ZPI_MOUSE
ID ZPI_MOUSE Reviewed; 448 AA.
AC Q8R121; Q8VCV8;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Protein Z-dependent protease inhibitor;
DE Short=PZ-dependent protease inhibitor;
DE Short=PZI;
DE AltName: Full=Serpin A10;
DE Flags: Precursor;
GN Name=Serpina10; Synonyms=Zpi;
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] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ; TISSUE=Liver;
RX PubMed=11372680;
RA Zhang J., Broze G.J. Jr.;
RT "Mouse protein Z-dependent protease inhibitor cDNA.";
RL Thromb. Haemost. 85:861-865(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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-81; ASN-184; ASN-278 AND
RP ASN-299.
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 GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-81.
RC STRAIN=C57BL/6J; TISSUE=Plasma;
RX PubMed=17330941; DOI=10.1021/pr0604559;
RA Bernhard O.K., Kapp E.A., Simpson R.J.;
RT "Enhanced analysis of the mouse plasma proteome using cysteine-containing
RT tryptic glycopeptides.";
RL J. Proteome Res. 6:987-995(2007).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Liver, and Lung;
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).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 22-448, AND MUTAGENESIS OF MET-96;
RP ASP-99; ASP-263; LYS-264; TYR-265 AND ASP-318.
RX PubMed=22786881; DOI=10.1182/blood-2012-03-419598;
RA Huang X., Yan Y., Tu Y., Gatti J., Broze G.J. Jr., Zhou A., Olson S.T.;
RT "Structural basis for catalytic activation of protein Z-dependent protease
RT inhibitor (ZPI) by protein Z.";
RL Blood 120:1726-1733(2012).
CC -!- FUNCTION: Inhibits activity of the coagulation protease factor Xa in
CC the presence of PROZ, calcium and phospholipids. Also inhibits factor
CC XIa in the absence of cofactors (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8R121-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8R121-2; Sequence=VSP_014439;
CC -!- TISSUE SPECIFICITY: Detectable in liver, but not in heart, brain,
CC spleen, lung, kidney, skeletal muscle or testes.
CC {ECO:0000269|PubMed:11372680}.
CC -!- PTM: Phosphorylated by FAM20C in the extracellular medium.
CC {ECO:0000250|UniProtKB:Q9UK55}.
CC -!- MISCELLANEOUS: Heparin acts as an important cofactor, producing 20 to
CC 100-fold accelerations of SERPINA10 reactions with factor Xa and factor
CC XIa. {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform 2]: May be due to a competing acceptor splice
CC site. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the serpin family. {ECO:0000305}.
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DR EMBL; AY324633; AAP87100.1; -; mRNA.
DR EMBL; BC018416; AAH18416.1; -; mRNA.
DR EMBL; BC025821; AAH25821.1; -; mRNA.
DR CCDS; CCDS26134.1; -. [Q8R121-1]
DR CCDS; CCDS79150.1; -. [Q8R121-2]
DR RefSeq; NP_001288333.1; NM_001301404.1. [Q8R121-2]
DR RefSeq; NP_659083.2; NM_144834.4. [Q8R121-1]
DR PDB; 4AJT; X-ray; 2.50 A; A=22-448.
DR PDBsum; 4AJT; -.
DR AlphaFoldDB; Q8R121; -.
DR SMR; Q8R121; -.
DR STRING; 10090.ENSMUSP00000048357; -.
DR MEROPS; I04.005; -.
DR GlyGen; Q8R121; 4 sites.
DR iPTMnet; Q8R121; -.
DR PhosphoSitePlus; Q8R121; -.
DR CPTAC; non-CPTAC-3888; -.
DR CPTAC; non-CPTAC-5623; -.
DR MaxQB; Q8R121; -.
DR PaxDb; Q8R121; -.
DR PeptideAtlas; Q8R121; -.
DR PRIDE; Q8R121; -.
DR ProteomicsDB; 275240; -. [Q8R121-1]
DR ProteomicsDB; 275241; -. [Q8R121-2]
DR Antibodypedia; 27029; 353 antibodies from 39 providers.
