.64 A; A=156-178, B=179-431.
DR PDB; 1GJ9; X-ray; 1.80 A; A=156-178, B=179-431.
DR PDB; 1GJA; X-ray; 1.56 A; A=156-178, B=179-431.
DR PDB; 1GJB; X-ray; 1.90 A; A=156-178, B=179-431.
DR PDB; 1GJC; X-ray; 1.73 A; A=156-178, B=179-431.
DR PDB; 1GJD; X-ray; 1.75 A; A=156-178, B=179-431.
DR PDB; 1KDU; NMR; -; A=69-153.
DR PDB; 1LMW; X-ray; 2.50 A; A/C=156-178, B/D=179-431.
DR PDB; 1O3P; X-ray; 1.81 A; A=156-178, B=179-431.
DR PDB; 1O5A; X-ray; 1.68 A; A=156-178, B=179-431.
DR PDB; 1O5B; X-ray; 1.85 A; A=156-178, B=179-431.
DR PDB; 1O5C; X-ray; 1.63 A; A=156-178, B=179-431.
DR PDB; 1OWD; X-ray; 2.32 A; A=179-423.
DR PDB; 1OWE; X-ray; 1.60 A; A=179-423.
DR PDB; 1OWH; X-ray; 1.61 A; A=179-423.
DR PDB; 1OWI; X-ray; 2.93 A; A=179-423.
DR PDB; 1OWJ; X-ray; 3.10 A; A=179-423.
DR PDB; 1OWK; X-ray; 2.80 A; A=179-423.
DR PDB; 1SC8; X-ray; 2.40 A; U=164-425.
DR PDB; 1SQA; X-ray; 2.00 A; A=179-423.
DR PDB; 1SQO; X-ray; 1.84 A; A=179-423.
DR PDB; 1SQT; X-ray; 1.90 A; A=179-423.
DR PDB; 1U6Q; X-ray; 2.02 A; A=179-423.
DR PDB; 1URK; NMR; -; A=26-155.
DR PDB; 1VJ9; X-ray; 2.40 A; U=164-425.
DR PDB; 1VJA; X-ray; 2.00 A; U=164-425.
DR PDB; 1W0Z; X-ray; 1.90 A; U=179-425.
DR PDB; 1W10; X-ray; 2.00 A; U=179-425.
DR PDB; 1W11; X-ray; 2.00 A; U=179-425.
DR PDB; 1W12; X-ray; 2.40 A; U=179-425.
DR PDB; 1W13; X-ray; 2.00 A; U=179-425.
DR PDB; 1W14; X-ray; 2.20 A; U=179-425.
DR PDB; 2FD6; X-ray; 1.90 A; A=31-152.
DR PDB; 2I9A; X-ray; 1.90 A; A/B/C/D=21-163.
DR PDB; 2I9B; X-ray; 2.80 A; A/B/C/D=21-163.
DR PDB; 2NWN; X-ray; 2.15 A; A=179-431.
DR PDB; 2O8T; X-ray; 1.45 A; A=179-431.
DR PDB; 2O8U; X-ray; 1.70 A; A=179-431.
DR PDB; 2O8W; X-ray; 1.86 A; A=179-431.
DR PDB; 2R2W; X-ray; 2.01 A; U=179-431.
DR PDB; 2VIN; X-ray; 1.90 A; A=179-431.
DR PDB; 2VIO; X-ray; 1.80 A; A=179-431.
DR PDB; 2VIP; X-ray; 1.72 A; A=179-431.
DR PDB; 2VIQ; X-ray; 2.00 A; A=179-431.
DR PDB; 2VIV; X-ray; 1.72 A; A=179-431.
DR PDB; 2VIW; X-ray; 2.05 A; A=179-431.
DR PDB; 2VNT; X-ray; 2.20 A; A/B/C/D/E/F=156-431.
DR PDB; 3BT1; X-ray; 2.80 A; A=21-153.
DR PDB; 3BT2; X-ray; 2.50 A; A=21-153.
DR PDB; 3IG6; X-ray; 1.83 A; A/C=156-178, B/D=179-431.
DR PDB; 3KGP; X-ray; 2.35 A; A=179-431.
DR PDB; 3KHV; X-ray; 2.35 A; A=179-431.
DR PDB; 3KID; X-ray; 2.71 A; U=179-431.
DR PDB; 3M61; X-ray; 1.68 A; U=179-431.
DR PDB; 3MHW; X-ray; 1.45 A; U=179-425.
DR PDB; 3MWI; X-ray; 2.03 A; U=179-424.
DR PDB; 3OX7; X-ray; 1.58 A; U=179-431.
DR PDB; 3OY5; X-ray; 2.31 A; U=179-431.
DR PDB; 3OY6; X-ray; 2.31 A; U=179-431.
DR PDB; 3PB1; X-ray; 2.30 A; E=179-431.
