GenomeNet

Database: UniProt
Entry: P05546
LinkDB: P05546
Original site: P05546 
ID   HEP2_HUMAN              Reviewed;         499 AA.
AC   P05546; B2RAI1; D3DX34; Q6IBZ5;
DT   01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1991, sequence version 3.
DT   29-SEP-2021, entry version 219.
DE   RecName: Full=Heparin cofactor 2;
DE   AltName: Full=Heparin cofactor II;
DE            Short=HC-II;
DE   AltName: Full=Protease inhibitor leuserpin-2;
DE            Short=HLS2;
DE   AltName: Full=Serpin D1;
DE   Flags: Precursor;
GN   Name=SERPIND1; Synonyms=HCF2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2894851; DOI=10.1021/bi00402a039;
RA   Blinder M.A., Marasa J.C., Reynolds C.H., Deaven L.L., Tollefsen D.M.;
RT   "Heparin cofactor II: cDNA sequence, chromosome localization, restriction
RT   fragment length polymorphism, and expression in Escherichia coli.";
RL   Biochemistry 27:752-759(1988).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=1671335; DOI=10.1021/bi00219a027;
RA   Herzog R., Lutz S., Blin N., Marasa J.C., Blinder M.A., Tollefsen D.M.;
RT   "Complete nucleotide sequence of the gene for human heparin cofactor II and
RT   mapping to chromosomal band 22q11.";
RL   Biochemistry 30:1350-1357(1991).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA   Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA   Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA   Beare D.M., Dunham I.;
RT   "A genome annotation-driven approach to cloning the human ORFeome.";
RL   Genome Biol. 5:R84.1-R84.11(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Liver;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 19-499.
RX   PubMed=3003690; DOI=10.1093/nar/14.2.1073;
RA   Ragg H.;
RT   "A new member of the plasma protease inhibitor gene family.";
RL   Nucleic Acids Res. 14:1073-1088(1986).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 333-499.
RX   PubMed=3755044; DOI=10.1016/0006-291x(86)91228-3;
RA   Inhorn R.C., Tollefsen D.M.;
RT   "Isolation and characterization of a partial cDNA clone for heparin
RT   cofactor II1.";
RL   Biochem. Biophys. Res. Commun. 137:431-436(1986).
RN   [8]
RP   PROTEIN SEQUENCE OF 20-52 AND 464-499.
RX   PubMed=3907702; DOI=10.1021/bi00345a008;
RA   Griffith M.J., Noyes C.M., Tyndall J.A., Church F.C.;
RT   "Structural evidence for leucine at the reactive site of heparin cofactor
RT   II.";
RL   Biochemistry 24:6777-6782(1985).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-119.
RX   PubMed=2841345;
RA   Ragg H., Preibisch G.;
RT   "Structure and expression of the gene coding for the human serpin hLS2.";
RL   J. Biol. Chem. 263:12129-12134(1988).
RN   [10]
RP   PROTEIN SEQUENCE OF 58-85.
RX   PubMed=1985958;
RA   Church F.C., Pratt C.W., Hoffman M.;
RT   "Leukocyte chemoattractant peptides from the serpin heparin cofactor II.";
RL   J. Biol. Chem. 266:704-709(1991).
RN   [11]
RP   FUNCTION OF N-TERMINAL ACIDIC DOMAIN.
RX   PubMed=1939083;
RA   van Deerlin V.M.D., Tollefsen D.M.;
RT   "The N-terminal acidic domain of heparin cofactor II mediates the
RT   inhibition of alpha-thrombin in the presence of glycosaminoglycans.";
RL   J. Biol. Chem. 266:20223-20231(1991).
RN   [12]
RP   MUTAGENESIS OF ARG-122 AND LYS-204.
RX   PubMed=2104620;
RA   Blinder M.A., Tollefsen D.M.;
RT   "Site-directed mutagenesis of arginine 103 and lysine 185 in the proposed
RT   glycosaminoglycan-binding site of heparin cofactor II.";
RL   J. Biol. Chem. 265:286-291(1990).
RN   [13]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-49 AND ASN-188.
