A purification experiment of heparin cofactor II was performed in 1981, in which it was discovered that the purified version of the protein consists of a single polypeptide chain.[6] Further experimentation demonstrated that whether β-Mercaptoethanol is present does not affect HCII's activity in gel electrophoresis. β-Mercaptoethanol is typically used for the reduction of disulfide bonds within a molecule, but the gel electrophoresis revealed that HCII does not have any of these bonds. The structure is similar to antithrombin III (ATIII), which was known to effectively inhibit thrombin as well as coagulation factor Xa.[6] This experiment suggested that HCII has strong thrombin inhibition, yet weak inhibition of coagulation factor Xa.
Heparin cofactor II may play a role in the immune response, as it has been associated with leukocyte-mediated protein degradation, which releases cytokines in the inflammatory response with neutrophils and monocytes.[7] Its role has been questioned because although it is a thrombin inhibitor, an absence of HCII does not result in significantly higher levels of thrombosis.[7] This does not negate the results of the 1981 study, but novel discoveries create more questions of the biological mechanism and function of the protein. However, this cofactor shows stronger capability in inhibiting thrombin in pregnant women, protecting them from thrombosis. Pregnant women have shown increased levels of heparin cofactor II as well as dermatan sulfate, which is a polysaccharide that is expected to be involved in wound repair, coagulation, and overall maintenance throughout the body. Pregnant women who had thrombosis are likely to also have low levels of heparin cofactor II, but whether this is a causation is still unknown.[8]
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000099937 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000022766 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ab"Entrez Gene: SERPIND1 serpin peptidase inhibitor, clade D (heparin cofactor), member 1".
^ abTollefsen, D M; Majerus, D W; Blank, M K (March 1982). "Heparin cofactor II. Purification and properties of a heparin-dependent inhibitor of thrombin in human plasma". Journal of Biological Chemistry. 257 (5): 2162–2169. doi:10.1016/s0021-9258(18)34900-7. ISSN 0021-9258. PMID 6895893.
^ abBrummel-Ziedins, Kathleen; Mann, Kenneth G. (2018-01-01). "Molecular Basis of Blood Coagulation". Hematology: 1885–1905.e8. doi:10.1016/B978-0-323-35762-3.00126-8. ISBN9780323357623.
^Huntington, James A. (2005-01-01). "Heparin Activation of Serpins". Chemistry and Biology of Heparin and Heparan Sulfate: 367–398. doi:10.1016/B978-008044859-6/50014-9. ISBN9780080448596.
Further readingedit
Griffith MJ, Carraway T, White GC, Dombrose FA (1983). "Serpin receptor 1: heparin cofactor activities in a family with hereditary antithrombin III deficiency: evidence for a second heparin cofactor in human plasma". Blood. 61 (1): 111–118. doi:10.1182/blood.V61.1.111.111.
Pizzo SV (1989). "Serpin receptor 1: a hepatic receptor that mediates the clearance of antithrombin III-proteinase complexes". Am. J. Med. 87 (3B): 10S–14S. doi:10.1016/0002-9343(89)80524-8. PMID 2552799.
Uszyński M (1992). "Tissue anticoagulants in the human placenta: preliminary study with a heparin-like anticoagulant and review of the literature". Gynecol. Obstet. Invest. 32 (3): 129–33. doi:10.1159/000293013. PMID 1836773.
Sutherland JS, Bhakta V, Filion ML, Sheffield WP (2006). "The transferable tail: fusion of the N-terminal acidic extension of heparin cofactor II to alpha1-proteinase inhibitor M358R specifically increases the rate of thrombin inhibition". Biochemistry. 45 (38): 11444–52. doi:10.1021/bi0609624. PMID 16981704.
Giri TK, Tollefsen DM (2006). "Placental dermatan sulfate: isolation, anticoagulant activity, and association with heparin cofactor II". Blood. 107 (7): 2753–8. doi:10.1182/blood-2005-09-3755. PMC1895383. PMID 16339402.
