Summary for peptidase M43.004: pappalysin-1

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Literature Human EST Substrates Inhibitors


MEROPS Namepappalysin-1
Other namesinsulin-like growth factor binding protein-4 protease, PAPPA g.p. (Homo sapiens), pregnancy-associated plasma protein A
Domain architecture
MEROPS Classification
Classification Clan MA >> Subclan MA(M) >> Family M43 >> Subfamily B >> M43.004
Holotypepappalysin-1 (Homo sapiens), Uniprot accession Q13219 (peptidase unit: 442-873), MERNUM MER0002217
History Identifier created: MEROPS 6.20 (24 March 2003)
Catalytic typeMetallo
PeplistIncluded in the Peplist with identifier PL00257
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.24 (Metalloendopeptidases) >> Peptidase
EnzymologyBRENDA database
Proteolytic eventsCutDB database (3 cleavages)
Activity statushuman: active (Oxvig et al., 2004)
mouse: active (by similarity to human) (Conover et al., 2004)
PhysiologyPappalysin-1 cleaves insulin-like growth factor (IGF) binding protein-4 (IGFBP-4), causing a dramatic reduction in its affinity for IGF-I and -II. Acting in this way it is a regulator of IGF bioactivity in the human ovary and the cardiovascular system (Laursen et al., 2002). Pappalysin-1 is also responsible for IGF-dependent degradation of IGFBP-2 (Monget et al., 2003). Also contributes to the physiological proteolysis of IGFBP-5 (Rivera & Fortune, 2003). There is evidence that pappalysin-1 plays an essential role in determining IGF-II bioavailability for optimal fetal growth and development in the mouse (Bale & Conover, 2005).
KnockoutMice homozygous for targeted disruption of the pappalysin-1 gene were viable but 60% the size of wild-type littermates at birth (Conover et al., 2004). .
Other databases TREEFAM
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
PAPPA 9q33.1 ENSG00000119398 5069 PAPPA 176385
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
Pappa 4:C1 ENSMUSG00000028370 18491 MGI:97479