XPNPEP3

XPNPEP3 belongs to the family of X-pro-aminopeptidases that utilize a metal cofactor, and remove the N-terminal amino acid from peptides with a proline residue in the penultimate position. XPNPEP3 localizes to the mitochondria of renal cells, and have a role in ciliary function. Mutations in XPNPEP3 are associated with nephronophthisis-like nephropathy-1.

Full Name

X-prolyl 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.

Biological Process

Biological Process glomerular filtration Source:MGI1 Publication
Biological Process protein processing Source:MGI1 Publication
Biological Process proteolysis Source:UniProtKB1 Publication

Cellular Location

Isoform 1
Mitochondrion
Cytoplasm
Mainly mitochondrial. Translocates to the cytoplasm following TNFRSF1B activation.
Isoform 2
Cytoplasm

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.