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    PZP PZP alpha-2-macroglobulin like [ Homo sapiens (human) ]

    Gene ID: 5858, updated on 3-Apr-2024

    Summary

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    Official Symbol
    PZPprovided by HGNC
    Official Full Name
    PZP alpha-2-macroglobulin likeprovided by HGNC
    Primary source
    HGNC:HGNC:9750
    See related
    Ensembl:ENSG00000126838 MIM:176420; AllianceGenome:HGNC:9750
    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
    CPAMD6
    Summary
    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]
    Expression
    Biased expression in liver (RPKM 5.3), endometrium (RPKM 1.0) and 2 other tissues See more
    Orthologs
    all
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    Genomic context

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    Location:
    12p13.31
    Exon count:
    39
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (9136472..9208395, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (9131038..9191012, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (9301436..9360991, complement)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene killer cell lectin like receptor G1 Neighboring gene keratin 17 pseudogene 8 Neighboring gene BTG anti-proliferation factor 1 pseudogene 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:9322697-9323208 Neighboring gene TPT1 pseudogene 12 Neighboring gene microRNA 1244-3 Neighboring gene alpha-2-macroglobulin pseudogene 1 Neighboring gene prothymosin alpha pseudogene 4

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Hypermethylation of the PZP gene is associated with hepatocellular carcinoma cell proliferation, invasion and migration. Wu M, et al. FEBS Open Bio, 2021 Mar. PMID 33471436, Free PMC Article
    2. Genetic ablation of pregnancy zone protein promotes breast cancer progression by activating TGF-β/SMAD signaling. Kumar R, et al. Breast Cancer Res Treat, 2021 Jan. PMID 33057846
    3. Human pregnancy zone protein stabilizes misfolded proteins including preeclampsia- and Alzheimer's-associated amyloid beta peptide. Cater JH, et al. Proc Natl Acad Sci U S A, 2019 Mar 26. PMID 30850528, Free PMC Article
    4. PZP and PAI-2: Structurally-diverse, functionally similar pregnancy proteins? Wyatt AR, et al. Int J Biochem Cell Biol, 2016 Oct. PMID 27554634
    5. Pregnancy Zone Protein is Increased in the Alzheimer's Disease Brain and Associates with Senile Plaques. Nijholt DA, et al. J Alzheimers Dis, 2015. PMID 25737043

    See all (43) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. High-Level Secretion of Pregnancy Zone Protein Is a Novel Biomarker of DNA Damage-Induced Senescence and Promotes Spontaneous Senescence.
      Title: High-Level Secretion of Pregnancy Zone Protein Is a Novel Biomarker of DNA Damage-Induced Senescence and Promotes Spontaneous Senescence.
    2. The Pregnancy Zone Protein (PZP) is significantly downregulated in the placenta of preeclampsia and HELLP syndrome patients.
      Title: The Pregnancy Zone Protein (PZP) is significantly downregulated in the placenta of preeclampsia and HELLP syndrome patients.
    3. Hypermethylation of the PZP gene is associated with hepatocellular carcinoma cell proliferation, invasion and migration.
      Title: Hypermethylation of the PZP gene is associated with hepatocellular carcinoma cell proliferation, invasion and migration.
    4. Pregnancy Zone Protein (PZP) is significantly upregulated in the decidua of recurrent and spontaneous miscarriage and negatively correlated to Glycodelin A (GdA).
      Title: Pregnancy Zone Protein (PZP) is significantly upregulated in the decidua of recurrent and spontaneous miscarriage and negatively correlated to Glycodelin A (GdA).
    5. Genetic ablation of pregnancy zone protein promotes breast cancer progression by activating TGF-beta/SMAD signaling.
      Title: Genetic ablation of pregnancy zone protein promotes breast cancer progression by activating TGF-β/SMAD signaling.
    6. Inflammation-associated LRG and PZP may be novel biomarkers of early-onset myocardial infarction
      Title: Screening and Identification of Pregnancy Zone Protein and Leucine-Rich Alpha-2-Glycoprotein as Potential Serum Biomarkers for Early-Onset Myocardial Infarction using Protein Profile Analysis.
    7. stabilizes misfolded proteins including preeclampsia- and Alzheimer's-associated amyloid beta peptide
      Title: Human pregnancy zone protein stabilizes misfolded proteins including preeclampsia- and Alzheimer's-associated amyloid beta peptide.
    8. The data of this study link the finding of elevated serum PZP levels with the characteristic Alzheimer's Disease pathology and identify PZP as a novel component in Alzheimer's Disease.
      Title: Pregnancy Zone Protein is Increased in the Alzheimer's Disease Brain and Associates with Senile Plaques.
    9. Quantitative measurements using a multiple reaction monitoring assay showed a significant increase in plasma pregnancy-zone protein in presymptomatic Alzheimer disease compared with controls
      Title: Serum levels of pregnancy zone protein are elevated in presymptomatic Alzheimer's disease.
    10. Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
      Title: Genome-wide association study identifies variants associated with histologic features of nonalcoholic Fatty liver disease.
    Submit: New GeneRIF Correction See all GeneRIFs (14)

    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

    EBI GWAS Catalog

    Description
    Genome-wide association study identifies variants associated with histologic features of nonalcoholic Fatty liver disease.
    EBI GWAS Catalog
    Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
    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)

    Genotypes

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC133093

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables endopeptidase inhibitor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables endopeptidase inhibitor activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables protease binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables serine-type endopeptidase inhibitor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in female pregnancy TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in blood microparticle HDA PubMed 
    colocalizes_with collagen-containing extracellular matrix HDA PubMed 
    located_in extracellular exosome HDA PubMed 
    located_in extracellular region NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    pregnancy zone protein
    Names
    C3 and PZP-like alpha-2-macroglobulin domain-containing protein 6
    Pregnancy zone protein
    pregnancy-zone protein

