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Aliases for PAPPA2 Gene

Aliases for PAPPA2 Gene

  • Pappalysin 2 2 3 5
  • Pregnancy-Associated Plasma Protein E1 3 4
  • Placenta-Specific 3 2 3
  • PAPP-A2 3 4
  • PAPP-E 3 4
  • PLAC3 3 4
  • Pregnancy-Associated Plasma Preproprotein-A2 3
  • Pregnancy-Associated Plasma Protein A2 4
  • Pappalysin-2 3
  • EC 3.4.24.- 4
  • PAPPE 3

External Ids for PAPPA2 Gene

Previous HGNC Symbols for PAPPA2 Gene

  • PLAC3

Previous GeneCards Identifiers for PAPPA2 Gene

  • GC01P173163
  • GC01P174698
  • GC01P147658

Summaries for PAPPA2 Gene

Entrez Gene Summary for PAPPA2 Gene

  • 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]

GeneCards Summary for PAPPA2 Gene

PAPPA2 (Pappalysin 2) is a Protein Coding gene. Diseases associated with PAPPA2 include Chromosomal Triplication and Hellp Syndrome. Among its related pathways are Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) and Metabolism of proteins. GO annotations related to this gene include metallopeptidase activity. An important paralog of this gene is PAPPA.

UniProtKB/Swiss-Prot for PAPPA2 Gene

  • Metalloproteinase which specifically cleaves IGFBP-5. Shows limited proteolysis toward IGFBP-3.

Gene Wiki entry for PAPPA2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for PAPPA2 Gene

Genomics for PAPPA2 Gene

Regulatory Elements for PAPPA2 Gene

Enhancers for PAPPA2 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH01F176781 0.3 FANTOM5 28.2 +318.2 318188 0.1 PAPPA2 GC01M176762 GC01P176674
GH01F176514 0.8 ENCODE 10.4 +52.3 52337 1.5 JUN FEZF1 RAD21 HIC1 CTBP1 ZNF366 SCRT2 PRDM10 FOSL2 FOS PAPPA2 PIR47530 GC01P176494
GH01F176655 0.7 Ensembl ENCODE 5.3 +193.7 193654 1.8 CTCF CEBPB PAPPA2 GC01P176674 PTP4A1P7
GH01F176630 0.3 FANTOM5 6.5 +167.2 167178 0.2 PAPPA2 PTP4A1P7 GC01P176674
GH01F176532 0.3 FANTOM5 3 +69.6 69584 0.1 PAPPA2 PIR47530 GC01P176494
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around PAPPA2 on UCSC Golden Path with GeneCards custom track

Genomic Location for PAPPA2 Gene

176,463,171 bp from pter
176,845,605 bp from pter
382,435 bases
Plus strand

Genomic View for PAPPA2 Gene

Genes around PAPPA2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PAPPA2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PAPPA2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PAPPA2 Gene

Proteins for PAPPA2 Gene

  • Protein details for PAPPA2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Protein Accession:
    Secondary Accessions:
    • A9Z1Y8
    • Q96PH7
    • Q96PH8
    • Q9H4C9

    Protein attributes for PAPPA2 Gene

    1791 amino acids
    Molecular mass:
    198539 Da
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
    Quaternary structure:
    • Monomer.
    • Sequence=AAL17779.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAL17780.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=CAC11134.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Alternative splice isoforms for PAPPA2 Gene


neXtProt entry for PAPPA2 Gene

Post-translational modifications for PAPPA2 Gene

  • Glycosylation at Asn 311, Asn 562, Asn 574, Asn 679, Asn 813, Asn 857, Asn 941, Asn 1243, Asn 1308, Asn 1326, Asn 1344, Asn 1408, Asn 1456, Asn 1476, and Asn 1694
  • Modification sites at PhosphoSitePlus

Antibody Products

  • R&D Systems Antibodies for PAPPA2 (Pappalysin-2/PAPP-A2)

No data available for DME Specific Peptides for PAPPA2 Gene

Domains & Families for PAPPA2 Gene

Gene Families for PAPPA2 Gene

Suggested Antigen Peptide Sequences for PAPPA2 Gene

Graphical View of Domain Structure for InterPro Entry



  • Contains 5 Sushi (CCP/SCR) domains.
  • Belongs to the peptidase M43B family.
  • Contains 5 Sushi (CCP/SCR) domains.
  • Belongs to the peptidase M43B family.
genes like me logo Genes that share domains with PAPPA2: view

Function for PAPPA2 Gene

Molecular function for PAPPA2 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
Cleavage of the 143-Ser- -Lys-144 bond in insulin-like growth factor binding protein (IGFBP)-5.
UniProtKB/Swiss-Prot Function:
Metalloproteinase which specifically cleaves IGFBP-5. Shows limited proteolysis toward IGFBP-3.

