WDR45
Domain
The L/FRRG motif is required for recruitment to PtdIns3P.
Function
Component of the autophagy machinery that controls the major intracellular degradation process by which cytoplasmic materials are packaged into autophagosomes and delivered to lysosomes for degradation (PubMed:23435086, PubMed:28561066). Binds phosphatidylinositol 3-phosphate (PtdIns3P) (PubMed:28561066). Activated by the STK11/AMPK signaling pathway upon starvation, WDR45 is involved in autophagosome assembly downstream of WIPI2, regulating the size of forming autophagosomes (PubMed:28561066). Together with WIPI1, promotes ATG2 (ATG2A or ATG2B)-mediated lipid transfer by enhancing ATG2-association with phosphatidylinositol 3-monophosphate (PI3P)-containing membranes (PubMed:31271352). Probably recruited to membranes through its PtdIns3P activity (PubMed:28561066).
Involvement in disease
Neurodegeneration with brain iron accumulation 5
NBIA5
A neurodegenerative disorder associated with iron accumulation in the brain, primarily in the basal ganglia. NBIA5 is characterized by global developmental delay in early childhood that is essentially static, with slow motor and cognitive gains until adolescence or early adulthood. In young adulthood, affected individuals develop progressive dystonia, parkinsonism, extrapyramidal signs, and dementia resulting in severe disability.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the WD repeat PROPPIN family.
Tissue Specificity
Ubiquitously expressed, with high expression in skeletal muscle and heart. Weakly expressed in liver and placenta. Expression is down-regulated in pancreatic and in kidney tumors.
Cellular localization
- Preautophagosomal structure
- Cytoplasm
- Diffusely localized in the cytoplasm under nutrient-rich conditions. Localizes to autophagic structures during starvation-induced autophagy.
Alternative names
WDRX1, WDRXI4, WIPI4, JM5, WDR45, WD repeat domain phosphoinositide-interacting protein 4, WIPI-4, WD repeat-containing protein 45