Liu T, Qian WJ, Gritsenko MA, et al. (2006). "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry". J. Proteome Res. 4 (6): 2070–80. doi:10.1021/pr0502065. PMC1850943. PMID 16335952.
Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
Schillinger M, Exner M, Sabeti S, et al. (2005). "High plasma heparin cofactor II activity protects from restenosis after femoropopliteal stenting". Thromb. Haemost. 92 (5): 1108–13. doi:10.1160/TH04-05-0311. PMID 15543340. S2CID 13806207.
Collins JE, Wright CL, Edwards CA, et al. (2005). "A genome annotation-driven approach to cloning the human ORFeome". Genome Biol. 5 (10): R84. doi:10.1186/gb-2004-5-10-r84. PMC545604. PMID 15461802.
Suzuki Y, Yamashita R, Shirota M, et al. (2004). "Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions". Genome Res. 14 (9): 1711–8. doi:10.1101/gr.2435604. PMC515316. PMID 15342556.
Corral J, Aznar J, Gonzalez-Conejero R, et al. (2006). "Homozygous deficiency of heparin cofactor II: relevance of P17 glutamate residue in serpins, relationship with conformational diseases, and role in thrombosis". Circulation. 110 (10): 1303–7. doi:10.1161/01.CIR.0000140763.51679.D9. PMID 15337701.
Fortenberry YM, Whinna HC, Gentry HR, et al. (2004). "Molecular mapping of the thrombin-heparin cofactor II complex". J. Biol. Chem. 279 (41): 43237–44. doi:10.1074/jbc.M406716200. PMID 15292227.
Zhang F, Wu Y, Ma Q, et al. (2004). "Studies on the effect of calcium in interactions between heparin and heparin cofactor II using surface plasmon resonance". Clin. Appl. Thromb. Hemost. 10 (3): 249–57. doi:10.1177/107602960401000307. PMID 15247982.
Anderson NL, Polanski M, Pieper R, et al. (2004). "The human plasma proteome: a nonredundant list developed by combination of four separate sources". Mol. Cell. Proteomics. 3 (4): 311–26. doi:10.1074/mcp.M300127-MCP200. PMID 14718574.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC139241. PMID 12477932.
Noda A, Wada H, Kusiya F, et al. (2003). "Plasma levels of heparin cofactor II (HCII) and thrombin-HCII complex in patients with disseminated intravascular coagulation". Clin. Appl. Thromb. Hemost. 8 (3): 265–71. doi:10.1177/107602960200800311. PMID 12361205.
Baglin TP, Carrell RW, Church FC, et al. (2002). "Crystal structures of native and thrombin-complexed heparin cofactor II reveal a multistep allosteric mechanism". Proc. Natl. Acad. Sci. U.S.A. 99 (17): 11079–84. Bibcode:2002PNAS...9911079B. doi:10.1073/pnas.162232399. PMC123213. PMID 12169660.
Cunningham MA, Bhakta V, Sheffield WP (2003). "Altering heparin cofactor II at VAL439 (P6) either impairs inhibition of thrombin or confers elastase resistance". Thromb. Haemost. 88 (1): 89–97. doi:10.1055/s-0037-1613159. PMID 12152684. S2CID 1467230.
Hayakawa Y, Hirashima Y, Kurimoto M, et al. (2002). "Contribution of basic residues of the A helix of heparin cofactor II to heparin- or dermatan sulfate-mediated thrombin inhibition". FEBS Lett. 522 (1–3): 147–50. doi:10.1016/S0014-5793(02)02930-7. PMID 12095635. S2CID 12634527.
Mitchell JW, Church FC (2002). "Aspartic acid residues 72 and 75 and tyrosine-sulfate 73 of heparin cofactor II promote intramolecular interactions during glycosaminoglycan binding and thrombin inhibition". J. Biol. Chem. 277 (22): 19823–30. doi:10.1074/jbc.M200630200. PMID 11856753.
