PLAA
Domain
The PUL domain is composed of 6 armadillo-like repeats and mediates the interaction with VCP C-terminus.
The PFU domain mediates interaction with ubiquitin.
Function
Plays a role in protein ubiquitination, sorting and degradation through its association with VCP (PubMed:27753622). Involved in ubiquitin-mediated membrane proteins trafficking to late endosomes in an ESCRT-dependent manner, and hence plays a role in synaptic vesicle recycling (By similarity). May play a role in macroautophagy, regulating for instance the clearance of damaged lysosomes (PubMed:27753622). Plays a role in cerebellar Purkinje cell development (By similarity). Positively regulates cytosolic and calcium-independent phospholipase A2 activities in a tumor necrosis factor alpha (TNF-alpha)- or lipopolysaccharide (LPS)-dependent manner, and hence prostaglandin E2 biosynthesis (PubMed:18291623, PubMed:28007986).
Involvement in disease
Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies
NDMSBA
An autosomal recessive neurodevelopmental disorder characterized by progressive microcephaly, spastic quadriparesis, global developmental delay, profound intellectual disability and severely impaired or absent motor function. More variable features include seizures and optic atrophy.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the WD repeat PLAP family.
Cellular localization
- Nucleus
- Cytoplasm
- Synapse
- Recruited to damaged lysosomes decorated with K48-linked ubiquitin chains.
Alternative names
PLAP, PLAA, Phospholipase A-2-activating protein, PLA2P