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] See more...

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
  • Pappalysin-2 3 4
  • PAPP-A2 3 4
  • PAPP-E 3 4
  • PLAC3 3 4
  • Pregnancy-Associated Plasma Preproprotein-A2 3
  • Pregnancy-Associated Plasma Protein A2 4
  • 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
  • GC01P176432
  • 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]

CIViC Summary for PAPPA2 Gene

GeneCards Summary for PAPPA2 Gene

PAPPA2 (Pappalysin 2) is a Protein Coding gene. Diseases associated with PAPPA2 include Hellp Syndrome and Schizophrenia 4. 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. Gene Ontology (GO) annotations related to this gene include metallopeptidase activity. An important paralog of this gene is PAPPA.

UniProtKB/Swiss-Prot Summary for PAPPA2 Gene

  • Metalloproteinase which specifically cleaves insulin-like growth factor binding protein (IGFBP)-5 at the '163-Ser- -Lys-164' bond. Shows limited proteolysis toward IGFBP-3.

Gene Wiki entry for PAPPA2 Gene

Additional gene information for PAPPA2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PAPPA2 Gene

Genomics for PAPPA2 Gene

GeneHancer (GH) Regulatory Elements for PAPPA2 Gene

Promoters and enhancers for PAPPA2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH01J176241 Promoter/Enhancer 1.3 EPDnew Ensembl ENCODE 500.1 -221.6 -221561 1.2 FOS POLR2A EP300 CTBP1 MYC ATF2 GABPA TRIM24 BRCA1 CEBPG PAPPA2 ENSG00000236021 COP1 RNU2-12P ENSG00000232463 RPL13P7
GH01J176462 Enhancer 0.6 Ensembl ENCODE 500.7 -0.4 -371 0.6 TEAD4 STAT1 ZNF512 PAPPA2 lnc-PAPPA2-4 piR-46847-020
GH01J176463 Promoter 0.4 EPDnew 500.7 0.0 -15 0.1 STAT1 PAPPA2 lnc-PAPPA2-4 piR-46847-020
GH01J176514 Enhancer 0.9 Ensembl ENCODE 10.4 +52.3 52337 1.5 TRIM28 EP300 CTBP1 FOXA2 CEBPG FOS CEBPB ZBTB33 JUN NR2F2 PAPPA2 lnc-BRINP2-2 piR-53531 lnc-PAPPA2-4
GH01J176781 Enhancer 0.2 FANTOM5 28.2 +318.2 318187 0.1 lnc-ASTN1-2 PAPPA2 ENSG00000286754
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PAPPA2 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PAPPA2

Top Transcription factor binding sites by QIAGEN in the PAPPA2 gene promoter:
  • Cdc5
  • E47
  • FOXJ2 (long isoform)
  • GATA-1
  • Hand1
  • HTF
  • Lmo2
  • STAT1
  • Tal-1

Genomic Locations for PAPPA2 Gene

Genomic Locations for PAPPA2 Gene
chr1:176,463,171-176,845,601
(GRCh38/hg38)
Size:
382,431 bases
Orientation:
Plus strand
chr1:176,432,307-176,814,735
(GRCh37/hg19)
Size:
382,429 bases
Orientation:
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:
    Q9BXP8-PAPP2_HUMAN
    Recommended name:
    Pappalysin-2
    Protein Accession:
    Q9BXP8
    Secondary Accessions:
    • A9Z1Y8
    • Q96PH7
    • Q96PH8
    • Q9H4C9

    Protein attributes for PAPPA2 Gene

    Size:
    1791 amino acids
    Molecular mass:
    198539 Da
    Cofactor:
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
    Quaternary structure:
    • Monomer.
    SequenceCaution:
    • 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

    UniProtKB/Swiss-Prot:

neXtProt entry for PAPPA2 Gene

Post-translational modifications for PAPPA2 Gene

  • Glycosylation at Asn311, Asn562, Asn574, Asn679, Asn813, Asn857, Asn941, Asn1243, Asn1308, Asn1326, Asn1344, Asn1408, Asn1456, Asn1476, and Asn1694
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for PAPPA2 Gene

Domains & Families for PAPPA2 Gene

Gene Families for PAPPA2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted membrane proteins
  • Predicted secreted proteins

Protein Domains for PAPPA2 Gene

Blocks:
  • Sushi domain/SCR domain/CCP module
  • N-6 Adenine-specific DNA methylase
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for PAPPA2 Gene

GenScript: Design optimal peptide antigens:
  • Pappalysin 2, isoform CRA_a (A9Z1Y8_HUMAN)
  • Pregnancy-associated plasma protein E1 (PAPP2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9BXP8

UniProtKB/Swiss-Prot:

PAPP2_HUMAN :
  • Belongs to the peptidase M43B family.
Family:
  • 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 Function:
Metalloproteinase which specifically cleaves insulin-like growth factor binding protein (IGFBP)-5 at the '163-Ser- -Lys-164' bond. Shows limited proteolysis toward IGFBP-3.