DR PDB; 3QN7; X-ray; 1.90 A; A=179-431.
DR PDB; 3U73; X-ray; 3.19 A; A=21-152.
DR PDB; 4DVA; X-ray; 1.94 A; U=179-424.
DR PDB; 4DW2; X-ray; 2.97 A; U=179-424.
DR PDB; 4FU7; X-ray; 2.00 A; A=179-424.
DR PDB; 4FU8; X-ray; 2.20 A; A=179-424.
DR PDB; 4FU9; X-ray; 1.60 A; A=179-424.
DR PDB; 4FUB; X-ray; 1.90 A; A=179-424.
DR PDB; 4FUC; X-ray; 1.72 A; A=179-424.
DR PDB; 4FUD; X-ray; 2.00 A; A=179-424.
DR PDB; 4FUE; X-ray; 2.00 A; A=179-424.
DR PDB; 4FUF; X-ray; 2.00 A; A=179-424.
DR PDB; 4FUG; X-ray; 1.80 A; A=179-424.
DR PDB; 4FUH; X-ray; 1.60 A; A=179-424.
DR PDB; 4FUI; X-ray; 2.00 A; A=179-424.
DR PDB; 4FUJ; X-ray; 2.05 A; A=179-424.
DR PDB; 4GLY; X-ray; 1.52 A; A=179-423.
DR PDB; 4H42; X-ray; 2.01 A; U=179-426.
DR PDB; 4JK5; X-ray; 1.55 A; A=179-423.
DR PDB; 4JK6; X-ray; 2.20 A; A=179-423.
DR PDB; 4K24; X-ray; 4.50 A; A=21-153.
DR PDB; 4MNV; X-ray; 1.80 A; A=179-423.
DR PDB; 4MNW; X-ray; 1.49 A; A=179-423.
DR PDB; 4MNX; X-ray; 1.85 A; A=179-423.
DR PDB; 4MNY; X-ray; 1.70 A; A/B=179-423.
DR PDB; 4OS1; X-ray; 2.20 A; A=179-423.
DR PDB; 4OS2; X-ray; 1.79 A; A=179-423.
DR PDB; 4OS4; X-ray; 2.00 A; A=179-423.
DR PDB; 4OS5; X-ray; 2.26 A; A=179-423.
DR PDB; 4OS6; X-ray; 1.75 A; A=179-423.
DR PDB; 4OS7; X-ray; 2.00 A; A=179-423.
DR PDB; 4X0W; X-ray; 2.10 A; U=179-425.
DR PDB; 4X1N; X-ray; 1.80 A; U=179-425.
DR PDB; 4X1P; X-ray; 1.60 A; U=179-425.
DR PDB; 4X1Q; X-ray; 2.28 A; U=179-425.
DR PDB; 4X1R; X-ray; 2.10 A; U=179-425.
DR PDB; 4X1S; X-ray; 1.90 A; U=179-425.
DR PDB; 4XSK; X-ray; 1.50 A; U=179-424.
DR PDB; 4ZHL; X-ray; 2.06 A; U=179-425.
DR PDB; 4ZHM; X-ray; 1.90 A; U=179-425.
DR PDB; 4ZKN; X-ray; 1.36 A; U=179-425.
DR PDB; 4ZKO; X-ray; 1.29 A; U=179-425.
DR PDB; 4ZKR; X-ray; 1.36 A; U=179-425.
DR PDB; 4ZKS; X-ray; 1.85 A; U=179-425.
DR PDB; 5HGG; X-ray; 1.97 A; A/B=179-424.
DR PDB; 5WXF; X-ray; 1.46 A; U=179-431.
DR PDB; 5WXO; X-ray; 1.64 A; U=179-431.
DR PDB; 5WXP; X-ray; 1.75 A; U=179-431.
DR PDB; 5WXQ; X-ray; 1.79 A; U=179-431.
DR PDB; 5WXR; X-ray; 1.75 A; U=179-431.
DR PDB; 5WXS; X-ray; 2.30 A; U=179-431.
DR PDB; 5WXT; X-ray; 2.10 A; U=179-431.
DR PDB; 5XG4; X-ray; 3.00 A; U=179-424.
DR PDB; 5YC6; X-ray; 1.18 A; U=179-424.
DR PDB; 5YC7; X-ray; 2.00 A; U=179-424.
DR PDB; 5Z1C; X-ray; 1.45 A; U=179-423.
DR PDB; 5ZA7; X-ray; 1.70 A; U=179-431.
DR PDB; 5ZA8; X-ray; 1.90 A; U=179-431.
DR PDB; 5ZA9; X-ray; 1.62 A; U=179-431.
DR PDB; 5ZAE; X-ray; 1.73 A; U=179-431.
DR PDB; 5ZAF; X-ray; 1.65 A; U=179-431.
DR PDB; 5ZAG; X-ray; 1.95 A; U=179-431.
