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    PROZ protein Z, vitamin K dependent plasma glycoprotein [ Homo sapiens (human) ]

    Gene ID: 8858, updated on 10-Dec-2024

    Summary

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    Official Symbol
    PROZprovided by HGNC
    Official Full Name
    protein Z, vitamin K dependent plasma glycoproteinprovided by HGNC
    Primary source
    HGNC:HGNC:9460
    See related
    Ensembl:ENSG00000126231 MIM:176895; AllianceGenome:HGNC:9460
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    PZ
    Summary
    This gene encodes a liver vitamin K-dependent glycoprotein that is synthesized in the liver and secreted into the plasma. The encoded protein plays a role in regulating blood coagulation by complexing with protein Z-dependent protease inhibitor to directly inhibit activated factor X at the phospholipid surface. Deficiencies in this protein are associated with an increased risk of ischemic arterial diseases and fetal loss. Mutations in this gene are the cause of protein Z deficiency. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]
    Expression
    Biased expression in liver (RPKM 5.4), kidney (RPKM 4.0) and 1 other tissue See more
    Orthologs
    mouse all
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    Genomic context

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    See PROZ in Genome Data Viewer
    Location:
    13q34
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 13 NC_000013.11 (113158648..113172386)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 13 NC_060937.1 (112406247..112424058)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 13 NC_000013.10 (113812962..113826700)

    Chromosome 13 - NC_000013.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5538 Neighboring gene uncharacterized LOC124903216 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:113812445-113813022 Neighboring gene F10 antisense RNA 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:113813599-113814176 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:113825981-113826504 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:113827099-113827599 Neighboring gene PCI domain containing 2 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr13:113841395-113842594 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:113862038-113862688 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:113862689-113863338 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5540 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5541 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5542 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:113874723-113875286 Neighboring gene cullin 4A Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:113876707-113877556 Neighboring gene microRNA 8075 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:113928297-113928796 Neighboring gene Sharpr-MPRA regulatory region 2925 Neighboring gene lactate dehydrogenase B pseudogene 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. A meta-analysis of potential risks of low levels of protein Z for diseases related to vascular thrombosis. Sofi F, et al. Thromb Haemost, 2010 Apr. PMID 20076855, Free PMC Article
    2. A naturally occurring E30Q mutation in the Gla domain of protein Z causes its impaired secretion and subsequent deficiency. Souri M, et al. Blood, 2005 Apr 15. PMID 15626740
    3. Intron F G79A polymorphism of the protein Z gene in Turkish Behçet patients. Demir HD, et al. Curr Eye Res, 2012 Jul. PMID 22559296
    4. Protein Z concentrations in patients with acute leukemia. Galar M, et al. Clin Appl Thromb Hemost, 2012 Sep. PMID 22297560
    5. Protein Z in normal pregnancy. Quack Loetscher KC, et al. Thromb Haemost, 2005 Apr. PMID 15841316

    See all (101) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Expression and diagnostic value of plasma protein Z and protein Z-dependent protease inhibitor in fetal growth restriction.
      Title: Expression and diagnostic value of plasma protein Z and protein Z-dependent protease inhibitor in fetal growth restriction.
    2. The Proteolytic Inactivation of Protein Z-Dependent Protease Inhibitor by Neutrophil Elastase Might Promote the Procoagulant Activity of Neutrophil Extracellular Traps in Sepsis.
      Title: The Proteolytic Inactivation of Protein Z-Dependent Protease Inhibitor by Neutrophil Elastase Might Promote the Procoagulant Activity of Neutrophil Extracellular Traps in Sepsis.
    3. Association of Protein Z with Prediabetes and Type 2 Diabetes.
      Title: Association of Protein Z with Prediabetes and Type 2 Diabetes.
    4. Data show that women with intrauterine growth restriction (IUGR) had significantly higher mean plasma concentrations of protein Z compared to women with normal pregnancies.
      Title: The Relationship between Z-Protein Level and other Parameters in Pregnant Women with Intrauterine Growth Retardation in Third Trimester.
    5. Protein Z-79 G/A gene polymorphism may be of a protective value against thrombosis in antiphospholipid syndrome (APS). The G79A polymorphism of protein Z was not found to be an independent risk factor of thrombosis in APS.
      Title: The relation between protein Z polymorphism and the risk of thrombosis in Egyptian patients with antiphospholipid syndrome.
    6. Polymorphisms of F2, PROC, PROZ, and F13A1 Genes are Associated With Recurrent Spontaneous Abortion in Chinese Han Women.
      Title: Polymorphisms of F2, PROC, PROZ, and F13A1 Genes are Associated With Recurrent Spontaneous Abortion in Chinese Han Women.
    7. Low PZ appears to be an underestimated risk factor for perioperative bleeding. Determination of PZ plasma concentrations might be useful in the preoperative workup in patients with a bleeding history, when detailed clotting analyses remain inconclusive.
      Title: Low plasma protein Z levels are associated with an increased risk for perioperative bleedings.
    8. PZ/ZPI polymorphisms do not appear to play an active role in the development of prosthesis heart valve thrombosis.
      Title: The Role of Protein Z and Protein Z-Dependent Protease Inhibitor Polymorphisms in the Development of Prosthetic Heart Valve Thrombosis.
    9. Report evidence of a non-linear positive association between PZ level and unexplained stroke, with a directionally consistent association for genetic variants related to PZ levels and cryptogenic stroke.
      Title: Circulating protein Z concentration, PROZ variants, and unexplained cerebral infarction in young and middle-aged adults.
    10. Data suggest oxidized lipid vesicles with phosphatidylserine/polyunsaturated fatty acids promote inactivation of ZPI-PZ complex or free ZPI; binding of PZ-complexed or free ZPI to oxidized vesicles mediates inactivation of ZPI (an inhibitor of FXa); blocking heparin- (anticoagulant-)binding site on ZPI interferes with binding to lipid or PZ. (ZPI = protein Z-dependent protease inhibitor; PZ = protein Z; FXa = factor Xa)
      Title: Lipid oxidation inactivates the anticoagulant function of protein Z-dependent protease inhibitor (ZPI).
    Submit: New GeneRIF Correction See all GeneRIFs (80)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Protein Z deficiency
    MedGen: C3151465 OMIM: 614024 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    Genome-wide association and linkage analyses of hemostatic factors and hematological phenotypes in the Framingham Heart Study.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables calcium ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables serine-type endopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in blood coagulation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in proteolysis IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in Golgi lumen TAS
    Traceable Author Statement
    more info
    		  
