GenAge entry for PAPPA (Homo sapiens)
Entry selected based on evidence directly linking the gene product to ageing in a mammalian model organism
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 directly linking the gene product to ageing in a mammalian model organism
- 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]. Inducing PAPPA deletion in adult female mice also increased lifespan. Median lifespan was increased by 21% and the mice had an extended healthspan [4514]. For this experiment it was not possible to induce PAPPA expression in adult male mice. 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
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
Hide GO termsFunction: GO:0004222; metalloendopeptidase activity
GO:0008237; metallopeptidase activity
GO:0008270; zinc ion binding
Protein interactions and network
Retrieve sequences for PAPPA
Homologs in model organisms
In other databases
- GenAge model organism genes
- A homolog of this gene for Mus musculus is present as Pappa