Heparin cofactor 2

Details

Name
Heparin cofactor 2
Synonyms
  • HC-II
  • HCF2
  • Heparin cofactor II
  • HLS2
  • Protease inhibitor leuserpin-2
  • Serpin D1
Gene Name
SERPIND1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0001546|Heparin cofactor 2
MKHSLNALLIFLIITSAWGGSKGPLDQLEKGGETAQSADPQWEQLNNKNLSMPLLPADFH
KENTVTNDWIPEGEEDDDYLDLEKIFSEDDDYIDIVDSLSVSPTDSDVSAGNILQLFHGK
SRIQRLNILNAKFAFNLYRVLKDQVNTFDNIFIAPVGISTAMGMISLGLKGETHEQVHSI
LHFKDFVNASSKYEITTIHNLFRKLTHRLFRRNFGYTLRSVNDLYIQKQFPILLDFKTKV
REYYFAEAQIADFSDPAFISKTNNHIMKLTKGLIKDALENIDPATQMMILNCIYFKGSWV
NKFPVEMTHNHNFRLNEREVVKVSMMQTKGNFLAANDQELDCDILQLEYVGGISMLIVVP
HKMSGMKTLEAQLTPRVVERWQKSMTNRTREVLLPKFKLEKNYNLVESLKLMGIRMLFDK
NGNMAGISDQRIAIDLFKHQGTITVNEEGTQATTVTTVGFMPLSTQVRFTVDRPFLFLIY
EHRTSCLLFMGRVANPSRS
Number of residues
499
Molecular Weight
57070.16
Theoretical pI
6.89
GO Classification
Functions
endopeptidase inhibitor activity / heparin binding / serine-type endopeptidase inhibitor activity
Processes
bioluminescence / blood coagulation / chemotaxis / negative regulation of endopeptidase activity
Components
extracellular exosome / extracellular region / extracellular space
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
Thrombin inhibitor activated by the glycosaminoglycans, heparin or dermatan sulfate. In the presence of the latter, HC-II becomes the predominant thrombin inhibitor in place of antithrombin III (AT-III). Also inhibits chymotrypsin, but in a glycosaminoglycan-independent manner.Peptides at the N-terminal of HC-II have chemotactic activity for both monocytes and neutrophils.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Not Available
Gene sequence
>lcl|BSEQ0021279|Heparin cofactor 2 (SERPIND1)
ATGAAACACTCATTAAACGCACTTCTCATTTTCCTCATCATAACATCTGCGTGGGGTGGG
AGCAAAGGCCCGCTGGATCAGCTAGAGAAAGGAGGGGAAACTGCTCAGTCTGCAGATCCC
CAGTGGGAGCAGTTAAATAACAAAAACCTGAGCATGCCTCTTCTCCCTGCCGACTTCCAC
AAGGAAAACACCGTCACCAACGACTGGATTCCAGAGGGGGAGGAGGACGACGACTATCTG
GACCTGGAGAAGATATTCAGTGAAGACGACGACTACATCGACATCGTCGACAGTCTGTCA
GTTTCCCCGACAGACTCTGATGTGAGTGCTGGGAACATCCTCCAGCTTTTTCATGGCAAG
AGCCGGATCCAGCGTCTTAACATCCTCAACGCCAAGTTCGCTTTCAACCTCTACCGAGTG
CTGAAAGACCAGGTCAACACTTTCGATAACATCTTCATAGCACCCGTTGGCATTTCTACT
GCGATGGGTATGATTTCCTTAGGTCTGAAGGGAGAGACCCATGAACAAGTGCACTCGATT
TTGCATTTTAAAGACTTTGTTAATGCCAGCAGCAAGTATGAAATCACGACCATTCATAAT
CTCTTCCGTAAGCTGACTCATCGCCTCTTCAGGAGGAATTTTGGGTACACACTGCGGTCA
GTCAATGACCTTTATATCCAGAAGCAGTTTCCAATCCTGCTTGACTTCAAAACTAAAGTA
AGAGAGTATTACTTTGCTGAGGCCCAGATAGCTGACTTCTCAGACCCTGCCTTCATATCA
AAAACCAACAACCACATCATGAAGCTCACCAAGGGCCTCATAAAAGATGCTCTGGAGAAT
ATAGACCCTGCTACCCAGATGATGATTCTCAACTGCATCTACTTCAAAGGATCCTGGGTG
AATAAATTCCCAGTGGAAATGACACACAACCACAACTTCCGGCTGAATGAGAGAGAGGTA
GTTAAGGTTTCCATGATGCAGACCAAGGGGAACTTCCTCGCAGCAAATGACCAGGAGCTG
