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").[1]
The product encoded by this gene is a serine proteinase 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 and other members of the alpha 1-antitrypsin superfamily. Mutations in this gene are associated with heparin cofactor II deficiency.[1]
Heparin Cofactor II deficiency can lead to increased thrombin generation and a hypercoagulable state.
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.
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. PMID2552799.
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. PMID1836773.
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. PMID16981704.
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. doi:10.1038/nature04209. PMID16189514.
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:10.1267/THRO04051108. PMID15543340.
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. PMID15337701.
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. PMID15292227.
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. PMID15247982.
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. PMID14718574.
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. PMID12361205.
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. PMID12152684.
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. PMID12095635.
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. PMID11856753.
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. PMID11846800.
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