Enzyme Numbers (IUBMB) for PAPPA2 Gene

Phenotypes From GWAS Catalog for PAPPA2 Gene

Gene Ontology (GO) - Molecular Function for PAPPA2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IEA --
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

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PAPPA2

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

Secreted.

Subcellular locations from

COMPARTMENTS
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 3
cytosol 3
cytoskeleton 1
mitochondrion 1
nucleus 1
endoplasmic reticulum 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Endoplasmic reticulum (2)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for PAPPA2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005829 cytosol IEA --
GO:0016324 apical plasma membrane IEA --
GO:0070062 extracellular exosome HDA 23533145
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:0009651 response to salt stress IEA --
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

Drugs & Compounds for PAPPA2 Gene

No Compound Related Data Available

Transcripts for PAPPA2 Gene

mRNA/cDNA for PAPPA2 Gene

2 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PAPPA2

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

ExUns: 1 ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12
SP1:
SP2:
SP3:
SP4:

Relevant External Links for PAPPA2 Gene

GeneLoc Exon Structure for
PAPPA2

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 and MOPED for PAPPA2 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PAPPA2

SOURCE GeneReport for Unigene cluster for PAPPA2 Gene:

Hs.187284

mRNA Expression by UniProt/SwissProt for PAPPA2 Gene:

Q9BXP8-PAPP2_HUMAN
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

No data available for Protein tissue co-expression partners , Evidence on tissue expression from TISSUES and Phenotype-based relationships between genes and organs from Gene ORGANizer for PAPPA2 Gene

Orthologs for PAPPA2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for PAPPA2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia PAPPA2 31 30
  • 99.59 (n)
OneToOne
dog
(Canis familiaris)
Mammalia PAPPA2 31 30
  • 85.73 (n)
OneToOne
cow
(Bos Taurus)
Mammalia PAPPA2 31 30
  • 85.09 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Pappa2 17 31 30
  • 82.39 (n)
rat
(Rattus norvegicus)
Mammalia LOC680415 30
  • 82.34 (n)
oppossum
(Monodelphis domestica)
Mammalia PAPPA2 31
  • 71 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia PAPPA2 31
  • 52 (a)
OneToOne
chicken
(Gallus gallus)
Aves PAPPA2 31 30
  • 69.01 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia PAPPA2 31
  • 65 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia pappa2 30
  • 59.99 (n)
zebrafish
(Danio rerio)
Actinopterygii pappa2 31 30
  • 57.46 (n)
OneToOne
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

ENSEMBL:
Gene Tree for PAPPA2 (if available)
TreeFam:
Gene Tree for PAPPA2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PAPPA2: view image

Paralogs for PAPPA2 Gene

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

  • PAPP2_HUMAN
genes like me logo Genes that share paralogs with PAPPA2: view

Variants for PAPPA2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PAPPA2 Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
711778 Benign: not provided 176,771,044(+) G/T MISSENSE_VARIANT
712091 Benign: not provided 176,769,675(+) C/T SYNONYMOUS_VARIANT
717136 Benign: not provided 176,671,099(+) C/T SYNONYMOUS_VARIANT
723215 Benign: not provided 176,556,865(+) C/T SYNONYMOUS_VARIANT
767730 Likely Benign: not provided 176,595,079(+) C/T MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for PAPPA2 Gene

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

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

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)

Additional Variant Information for PAPPA2 Gene

Human Gene Mutation Database (HGMD)
PAPPA2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
PAPPA2

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

Disorders for PAPPA2 Gene

MalaCards: The human disease database

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

Disorder Aliases PubMed IDs
hellp syndrome
  • hemolysis, elevated liver enzymes, lowered platelets
schizophrenia 4
  • sczd4
down syndrome
  • trisomy 21
pre-eclampsia
  • toxemia of pregnancy
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for PAPPA2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
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 MT … Oxvig C (The Journal of biological chemistry 2001) 2 3 4 23 54
  2. Pregnancy-associated plasma protein-E (PAPP-E). (PMID: 11018262) Farr M … Tschesche H (Biochimica et biophysica acta 2000) 2 3 4 23 54
  3. The characterization of pregnancy associated plasma protein-E and the identification of an alternative splice variant. (PMID: 11597188) Page NM … Lowry PJ (Placenta 2001) 3 4 23 54
  4. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41 54
  5. Sequential use of transcriptional profiling, expression quantitative trait mapping, and gene association implicates MMP20 in human kidney aging. (PMID: 19834535) Wheeler HE … Kim SK (PLoS genetics 2009) 3 41 54

Products for PAPPA2 Gene

  • Boster Bio Antibodies for PAPPA2
  • Boster Bio ELISA Kits for PAPPA2

Sources for PAPPA2 Gene