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PAPPA2 pappalysin 2 [ Homo sapiens (human) ]

Gene ID: 60676, updated on 5-Mar-2024

Summary

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Official Symbol
PAPPA2provided by HGNC
Official Full Name
pappalysin 2provided by HGNC
Primary source
HGNC:HGNC:14615
See related
Ensembl:ENSG00000116183 MIM:619485; AllianceGenome:HGNC:14615
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
SSDA; PAPPE; PLAC3; PAPP-E; PAPP-A2
Summary
This gene encodes a member of the pappalysin family of metzincin metalloproteinases. The encoded protein cleaves insulin-like growth factor-binding protein 5 and is thought to be a local regulator of insulin-like growth factor (IGF) bioavailability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2010]
Expression
Biased expression in placenta (RPKM 23.7), kidney (RPKM 2.2) and 1 other tissue See more
Orthologs
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Genomic context

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See PAPPA2 in Genome Data Viewer
Location:
1q25.2
Exon count:
26
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (176463175..176845601)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (175818447..176200273)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (176432311..176814737)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene zinc finger AN1-type containing 1 pseudogene Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:176282688-176283193 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1571 Neighboring gene mortality factor 4 like 1 pseudogene 7 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr1:176525984-176527183 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1572 Neighboring gene PTP4A1 pseudogene 7 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:176694898-176695118 Neighboring gene NANOG hESC enhancer GRCh37_chr1:176702698-176703199 Neighboring gene MPRA-validated peak474 silencer Neighboring gene GATA motif-containing MPRA enhancer 65 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:176873029-176873530 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:176873531-176874030 Neighboring gene astrotactin 1 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr1:177013479-177014043 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr1:177017656-177018356 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr1:177029877-177031076 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr1:177034489-177035123 Neighboring gene microRNA 488 Neighboring gene OCT4-H3K4me1 hESC enhancer GRCh37_chr1:177139732-177140321 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:177140322-177140910 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:177150672-177151233 Neighboring gene uncharacterized LOC105371625 Neighboring gene BMP/retinoic acid inducible neural specific 2 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr1:177224616-177225815

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. Serum Inhibin-A and PAPP-A2 in the prediction of pre-eclampsia during the first and second trimesters in high-risk women. Keikkala E, et al. Pregnancy Hypertens, 2021 Aug. PMID 34116346
  2. Associations of plasma PAPP-A2 and genetic variations with salt sensitivity, blood pressure changes and hypertension incidence in Chinese adults. Wang Y, et al. J Hypertens, 2021 Sep 1. PMID 33783375
  3. Disorders caused by genetic defects associated with GH-dependent genes: PAPPA2 defects. Fujimoto M, et al. Mol Cell Endocrinol, 2020 Dec 1. PMID 32739295, Free PMC Article
  4. Uteroplacental Ischemia Is Associated with Increased PAPP-A2. Lamale-Smith LM, et al. Reprod Sci, 2020 Feb. PMID 31994005, Free PMC Article
  5. The potential role of pregnancy-associated plasma protein-A2 in angiogenesis and development of preeclampsia. Chen X, et al. Hypertens Res, 2019 Jul. PMID 30816319

See all (54) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Dynamic Changes in Serum IGF-I and Growth During Infancy: Associations to Body Fat, Target Height, and PAPPA2 Genotype.
    Title: Dynamic Changes in Serum IGF-I and Growth During Infancy: Associations to Body Fat, Target Height, and PAPPA2 Genotype.
  2. Short stature with low insulin-like growth factor 1 availability due to pregnancy-associated plasma protein A2 deficiency in a Saudi family.
    Title: Short stature with low insulin-like growth factor 1 availability due to pregnancy-associated plasma protein A2 deficiency in a Saudi family.
  3. Genetic Study of IL6, GDF5 and PAPPA2 in Association with Developmental Dysplasia of the Hip.
    Title: Genetic Study of IL6, GDF5 and PAPPA2 in Association with Developmental Dysplasia of the Hip.
  4. Serum Inhibin-A and PAPP-A2 in the prediction of pre-eclampsia during the first and second trimesters in high-risk women.
    Title: Serum Inhibin-A and PAPP-A2 in the prediction of pre-eclampsia during the first and second trimesters in high-risk women.
  5. Associations of plasma PAPP-A2 and genetic variations with salt sensitivity, blood pressure changes and hypertension incidence in Chinese adults.
    Title: Associations of plasma PAPP-A2 and genetic variations with salt sensitivity, blood pressure changes and hypertension incidence in Chinese adults.
  6. Disorders caused by genetic defects associated with GH-dependent genes: PAPPA2 defects.
    Title: Disorders caused by genetic defects associated with GH-dependent genes: PAPPA2 defects.
  7. Netazepide Inhibits Expression of Pappalysin 2 in Type 1 Gastric Neuroendocrine Tumors.
    Title: Netazepide Inhibits Expression of Pappalysin 2 in Type 1 Gastric Neuroendocrine Tumors.
  8. PAPP-A2 and Inhibin A as Novel Predictors for Pregnancy Complications in Women With Suspected or Confirmed Preeclampsia.
    Title: PAPP-A2 and Inhibin A as Novel Predictors for Pregnancy Complications in Women With Suspected or Confirmed Preeclampsia.
  9. Uteroplacental Ischemia Is Associated with Increased PAPP-A2.
    Title: Uteroplacental Ischemia Is Associated with Increased PAPP-A2.
  10. The potential role of pregnancy-associated plasma protein-A2 in angiogenesis and development of preeclampsia.
    Title: The potential role of pregnancy-associated plasma protein-A2 in angiogenesis and development of preeclampsia.
Submit: New GeneRIF Correction See all GeneRIFs (36)

