Plasma serine protease inhibitor

Details

Name
Plasma serine protease inhibitor
Synonyms
  • Acrosomal serine protease inhibitor
  • PAI-3
  • PAI3
  • PCI
  • PLANH3
  • Plasminogen activator inhibitor 3
  • PROCI
  • Protein C inhibitor
  • Serpin A5
Gene Name
SERPINA5
Organism
Humans
Amino acid sequence
>lcl|BSEQ0011531|Plasma serine protease inhibitor
MQLFLLLCLVLLSPQGASLHRHHPREMKKRVEDLHVGATVAPSSRRDFTFDLYRALASAA
PSQSIFFSPVSISMSLAMLSLGAGSSTKMQILEGLGLNLQKSSEKELHRGFQQLLQELNQ
PRDGFQLSLGNALFTDLVVDLQDTFVSAMKTLYLADTFPTNFRDSAGAMKQINDYVAKQT
KGKIVDLLKNLDSNAVVIMVNYIFFKAKWETSFNHKGTQEQDFYVTSETVVRVPMMSRED
QYHYLLDRNLSCRVVGVPYQGNATALFILPSEGKMQQVENGLSEKTLRKWLKMFKKRQLE
LYLPKFSIEGSYQLEKVLPSLGISNVFTSHADLSGISNHSNIQVSEMVHKAVVEVDESGT
RAAAATGTIFTFRSARLNSQRLVFNRPFLMFIVDNNILFLGKVNRP
Number of residues
406
Molecular Weight
45674.315
Theoretical pI
9.76
GO Classification
Functions
acrosin binding / glycosaminoglycan binding / heparin binding / phosphatidylcholine binding / protease binding / retinoic acid binding / serine-type endopeptidase inhibitor activity
Processes
blood coagulation / fusion of sperm to egg plasma membrane / lipid transport / negative regulation of endopeptidase activity / negative regulation of hydrolase activity / spermatogenesis
Components
acrosomal membrane / external side of plasma membrane / extracellular exosome / extracellular region / extracellular space / membrane / platelet alpha granule / platelet dense tubular network / protein C inhibitor-coagulation factor V complex / protein C inhibitor-coagulation factor Xa complex / protein C inhibitor-coagulation factor XI complex / protein C inhibitor-KLK3 complex / protein C inhibitor-plasma kallikrein complex / protein C inhibitor-PLAT complex / protein C inhibitor-PLAU complex / protein C inhibitor-thrombin complex / protein C inhibitor-TMPRSS11E complex / protein C inhibitor-TMPRSS7 complex / protein complex
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
Heparin-dependent serine protease inhibitor acting in body fluids and secretions. Inactivates serine proteases by binding irreversibly to their serine activation site. Involved in the regulation of intravascular and extravascular proteolytic activities. Plays hemostatic roles in the blood plasma. Acts as a procoagulant and proinflammatory factor by inhibiting the anticoagulant activated protein C factor as well as the generation of activated protein C factor by the thrombin/thrombomodulin complex. Acts as an anticoagulant factor by inhibiting blood coagulation factors like prothrombin, factor XI, factor Xa, plasma kallikrein and fibrinolytic enzymes such as tissue- and urinary-type plasminogen activators. In seminal plasma, inactivates several serine proteases implicated in the reproductive system. Inhibits the serpin acrosin; indirectly protects component of the male genital tract from being degraded by excessive released acrosin. Inhibits tissue-and urinary-type plasminogen activator, prostate-specific antigen and kallikrein activities; has a control on the sperm motility and fertilization. Inhibits the activated protein C-catalyzed degradation of SEMG1 and SEMG2; regulates the degradation of semenogelin during the process of transfer of spermatozoa from the male reproductive tract into the female tract. In urine, inhibits urinary-type plasminogen activator and kallikrein activities. Inactivates membrane-anchored serine proteases activities such as MPRSS7 and TMPRSS11E. Inhibits urinary-type plasminogen activator-dependent tumor cell invasion and metastasis. May also play a non-inhibitory role in seminal plasma and urine as a hydrophobic hormone carrier by its binding to retinoic acid.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
