ZPI_HUMAN
ID ZPI_HUMAN Reviewed; 444 AA.
AC Q9UK55; A5Z2A5; Q6UWX9; Q86U20;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 193.
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; ORFNames=UNQ707/PRO1358;
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], AND MUTAGENESIS OF TYR-408.
RC TISSUE=Liver;
RX PubMed=10460162; DOI=10.1021/bi990641a;
RA Han X., Huang Z.-F., Fiehler R., Broze G.J. Jr.;
RT "The protein Z-dependent protease inhibitor is a serpin.";
RL Biochemistry 38:11073-11078(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ARG-46; GLY-61;
RP SER-161 AND ARG-384.
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Fetal liver;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-46; GLY-61; ARG-139;
RP SER-161; SER-271 AND PRO-384.
RG SeattleSNPs variation discovery resource;
RL Submitted (MAY-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC 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 [6]
RP PROTEIN SEQUENCE OF 22-33, AND CHARACTERIZATION.
RC TISSUE=Plasma;
RX PubMed=9689066; DOI=10.1073/pnas.95.16.9250;
RA Han X., Fiehler R., Broze G.J. Jr.;
RT "Isolation of a protein Z-dependent plasma protease inhibitor.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:9250-9255(1998).
RN [7]
RP FUNCTION, AND INTERACTION WITH PROZ.
RX PubMed=11049983;
RA Han X., Fiehler R., Broze G.J. Jr.;
RT "Characterization of the protein Z-dependent protease inhibitor.";
RL Blood 96:3049-3055(2000).
RN [8]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-180 AND ASN-295.
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 [9]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-36.
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 [10]
RP HEPARIN-BINDING REGION.
RX PubMed=22540147; DOI=10.1021/bi300353c;
RA Yang L., Ding Q., Huang X., Olson S.T., Rezaie A.R.;
RT "Characterization of the heparin-binding site of the protein z-dependent
RT protease inhibitor.";
RL Biochemistry 51:4078-4085(2012).
RN [11]
RP PHOSPHORYLATION AT SER-56.
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 [12]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 60-444 IN COMPLEX WITH PROZ.
RX PubMed=19528533; DOI=10.1182/blood-2009-04-210021;
RA Wei Z., Yan Y., Carrell R.W., Zhou A.;
RT "Crystal structure of protein Z-dependent inhibitor complex shows how
RT protein Z functions as a cofactor in the membrane inhibition of factor X.";
RL Blood 114:3662-3667(2009).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (3.26 ANGSTROMS) OF 22-444 IN COMPLEX WITH PROZ,
RP GLYCOSYLATION AT ASN-197 AND ASN-295, AND SUBUNIT.
RX PubMed=20427285; DOI=10.1074/jbc.m110.112748;
RA Huang X., Dementiev A., Olson S.T., Gettins P.G.;
RT "Basis for the specificity and activation of the serpin protein Z-dependent
RT proteinase inhibitor (ZPI) as an inhibitor of membrane-associated factor
RT Xa.";
RL J. Biol. Chem. 285:20399-20409(2010).
RN [14]
RP VARIANT LEU-420.
RX PubMed=23375655; DOI=10.1016/j.ajhg.2013.01.003;
RA Parry D.A., Poulter J.A., Logan C.V., Brookes S.J., Jafri H.,
RA Ferguson C.H., Anwari B.M., Rashid Y., Zhao H., Johnson C.A.,
RA Inglehearn C.F., Mighell A.J.;
RT "Identification of mutations in SLC24A4, encoding a potassium-dependent
RT sodium/calcium exchanger, as a cause of amelogenesis imperfecta.";
RL Am. J. Hum. Genet. 92:307-312(2013).
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. {ECO:0000269|PubMed:11049983}.
CC -!- SUBUNIT: Interacts with PROZ. {ECO:0000269|PubMed:11049983,
CC ECO:0000269|PubMed:19528533, ECO:0000269|PubMed:20427285}.