Enzyme Numbers (IUBMB) for PAPPA2 Gene

Gene Ontology (GO) - Molecular Function for PAPPA2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004222 metalloendopeptidase activity TAS --
GO:0008233 peptidase activity IEA --
GO:0008237 metallopeptidase activity IDA 11264294
GO:0008270 zinc ion binding NAS 11264294
GO:0016787 hydrolase activity IEA --
genes like me logo Genes that share ontologies with PAPPA2: view
genes like me logo Genes that share phenotypes with PAPPA2: view

Animal Models for PAPPA2 Gene

MGI Knock Outs for PAPPA2:

Animal Model Products

  • Taconic Biosciences Mouse Models for PAPPA2

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for PAPPA2 Gene

Localization for PAPPA2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for PAPPA2 Gene


Subcellular locations from

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 PAPPA2 gene
Compartment Confidence
extracellular 5
plasma membrane 2
cytoskeleton 1
endoplasmic reticulum 1
cytosol 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for PAPPA2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005622 intracellular NAS 11264294
GO:0070062 extracellular exosome IDA 23376485
genes like me logo Genes that share ontologies with PAPPA2: view

Pathways & Interactions for PAPPA2 Gene

genes like me logo Genes that share pathways with PAPPA2: view

Gene Ontology (GO) - Biological Process for PAPPA2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001558 regulation of cell growth NAS 11264294
GO:0006508 proteolysis IDA 11264294
GO:0044267 cellular protein metabolic process TAS --
GO:0060349 bone morphogenesis IEA --
genes like me logo Genes that share ontologies with PAPPA2: view

No data available for SIGNOR curated interactions for PAPPA2 Gene

Transcripts for PAPPA2 Gene

Unigene Clusters for PAPPA2 Gene

Pappalysin 2:
Representative Sequences:

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for PAPPA2 Gene

ExUns: 1 ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12

Relevant External Links for PAPPA2 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for PAPPA2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PAPPA2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for PAPPA2 Gene

This gene is overexpressed in Cervix - Ectocervix (x4.6) and Kidney - Cortex (x4.5).

Protein differential expression in normal tissues from HIPED for PAPPA2 Gene

This gene is overexpressed in Vitreous humor (60.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for PAPPA2 Gene

Protein tissue co-expression partners for PAPPA2 Gene

NURSA nuclear receptor signaling pathways regulating expression of PAPPA2 Gene:


SOURCE GeneReport for Unigene cluster for PAPPA2 Gene:


mRNA Expression by UniProt/SwissProt for PAPPA2 Gene:

Tissue specificity: Expressed abundantly in placenta, and non-pregnant mammary gland with low expression in the kidney, fetal brain and pancreas.
genes like me logo Genes that share expression patterns with PAPPA2: view

Primer Products

Orthologs for PAPPA2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for PAPPA2 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia PAPPA2 34 35
  • 99.59 (n)
(Canis familiaris)
Mammalia PAPPA2 34 35
  • 85.73 (n)
(Bos Taurus)
Mammalia PAPPA2 34 35
  • 85.09 (n)
(Mus musculus)
Mammalia Pappa2 34 16 35
  • 82.39 (n)
(Rattus norvegicus)
Mammalia LOC680415 34
  • 82.34 (n)
(Monodelphis domestica)
Mammalia PAPPA2 35
  • 71 (a)
(Ornithorhynchus anatinus)
Mammalia PAPPA2 35
  • 52 (a)
(Gallus gallus)
Aves PAPPA2 34 35
  • 69.01 (n)
(Anolis carolinensis)
Reptilia PAPPA2 35
  • 65 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia pappa2 34
  • 59.99 (n)
(Danio rerio)
Actinopterygii pappa2 34 35
  • 57.46 (n)
Species where no ortholog for PAPPA2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (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)

Evolution for PAPPA2 Gene

Gene Tree for PAPPA2 (if available)
Gene Tree for PAPPA2 (if available)