RC   TISSUE=Plasma;
RX   PubMed=16335952; DOI=10.1021/pr0502065;
RA   Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA   Smith R.D.;
RT   "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT   hydrazide chemistry, and mass spectrometry.";
RL   J. Proteome Res. 4:2070-2080(2005).
RN   [14]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-49 AND ASN-188.
RC   TISSUE=Liver;
RX   PubMed=19159218; DOI=10.1021/pr8008012;
RA   Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT   "Glycoproteomics analysis of human liver tissue by combination of multiple
RT   enzyme digestion and hydrazide chemistry.";
RL   J. Proteome Res. 8:651-661(2009).
RN   [15]
RP   GLYCOSYLATION AT ASN-49.
RX   PubMed=19139490; DOI=10.1074/mcp.m800504-mcp200;
RA   Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B.,
RA   Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L.,
RA   Ying W.T., He S.M., Qian X.H.;
RT   "A strategy for precise and large scale identification of core fucosylated
RT   glycoproteins.";
RL   Mol. Cell. Proteomics 8:913-923(2009).
RN   [16]
RP   PHOSPHORYLATION AT SER-37.
RX   PubMed=26091039; DOI=10.1016/j.cell.2015.05.028;
RA   Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J.,
RA   Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N.,
RA   Pinna L.A., Pagliarini D.J., Dixon J.E.;
RT   "A single kinase generates the majority of the secreted phosphoproteome.";
RL   Cell 161:1619-1632(2015).
RN   [17]
RP   X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 20-499, GLYCOSYLATION AT ASN-188
RP   AND ASN-387, AND SULFATION AT TYR-79 AND TYR-92.
RX   PubMed=12169660; DOI=10.1073/pnas.162232399;
RA   Baglin T.P., Carrell R.W., Church F.C., Esmon C.T., Huntington J.A.;
RT   "Crystal structures of native and thrombin-complexed heparin cofactor II
RT   reveal a multistep allosteric mechanism.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:11079-11084(2002).
RN   [18]
RP   VARIANT THPH10 HIS-208.
RX   PubMed=2647747;
RA   Blinder M.A., Andersson T.R., Abildgaard U., Tollefsen D.M.;
RT   "Heparin cofactor IIOslo. Mutation of Arg-189 to His decreases the affinity
RT   for dermatan sulfate.";
RL   J. Biol. Chem. 264:5128-5133(1989).
RN   [19]
RP   VARIANT THPH10 HIS-208, AND VARIANTS THR-7 AND MET-442.
RX   PubMed=10391209; DOI=10.1038/10290;
RA   Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA   Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA   Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA   Lander E.S.;
RT   "Characterization of single-nucleotide polymorphisms in coding regions of
RT   human genes.";
RL   Nat. Genet. 22:231-238(1999).
RN   [20]
RP   ERRATUM OF PUBMED:10391209.
RA   Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA   Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA   Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA   Lander E.S.;
RL   Nat. Genet. 23:373-373(1999).
RN   [21]
RP   VARIANT THPH10 LEU-462, AND CHARACTERIZATION OF VARIANT THPH10 LEU-462.
RX   PubMed=11204559;
RA   Kanagawa Y., Shigekiyo T., Aihara K., Akaike M., Azuma H., Matsumoto T.;
RT   "Molecular mechanism of type I congenital heparin cofactor (HC) II
RT   deficiency caused by a missense mutation at reactive P2 site: HC II
RT   Tokushima.";
RL   Thromb. Haemost. 85:101-107(2001).
RN   [22]
RP   VARIANT THPH10 LYS-447.
RX   PubMed=15337701; DOI=10.1161/01.cir.0000140763.51679.d9;
RA   Corral J., Aznar J., Gonzalez-Conejero R., Villa P., Minano A., Vaya A.,
RA   Carrell R.W., Huntington J.A., Vicente V.;
RT   "Homozygous deficiency of heparin cofactor II: relevance of P17 glutamate
RT   residue in serpins, relationship with conformational diseases, and role in
RT   thrombosis.";
RL   Circulation 110:1303-1307(2004).