GACTGCGACATCCTCCAGCTGGAATACGTGGGGGGCATCAGCATGCTAATTGTGGTCCCA
CACAAGATGTCTGGGATGAAGACCCTCGAAGCGCAACTGACACCCCGGGTGGTGGAGAGA
TGGCAAAAAAGCATGACAAACAGAACTCGAGAAGTGCTTCTGCCGAAATTCAAGCTGGAG
AAGAACTACAATCTAGTGGAGTCCCTGAAGTTGATGGGGATCAGGATGCTGTTTGACAAA
AATGGCAACATGGCAGGCATCTCAGACCAAAGGATCGCCATCGACCTGTTCAAGCACCAA
GGCACGATCACAGTGAACGAGGAAGGCACCCAAGCCACCACTGTGACCACGGTGGGGTTC
ATGCCGCTGTCCACCCAAGTCCGCTTCACTGTCGACCGCCCCTTTCTTTTCCTCATCTAC
GAGCATCGCACCAGCTGCCTGCTCTTCATGGGAAGAGTGGCCAACCCCAGCAGGTCCTAG
Chromosome Location
22
Locus
22q11.2|22q11.21
External Identifiers
ResourceLink
UniProtKB IDP05546
UniProtKB Entry NameHEP2_HUMAN
GenBank Protein ID183910
GenBank Gene IDM12849
GenAtlas IDSERPIND1
HGNC IDHGNC:4838
General References
  1. Blinder MA, Marasa JC, Reynolds CH, Deaven LL, Tollefsen DM: Heparin cofactor II: cDNA sequence, chromosome localization, restriction fragment length polymorphism, and expression in Escherichia coli. Biochemistry. 1988 Jan 26;27(2):752-9. [PubMed:2894851]
  2. Herzog R, Lutz S, Blin N, Marasa JC, Blinder MA, Tollefsen DM: Complete nucleotide sequence of the gene for human heparin cofactor II and mapping to chromosomal band 22q11. Biochemistry. 1991 Feb 5;30(5):1350-7. [PubMed:1671335]
  3. Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I: A genome annotation-driven approach to cloning the human ORFeome. Genome Biol. 2004;5(10):R84. Epub 2004 Sep 30. [PubMed:15461802]
  4. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039]
  5. Ragg H: A new member of the plasma protease inhibitor gene family. Nucleic Acids Res. 1986 Jan 24;14(2):1073-88. [PubMed:3003690]
  6. Inhorn RC, Tollefsen DM: Isolation and characterization of a partial cDNA clone for heparin cofactor II1. Biochem Biophys Res Commun. 1986 May 29;137(1):431-6. [PubMed:3755044]
  7. Griffith MJ, Noyes CM, Tyndall JA, Church FC: Structural evidence for leucine at the reactive site of heparin cofactor II. Biochemistry. 1985 Nov 19;24(24):6777-82. [PubMed:3907702]
  8. Ragg H, Preibisch G: Structure and expression of the gene coding for the human serpin hLS2. J Biol Chem. 1988 Aug 25;263(24):12129-34. [PubMed:2841345]
  9. Church FC, Pratt CW, Hoffman M: Leukocyte chemoattractant peptides from the serpin heparin cofactor II. J Biol Chem. 1991 Jan 15;266(2):704-9. [PubMed:1985958]
  10. Van Deerlin VM, Tollefsen DM: The N-terminal acidic domain of heparin cofactor II mediates the inhibition of alpha-thrombin in the presence of glycosaminoglycans. J Biol Chem. 1991 Oct 25;266(30):20223-31. [PubMed:1939083]
  11. Blinder MA, Tollefsen DM: Site-directed mutagenesis of arginine 103 and lysine 185 in the proposed glycosaminoglycan-binding site of heparin cofactor II. J Biol Chem. 1990 Jan 5;265(1):286-91. [PubMed:2104620]
