Canmetcon
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Identification
HMDB Protein ID HMDBP01712
Secondary Accession Numbers
  • 7052
Name Heparin cofactor 2
Synonyms
  1. HC-II
  2. HLS2
  3. Heparin cofactor II
  4. Protease inhibitor leuserpin-2
  5. Serpin D1
Gene Name SERPIND1
Protein Type Enzyme
Biological Properties
General Function Involved in heparin binding
Specific Function Peptides at the N-terminal of HC-II have chemotactic activity for both monocytes and neutrophils
Pathways Not Available
Reactions Not Available
GO Classification
Function
peptidase inhibitor activity
endopeptidase inhibitor activity
serine-type endopeptidase inhibitor activity
enzyme regulator activity
enzyme inhibitor activity
Cellular Location Not Available
Gene Properties
Chromosome Location Chromosome:2
Locus 22q11.2|22q11.21
SNPs SERPIND1
Gene Sequence
>1500 bp
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
Protein Properties
Number of Residues 499
Molecular Weight 57070.2
Theoretical pI 6.89
Pfam Domain Function
Signals
  • 1-19
Transmembrane Regions
  • None
Protein Sequence
>Heparin cofactor 2
MKHSLNALLIFLIITSAWGGSKGPLDQLEKGGETAQSADPQWEQLNNKNLSMPLLPADFH
KENTVTNDWIPEGEEDDDYLDLEKIFSEDDDYIDIVDSLSVSPTDSDVSAGNILQLFHGK
SRIQRLNILNAKFAFNLYRVLKDQVNTFDNIFIAPVGISTAMGMISLGLKGETHEQVHSI
LHFKDFVNASSKYEITTIHNLFRKLTHRLFRRNFGYTLRSVNDLYIQKQFPILLDFKTKV
REYYFAEAQIADFSDPAFISKTNNHIMKLTKGLIKDALENIDPATQMMILNCIYFKGSWV
NKFPVEMTHNHNFRLNEREVVKVSMMQTKGNFLAANDQELDCDILQLEYVGGISMLIVVP
HKMSGMKTLEAQLTPRVVERWQKSMTNRTREVLLPKFKLEKNYNLVESLKLMGIRMLFDK
NGNMAGISDQRIAIDLFKHQGTITVNEEGTQATTVTTVGFMPLSTQVRFTVDRPFLFLIY
EHRTSCLLFMGRVANPSRS
GenBank ID Protein 189054358
UniProtKB/Swiss-Prot ID P05546
UniProtKB/Swiss-Prot Entry Name HEP2_HUMAN
PDB IDs
GenBank Gene ID AK314200
GeneCard ID SERPIND1
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  2. 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 ]
  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. 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 ]
  5. 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 ]
  6. Zhou W, Ross MM, Tessitore A, Ornstein D, Vanmeter A, Liotta LA, Petricoin EF 3rd: An initial characterization of the serum phosphoproteome. J Proteome Res. 2009 Dec;8(12):5523-31. doi: 10.1021/pr900603n. [PubMed:19824718 ]
  7. 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 ]
  8. 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 ]
  9. Ragg H: A new member of the plasma protease inhibitor gene family. Nucleic Acids Res. 1986 Jan 24;14(2):1073-88. [PubMed:3003690 ]
  10. 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 ]
  11. 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 ]
  12. 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 ]
  13. 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 ]
  14. 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 ]
  15. 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 ]
  16. 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 ]
  17. 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 ]
  18. 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 ]