DR PDB; 5ZAH; X-ray; 2.98 A; U=179-431.
DR PDB; 5ZAJ; X-ray; 1.65 A; U=179-431.
DR PDB; 5ZC5; X-ray; 1.90 A; U=179-431.
DR PDB; 6AG2; X-ray; 1.77 A; U=179-431.
DR PDB; 6AG3; X-ray; 2.48 A; U=179-431.
DR PDB; 6AG7; X-ray; 1.90 A; U=179-423.
DR PDB; 6AG9; X-ray; 1.63 A; U=179-431.
DR PDB; 6JYP; X-ray; 2.25 A; U=179-424.
DR PDB; 6JYQ; X-ray; 1.75 A; U=179-424.
DR PDB; 6L04; X-ray; 2.21 A; U=179-423.
DR PDB; 6L05; X-ray; 2.49 A; U=179-423.
DR PDB; 6NMB; X-ray; 2.30 A; A/B/C/D=162-431.
DR PDB; 6XVD; X-ray; 1.40 A; U=179-431.
DR PDB; 7DZD; X-ray; 2.00 A; U=179-423.
DR PDB; 7VM4; X-ray; 2.01 A; U=179-423.
DR PDB; 7VM5; X-ray; 1.97 A; U=179-424.
DR PDB; 7VM6; X-ray; 1.79 A; U=179-426.
DR PDB; 7VM7; X-ray; 1.87 A; U=179-423.
DR PDB; 7ZRR; X-ray; 1.64 A; A=154-431.
DR PDB; 7ZRT; X-ray; 1.80 A; A=179-431.
DR PDBsum; 1C5W; -.
DR PDBsum; 1C5X; -.
DR PDBsum; 1C5Y; -.
DR PDBsum; 1C5Z; -.
DR PDBsum; 1EJN; -.
DR PDBsum; 1F5K; -.
DR PDBsum; 1F5L; -.
DR PDBsum; 1F92; -.
DR PDBsum; 1FV9; -.
DR PDBsum; 1GI7; -.
DR PDBsum; 1GI8; -.
DR PDBsum; 1GI9; -.
DR PDBsum; 1GJ7; -.
DR PDBsum; 1GJ8; -.
DR PDBsum; 1GJ9; -.
DR PDBsum; 1GJA; -.
DR PDBsum; 1GJB; -.
DR PDBsum; 1GJC; -.
DR PDBsum; 1GJD; -.
DR PDBsum; 1KDU; -.
DR PDBsum; 1LMW; -.
DR PDBsum; 1O3P; -.
DR PDBsum; 1O5A; -.
DR PDBsum; 1O5B; -.
DR PDBsum; 1O5C; -.
DR PDBsum; 1OWD; -.
DR PDBsum; 1OWE; -.
DR PDBsum; 1OWH; -.
DR PDBsum; 1OWI; -.
DR PDBsum; 1OWJ; -.
DR PDBsum; 1OWK; -.
DR PDBsum; 1SC8; -.
DR PDBsum; 1SQA; -.
DR PDBsum; 1SQO; -.
DR PDBsum; 1SQT; -.
DR PDBsum; 1U6Q; -.
DR PDBsum; 1URK; -.
DR PDBsum; 1VJ9; -.
DR PDBsum; 1VJA; -.
DR PDBsum; 1W0Z; -.
DR PDBsum; 1W10; -.
DR PDBsum; 1W11; -.
DR PDBsum; 1W12; -.
DR PDBsum; 1W13; -.
DR PDBsum; 1W14; -.
DR PDBsum; 2FD6; -.
DR PDBsum; 2I9A; -.
DR PDBsum; 2I9B; -.
DR PDBsum; 2NWN; -.
DR PDBsum; 2O8T; -.
DR PDBsum; 2O8U; -.
DR PDBsum; 2O8W; -.
DR PDBsum; 2R2W; -.
DR PDBsum; 2VIN; -.
DR PDBsum; 2VIO; -.
DR PDBsum; 2VIP; -.
DR PDBsum; 2VIQ; -.
DR PDBsum; 2VIV; -.
DR PDBsum; 2VIW; -.
DR PDBsum; 2VNT; -.
DR PDBsum; 3BT1; -.
DR PDBsum; 3BT2; -.
DR PDBsum; 3IG6; -.
DR PDBsum; 3KGP; -.
DR PDBsum; 3KHV; -.
DR PDBsum; 3KID; -.
DR PDBsum; 3M61; -.
DR PDBsum; 3MHW; -.
DR PDBsum; 3MWI; -.
DR PDBsum; 3OX7; -.
DR PDBsum; 3OY5; -.
DR PDBsum; 3OY6; -.
DR PDBsum; 3PB1; -.
DR PDBsum; 3QN7; -.
DR PDBsum; 3U73; -.
DR PDBsum; 4DVA; -.
DR PDBsum; 4DW2; -.