CC   -!- FUNCTION: Thrombin inhibitor activated by the glycosaminoglycans,
CC       heparin or dermatan sulfate. In the presence of the latter, HC-II
CC       becomes the predominant thrombin inhibitor in place of antithrombin III
CC       (AT-III). Also inhibits chymotrypsin, but in a glycosaminoglycan-
CC       independent manner. {ECO:0000269|PubMed:1939083}.
CC   -!- FUNCTION: Peptides at the N-terminal of HC-II have chemotactic activity
CC       for both monocytes and neutrophils. {ECO:0000269|PubMed:1939083}.
CC   -!- TISSUE SPECIFICITY: Expressed predominantly in liver. Also present in
CC       plasma.
CC   -!- DOMAIN: The N-terminal acidic repeat region mediates, in part, the
CC       glycosaminoglycan-accelerated thrombin inhibition.
CC   -!- PTM: Phosphorylated by FAM20C in the extracellular medium.
CC       {ECO:0000269|PubMed:26091039}.
CC   -!- DISEASE: Thrombophilia due to heparin cofactor 2 deficiency (THPH10)
CC       [MIM:612356]: A hemostatic disorder characterized by a tendency to
CC       recurrent thrombosis. {ECO:0000269|PubMed:10391209,
CC       ECO:0000269|PubMed:11204559, ECO:0000269|PubMed:15337701,
CC       ECO:0000269|PubMed:2647747}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the serpin family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAG30459.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; M12849; AAA52642.1; -; mRNA.
DR   EMBL; M58600; AAA52641.1; -; Genomic_DNA.
DR   EMBL; CR456573; CAG30459.1; ALT_INIT; mRNA.
DR   EMBL; AK314200; BAG36878.1; -; mRNA.
DR   EMBL; CH471176; EAX02941.1; -; Genomic_DNA.
DR   EMBL; CH471176; EAX02942.1; -; Genomic_DNA.
DR   EMBL; X03498; CAA27218.1; -; mRNA.
DR   EMBL; M33660; AAA36185.1; -; Genomic_DNA.
DR   CCDS; CCDS13783.1; -.
DR   PIR; A37924; A37924.
DR   RefSeq; NP_000176.2; NM_000185.3.
DR   PDB; 1JMJ; X-ray; 2.35 A; A/B=20-499.
DR   PDB; 1JMO; X-ray; 2.20 A; A=20-499.
DR   PDB; 2NAT; NMR; -; A=192-219.
DR   PDB; 2NCU; NMR; -; A=192-212.
DR   PDB; 2NCV; NMR; -; A=192-212.
DR   PDB; 2NCW; NMR; -; A=189-212.
DR   PDB; 6J12; NMR; -; A=192-219.
DR   PDB; 6KBO; NMR; -; B=192-219.
DR   PDB; 6KBV; NMR; -; B=192-219.
DR   PDBsum; 1JMJ; -.
DR   PDBsum; 1JMO; -.
DR   PDBsum; 2NAT; -.
DR   PDBsum; 2NCU; -.
DR   PDBsum; 2NCV; -.
DR   PDBsum; 2NCW; -.
DR   PDBsum; 6J12; -.
DR   PDBsum; 6KBO; -.
DR   PDBsum; 6KBV; -.
DR   SMR; P05546; -.
DR   BioGRID; 109303; 5.
DR   CORUM; P05546; -.
DR   IntAct; P05546; 6.
DR   STRING; 9606.ENSP00000215727; -.
DR   DrugBank; DB00407; Ardeparin.
DR   DrugBank; DB09258; Bemiparin.
DR   DrugBank; DB09130; Copper.
DR   DrugBank; DB06271; Sulodexide.
DR   DrugBank; DB01593; Zinc.
DR   DrugBank; DB14487; Zinc acetate.
DR   DrugBank; DB14533; Zinc chloride.
DR   DrugBank; DB14548; Zinc sulfate, unspecified form.
DR   MEROPS; I04.019; -.
DR   GlyConnect; 695; 18 N-Linked glycans (2 sites).
