Target type: cellularcomponent
A class III phosphatidylinositol 3-kinase complex that is involved in vacuolar protein sorting (VPS) via endosomes. In budding yeast, this complex consists of Vps30p, Vps34p, Vps38 and Vps15p. [GOC:ha, GOC:rb, PMID:11157979, PMID:16421251]
The phosphatidylinositol 3-kinase (PI3K) complex class III, type II is a multi-protein complex involved in autophagy, a cellular process of degrading and recycling cellular components. It is a crucial component of the autophagosome formation pathway, playing a vital role in the initiation and maturation of these double-membrane vesicles.
The complex consists of multiple core components, including:
* **VPS34:** This is the catalytic subunit, responsible for the phosphorylation of phosphatidylinositol (PtdIns) to produce phosphatidylinositol-3-phosphate (PtdIns3P). PtdIns3P acts as a key signaling molecule, recruiting specific proteins to the autophagosome membrane.
* **VPS15:** Also known as p150, this protein acts as a regulatory subunit. It is crucial for the stability and proper localization of the complex. It interacts with VPS34 and other components, facilitating the activation and assembly of the complex.
* **Beclin-1:** This protein is an essential autophagy-related protein and is a core component of the class III PI3K complex. It binds to VPS34 and facilitates the recruitment of other autophagy proteins, including ATG14.
* **ATG14:** This protein serves as a scaffolding protein, recruiting other autophagy proteins to the complex. It plays a crucial role in the initiation of autophagosome formation.
* **UVRAG:** This protein interacts with Beclin-1 and promotes the formation of the autophagosome. It is also involved in the regulation of autophagy.
The class III PI3K complex, type II is localized to the endoplasmic reticulum (ER) membrane. It interacts with various signaling molecules and autophagy proteins, influencing the formation of the autophagosome. The complex is activated by specific stimuli, such as nutrient starvation or cellular stress.
Upon activation, the complex generates PtdIns3P, which acts as a recruitment signal. This signaling molecule attracts various autophagy proteins to the nascent autophagosome membrane, leading to the formation of a double-membrane vesicle. These autophagosomes engulf cellular components, like damaged organelles or misfolded proteins, and deliver them to lysosomes for degradation and recycling.
The class III PI3K complex, type II is essential for maintaining cellular homeostasis. It plays a critical role in autophagy, a fundamental process involved in cellular degradation and recycling. Disruptions in the function of this complex can lead to various cellular defects and pathologies, emphasizing its significance in cellular health.'
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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 |