GO:0034272 phosphatidylinositol 3-kinase complex, class III, type II: Components, Assembly and Research Methods, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0034272 describes the class III phosphatidylinositol 3-kinase complex, type II, a vacuolar protein sorting (VPS) complex that acts on endosomes and is composed in budding yeast of Vps30p, Vps34p, Vps38 and Vps15p.
• The complex is defined by its role in endosomal trafficking and vacuolar protein sorting, distinguishing it from the autophagy-specific class III PI3K complex I.
• Its catalytic core is the lipid kinase Vps34p, which phosphorylates phosphatidylinositol to generate phosphatidylinositol 3-phosphate (PtdIns3P) at endosomal membranes.
• Assembly and activity of class III PI3K complexes are controlled by ubiquitin and SUMO modifications, linking them to tumor-suppressor functions.
• Related class III PI3K complex components such as NRBF2 and STYK1 modulate complex assembly and autophagy, providing mechanistic insight into how these complexes are regulated.
• Studying GO:0034272 requires combining genetic perturbation, biochemical reconstitution and imaging approaches to resolve endosomal versus autophagic functions.
Description
GO:0034272, phosphatidylinositol 3-kinase complex, class III, type II, is a cellular component annotation that defines a specific class III phosphatidylinositol 3-kinase (PI3K) complex involved in vacuolar protein sorting (VPS) via endosomes. In budding yeast, this complex is composed of Vps30p, Vps34p, Vps38 and Vps15p, and it is distinct from the autophagy-specific class III PI3K complex I, which uses different accessory subunits. The type II complex is therefore a key node for understanding how cells sort cargo through endosomes toward the vacuole, a process fundamental to membrane homeostasis and nutrient sensing. Researchers care about GO:0034272 because class III PI3K complexes sit at the intersection of endosomal trafficking, autophagy and cell survival signaling. The catalytic subunit Vps34p generates phosphatidylinositol 3-phosphate (PtdIns3P), a lipid mark that recruits effector proteins to endosomal membranes and shapes downstream trafficking decisions. Because the same catalytic subunit can be assembled into different complexes with distinct accessory proteins, defining the type II complex precisely is essential for interpreting genetic and pharmacological experiments. This article summarizes the QuickGO definition, the subunit composition, the molecular mechanism, the genes involved, disease links and the experimental methods used to study GO:0034272. It is written for researchers who need a publication-ready overview that can support experimental design, grant writing and target evaluation in endosomal trafficking and autophagy research.
phosphatidylinositol 3-kinase complex, class III, type II At A Glance
| GO ID | GO:0034272 |
|---|---|
| GO term | phosphatidylinositol 3-kinase complex, class III, type II |
| Ontology | cellular_component |
| Synonym | phosphatidylinositol 3-kinase complex II; PtdIns-3-kinase complex II |
| Major function | Vacuolar protein sorting (VPS) via endosomes |
| Catalytic subunit | Vps34p (class III PI3K) |
| Yeast subunits | Vps30p, Vps34p, Vps38, Vps15p |
| Related complex | Class III PI3K complex I (autophagy-specific) |
| Lipid product | Phosphatidylinositol 3-phosphate (PtdIns3P) |
What Is GO:0034272?
GO:0034272 is a Gene Ontology cellular component term for a class III phosphatidylinositol 3-kinase complex that functions in vacuolar protein sorting via endosomes. In budding yeast, this complex consists of Vps30p, Vps34p, Vps38 and Vps15p. It is synonymous with phosphatidylinositol 3-kinase complex II and PtdIns-3-kinase complex II. The term captures a specific assembly state of the class III PI3K machinery, distinguished from the autophagy-specific complex I by its accessory subunits and its endosomal trafficking role.
Why Is phosphatidylinositol 3-kinase complex, class III, type II Important in Cell Biology?
GO:0034272 is important because it defines a specific endosomal class III PI3K assembly that controls vacuolar protein sorting, a process that determines how receptors, transporters and signaling molecules are delivered to the vacuole or lysosome for degradation or recycling. Because the catalytic subunit Vps34p is shared with autophagy-specific complex I, understanding the type II complex is essential for dissecting which downstream phenotypes arise from endosomal trafficking versus autophagy. Dysregulation of class III PI3K complexes has been linked to tumor-suppressor functions and to autophagy-related human diseases, making this term a useful anchor for mechanistic and translational studies.
• Defines the endosomal class III PI3K complex that mediates vacuolar protein sorting.
