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Aliases for PAPPA Gene

Aliases for PAPPA Gene

  • Pappalysin 1 2 3 5
  • Insulin-Like Growth Factor-Dependent IGF Binding Protein-4 Protease 2 3
  • Pregnancy-Associated Plasma Protein A, Pappalysin 1 2 3
  • Differentially Placenta 1 Expressed Protein 2 3
  • Aspecific BCL2 ARE-Binding Protein 2 2 3
  • IGF-Dependent IGFBP-4 Protease 3 4
  • Pappalysin-1 3 4
  • IGFBP-4ase 3 4
  • PAPP-A 3 4
  • Insulin-Like Growth Factor-Dependent IGF-Binding Protein 4 Protease 4
  • Pregnancy-Associated Plasma Protein A 4
  • EC 3.4.24.79 4
  • ASBABP2 3
  • DIPLA1 3
  • PAPPA1 3
  • PAPA 3

External Ids for PAPPA Gene

Previous GeneCards Identifiers for PAPPA Gene

  • GC09P109744
  • GC09P110677
  • GC09P112369
  • GC09P114292
  • GC09P115995
  • GC09P117955
  • GC09P118916
  • GC09P116154
  • GC09P116160
  • GC09P116157

Summaries for PAPPA Gene

Entrez Gene Summary for PAPPA Gene

  • 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]

GeneCards Summary for PAPPA Gene

PAPPA (Pappalysin 1) is a Protein Coding gene. Diseases associated with PAPPA include Orofaciodigital Syndrome Viii and Down 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. Gene Ontology (GO) annotations related to this gene include metalloendopeptidase activity and endopeptidase activity. An important paralog of this gene is PAPPA2.

UniProtKB/Swiss-Prot for PAPPA Gene

  • Metalloproteinase which specifically cleaves IGFBP-4 and IGFBP-5, resulting in release of bound IGF. Cleavage of IGFBP-4 is dramatically enhanced by the presence of IGF, whereas cleavage of IGFBP-5 is slightly inhibited by the presence of IGF.

Gene Wiki entry for PAPPA Gene

Additional gene information for PAPPA Gene

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

Genomics for PAPPA Gene

GeneHancer (GH) Regulatory Elements for PAPPA Gene

Promoters and enhancers for PAPPA 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
GH09J116151 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 607.6 +1.2 1192 7.6 NFIB CTCF TRIM24 PRDM1 SMARCA4 CREB1 GLIS2 POLR2A ZBTB8A ZNF544 PAPPA GC09P116163 GC09P116159 GC09P116173
GH09J115938 Promoter/Enhancer 2.2 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 600.1 -210.9 -210867 9 ELF3 MNT CEBPG RERE MAFK TFE3 ELF1 SP1 PPARG SP5 PAPPA LINC00474 LOC105376236
GH09J116464 Enhancer 1.3 Ensembl ENCODE dbSUPER 10.5 +312.2 312150 2.7 CC2D1A ZKSCAN8 ZNF148 MLLT1 CSDE1 NCOA6 TRIM24 EGR1 ZNF639 HNRNPUL1 PAPPA-AS1 PAPPA ENSG00000244757 RPL10P3 ASTN2-AS1 ASTN2
GH09J116686 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE 4.5 +537.6 537609 10.4 SP1 ELF3 CBFA2T2 ZNF148 NKRF POLR2A CEBPG ZNF687 PPARG CREM ASTN2 TRIM32 ASTN2-AS1 PAPPA GC09P116705
GH09J116470 Enhancer 1.1 ENCODE dbSUPER 10.4 +317.6 317629 2.3 ZFX ZKSCAN8 MLLT1 TRIM24 ZNF639 EGR1 SMARCA4 CAVIN1 GMEB1 DPF2 PAPPA-AS1 ENSG00000244757 PAPPA ASTN2-AS1 ASTN2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PAPPA on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the PAPPA gene promoter:
  • Nkx2-5
  • Oct-B1
  • oct-B2
  • oct-B3
  • PPAR-alpha
  • PPAR-gamma1
  • PPAR-gamma2
  • YY1
  • ZID

Genomic Locations for PAPPA Gene

Genomic Locations for PAPPA Gene
chr9:116,153,791-116,402,321
(GRCh38/hg38)
Size:
248,531 bases
Orientation:
Plus strand
chr9:118,916,071-119,164,601
(GRCh37/hg19)
Size:
248,531 bases
Orientation:
Plus strand