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
Short stature, Dauber-Argente type
MedGen: C5561968 OMIM: 619489 GeneReviews: Not available
Compare labs

EBI GWAS Catalog

Description
A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis.
EBI GWAS Catalog
Fraction of exhaled nitric oxide values in childhood are associated with 17q11.2-q12 and 17q12-q21 variants.
EBI GWAS Catalog
Hundreds of variants clustered in genomic loci and biological pathways affect human height.
EBI GWAS Catalog
Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci.
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 zinc ion binding NAS
Non-traceable Author Statement
more info
 PubMed 
Process Evidence Code Pubs
involved_in bone morphogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in cell surface receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
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 proteolysis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of cell growth NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in response to salt stress IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in apical plasma membrane IEA
Inferred from Electronic Annotation
more info
  
located_in extracellular exosome HDA 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-2
Names
placenta-specific 3
pregnancy-associated plasma preproprotein-A2
pregnancy-associated plasma protein E1

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_023390.2 RefSeqGene

    Range
    5002..387428
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_020318.3 → NP_064714.2  pappalysin-2 isoform 1 precursor

    See identical proteins and their annotated locations for NP_064714.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longer isoform (1).
    Source sequence(s)
    AF311940, AF342989, AL031290, BC062665
    Consensus CDS
    CCDS41438.1
    UniProtKB/Swiss-Prot
    A9Z1Y8, Q96PH7, Q96PH8, Q9BXP8, Q9H4C9
    Related
    ENSP00000356634.3, ENST00000367662.5
    Conserved Domains (7) summary
    cd00033
    Location:1525 → 1591
    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:1722 → 1758
    NL; Domain found in Notch and Lin-12
    TIGR02232
    Location:1112 → 1151
    myxo_disulf_rpt; Myxococcus cysteine-rich repeat
    cd04275
    Location:634 → 831
    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:1467 → 1521
    Sushi; Sushi repeat (SCR repeat)
    pfam13385
    Location:282 → 433
    Laminin_G_3; Concanavalin A-like lectin/glucanases superfamily
    cl02419
    Location:585 → 612
    Notch; LNR domain

  2. NM_021936.3 → NP_068755.2  pappalysin-2 isoform 2 precursor

    See identical proteins and their annotated locations for NP_068755.2

    Status: REVIEWED

    Description
    Transcript Variant: # This Variant: This variant (2) differs in the 3' UTR and has multiple coding region differences, compared to variant 1. The resulting protein (isoform 2) has a distinct C-terminus and is shorter than isoform 1.
    Source sequence(s)
    AL139282, AL596254, BC062665, BC117195
    Consensus CDS
    CCDS41439.1
    UniProtKB/Swiss-Prot
    Q9BXP8
    Related
    ENSP00000356633.3, ENST00000367661.7
    Conserved Domains (3) summary
    smart00004
    Location:585 → 612
    NL; Domain found in Notch and Lin-12
    pfam13385
    Location:282 → 433
    Laminin_G_3; Concanavalin A-like lectin/glucanases superfamily
    cl00064
    Location:634 → 811
    ZnMc; Zinc-dependent metalloprotease. This super-family of metalloproteases contains two major branches, the astacin-like proteases and the adamalysin/reprolysin-like proteases. Both branches have wide phylogenetic distribution, and contain sub-families, which ...