• Provides a framework to distinguish endosomal trafficking from autophagy-specific complex I functions.
• Vps34p catalytic activity generates PtdIns3P, a key lipid mark for endosomal recruitment.
• Links class III PI3K biology to tumor-suppressor regulation through ubiquitin and SUMO pathways.
• Supports interpretation of autophagy studies where class III PI3K complexes are central.
• Helps explain how accessory proteins such as NRBF2 and STYK1 modulate complex assembly.
• Relevant to human diseases involving autophagy and reactive oxygen species.
• Guides design of knockout, knock-in and overexpression models for trafficking research.
• Provides a controlled vocabulary for annotating endosomal PI3K complex components.
• Connects yeast VPS genetics to conserved eukaryotic endolysosomal biology.
What Happens During phosphatidylinositol 3-kinase complex, class III, type II?
Complex assembly at endosomal membranes
In simple terms: The complex is built from several proteins that come together on the endosome surface.
The type II class III PI3K complex assembles from Vps34p, Vps15p, Vps30p and Vps38 in budding yeast, forming a holoenzyme that is targeted to endosomal membranes for vacuolar protein sorting. Assembly is not a passive event; accessory and regulatory proteins can influence how the complex forms and where it acts, as shown for related class III PI3K complexes where NRBF2 homodimerization strengthens association with the PtdIns3K complex. The identity of the accessory subunit is a major determinant of whether the catalytic subunit functions in endosomal sorting or in autophagy.
Lipid phosphorylation and PtdIns3P generation
In simple terms: The complex adds a phosphate tag to a membrane lipid, creating a docking site for other proteins.
The catalytic subunit Vps34p phosphorylates phosphatidylinositol to produce phosphatidylinositol 3-phosphate (PtdIns3P), a lipid that recruits effector proteins to endosomal membranes. This lipid phosphorylation step is the core biochemical output of the complex and is shared with other class III PI3K assemblies, including the autophagy-specific complex I. Because PtdIns3P is a signaling lipid rather than a structural component, its local production must be tightly controlled to avoid mis-targeting of trafficking effectors.
Cargo sorting and vacuolar delivery
In simple terms: Proteins destined for the vacuole are sorted through endosomes and delivered for degradation.
The defining function of GO:0034272 is vacuolar protein sorting via endosomes, meaning that the complex helps route cargo through the endosomal system toward the vacuole. This endosomal role distinguishes the type II complex from the autophagy-specific class III PI3K complex I, which acts in autophagosome nucleation rather than endosomal sorting. Proper cargo sorting depends on the lipid and protein environment generated by the complex, and perturbations in class III PI3K function can disrupt endosomal trafficking and downstream degradation.
Regulation by ubiquitin and SUMO
In simple terms: Small protein tags can switch the complex on or off and control its stability.
The tumor-suppressor function of the class III phosphatidylinositol 3-kinase complex is regulated by ubiquitin and SUMO modifications, which can alter complex stability, localization or activity. These post-translational modifications provide a layer of control that links the complex to cellular stress responses and to pathways that decide cell fate. Because ubiquitin and SUMO pathways are frequently dysregulated in disease, this regulation is a plausible mechanism by which class III PI3K complex dysfunction contributes to pathology.
Crosstalk with autophagy machinery
In simple terms: The same core kinase can be used in different complexes, so endosomal and autophagy functions are connected.
Class III PI3K complexes share the catalytic subunit Vps34p, and accessory proteins such as STYK1 and NRBF2 can promote assembly of autophagy-specific complex I, illustrating crosstalk between endosomal and autophagic functions. Atg8-PE-based biochemical approaches have been developed to study autophagy steps that depend on class III PI3K activity, providing tools to dissect where the type II complex impinges on autophagic flux. This crosstalk means that phenotypes observed after perturbing class III PI3K genes must be interpreted with attention to which complex is affected.
