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    PAPPA pappalysin 1 [ Homo sapiens (human) ]

    Gene ID: 5069, updated on 2-Nov-2024

    Summary

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    Official Symbol
    PAPPAprovided by HGNC
    Official Full Name
    pappalysin 1provided by HGNC
    Primary source
    HGNC:HGNC:8602
    See related
    Ensembl:ENSG00000182752 MIM:176385; AllianceGenome:HGNC:8602
    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
    PAPA; DIPLA1; PAPP-A; PAPPA1; ASBABP2; IGFBP-4ase
    Summary
    This gene encodes a secreted metalloproteinase which cleaves insulin-like growth factor binding proteins (IGFBPs). Following IGFBP cleavage, insulin growth factors dissociate from IGFBPs and bind to IGF receptors, resulting in activation of the IGF pathway. The encoded protein plays a role in bone formation, inflammation, wound healing and female fertility. Enhanced expression of this protein is associated with diabetic nephropathy in human patients and this protein may promote tumor invasion and growth in various human cancers. [provided by RefSeq, Aug 2017]
    Expression
    Biased expression in placenta (RPKM 34.5) and kidney (RPKM 1.5) See more
    Orthologs
    mouse all
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    Genomic context

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    See PAPPA in Genome Data Viewer
    Location:
    9q33.1
    Exon count:
    22
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 9 NC_000009.12 (116153791..116402321)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 9 NC_060933.1 (128346843..128595327)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (118916070..119164600)

    Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124902258 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr9:118706021-118707220 Neighboring gene uncharacterized LOC105376236 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20219 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:118918797-118919298 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:118919299-118919798 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr9:119034400-119035064 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr9:119041319-119041950 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr9:119044717-119045395 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr9:119048252-119048828 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr9:119048829-119049403 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr9:119093474-119094066 Neighboring gene PAPPA antisense RNA 2 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr9:119117289-119117861 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28883 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20220 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:119157715-119158214 Neighboring gene ReSE screen-validated silencer GRCh37_chr9:119185010-119185266 Neighboring gene PAPPA antisense RNA 1 Neighboring gene GATA motif-containing MPRA enhancer 254 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr9:119233104-119233695 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr9:119233696-119234286 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:119243946-119244892 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_106426 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr9:119301784-119302983 Neighboring gene Sharpr-MPRA regulatory region 10185 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_106457 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_106460 Neighboring gene ASTN2 antisense RNA 1 Neighboring gene astrotactin 2 Neighboring gene uncharacterized LOC107987014

    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. Homodimeric pregnancy-associated plasma protein-A in normal human placenta of first and third trimester of pregnancy: biochemical and morphological observations. D'Elia P, et al. Placenta, 2012 Nov. PMID 23010598
    2. Association of pregnancy-associated plasma protein-A gene polymorphism with ischemic stroke in northern Chinese Han population. Zhu R, et al. Neurol Res, 2014 Feb. PMID 24099568
    3. Additive effect of factors related to assisted conception on the reduction of maternal serum pregnancy-associated plasma protein A concentrations and the increased false-positive rates in first-trimester Down syndrome screening. Bellver J, et al. Fertil Steril, 2013 Nov. PMID 23891271
    4. Elevated pregnancy-associated plasma protein A predicts myocardial dysfunction and death in severe sepsis. Zhang Z, et al. Ann Clin Biochem, 2014 Jan. PMID 23880622
    5. Relation between serum PAPP-A level and umbilical cord thickness during first trimester of pregnancy. Duran M, et al. J Matern Fetal Neonatal Med, 2014 Mar. PMID 23795813

    See all (288) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Specific cleavage of IGFBP-4 by papp-a in nervous tissue.
      Title: Specific cleavage of IGFBP-4 by papp-a in nervous tissue.
    2. TGFbeta1, SNAIL2, and PAPP-A Expression in Placenta of Gestational Diabetes Mellitus Patients.
      Title: TGFβ1, SNAIL2, and PAPP-A Expression in Placenta of Gestational Diabetes Mellitus Patients.
    3. Serum hydroxysteroid (17beta) dehydrogenase 1 concentration in pregnant women correlates with pregnancy-associated plasma protein A but does not serve as an independent marker for preeclampsiadagger.
      Title: Serum hydroxysteroid (17beta) dehydrogenase 1 concentration in pregnant women correlates with pregnancy-associated plasma protein A but does not serve as an independent marker for preeclampsia†.
    4. Correlation between PAPP-A serum levels in the first trimester of pregnancy with the occurrence of gestational diabetes, a multicenter cohort study.
      Title: Correlation between PAPP-A serum levels in the first trimester of pregnancy with the occurrence of gestational diabetes, a multicenter cohort study.
    5. The Pregnancy-Associated Plasma Protein-A (PAPP-A) Story.
      Title: The Pregnancy-Associated Plasma Protein-A (PAPP-A) Story.
    6. Elevated first-trimester PAPP-A is a marker in high-risk pregnancies with an increased risk of placenta accreta in predicting adverse outcomes.
      Title: Elevated first-trimester PAPP-A is a marker in high-risk pregnancies with an increased risk of placenta accreta in predicting adverse outcomes.
    7. m[6]A mRNA methylation regulates the ERK/NF-kappaB/AKT signaling pathway through the PAPPA/IGFBP4 axis to promote proliferation and tumor formation in endometrial cancer.
      Title: m(6)A mRNA methylation regulates the ERK/NF-κB/AKT signaling pathway through the PAPPA/IGFBP4 axis to promote proliferation and tumor formation in endometrial cancer.
    8. Associations between nausea and vomiting in pregnancy, disgust sensitivity, and first-trimester maternal serum free beta-hCG and PAPP-A.
      Title: Associations between nausea and vomiting in pregnancy, disgust sensitivity, and first-trimester maternal serum free β-hCG and PAPP-A.
    9. PAPP-A-Specific IGFBP-4 Proteolysis in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.
      Title: PAPP-A-Specific IGFBP-4 Proteolysis in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.
    10. Senescence induces proteolytically-active PAPP-A secretion and association with extracellular vesicles in human pre-adipocytes.
      Title: Senescence induces proteolytically-active PAPP-A secretion and association with extracellular vesicles in human pre-adipocytes.
    Submit: New GeneRIF Correction See all GeneRIFs (239)

