You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Toxin, Toxin Target Database.
NameUrokinase-type plasminogen activator
Synonyms
  • 3.4.21.73
  • U-plasminogen activator
Gene NamePLAU
OrganismHuman
Amino acid sequence
>lcl|BSEQ0037097|Urokinase-type plasminogen activator
MRALLARLLLCVLVVSDSKGSNELHQVPSNCDCLNGGTCVSNKYFSNIHWCNCPKKFGGQ
HCEIDKSKTCYEGNGHFYRGKASTDTMGRPCLPWNSATVLQQTYHAHRSDALQLGLGKHN
YCRNPDNRRRPWCYVQVGLKPLVQECMVHDCADGKKPSSPPEELKFQCGQKTLRPRFKII
GGEFTTIENQPWFAAIYRRHRGGSVTYVCGGSLISPCWVISATHCFIDYPKKEDYIVYLG
RSRLNSNTQGEMKFEVENLILHKDYSADTLAHHNDIALLKIRSKEGRCAQPSRTIQTICL
PSMYNDPQFGTSCEITGFGKENSTDYLYPEQLKMTVVKLISHRECQQPHYYGSEVTTKML
CAADPQWKTDSCQGDSGGPLVCSLQGRMTLTGIVSWGRGCALKDKPGVYTRVSHFLPWIR
SHTKEENGLAL
Number of residues431
Molecular Weight48507.09
Theoretical pI8.48
GO Classification
Functions
  • serine-type endopeptidase activity
Processes
  • angiogenesis
  • regulation of smooth muscle cell migration
  • cellular response to lipopolysaccharide
  • signal transduction
  • neuron death
  • blood coagulation
  • cellular response to staurosporine
  • positive regulation of ovulation
  • positive regulation of smooth muscle cell migration
  • regulation of smooth muscle cell-matrix adhesion
  • cellular response to hypoxia
  • proteolysis
  • regulation of wound healing
  • regulation of receptor activity
  • embryo implantation
  • spermatogenesis
  • cellular response to glucose stimulus
  • chemotaxis
  • cellular response to fluid shear stress
  • regulation of hepatocyte proliferation
  • response to hyperoxia
  • plasminogen activation
  • fibrinolysis
  • smooth muscle cell migration
  • positive regulation of cell proliferation
  • cellular response to hepatocyte growth factor stimulus
  • positive regulation of reactive oxygen species metabolic process
  • regulation of cell adhesion mediated by integrin
  • response to activity
  • skeletal muscle tissue regeneration
Components
  • focal adhesion
  • extracellular region
  • plasma membrane
  • extracellular space
  • cell surface
  • extracellular exosome
General FunctionSerine-type endopeptidase activity
Specific FunctionSpecifically cleaves the zymogen plasminogen to form the active enzyme plasmin.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID1834524
UniProtKB IDP00749
UniProtKB Entry NameUROK_HUMAN
Cellular LocationSecreted
Gene sequence
>lcl|BSEQ0021654|Urokinase-type plasminogen activator (PLAU)
ATGGTCTTCCATTTGAGAACTAGATACGAACAGGCGAACTGTGACTGTCTAAATGGAGGA
ACATGTGTGTCCAACAAGTACTTCTCCAACATTCACTGGTGCAACTGCCCAAAGAAATTC
GGAGGGCAGCACTGTGAAATAGATAAGTCAAAAACCTGCTATGAGGGGAATGGTCACTTT
TACCGAGGAAAGGCCAGCACTGACACCATGGGCCGGCCCTGCCTGCCCTGGAACTCTGCC
ACTGTCCTTCAGCAAACGTACCATGCCCACAGATCTGATGCTCTTCAGCTGGGCCTGGGG
AAACATAATTACTGCAGGAACCCAGACAACCGGAGGCGACCCTGGTGCTATGTGCAGGTG
GGCCTAAAGCCGCTTGTCCAAGAGTGCATGGTGCATGACTGCGCAGATGGAAAAAAGCCC
TCCTCTCCTCCAGAAGAATTAAAATTTCAGTGTGGCCAAAAGACTCTGAGGCCCCGCTTT
AAGATTATTGGGGGAGAATTCACCACCATCGAGAACCAGCCCTGGTTTGCGGCCATCTAC
