Xaa-Pro aminopeptidase 3
Function
Catalyzes the removal of a penultimate prolyl residue from the N-termini of peptides, such as Leu-Pro-Ala (PubMed:25609706, PubMed:28476889). Also shows low activity towards peptides with Ala or Ser at the P1 position (PubMed:28476889).
Isoform 1
Promotes TNFRSF1B-mediated phosphorylation of MAPK8/JNK1 and MAPK9/JNK2, suggesting a function as an adapter protein for TNFRSF1B; the effect is independent of XPNPEP3 peptidase activity. May inhibit apoptotic cell death induced via TNF-TNFRSF1B signaling.
Involvement in disease
Nephronophthisis-like nephropathy 1
NPHPL1
An autosomal recessive disorder with features of nephronophthisis, a cystic kidney disease leading to end-stage renal failure. Nephronophthisis is histologically characterized by modifications of the tubules with thickening of the basement membrane, interstitial fibrosis and, in the advanced stages, medullary cysts. Typical clinical manifestation are chronic renal failure, anemia, polyuria, polydipsia, isosthenuria, and growth retardation. Associations with extrarenal symptoms are frequent. In NPHPL1 patients, extrarenal symptoms include hypertension, essential tremor, sensorineural hearing loss and gout. Severely affected individuals can manifest a mitochondrial disorder with isolated complex I deficiency activity in muscle, seizures, intellectual disability and hypertrophic dilated cardiomyopathy.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the peptidase M24B family.
Tissue Specificity
Isoform 1 and isoform 2 are widely expressed, with isoform 1 being more abundant.
Cellular localization
- Isoform 1
- Mitochondrion
- Cytoplasm
- Mainly mitochondrial. Translocates to the cytoplasm following TNFRSF1B activation.
- Isoform 2
- Cytoplasm
Alternative names
Xaa-Pro aminopeptidase 3, X-Pro aminopeptidase 3, Aminopeptidase P3, APP3, XPNPEP3