Key Genes Involved in GO:0034272 phosphatidylinositol 3-kinase complex, class III, type II
The genes and proteins most directly associated with GO:0034272 include the yeast VPS genes encoding the complex subunits and conserved metazoan orthologs and regulators that modulate class III PI3K complex assembly and function.
| Gene | Major Role | Research Relevance |
|---|---|---|
| VPS34 (yeast) | Catalytic class III PI3K subunit that generates PtdIns3P | Core enzymatic activity of the type II complex |
| VPS15 (yeast) | Regulatory subunit that anchors and activates Vps34p | Essential for complex assembly and membrane recruitment |
| VPS30 (yeast) | Accessory subunit shared with autophagy-related complexes | Defines complex identity and function |
| VPS38 (yeast) | Type II-specific accessory subunit | Distinguishes endosomal complex II from autophagy complex I |
| PIK3C3 (human) | Human ortholog of Vps34p | Central to endosomal and autophagic PI3K signaling |
| PIK3R4 (human) | Human ortholog of Vps15p | Regulatory subunit for class III PI3K complexes |
| BECN1 (human) | Autophagy-related accessory protein | Links class III PI3K complexes to autophagy |
| UVRAG (human) | Accessory protein in class III PI3K complexes | Modulates complex function and trafficking |
| NRBF2 | Regulator that strengthens PtdIns3K complex association | Modulates complex assembly via coiled-coil and MIT domains |
| STYK1 | Promotes assembly of autophagy-specific class III PI3K complex I | Provides mechanistic insight into complex selection |
| ATG16L1 | Autophagy protein modified by S-palmitoylation | Connects autophagy machinery to membrane events |
| ZDHHC7 | Palmitoyltransferase acting on ATG16L1 | Regulates LC3 lipidation and autophagosome formation |
| ATG8 | Ubiquitin-like protein conjugated to PE | Used in biochemical assays of autophagy |
| MIF | Cytokine with broader cellular roles | Illustrates context-dependent signaling studies |
| PLN (phospholamban) | Cardiac regulatory protein | Example of phosphorylation-dependent regulation |
| ROS-related genes | Modulate oxidative stress and autophagy | Link autophagy to human disease mechanisms |
How Is phosphatidylinositol 3-kinase complex, class III, type II Regulated?
The class III phosphatidylinositol 3-kinase complex is regulated by post-translational modifications including ubiquitin and SUMO, which influence its tumor-suppressor function and stability. Accessory proteins such as NRBF2 can strengthen association with the PtdIns3K complex through coiled-coil and MIT domain interactions, thereby modulating complex activity. In addition, proteins such as STYK1 promote assembly of the autophagy-specific class III PI3K complex I, showing that complex selection is actively regulated rather than fixed. Autophagy-related modifications, such as ZDHHC7-mediated S-palmitoylation of ATG16L1, further illustrate how membrane-associated machinery is controlled during autophagic processes that intersect with class III PI3K signaling.
phosphatidylinositol 3-kinase complex, class III, type II and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| PIK3C3 | Autophagy and endosomal trafficking in cancer | Knockout and point-mutation cell models |
| PIK3R4 | Class III PI3K regulation in disease | Knock-in and tagged knock-in models |
| BECN1 | Autophagy-related disease mechanisms | Overexpression and knockout models |
| NRBF2 | Modulation of PtdIns3K complex assembly | Point-mutation and knockout models |
| STYK1 | Autophagy-specific complex I assembly | Overexpression and knockout models |
Cancer and tumor-suppressor function
The class III phosphatidylinositol 3-kinase complex has been linked to tumor-suppressor function, and its regulation by ubiquitin and SUMO pathways provides a mechanistic basis for how its dysfunction could contribute to cancer. Because class III PI3K signaling intersects with autophagy and endosomal trafficking, perturbations in complex components may alter cell survival and stress responses relevant to tumor biology.
Autophagy-related human diseases
Autophagy dysfunction is implicated in a range of human diseases, and reactive oxygen species and autophagy are interconnected in disease mechanisms. Class III PI3K complexes are central to autophagy initiation, and regulators such as STYK1 and NRBF2 modulate the assembly of autophagy-specific complexes, suggesting that complex composition can influence disease-relevant autophagic flux.
Endosomal trafficking and lysosomal biology
The defining role of GO:0034272 in vacuolar protein sorting via endosomes means that its dysfunction could affect delivery of cargo to lysosomes or vacuoles. Although direct human disease associations for the type II complex are less well established than for the autophagy-specific complex, the conserved nature of class III PI3K signaling suggests that endosomal trafficking defects could contribute to lysosomal and neurodegenerative phenotypes.
