Plasminogen activator inhibitor 1

Details

Name
Plasminogen activator inhibitor 1
Kind
protein
Synonyms
  • Endothelial plasminogen activator inhibitor
  • PAI
  • PAI-1
  • PAI1
  • PLANH1
  • Serpin E1
Gene Name
SERPINE1
UniProtKB Entry
P05121Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0000479|Plasminogen activator inhibitor 1
MQMSPALTCLVLGLALVFGEGSAVHHPPSYVAHLASDFGVRVFQQVAQASKDRNVVFSPY
GVASVLAMLQLTTGGETQQQIQAAMGFKIDDKGMAPALRHLYKELMGPWNKDEISTTDAI
FVQRDLKLVQGFMPHFFRLFRSTVKQVDFSEVERARFIINDWVKTHTKGMISNLLGKGAV
DQLTRLVLVNALYFNGQWKTPFPDSSTHRRLFHKSDGSTVSVPMMAQTNKFNYTEFTTPD
GHYYDILELPYHGDTLSMFIAAPYEKEVPLSALTNILSAQLISHWKGNMTRLPRLLVLPK
FSLETEVDLRKPLENLGMTDMFRQFQADFTSLSDQEPLHVAQALQKVKIEVNESGTVASS
STAVIVSARMAPEEIIMDRPFLFVVRHNPTGTVLFMGQVMEP
Number of residues
402
Molecular Weight
45059.695
Theoretical pI
7.22
GO Classification
Functions
protease binding / serine-type endopeptidase inhibitor activity
Processes
angiogenesis / cellular response to lipopolysaccharide / defense response to Gram-negative bacterium / fibrinolysis / negative regulation of blood coagulation / negative regulation of cell adhesion mediated by integrin / negative regulation of cell migration / negative regulation of endopeptidase activity / negative regulation of endothelial cell apoptotic process / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / negative regulation of fibrinolysis / negative regulation of plasminogen activation / negative regulation of smooth muscle cell migration / negative regulation of smooth muscle cell-matrix adhesion / negative regulation of vascular wound healing / negative regulation of wound healing / positive regulation of angiogenesis / positive regulation of blood coagulation / positive regulation of inflammatory response / positive regulation of interleukin-8 production / positive regulation of leukotriene production involved in inflammatory response / positive regulation of monocyte chemotaxis / positive regulation of receptor-mediated endocytosis
Components
extracellular exosome / extracellular region / extracellular space / plasma membrane / platelet alpha granule lumen
General Function
Serine protease inhibitor. Inhibits TMPRSS7 (PubMed:15853774). Is a primary inhibitor of tissue-type plasminogen activator (PLAT) and urokinase-type plasminogen activator (PLAU). As PLAT inhibitor, it is required for fibrinolysis down-regulation and is responsible for the controlled degradation of blood clots (PubMed:17912461, PubMed:8481516, PubMed:9207454). As PLAU inhibitor, it is involved in the regulation of cell adhesion and spreading (PubMed:9175705). Acts as a regulator of cell migration, independently of its role as protease inhibitor (PubMed:15001579, PubMed:9168821). It is required for stimulation of keratinocyte migration during cutaneous injury repair (PubMed:18386027). It is involved in cellular and replicative senescence (PubMed:16862142). Plays a role in alveolar type 2 cells senescence in the lung (By similarity). Is involved in the regulation of cementogenic differentiation of periodontal ligament stem cells, and regulates odontoblast differentiation and dentin formation during odontogenesis (PubMed:25808697, PubMed:27046084)
Specific Function
protease binding
Pfam Domain Function
Signal Regions
1-23
Transmembrane Regions
Not Available
Cellular Location
Secreted
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
Chromosome Location
7
Locus
7q22.1
External Identifiers
ResourceLink
UniProtKB IDP05121
UniProtKB Entry NamePAI1_HUMAN
GenBank Protein ID35272
GenBank Gene IDX04429
GeneCard IDSERPINE1
GenAtlas IDSERPINE1
HGNC IDHGNC:8583
PDB ID(s)1A7C, 1B3K, 1C5G, 1DB2, 1DVM, 1DVN, 1LJ5, 1OC0, 3CVM, 3EOX, 3PB1, 3Q02, 3Q03, 3R4L, 3UT3, 4AQH, 4G8O, 4G8R, 4IC0, 5BRR, 5ZLZ, 6GWN, 6GWP, 6GWQ, 6I8S, 6ZRV, 7AQF, 7AQG, 9PAI
KEGG IDhsa:5054
NCBI Gene ID5054
General 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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
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  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. [Article]
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  13. Sigurdardottir O, Wiman B: Identification of a PAI-1 binding site in vitronectin. Biochim Biophys Acta. 1994 Sep 21;1208(1):104-10. [Article]
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Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Drotrecogin alfaapproved, investigational, withdrawnunknowntargetDetails
Urokinaseapproved, investigational, withdrawnyestargetsubstrateinducerDetails
TenecteplaseapprovedunknowntargetDetails
Troglitazoneapproved, investigational, withdrawnunknowntargetantagonistDetails
FibrinolysininvestigationalunknowntargetDetails
Alteplaseapproved, investigationalunknowntargetDetails
AnistreplaseapprovedunknowntargetDetails
Reteplaseapproved, investigationalunknowntargetDetails
Copperapproved, investigationalunknowntargetDetails
TM5614investigationalunknowntargetDetails
Colforsinexperimental, investigationalunknowntargetinhibitorDetails
BucladesineexperimentalunknowntargetinhibitorDetails
AleplasinininvestigationalyestargetinhibitorDetails