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 27-MAR-2024, entry version 231. 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; DOI=10.1016/s0021-9258(18)37902-x; 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; DOI=10.1016/s0021-9258(17)35228-6; 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; DOI=10.1016/s0021-9258(18)54913-9; 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; DOI=10.1016/s0021-9258(19)40228-7; 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; DOI=10.1016/s0021-9258(18)83708-5; 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 AlphaFoldDB; P05546; -. DR SMR; P05546; -. DR BioGRID; 109303; 15. DR CORUM; P05546; -. DR IntAct; P05546; 8. DR MINT; P05546; -. 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 GlyCosmos; P05546; 11 sites, 26 glycans. DR GlyGen; P05546; 13 sites, 27 N-linked glycans (2 sites), 5 O-linked glycans (10 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; 9606-ENSP00000215727; -. DR PeptideAtlas; P05546; -. DR ProteomicsDB; 51846; -. DR Antibodypedia; 3265; 355 antibodies from 32 providers. DR DNASU; 3053; -. DR Ensembl; ENST00000215727.10; ENSP00000215727.5; ENSG00000099937.11. DR Ensembl; ENST00000406799.1; ENSP00000384050.1; ENSG00000099937.11. DR GeneID; 3053; -. DR KEGG; hsa:3053; -. DR MANE-Select; ENST00000215727.10; ENSP00000215727.5; NM_000185.4; NP_000176.2. DR UCSC; uc002ztb.2; human. DR AGR; HGNC:4838; -. 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; NYNLVEP; -. DR OrthoDB; 3218836at2759; -. 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 SignaLink; P05546; -. DR SIGNOR; P05546; -. DR BioGRID-ORCS; 3053; 23 hits in 1158 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 92 other cell types or tissues. 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 CDD; cd02047; serpinD1_HCF2; 1. DR Gene3D; 2.30.39.10; Alpha-1-antitrypsin, domain 1; 1. DR Gene3D; 3.30.497.10; Antithrombin, subunit I, domain 2; 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:SF30; HEPARIN COFACTOR 2; 1. DR PANTHER; PTHR11461; SERINE PROTEASE INHIBITOR, SERPIN; 1. DR Pfam; PF00079; Serpin; 1. DR PRINTS; PR00780; LEUSERPINII. DR SMART; SM00093; SERPIN; 1. DR SUPFAM; SSF56574; Serpins; 1. DR PROSITE; PS00284; SERPIN; 1. DR Genevisible; P05546; HS. 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 FT sulfate-activated inhibition." FT /evidence="ECO:0000269|PubMed:2104620" FT MUTAGEN 204 FT /note="K->N: Reduced heparin- and no dermatan FT sulfate-activated inhibition." FT /evidence="ECO:0000269|PubMed:2104620" FT MUTAGEN 204 FT /note="K->T: Reduced heparin- and no dermatan FT sulfate-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 //