Plasminogen activator inhibitor 1

NamePlasminogen activator inhibitor 1
Synonyms
  • Endothelial plasminogen activator inhibitor
  • PAI
  • PAI1
  • PLANH1
  • Serpin E1
Gene NameSERPINE1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0000479|Plasminogen activator inhibitor 1
MQMSPALTCLVLGLALVFGEGSAVHHPPSYVAHLASDFGVRVFQQVAQASKDRNVVFSPY
GVASVLAMLQLTTGGETQQQIQAAMGFKIDDKGMAPALRHLYKELMGPWNKDEISTTDAI
FVQRDLKLVQGFMPHFFRLFRSTVKQVDFSEVERARFIINDWVKTHTKGMISNLLGKGAV
DQLTRLVLVNALYFNGQWKTPFPDSSTHRRLFHKSDGSTVSVPMMAQTNKFNYTEFTTPD
GHYYDILELPYHGDTLSMFIAAPYEKEVPLSALTNILSAQLISHWKGNMTRLPRLLVLPK
FSLETEVDLRKPLENLGMTDMFRQFQADFTSLSDQEPLHVAQALQKVKIEVNESGTVASS
STAVIVSARMAPEEIIMDRPFLFVVRHNPTGTVLFMGQVMEP
Number of residues402
Molecular Weight45059.695
Theoretical pI7.22
GO Classification
Functions
  • receptor binding
  • serine-type endopeptidase inhibitor activity
  • protease binding
Processes
  • negative regulation of vascular wound healing
  • positive regulation of blood coagulation
  • negative regulation of wound healing
  • positive regulation of inflammatory response
  • positive regulation of angiogenesis
  • circadian rhythm
  • positive regulation of interleukin-8 production
  • angiogenesis
  • positive regulation of leukotriene production involved in inflammatory response
  • cellular response to lipopolysaccharide
  • platelet activation
  • positive regulation of monocyte chemotaxis
  • negative regulation of endopeptidase activity
  • gene expression
  • positive regulation of receptor-mediated endocytosis
  • transcription initiation from RNA polymerase II promoter
  • regulation of receptor activity
  • chronological cell aging
  • transcription, DNA-templated
  • defense response to Gram-negative bacterium
  • extracellular matrix organization
  • transforming growth factor beta receptor signaling pathway
  • negative regulation of blood coagulation
  • negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
  • negative regulation of cell adhesion mediated by integrin
  • positive regulation of transcription from RNA polymerase II promoter
  • negative regulation of cell migration
  • negative regulation of endothelial cell apoptotic process
  • platelet degranulation
  • negative regulation of plasminogen activation
  • negative regulation of smooth muscle cell migration
  • fibrinolysis
  • negative regulation of smooth muscle cell-matrix adhesion
  • negative regulation of fibrinolysis
  • blood coagulation
Components
  • extracellular region
  • plasma membrane
  • extracellular space
  • extracellular exosome
  • platelet alpha granule lumen
  • extracellular matrix
General FunctionSerine-type endopeptidase inhibitor activity
Specific FunctionSerine protease inhibitor. This inhibitor acts as 'bait' for tissue plasminogen activator, urokinase, protein C and matriptase-3/TMPRSS7. Its rapid interaction with PLAT may function as a major control point in the regulation of fibrinolysis.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID35272
UniProtKB IDP05121