    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_052998.1 RefSeqGene

      Range
      4976..64531
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_002864.3 → NP_002855.2  pregnancy zone protein precursor

      See identical proteins and their annotated locations for NP_002855.2

      Status: REVIEWED

      Source sequence(s)
      AC010175, DB040351, X54380
      Consensus CDS
      CCDS8600.1
      UniProtKB/Swiss-Prot
      A6ND27, P20742, Q15273, Q2NKL2, Q7M4N7
      UniProtKB/TrEMBL
      B2R950
      Related
      ENSP00000261336.2, ENST00000261336.7
      Conserved Domains (7) summary
      cd02897
      Location:964 → 1270
      A2M_2; Proteins similar to alpha2-macroglobulin (alpha (2)-M). This group also contains the pregnancy zone protein (PZP). Alpha(2)-M and PZP are broadly specific proteinase inhibitors. Alpha (2)-M is a major carrier protein in serum. The structural thioester ...
      pfam00207
      Location:744 → 834
      A2M; Alpha-2-macroglobulin family
      pfam01835
      Location:128 → 220
      A2M_N; MG2 domain
      pfam05326
      Location:796 → 891
      SVA; Seminal vesicle autoantigen (SVA)
      pfam07677
      Location:1382 → 1469
      A2M_recep; A-macroglobulin receptor
      pfam07678
      Location:1016 → 1272
      A2M_comp; A-macroglobulin complement component
      pfam07703
      Location:457 → 602
      A2M_N_2; Alpha-2-macroglobulin family N-terminal region

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      9136472..9208395 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047429274.1 → XP_047285230.1  pregnancy zone protein isoform X3

    2. XM_017019763.2 → XP_016875252.1  pregnancy zone protein isoform X1

      UniProtKB/TrEMBL
      B2R950
      Conserved Domains (7) summary
      cd02897
      Location:964 → 1270
      A2M_2; Proteins similar to alpha2-macroglobulin (alpha (2)-M). This group also contains the pregnancy zone protein (PZP). Alpha(2)-M and PZP are broadly specific proteinase inhibitors. Alpha (2)-M is a major carrier protein in serum. The structural thioester ...
      pfam00207
      Location:744 → 834
      A2M; Alpha-2-macroglobulin family
      pfam01835
      Location:128 → 220
      A2M_N; MG2 domain
      pfam05326
      Location:796 → 891
      SVA; Seminal vesicle autoantigen (SVA)
      pfam07677
      Location:1382 → 1464
      A2M_recep; A-macroglobulin receptor
      pfam07678
      Location:1016 → 1272
      A2M_comp; A-macroglobulin complement component
      pfam07703
      Location:457 → 602
      A2M_N_2; Alpha-2-macroglobulin family N-terminal region

    3. XM_047429276.1 → XP_047285232.1  pregnancy zone protein isoform X8

    4. XM_047429275.1 → XP_047285231.1  pregnancy zone protein isoform X7

    5. XM_017019764.2 → XP_016875253.1  pregnancy zone protein isoform X2

      UniProtKB/TrEMBL
      B2R950

    6. XM_024449111.1 → XP_024304879.1  pregnancy zone protein isoform X4

      UniProtKB/TrEMBL
      B2R950
      Conserved Domains (5) summary
      cd02897
      Location:750 → 1056
      A2M_2; Proteins similar to alpha2-macroglobulin (alpha (2)-M). This group also contains the pregnancy zone protein (PZP). Alpha(2)-M and PZP are broadly specific proteinase inhibitors. Alpha (2)-M is a major carrier protein in serum. The structural thioester ...
      pfam00207
      Location:613 → 700
      A2M; Alpha-2-macroglobulin family
      pfam01835
      Location:12 → 89
      A2M_N; MG2 domain
      pfam07677
      Location:1168 → 1255
      A2M_recep; A-macroglobulin receptor
      pfam07703
      Location:324 → 472
      A2M_N_2; Alpha-2-macroglobulin family N-terminal region

    7. XM_011520806.2 → XP_011519108.1  pregnancy zone protein isoform X5

      Conserved Domains (5) summary
      pfam00207
      Location:744 → 834
      A2M; Alpha-2-macroglobulin family
      pfam01835
      Location:128 → 220
      A2M_N; MG2 domain
      pfam05326
      Location:796 → 891
      SVA; Seminal vesicle autoantigen (SVA)
      pfam07703
      Location:457 → 602
      A2M_N_2; Alpha-2-macroglobulin family N-terminal region
      cl08267
      Location:964 → 1045
      ISOPREN_C2_like; This group contains class II terpene cyclases, protein prenyltransferases beta subunit, two broadly specific proteinase inhibitors alpha2-macroglobulin (alpha (2)-M) and pregnancy zone protein (PZP) and, the C3 C4 and C5 components of vertebrate ...

    8. XM_011520807.3 → XP_011519109.1  pregnancy zone protein isoform X6

      Conserved Domains (3) summary
      pfam00207
      Location:744 → 830
      A2M; Alpha-2-macroglobulin family
      pfam01835
      Location:128 → 220
      A2M_N; MG2 domain
      pfam07703
      Location:457 → 602
      A2M_N_2; Alpha-2-macroglobulin family N-terminal region

    RNA

    1. XR_001748834.2 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      9131038..9191012 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    RNA

    1. XR_008488655.1 RNA Sequence

    2. XR_008488654.1 RNA Sequence

    3. XR_008488653.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P20742.4 GenPept UniProtKB/Swiss-Prot:P20742

    Gene LinkOut

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