DR DNASU; 217847; -.
DR Ensembl; ENSMUST00000044231; ENSMUSP00000048357; ENSMUSG00000061947. [Q8R121-1]
DR Ensembl; ENSMUST00000121625; ENSMUSP00000113644; ENSMUSG00000061947. [Q8R121-2]
DR GeneID; 217847; -.
DR KEGG; mmu:217847; -.
DR UCSC; uc007ovz.2; mouse. [Q8R121-1]
DR UCSC; uc011yra.2; mouse. [Q8R121-2]
DR CTD; 51156; -.
DR MGI; MGI:2667725; Serpina10.
DR VEuPathDB; HostDB:ENSMUSG00000061947; -.
DR eggNOG; KOG2392; Eukaryota.
DR GeneTree; ENSGT00940000159462; -.
DR HOGENOM; CLU_023330_2_1_1; -.
DR InParanoid; Q8R121; -.
DR OMA; SKQYFDM; -.
DR OrthoDB; 1124079at2759; -.
DR PhylomeDB; Q8R121; -.
DR TreeFam; TF343094; -.
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; 217847; 2 hits in 71 CRISPR screens.
DR PRO; PR:Q8R121; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q8R121; protein.
DR Bgee; ENSMUSG00000061947; Expressed in left lobe of liver and 51 other tissues.
DR Genevisible; Q8R121; MM.
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 GO; GO:0097421; P:liver regeneration; IEA:Ensembl.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IBA:GO_Central.
DR CDD; cd02055; serpinA10_PZI; 1.
DR Gene3D; 2.30.39.10; -; 1.
DR Gene3D; 3.30.497.10; -; 1.
DR InterPro; IPR033835; PZI_serpin_dom.
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.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Blood coagulation; Glycoprotein;
KW Hemostasis; Heparin-binding; Protease inhibitor; Reference proteome;
KW Secreted; Serine protease inhibitor; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..448
FT /note="Protein Z-dependent protease inhibitor"
FT /id="PRO_0000032483"
FT REGION 33..70
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 140..157
FT /note="Heparin-binding"
FT /evidence="ECO:0000250"
FT COMPBIAS 52..66
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 265
FT /note="Essential for interaction with PROZ"
FT SITE 318
FT /note="Essential for interaction with PROZ"
FT SITE 412..413
FT /note="Reactive bond"
FT /evidence="ECO:0000250"
FT CARBOHYD 81
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16944957,
FT ECO:0000269|PubMed:17330941"
FT CARBOHYD 184
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16944957"
FT CARBOHYD 278
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16944957"
FT CARBOHYD 299
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16944957"
FT VAR_SEQ 245..298
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_014439"
FT MUTAGEN 96
FT /note="M->A: 2-fold decrease in rates of factor Xa
FT inhibition."
FT /evidence="ECO:0000269|PubMed:22786881"
FT MUTAGEN 99
FT /note="D->A: 5-fold decrease in rates of factor Xa
FT inhibition."
FT /evidence="ECO:0000269|PubMed:22786881"
FT MUTAGEN 263
FT /note="D->A: No change in rates of factor Xa inhibition."
FT /evidence="ECO:0000269|PubMed:22786881"
FT MUTAGEN 264
FT /note="K->A: No change in rates of factor Xa inhibition."
FT /evidence="ECO:0000269|PubMed:22786881"
FT MUTAGEN 265
FT /note="Y->A: 50-fold decrease in rates of factor Xa
FT inhibition."
FT /evidence="ECO:0000269|PubMed:22786881"
FT MUTAGEN 318
FT /note="D->A: 400-fold decrease in rates of factor Xa
FT inhibition."
