Phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3)
The protein contains 887 amino acids for an estimated molecular weight of 101549 Da.
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. 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 abcission step in cytokinesis, probably in the context of PI3KC3-C2 (PubMed:20643123, PubMed:20208530). Involved in the transport of lysosomal enzyme precursors to lysosomes. Required for transport from early to late endosomes (By similarity). (updated: April 7, 2021)
Protein identification was indicated in the following studies:
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Autophagosome assembly
Autophagy
Autophagy of peroxisome
Cell cycle
Cell division
Cellular response to glucose starvation
Early endosome to late endosome transport
Endocytosis
Endosome organization
Macroautophagy
Phosphatidylinositol biosynthetic process
Phosphatidylinositol phosphate biosynthetic process
Phosphatidylinositol-3-phosphate biosynthetic process
Phosphatidylinositol-mediated signaling
Protein lipidation
Protein localization to phagophore assembly site
Protein phosphorylation
Protein processing
Regulation of cytokinesis
Regulation of protein secretion
Response to leucine
Toll-like receptor 9 signaling pathway
Cellular Component
Autolysosome
Axoneme
Cytoplasm
Cytosol
Endosome
Late endosome
Membrane
Midbody
Peroxisome
Phagocytic vesicle membrane
Phagophore assembly site
Phosphatidylinositol 3-kinase complex, class III
Phosphatidylinositol 3-kinase complex, class III, type I
Phosphatidylinositol 3-kinase complex, class III, type II
The reference OMIM entry for this protein is 602609
Phosphatidylinositol 3-kinase, class 3; pik3c3
Vps34, yeast, homolog of
Phosphoinositide (PI) 3-kinases are involved in both receptor-mediated signal transduction and intracellular trafficking. In yeast, the vps34 gene product is a PI 3-kinase that mediates the active diversion of proteins from the secretory pathway to vacuoles. Mammals appear to have a family of PI 3-kinases, which also includes PIK3CG (601232) and PIK3CA (171834).
CLONING
Volinia et al. (1995) cloned the human homolog of the yeast vps34 PI 3-kinase. The full-length PIK3C3 cDNA encodes an 887-amino acid polypeptide that is 37% identical to yeast vps34 over its entire length. Its predicted and observed molecular mass is approximately 100 kD. By Northern blot analysis, the PIK3C3 gene was expressed as a 3.7-kb transcript in all human tissues examined. Volinia et al. (1995) showed that PIK3C3 has a substrate specificity and ion requirements that are distinct from the other known mammalian PI 3-kinases. The PIK3C3 gene does not associate with the p85 regulatory subunit (171833) but does form a complex with p150 (602610), a mammalian homolog of another protein in the yeast vps pathway.BIOCHEMICAL FEATURES
- Crystal Structure Miller et al. (2010) solved the crystal structure of Vps34 at 2.9-angstrom resolution, which revealed a constricted adenine-binding pocket, suggesting the reason that specific inhibitors of this class of PI3K have proven elusive. Both the phosphoinositide-binding loop and the carboxyl-terminal helix of Vps34 mediate catalysis on membranes and suppress futile adenosine triphosphatase cycles. Vps34 appears to alternate between a closed cytosolic form and an open form on the membrane. Structures of Vps34 complexes with a series of inhibitors revealed the reason that an autophagy inhibitor preferentially inhibits Vps34 and underpinned the development of new potent and specific Vps34 inhibitors. ... More on the omim web site
April 10, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 602609 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).