Genomic View for PAPPA Gene

Genes around PAPPA on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for PAPPA Gene

Proteins for PAPPA Gene

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

    Protein Symbol:
    Q13219-PAPP1_HUMAN
    Recommended name:
    Pappalysin-1
    Protein Accession:
    Q13219
    Secondary Accessions:
    • B1AMF9
    • Q08371
    • Q68G52
    • Q9UDK7

    Protein attributes for PAPPA Gene

    Size:
    1627 amino acids
    Molecular mass:
    180973 Da
    Cofactor:
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
    Quaternary structure:
    • Homodimer; disulfide-linked. In pregnancy serum, predominantly found as a disulfide-linked 2:2 heterotetramer with the proform of PRG2.
    SequenceCaution:
    • Sequence=AAC50543.1; Type=Frameshift; Positions=51, 67; Evidence={ECO:0000305};

neXtProt entry for PAPPA Gene

Post-translational modifications for PAPPA Gene

  • There appear to be no free sulfhydryl groups.
  • Glycosylation at isoforms=1026, isoforms=390, isoforms=480, isoforms=1226, isoforms=601, isoforms=825, isoforms=1465, posLast=619619, isoforms=725, posLast=429429, posLast=402402, isoforms=1222, posLast=15191519, and posLast=13231323
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • PAPP1_HUMAN (1594)

Other Protein References for PAPPA Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for PAPPA Gene

Domains & Families for PAPPA Gene

Gene Families for PAPPA Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Candidate cardiovascular disease genes
  • Enzymes
  • Plasma proteins
  • Predicted secreted proteins

Suggested Antigen Peptide Sequences for PAPPA Gene

GenScript: Design optimal peptide antigens:
  • Pregnancy-associated plasma protein A (PAPP1_HUMAN)
  • Pregnacy-associated plasma protein A (Q5QFB7_HUMAN)
  • Replicative senescence upregulated protein (Q7Z613_HUMAN)
  • Aspecific BCL2 ARE-binding protein 2 (Q8IWT8_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q13219

UniProtKB/Swiss-Prot:

PAPP1_HUMAN :
  • Belongs to the peptidase M43B family.
Family:
  • Belongs to the peptidase M43B family.
genes like me logo Genes that share domains with PAPPA: view

Function for PAPPA Gene

Molecular function for PAPPA Gene

UniProtKB/Swiss-Prot Function:
Metalloproteinase which specifically cleaves IGFBP-4 and IGFBP-5, resulting in release of bound IGF. Cleavage of IGFBP-4 is dramatically enhanced by the presence of IGF, whereas cleavage of IGFBP-5 is slightly inhibited by the presence of IGF.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=Cleavage of the 135-Met- -Lys-136 bond in insulin-like growth factor binding protein (IGFBP)-4, and the 143-Ser- -Lys-144 bond in IGFBP-5.; EC=3.4.24.79;.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by complexation with the proform of PRG2.
UniProtKB/Swiss-Prot Induction:
By 8-bromoadenosine-3',5'-phosphate.
GENATLAS Biochemistry:
pregnancy-associated plasma protein A

Enzyme Numbers (IUBMB) for PAPPA Gene

Phenotypes From GWAS Catalog for PAPPA Gene

Gene Ontology (GO) - Molecular Function for PAPPA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004222 metalloendopeptidase activity IEA --
GO:0008233 peptidase activity IEA --
GO:0008237 metallopeptidase activity NAS 10913121
GO:0008270 zinc ion binding TAS,NAS 10077652
GO:0016787 hydrolase activity IEA --
genes like me logo Genes that share ontologies with PAPPA: view
genes like me logo Genes that share phenotypes with PAPPA: view

Animal Models for PAPPA Gene

MGI Knock Outs for PAPPA:

Animal Model Products

  • Taconic Biosciences Mouse Models for PAPPA

CRISPR Products

Clone Products

  • Applied Biological Materials (abm): Clones for PAPPA - Now 50% OFF >
  • * PAPPA as ready-to-use vector or virus: ORF | Lenti- | Retro- | Adeno- | AAV- | Protein Vector - Browse All
  • * PAPPA tags and reporters available: His, HA, Myc, Flag, GFP, RFP, Luciferase - Browse All

