The protein encoded by this gene is highly expressed in late-pregnancy serum and is similar in structure to alpha-2-macroglobulin. The encoded protein, which acts as a homotetramer, inhibits the activity of all four classes of proteinases. This protein contains cleavage sites for several proteinases. Upon binding of a proteinase, the conformation of this protein changes to trap... See more...

Aliases for PZP Gene

Aliases for PZP Gene

  • PZP Alpha-2-Macroglobulin Like 2 3 5
  • Pregnancy Zone Protein 3 3 4
  • CPAMD6 2 3 4
  • C3 And PZP-Like Alpha-2-Macroglobulin Domain-Containing Protein 6 3 4
  • Pregnancy-Zone Protein 2 3
  • PZP, Alpha-2-Macroglobulin Like 2
  • PZP 5

External Ids for PZP Gene

Previous GeneCards Identifiers for PZP Gene

  • GC12M009009
  • GC12M009449
  • GC12M009201
  • GC12M009192
  • GC12M009301

Summaries for PZP Gene

Entrez Gene Summary for PZP Gene

  • The protein encoded by this gene is highly expressed in late-pregnancy serum and is similar in structure to alpha-2-macroglobulin. The encoded protein, which acts as a homotetramer, inhibits the activity of all four classes of proteinases. This protein contains cleavage sites for several proteinases. Upon binding of a proteinase, the conformation of this protein changes to trap the proteinase, limiting its activity. This protein appears to be elevated in the sera of presymptomatic Alzheimer's disease patients. [provided by RefSeq, Dec 2016]

GeneCards Summary for PZP Gene

PZP (PZP Alpha-2-Macroglobulin Like) is a Protein Coding gene. Diseases associated with PZP include Inflammatory Bowel Disease 17 and Alzheimer Disease. Among its related pathways are Cell adhesion_Plasmin signaling. Gene Ontology (GO) annotations related to this gene include serine-type endopeptidase inhibitor activity and endopeptidase inhibitor activity. An important paralog of this gene is A2M.

UniProtKB/Swiss-Prot Summary for PZP Gene

  • Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for different proteinases. When a proteinase cleaves the bait region, a conformational change is induced in the protein which traps the proteinase. The entrapped enzyme remains active against low molecular weight substrates (activity against high molecular weight substrates is greatly reduced). Following cleavage in the bait region a thioester bond is hydrolyzed and mediates the covalent binding of the protein to the proteinase.

Gene Wiki entry for PZP Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PZP Gene

Genomics for PZP Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for PZP Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH12J009167 Promoter/Enhancer 0.8 EPDnew Ensembl ENCODE 619.1 +39.4 39394 4.4 NR2F2 PZP A2M BTG1P1 KRT17P8 KLRB1 DDX12P A2M-AS1 KLRG1 ENSG00000111788 piR-41457
GH12J009208 Promoter 0.4 EPDnew 600.7 0.0 -20 0.1 RXRA PZP piR-59297-113 LOC105376678 KLRG1
GH12J009113 Promoter/Enhancer 1.6 EPDnew Ensembl ENCODE 10.1 +92.7 92694 5.8 HNRNPL GATAD2A ATF7 REST TFE3 SOX13 NFKBIZ RCOR2 GABPA RBFOX2 A2M lnc-PZP-6 ENSG00000111788 DDX12P ENSG00000255753 LINC00612 M6PR ENSG00000213443 KLRG1 PZP
GH12J009240 Promoter/Enhancer 1.4 EPDnew Ensembl ENCODE CraniofacialAtlas 11.2 -32.1 -32105 1.4 YY1 RAD21 ZNF513 ENSG00000256427 LINC00987 MIR1244-3 PTMAP4 lnc-PZP-5 A2MP1 DDX12P PZP LINC02367 ENSG00000111788
GH12J009756 Promoter/Enhancer 2.1 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 5.1 -552.9 -552935 10.1 SP1 HNRNPL LEF1 IKZF1 POLR2A BACH1 JUND ETV6 RELA PKNOX1 CD69 lnc-CLEC2D-11 lnc-CD69-1 CLECL1 KLRF1 DDX12P ENSG00000213443 CLEC7A KLRA1P ENSG00000111788
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PZP on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PZP