UniProtKB Entry NamePAI1_HUMAN
Cellular LocationSecreted
Gene sequence
>lcl|BSEQ0010214|Plasminogen activator inhibitor 1 (SERPINE1)
ATGCAGATGTCTCCAGCCCTCACCTGCCTAGTCCTGGGCCTGGCCCTTGTCTTTGGTGAA
GGGTCTGCTGTGCACCATCCCCCATCCTACGTGGCCCACCTGGCCTCAGACTTCGGGGTG
AGGGTGTTTCAGCAGGTGGCGCAGGCCTCCAAGGACCGCAACGTGGTTTTCTCACCCTAT
GGGGTGGCCTCGGTGTTGGCCATGCTCCAGCTGACAACAGGAGGAGAAACCCAGCAGCAG
ATTCAAGCAGCTATGGGATTCAAGATTGATGACAAGGGCATGGCCCCCGCCCTCCGGCAT
CTGTACAAGGAGCTCATGGGGCCATGGAACAAGGATGAGATCAGCACCACAGACGCGATC
TTCGTCCAGCGGGATCTGAAGCTGGTCCAGGGCTTCATGCCCCACTTCTTCAGGCTGTTC
CGGAGCACGGTCAAGCAAGTGGACTTTTCAGAGGTGGAGAGAGCCAGATTCATCATCAAT
GACTGGGTGAAGACACACACAAAAGGTATGATCAGCAACTTGCTTGGGAAAGGAGCCGTG
GACCAGCTGACACGGCTGGTGCTGGTGAATGCCCTCTACTTCAACGGCCAGTGGAAGACT
CCCTTCCCCGACTCCAGCACCCACCGCCGCCTCTTCCACAAATCAGACGGCAGCACTGTC
TCTGTGCCCATGATGGCTCAGACCAACAAGTTCAACTATACTGAGTTCACCACGCCCGAT
GGCCATTACTACGACATCCTGGAACTGCCCTACCACGGGGACACCCTCAGCATGTTCATT
GCTGCCCCTTATGAAAAAGAGGTGCCTCTCTCTGCCCTCACCAACATTCTGAGTGCCCAG
CTCATCAGCCACTGGAAAGGCAACATGACCAGGCTGCCCCGCCTCCTGGTTCTGCCCAAG
TTCTCCCTGGAGACTGAAGTCGACCTCAGGAAGCCCCTAGAGAACCTGGGAATGACCGAC
ATGTTCAGACAGTTTCAGGCTGACTTCACGAGTCTTTCAGACCAAGAGCCTCTCCACGTC
GCGCAGGCGCTGCAGAAAGTGAAGATCGAGGTGAACGAGAGTGGCACGGTGGCCTCCTCA
TCCACAGCTGTCATAGTCTCAGCCCGCATGGCCCCCGAGGAGATCATCATGGACAGACCC
TTCCTCTTTGTGGTCCGGCACAACCCCACAGGAACAGTCCTTTTCATGGGCCAAGTGATG
GAACCCTGA
GenBank Gene IDX04429
GeneCard IDNot Available
GenAtlas IDSERPINE1
HGNC IDHGNC:8583
Chromosome Location7
Locus7q21.3-q22
References
  1. Pannekoek H, Veerman H, Lambers H, Diergaarde P, Verweij CL, van Zonneveld AJ, van Mourik JA: Endothelial plasminogen activator inhibitor (PAI): a new member of the Serpin gene family. EMBO J. 1986 Oct;5(10):2539-44. 2430793
  2. Loskutoff DJ, Linders M, Keijer J, Veerman H, van Heerikhuizen H, Pannekoek H: Structure of the human plasminogen activator inhibitor 1 gene: nonrandom distribution of introns. Biochemistry. 1987 Jun 30;26(13):3763-8. 2820474
  3. Ginsburg D, Zeheb R, Yang AY, Rafferty UM, Andreasen PA, Nielsen L, Dano K, Lebo RV, Gelehrter TD: cDNA cloning of human plasminogen activator-inhibitor from endothelial cells. J Clin Invest. 1986 Dec;78(6):1673-80. 3097076
  4. Follo M, Ginsburg D: Structure and expression of the human gene encoding plasminogen activator inhibitor, PAI-1. Gene. 1989 Dec 14;84(2):447-53. 2612914
  5. Strandberg L, Lawrence D, Ny T: The organization of the human-plasminogen-activator-inhibitor-1 gene. Implications on the evolution of the serine-protease inhibitor family. Eur J Biochem. 1988 Oct 1;176(3):609-16. 3262512
  6. Bosma PJ, van den Berg EA, Kooistra T, Siemieniak DR, Slightom JL: Human plasminogen activator inhibitor-1 gene. Promoter and structural gene nucleotide sequences. J Biol Chem. 1988 Jul 5;263(19):9129-41. 3132455
  7. 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
  8. Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK: The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64. 12853948
  9. 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