DR PDBsum; 4FU7; -.
DR PDBsum; 4FU8; -.
DR PDBsum; 4FU9; -.
DR PDBsum; 4FUB; -.
DR PDBsum; 4FUC; -.
DR PDBsum; 4FUD; -.
DR PDBsum; 4FUE; -.
DR PDBsum; 4FUF; -.
DR PDBsum; 4FUG; -.
DR PDBsum; 4FUH; -.
DR PDBsum; 4FUI; -.
DR PDBsum; 4FUJ; -.
DR PDBsum; 4GLY; -.
DR PDBsum; 4H42; -.
DR PDBsum; 4JK5; -.
DR PDBsum; 4JK6; -.
DR PDBsum; 4K24; -.
DR PDBsum; 4MNV; -.
DR PDBsum; 4MNW; -.
DR PDBsum; 4MNX; -.
DR PDBsum; 4MNY; -.
DR PDBsum; 4OS1; -.
DR PDBsum; 4OS2; -.
DR PDBsum; 4OS4; -.
DR PDBsum; 4OS5; -.
DR PDBsum; 4OS6; -.
DR PDBsum; 4OS7; -.
DR PDBsum; 4X0W; -.
DR PDBsum; 4X1N; -.
DR PDBsum; 4X1P; -.
DR PDBsum; 4X1Q; -.
DR PDBsum; 4X1R; -.
DR PDBsum; 4X1S; -.
DR PDBsum; 4XSK; -.
DR PDBsum; 4ZHL; -.
DR PDBsum; 4ZHM; -.
DR PDBsum; 4ZKN; -.
DR PDBsum; 4ZKO; -.
DR PDBsum; 4ZKR; -.
DR PDBsum; 4ZKS; -.
DR PDBsum; 5HGG; -.
DR PDBsum; 5WXF; -.
DR PDBsum; 5WXO; -.
DR PDBsum; 5WXP; -.
DR PDBsum; 5WXQ; -.
DR PDBsum; 5WXR; -.
DR PDBsum; 5WXS; -.
DR PDBsum; 5WXT; -.
DR PDBsum; 5XG4; -.
DR PDBsum; 5YC6; -.
DR PDBsum; 5YC7; -.
DR PDBsum; 5Z1C; -.
DR PDBsum; 5ZA7; -.
DR PDBsum; 5ZA8; -.
DR PDBsum; 5ZA9; -.
DR PDBsum; 5ZAE; -.
DR PDBsum; 5ZAF; -.
DR PDBsum; 5ZAG; -.
DR PDBsum; 5ZAH; -.
DR PDBsum; 5ZAJ; -.
DR PDBsum; 5ZC5; -.
DR PDBsum; 6AG2; -.
DR PDBsum; 6AG3; -.
DR PDBsum; 6AG7; -.
DR PDBsum; 6AG9; -.
DR PDBsum; 6JYP; -.
DR PDBsum; 6JYQ; -.
DR PDBsum; 6L04; -.
DR PDBsum; 6L05; -.
DR PDBsum; 6NMB; -.
DR PDBsum; 6XVD; -.
DR PDBsum; 7DZD; -.
DR PDBsum; 7VM4; -.
DR PDBsum; 7VM5; -.
DR PDBsum; 7VM6; -.
DR PDBsum; 7VM7; -.
DR PDBsum; 7ZRR; -.
DR PDBsum; 7ZRT; -.
DR AlphaFoldDB; P00749; -.
DR BMRB; P00749; -.
DR SASBDB; P00749; -.
DR SMR; P00749; -.
DR BioGRID; 111344; 83.
DR ComplexPortal; CPX-483; uPA-PAI-1 complex.
DR ComplexPortal; CPX-487; uPA-uPAR complex.
DR ComplexPortal; CPX-501; uPA-uPAR-vitronectin complex.
DR CORUM; P00749; -.
DR DIP; DIP-46387N; -.
DR ELM; P00749; -.
DR IntAct; P00749; 16.
DR MINT; P00749; -.
DR STRING; 9606.ENSP00000361850; -.
DR BindingDB; P00749; -.
DR ChEMBL; CHEMBL3286; -.
DR DrugBank; DB07129; (2R)-1-(2,6-dimethylphenoxy)propan-2-amine.
DR DrugBank; DB07122; 1-[4-(2-oxo-2-phenylethyl)phenyl]guanidine.
DR DrugBank; DB01905; 2-(2-Hydroxy-5-Methoxy-Phenyl)-1h-Benzoimidazole-5-Carboxamidine.
DR DrugBank; DB02287; 2-(2-hydroxy-phenyl)-3H-benzoimidazole-5-carboxamidine.
DR DrugBank; DB03729; 2-Amino-1H-benzimidazol-5-ol.
DR DrugBank; DB01725; 2-{2-hydroxy-[1,1'-biphenyl]-3-yl}-1H-1,3-benzodiazole-5-carboximidamide.