Böhme C, Nimtz M, Grabenhorst E, et al. (2002). "Tyrosine sulfation and N-glycosylation of human heparin cofactor II from plasma and recombinant Chinese hamster ovary cells and their effects on heparin binding". Eur. J. Biochem. 269 (3): 977–88. doi:10.1046/j.0014-2956.2001.02732.x. PMID 11846800.
External linksedit
The MEROPS online database for peptidases and their inhibitors: I04.019
heparin, cofactor, hcii, protein, encoded, serpind1, gene, coagulation, factor, that, inhibits, cofactor, heparin, dermatan, sulfate, minor, antithrombin, serpind1available, structurespdbortholog, search, pdbe, rcsblist, codes1jmo, 1jmj, 2natidentifiersaliases. Heparin cofactor II HCII a protein encoded by the SERPIND1 gene is a coagulation factor that inhibits IIa and is a cofactor for heparin and dermatan sulfate minor antithrombin 5 SERPIND1Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes1JMO 1JMJ 2NATIdentifiersAliasesSERPIND1 D22S673 HC2 HCF2 HCII HLS2 LS2 THPH10 serpin family D member 1External IDsOMIM 142360 MGI 96051 HomoloGene 36018 GeneCards SERPIND1Gene location Human Chr Chromosome 22 human 1 Band22q11 21Start20 774 113 bp 1 End20 787 720 bp 1 Gene location Mouse Chr Chromosome 16 mouse 2 Band16 A3 16 10 74 cMStart17 149 235 bp 2 End17 161 439 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inliverright lobe of livertrigeminal ganglionnucleus accumbensislet of Langerhanscanal of the cervixcorpus callosumcaudate nucleussmooth muscle tissuemyometriumTop expressed inliverleft lobe of liveroptic nervesciatic nervegallbladderyolk sacmirrorsexually immature organismabdominal wallspinal cordMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionpeptidase inhibitor activity endopeptidase inhibitor activity heparin binding serine type endopeptidase inhibitor activityCellular componentextracellular exosome extracellular space endoplasmic reticulum lumen extracellular regionBiological processnegative regulation of peptidase activity bioluminescence hemostasis chemotaxis blood coagulation negative regulation of endopeptidase activity post translational protein modificationSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez305315160EnsemblENSG00000099937ENSMUSG00000022766UniProtP05546P49182RefSeq mRNA NM 000185NM 008223NM 001331047RefSeq protein NP 000176NP 001317976NP 032249Location UCSC Chr 22 20 77 20 79 MbChr 16 17 15 17 16 MbPubMed search 3 4 WikidataView Edit HumanView Edit MouseThe product encoded by this gene is a serine protease inhibitor which rapidly inhibits thrombin in the presence of dermatan sulfate or heparin The gene contains five exons and four introns This protein shares homology with antithrombin III and other members of the alpha 1 antitrypsin superfamily Mutations in this gene are associated with heparin cofactor II deficiency 5 Heparin cofactor II deficiency can lead to increased thrombin generation and a hypercoagulable state A purification experiment of heparin cofactor II was performed in 1981 in which it was discovered that the purified version of the protein consists of a single polypeptide chain 6 Further experimentation demonstrated that whether b Mercaptoethanol is present does not affect HCII s activity in gel electrophoresis b Mercaptoethanol is typically used for the reduction of disulfide bonds within a molecule but the gel electrophoresis revealed that HCII does not have any of these bonds The structure is similar to antithrombin III ATIII which was known to effectively inhibit thrombin as well as coagulation factor Xa 6 This experiment suggested that HCII has strong thrombin inhibition yet weak inhibition of coagulation factor Xa Heparin cofactor II may play a role in the immune response as it has