  10. Ny T, Sawdey M, Lawrence D, Millan JL, Loskutoff DJ: Cloning and sequence of a cDNA coding for the human beta-migrating endothelial-cell-type plasminogen activator inhibitor. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6776-80. 3092219
  11. Andreasen PA, Riccio A, Welinder KG, Douglas R, Sartorio R, Nielsen LS, Oppenheimer C, Blasi F, Dano K: Plasminogen activator inhibitor type-1: reactive center and amino-terminal heterogeneity determined by protein and cDNA sequencing. FEBS Lett. 1986 Dec 15;209(2):213-8. 3025016
  12. Wun TC, Kretzmer KK: cDNA cloning and expression in E. coli of a plasminogen activator inhibitor (PAI) related to a PAI produced by Hep G2 hepatoma cell. FEBS Lett. 1987 Jan 1;210(1):11-6. 3026837
  13. Sigurdardottir O, Wiman B: Identification of a PAI-1 binding site in vitronectin. Biochim Biophys Acta. 1994 Sep 21;1208(1):104-10. 7522053
  14. Fay WP, Parker AC, Condrey LR, Shapiro AD: Human plasminogen activator inhibitor-1 (PAI-1) deficiency: characterization of a large kindred with a null mutation in the PAI-1 gene. Blood. 1997 Jul 1;90(1):204-8. 9207454
  15. 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
  16. Szabo R, Netzel-Arnett S, Hobson JP, Antalis TM, Bugge TH: Matriptase-3 is a novel phylogenetically preserved membrane-anchored serine protease with broad serpin reactivity. Biochem J. 2005 Aug 15;390(Pt 1):231-42. 15853774
  17. Rosenow A, Noben JP, Jocken J, Kallendrusch S, Fischer-Posovszky P, Mariman EC, Renes J: Resveratrol-induced changes of the human adipocyte secretion profile. J Proteome Res. 2012 Sep 7;11(9):4733-43. doi: 10.1021/pr300539b. Epub 2012 Aug 27. 22905912
  18. Mottonen J, Strand A, Symersky J, Sweet RM, Danley DE, Geoghegan KF, Gerard RD, Goldsmith EJ: Structural basis of latency in plasminogen activator inhibitor-1. Nature. 1992 Jan 16;355(6357):270-3. 1731226
  19. Aertgeerts K, De Bondt HL, De Ranter CJ, Declerck PJ: Mechanisms contributing to the conformational and functional flexibility of plasminogen activator inhibitor-1. Nat Struct Biol. 1995 Oct;2(10):891-7. 7552714
  20. Xue Y, Bjorquist P, Inghardt T, Linschoten M, Musil D, Sjolin L, Deinum J: Interfering with the inhibitory mechanism of serpins: crystal structure of a complex formed between cleaved plasminogen activator inhibitor type 1 and a reactive-centre loop peptide. Structure. 1998 May 15;6(5):627-36. 9634700
  21. Sharp AM, Stein PE, Pannu NS, Carrell RW, Berkenpas MB, Ginsburg D, Lawrence DA, Read RJ: The active conformation of plasminogen activator inhibitor 1, a target for drugs to control fibrinolysis and cell adhesion. Structure. 1999 Feb 15;7(2):111-8. 10368279
  22. Nar H, Bauer M, Stassen JM, Lang D, Gils A, Declerck PJ: Plasminogen activator inhibitor 1. Structure of the native serpin, comparison to its other conformers and implications for serpin inactivation. J Mol Biol. 2000 Mar 31;297(3):683-95. 10731421
  23. 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
  24. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. 10391209