    located_in endoplasmic reticulum lumen TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    vitamin K-dependent protein Z

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_031993.2 RefSeqGene

      Range
      4995..18733
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_573

    mRNA and Protein(s)

    1. NM_001256134.2 → NP_001243063.1  vitamin K-dependent protein Z isoform 1 precursor

      See identical proteins and their annotated locations for NP_001243063.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AL137002
      Consensus CDS
      CCDS58300.1
      UniProtKB/TrEMBL
      B0YJC6
      Related
      ENSP00000344458.4, ENST00000342783.5
      Conserved Domains (5) summary
      smart00069
      Location:44 → 108
      GLA; Domain containing Gla (gamma-carboxyglutamate) residues
      cd00054
      Location:117 → 145
      EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...
      pfam00089
      Location:211 → 363
      Trypsin; Trypsin
      pfam14670
      Location:158 → 187
      FXa_inhibition; Coagulation Factor Xa inhibitory site
      cl21584
      Location:211 → 363
      Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

    2. NM_003891.3 → NP_003882.1  vitamin K-dependent protein Z isoform 2 precursor

      See identical proteins and their annotated locations for NP_003882.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an in-frame exon in the coding region, compared to variant 1. The encoded isoform (2) is shorter, compared to isoform 1.
      Source sequence(s)
      AL137002
      Consensus CDS
      CCDS9531.1
      UniProtKB/Swiss-Prot
      A6NMB4, P22891, Q15213, Q5JVF5, Q5JVF6
      UniProtKB/TrEMBL
      B0YJC6
      Related
      ENSP00000364697.2, ENST00000375547.7
      Conserved Domains (4) summary
      smart00069
      Location:22 → 86
      GLA; Domain containing Gla (gamma-carboxyglutamate) residues
      cd00054
      Location:95 → 123
      EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...
      pfam00089
      Location:189 → 341
      Trypsin; Trypsin
      pfam14670
      Location:136 → 165
      FXa_inhibition; Coagulation Factor Xa inhibitory site

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000013.11 Reference GRCh38.p14 Primary Assembly

      Range
      113158648..113172386
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017020813.2 → XP_016876302.1  vitamin K-dependent protein Z isoform X1

    2. XM_047430720.1 → XP_047286676.1  vitamin K-dependent protein Z isoform X2

    3. XM_047430721.1 → XP_047286677.1  vitamin K-dependent protein Z isoform X3

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060937.1 Alternate T2T-CHM13v2.0

      Range
      112406247..112424058
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054375111.1 → XP_054231086.1  vitamin K-dependent protein Z isoform X5

    2. XM_054375110.1 → XP_054231085.1  vitamin K-dependent protein Z isoform X4

      UniProtKB/TrEMBL
      B0YJC6

    RNA

    1. XR_008488790.1 RNA Sequence

    2. XR_008488791.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P22891.2 GenPept UniProtKB/Swiss-Prot:P22891

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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