CC -!- INTERACTION:
CC Q9UK55; P00742: F10; NbExp=2; IntAct=EBI-3941758, EBI-719750;
CC Q9UK55; P22891: PROZ; NbExp=7; IntAct=EBI-3941758, EBI-22220337;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the liver and secreted in plasma.
CC -!- PTM: Phosphorylated by FAM20C in the extracellular medium.
CC {ECO:0000269|PubMed:26091039}.
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.
CC -!- SIMILARITY: Belongs to the serpin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAD62339.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/serpina10/";
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DR EMBL; AF181467; AAD53962.1; -; mRNA.
DR EMBL; AY358597; AAQ88960.1; -; mRNA.
DR EMBL; BX248011; CAD62339.1; ALT_INIT; mRNA.
DR EMBL; EF621762; ABR09269.1; -; Genomic_DNA.
DR EMBL; BC022261; AAH22261.1; -; mRNA.
DR CCDS; CCDS9923.1; -.
DR RefSeq; NP_001094077.1; NM_001100607.2.
DR RefSeq; NP_057270.1; NM_016186.2.
DR RefSeq; XP_005267790.1; XM_005267733.4.
DR PDB; 3F1S; X-ray; 2.30 A; A=60-444.
DR PDB; 3H5C; X-ray; 3.26 A; A=22-444.
DR PDB; 4AFX; X-ray; 2.09 A; A=23-408, B=409-444.
DR PDB; 4AJU; X-ray; 2.65 A; A=23-408, B=409-444.
DR PDBsum; 3F1S; -.
DR PDBsum; 3H5C; -.
DR PDBsum; 4AFX; -.
DR PDBsum; 4AJU; -.
DR AlphaFoldDB; Q9UK55; -.
DR SMR; Q9UK55; -.
DR BioGRID; 119339; 16.
DR IntAct; Q9UK55; 9.
DR STRING; 9606.ENSP00000261994; -.
DR MEROPS; I04.005; -.
DR GlyConnect; 1673; 8 N-Linked glycans (3 sites).
DR GlyGen; Q9UK55; 4 sites, 10 N-linked glycans (3 sites).
DR iPTMnet; Q9UK55; -.
DR PhosphoSitePlus; Q9UK55; -.
DR BioMuta; SERPINA10; -.
DR DMDM; 12585541; -.
DR CPTAC; non-CPTAC-2690; -.
DR jPOST; Q9UK55; -.
DR MassIVE; Q9UK55; -.
DR PaxDb; Q9UK55; -.
DR PeptideAtlas; Q9UK55; -.
DR PRIDE; Q9UK55; -.
DR ProteomicsDB; 84723; -.
DR Antibodypedia; 27029; 353 antibodies from 39 providers.
DR DNASU; 51156; -.
DR Ensembl; ENST00000261994.9; ENSP00000261994.4; ENSG00000140093.10.
DR Ensembl; ENST00000393096.5; ENSP00000376809.1; ENSG00000140093.10.
DR Ensembl; ENST00000554173.1; ENSP00000450971.1; ENSG00000140093.10.
DR Ensembl; ENST00000614630.4; ENSP00000484632.1; ENSG00000278767.4.
DR GeneID; 51156; -.
DR KEGG; hsa:51156; -.
DR MANE-Select; ENST00000261994.9; ENSP00000261994.4; NM_001100607.3; NP_001094077.1.
DR UCSC; uc001ycu.6; human.
DR CTD; 51156; -.
DR DisGeNET; 51156; -.
DR GeneCards; SERPINA10; -.
DR HGNC; HGNC:15996; SERPINA10.
DR HPA; ENSG00000140093; Tissue enriched (liver).
DR MIM; 602455; gene.
DR MIM; 605271; gene+phenotype.
DR neXtProt; NX_Q9UK55; -.
DR OpenTargets; ENSG00000140093; -.
DR Orphanet; 64738; NON RARE IN EUROPE: Non rare thrombophilia.
DR PharmGKB; PA38078; -.
DR VEuPathDB; HostDB:ENSG00000140093; -.
DR eggNOG; KOG2392; Eukaryota.