From phosphatidylinositol 3-kinase complex, class III, type II-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is the catalytic subunit required for endosomal sorting? | Knockout of VPS34/PIK3C3 |
| Does a specific residue control complex assembly? | Point-mutation knock-in |
| Where does the complex localize in cells? | Tagged knock-in with fluorescent tag |
| Does increased complex activity alter trafficking? | Overexpression of complex subunits |
| Which accessory proteins define complex II versus I? | Knockout of VPS38/UVRAG and related genes |
| How does complex perturbation affect autophagy flux? | Combined knockout and autophagy reporter assays |
How to Study the phosphatidylinositol 3-kinase complex, class III, type II Process
| Method | What It Measures | Typical Application |
|---|---|---|
| In vitro lipid kinase assay | PtdIns3P generation by Vps34p | Measuring catalytic activity of complex II |
| Atg8-PE conjugation assay | Autophagy-related lipid conjugation | Dissecting autophagy steps linked to class III PI3K |
| Fluorescence imaging | Localization of tagged complex subunits | Tracking endosomal versus autophagic pools |
| Co-immunoprecipitation | Protein-protein interactions in the complex | Defining subunit composition |
| Ubiquitin/SUMO modification assays | Post-translational regulation | Linking complex stability to disease |
| Knockout phenotyping | Requirement for specific subunits | Assigning functions to complex II |
| Overexpression studies | Gain-of-function effects | Testing whether increased complex activity alters trafficking |
| Proteomic profiling | Changes in trafficking and autophagy proteins | Identifying downstream effectors |
Biochemical reconstitution of complex activity
Atg8-PE-based in vitro biochemical approaches have been developed to study autophagy steps and can be adapted to measure lipid conjugation and complex-dependent reactions. Such reconstitution experiments help define the minimal components required for class III PI3K complex activity and for downstream PtdIns3P-dependent events.
Genetic perturbation and phenotypic analysis
Knockout and point-mutation studies of class III PI3K complex subunits are used to determine which functions depend on the type II complex versus other assemblies. Phenotypic readouts include endosomal trafficking assays, vacuolar protein sorting and autophagy flux measurements.
Imaging of endosomal and autophagic structures
Fluorescent tagging of complex subunits and of downstream effectors allows visualization of where the complex acts and how perturbations alter endosomal and autophagic structures. Tagged knock-in models are particularly useful for tracking endogenous complex localization without overexpression artifacts.
Post-translational modification analysis
Because ubiquitin and SUMO modifications regulate the class III PI3K complex, biochemical and proteomic methods are used to map modification sites and assess their impact on complex function. Similar approaches have been applied to other autophagy-related modifications such as S-palmitoylation of ATG16L1.
How CRISPR Can Be Used to Study GO:0034272 phosphatidylinositol 3-kinase complex, class III, type II
Knockout
CRISPR knockout of class III PI3K complex subunits such as VPS34/PIK3C3, VPS15/PIK3R4 or accessory genes can reveal which endosomal and autophagic functions depend on the type II complex. Knockout models are particularly useful for distinguishing complex II from complex I functions when combined with trafficking and autophagy readouts.
Point Mutation
Point-mutation knock-in can be used to test specific residues implicated in complex assembly, such as domains required for NRBF2 association with the PtdIns3K complex. Such models help separate catalytic activity from protein-protein interaction functions within the complex.
Knock-in
Tagged knock-in of complex subunits allows endogenous localization and interaction studies without overexpression artifacts. This is valuable for determining whether the type II complex acts primarily at endosomes or whether it also contributes to autophagic membranes.
Overexpression
Overexpression of class III PI3K complex components or regulators such as STYK1 can test whether increased complex assembly enhances autophagy or alters endosomal trafficking. Overexpression models complement loss-of-function studies by revealing gain-of-function phenotypes.
How EDITGENE Supports phosphatidylinositol 3-kinase complex, class III, type II Research
Researchers studying phosphatidylinositol 3-kinase complex, class III, type II-related genes often need to determine whether a candidate gene is causally involved in endosomal trafficking, autophagy or disease-relevant phenotypes. Rigorous causal testing requires well-controlled genetic models that isolate the type II complex from related class III PI3K assemblies, and CRISPR-based approaches are well suited to this task.
Contact EDITGENE today to design your custom CRISPR model for phosphatidylinositol 3-kinase complex, class III, type II research.
Frequently Asked Questions About phosphatidylinositol 3-kinase complex, class III, type II
What is GO:0034272?
GO:0034272 is the Gene Ontology cellular component term for phosphatidylinositol 3-kinase complex, class III, type II, a class III PI3K complex involved in vacuolar protein sorting via endosomes and composed in budding yeast of Vps30p, Vps34p, Vps38 and Vps15p.