Top Transcription factor binding sites by QIAGEN in the PZP gene promoter:
  • Nkx2-2

Genomic Locations for PZP Gene

Genomic Locations for PZP Gene
chr12:9,140,730-9,208,395
(GRCh38/hg38)
Size:
67,666 bases
Orientation:
Minus strand
chr12:9,301,436-9,360,966
(GRCh37/hg19)
Size:
59,531 bases
Orientation:
Minus strand

Genomic View for PZP Gene

Genes around PZP on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PZP Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PZP Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PZP Gene

Proteins for PZP Gene

  • Protein details for PZP Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P20742-PZP_HUMAN
    Recommended name:
    Pregnancy zone protein
    Protein Accession:
    P20742
    Secondary Accessions:
    • A6ND27
    • Q15273
    • Q2NKL2
    • Q7M4N7

    Protein attributes for PZP Gene

    Size:
    1482 amino acids
    Molecular mass:
    163863 Da
    Quaternary structure:
    • Homotetramer, which consists of two pairs of disulfide-linked chains.

    Alternative splice isoforms for PZP Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PZP Gene

Post-translational modifications for PZP Gene

  • Glycosylation at Asn54, Asn69, Asn246, Asn392, Asn406, Asn753, Asn932, Asn997, Asn875, and Asn1430
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect

No data available for DME Specific Peptides for PZP Gene

Domains & Families for PZP Gene

Gene Families for PZP Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Plasma proteins
  • Predicted secreted proteins

Protein Domains for PZP Gene

InterPro:
Blocks:
  • Alpha-2-macroglobulin
  • Alpha-2-macroglobulin, N-terminal
  • Alpha-macroglobulin, receptor-binding
ProtoNet:

Suggested Antigen Peptide Sequences for PZP Gene

GenScript: Design optimal peptide antigens:
  • C3 and PZP-like alpha-2-macroglobulin domain-containing protein 6 (PZP_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P20742

UniProtKB/Swiss-Prot:

PZP_HUMAN :
  • Belongs to the protease inhibitor I39 (alpha-2-macroglobulin) family.
Family:
  • Belongs to the protease inhibitor I39 (alpha-2-macroglobulin) family.
genes like me logo Genes that share domains with PZP: view

Function for PZP Gene

Molecular function for PZP Gene

UniProtKB/Swiss-Prot Function:
Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for different proteinases. When a proteinase cleaves the bait region, a conformational change is induced in the protein which traps the proteinase. The entrapped enzyme remains active against low molecular weight substrates (activity against high molecular weight substrates is greatly reduced). Following cleavage in the bait region a thioester bond is hydrolyzed and mediates the covalent binding of the protein to the proteinase.
GENATLAS Biochemistry:
pregnancy zone protein (see A2MR@)

Phenotypes From GWAS Catalog for PZP Gene

Gene Ontology (GO) - Molecular Function for PZP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002020 protease binding IBA 21873635
GO:0004866 endopeptidase inhibitor activity TAS 2476433
GO:0004867 serine-type endopeptidase inhibitor activity IEA --
GO:0030414 peptidase inhibitor activity IEA --
genes like me logo Genes that share ontologies with PZP: view
genes like me logo Genes that share phenotypes with PZP: view

Animal Model Products

  • Taconic Biosciences Mouse Models for PZP

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PZP

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , miRNA , Transcription Factor Targets and HOMER Transcription for PZP Gene