AGGAGGCACCGGGGGGGCTCTGTCACCTACGTGTGTGGAGGCAGCCTCATCAGCCCTTGC
TGGGTGATCAGCGCCACACACTGCTTCATTGATTACCCAAAGAAGGAGGACTACATCGTC
TACCTGGGTCGCTCAAGGCTTAACTCCAACACGCAAGGGGAGATGAAGTTTGAGGTGGAA
AACCTCATCCTACACAAGGACTACAGCGCTGACACGCTTGCTCACCACAACGACATTGCC
TTGCTGAAGATCCGTTCCAAGGAGGGCAGGTGTGCGCAGCCATCCCGGACTATACAGACC
ATCTGCCTGCCCTCGATGTATAACGATCCCCAGTTTGGCACAAGCTGTGAGATCACTGGC
TTTGGAAAAGAGAATTCTACCGACTATCTCTATCCGGAGCAGCTGAAAATGACTGTTGTG
AAGCTGATTTCCCACCGGGAGTGTCAGCAGCCCCACTACTACGGCTCTGAAGTCACCACC
AAAATGCTGTGTGCTGCTGACCCACAGTGGAAAACAGATTCCTGCCAGGGAGACTCAGGG
GGACCCCTCGTCTGTTCCCTCCAAGGCCGCATGACTTTGACTGGAATTGTGAGCTGGGGC
CGTGGATGTGCCCTGAAGGACAAGCCAGGCGTCTACACGAGAGTCTCACACTTCTTACCC
TGGATCCGCAGTCACACCAAGGAAGAGAATGGCCTGGCCCTCTGA
GenBank Gene IDX02419
GeneCard IDNot Available
GenAtlas IDPLAU
HGNC IDHGNC:9052
Chromosome Location10
Locus10q24
References
  1. Jacobs P, Cravador A, Loriau R, Brockly F, Colau B, Chuchana P, van Elsen A, Herzog A, Bollen A: Molecular cloning, sequencing, and expression in Escherichia coli of human preprourokinase cDNA. DNA. 1985 Apr;4(2):139-46. 3888571
  2. Nagai M, Hiramatsu R, Kaneda T, Hayasuke N, Arimura H, Nishida M, Suyama T: Molecular cloning of cDNA coding for human preprourokinase. Gene. 1985;36(1-2):183-8. 2415429
  3. Riccio A, Grimaldi G, Verde P, Sebastio G, Boast S, Blasi F: The human urokinase-plasminogen activator gene and its promoter. Nucleic Acids Res. 1985 Apr 25;13(8):2759-71. 2987867
  4. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  5. Deloukas P, Earthrowl ME, Grafham DV, Rubenfield M, French L, Steward CA, Sims SK, Jones MC, Searle S, Scott C, Howe K, Hunt SE, Andrews TD, Gilbert JG, Swarbreck D, Ashurst JL, Taylor A, Battles J, Bird CP, Ainscough R, Almeida JP, Ashwell RI, Ambrose KD, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Bates K, Beasley H, Bray-Allen S, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Cahill P, Camire D, Carter NP, Chapman JC, Clark SY, Clarke G, Clee CM, Clegg S, Corby N, Coulson A, Dhami P, Dutta I, Dunn M, Faulkner L, Frankish A, Frankland JA, Garner P, Garnett J, Gribble S, Griffiths C, Grocock R, Gustafson E, Hammond S, Harley JL, Hart E, Heath PD, Ho TP, Hopkins B, Horne J, Howden PJ, Huckle E, Hynds C, Johnson C, Johnson D, Kana A, Kay M, Kimberley AM, Kershaw JK, Kokkinaki M, Laird GK, Lawlor S, Lee HM, Leongamornlert DA, Laird G, Lloyd C, Lloyd DM, Loveland J, Lovell J, McLaren S, McLay KE, McMurray A, Mashreghi-Mohammadi M, Matthews L, Milne S, Nickerson T, Nguyen M, Overton-Larty E, Palmer SA, Pearce AV, Peck AI, Pelan S, Phillimore B, Porter K, Rice CM, Rogosin A, Ross MT, Sarafidou T, Sehra HK, Shownkeen R, Skuce CD, Smith M, Standring L, Sycamore N, Tester J, Thorpe A, Torcasso W, Tracey A, Tromans A, Tsolas J, Wall M, Walsh J, Wang H, Weinstock K, West AP, Willey DL, Whitehead SL, Wilming L, Wray PW, Young L, Chen Y, Lovering RC, Moschonas NK, Siebert R, Fechtel K, Bentley D, Durbin R, Hubbard T, Doucette-Stamm L, Beck S, Smith DR, Rogers J: The DNA sequence and comparative analysis of human chromosome 10. Nature. 2004 May 27;429(6990):375-81. 15164054