    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 of maternal and inherited loci for conotruncal heart defects.
    EBI GWAS Catalog
    Hundreds of variants clustered in genomic loci and biological pathways affect human height.
    EBI GWAS Catalog
    Identification of ten loci associated with height highlights new biological pathways in human growth.
    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)

    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 metalloendopeptidase activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables metalloendopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables metalloendopeptidase activity TAS
    Traceable Author Statement
    more info
    		  
    enables metallopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables metallopeptidase activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables zinc ion binding NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cell surface receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in female pregnancy NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in protein catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in proteolysis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in response to dexamethasone IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to follicle-stimulating hormone IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in extracellular region IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in extracellular region NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    pappalysin-1
    Names
    IGF-dependent IGFBP-4 protease
    aspecific BCL2 ARE-binding protein 2
    differentially placenta 1 expressed protein
    insulin-like growth factor-dependent IGF binding protein-4 protease
    pregnancy-associated plasma protein A, pappalysin 1
    NP_002572.2
    XP_006717192.1
    XP_016870273.1
    XP_054219020.1
    XP_054219021.1

    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.

    mRNA and Protein(s)

    1. NM_002581.5 → NP_002572.2  pappalysin-1 preproprotein

      See identical proteins and their annotated locations for NP_002572.2

      Status: REVIEWED

      Source sequence(s)
      AK300129, AL137024, AL691426, AU134599, AY623010, BC078657, BY795841, X68280
      Consensus CDS
      CCDS6813.1
      UniProtKB/Swiss-Prot
      B1AMF9, Q08371, Q13219, Q68G52, Q9UDK7
      Related
      ENSP00000330658.3, ENST00000328252.4
      Conserved Domains (7) summary
      cd00033
      Location:1346 → 1421
      CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
      smart00004
      Location:1547 → 1583
      NL; Domain found in Notch and Lin-12
      TIGR02232
      Location:944 → 983
      myxo_disulf_rpt; Myxococcus cysteine-rich repeat
      smart00560
      Location:117 → 266
      LamGL; LamG-like jellyroll fold domain
      cd04275
      Location:424 → 660
      ZnMc_pappalysin_like; Zinc-dependent metalloprotease, pappalysin_like subfamily. The pregnancy-associated plasma protein A (PAPP-A or pappalysin-1) cleaves insulin-like growth factor-binding proteins 4 and 5, thereby promoting cell growth by releasing bound growth factor. ...
      pfam00084
      Location:1415 → 1471
      Sushi; Sushi repeat (SCR repeat)
      pfam13948
      Location:946 → 972
      DUF4215; Domain of unknown function (DUF4215)

    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_000009.12 Reference GRCh38.p14 Primary Assembly

      Range
      116153791..116402321
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017014784.3 → XP_016870273.1  pappalysin-1 isoform X1

    2. XM_006717129.4 → XP_006717192.1  pappalysin-1 isoform X2

      Conserved Domains (4) summary
      cd00033
      Location:648 → 723
      CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
      smart00004
      Location:849 → 885
      NL; Domain found in Notch and Lin-12
      TIGR02232
      Location:246 → 285
      myxo_disulf_rpt; Myxococcus cysteine-rich repeat
      pfam00084
      Location:717 → 773
      Sushi; Sushi repeat (SCR repeat)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060933.1 Alternate T2T-CHM13v2.0

      Range
      128346843..128595327
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054363045.1 → XP_054219020.1  pappalysin-1 isoform X1

    2. XM_054363046.1 → XP_054219021.1  pappalysin-1 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q13219.3 GenPept UniProtKB/Swiss-Prot:Q13219

    Gene LinkOut

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

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