DR DrugBank; DB08072; 4-(2-AMINOETHOXY)-3,5-DICHLORO-N-[3-(1-METHYLETHOXY)PHENYL]BENZAMIDE.
DR DrugBank; DB07625; 4-(2-aminoethoxy)-N-(2,5-diethoxyphenyl)-3,5-dimethylbenzamide.
DR DrugBank; DB07626; 4-(2-aminoethoxy)-N-(3-chloro-2-ethoxy-5-piperidin-1-ylphenyl)-3,5-dimethylbenzamide.
DR DrugBank; DB08697; 4-(2-aminoethoxy)-N-(3-chloro-5-piperidin-1-ylphenyl)-3,5-dimethylbenzamide.
DR DrugBank; DB03136; 4-Iodobenzo[B]Thiophene-2-Carboxamidine.
DR DrugBank; DB01977; 6-(N-Phenylcarbamyl)-2-Naphthalenecarboxamidine.
DR DrugBank; DB07076; 6-[(Z)-AMINO(IMINO)METHYL]-N-[3-(CYCLOPENTYLOXY)PHENYL]-2-NAPHTHAMIDE.
DR DrugBank; DB03082; 6-[(Z)-Amino(Imino)Methyl]-N-[4-(Aminomethyl)Phenyl]-4-(Pyrimidin-2-Ylamino)-2-Naphthamide.
DR DrugBank; DB02705; 6-[N-(1-Isopropyl-1,2,3,4-Tetrahydro-7-Isoquinolinyl)Carbamyl]-2-Naphthalenecarboxamidine.
DR DrugBank; DB02473; 6-[N-(1-Isopropyl-3,4-Dihydro-7-Isoquinolinyl)Carbamyl]-2-Naphthalenecarboxamidine.
DR DrugBank; DB02398; 6-[N-(4-(Aminomethyl)Phenyl)Carbamyl]-2-Naphthalenecarboxamidine.
DR DrugBank; DB02551; 6-[N-(4-Ethyl-1,2,3,4-Tetrahydro-6-Isoquinolinyl)Carbamyl]-2-Naphthalenecarboxamidine.
DR DrugBank; DB03865; 6-Chloro-2-(2-Hydroxy-Biphenyl-3-Yl)-1h-Indole-5-Carboxamidine.
DR DrugBank; DB06855; 6-fluoro-2-(2-hydroxy-3-isobutoxy-phenyl)-1H-benzoimidazole-5-carboxamidine.
DR DrugBank; DB06856; 6-FLUORO-2-[2-HYDROXY-3-(2-METHYL-CYCLOHEXYLOXY)-PHENYL]-1H-INDOLE-5-CARBOXAMIDINE.
DR DrugBank; DB03046; 7-Methoxy-8-[1-(Methylsulfonyl)-1h-Pyrazol-4-Yl]Naphthalene-2-Carboximidamide.
DR DrugBank; DB04059; 8-(Pyrimidin-2-Ylamino)Naphthalene-2-Carboximidamide.
DR DrugBank; DB04172; [2,4,6-Triisopropyl-Phenylsulfonyl-L-[3-Amidino-Phenylalanine]]-Piperazine-N'-Beta-Alanine.
DR DrugBank; DB00594; Amiloride.
DR DrugBank; DB03127; Benzamidine.
DR DrugBank; DB02526; CRA_10655.
DR DrugBank; DB03159; CRA_8696.
DR DrugBank; DB05254; Fibrinolysin.
DR DrugBank; DB03782; N-(1-adamantyl)-N'-(4-guanidinobenzyl)urea.
DR DrugBank; DB06857; N-(4-CARBAMIMIDOYL-3-CHORO-PHENYL)-2-HYDROXY-3-IODO-5-METHYL-BENZAMIDE.
DR DrugBank; DB16701; Plasminogen.
DR DrugBank; DB03876; Thieno[2,3-B]Pyridine-2-Carboxamidine.
DR DrugBank; DB03476; Trans-6-(2-Phenylcyclopropyl)-Naphthalene-2-Carboxamidine.
DR DrugCentral; P00749; -.
DR GuidetoPHARMACOLOGY; 2393; -.
DR MEROPS; S01.231; -.
DR GlyConnect; 612; 2 N-Linked glycans (1 site), 1 O-Fuc glycan (1 site).
DR GlyConnect; 86; 16 N-Linked glycans (1 site).
DR GlyCosmos; P00749; 3 sites, 31 glycans.
DR GlyGen; P00749; 4 sites, 13 N-linked glycans (2 sites), 2 O-linked glycans (3 sites).
DR iPTMnet; P00749; -.
DR PhosphoSitePlus; P00749; -.
DR SwissPalm; P00749; -.
DR BioMuta; PLAU; -.
DR DMDM; 254763341; -.
DR EPD; P00749; -.
