GenAge entry for PAPPA (Homo sapiens)

Gene name (HAGRID: 254)

HGNC symbol
PAPPA 
Aliases
PAPP-A; PAPPA1; IGFBP-4ase; PAPA; ASBABP2; DIPLA1 
Common name
pregnancy-associated plasma protein A, pappalysin 1 

Potential relevance to the human ageing process

Main reason for selection
Entry selected based on evidence linking the gene product to a pathway or mechanism linked to ageing
Description

PAPPA is a secreted metalloproteinase that cleaves insulin-like growth factor binding proteins, promoting local insulin-like growth factor (IGF) signalling. PAPPA may be involved in local cell proliferative processes. In humans, PAPPA levels have been associated with coronary heart disease [1893].

Genetic deletion of PAPPA in mice extends mean and maximum lifespan by 30-40% and reduces cancer incidence with no reduction in food intake or secondary endocrine abnormalities [1843]. However, it was not established whether the ageing process was delayed in these animals. Knockout mice are also smaller at birth than controls [1879]. Mitochondrial oxidative capacity is significantly increased in the skeletal muscle of PAPPA knockout mice. Aged PAPPA knockout mice exhibit significantly enhanced endurance. Genes related to muscle function, increased metabolism (particularly lipid metabolism) and decreased stress are upregulated when compared to wild type mice [4349]. PAPPA knockout mice fed a high fat diet have a significant increase in lifespan (27%) when compared to wild type mice. As PAPPA may play a role in dietary restriction, resistance to metabolic dysfunction with age could contribute to the enhanced longevity of PAPPA knockout mice [4341].

Cytogenetic information

Cytogenetic band
9q33.2
Location
116,153,792 bp to 116,402,321 bp
Orientation
Plus strand
Display region using the UCSC Genome Browser (GRCh38/hg38)

Protein information

Gene Ontology
Process: GO:0006508; proteolysis
GO:0007565; female pregnancy
GO:0032354; response to follicle-stimulating hormone
GO:0044267; cellular protein metabolic process
GO:0051384; response to glucocorticoid
Cellular component: GO:0005576; extracellular region
GO:0005615; extracellular space
Function: GO:0004222; metalloendopeptidase activity
GO:0008237; metallopeptidase activity
GO:0008270; zinc ion binding
Show all GO terms

Protein interactions and network

Protein-protein interacting partners in GenAge
H2AFX
STRING interaction network
Protein-Protein network diagram for PAPPA

Retrieve sequences for PAPPA

ORF
ORF
CDS
CDS

Homologs in model organisms

Danio rerio
CABZ01089223.1
Mus musculus
Pappa
Rattus norvegicus
Pappa

In other databases

GenAge model organism genes
  • A homolog of this gene for Mus musculus is present as Pappa

Selected references

External links

EPD
ORF Accession
NM_002581
CDS Accession
NP_002572
OMIM
176385
HPRD
01448
Ensembl
PAPPA
UniProt/Swiss-Prot
PAPP1_HUMAN
GeneCards
PAPPA
Entrez Gene
5069
UniGene
643599
GenAtlas
PAPPA
Internet
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