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PAPPA pappalysin 1 [ Homo sapiens (human) ]

Gene ID: 5069, updated on 5-Mar-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
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Genomic context

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Location:
9q33.1
Exon count:
22
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 9 NC_000009.12 (116153791..116402321)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 9 NC_060933.1 (128346843..128595327)
105.20220307 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

Bibliography

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Related articles in PubMed

  1. Senescence induces proteolytically-active PAPP-A secretion and association with extracellular vesicles in human pre-adipocytes. Conover CA, et al. Exp Gerontol, 2023 Feb. PMID 36549546, Free PMC Article
  2. PAPPA Expression in Indeterminate Thyroid Nodules as Screening Test to Select Patients for Molecular Testing. Marzocchi C, et al. Int J Mol Sci, 2022 Apr 22. PMID 35563038, Free PMC Article
  3. Low first trimester maternal serum PAPP-A concentrations in women with non-cavity-distorting intramural uterine fibroids. Kahraman A, et al. J Obstet Gynaecol Res, 2022 May. PMID 35174583
  4. Maternal serum pregnancy-associated plasma protein-A concentration at 11-14 weeks of gestation and preeclampsia risk of women with common congenital anatomic uterine abnormalities. Sotiriou S, et al. J Obstet Gynaecol, 2022 Aug. PMID 35164639
  5. Pregnancy-associated plasma protein-A (PAPP-A) is a key component of an interactive cellular mechanism promoting pulmonary fibrosis. Bale LK, et al. J Cell Physiol, 2022 Apr. PMID 35098542, Free PMC Article

See all (280) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. The Pregnancy-Associated Plasma Protein-A (PAPP-A) Story.
    Title: The Pregnancy-Associated Plasma Protein-A (PAPP-A) Story.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. The predictive value of maternal serum AFP to PAPP-A or b-hCG ratios in spontaneous preterm birth.
    Title: The predictive value of maternal serum AFP to PAPP-A or b-hCG ratios in spontaneous preterm birth.
  9. Maternal serum pregnancy-associated plasma protein-A concentration at 11-14 weeks of gestation and preeclampsia risk of women with common congenital anatomic uterine abnormalities.
    Title: Maternal serum pregnancy-associated plasma protein-A concentration at 11-14 weeks of gestation and preeclampsia risk of women with common congenital anatomic uterine abnormalities.
  10. Preliminary investigation of gene expression levels of PAPP-A, STC-2, and HIF-1alpha in SARS-Cov-2 infected patients.
    Title: Preliminary investigation of gene expression levels of PAPP-A, STC-2, and HIF-1α in SARS-Cov-2 infected patients.
Submit: New GeneRIF Correction See all GeneRIFs (236)

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)

Genotypes

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 protein metabolic process TAS
Traceable Author Statement
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_2023_10

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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