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_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    176463175..176845601
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047427180.1 → XP_047283136.1  pappalysin-2 isoform X1

    UniProtKB/Swiss-Prot
    A9Z1Y8, Q96PH7, Q96PH8, Q9BXP8, Q9H4C9

  2. XM_017002024.2 → XP_016857513.1  pappalysin-2 isoform X1

    UniProtKB/Swiss-Prot
    A9Z1Y8, Q96PH7, Q96PH8, Q9BXP8, Q9H4C9
    Conserved Domains (7) summary
    cd00033
    Location:1525 → 1591
    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:1722 → 1758
    NL; Domain found in Notch and Lin-12
    TIGR02232
    Location:1112 → 1151
    myxo_disulf_rpt; Myxococcus cysteine-rich repeat
    cd04275
    Location:634 → 831
    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:1467 → 1521
    Sushi; Sushi repeat (SCR repeat)
    pfam13385
    Location:282 → 433
    Laminin_G_3; Concanavalin A-like lectin/glucanases superfamily
    cl02419
    Location:585 → 612
    Notch; LNR domain

  3. XM_017002023.2 → XP_016857512.1  pappalysin-2 isoform X1

    UniProtKB/Swiss-Prot
    A9Z1Y8, Q96PH7, Q96PH8, Q9BXP8, Q9H4C9
    Conserved Domains (7) summary
    cd00033
    Location:1525 → 1591
    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:1722 → 1758
    NL; Domain found in Notch and Lin-12
    TIGR02232
    Location:1112 → 1151
    myxo_disulf_rpt; Myxococcus cysteine-rich repeat
    cd04275
    Location:634 → 831
    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:1467 → 1521
    Sushi; Sushi repeat (SCR repeat)
    pfam13385
    Location:282 → 433
    Laminin_G_3; Concanavalin A-like lectin/glucanases superfamily
    cl02419
    Location:585 → 612
    Notch; LNR domain

  4. XM_011509857.1 → XP_011508159.1  pappalysin-2 isoform X1

    See identical proteins and their annotated locations for XP_011508159.1

    UniProtKB/Swiss-Prot
    A9Z1Y8, Q96PH7, Q96PH8, Q9BXP8, Q9H4C9
    Conserved Domains (7) summary
    cd00033
    Location:1525 → 1591
    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:1722 → 1758
    NL; Domain found in Notch and Lin-12
    TIGR02232
    Location:1112 → 1151
    myxo_disulf_rpt; Myxococcus cysteine-rich repeat
    cd04275
    Location:634 → 831
    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:1467 → 1521
    Sushi; Sushi repeat (SCR repeat)
    pfam13385
    Location:282 → 433
    Laminin_G_3; Concanavalin A-like lectin/glucanases superfamily
    cl02419
    Location:585 → 612
    Notch; LNR domain

  5. XM_005245422.4 → XP_005245479.1  pappalysin-2 isoform X1

    See identical proteins and their annotated locations for XP_005245479.1

    UniProtKB/Swiss-Prot
    A9Z1Y8, Q96PH7, Q96PH8, Q9BXP8, Q9H4C9
    Conserved Domains (7) summary
    cd00033
    Location:1525 → 1591
    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:1722 → 1758
    NL; Domain found in Notch and Lin-12
    TIGR02232
    Location:1112 → 1151
    myxo_disulf_rpt; Myxococcus cysteine-rich repeat
    cd04275
    Location:634 → 831
    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:1467 → 1521
    Sushi; Sushi repeat (SCR repeat)
    pfam13385
    Location:282 → 433
    Laminin_G_3; Concanavalin A-like lectin/glucanases superfamily
    cl02419
    Location:585 → 612
    Notch; LNR domain

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    175818447..176200273
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054338079.1 → XP_054194054.1  pappalysin-2 isoform X1

    UniProtKB/Swiss-Prot
    A9Z1Y8, Q96PH7, Q96PH8, Q9BXP8, Q9H4C9

  2. XM_054338081.1 → XP_054194056.1  pappalysin-2 isoform X1

    UniProtKB/Swiss-Prot
    A9Z1Y8, Q96PH7, Q96PH8, Q9BXP8, Q9H4C9

  3. XM_054338082.1 → XP_054194057.1  pappalysin-2 isoform X1

    UniProtKB/Swiss-Prot
    A9Z1Y8, Q96PH7, Q96PH8, Q9BXP8, Q9H4C9

  4. XM_054338080.1 → XP_054194055.1  pappalysin-2 isoform X1

    UniProtKB/Swiss-Prot
    A9Z1Y8, Q96PH7, Q96PH8, Q9BXP8, Q9H4C9

  5. XM_054338083.1 → XP_054194058.1  pappalysin-2 isoform X1

    UniProtKB/Swiss-Prot
    A9Z1Y8, Q96PH7, Q96PH8, Q9BXP8, Q9H4C9

  6. XM_054338085.1 → XP_054194060.1  pappalysin-2 isoform X1

    UniProtKB/Swiss-Prot
    A9Z1Y8, Q96PH7, Q96PH8, Q9BXP8, Q9H4C9

  7. XM_054338084.1 → XP_054194059.1  pappalysin-2 isoform X1

    UniProtKB/Swiss-Prot
    A9Z1Y8, Q96PH7, Q96PH8, Q9BXP8, Q9H4C9
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9BXP8.4 GenPept UniProtKB/Swiss-Prot:Q9BXP8

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