DR jPOST; P00749; -.
DR MassIVE; P00749; -.
DR MaxQB; P00749; -.
DR PaxDb; 9606-ENSP00000361850; -.
DR PeptideAtlas; P00749; -.
DR ProteomicsDB; 51279; -. [P00749-1]
DR ProteomicsDB; 51280; -. [P00749-2]
DR ABCD; P00749; 2 sequenced antibodies.
DR Antibodypedia; 1899; 1126 antibodies from 45 providers.
DR DNASU; 5328; -.
DR Ensembl; ENST00000372764.4; ENSP00000361850.3; ENSG00000122861.16. [P00749-1]
DR Ensembl; ENST00000446342.5; ENSP00000388474.1; ENSG00000122861.16. [P00749-2]
DR GeneID; 5328; -.
DR KEGG; hsa:5328; -.
DR MANE-Select; ENST00000372764.4; ENSP00000361850.3; NM_002658.6; NP_002649.2.
DR UCSC; uc001jwa.4; human. [P00749-1]
DR AGR; HGNC:9052; -.
DR CTD; 5328; -.
DR DisGeNET; 5328; -.
DR GeneCards; PLAU; -.
DR HGNC; HGNC:9052; PLAU.
DR HPA; ENSG00000122861; Tissue enhanced (kidney, urinary bladder).
DR MalaCards; PLAU; -.
DR MIM; 191840; gene.
DR MIM; 601709; phenotype.
DR neXtProt; NX_P00749; -.
DR OpenTargets; ENSG00000122861; -.
DR Orphanet; 220436; Quebec platelet disorder.
DR PharmGKB; PA33382; -.
DR VEuPathDB; HostDB:ENSG00000122861; -.
DR eggNOG; ENOG502QRMI; Eukaryota.
DR GeneTree; ENSGT01050000244971; -.
DR InParanoid; P00749; -.
DR OMA; WPWCYVQ; -.
DR OrthoDB; 4629979at2759; -.
DR PhylomeDB; P00749; -.
DR TreeFam; TF329901; -.
DR BRENDA; 3.4.21.73; 2681.
DR PathwayCommons; P00749; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-75205; Dissolution of Fibrin Clot.
DR SABIO-RK; P00749; -.
DR SignaLink; P00749; -.
DR SIGNOR; P00749; -.
DR BioGRID-ORCS; 5328; 15 hits in 1171 CRISPR screens.
DR ChiTaRS; PLAU; human.
DR EvolutionaryTrace; P00749; -.
DR GeneWiki; PLAU; -.
DR GenomeRNAi; 5328; -.
DR Pharos; P00749; Tchem.
DR PRO; PR:P00749; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P00749; Protein.
DR Bgee; ENSG00000122861; Expressed in renal medulla and 165 other cell types or tissues.
DR ExpressionAtlas; P00749; baseline and differential.
DR Genevisible; P00749; HS.
DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR GO; GO:0009897; C:external side of plasma membrane; NAS:ComplexPortal.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0098637; C:protein complex involved in cell-matrix adhesion; IPI:ComplexPortal.
DR GO; GO:0097180; C:serine protease inhibitor complex; IPI:ComplexPortal.
DR GO; GO:1905370; C:serine-type endopeptidase complex; IPI:ComplexPortal.
DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome.
DR GO; GO:0070821; C:tertiary granule membrane; TAS:Reactome.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0007596; P:blood coagulation; IEA:UniProtKB-KW.
DR GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
DR GO; GO:0042730; P:fibrinolysis; IBA:GO_Central.
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; IDA:AgBase.
DR GO; GO:0030335; P:positive regulation of cell migration; IDA:MGI.
DR GO; GO:0006508; P:proteolysis; TAS:ProtInc.
DR GO; GO:0030155; P:regulation of cell adhesion; IDA:ComplexPortal.
DR GO; GO:0033628; P:regulation of cell adhesion mediated by integrin; IDA:BHF-UCL.
DR GO; GO:0042127; P:regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0051917; P:regulation of fibrinolysis; NAS:ComplexPortal.
DR GO; GO:0010755; P:regulation of plasminogen activation; NAS:ComplexPortal.
DR GO; GO:0010469; P:regulation of signaling receptor activity; IDA:BHF-UCL.
DR GO; GO:0014910; P:regulation of smooth muscle cell migration; IDA:BHF-UCL.
DR GO; GO:2000097; P:regulation of smooth muscle cell-matrix adhesion; IDA:BHF-UCL.
DR GO; GO:0061041; P:regulation of wound healing; IC:BHF-UCL.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0014909; P:smooth muscle cell migration; IEA:Ensembl.
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; 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; IPR018114; TRYPSIN_HIS.
