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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
  • 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
  • Pregnacy-Associated Plasma Protein A 3
  • Pappalysin-1 3
  • 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

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). It is thought to be involved in local proliferative processes such as wound healing and bone remodeling. Low plasma level of this protein has been suggested as a biochemical marker for pregnancies with aneuploid fetuses. [provided by RefSeq, Jul 2008]

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. 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

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

Genomics for PAPPA Gene

Regulatory Elements for PAPPA Gene

Enhancers for PAPPA 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
GH09F116470 1.2 Ensembl ENCODE 10.4 +317.6 317628 2.3 TBP HDAC1 PKNOX1 ATF1 ARNT TBL1XR1 GATA2 ZBTB2 CEBPB ZEB2 PAPPA-AS1 LOC105376241 PAPPA ASTN2-AS1
GH09F116464 1 ENCODE 10.5 +312.1 312069 2.5 PKNOX1 ATF1 ARNT CREB3L1 ELK1 GATA2 GTF2B NCOA1 REST CREB3 PAPPA-AS1 PAPPA LOC105376241 ASTN2-AS1
GH09F116151 1.3 FANTOM5 ENCODE 7.6 +1.2 1191 7.6 TBP SIN3A FEZF1 RAD21 GLIS2 FOS CEBPB ZEB2 REST ZNF341 PAPPA GC09P116156 GC09P116173
GH09F116661 0.9 Ensembl ENCODE 10.5 +507.4 507410 0.4 CTCF ZNF654 TRIM22 ZNF384 REST RAD21 RFX5 ZNF143 SMC3 MIXL1 TRIM32 ASTN2 PAPPA ENSG00000230894 LOC105376240
GH09F116500 0.6 Ensembl 14.8 +346.6 346610 0.4 JUND ATF3 GLIS1 BHLHE40 HMBOX1 TRIM24 ZNF652 ATF2 PAPPA ASTN2-AS1 PAPPA-AS1 ENSG00000230894
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around PAPPA on UCSC Golden Path with GeneCards custom track

Promoters for PAPPA Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00001312654 1108 3401 TBP TAF1 SIN3A E2F1 ZFHX2 POLR2A PRDM10 NFIA RNF2 BHLHE40

Genomic Location for PAPPA Gene

Chromosome:
9
Start:
116,153,792 bp from pter
End:
116,402,322 bp from pter
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 Asn 390, Asn 402, Asn 429, Asn 480, Asn 601, Asn 619, Asn 725, Asn 825, Asn 1026, Asn 1222, Asn 1226, Asn 1323, Asn 1465, and Asn 1519
  • Modification sites at PhosphoSitePlus

Other Protein References for PAPPA Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • R&D Systems Antibodies for PAPPA (Pappalysin-1/PAPP-A)
  • Abcam antibodies for PAPPA
  • Santa Cruz Biotechnology (SCBT) Antibodies for PAPPA

No data available for DME Specific Peptides for PAPPA Gene

Domains & Families for PAPPA Gene

Gene Families for PAPPA Gene

Graphical View of Domain Structure for InterPro Entry

Q13219

UniProtKB/Swiss-Prot:

PAPP1_HUMAN :
  • Contains 5 Sushi (CCP/SCR) domains.
  • Belongs to the peptidase M43B family.
Domain:
  • Contains 5 Sushi (CCP/SCR) domains.
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

GENATLAS Biochemistry:
pregnancy-associated plasma protein A
UniProtKB/Swiss-Prot CatalyticActivity:
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.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by complexation with the proform of PRG2.
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 Induction:
By 8-bromoadenosine-3,5-phosphate.

Enzyme Numbers (IUBMB) for PAPPA Gene

Gene Ontology (GO) - Molecular Function for PAPPA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004222 metalloendopeptidase activity TAS --
GO:0008233 peptidase activity IEA --
GO:0008237 metallopeptidase activity NAS 10913121
GO:0008270 zinc ion binding NAS,TAS 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

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

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
cytoskeleton 2
cytosol 2
nucleus 1
lysosome 1

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 NAS,TAS 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

(15) Drugs for PAPPA Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(15) 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

Unigene Clusters for PAPPA Gene

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

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

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 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, PaxDb, 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.
genes like me logo Genes that share expression patterns with PAPPA: view

Primer Products

No data available for mRNA differential expression in normal tissues and Protein tissue co-expression partners 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 34 16 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)

Paralogs for PAPPA Gene

Paralogs for PAPPA Gene

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

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 Sequence Context AA Info Type
rs1003858 -- 116,202,676(+) TTGTT(C/G)TTTGT intron-variant
rs1003859 -- 116,202,814(+) GCTCC(A/G)AAAAT intron-variant
rs10113955 -- 116,277,872(+) catgt(C/T)ggaca intron-variant
rs10114003 -- 116,277,791(+) cctac(C/G)tcagc intron-variant
rs10118006 -- 116,257,689(+) agagc(A/G)agact intron-variant

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

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

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)

Relevant External Links for PAPPA Gene

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

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
  • edwards syndrome
down syndrome
  • complete trisomy 21 syndrome
trisomy 22
  • chromosome 22 trisomy
ectopic pregnancy
  • eccyesis
gestational diabetes
  • gdm
- elite association - COSMIC cancer census association via MalaCards
Search PAPPA in MalaCards View complete list of genes associated with diseases

Relevant External Links for PAPPA

Genetic Association Database (GAD)
PAPPA
Human Genome Epidemiology (HuGE) Navigator
PAPPA
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
PAPPA
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 sites. (PMID: 12421832) Overgaard M.T. … Oxvig C. (J. Biol. Chem. 2003) 3 4 22 64
  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 L.S. … Oxvig C. (FEBS Lett. 2001) 3 4 22 64
  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 M.T. … Oxvig C. (J. Biol. Chem. 2000) 3 4 22 64
  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 22 64
  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 G.J. (Lab. Invest. 1994) 3 4 22 64

Products for PAPPA Gene

Sources for PAPPA Gene

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