Target type: cellularcomponent
A class III phosphatidylinositol 3-kinase complex that is involved in autophagy. In budding yeast, this complex consists of Vps30p, Vps34p, Apg14p and Vps15p. [GOC:ha, GOC:rb, PMID:11157979, PMID:16421251]
The phosphatidylinositol 3-kinase (PI3K) complex, class III, type I, is a multi-protein complex involved in the regulation of autophagy and other cellular processes. This complex is comprised of four core components:
1. **VPS34 (vacuolar protein sorting 34)**: This is the catalytic subunit of the complex, responsible for the phosphorylation of phosphatidylinositol (PtdIns) to produce phosphatidylinositol-3-phosphate (PtdIns(3)P). VPS34 is a lipid kinase that belongs to the PI3K family.
2. **VPS15 (vacuolar protein sorting 15)**: This is a regulatory subunit that acts as a scaffold protein, interacting with VPS34 and other components of the complex. VPS15 is also a protein kinase and is required for the activation of VPS34.
3. **ATG14 (autophagy-related protein 14)**: This protein is essential for the formation of autophagosomes, the double-membrane vesicles that engulf cellular components during autophagy. ATG14 binds to VPS34 and VPS15, and its presence directs the complex to specific membranes where autophagosome formation occurs.
4. **Beclin 1 (BECN1)**: This protein is a key regulator of autophagy and plays a critical role in the initiation of autophagosome formation. Beclin 1 interacts with VPS34, VPS15, and ATG14, and its phosphorylation by VPS15 promotes the activation of the complex.
The class III PI3K complex type I is localized to specific cellular compartments, including the endoplasmic reticulum (ER), the Golgi apparatus, and endosomes. It is also found at sites of autophagosome formation. The complex is involved in a variety of cellular processes, including autophagy, vesicle trafficking, and membrane homeostasis.
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| Protein | Definition | Taxonomy |
|---|---|---|
| Phosphatidylinositol 3-kinase catalytic subunit type 3 | A phosphatidylinositol 3-kinase catalytic subunit type 3 that is encoded in the genome of human. [PRO:DNx] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| ML162 | ML162 : A monochlorobenzene that is benzene substituted by (chloroacetyl){2-oxo-2-[(2-phenylethyl)amino]-1-(thiophen-2-yl)ethyl}amino, chloro and methoxy groups at positions 1, 3 and 4, respectively. It is a covalent inhibitor of glutathione peroxidase 4 (GPX4) that induces ferroptosis in cells. | monochlorobenzenes; monomethoxybenzene; organochlorine compound; secondary carboxamide; tertiary carboxamide; thiophenes | EC 1.11.1.9 (glutathione peroxidase) inhibitor; ferroptosis inducer |
| PI3-Kinase alpha Inhibitor 2 | organic heterobicyclic compound; organonitrogen heterocyclic compound; organosulfur heterocyclic compound | ||
| idelalisib | idelalisib : A member of the class of quinazolines that is 5-fluoro-3-phenylquinazolin-4-one in which the hydrogen at position 2 is replaced by a (1S)-1-(3H-purin-6-ylamino)propyl group. used for for the treatment of refractory indolent non-Hodgkin's lymphoma and relapsed chronic lymphocytic leukemia. idelalisib: an antineoplastic agent and p110delta inhibitor; structure in first source | aromatic amine; organofluorine compound; purines; quinazolines; secondary amino compound | antineoplastic agent; apoptosis inducer; EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor |
| zstk474 | ZSTK-474 : A triamino-1,3,5-triazine that is 1,3,5-triazine in which two of the hydrogens have been replaced by morpholin-4-yl groups while the third hydrogen has been replaced by a 2-(difluoromethyl)benzimidazol-1-yl group. It is an inhibitor of phosphatidylinositol 3-kinase. | benzimidazoles; morpholines; organofluorine compound; triamino-1,3,5-triazine | antineoplastic agent; EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor |
| dactolisib | dactolisib : An imidazoquinoline that is 3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]quinoline substituted at position 1 by a 4-(1-cyanoisopropyl)phenyl group and at position 8 by a quinolin-3-yl group. A dual PI3K/mTOR inhibitor used in cancer treatment. dactolisib: antineoplastic agent that inhibits both phosphatidylinositol 3-kinase and mTOR | imidazoquinoline; nitrile; quinolines; ring assembly; ureas | antineoplastic agent; EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor; mTOR inhibitor |
| ku 60019 | |||
| buparlisib | NVP-BKM120: a pan class I PI3 kinase inhibitor with antineoplastic activity; structure in first source | aminopyridine; aminopyrimidine; morpholines; organofluorine compound | antineoplastic agent; EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor |
| gdc 0941 | pictrelisib : A sulfonamide composed of indazole, morpholine, and methylsulfonyl-substituted piperazine rings bound to a thienopyrimidine ring. | indazoles; morpholines; piperazines; sulfonamide; thienopyrimidine | EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor |
| gdc 0980 | |||
| azd2014 | vistusertib: potent and selective dual mTORC1 and mTORC2 inhibitor; structure in first source | ||
| pki 587 | gedatolisib: inhibits both phosphatidylinositol 3-kinase and mTOR; structure in first source | ||
| 5-(4-amino-1-propan-2-yl-3-pyrazolo[3,4-d]pyrimidinyl)-1,3-benzoxazol-2-amine | sapanisertib: an mTOR inhibitor | benzoxazole | |
| ch 5132799 | CH 5132799: structure in first source | ||
| torin 1 | torin 1 : A member of the class of pyridoquinolines that is 9-(quinolin-3-yl)benzo[h][1,6]naphthyridin-2-one bearing an additional 4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl substituent at position 1. It is a potent inhibitor of mTOR and exhibits anti-cancer properties. | N-acylpiperazine; N-arylpiperazine; organofluorine compound; pyridoquinoline; quinolines | antineoplastic agent; mTOR inhibitor |
| gdc-0032 | |||
| spautin-1 | |||
| torin 2 | torin 2 : A member of the class of pyridoquinolines that is benzo[h][1,6]naphthyridin-2-one carrying additional 3-(trifluoromethyl)phenyl and 6-aminopyridin-3-yl substituents at positions 1 and 9 respectively. It is a potent inhibitor of mTOR and exhibits anti-cancer properties. | aminopyridine; organofluorine compound; primary amino compound; pyridoquinoline | antineoplastic agent; mTOR inhibitor |
| cudc-907 | |||
| sar245408 | |||
| byl719 | proline derivative | ||
| amg 511 | AMG 511: structure in first source | ||
| cc-223 | |||
| sar405 | SAR405: a Vps34 inhibitor with antineoplastic activity; structure in first source |