been associated with leukocyte mediated protein degradation which releases cytokines in the inflammatory response with neutrophils and monocytes 7 Its role has been questioned because although it is a thrombin inhibitor an absence of HCII does not result in significantly higher levels of thrombosis 7 This does not negate the results of the 1981 study but novel discoveries create more questions of the biological mechanism and function of the protein However this cofactor shows stronger capability in inhibiting thrombin in pregnant women protecting them from thrombosis Pregnant women have shown increased levels of heparin cofactor II as well as dermatan sulfate which is a polysaccharide that is expected to be involved in wound repair coagulation and overall maintenance throughout the body Pregnant women who had thrombosis are likely to also have low levels of heparin cofactor II but whether this is a causation is still unknown 8 References edit a b c GRCh38 Ensembl release 89 ENSG00000099937 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000022766 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine a b Entrez Gene SERPIND1 serpin peptidase inhibitor clade D heparin cofactor member 1 a b Tollefsen D M Majerus D W Blank M K March 1982 Heparin cofactor II Purification and properties of a heparin dependent inhibitor of thrombin in human plasma Journal of Biological Chemistry 257 5 2162 2169 doi 10 1016 s0021 9258 18 34900 7 ISSN 0021 9258 PMID 6895893 a b Brummel Ziedins Kathleen Mann Kenneth G 2018 01 01 Molecular Basis of Blood Coagulation Hematology 1885 1905 e8 doi 10 1016 B978 0 323 35762 3 00126 8 ISBN 9780323357623 Huntington James A 2005 01 01 Heparin Activation of Serpins Chemistry and Biology of Heparin and Heparan Sulfate 367 398 doi 10 1016 B978 008044859 6 50014 9 ISBN 9780080448596 Further reading editGriffith MJ Carraway T White GC Dombrose FA 1983 Serpin receptor 1 heparin cofactor activities in a family with hereditary antithrombin III deficiency evidence for a second heparin cofactor in human plasma Blood 61 1 111 118 doi 10 1182 blood V61 1 111 111 Pizzo SV 1989 Serpin receptor 1 a hepatic receptor that mediates the clearance of antithrombin III proteinase complexes Am J Med 87 3B 10S 14S doi 10 1016 0002 9343 89 80524 8 PMID 2552799 Uszynski M 1992 Tissue anticoagulants in the human placenta preliminary study with a heparin like anticoagulant and review of the literature Gynecol Obstet Invest 32 3 129 33 doi 10 1159 000293013 PMID 1836773 Sutherland JS Bhakta V Filion ML Sheffield WP 2006 The transferable tail fusion of the N terminal acidic extension of heparin cofactor II to alpha1 proteinase inhibitor M358R specifically increases the rate of thrombin inhibition Biochemistry 45 38 11444 52 doi 10 1021 bi0609624 PMID 16981704 Giri TK Tollefsen DM 2006 Placental dermatan sulfate isolation anticoagulant activity and association with heparin cofactor II Blood 107 7 2753 8 doi 10 1182 blood 2005 09 3755 PMC 1895383 PMID 16339402 Liu T Qian WJ Gritsenko MA et al 2006 Human plasma N glycoproteome analysis by immunoaffinity subtraction hydrazide chemistry and mass spectrometry J Proteome Res 4 6 2070 80 doi 10 1021 pr0502065 PMC 1850943 PMID 16335952 Rual JF Venkatesan K Hao T et al 2005 Towards a proteome scale map of the human protein protein interaction network Nature 437 7062 1173 8 Bibcode 2005Natur 437 1173R doi 10 1038 nature04209 PMID 16189514 S2CID 4427026 Schillinger M Exner M Sabeti S et al 2005 High plasma heparin cofactor II activity protects from restenosis after femoropopliteal stenting Thromb Haemost 92 5 1108 13 doi 10 1160 TH04 05 0311 PMID 15543340 S2CID 13806207 Collins JE Wright CL Edwards CA