FT /evidence="ECO:0000269|PubMed:22786881"
FT HELIX 71..75
FT /evidence="ECO:0007829|PDB:4AJT"
FT HELIX 77..97
FT /evidence="ECO:0007829|PDB:4AJT"
FT STRAND 102..104
FT /evidence="ECO:0007829|PDB:4AJT"
FT HELIX 106..119
FT /evidence="ECO:0007829|PDB:4AJT"
FT HELIX 123..132
FT /evidence="ECO:0007829|PDB:4AJT"
FT HELIX 135..138
FT /evidence="ECO:0007829|PDB:4AJT"
FT HELIX 144..157
FT /evidence="ECO:0007829|PDB:4AJT"
FT STRAND 164..173
FT /evidence="ECO:0007829|PDB:4AJT"
FT HELIX 180..189
FT /evidence="ECO:0007829|PDB:4AJT"
FT STRAND 194..197
FT /evidence="ECO:0007829|PDB:4AJT"
FT HELIX 202..216
FT /evidence="ECO:0007829|PDB:4AJT"
FT TURN 217..219
FT /evidence="ECO:0007829|PDB:4AJT"
FT STRAND 234..242
FT /evidence="ECO:0007829|PDB:4AJT"
FT STRAND 246..248
FT /evidence="ECO:0007829|PDB:4AJT"
FT HELIX 252..254
FT /evidence="ECO:0007829|PDB:4AJT"
FT STRAND 256..265
FT /evidence="ECO:0007829|PDB:4AJT"
FT STRAND 267..284
FT /evidence="ECO:0007829|PDB:4AJT"
FT TURN 285..288
FT /evidence="ECO:0007829|PDB:4AJT"
FT STRAND 289..296
FT /evidence="ECO:0007829|PDB:4AJT"
FT HELIX 297..299
FT /evidence="ECO:0007829|PDB:4AJT"
FT STRAND 300..307
FT /evidence="ECO:0007829|PDB:4AJT"
FT HELIX 313..316
FT /evidence="ECO:0007829|PDB:4AJT"
FT TURN 317..319
FT /evidence="ECO:0007829|PDB:4AJT"
FT HELIX 322..330
FT /evidence="ECO:0007829|PDB:4AJT"
FT STRAND 333..342
FT /evidence="ECO:0007829|PDB:4AJT"
FT STRAND 344..351
FT /evidence="ECO:0007829|PDB:4AJT"
FT HELIX 353..358
FT /evidence="ECO:0007829|PDB:4AJT"
FT HELIX 363..365
FT /evidence="ECO:0007829|PDB:4AJT"
FT TURN 372..374
FT /evidence="ECO:0007829|PDB:4AJT"
FT STRAND 385..394
FT /evidence="ECO:0007829|PDB:4AJT"
FT STRAND 417..419
FT /evidence="ECO:0007829|PDB:4AJT"
FT STRAND 424..430
FT /evidence="ECO:0007829|PDB:4AJT"
FT TURN 431..434
FT /evidence="ECO:0007829|PDB:4AJT"
FT STRAND 435..444
FT /evidence="ECO:0007829|PDB:4AJT"
SQ SEQUENCE 448 AA; 51797 MW; C7948A64BBA65B3F CRC64;
MRVASSLFLP VLLTEVWLVT SFNLSSHSPE ASVHLESQDY ENQTWEEYTR TDPREEEEEE
EEKEEGKDEE YWLRASQQLS NETSSFGFNL LRKISMRHDG NVIFSPFGLS VAMVNLMLGT
KGETKVQIEN GLNLQALSQA GPLILPALFK KVKETFSSNR DLGLSQGSFA FIHKDFDIKE
TYFNLSKKYF DIEYVSINFQ NSSQARGLIN HCIVKETEGK IPKLFDEINP ETKLILVDYV
LFKGKWLTPF DPSFTEADTF HLDKYRAIKV PMMYREGNFT STFDKKFRCH ILKLPYQGNA
TMLVVLMEKT GDYLALEDYL TVDLVETWLQ NMKTRKMEVF FPKFKLNQRY EMHELLKQMG
IRRLFSTSAD LSELSAMARN LQVSRVLQQS VLEVDERGTE AVSGTLSEII AYSMPPAIKV
NRPFHFIIYE EMSRMLLFLG RVVNPTVL
