The human aminopeptidase P gene (XPNPEP) encodes an enzyme (EC 126.96.36.199) capable of hydrolyzing a terminal imido bond. The gene exhibits sequence homology to other metallopeptidases of the "pita-bread-fold" family, including five putative metal-binding sites. Human aminopeptidase P cDNA was recently cloned (Genbank U90724). Although a gene product of 75,490 daltons is predicted by the sequence, it is GPI-anchored, and therefore, it is likely that a signal peptide is removed during processing on the ER. Two genomic clones were obtained using PCR screening of 5'-UTR and most 3' cds into 3'UTR primer pairs designed from the cDNA sequence. The GPI-anchored form of aminopeptidase P was localized to X and further sublocalized specifically to human chromosome Xq25. Gene ordering about that locus is in progress. Localization of the soluble form of the enzyme has not yet been determined. Additional sequence has been obtained from these clones and will be presented. A previous case study on a peptiduria in two related male subjects was reported some time ago. One subject was treated for epilepsy and was severely mentally retarded. The subject's brother also exhibited the peptiduria, but was asymptomatic. Both individuals did not have measurable levels of aminopeptidase P above background. This may represent a sex-lined mutation and is under investigation. The bond cleaved by this enzyme is common to several collagen degradation products, vasoactive peptides and cytokines, and some neuropeptides.
|Original language||English (US)|
|State||Published - 1998|
ASJC Scopus subject areas
- Molecular Biology