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  7. Yoshimoto M, Ushiyama Y, Sakai M, Tamaki S, Hara H, Takahashi K, Sawasaki Y, Hanada K: Characterization of single chain urokinase-type plasminogen activator with a novel amino-acid substitution in the kringle structure. Biochim Biophys Acta. 1996 Mar 7;1293(1):83-9. 8652631
  8. Buko AM, Kentzer EJ, Petros A, Menon G, Zuiderweg ER, Sarin VK: Characterization of a posttranslational fucosylation in the growth factor domain of urinary plasminogen activator. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3992-6. 2023947
  9. Verde P, Stoppelli MP, Galeffi P, Di Nocera P, Blasi F: Identification and primary sequence of an unspliced human urokinase poly(A)+ RNA. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4727-31. 6589620
  10. Gunzler WA, Steffens GJ, Otting F, Kim SM, Frankus E, Flohe L: The primary structure of high molecular mass urokinase from human urine. The complete amino acid sequence of the A chain. Hoppe Seylers Z Physiol Chem. 1982 Oct;363(10):1155-65. 6754569
  11. Schaller J, Nick H, Rickli EE, Gillessen D, Lergier W, Studer RO: Human low-molecular-weight urinary urokinase. Partial characterization and preliminary sequence data of the two polypeptide chains. Eur J Biochem. 1982 Jul;125(2):251-7. 6749491
  12. Steffens GJ, Gunzler WA, Otting F, Frankus E, Flohe L: The complete amino acid sequence of low molecular mass urokinase from human urine. Hoppe Seylers Z Physiol Chem. 1982 Sep;363(9):1043-58. 6754572
  13. Stief TW, Radtke KP, Heimburger N: Inhibition of urokinase by protein C-inhibitor (PCI). Evidence for identity of PCI and plasminogen activator inhibitor 3. Biol Chem Hoppe Seyler. 1987 Oct;368(10):1427-33. 3501295
  14. Franco P, Iaccarino C, Chiaradonna F, Brandazza A, Iavarone C, Mastronicola MR, Nolli ML, Stoppelli MP: Phosphorylation of human pro-urokinase on Ser138/303 impairs its receptor-dependent ability to promote myelomonocytic adherence and motility. J Cell Biol. 1997 May 5;137(3):779-91. 9151681
  15. He S, Lin YL, Liu YX: Functionally inactive protein C inhibitor in seminal plasma may be associated with infertility. Mol Hum Reprod. 1999 Jun;5(6):513-9. 10340997
  16. Behrendt N, Jensen ON, Engelholm LH, Mortz E, Mann M, Dano K: A urokinase receptor-associated protein with specific collagen binding properties. J Biol Chem. 2000 Jan 21;275(3):1993-2002. 10636902
  17. Liu CX, Li Y, Obermoeller-McCormick LM, Schwartz AL, Bu G: The putative tumor suppressor LRP1B, a novel member of the low density lipoprotein (LDL) receptor family, exhibits both overlapping and distinct properties with the LDL receptor-related protein. J Biol Chem. 2001 Aug 3;276(31):28889-96. Epub 2001 May 30. 11384978
  18. Wakita T, Hayashi T, Nishioka J, Tamaru H, Akita N, Asanuma K, Kamada H, Gabazza EC, Ido M, Kawamura J, Suzuki K: Regulation of carcinoma cell invasion by protein C inhibitor whose expression is decreased in renal cell carcinoma. Int J Cancer. 2004 Feb 10;108(4):516-23. 14696115
