Q9UK55 (ZPI_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein Z-dependent protease inhibitor
Short name=PZ-dependent protease inhibitor
Short name=PZI

Alternative name(s):
Serpin A10

Gene names

Name:	SERPINA10
Synonyms:	ZPI
ORF Names:	UNQ707/PRO1358

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	444 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Inhibits activity of the coagulation protease factor Xa in the presence of PROZ, calcium and phospholipids. Also inhibits factor XIa in the absence of cofactors. Ref.7
Subunit structure	Interacts with PROZ. Ref.7 Ref.12
Subcellular location	Secreted.
Tissue specificity	Expressed by the liver and secreted in plasma.
Post-translational modification	Phosphorylation sites are present in the extracellular medium.
Miscellaneous	Heparin acts as an important cofactor, producing 20 to 100-fold accelerations of SERPINA10 reactions with factor Xa and factor XIa.
Sequence similarities	Belongs to the serpin family.
Sequence caution	The sequence CAD62339.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Blood coagulation Hemostasis
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Ligand	Heparin-binding
Molecular function	Protease inhibitor Serine protease inhibitor
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	blood coagulation Inferred from electronic annotation. Source: UniProtKB-KW regulation of proteolysis Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	serine-type endopeptidase inhibitor activity Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Ref.6

Chain

22 – 444

423

Protein Z-dependent protease inhibitor

PRO_0000032482

Regions

Region

136 – 153

18

Heparin-binding

Sites

Site

261

1

Essential for interaction with PROZ By similarity

Site

314

1

Essential for interaction with PROZ By similarity

Site

408 – 409

2

Reactive bond By similarity

Amino acid modifications

Glycosylation

36

1

N-linked (GlcNAc...) Ref.9

Glycosylation

180

1

N-linked (GlcNAc...) Ref.8

Glycosylation

197

1

N-linked (GlcNAc...) Ref.12

Glycosylation

295

1

N-linked (GlcNAc...) Ref.8 Ref.12

Natural variations

Natural variant

46

1

K → R. Ref.2 Ref.4
Corresponds to variant rs941590 [ dbSNP | Ensembl ].

VAR_020325

Natural variant

61

1

S → G. Ref.2 Ref.4
Corresponds to variant rs941591 [ dbSNP | Ensembl ].

VAR_020326

Natural variant

139

1

G → R. Ref.4
Corresponds to variant rs56137907 [ dbSNP | Ensembl ].

VAR_038833

Natural variant

158

1

L → Q.
Corresponds to variant rs2232699 [ dbSNP | Ensembl ].

VAR_051940

Natural variant

161

1

T → S. Ref.2 Ref.4
Corresponds to variant rs2232700 [ dbSNP | Ensembl ].

VAR_020327

Natural variant

196

1

R → H.
Corresponds to variant rs2232701 [ dbSNP | Ensembl ].

VAR_051941

Natural variant

271

1

G → S. Ref.4
Corresponds to variant rs2232708 [ dbSNP | Ensembl ].

VAR_038834

Natural variant

384

1

Q → P. Ref.4

VAR_038835

Natural variant

384

1

Q → R. Ref.2
Corresponds to variant rs2232710 [ dbSNP | Ensembl ].

VAR_051942

Experimental info

Mutagenesis

408

1

Y → A: Loss of inhibitory activity. Ref.1

Secondary structure

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444

Helix Strand Turn

Details...

