PIK3C3
Function
Catalytic subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis (PubMed:14617358, PubMed:33637724, PubMed:7628435). As part of PI3KC3-C1, promotes endoplasmic reticulum membrane curvature formation prior to vesicle budding (PubMed:32690950). Involved in regulation of degradative endocytic trafficking and required for the abscission step in cytokinesis, probably in the context of PI3KC3-C2 (PubMed:20208530, PubMed:20643123). Involved in the transport of lysosomal enzyme precursors to lysosomes (By similarity). Required for transport from early to late endosomes (By similarity).
(Microbial infection) Kinase activity is required for SARS coronavirus-2/SARS-CoV-2 replication.
Post-translational modifications
Ubiquitinated via 'Lys-29'- and 'Lys-48'-linked ubiquitination by UBE3C, promoting its degradation (PubMed:33637724). Deubiquitination by ZRANB1/TRABID promotes its stabilization, leading to autophagosome maturation (PubMed:33637724).
Sequence Similarities
Belongs to the PI3/PI4-kinase family.
Tissue Specificity
Ubiquitously expressed, with a highest expression in skeletal muscle.
Cellular localization
- Midbody
- Late endosome
- Cytoplasmic vesicle
- Autophagosome
- As component of the PI3K complex I localized to pre-autophagosome structures. As component of the PI3K complex II localized predominantly to endosomes (PubMed:14617358). Localizes also to discrete punctae along the ciliary axoneme and to the base of the ciliary axoneme (By similarity).
Alternative names
VPS34, PIK3C3, Phosphatidylinositol 3-kinase catalytic subunit type 3, PI3-kinase type 3, PI3K type 3, PtdIns-3-kinase type 3, Phosphatidylinositol 3-kinase p100 subunit, Phosphoinositide-3-kinase class 3, hVps34