ID   HEP2_MOUSE              Reviewed;         478 AA.
AC   P49182;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 1.
DT   27-MAR-2024, entry version 173.
DE   RecName: Full=Heparin cofactor 2;
DE   AltName: Full=Heparin cofactor II;
DE            Short=HC-II;
DE   AltName: Full=Protease inhibitor leuserpin-2;
DE   AltName: Full=Serpin D1;
DE   Flags: Precursor;
GN   Name=Serpind1; Synonyms=Hcf2, Hcii;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 24-44.
RC   STRAIN=BALB/cJ; TISSUE=Liver;
RX   PubMed=7908224; DOI=10.1021/bi00178a021;
RA   Zhang G.S., Mehringer J.H., van Deerlin V.M.D., Kozak C.A., Tollefsen D.M.;
RT   "Murine heparin cofactor II: purification, cDNA sequence, expression, and
RT   gene structure.";
RL   Biochemistry 33:3632-3642(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Liver;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-30 AND ASN-167.
RC   STRAIN=C57BL/6J; TISSUE=Plasma;
RX   PubMed=16944957; DOI=10.1021/pr060186m;
RA   Ghesquiere B., Van Damme J., Martens L., Vandekerckhove J., Gevaert K.;
RT   "Proteome-wide characterization of N-glycosylation events by diagonal
RT   chromatography.";
RL   J. Proteome Res. 5:2438-2447(2006).
RN   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brown adipose tissue, Heart, Liver, Lung, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
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). Also inhibits chymotrypsin, but in a glycosaminoglycan-
CC       independent manner.
CC   -!- TISSUE SPECIFICITY: Expressed predominantly in liver.
CC   -!- DOMAIN: The N-terminal acidic repeat region mediates, in part, the
CC       glycosaminoglycan-accelerated thrombin inhibition. {ECO:0000250}.
CC   -!- PTM: N-glycosylated; different glycan composition appears to lead to
CC       two forms of this protein (68 and 72 kDa).
CC       {ECO:0000269|PubMed:16944957}.
CC   -!- SIMILARITY: Belongs to the serpin family. {ECO:0000305}.
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DR   EMBL; U07425; AAA18452.1; -; mRNA.
DR   EMBL; BC034543; AAH34543.1; -; mRNA.
DR   CCDS; CCDS28000.1; -.
DR   PIR; A54248; A54248.
DR   RefSeq; NP_001317976.1; NM_001331047.1.
DR   RefSeq; NP_032249.3; NM_008223.4.
DR   AlphaFoldDB; P49182; -.
DR   SMR; P49182; -.
DR   STRING; 10090.ENSMUSP00000023450; -.
DR   MEROPS; I04.019; -.
DR   GlyCosmos; P49182; 4 sites, No reported glycans.
DR   GlyGen; P49182; 4 sites.
DR   iPTMnet; P49182; -.
DR   PhosphoSitePlus; P49182; -.
DR   CPTAC; non-CPTAC-5601; -.
DR   CPTAC; non-CPTAC-5602; -.
DR   MaxQB; P49182; -.
DR   PaxDb; 10090-ENSMUSP00000023450; -.
DR   PeptideAtlas; P49182; -.
DR   ProteomicsDB; 269697; -.
DR   Antibodypedia; 3265; 355 antibodies from 32 providers.
DR   DNASU; 15160; -.
DR   Ensembl; ENSMUST00000023450.15; ENSMUSP00000023450.7; ENSMUSG00000022766.15.
DR   Ensembl; ENSMUST00000231884.2; ENSMUSP00000156303.2; ENSMUSG00000022766.15.
DR   GeneID; 15160; -.
DR   KEGG; mmu:15160; -.
DR   UCSC; uc007yks.2; mouse.
DR   AGR; MGI:96051; -.
DR   CTD; 3053; -.
DR   MGI; MGI:96051; Serpind1.
DR   VEuPathDB; HostDB:ENSMUSG00000022766; -.
DR   eggNOG; KOG2392; Eukaryota.
DR   GeneTree; ENSGT00940000158664; -.
DR   HOGENOM; CLU_023330_8_0_1; -.
DR   InParanoid; P49182; -.
DR   OMA; NYNLVEP; -.
DR   OrthoDB; 3218836at2759; -.
DR   PhylomeDB; P49182; -.
DR   TreeFam; TF343094; -.
DR   Reactome; R-MMU-140837; Intrinsic Pathway of Fibrin Clot Formation.
DR   Reactome; R-MMU-140875; Common Pathway of Fibrin Clot Formation.
DR   Reactome; R-MMU-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR   Reactome; R-MMU-8957275; Post-translational protein phosphorylation.
DR   BioGRID-ORCS; 15160; 0 hits in 76 CRISPR screens.
DR   PRO; PR:P49182; -.
DR   Proteomes; UP000000589; Chromosome 16.
DR   RNAct; P49182; Protein.
DR   Bgee; ENSMUSG00000022766; Expressed in liver and 88 other cell types or tissues.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
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   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; P49182; MM.
PE   1: Evidence at protein level;
KW   Blood coagulation; Direct protein sequencing; Glycoprotein; Hemostasis;
KW   Heparin-binding; Protease inhibitor; Reference proteome; Repeat;
KW   Serine protease inhibitor; Signal; Sulfation.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000269|PubMed:7908224"
FT   CHAIN           24..478
FT                   /note="Heparin cofactor 2"
FT                   /id="PRO_0000032495"
FT   REPEAT          54..64
FT                   /note="1"
FT   REPEAT          68..78
FT                   /note="2"
FT   REGION          54..78
FT                   /note="2 X 11 AA approximate repeats, Asp/Glu-rich (acidic)
FT                   (hirudin-like)"
FT   REGION          171..191
FT                   /note="Glycosaminoglycan-binding site"
FT                   /evidence="ECO:0000250"
FT   SITE            442..443
FT                   /note="Reactive bond"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         60
FT                   /note="Sulfotyrosine"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         73
FT                   /note="Sulfotyrosine"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        30
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:16944957"
FT   CARBOHYD        167
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:16944957"
FT   CARBOHYD        366
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        402
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   478 AA;  54497 MW;  7234711F0083865D CRC64;
     MKHPLCTLLS LITFMCIGSK GLAEQLTNEN LTTSFLPANF HKENTVTNDW IPEGEEDEDY
     LDLEKLLGED DDYIYIIDAV SPTDSESSAG NILQLFQGKS RIQRLNILNA KFAFNLYRVL
     KDQATTSDNL FIAPVGISTA MGMISLGLRG ETHEEVHSVL HFRDFVNASS KYEVTTIHNL
     FRKLTHRLFR RNFGYTLRSV NGLYIQKQFP IREDFKAAMR EFYFAEAQEA NFPDPAFISK
     ANNHILKLTK GLIKEALENI DPATQMLILN CIYFKGTWVN KFPVEMTHNH NFRLNEREVV
     KVSMMQTKGN FLAANDQELD CDILQLEYVG GISMLIVVPR KLSGMKTLEA QLTPQVVERW
     QKSMTNRTRE VLLPKFKLEK NYNLVEVLKS MGITKLFNKN GNMSGISDQR IAIDLFKHQS
     TITVNEEGTQ AAAVTTVGFM PLSTQVRFTV DRPFLFLVYE HRTSCLLFMG KVTNPAKS
//