Summary for peptidase M43.004: pappalysin-1

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

 

Names
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)
Activity
Catalytic typeMetallo
PeplistIncluded in the Peplist with identifier PL00257
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.24 (Metalloendopeptidases) >> Peptidase 3.4.24.79
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 TREEFAMhttp://www.treefam.org/family/TF331636
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