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; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Blood coagulation;
KW Direct protein sequencing; Disulfide bond; EGF-like domain; Fibrinolysis;
KW Glycoprotein; Hemostasis; Hydrolase; Kringle; Pharmaceutical;
KW Phosphoprotein; Plasminogen activation; Protease; Reference proteome;
KW Secreted; Serine protease; Signal; Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000269|PubMed:2023947,
FT ECO:0000269|PubMed:6754569"
FT CHAIN 21..431
FT /note="Urokinase-type plasminogen activator"
FT /id="PRO_0000028318"
FT CHAIN 21..177
FT /note="Urokinase-type plasminogen activator long chain A"
FT /id="PRO_0000028319"
FT CHAIN 156..177
FT /note="Urokinase-type plasminogen activator short chain A"
FT /id="PRO_0000028320"
FT CHAIN 179..431
FT /note="Urokinase-type plasminogen activator chain B"
FT /id="PRO_0000028321"
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..424
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 /evidence="ECO:0000250"
FT REGION 152..177
FT /note="Connecting peptide"
FT ACT_SITE 224
FT /note="Charge relay system"
FT ACT_SITE 275
FT /note="Charge relay system"
FT ACT_SITE 376
FT /note="Charge relay system"
FT SITE 177..178
FT /note="Cleavage; during zymogen activation"
FT MOD_RES 158
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:9151681"
FT MOD_RES 323
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:9151681"
FT CARBOHYD 38
FT /note="O-linked (Fuc) threonine"
FT /evidence="ECO:0000269|PubMed:2023947"
FT CARBOHYD 322
FT /note="N-linked (GlcNAc...) asparagine"
FT /id="CAR_000026"
FT DISULFID 31..39
FT DISULFID 33..51
FT DISULFID 53..62
FT DISULFID 70..151
FT DISULFID 91..133
FT DISULFID 122..146
FT DISULFID 168..299
FT /note="Interchain (between A and B chains)"
FT DISULFID 209..225
FT DISULFID 217..288
FT DISULFID 313..382
FT DISULFID 345..361
FT DISULFID 372..400
FT VAR_SEQ 1..29
FT /note="MRALLARLLLCVLVVSDSKGSNELHQVPS -> MVFHLRTRYEQA (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_038368"
FT VARIANT 15
FT /note="V -> L (in dbSNP:rs2227580)"
FT /evidence="ECO:0000269|Ref.7"
FT /id="VAR_038730"
FT VARIANT 141
FT /note="L -> P (in dbSNP:rs2227564)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:18987736,
FT ECO:0000269|PubMed:2415429, ECO:0000269|PubMed:2987867,
FT ECO:0000269|PubMed:3888571, ECO:0000269|PubMed:6589620,
FT ECO:0000269|PubMed:6754569, ECO:0000269|PubMed:9065988,
FT ECO:0000269|PubMed:9194591, ECO:0000269|Ref.1,
FT ECO:0000269|Ref.5, ECO:0000269|Ref.7, ECO:0000269|Ref.9"
FT /id="VAR_006722"
FT VARIANT 214
FT /note="I -> M (in dbSNP:rs1050120)"
FT /evidence="ECO:0000269|PubMed:2987867,
FT ECO:0000269|PubMed:6589620"
FT /id="VAR_013102"
FT VARIANT 231
FT /note="K -> Q (in dbSNP:rs2227567)"
FT /evidence="ECO:0000269|Ref.7"
FT /id="VAR_038731"
FT MUTAGEN 158
FT /note="S->E: Abolishes phosphorylation, proadhesive
FT function and ability to induce chemotactic response; when
FT associated with E-323."
FT /evidence="ECO:0000269|PubMed:9151681"
FT MUTAGEN 323
FT /note="S->E: Abolishes phosphorylation, proadhesive
FT function and ability to induce chemotactic response; when
FT associated with E-158."
