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Gene Review

Serpind1  -  serine (or cysteine) peptidase inhibitor,...

Mus musculus

Synonyms: AA985900, AI303446, HC II, HC-II, HCII, ...
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Disease relevance of Serpind1


High impact information on Serpind1

  • Biochemical assays confirmed the absence of dermatan sulfate-dependent thrombin inhibition in the plasma of HCII(-/-) animals [1].
  • To investigate the physiologic function of HCII, about 2 kb of the mouse HCII gene, encoding the N-terminal half of the protein, was deleted by homologous recombination in embryonic stem cells [1].
  • This abnormality was corrected by infusion of purified HCII but not ovalbumin [1].
  • Heparin cofactor II (HCII) is a plasma protein that inhibits thrombin rapidly in the presence of dermatan sulfate or heparin [5].
  • We previously reported that the time to thrombotic occlusion of the carotid artery after photochemical injury was shorter in HCII-deficient mice than in wild-type control animals [5].

Biological context of Serpind1

  • Thus, murine plasma contains two forms of HCII that appear to have identical amino acid sequences but differ in the composition of their N-linked oligosaccharides [6].
  • HCII cDNA clones isolated from a murine liver library include a 1434 bp open reading frame following the first Met codon, a TAA stop codon, and 580 bp of 3'-untranslated sequence terminating in a poly(A) tail [6].
  • The murine HCII gene is approximately 7.1 kb in size and consists of at least four exons and three introns [6].
  • Our results demonstrate that not only does HC function as a thrombin inhibitor, but that limited proteolysis of HC near the amino terminus yields biologically active peptide(s) which might participate in inflammation and in wound healing and tissue repair processes [7].

Anatomical context of Serpind1

  • Northern blot analysis reveals a 2.3-kb HCII mRNA in murine and human liver, but no HCII mRNA is detectable in heart, brain, spleen, lung, skeletal muscle, kidney, testis, placenta, pancreas, or intestine [6].
  • These results indicate that HCII mediates the antithrombotic effect of porcine skin dermatan sulfate after injury to the carotid arterial endothelium in mice, whereas more highly charged dermatan sulfates possess weak antithrombotic activity independent of HCII [5].
  • IMR-90 normal human fetal lung fibroblasts treated with heparinase or heparitinase accelerated the thrombin-HCII reaction to the same degree as untreated cells [8].
  • Activation of heparin cofactor II by fibroblasts and vascular smooth muscle cells [8].
  • Fibroblasts and porcine aortic smooth muscle cells accelerated inhibition of thrombin by HCII 2.3-7.5-fold but had no effect on other thrombin inhibitors in plasma [8].

Associations of Serpind1 with chemical compounds

  • Heparin cofactor II (HCII) is a glycoprotein in human plasma that inhibits thrombin rapidly in the presence of dermatan sulfate or heparin [6].
  • Heparin cofactor II (HC) is a plasma serine proteinase inhibitor (serpin) that inhibits the coagulant proteinase alpha-thrombin [7].
  • Agents are formulated with the anionic glycosaminoglycan, 435-type dermatan sulfate (DS 435, 22.2 kDa), chemically enriched for oligosaccharide sequences that confer high heparin cofactor II binding and correlate with high tumor uptake [9].

Physical interactions of Serpind1


Other interactions of Serpind1


Analytical, diagnostic and therapeutic context of Serpind1

  • Purified HCII or defibrinated plasma was incubated with washed confluent cell monolayers, 125I-thrombin was added, and the rate of formation of covalent 125I-thrombin-inhibitor complexes was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography [8].


  1. Heparin cofactor II inhibits arterial thrombosis after endothelial injury. He, L., Vicente, C.P., Westrick, R.J., Eitzman, D.T., Tollefsen, D.M. J. Clin. Invest. (2002) [Pubmed]
  2. Isolation of frog and chicken cDNAs encoding heparin cofactor II. Colwell, N.S., Tollefsen, D.M. Thromb. Haemost. (1998) [Pubmed]
  3. Accelerated atherogenesis and neointima formation in heparin cofactor II deficient mice. Vicente, C.P., He, L., Tollefsen, D.M. Blood (2007) [Pubmed]
  4. Strain-dependent embryonic lethality and exaggerated vascular remodeling in heparin cofactor II-deficient mice. Aihara, K., Azuma, H., Akaike, M., Ikeda, Y., Sata, M., Takamori, N., Yagi, S., Iwase, T., Sumitomo, Y., Kawano, H., Yamada, T., Fukuda, T., Matsumoto, T., Sekine, K., Sato, T., Nakamichi, Y., Yamamoto, Y., Yoshimura, K., Watanabe, T., Nakamura, T., Oomizu, A., Tsukada, M., Hayashi, H., Sudo, T., Kato, S., Matsumoto, T. J. Clin. Invest. (2007) [Pubmed]
  5. Antithrombotic activity of dermatan sulfate in heparin cofactor II-deficient mice. Vicente, C.P., He, L., Pavão, M.S., Tollefsen, D.M. Blood (2004) [Pubmed]
  6. Murine heparin cofactor II: purification, cDNA sequence, expression, and gene structure. Zhang, G.S., Mehringer, J.H., Van Deerlin, V.M., Kozak, C.A., Tollefsen, D.M. Biochemistry (1994) [Pubmed]
  7. Leukocyte chemoattractant peptides from the serpin heparin cofactor II. Church, F.C., Pratt, C.W., Hoffman, M. J. Biol. Chem. (1991) [Pubmed]
  8. Activation of heparin cofactor II by fibroblasts and vascular smooth muscle cells. McGuire, E.A., Tollefsen, D.M. J. Biol. Chem. (1987) [Pubmed]
  9. Dermatan carriers for neovascular transport targeting, deep tumor penetration and improved therapy. Ranney, D., Antich, P., Dadey, E., Mason, R., Kulkarni, P., Singh, O., Chen, H., Constantanescu, A., Parkey, R. Journal of controlled release : official journal of the Controlled Release Society. (2005) [Pubmed]
  10. Conformational lability of vitronectin: induction of an antigenic change by alpha-thrombin-serpin complexes and by proteolytically modified thrombin. Tomasini, B.R., Owen, M.C., Fenton, J.W., Mosher, D.F. Biochemistry (1989) [Pubmed]
  11. Cellular internalization and degradation of antithrombin III-thrombin, heparin cofactor II-thrombin, and alpha 1-antitrypsin-trypsin complexes is mediated by the low density lipoprotein receptor-related protein. Kounnas, M.Z., Church, F.C., Argraves, W.S., Strickland, D.K. J. Biol. Chem. (1996) [Pubmed]
  12. Conformational change in antithrombin induced by heparin probed with a monoclonal antibody against the 1C/4B region. Dawes, J., James, K., Lane, D.A. Biochemistry (1994) [Pubmed]
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