What genes are involved in phosphatidylinositol 3-kinase complex, class III, type II?
In budding yeast the complex includes VPS30, VPS34, VPS38 and VPS15, with conserved metazoan orthologs such as PIK3C3 and PIK3R4 and accessory proteins like BECN1 and UVRAG.
How is GO:0034272 different from the autophagy-specific class III PI3K complex?
The type II complex acts in vacuolar protein sorting via endosomes, whereas the autophagy-specific complex I uses different accessory subunits and functions in autophagosome nucleation.
What lipid does the class III PI3K complex produce?
The catalytic subunit Vps34p phosphorylates phosphatidylinositol to generate phosphatidylinositol 3-phosphate (PtdIns3P), which recruits downstream effectors.
Is the class III PI3K complex regulated by ubiquitin and SUMO?
Yes, the tumor-suppressor function of the class III phosphatidylinositol 3-kinase complex is regulated by ubiquitin and SUMO modifications.
Which proteins modulate class III PI3K complex assembly?
NRBF2 homodimerization strengthens association with the PtdIns3K complex, and STYK1 promotes assembly of the autophagy-specific complex I, illustrating active regulation of complex composition.
How can I study phosphatidylinositol 3-kinase complex, class III, type II in the lab?
Common approaches include in vitro lipid kinase assays, Atg8-PE conjugation assays, fluorescence imaging of tagged subunits, co-immunoprecipitation and CRISPR-based genetic perturbation.
What diseases are linked to class III PI3K complex dysfunction?
Class III PI3K complex dysfunction has been linked to tumor-suppressor pathways and to autophagy-related human diseases, with reactive oxygen species and autophagy interconnected in disease mechanisms.
Can CRISPR be used to model GO:0034272-related genes?
Yes, CRISPR knockout, point-mutation, knock-in and overexpression models can be used to dissect the functions of class III PI3K complex subunits and regulators.
Why is the type II complex important for endosomal trafficking?
It defines a specific endosomal class III PI3K assembly that generates PtdIns3P and supports vacuolar protein sorting, a process essential for delivering cargo to the vacuole or lysosome.
Conclusion
GO:0034272, phosphatidylinositol 3-kinase complex, class III, type II, is a precisely defined cellular component that captures the endosomal class III PI3K assembly responsible for vacuolar protein sorting. Its subunit composition, catalytic generation of PtdIns3P and regulation by ubiquitin and SUMO pathways make it a central node for understanding endosomal trafficking and its crosstalk with autophagy. For researchers, the term provides a controlled vocabulary for designing and interpreting experiments that distinguish the type II complex from related class III PI3K assemblies. Combining CRISPR-based genetic models with biochemical and imaging approaches offers a robust path to define how this complex contributes to normal cell biology and to disease-relevant phenotypes.
References
- 1. Wei F et al.. 2024. ZDHHC7-mediated S-palmitoylation of ATG16L1 facilitates LC3 lipidation and autophagosome formation.. Autophagy 20(12):2719-2737 PMID: 39087410
- 2. Reidick C et al.. 2014. Regulation of the Tumor-Suppressor Function of the Class III Phosphatidylinositol 3-Kinase Complex by Ubiquitin and SUMO.. Cancers (Basel) 7(1):1-29 PMID: 25545884
- 3. Zhou C et al.. 2020. STYK1 promotes autophagy through enhancing the assembly of autophagy-specific class III phosphatidylinositol 3-kinase complex I.. Autophagy 16(10):1786-1806 PMID: 31696776
- 4. Vogt PK et al.. 2010. Phosphatidylinositol 3-kinase: the oncoprotein.. Curr Top Microbiol Immunol 347:79-104 PMID: 20582532
- 5. Tang Z et al.. 2025. Macrophage migration inhibitory factor induces phospholamban phosphorylation in cardiac muscle.. Cell Calcium 130:103051 PMID: 40680416
- 6. Huang X et al.. 2022. Atg8-PE protein-based in vitro biochemical approaches to autophagy studies.. Autophagy 18(9):2020-2035 PMID: 35072587
- 7. Li N et al.. 2026. NRBF2 homodimerization by its coiled-coil domain strengthens association with the PtdIns3K complex mediated by the MIT domain to promote autophagy.. Autophagy 22(1):168-181 PMID: 41162841
- 8. Wen X et al.. 2013. Deconvoluting the role of reactive oxygen species and autophagy in human diseases.. Free Radic Biol Med 65:402-410 PMID: 23872397