Helix

62 – 93

32

Beta strand

98 – 100

3

Helix

102 – 112

11

Turn

113 – 115

3

Helix

119 – 127

9

Helix

137 – 139

3

Helix

140 – 154

15

Beta strand

156 – 158

3

Beta strand

160 – 169

10

Helix

176 – 186

11

Beta strand

188 – 193

6

Beta strand

195 – 197

3

Helix

198 – 212

15

Turn

213 – 215

3

Beta strand

216 – 218

3

Beta strand

230 – 239

10

Beta strand

242 – 244

3

Helix

248 – 250

3

Beta strand

252 – 259

8

Beta strand

262 – 280

19

Turn

281 – 284

4

Beta strand

285 – 292

8

Turn

293 – 295

3

Beta strand

296 – 303

8

Beta strand

305 – 307

3

Helix

309 – 312

4

Helix

313 – 315

3

Helix

318 – 326

9

Beta strand

329 – 338

10

Beta strand

340 – 347

8

Helix

349 – 354

6

Helix

359 – 361

3

Turn

368 – 370

3

Beta strand

381 – 390

10

Beta strand

396 – 398

3

Beta strand

413 – 415

3

Beta strand

420 – 426

7

Turn

427 – 429

3

Beta strand

432 – 439

8

Sequences

	Sequence		Length	Mass (Da)
	Q9UK55 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 06BD47C97BBDD700	FASTA	444	50,707
	10 20 30 40 50 60 MKVVPSLLLS VLLAQVWLVP GLAPSPQSPE TPAPQNQTSR VVQAPKEEEE DEQEASEEKA 70 80 90 100 110 120 SEEEKAWLMA SRQQLAKETS NFGFSLLRKI SMRHDGNMVF SPFGMSLAMT GLMLGATGPT 130 140 150 160 170 180 ETQIKRGLHL QALKPTKPGL LPSLFKGLRE TLSRNLELGL TQGSFAFIHK DFDVKETFFN 190 200 210 220 230 240 LSKRYFDTEC VPMNFRNASQ AKRLMNHYIN KETRGKIPKL FDEINPETKL ILVDYILFKG 250 260 270 280 290 300 KWLTPFDPVF TEVDTFHLDK YKTIKVPMMY GAGKFASTFD KNFRCHVLKL PYQGNATMLV 310 320 330 340 350 360 VLMEKMGDHL ALEDYLTTDL VETWLRNMKT RNMEVFFPKF KLDQKYEMHE LLRQMGIRRI 370 380 390 400 410 420 FSPFADLSEL SATGRNLQVS RVLQRTVIEV DERGTEAVAG ILSEITAYSM PPVIKVDRPF 430 440 HFMIYEETSG MLLFLGRVVN PTLL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The protein Z-dependent protease inhibitor is a serpin." Han X., Huang Z.-F., Fiehler R., Broze G.J. Jr. Biochemistry 38:11073-11078(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF TYR-408. Tissue: Liver.
[2]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ARG-46; GLY-61; SER-161 AND ARG-384.
[3]	"Full-length cDNA libraries and normalization." Li W.B., Gruber C., Jessee J., Polayes D. Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Fetal liver.
[4]	SeattleSNPs variation discovery resource Submitted (MAY-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-46; GLY-61; ARG-139; SER-161; SER-271 AND PRO-384.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Liver.
[6]	"Isolation of a protein Z-dependent plasma protease inhibitor." Han X., Fiehler R., Broze G.J. Jr. Proc. Natl. Acad. Sci. U.S.A. 95:9250-9255(1998) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 22-33, CHARACTERIZATION. Tissue: Plasma.
[7]	"Characterization of the protein Z-dependent protease inhibitor." Han X., Fiehler R., Broze G.J. Jr. Blood 96:3049-3055(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PROZ.
[8]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-180 AND ASN-295, MASS SPECTROMETRY. Tissue: Plasma.
[9]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-36, MASS SPECTROMETRY. Tissue: Liver.
[10]	"Characterization of the heparin-binding site of the protein z-dependent protease inhibitor." Yang L., Ding Q., Huang X., Olson S.T., Rezaie A.R. Biochemistry 51:4078-4085(2012) [PubMed] [Europe PMC] [Abstract] Cited for: HEPARIN-BINDING REGION.
[11]	"Crystal structure of protein Z-dependent inhibitor complex shows how protein Z functions as a cofactor in the membrane inhibition of factor X." Wei Z., Yan Y., Carrell R.W., Zhou A. Blood 114:3662-3667(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 60-444 IN COMPLEX WITH PROZ.
[12]	"Basis for the specificity and activation of the serpin protein Z-dependent proteinase inhibitor (ZPI) as an inhibitor of membrane-associated factor Xa." Huang X., Dementiev A., Olson S.T., Gettins P.G. J. Biol. Chem. 285:20399-20409(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.26 ANGSTROMS) OF 22-444 IN COMPLEX WITH PROZ, GLYCOSYLATION AT ASN-197 AND ASN-295, SUBUNIT.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF181467 mRNA. Translation: AAD53962.1.
AY358597 mRNA. Translation: AAQ88960.1.
BX248011 mRNA. Translation: CAD62339.1. Different initiation.
EF621762 Genomic DNA. Translation: ABR09269.1.
BC022261 mRNA. Translation: AAH22261.1.

IPI

IPI00007199.

RefSeq

NP_001094077.1. NM_001100607.2.
NP_057270.1. NM_016186.2.

UniGene

Hs.118620.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3F1S	X-ray	2.30	A	60-444	[»]
3H5C	X-ray	3.26	A	22-444	[»]
4AFX	X-ray	2.09	A	23-407	[»]
			B	409-444	[»]
4AJU	X-ray	2.65	A	23-407	[»]
			B	409-444	[»]

ProteinModelPortal

Q9UK55.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UK55. 1 interaction.

STRING

9606.ENSP00000261994.

Protein family/group databases

MEROPS

I04.005.

PTM databases

PhosphoSite

Q9UK55.

Polymorphism databases

DMDM

12585541.

Proteomic databases

PaxDb

Q9UK55.

PRIDE

Q9UK55.

Protocols and materials databases

DNASU

51156.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000261994; ENSP00000261994; ENSG00000140093.
ENST00000393096; ENSP00000376809; ENSG00000140093.
ENST00000554173; ENSP00000450971; ENSG00000140093.

GeneID

51156.

KEGG

hsa:51156.

UCSC

uc001yct.3. human.

Organism-specific databases

CTD

51156.

GeneCards

GC14M094749.

HGNC

HGNC:15996. SERPINA10.

HPA

HPA048739.

MIM

602455. gene.
605271. gene+phenotype.

neXtProt

NX_Q9UK55.

PharmGKB

PA38078.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG4826.

HOGENOM

HOG000238519.

HOVERGEN

HBG101138.

InParanoid

Q9UK55.

OrthoDB

EOG4VT5X7.

PhylomeDB

Q9UK55.

Gene expression databases

ArrayExpress

Q9UK55.

Bgee

Q9UK55.

CleanEx

HS_SERPINA10.

Genevestigator

Q9UK55.

GermOnline

ENSG00000140093. Homo sapiens.

Family and domain databases

InterPro

IPR023796. Serpin_dom.
IPR000215. Serpin_fam.
[Graphical view]

PANTHER

PTHR11461. PTHR11461. 1 hit.

Pfam

PF00079. Serpin. 1 hit.
[Graphical view]

SMART

SM00093. SERPIN. 1 hit.
[Graphical view]

SUPFAM

SSF56574. Prot_inh_serpin. 1 hit.

PROSITE

PS00284. SERPIN. False negative.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9UK55.

GenomeRNAi

51156.

NextBio

54061.

SOURCE

Search...

Entry information

Entry name

ZPI_HUMAN

Accession

Primary (citable) accession number: Q9UK55
Secondary accession number(s): A5Z2A5, Q6UWX9, Q86U20

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 24, 2001
Last sequence update:	May 1, 2000
Last modified:	May 1, 2013
This is version 124 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.