DR   GlyGen; P05546; 11 sites, 23 N-linked glycans (2 sites), 3 O-linked glycans (8 sites).
DR   iPTMnet; P05546; -.
DR   PhosphoSitePlus; P05546; -.
DR   BioMuta; SERPIND1; -.
DR   DMDM; 123055; -.
DR   CPTAC; CPTAC-1508; -.
DR   CPTAC; non-CPTAC-1132; -.
DR   EPD; P05546; -.
DR   jPOST; P05546; -.
DR   MassIVE; P05546; -.
DR   MaxQB; P05546; -.
DR   PaxDb; P05546; -.
DR   PeptideAtlas; P05546; -.
DR   PRIDE; P05546; -.
DR   ProteomicsDB; 51846; -.
DR   Antibodypedia; 3265; 334 antibodies.
DR   DNASU; 3053; -.
DR   Ensembl; ENST00000215727; ENSP00000215727; ENSG00000099937.
DR   Ensembl; ENST00000406799; ENSP00000384050; ENSG00000099937.
DR   GeneID; 3053; -.
DR   KEGG; hsa:3053; -.
DR   UCSC; uc002ztb.2; human.
DR   CTD; 3053; -.
DR   DisGeNET; 3053; -.
DR   GeneCards; SERPIND1; -.
DR   HGNC; HGNC:4838; SERPIND1.
DR   HPA; ENSG00000099937; Tissue enriched (liver).
DR   MalaCards; SERPIND1; -.
DR   MIM; 142360; gene.
DR   MIM; 612356; phenotype.
DR   neXtProt; NX_P05546; -.
DR   OpenTargets; ENSG00000099937; -.
DR   PharmGKB; PA35053; -.
DR   VEuPathDB; HostDB:ENSG00000099937; -.
DR   eggNOG; KOG2392; Eukaryota.
DR   GeneTree; ENSGT00940000158664; -.
DR   HOGENOM; CLU_023330_8_0_1; -.
DR   InParanoid; P05546; -.
DR   OMA; TDCLVFI; -.
DR   OrthoDB; 1124079at2759; -.
DR   PhylomeDB; P05546; -.
DR   TreeFam; TF343094; -.
DR   PathwayCommons; P05546; -.
DR   Reactome; R-HSA-140837; Intrinsic Pathway of Fibrin Clot Formation.
DR   Reactome; R-HSA-140875; Common Pathway of Fibrin Clot Formation.
DR   Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR   Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR   SIGNOR; P05546; -.
DR   BioGRID-ORCS; 3053; 16 hits in 1011 CRISPR screens.
DR   EvolutionaryTrace; P05546; -.
DR   GeneWiki; Heparin_cofactor_II; -.
DR   GenomeRNAi; 3053; -.
DR   Pharos; P05546; Tbio.
DR   PRO; PR:P05546; -.
DR   Proteomes; UP000005640; Chromosome 22.
DR   RNAct; P05546; protein.
DR   Bgee; ENSG00000099937; Expressed in liver and 96 other tissues.
DR   Genevisible; P05546; HS.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; HDA:BHF-UCL.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0004866; F:endopeptidase inhibitor activity; TAS:ProtInc.
DR   GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR   GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IBA:GO_Central.
DR   GO; GO:0007596; P:blood coagulation; IEA:UniProtKB-KW.
DR   GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR   GO; GO:0010951; P:negative regulation of endopeptidase activity; IBA:GO_Central.
DR   CDD; cd02047; serpinD1_HCF2; 1.
DR   Gene3D; 2.30.39.10; -; 1.
DR   Gene3D; 3.30.497.10; -; 1.
DR   InterPro; IPR033831; HCII_serpin_dom.
DR   InterPro; IPR023795; Serpin_CS.
DR   InterPro; IPR023796; Serpin_dom.
DR   InterPro; IPR000215; Serpin_fam.
DR   InterPro; IPR036186; Serpin_sf.
DR   InterPro; IPR042178; Serpin_sf_1.
DR   InterPro; IPR042185; Serpin_sf_2.
DR   PANTHER; PTHR11461; PTHR11461; 1.