>lcl|BSEQ0011532|Plasma serine protease inhibitor (SERPINA5)
ATGCAGCTCTTCCTCCTCTTGTGCCTGGTGCTTCTCAGCCCTCAGGGGGCCTCCCTTCAC
CGCCACCACCCCCGGGAGATGAAGAAGAGAGTCGAGGACCTCCATGTAGGTGCCACGGTG
GCCCCCAGCAGCAGAAGGGACTTTACCTTTGACCTCTACAGGGCCTTGGCTTCCGCTGCC
CCCAGCCAGAGCATCTTCTTCTCCCCTGTGAGCATCTCCATGAGCCTGGCCATGCTCTCC
CTGGGGGCTGGGTCCAGCACAAAGATGCAGATCCTGGAGGGCCTGGGCCTCAACCTCCAG
AAAAGCTCAGAGAAGGAGCTGCACAGAGGCTTTCAGCAGCTCCTTCAGGAACTCAACCAG
CCCAGAGATGGCTTCCAGCTGAGCCTCGGCAATGCCCTTTTCACCGACCTGGTGGTAGAC
CTGCAGGACACCTTCGTAAGTGCCATGAAGACGCTGTACCTGGCAGACACTTTCCCTACC
AACTTTAGGGACTCTGCAGGGGCCATGAAGCAGATCAATGATTATGTGGCAAAGCAAACG
AAGGGCAAGATTGTGGACTTGCTTAAGAACCTCGATAGCAATGCGGTCGTGATCATGGTG
AATTACATCTTCTTTAAAGCTAAGTGGGAGACAAGCTTCAACCACAAAGGCACCCAAGAG
CAAGACTTCTACGTGACCTCGGAGACTGTGGTGCGGGTACCCATGATGAGCCGCGAGGAT
CAGTATCACTACCTCCTGGACCGGAACCTCTCCTGCAGGGTGGTGGGGGTCCCCTACCAA
GGCAATGCCACGGCTTTGTTCATTCTCCCCAGTGAGGGAAAGATGCAGCAGGTGGAGAAT
GGACTGAGTGAGAAAACGCTGAGGAAGTGGCTTAAGATGTTCAAAAAGAGGCAGCTCGAG
CTTTACCTTCCCAAATTCTCCATTGAGGGCTCCTATCAGCTGGAGAAAGTCCTCCCCAGT
CTGGGGATCAGTAACGTCTTCACCTCCCATGCTGATCTGTCCGGCATCAGCAACCACTCA
AATATCCAGGTGTCTGAGATGGTGCACAAAGCTGTGGTGGAGGTGGACGAGTCGGGAACC
AGAGCAGCGGCAGCCACGGGGACAATATTCACTTTCAGGTCGGCCCGCCTGAACTCTCAG
AGGCTAGTGTTCAACAGGCCCTTTCTGATGTTCATTGTGGATAACAACATCCTCTTCCTT
GGCAAAGTGAACCGCCCCTGA
Chromosome Location
14
Locus
14q32.1
External Identifiers
ResourceLink
UniProtKB IDP05154
UniProtKB Entry NameIPSP_HUMAN
GenBank Protein ID180550
GenBank Gene IDJ02639
GenAtlas IDSERPINA5
HGNC IDHGNC:8723
General References
  1. Suzuki K, Deyashiki Y, Nishioka J, Kurachi K, Akira M, Yamamoto S, Hashimoto S: Characterization of a cDNA for human protein C inhibitor. A new member of the plasma serine protease inhibitor superfamily. J Biol Chem. 1987 Jan 15;262(2):611-6. [PubMed:3027058]
  2. Meijers JC, Chung DW: Evidence for a glycine residue at position 316 in human protein C inhibitor. Thromb Res. 1990 Jul 15;59(2):389-93. [PubMed:2173165]
  3. Meijers JC, Chung DW: Organization of the gene coding for human protein C inhibitor (plasminogen activator inhibitor-3). Assignment of the gene to chromosome 14. J Biol Chem. 1991 Aug 15;266(23):15028-34. [PubMed:1714450]
  4. Hayashi T, Suzuki K: Gene organization of human protein C inhibitor, a member of SERPIN family proteins encoded in five exons. Int J Hematol. 1993 Oct;58(3):213-24. [PubMed:8148499]
  5. Radtke KP, Greengard JS, Fernandez JA, Villoutreix BO, Griffin JH: A two-allele polymorphism in protein C inhibitor with varying frequencies in different ethnic populations. Thromb Haemost. 1996 Jan;75(1):62-9. [PubMed:8713781]
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  8. Moore A, Penfold LM, Johnson JL, Latchman DS, Moore HD: Human sperm-egg binding is inhibited by peptides corresponding to core region of an acrosomal serine protease inhibitor. Mol Reprod Dev. 1993 Mar;34(3):280-91. [PubMed:8471250]
  9. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [PubMed:17974005]
  10. Laurell M, Stenflo J: Protein C inhibitor from human plasma: characterization of native and cleaved inhibitor and demonstration of inhibitor complexes with plasma kallikrein. Thromb Haemost. 1989 Nov 24;62(3):885-91. [PubMed:2556811]
  11. Suzuki K, Nishioka J, Kusumoto H, Hashimoto S: Mechanism of inhibition of activated protein C by protein C inhibitor. J Biochem. 1984 Jan;95(1):187-95. [PubMed:6323392]
  12. 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. [PubMed:3501295]
  13. Meijers JC, Kanters DH, Vlooswijk RA, van Erp HE, Hessing M, Bouma BN: Inactivation of human plasma kallikrein and factor XIa by protein C inhibitor. Biochemistry. 1988 Jun 14;27(12):4231-7. [PubMed:2844223]
