| 简介 | Enables 1-phosphatidylinositol-3-kinase activity. Involved in several processes, including early endosome to late endosome transport; macroautophagy; and phosphatidylinositol-3-phosphate biosynthetic process. Acts upstream of or within autophagy and protein lipidation. Located in autolysosome; late endosome; and midbody. Part of phosphatidylinositol 3-kinase complex, class III. [provided by Alliance of Genome Resources, Nov 2024]
Diseases associated with PIK3C3 include Cowden Syndrome 1 and Lung Cancer. Among its related pathways are Insulin receptor signalling cascade and Early SARS-CoV-2 Infection Events. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and binding. An important paralog of this gene is PIK3CB.
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, 33637724, 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, 20643123).
Involved in the transport of lysosomal enzyme precursors to lysosomes (By similarity).
Required for transport from early to late endosomes (By similarity).
Midbody {ECO:0000269 PubMed:20208530}
Late endosome {ECO:0000269 PubMed:14617358}5
Cytoplasmic vesicle, autophagosome {ECO:0000305 PubMed:14617358}
Note: 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) {ECO:0000250 UniProtKB:Q6PF93 | ECO:0000305 PubMed:14617358}
Quaternary structure:
Component of the PI3K (PI3KC3/PI3K-III/class III phosphatidylinositol 3-kinase) complex the core of which is composed of the catalytic subunit PIK3C3, the regulatory subunit PIK3R4 and BECN1 associating with additional regulatory/auxiliary subunits to form alternative complex forms.
Alternative complex forms containing a fourth regulatory subunit in a mutually exclusive manner are: the PI3K complex I (PI3KC3-C1) containing ATG14, and the PI3K complex II (PI3KC3-C2) containing UVRAG.
PI3KC3-C1 displays a V-shaped architecture with PIK3R4 serving as a bridge between PIK3C3 and the ATG14:BECN1 subcomplex.
Both, PI3KC3-C1 and PI3KC3-C2, can associate with further regulatory subunits such as RUBCN, SH3GLB1/Bif-1 and AMBRA1 (PubMed:19050071, 19270696, 20643123, 23878393, 25490155, 7628435).
PI3KC3-C1 probably associates with PIK3CB (By similarity).
Interacts with RAB7A in the presence of PIK3R4 (PubMed:14617358).
Interacts with AMBRA1 (By similarity).
Interacts with BECN1P1/BECN2 (PubMed:23954414).
Interacts with SLAMF1 (PubMed:22493499).
May be a component of a complex composed of RAB5A (in GDP-bound form), DYN2 and PIK3C3 (By similarity).
Interacts with NCKAP1L (PubMed:16417406).
Interacts with ATG14; this interaction is increased in the absence of TMEM39A (PubMed:31806350).
Interacts with STEEP1; the interaction is STING1-dependent and required for trafficking of STING1 from the endoplasmic reticulum (PubMed:32690950).
Interacts with YWHAG (PubMed:33473107).
Interacts with ARMC3 (By similarity). |
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