DR   Pfam; PF00079; Serpin; 1.
DR   SMART; SM00093; SERPIN; 1.
DR   SUPFAM; SSF56574; SSF56574; 1.
DR   PROSITE; PS00284; SERPIN; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Blood coagulation; Chemotaxis; Direct protein sequencing;
KW   Disease variant; Glycoprotein; Hemostasis; Heparin-binding; Phosphoprotein;
KW   Protease inhibitor; Reference proteome; Repeat; Serine protease inhibitor;
KW   Signal; Sulfation; Thrombophilia.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000269|PubMed:3907702"
FT   CHAIN           20..499
FT                   /note="Heparin cofactor 2"
FT                   /id="PRO_0000032494"
FT   REPEAT          73..83
FT                   /note="1"
FT   REPEAT          87..97
FT                   /note="2"
FT   REGION          68..79
FT                   /note="Chemotactic activity"
FT   REGION          73..97
FT                   /note="2 X 11 AA approximate repeats, Asp/Glu-rich (acidic)
FT                   (hirudin-like)"
FT   REGION          192..212
FT                   /note="Glycosaminoglycan-binding site"
FT   SITE            463..464
FT                   /note="Reactive bond"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         37
FT                   /note="Phosphoserine; by FAM20C"
FT                   /evidence="ECO:0000269|PubMed:26091039"
FT   MOD_RES         79
FT                   /note="Sulfotyrosine"
FT                   /evidence="ECO:0000269|PubMed:12169660"
FT   MOD_RES         92
FT                   /note="Sulfotyrosine"
FT                   /evidence="ECO:0000269|PubMed:12169660"
FT   CARBOHYD        49
FT                   /note="N-linked (GlcNAc...) (complex) asparagine"
FT                   /evidence="ECO:0000269|PubMed:16335952,
FT                   ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218"
FT   CARBOHYD        188
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:12169660,
FT                   ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218"
FT   CARBOHYD        387
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:12169660"
FT   VARIANT         7
FT                   /note="A -> T (in dbSNP:rs5905)"
FT                   /evidence="ECO:0000269|PubMed:10391209"
FT                   /id="VAR_011746"
FT   VARIANT         60
FT                   /note="H -> P (in dbSNP:rs165867)"
FT                   /id="VAR_011747"
FT   VARIANT         87
FT                   /note="S -> N (in dbSNP:rs34324685)"
FT                   /id="VAR_051953"
FT   VARIANT         129
FT                   /note="L -> V (in dbSNP:rs11542069)"
FT                   /id="VAR_051954"
FT   VARIANT         208
FT                   /note="R -> H (in THPH10; Oslo; decreased affinity for
FT                   dermatan sulfate; dbSNP:rs5907)"
FT                   /evidence="ECO:0000269|PubMed:10391209,
FT                   ECO:0000269|PubMed:2647747"
FT                   /id="VAR_007112"
FT   VARIANT         237
FT                   /note="K -> R (in dbSNP:rs1042435)"
FT                   /id="VAR_011748"
FT   VARIANT         442
FT                   /note="T -> M (in dbSNP:rs5904)"
FT                   /evidence="ECO:0000269|PubMed:10391209"
FT                   /id="VAR_011749"
FT   VARIANT         447
FT                   /note="E -> K (in THPH10; dbSNP:rs142451096)"
FT                   /evidence="ECO:0000269|PubMed:15337701"
FT                   /id="VAR_054977"
FT   VARIANT         462
FT                   /note="P -> L (in THPH10; Tokushima; impaired secretion of
FT                   the mutant molecules; dbSNP:rs121912420)"
FT                   /evidence="ECO:0000269|PubMed:11204559"
FT                   /id="VAR_054978"
FT   MUTAGEN         122
FT                   /note="R->L: Normal thrombin inhibition and
FT                   glycosaminoglycan affinity."
FT                   /evidence="ECO:0000269|PubMed:2104620"
FT   MUTAGEN         122
FT                   /note="R->Q: Greatly reduced thrombin inhibition. Normal
FT                   glycosaminoglycan affinity."
