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 24-JAN-2024, entry version 201. 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/"; 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; 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 GlyCosmos; Q9UK55; 4 sites, 10 glycans. 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; 9606-ENSP00000261994; -. DR PeptideAtlas; Q9UK55; -. DR ProteomicsDB; 84723; -. DR Antibodypedia; 27029; 382 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 AGR; HGNC:15996; -. 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; 3218836at2759; -. 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 1139 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 78 other cell types or tissues. DR ExpressionAtlas; Q9UK55; baseline and differential. 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 CDD; cd02055; serpinA10_PZI; 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; 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:SF191; PROTEIN Z-DEPENDENT PROTEASE INHIBITOR; 1. DR PANTHER; PTHR11461; SERINE PROTEASE INHIBITOR, SERPIN; 1. DR Pfam; PF00079; Serpin; 1. DR SMART; SM00093; SERPIN; 1. DR SUPFAM; SSF56574; Serpins; 1. DR Genevisible; Q9UK55; HS. 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 //