DR GeneTree; ENSGT00940000159462; -.
DR HOGENOM; CLU_023330_2_1_1; -.
DR InParanoid; Q9UK55; -.
DR OrthoDB; 1124079at2759; -.
DR PhylomeDB; Q9UK55; -.
DR TreeFam; TF343094; -.
DR PathwayCommons; Q9UK55; -.
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; Q9UK55; -.
DR BioGRID-ORCS; 51156; 10 hits in 1061 CRISPR screens.
DR EvolutionaryTrace; Q9UK55; -.
DR GenomeRNAi; 51156; -.
DR Pharos; Q9UK55; Tbio.
DR PRO; PR:Q9UK55; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q9UK55; protein.
DR Bgee; ENSG00000140093; Expressed in right lobe of liver and 77 other tissues.
DR ExpressionAtlas; Q9UK55; baseline and differential.
DR Genevisible; Q9UK55; HS.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
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; Blood coagulation; Direct protein sequencing; Glycoprotein;
KW Hemostasis; Heparin-binding; Phosphoprotein; Protease inhibitor;
KW Reference proteome; Secreted; Serine protease inhibitor; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000269|PubMed:9689066"
FT CHAIN 22..444
FT /note="Protein Z-dependent protease inhibitor"
FT /id="PRO_0000032482"
FT REGION 24..65
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 136..153
FT /note="Heparin-binding"
FT SITE 261
FT /note="Essential for interaction with PROZ"
FT /evidence="ECO:0000250"
FT SITE 314
FT /note="Essential for interaction with PROZ"
FT /evidence="ECO:0000250"
FT SITE 408..409
FT /note="Reactive bond"
FT /evidence="ECO:0000250"
FT MOD_RES 56
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT CARBOHYD 36
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 180
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952"
FT CARBOHYD 197
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:20427285"
FT CARBOHYD 295
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:20427285"
FT VARIANT 46
FT /note="K -> R (in dbSNP:rs941590)"
FT /evidence="ECO:0000269|PubMed:12975309, ECO:0000269|Ref.4"
FT /id="VAR_020325"
FT VARIANT 61
FT /note="S -> G (in dbSNP:rs941591)"
FT /evidence="ECO:0000269|PubMed:12975309, ECO:0000269|Ref.4"
FT /id="VAR_020326"
FT VARIANT 139
FT /note="G -> R (in dbSNP:rs56137907)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_038833"
FT VARIANT 158
FT /note="L -> Q (in dbSNP:rs2232699)"
FT /id="VAR_051940"
FT VARIANT 161
FT /note="T -> S (in dbSNP:rs2232700)"
FT /evidence="ECO:0000269|PubMed:12975309, ECO:0000269|Ref.4"
FT /id="VAR_020327"
FT VARIANT 196
FT /note="R -> H (in dbSNP:rs2232701)"
FT /id="VAR_051941"
FT VARIANT 271
FT /note="G -> S (in dbSNP:rs2232708)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_038834"
FT VARIANT 384
FT /note="Q -> P"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_038835"
FT VARIANT 384
FT /note="Q -> R (in dbSNP:rs2232710)"
FT /evidence="ECO:0000269|PubMed:12975309"
FT /id="VAR_051942"
FT VARIANT 420
FT /note="F -> L (in dbSNP:rs546304706)"
FT /evidence="ECO:0000269|PubMed:23375655"
FT /id="VAR_070192"
FT MUTAGEN 408
FT /note="Y->A: Loss of inhibitory activity."