  12. Liu T, Qian WJ, Gritsenko MA, Camp DG 2nd, Monroe ME, Moore RJ, Smith RD: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. J Proteome Res. 2005 Nov-Dec;4(6):2070-80. [PubMed:16335952]
  13. Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, Wang L, Zou H: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J Proteome Res. 2009 Feb;8(2):651-61. doi: 10.1021/pr8008012. [PubMed:19159218]
  14. Jia W, Lu Z, Fu Y, Wang HP, Wang LH, Chi H, Yuan ZF, Zheng ZB, Song LN, Han HH, Liang YM, Wang JL, Cai Y, Zhang YK, Deng YL, Ying WT, He SM, Qian XH: A strategy for precise and large scale identification of core fucosylated glycoproteins. Mol Cell Proteomics. 2009 May;8(5):913-23. doi: 10.1074/mcp.M800504-MCP200. Epub 2009 Jan 12. [PubMed:19139490]
  15. Tagliabracci VS, Wiley SE, Guo X, Kinch LN, Durrant E, Wen J, Xiao J, Cui J, Nguyen KB, Engel JL, Coon JJ, Grishin N, Pinna LA, Pagliarini DJ, Dixon JE: A Single Kinase Generates the Majority of the Secreted Phosphoproteome. Cell. 2015 Jun 18;161(7):1619-32. doi: 10.1016/j.cell.2015.05.028. [PubMed:26091039]
  16. Baglin TP, Carrell RW, Church FC, Esmon CT, Huntington JA: Crystal structures of native and thrombin-complexed heparin cofactor II reveal a multistep allosteric mechanism. Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11079-84. Epub 2002 Aug 8. [PubMed:12169660]
  17. Blinder MA, Andersson TR, Abildgaard U, Tollefsen DM: Heparin cofactor IIOslo. Mutation of Arg-189 to His decreases the affinity for dermatan sulfate. J Biol Chem. 1989 Mar 25;264(9):5128-33. [PubMed:2647747]
  18. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed:10391209]
  19. Kanagawa Y, Shigekiyo T, Aihara K, Akaike M, Azuma H, Matsumoto T: Molecular mechanism of type I congenital heparin cofactor (HC) II deficiency caused by a missense mutation at reactive P2 site: HC II Tokushima. Thromb Haemost. 2001 Jan;85(1):101-7. [PubMed:11204559]
  20. Corral J, Aznar J, Gonzalez-Conejero R, Villa P, Minano A, Vaya A, Carrell RW, Huntington JA, Vicente V: Homozygous deficiency of heparin cofactor II: relevance of P17 glutamate residue in serpins, relationship with conformational diseases, and role in thrombosis. Circulation. 2004 Sep 7;110(10):1303-7. Epub 2004 Aug 30. [PubMed:15337701]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00407Ardeparinapproved, investigational, withdrawnyesagonistDetails
DB06271Sulodexideapproved, investigationalyesagonistDetails
DB09130Copperapproved, investigationalunknownDetails
DB01593Zincapproved, investigationalunknownDetails
DB09258Bemiparinapproved, investigationalunknownantagonistDetails
DB14487Zinc acetateapproved, investigationalunknownDetails
DB14533Zinc chlorideapproved, investigationalunknownDetails