FT                   /evidence="ECO:0000269|PubMed:2104620"
FT   MUTAGEN         122
FT                   /note="R->W: Greatly reduced thrombin inhibition. Normal
FT                   glycosaminoglycan affinity."
FT                   /evidence="ECO:0000269|PubMed:2104620"
FT   MUTAGEN         204
FT                   /note="K->M: Reduced heparin- and no dermatan sulfate-
FT                   activated inhibition."
FT                   /evidence="ECO:0000269|PubMed:2104620"
FT   MUTAGEN         204
FT                   /note="K->N: Reduced heparin- and no dermatan sulfate-
FT                   activated inhibition."
FT                   /evidence="ECO:0000269|PubMed:2104620"
FT   MUTAGEN         204
FT                   /note="K->T: Reduced heparin- and no dermatan sulfate-
FT                   activated inhibition."
FT                   /evidence="ECO:0000269|PubMed:2104620"
FT   CONFLICT        49
FT                   /note="Missing (in Ref. 8; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        483
FT                   /note="R -> P (in Ref. 8; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        486
FT                   /note="C -> T (in Ref. 8; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        499
FT                   /note="S -> Q (in Ref. 8; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   HELIX           82..87
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   HELIX           90..92
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   HELIX           122..142
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   STRAND          151..153
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   HELIX           155..165
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   HELIX           166..168
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   HELIX           171..180
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   HELIX           183..189
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   HELIX           191..194
FT                   /evidence="ECO:0007829|PDB:2NCW"
FT   HELIX           195..210
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   STRAND          214..227
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   HELIX           234..244
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   STRAND          248..251
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   HELIX           256..269
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   TURN            270..272
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   TURN            277..280
FT                   /evidence="ECO:0007829|PDB:1JMJ"
FT   STRAND          287..296
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   STRAND          299..301
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   HELIX           305..307
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   STRAND          309..314
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   STRAND          316..318
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   STRAND          320..337
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   TURN            338..341
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   STRAND          342..349
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   TURN            350..352
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   STRAND          353..362
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   HELIX           363..365
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   HELIX           366..372
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   HELIX           375..384
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   STRAND          386..395
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   STRAND          397..400
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   HELIX           406..412
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   HELIX           416..418
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   TURN            425..427
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   STRAND          434..445
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   STRAND          447..451
FT                   /evidence="ECO:0007829|PDB:1JMJ"
FT   STRAND          459..462
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   STRAND          468..470
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   STRAND          475..481
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   TURN            482..485
FT                   /evidence="ECO:0007829|PDB:1JMO"
FT   STRAND          486..494
FT                   /evidence="ECO:0007829|PDB:1JMO"
SQ   SEQUENCE   499 AA;  57071 MW;  3B0E353FE1F6DF05 CRC64;
     MKHSLNALLI FLIITSAWGG SKGPLDQLEK GGETAQSADP QWEQLNNKNL SMPLLPADFH
     KENTVTNDWI PEGEEDDDYL DLEKIFSEDD DYIDIVDSLS VSPTDSDVSA GNILQLFHGK
     SRIQRLNILN AKFAFNLYRV LKDQVNTFDN IFIAPVGIST AMGMISLGLK GETHEQVHSI
     LHFKDFVNAS SKYEITTIHN LFRKLTHRLF RRNFGYTLRS VNDLYIQKQF PILLDFKTKV
     REYYFAEAQI ADFSDPAFIS KTNNHIMKLT KGLIKDALEN IDPATQMMIL NCIYFKGSWV
     NKFPVEMTHN HNFRLNEREV VKVSMMQTKG NFLAANDQEL DCDILQLEYV GGISMLIVVP
     HKMSGMKTLE AQLTPRVVER WQKSMTNRTR EVLLPKFKLE KNYNLVESLK LMGIRMLFDK
     NGNMAGISDQ RIAIDLFKHQ GTITVNEEGT QATTVTTVGF MPLSTQVRFT VDRPFLFLIY
     EHRTSCLLFM GRVANPSRS
//
DBGET integrated database retrieval system