FT /evidence="ECO:0000269|PubMed:9151681"
FT CONFLICT 150
FT /note="D -> G (in Ref. 6; BAG60754)"
FT /evidence="ECO:0000305"
FT CONFLICT 151
FT /note="C -> W (in Ref. 2; CAA26535)"
FT /evidence="ECO:0000305"
FT CONFLICT 386
FT /note="G -> C (in Ref. 2; CAA26535)"
FT /evidence="ECO:0000305"
FT CONFLICT 430
FT /note="A -> V (in Ref. 2; CAA26535)"
FT /evidence="ECO:0000305"
FT STRAND 34..36
FT /evidence="ECO:0007829|PDB:1URK"
FT STRAND 38..41
FT /evidence="ECO:0007829|PDB:2FD6"
FT TURN 43..47
FT /evidence="ECO:0007829|PDB:2FD6"
FT STRAND 49..52
FT /evidence="ECO:0007829|PDB:2FD6"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:2FD6"
FT STRAND 64..67
FT /evidence="ECO:0007829|PDB:2FD6"
FT STRAND 70..72
FT /evidence="ECO:0007829|PDB:2I9B"
FT STRAND 73..77
FT /evidence="ECO:0007829|PDB:3U73"
FT STRAND 86..89
FT /evidence="ECO:0007829|PDB:1URK"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:1KDU"
FT HELIX 99..101
FT /evidence="ECO:0007829|PDB:2FD6"
FT STRAND 102..104
FT /evidence="ECO:0007829|PDB:2FD6"
FT STRAND 106..108
FT /evidence="ECO:0007829|PDB:3BT1"
FT HELIX 111..114
FT /evidence="ECO:0007829|PDB:2FD6"
FT STRAND 117..119
FT /evidence="ECO:0007829|PDB:2FD6"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:2I9A"
FT STRAND 132..137
FT /evidence="ECO:0007829|PDB:2FD6"
FT STRAND 140..147
FT /evidence="ECO:0007829|PDB:2FD6"
FT HELIX 162..165
FT /evidence="ECO:0007829|PDB:1GJA"
FT STRAND 180..184
FT /evidence="ECO:0007829|PDB:5YC6"
FT HELIX 187..189
FT /evidence="ECO:0007829|PDB:5YC6"
FT STRAND 193..199
FT /evidence="ECO:0007829|PDB:5YC6"
FT STRAND 201..203
FT /evidence="ECO:0007829|PDB:4XSK"
FT STRAND 205..215
FT /evidence="ECO:0007829|PDB:5YC6"
FT STRAND 218..221
FT /evidence="ECO:0007829|PDB:5YC6"
FT HELIX 223..225
FT /evidence="ECO:0007829|PDB:5YC6"
FT TURN 226..228
FT /evidence="ECO:0007829|PDB:5YC6"
FT HELIX 232..234
FT /evidence="ECO:0007829|PDB:5YC6"
FT STRAND 235..240
FT /evidence="ECO:0007829|PDB:5YC6"
FT STRAND 243..246
FT /evidence="ECO:0007829|PDB:5YC6"
FT STRAND 252..261
FT /evidence="ECO:0007829|PDB:5YC6"
FT STRAND 268..271
FT /evidence="ECO:0007829|PDB:5HGG"
FT STRAND 272..274
FT /evidence="ECO:0007829|PDB:5YC6"
FT STRAND 277..282
FT /evidence="ECO:0007829|PDB:5YC6"
FT STRAND 293..295
FT /evidence="ECO:0007829|PDB:1LMW"
FT STRAND 312..318
FT /evidence="ECO:0007829|PDB:5YC6"
FT STRAND 329..331
FT /evidence="ECO:0007829|PDB:4DW2"
FT STRAND 333..340
FT /evidence="ECO:0007829|PDB:5YC6"
FT HELIX 342..345
FT /evidence="ECO:0007829|PDB:5YC6"
FT TURN 348..351
FT /evidence="ECO:0007829|PDB:5YC6"
FT HELIX 352..354
FT /evidence="ECO:0007829|PDB:5YC6"
FT TURN 356..358
FT /evidence="ECO:0007829|PDB:4DW2"
FT STRAND 359..363
FT /evidence="ECO:0007829|PDB:5YC6"
FT STRAND 365..367
FT /evidence="ECO:0007829|PDB:3KHV"
FT STRAND 379..384
FT /evidence="ECO:0007829|PDB:5YC6"
FT STRAND 387..396
FT /evidence="ECO:0007829|PDB:5YC6"
FT STRAND 398..402
FT /evidence="ECO:0007829|PDB:5YC6"
FT STRAND 407..411
FT /evidence="ECO:0007829|PDB:5YC6"
FT HELIX 412..414
FT /evidence="ECO:0007829|PDB:5YC6"
FT HELIX 416..422
FT /evidence="ECO:0007829|PDB:5YC6"
SQ SEQUENCE 431 AA; 48523 MW; 2F7E6005A8765AC1 CRC64;
MRALLARLLL CVLVVSDSKG SNELHQVPSN CDCLNGGTCV SNKYFSNIHW CNCPKKFGGQ
HCEIDKSKTC YEGNGHFYRG KASTDTMGRP CLPWNSATVL QQTYHAHRSD ALQLGLGKHN
YCRNPDNRRR PWCYVQVGLK LLVQECMVHD CADGKKPSSP PEELKFQCGQ KTLRPRFKII
GGEFTTIENQ PWFAAIYRRH RGGSVTYVCG GSLISPCWVI SATHCFIDYP KKEDYIVYLG
RSRLNSNTQG EMKFEVENLI LHKDYSADTL AHHNDIALLK IRSKEGRCAQ PSRTIQTICL
PSMYNDPQFG TSCEITGFGK ENSTDYLYPE QLKMTVVKLI SHRECQQPHY YGSEVTTKML
CAADPQWKTD SCQGDSGGPL VCSLQGRMTL TGIVSWGRGC ALKDKPGVYT RVSHFLPWIR
SHTKEENGLA L
//