Paralogs for PAPPA2 Gene

Paralogs for PAPPA2 Gene

(1) SIMAP similar genes for PAPPA2 Gene using alignment to 1 proteins:

genes like me logo Genes that share paralogs with PAPPA2: view

Variants for PAPPA2 Gene

Sequence variations from dbSNP and Humsavar for PAPPA2 Gene

SNP ID Clin Chr 01 pos Sequence Context AA Info Type
rs10082009 -- 176,735,898(+) CTAAC(A/T)GTACT intron-variant
rs10127938 -- 176,519,357(+) CAGAG(A/T)CTGAG intron-variant
rs10128032 -- 176,521,532(+) CCAAG(A/G)ATCAT intron-variant
rs1014718 -- 176,833,838(-) ACACA(C/T)ATACA intron-variant
rs1014719 -- 176,833,630(-) AAAAC(A/C)TAACA intron-variant

Structural Variations from Database of Genomic Variants (DGV) for PAPPA2 Gene

Variant ID Type Subtype PubMed ID
nsv946516 CNV duplication 23825009
nsv831982 CNV gain 17160897
nsv831970 CNV gain 17160897
nsv818589 CNV loss 17921354
nsv548250 CNV loss 21841781
nsv548249 CNV loss 21841781
nsv511719 CNV loss 21212237
nsv508049 OTHER sequence alteration 20534489
nsv498694 CNV loss 21111241
nsv472335 CNV novel sequence insertion 20440878
nsv466105 CNV loss 19166990
nsv466094 CNV loss 19166990
nsv3666 CNV deletion 18451855
nsv159940 CNV deletion 16902084
nsv1133921 CNV deletion 24896259
nsv1071303 CNV deletion 25765185
nsv1004658 CNV gain 25217958
esv992315 CNV deletion 20482838
esv6740 CNV loss 19470904
esv3588008 CNV loss 21293372
esv3588006 CNV loss 21293372
esv3588004 CNV loss 21293372
esv3578284 CNV loss 25503493
esv3542966 CNV deletion 23714750
esv33914 CNV gain 17666407
esv28963 CNV loss 19812545
esv275585 CNV loss 21479260
esv275131 CNV gain+loss 21479260
esv2719795 CNV deletion 23290073
esv2669673 CNV deletion 23128226
esv2669646 CNV deletion 23128226
esv2467680 CNV deletion 19546169
esv2094934 CNV deletion 18987734
esv1596288 CNV deletion 17803354
esv1170602 CNV deletion 17803354
esv1005770 CNV deletion 20482838
dgv467n100 CNV gain 25217958
dgv222n106 CNV deletion 24896259
dgv10n73 CNV deletion 24416366

Variation tolerance for PAPPA2 Gene

Residual Variation Intolerance Score: 53% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.29; 62.80% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for PAPPA2 Gene

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

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PAPPA2 Gene

Disorders for PAPPA2 Gene

MalaCards: The human disease database

(2) MalaCards diseases for PAPPA2 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
chromosomal triplication
  • trisomy
hellp syndrome
  • syndrome of haemolysis, elevated liver enzymes and low platelet
- elite association - COSMIC cancer census association via MalaCards

Relevant External Links for PAPPA2

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
genes like me logo Genes that share disorders with PAPPA2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for PAPPA2 Gene

Publications for PAPPA2 Gene

  1. Pregnancy-associated plasma protein-A2 (PAPP-A2), a novel insulin- like growth factor-binding protein-5 proteinase. (PMID: 11264294) Overgaard M.T. … Oxvig C. (J. Biol. Chem. 2001) 2 3 4 22 64
  2. Pregnancy-associated plasma protein-E (PAPP-E). (PMID: 11018262) Farr M. … Tschesche H. (Biochim. Biophys. Acta 2000) 2 3 4 22 64
  3. The characterization of pregnancy associated plasma protein-E and the identification of an alternative splice variant. (PMID: 11597188) Page N.M. … Lowry P.J. (Placenta 2001) 3 4 22 64
  4. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose J.E. … Uhl G.R. (Mol. Med. 2010) 3 46 64
  5. Sequential use of transcriptional profiling, expression quantitative trait mapping, and gene association implicates MMP20 in human kidney aging. (PMID: 19834535) Wheeler H.E. … Kim S.K. (PLoS Genet. 2009) 3 46 64

Products for PAPPA2 Gene

Sources for PAPPA2 Gene

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