HEP2_HUMAN
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 03-AUG-2022, entry version 222.
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};
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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; 14.
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, 27 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; 337 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 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; QRLNMVN; -.
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 SignaLink; P05546; -.
DR SIGNOR; P05546; -.
DR BioGRID-ORCS; 3053; 23 hits in 1074 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 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