  14. Espana F, Gilabert J, Estelles A, Romeu A, Aznar J, Cabo A: Functionally active protein C inhibitor/plasminogen activator inhibitor-3 (PCI/PAI-3) is secreted in seminal vesicles, occurs at high concentrations in human seminal plasma and complexes with prostate-specific antigen. Thromb Res. 1991 Nov 1;64(3):309-20. [PubMed:1725227]
  15. Laurell M, Christensson A, Abrahamsson PA, Stenflo J, Lilja H: Protein C inhibitor in human body fluids. Seminal plasma is rich in inhibitor antigen deriving from cells throughout the male reproductive system. J Clin Invest. 1992 Apr;89(4):1094-101. [PubMed:1372913]
  16. Zheng X, Geiger M, Ecke S, Bielek E, Donner P, Eberspacher U, Schleuning WD, Binder BR: Inhibition of acrosin by protein C inhibitor and localization of protein C inhibitor to spermatozoa. Am J Physiol. 1994 Aug;267(2 Pt 1):C466-72. [PubMed:7521127]
  17. Cooper ST, Whinna HC, Jackson TP, Boyd JM, Church FC: Intermolecular interactions between protein C inhibitor and coagulation proteases. Biochemistry. 1995 Oct 10;34(40):12991-7. [PubMed:7548057]
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  19. Kise H, Nishioka J, Kawamura J, Suzuki K: Characterization of semenogelin II and its molecular interaction with prostate-specific antigen and protein C inhibitor. Eur J Biochem. 1996 May 15;238(1):88-96. [PubMed:8665956]
  20. Elisen MG, von dem Borne PA, Bouma BN, Meijers JC: Protein C inhibitor acts as a procoagulant by inhibiting the thrombomodulin-induced activation of protein C in human plasma. Blood. 1998 Mar 1;91(5):1542-7. [PubMed:9473218]
  21. Elisen MG, van Kooij RJ, Nolte MA, Marquart JA, Lock TM, Bouma BN, Meijers JC: Protein C inhibitor may modulate human sperm-oocyte interactions. Biol Reprod. 1998 Mar;58(3):670-7. [PubMed:9510955]
  22. Nishioka J, Ning M, Hayashi T, Suzuki K: Protein C inhibitor secreted from activated platelets efficiently inhibits activated protein C on phosphatidylethanolamine of platelet membrane and microvesicles. J Biol Chem. 1998 May 1;273(18):11281-7. [PubMed:9556620]
  23. 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. [PubMed:10340997]
  24. Jerabek I, Zechmeister-Machhart M, Binder BR, Geiger M: Binding of retinoic acid by the inhibitory serpin protein C inhibitor. Eur J Biochem. 2001 Nov;268(22):5989-96. [PubMed:11722589]
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  32. Sun W, Parry S, Panico M, Morris HR, Kjellberg M, Engstrom A, Dell A, Schedin-Weiss S: N-glycans and the N terminus of protein C inhibitor affect the cofactor-enhanced rates of thrombin inhibition. J Biol Chem. 2008 Jul 4;283(27):18601-11. doi: 10.1074/jbc.M800608200. Epub 2008 May 8. [PubMed:18467335]
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  34. Sun W, Parry S, Ubhayasekera W, Engstrom A, Dell A, Schedin-Weiss S: Further insight into the roles of the glycans attached to human blood protein C inhibitor. Biochem Biophys Res Commun. 2010 Dec 10;403(2):198-202. doi: 10.1016/j.bbrc.2010.11.005. Epub 2010 Nov 5. [PubMed:21056543]
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  36. Kuhn LA, Griffin JH, Fisher CL, Greengard JS, Bouma BN, Espana F, Tainer JA: Elucidating the structural chemistry of glycosaminoglycan recognition by protein C inhibitor. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8506-10. [PubMed:2172989]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00013Urokinaseapproved, investigational, withdrawnunknownDetails
DB00055Drotrecogin alfaapproved, investigational, withdrawnunknownDetails
DB05413TifuvirtideinvestigationalunknownDetails
DB05961PPL-100investigationalunknownDetails