  19. Ustach CV, Kim HR: Platelet-derived growth factor D is activated by urokinase plasminogen activator in prostate carcinoma cells. Mol Cell Biol. 2005 Jul;25(14):6279-88. 15988036
  20. Paterson AD, Rommens JM, Bharaj B, Blavignac J, Wong I, Diamandis M, Waye JS, Rivard GE, Hayward CP: Persons with Quebec platelet disorder have a tandem duplication of PLAU, the urokinase plasminogen activator gene. Blood. 2010 Feb 11;115(6):1264-6. doi: 10.1182/blood-2009-07-233965. Epub 2009 Dec 9. 20007542
  21. Oswald RE, Bogusky MJ, Bamberger M, Smith RA, Dobson CM: Dynamics of the multidomain fibrinolytic protein urokinase from two-dimensional NMR. Nature. 1989 Feb 9;337(6207):579-82. 2536903
  22. Li X, Smith RA, Dobson CM: Sequential 1H NMR assignments and secondary structure of the kringle domain from urokinase. Biochemistry. 1992 Oct 13;31(40):9562-71. 1327118
  23. Li X, Bokman AM, Llinas M, Smith RA, Dobson CM: Solution structure of the kringle domain from urokinase-type plasminogen activator. J Mol Biol. 1994 Feb 4;235(5):1548-59. 8107091
  24. Spraggon G, Phillips C, Nowak UK, Ponting CP, Saunders D, Dobson CM, Stuart DI, Jones EY: The crystal structure of the catalytic domain of human urokinase-type plasminogen activator. Structure. 1995 Jul 15;3(7):681-91. 8591045
  25. Sperl S, Jacob U, Arroyo de Prada N, Sturzebecher J, Wilhelm OG, Bode W, Magdolen V, Huber R, Moroder L: (4-aminomethyl)phenylguanidine derivatives as nonpeptidic highly selective inhibitors of human urokinase. Proc Natl Acad Sci U S A. 2000 May 9;97(10):5113-8. 10805774
  26. Huai Q, Mazar AP, Kuo A, Parry GC, Shaw DE, Callahan J, Li Y, Yuan C, Bian C, Chen L, Furie B, Furie BC, Cines DB, Huang M: Structure of human urokinase plasminogen activator in complex with its receptor. Science. 2006 Feb 3;311(5761):656-9. 16456079
  27. Conne B, Berczy M, Belin D: Detection of polymorphisms in the human urokinase-type plasminogen activator gene. Thromb Haemost. 1997 Mar;77(3):434-5. 9065988
  28. Turkmen B, Schmitt M, Schmalfeldt B, Trommler P, Hell W, Creutzburg S, Graeff H, Magdolen V: Mutational analysis of the genes encoding urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in advanced ovarian cancer. Electrophoresis. 1997 May;18(5):686-9. 9194591
  29. Ley TJ, Mardis ER, Ding L, Fulton B, McLellan MD, Chen K, Dooling D, Dunford-Shore BH, McGrath S, Hickenbotham M, Cook L, Abbott R, Larson DE, Koboldt DC, Pohl C, Smith S, Hawkins A, Abbott S, Locke D, Hillier LW, Miner T, Fulton L, Magrini V, Wylie T, Glasscock J, Conyers J, Sander N, Shi X, Osborne JR, Minx P, Gordon D, Chinwalla A, Zhao Y, Ries RE, Payton JE, Westervelt P, Tomasson MH, Watson M, Baty J, Ivanovich J, Heath S, Shannon WD, Nagarajan R, Walter MJ, Link DC, Graubert TA, DiPersio JF, Wilson RK: DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature. 2008 Nov 6;456(7218):66-72. doi: 10.1038/nature07485. 18987736