FT /evidence="ECO:0000269|PubMed:10460162"
FT HELIX 62..93
FT /evidence="ECO:0007829|PDB:4AFX"
FT STRAND 98..100
FT /evidence="ECO:0007829|PDB:4AFX"
FT HELIX 102..113
FT /evidence="ECO:0007829|PDB:4AFX"
FT HELIX 119..127
FT /evidence="ECO:0007829|PDB:4AFX"
FT HELIX 137..139
FT /evidence="ECO:0007829|PDB:3H5C"
FT HELIX 140..154
FT /evidence="ECO:0007829|PDB:4AFX"
FT HELIX 156..158
FT /evidence="ECO:0007829|PDB:4AFX"
FT STRAND 160..169
FT /evidence="ECO:0007829|PDB:4AFX"
FT HELIX 176..186
FT /evidence="ECO:0007829|PDB:4AFX"
FT STRAND 189..193
FT /evidence="ECO:0007829|PDB:4AFX"
FT STRAND 195..197
FT /evidence="ECO:0007829|PDB:4AJU"
FT HELIX 198..212
FT /evidence="ECO:0007829|PDB:4AFX"
FT TURN 213..215
FT /evidence="ECO:0007829|PDB:4AFX"
FT STRAND 216..218
FT /evidence="ECO:0007829|PDB:4AFX"
FT STRAND 228..244
FT /evidence="ECO:0007829|PDB:4AFX"
FT HELIX 248..250
FT /evidence="ECO:0007829|PDB:4AFX"
FT STRAND 252..261
FT /evidence="ECO:0007829|PDB:4AFX"
FT STRAND 263..280
FT /evidence="ECO:0007829|PDB:4AFX"
FT TURN 281..284
FT /evidence="ECO:0007829|PDB:4AFX"
FT STRAND 285..292
FT /evidence="ECO:0007829|PDB:4AFX"
FT STRAND 295..304
FT /evidence="ECO:0007829|PDB:4AFX"
FT STRAND 305..307
FT /evidence="ECO:0007829|PDB:3H5C"
FT HELIX 312..314
FT /evidence="ECO:0007829|PDB:4AFX"
FT HELIX 318..326
FT /evidence="ECO:0007829|PDB:4AFX"
FT STRAND 329..338
FT /evidence="ECO:0007829|PDB:4AFX"
FT STRAND 340..347
FT /evidence="ECO:0007829|PDB:4AFX"
FT HELIX 349..354
FT /evidence="ECO:0007829|PDB:4AFX"
FT HELIX 359..361
FT /evidence="ECO:0007829|PDB:4AFX"
FT TURN 368..370
FT /evidence="ECO:0007829|PDB:4AFX"
FT STRAND 371..373
FT /evidence="ECO:0007829|PDB:4AFX"
FT STRAND 378..390
FT /evidence="ECO:0007829|PDB:4AFX"
FT STRAND 392..406
FT /evidence="ECO:0007829|PDB:4AFX"
FT STRAND 413..415
FT /evidence="ECO:0007829|PDB:4AFX"
FT STRAND 420..426
FT /evidence="ECO:0007829|PDB:4AFX"
FT TURN 427..430
FT /evidence="ECO:0007829|PDB:4AFX"
FT STRAND 431..439
FT /evidence="ECO:0007829|PDB:4AFX"
SQ SEQUENCE 444 AA; 50707 MW; 06BD47C97BBDD700 CRC64;
MKVVPSLLLS VLLAQVWLVP GLAPSPQSPE TPAPQNQTSR VVQAPKEEEE DEQEASEEKA
SEEEKAWLMA SRQQLAKETS NFGFSLLRKI SMRHDGNMVF SPFGMSLAMT GLMLGATGPT
ETQIKRGLHL QALKPTKPGL LPSLFKGLRE TLSRNLELGL TQGSFAFIHK DFDVKETFFN
LSKRYFDTEC VPMNFRNASQ AKRLMNHYIN KETRGKIPKL FDEINPETKL ILVDYILFKG
KWLTPFDPVF TEVDTFHLDK YKTIKVPMMY GAGKFASTFD KNFRCHVLKL PYQGNATMLV
VLMEKMGDHL ALEDYLTTDL VETWLRNMKT RNMEVFFPKF KLDQKYEMHE LLRQMGIRRI
FSPFADLSEL SATGRNLQVS RVLQRTVIEV DERGTEAVAG ILSEITAYSM PPVIKVDRPF
HFMIYEETSG MLLFLGRVVN PTLL
