Description: Homo sapiens pregnancy-associated plasma protein A, pappalysin 1 (PAPPA), mRNA. RefSeq Summary (NM_002581): 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]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. Transcript (Including UTRs) Position: hg19 chr9:118,916,071-119,164,600 Size: 248,530 Total Exon Count: 22 Strand: + Coding Region Position: hg19 chr9:118,916,452-119,158,895 Size: 242,444 Coding Exon Count: 22
ID:PAPP1_HUMAN DESCRIPTION: RecName: Full=Pappalysin-1; EC=3.4.24.79; AltName: Full=Insulin-like growth factor-dependent IGF-binding protein 4 protease; Short=IGF-dependent IGFBP-4 protease; Short=IGFBP-4ase; AltName: Full=Pregnancy-associated plasma protein A; Short=PAPP-A; Flags: Precursor; 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. CATALYTIC ACTIVITY: 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. COFACTOR: Binds 1 zinc ion per subunit (By similarity). ENZYME REGULATION: Inhibited by complexation with the proform of PRG2. SUBUNIT: Homodimer; disulfide-linked. In pregnancy serum, predominantly found as a disulfide-linked 2:2 heterotetramer with the proform of PRG2. SUBCELLULAR LOCATION: Secreted. 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. DEVELOPMENTAL STAGE: Present in serum and placenta during pregnancy; levels increase throughout pregnancy. INDUCTION: By 8-bromoadenosine-3',5'-phosphate. PTM: There appear to be no free sulfhydryl groups. SIMILARITY: Belongs to the peptidase M43B family. SIMILARITY: Contains 5 Sushi (CCP/SCR) domains. SEQUENCE CAUTION: Sequence=AAC50543.1; Type=Frameshift; Positions=51, 67;
Body Height Guillaume Lettre et al. Nature genetics 2008, Identification of ten loci associated with height highlights new biological pathways in human growth., Nature genetics.
[PubMed 18391950]
Echocardiography Ramachandran S Vasan et al. BMC medical genetics 2007, Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study., BMC medical genetics.
[PubMed 17903301]
In hypothesis-generating GWAS of echocardiography, ETT and BA vascular function in a moderate-sized community-based sample, we identified several SNPs that are candidates for replication attempts and we provide a web-based GWAS resource for the research community.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q13219
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
