X-prolyl aminopeptidase (EC 3.4.11.9) is a proline-specific metalloaminopeptidase that specifically catalyzes the removal of any unsubstituted N-terminal amino acid that is adjacent to a penultimate proline residue. Because of its specificity toward proline, it has been suggested that X-prolyl aminopeptidase is important in the maturation and degradation of peptide hormones, neuropeptides, and tachykinins, as well as in the digestion of otherwise resistant dietary protein fragments, thereby complementing the pancreatic peptidases. Deficiency of X-prolyl aminopeptidase results in excretion of large amounts of imino-oligopeptides in urine (Blau et al., 1988).[supplied by OMIM][1]
Model organisms
Model organisms have been used in the study of XPNPEP1 function. A conditional knockout mouse line called Xpnpep1tm1a(KOMP)Wtsi was generated at the Wellcome Trust Sanger Institute.[2] Male and female animals underwent a standardized phenotypic screen[3] to determine the effects of deletion.[4][5][6][7] Additional screens performed: - In-depth immunological phenotyping[8] - in-depth bone and cartilage phenotyping[9]
↑Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
Vanhoof G, De Meester I, Goossens F, Hendriks D, Scharpé S, Yaron A (Aug 1992). "Kininase activity in human platelets: cleavage of the Arg1-Pro2 bond of bradykinin by aminopeptidase P". Biochemical Pharmacology. 44 (3): 479–87. doi:10.1016/0006-2952(92)90439-P. PMID1510698.
Blau N, Niederwieser A, Shmerling DH (1988). "Peptiduria presumably caused by aminopeptidase-P deficiency. A new inborn error of metabolism". Journal of Inherited Metabolic Disease. 11 Suppl 2: 240–2. doi:10.1007/BF01804246. PMID3141711.
Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID8125298.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.
Vanhoof G, Goossens F, Juliano MA, Juliano L, Hendriks D, Schatteman K, Lin AH, Scharpé S (1998). "Isolation and sequence analysis of a human cDNA clone (XPNPEPL) homologous to X-prolyl aminopeptidase (aminopeptidase P)". Cytogenetics and Cell Genetics. 78 (3–4): 275–80. doi:10.1159/000134671. PMID9465902.
Sprinkle TJ, Caldwell C, Ryan JW (Jun 2000). "Cloning, chromosomal sublocalization of the human soluble aminopeptidase P gene (XPNPEP1) to 10q25.3 and conservation of the putative proton shuttle and metal ligand binding sites with XPNPEP2". Archives of Biochemistry and Biophysics. 378 (1): 51–6. doi:10.1006/abbi.2000.1792. PMID10871044.
Cottrell GS, Hooper NM, Turner AJ (Dec 2000). "Cloning, expression, and characterization of human cytosolic aminopeptidase P: a single manganese(II)-dependent enzyme". Biochemistry. 39 (49): 15121–8. doi:10.1021/bi001585c. PMID11106490.
Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J (May 2003). "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides". Nature Biotechnology. 21 (5): 566–9. doi:10.1038/nbt810. PMID12665801.