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

Localization for PAPPA Gene

Subcellular locations from UniProtKB/Swiss-Prot for PAPPA 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 PAPPA gene
Compartment Confidence
extracellular 5
plasma membrane 3
cytosol 2
cytoskeleton 1
nucleus 0
lysosome 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (1)
  • Plasma membrane (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for PAPPA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IEA --
genes like me logo Genes that share ontologies with PAPPA: view

Pathways & Interactions for PAPPA Gene

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

Gene Ontology (GO) - Biological Process for PAPPA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IEA --
GO:0007565 female pregnancy IEA,NAS 10077652
GO:0032354 response to follicle-stimulating hormone IEA --
GO:0044267 cellular protein metabolic process TAS --
GO:0051384 response to glucocorticoid IEA --
genes like me logo Genes that share ontologies with PAPPA: view

No data available for SIGNOR curated interactions for PAPPA Gene

Drugs & Compounds for PAPPA Gene

(17) Drugs for PAPPA Gene - From: DrugBank and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Phenethyl isothiocyanate Investigational Pharma Target 13

(14) Additional Compounds for PAPPA Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with PAPPA: view

Transcripts for PAPPA Gene

mRNA/cDNA for PAPPA Gene

(1) REFSEQ mRNAs :
(33) Additional mRNA sequences :
(8) Selected AceView cDNA sequences:
(3) Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Unigene Clusters for PAPPA Gene

Pregnancy-associated plasma protein A, pappalysin 1:
Representative Sequences:

CRISPR Products

Clone Products

  • Applied Biological Materials (abm): Clones for PAPPA - Now 50% OFF >
  • * PAPPA as ready-to-use vector or virus: ORF | Lenti- | Retro- | Adeno- | AAV- | Protein Vector - Browse All
  • * PAPPA tags and reporters available: His, HA, Myc, Flag, GFP, RFP, Luciferase - Browse All

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

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4a · 4b ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12a · 12b ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21a · 21b ^ 22 ^
SP1: - - -
SP2: - - - - - - -
SP3: -
SP4:
SP5:
SP6:
SP7: -
SP8: -
SP9:

ExUns: 23 ^ 24 ^ 25 ^ 26
SP1: -
SP2:
SP3:
SP4: -
SP5:
SP6:
SP7:
SP8:
SP9:

Relevant External Links for PAPPA Gene

GeneLoc Exon Structure for
PAPPA
ECgene alternative splicing isoforms for
PAPPA

Expression for PAPPA Gene

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

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for PAPPA Gene

This gene is overexpressed in Placenta (45.3), Gallbladder (12.0), and Testis (6.5).

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



NURSA nuclear receptor signaling pathways regulating expression of PAPPA Gene:

PAPPA

SOURCE GeneReport for Unigene cluster for PAPPA Gene:

Hs.643599

mRNA Expression by UniProt/SwissProt for PAPPA Gene:

Q13219-PAPP1_HUMAN
Tissue specificity: High levels in placenta and pregnancy serum. In placenta, expressed in X cells in septa and anchoring villi, and in syncytiotrophoblasts in the chorionic villi. Lower levels are found in a variety of other tissues including kidney, myometrium, endometrium, ovaries, breast, prostate, bone marrow, colon, fibroblasts and osteoblasts.

Evidence on tissue expression from TISSUES for PAPPA Gene

  • Nervous system(3.1)
  • Blood(2.3)
  • Heart(2)
genes like me logo Genes that share expression patterns with PAPPA: view

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for PAPPA Gene

Orthologs for PAPPA Gene

This gene was present in the common ancestor of chordates.

Orthologs for PAPPA Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia PAPPA 34 35
  • 99.36 (n)
dog
(Canis familiaris)
Mammalia PAPPA 34 35
  • 89.57 (n)
cow
(Bos Taurus)
Mammalia PAPPA 34 35
  • 89.23 (n)
mouse
(Mus musculus)
Mammalia Pappa 17 34 35
  • 88.75 (n)
rat
(Rattus norvegicus)
Mammalia Pappa 34
  • 88.29 (n)
oppossum
(Monodelphis domestica)
Mammalia PAPPA 35
  • 84 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia PAPPA 35
  • 80 (a)
OneToOne
chicken
(Gallus gallus)
Aves PAPPA 34 35
  • 78.05 (n)
lizard
(Anolis carolinensis)
Reptilia PAPPA 35
  • 71 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia pappa 34
  • 69.28 (n)
zebrafish
(Danio rerio)
Actinopterygii pappab 34 35
  • 63.94 (n)
pappaa 35
  • 59 (a)
OneToMany
Dr.17149 34
Species where no ortholog for PAPPA 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 PAPPA Gene