Localization for PZP Gene

Subcellular locations from UniProtKB/Swiss-Prot for PZP Gene

Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PZP gene
Compartment Confidence
extracellular 5
plasma membrane 3
endoplasmic reticulum 2
cytoskeleton 1
mitochondrion 1
nucleus 1
cytosol 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for PZP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region NAS 14718574
GO:0005615 extracellular space IBA --
GO:0062023 colocalizes_with collagen-containing extracellular matrix HDA 28327460
GO:0070062 extracellular exosome HDA 21362503
GO:0072562 blood microparticle HDA 22516433
genes like me logo Genes that share ontologies with PZP: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for PZP Gene

Pathways & Interactions for PZP Gene

PathCards logo

SuperPathways for PZP Gene

SuperPathway Contained pathways
1 Cell adhesion_Plasmin signaling
-
genes like me logo Genes that share pathways with PZP: view

Pathways by source for PZP Gene

1 GeneGo (Thomson Reuters) pathway for PZP Gene
  • Cell adhesion_Plasmin signaling

Gene Ontology (GO) - Biological Process for PZP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007565 female pregnancy TAS 2692707
GO:0010466 negative regulation of peptidase activity IEA --
GO:0010951 negative regulation of endopeptidase activity IEA --
genes like me logo Genes that share ontologies with PZP: view

No data available for SIGNOR curated interactions for PZP Gene

Drugs & Compounds for PZP Gene

(5) Drugs for PZP Gene - From: DrugBank and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Zinc Approved, Investigational Pharma Target 1594
zinc acetate Approved, Investigational Pharma Target 0
Zinc chloride Approved, Investigational Pharma Target, binder 0
Zinc sulfate, unspecified form Approved, Experimental Pharma Target, binder 0

(1) Additional Compounds for PZP Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with PZP: view

Transcripts for PZP Gene

mRNA/cDNA for PZP Gene

1 REFSEQ mRNAs :
6 NCBI additional mRNA sequence :
7 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PZP

Alternative Splicing Database (ASD) splice patterns (SP) for PZP Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3a · 3b
SP1: -
SP2:

Relevant External Links for PZP Gene

GeneLoc Exon Structure for
PZP

Expression for PZP Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PZP Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for PZP Gene

This gene is overexpressed in Liver (x33.4).

Protein differential expression in normal tissues from HIPED for PZP Gene

This gene is overexpressed in Plasma (20.6), Serum (16.4), Amniocyte (13.9), and Skin (6.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for PZP Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PZP

SOURCE GeneReport for Unigene cluster for PZP Gene:

Hs.707491

mRNA Expression by UniProt/SwissProt for PZP Gene:

P20742-PZP_HUMAN
Tissue specificity: Plasma. Prominent constituent of late-pregnancy sera.

Evidence on tissue expression from TISSUES for PZP Gene

  • Liver(4.6)
  • Bone marrow(4.1)
  • Heart(3.5)
  • Adrenal gland(3.2)
  • Kidney(3.2)
  • Pancreas(3.1)
  • Blood(3)
  • Eye(2.9)
  • Intestine(2.4)
  • Lung(2.3)
  • Nervous system(2.3)
  • Gall bladder(2.1)
genes like me logo Genes that share expression patterns with PZP: view

No data available for Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for PZP Gene

Orthologs for PZP Gene

This gene was present in the common ancestor of chordates.

Orthologs for PZP Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia PZP 30 31
  • 99.35 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia -- 31
  • 59 (a)
ManyToMany
Oppossum
(Monodelphis domestica)
Mammalia -- 31
  • 59 (a)
OneToMany
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 58 (a)
ManyToMany
-- 31
  • 54 (a)
ManyToMany
-- 31
  • 41 (a)
ManyToMany
Cow
(Bos Taurus)
Mammalia -- 31
  • 56 (a)
ManyToMany
Mouse
(Mus musculus)
Mammalia Mug2 31
  • 56 (a)
ManyToMany
Chicken
(Gallus gallus)
Aves -- 31
  • 58 (a)
ManyToMany
-- 31
  • 55 (a)
ManyToMany
-- 31
  • 53 (a)
ManyToMany
Lizard
(Anolis carolinensis)
Reptilia -- 31
  • 50 (a)
ManyToMany
-- 31
  • 49 (a)
ManyToMany
African clawed frog
(Xenopus laevis)
Amphibia MGC68875 30
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia Str.8331 30
Species where no ortholog for PZP was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rat (Rattus norvegicus)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)
  • Zebrafish (Danio rerio)