et al 2005 A genome annotation driven approach to cloning the human ORFeome Genome Biol 5 10 R84 doi 10 1186 gb 2004 5 10 r84 PMC 545604 PMID 15461802 Suzuki Y Yamashita R Shirota M et al 2004 Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions Genome Res 14 9 1711 8 doi 10 1101 gr 2435604 PMC 515316 PMID 15342556 Corral J Aznar J Gonzalez Conejero R et al 2006 Homozygous deficiency of heparin cofactor II relevance of P17 glutamate residue in serpins relationship with conformational diseases and role in thrombosis Circulation 110 10 1303 7 doi 10 1161 01 CIR 0000140763 51679 D9 PMID 15337701 Fortenberry YM Whinna HC Gentry HR et al 2004 Molecular mapping of the thrombin heparin cofactor II complex J Biol Chem 279 41 43237 44 doi 10 1074 jbc M406716200 PMID 15292227 Zhang F Wu Y Ma Q et al 2004 Studies on the effect of calcium in interactions between heparin and heparin cofactor II using surface plasmon resonance Clin Appl Thromb Hemost 10 3 249 57 doi 10 1177 107602960401000307 PMID 15247982 Anderson NL Polanski M Pieper R et al 2004 The human plasma proteome a nonredundant list developed by combination of four separate sources Mol Cell Proteomics 3 4 311 26 doi 10 1074 mcp M300127 MCP200 PMID 14718574 Strausberg RL Feingold EA Grouse LH et al 2003 Generation and initial analysis of more than 15 000 full length human and mouse cDNA sequences Proc Natl Acad Sci U S A 99 26 16899 903 Bibcode 2002PNAS 9916899M doi 10 1073 pnas 242603899 PMC 139241 PMID 12477932 Noda A Wada H Kusiya F et al 2003 Plasma levels of heparin cofactor II HCII and thrombin HCII complex in patients with disseminated intravascular coagulation Clin Appl Thromb Hemost 8 3 265 71 doi 10 1177 107602960200800311 PMID 12361205 Baglin TP Carrell RW Church FC et al 2002 Crystal structures of native and thrombin complexed heparin cofactor II reveal a multistep allosteric mechanism Proc Natl Acad Sci U S A 99 17 11079 84 Bibcode 2002PNAS 9911079B doi 10 1073 pnas 162232399 PMC 123213 PMID 12169660 Cunningham MA Bhakta V Sheffield WP 2003 Altering heparin cofactor II at VAL439 P6 either impairs inhibition of thrombin or confers elastase resistance Thromb Haemost 88 1 89 97 doi 10 1055 s 0037 1613159 PMID 12152684 S2CID 1467230 Hayakawa Y Hirashima Y Kurimoto M et al 2002 Contribution of basic residues of the A helix of heparin cofactor II to heparin or dermatan sulfate mediated thrombin inhibition FEBS Lett 522 1 3 147 50 doi 10 1016 S0014 5793 02 02930 7 PMID 12095635 S2CID 12634527 Mitchell JW Church FC 2002 Aspartic acid residues 72 and 75 and tyrosine sulfate 73 of heparin cofactor II promote intramolecular interactions during glycosaminoglycan binding and thrombin inhibition J Biol Chem 277 22 19823 30 doi 10 1074 jbc M200630200 PMID 11856753 Bohme C Nimtz M Grabenhorst E et al 2002 Tyrosine sulfation and N glycosylation of human heparin cofactor II from plasma and recombinant Chinese hamster ovary cells and their effects on heparin binding Eur J Biochem 269 3 977 88 doi 10 1046 j 0014 2956 2001 02732 x PMID 11846800 External links editThe MEROPS online database for peptidases and their inhibitors I04 019 Heparin Cofactor II at the U S National Library of Medicine Medical Subject Headings MeSH He L Vicente C Westrick R Eitzman D Tollefsen D 2002 Heparin cofactor II inhibits arterial thrombosis after endothelial injury J Clin Invest 109 2 213 9 doi 10 1172 JCI13432 PMC 150836 PMID 11805133 nbsp This article on a gene on human chromosome 22 is a stub You can help Wikipedia by expanding it vte nbsp This biochemistry article is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title Heparin cofactor II amp oldid 1164479607, wikipedia, wiki, book, books, library,