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

Paralogs for PAPPA Gene

(1) SIMAP similar genes for PAPPA Gene using alignment to 3 proteins:

  • PAPP1_HUMAN
  • F5GZ19_HUMAN
  • Q5QFB7_HUMAN
genes like me logo Genes that share paralogs with PAPPA: view

Variants for PAPPA Gene

Sequence variations from dbSNP and Humsavar for PAPPA Gene

SNP ID Clin Chr 09 pos Variation AA Info Type
rs1000027712 -- 116,363,430(+) G/T intron_variant
rs1000043299 -- 116,337,597(+) C/T intron_variant
rs1000045827 -- 116,253,451(+) C/A intron_variant
rs1000046094 -- 116,386,561(+) T/G intron_variant
rs1000054500 -- 116,179,795(+) A/G genic_upstream_transcript_variant, intron_variant

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

Variant ID Type Subtype PubMed ID
dgv4132n106 CNV deletion 24896259
dgv7707n100 CNV gain 25217958
esv1223240 CNV deletion 17803354
esv2047171 CNV deletion 18987734
esv2661287 CNV deletion 23128226
esv2677393 CNV deletion 23128226
esv2738972 CNV deletion 23290073
esv2738974 CNV deletion 23290073
esv2738975 CNV deletion 23290073
esv3621585 CNV loss 21293372
esv3621586 CNV loss 21293372
nsv1115223 CNV deletion 24896259
nsv1152430 CNV deletion 26484159
nsv615253 CNV gain 21841781
nsv7434 OTHER inversion 18451855
nsv825063 CNV gain 20364138
nsv825064 CNV loss 20364138

Variation tolerance for PAPPA Gene

Residual Variation Intolerance Score: 15.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.27; 62.58% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PAPPA Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
PAPPA

SNP Genotyping and Copy Number Assay Products

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

Disorders for PAPPA Gene

MalaCards: The human disease database

(15) MalaCards diseases for PAPPA Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
orofaciodigital syndrome viii
  • cleft lip/palate with abnormal thumbs and microcephaly
down syndrome
  • trisomy 21
trisomy 22
  • chromosome 22 trisomy
pre-eclampsia
  • toxemia of pregnancy
ectopic pregnancy
  • eccyesis
- elite association - COSMIC cancer census association via MalaCards
Search PAPPA in MalaCards View complete list of genes associated with diseases

Additional Disease Information for PAPPA

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 PAPPA: view

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

Publications for PAPPA Gene

  1. Complex of pregnancy-associated plasma protein-A and the proform of eosinophil major basic protein. Disulfide structure and carbohydrate attachment. (PMID: 12421832) Overgaard MT … Oxvig C (The Journal of biological chemistry 2003) 3 4 23 58
  2. Pregnancy-associated plasma protein-A (PAPP-A) cleaves insulin-like growth factor binding protein (IGFBP)-5 independent of IGF: implications for the mechanism of IGFBP-4 proteolysis by PAPP-A. (PMID: 11522292) Laursen LS … Oxvig C (FEBS letters 2001) 3 4 23 58
  3. Expression of recombinant human pregnancy-associated plasma protein-A and identification of the proform of eosinophil major basic protein as its physiological inhibitor. (PMID: 10913121) Overgaard MT … Oxvig C (The Journal of biological chemistry 2000) 3 4 23 58
  4. Amino acid sequence of human pregnancy-associated plasma protein-A derived from cloned cDNA. (PMID: 7508748) Kristensen T … Sottrup-Jensen L (Biochemistry 1994) 3 4 23 58
  5. Localization of pregnancy-associated plasma protein-A and colocalization of pregnancy-associated plasma protein-A messenger ribonucleic acid and eosinophil granule major basic protein messenger ribonucleic acid in placenta. (PMID: 7526035) Bonno M … Gleich GJ (Laboratory investigation; a journal of technical methods and pathology 1994) 3 4 23 58

Products for PAPPA Gene

Sources for PAPPA Gene

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