PREPL
Function
Serine peptidase whose precise substrate specificity remains unclear (PubMed:16143824, PubMed:16385448, PubMed:28726805). Does not cleave peptides after a arginine or lysine residue (PubMed:16143824). Regulates trans-Golgi network morphology and sorting by regulating the membrane binding of the AP-1 complex (PubMed:23321636). May play a role in the regulation of synaptic vesicle exocytosis (PubMed:24610330).
Involvement in disease
Hypotonia-cystinuria syndrome
HCS
Characterized generalized hypotonia at birth, nephrolithiasis, growth hormone deficiency, minor facial dysmorphism, failure to thrive, followed by hyperphagia and rapid weight gain in late childhood.
None
The gene represented in this entry is involved in disease pathogenesis. Hypotonia-cystinuria syndrome is a contiguous gene syndrome caused by a homozygous deletion on chromosome 2p21 that disrupts the gene represented in this entry and SLC3A1 (PubMed:16385448, PubMed:21686663). A homozygous 77.4-kb deletion that disrupts the gene represented in this entry, SLC3A1 and CAMKMT, causes atypical hypotonia-cystinuria syndrome, characterized by mild to moderate intellectual disability and respiratory chain complex IV deficiency (PubMed:21686663). Patient cells exhibit a larger trans-Golgi network and a reduced redistribution of AP-1 complex, which causes impairment in AP-1 mediated membrane-cytoplasm recycling and secretion (PubMed:23321636).
Myasthenic syndrome, congenital, 22
CMS22
A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features include easy fatigability and muscle weakness. CMS22 is an autosomal recessive form characterized by neonatal hypotonia.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the peptidase S9A family.
Tissue Specificity
Expressed in pyramidal neurons of the temporal cortex and neocortex (at protein level) (PubMed:23485813). Widely expressed (PubMed:15913950, PubMed:16385448). Expressed at higher level in brain, skeletal muscle, heart and kidney (PubMed:15913950, PubMed:16385448). Expressed at the endplates in the neuromuscular junction (PubMed:24610330).
Cellular localization
- Cytoplasm
- Cytosol
- Golgi apparatus
- trans-Golgi network
- Cytoplasm
- Cytoskeleton
- Golgi apparatus
- Nucleus
- Co-localizes with AP-1 in the trans-Golgi network (By similarity). Co-localizes with MAP2 and ACTB on the cytoskeleton (By similarity). Co-localizes with STX6 and GOSR2 at the Golgi apparatus (By similarity).
Alternative names
KIAA0436, PREPL, Prolyl endopeptidase-like, Prolylendopeptidase-like