Evolution for PZP Gene

ENSEMBL:
Gene Tree for PZP (if available)
TreeFam:
Gene Tree for PZP (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PZP: view image

Paralogs for PZP Gene

Paralogs for PZP Gene

(5) SIMAP similar genes for PZP Gene using alignment to 3 proteins:

  • PZP_HUMAN
  • F5GXY0_HUMAN
  • L8EC98_HUMAN

Pseudogenes.org Pseudogenes for PZP Gene

genes like me logo Genes that share paralogs with PZP: view

Variants for PZP Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PZP Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
715780 Benign: not provided 9,197,002(-) G/A INTRON_VARIANT
755661 Likely Benign: not provided 9,150,686(-) A/G SYNONYMOUS_VARIANT
769813 Benign: not provided 9,165,289(-) G/A SYNONYMOUS_VARIANT
778583 Benign: not provided 9,181,999(-) C/T SYNONYMOUS_VARIANT
779517 Benign: not provided 9,158,429(-) A/G SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for PZP Gene

Structural Variations from Database of Genomic Variants (DGV) for PZP Gene

Variant ID Type Subtype PubMed ID
nsv1051530 CNV gain 25217958
nsv469101 CNV loss 19166990
nsv523958 CNV loss 19592680
nsv527404 CNV gain 19592680
nsv557355 CNV gain 21841781
nsv557356 CNV loss 21841781
nsv983273 CNV duplication 23825009

Variation tolerance for PZP Gene

Residual Variation Intolerance Score: 88.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 16.89; 97.95% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PZP Gene

Human Gene Mutation Database (HGMD)
PZP
SNPedia medical, phenotypic, and genealogical associations of SNPs for
PZP

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PZP Gene

Disorders for PZP Gene

MalaCards: The human disease database

(2) MalaCards diseases for PZP Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
inflammatory bowel disease 17
  • ibd17
alzheimer disease
  • ad
- elite association - COSMIC cancer census association via MalaCards
Search PZP in MalaCards View complete list of genes associated with diseases

Additional Disease Information for PZP

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with PZP: view

No data available for UniProtKB/Swiss-Prot and Genatlas for PZP Gene

Publications for PZP Gene

  1. Primary structure of pregnancy zone protein. Molecular cloning of a full-length PZP cDNA clone by the polymerase chain reaction. (PMID: 1989698) Devriendt K … Marynen P (Biochimica et biophysica acta 1991) 3 4 23
  2. A genetic polymorphism in a functional domain of human pregnancy zone protein: the bait region. Genomic structure of the bait domains of human pregnancy zone protein and alpha 2 macroglobulin. (PMID: 1692292) Marynen P … Cassiman JJ (FEBS letters 1990) 3 4 23
  3. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41
  4. Genome-wide association study identifies variants associated with histologic features of nonalcoholic Fatty liver disease. (PMID: 20708005) Chalasani N … Nonalcoholic Steatohepatitis Clinical Research Network (Gastroenterology 2010) 3 41
  5. An association analysis of Alzheimer disease candidate genes detects an ancestral risk haplotype clade in ACE and putative multilocus association between ACE, A2M, and LRRTM3. (PMID: 19105203) Edwards TL … Ritchie MD (American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2009) 3 41

Products for PZP Gene

  • Boster Bio Antibodies for PZP
  • Boster Bio ELISA Kits for PZP

Sources for PZP Gene