P22543 · VPS34_YEAST
- ProteinPhosphatidylinositol 3-kinase VPS34
- GeneVPS34
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids875 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Phosphatidylinositol 3-kinase required for cytoplasm to vacuole transport (Cvt) and autophagy as a part of the autophagy-specific VPS34 PI3-kinase complex I. This complex is essential to recruit the ATG8-phosphatidylinositol conjugate and the ATG12-ATG5 conjugate to the pre-autophagosomal structure. Also involved in endosome-to-Golgi retrograde transport as part of the VPS34 PI3-kinase complex II. This second complex is required for the endosome-to-Golgi retrieval of PEP1 and KEX2, and the recruitment of VPS5 and VPS7, two components of the retromer complex, to endosomal membranes (probably through the synthesis of a specific pool of phosphatidylinositol 3-phosphate recruiting the retromer to the endosomes). Its activation by VPS15 may lead to the phosphorylation of phosphatidylinositol in the sorting compartment membrane. Finally, it might also be involved in ethanol tolerance and cell wall integrity.
Miscellaneous
Present with 1080 molecules/cell in log phase SD medium.
Catalytic activity
- a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + ADP + H+This reaction proceeds in the forward direction.
Activity regulation
Phosphatidylinositol 3-kinase activity is directly dependent on VPS15 protein kinase activity.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namePhosphatidylinositol 3-kinase VPS34
- EC number
- Short namesPI3-kinase VPS34 ; PI3K VPS34 ; PtdIns-3-kinase VPS34
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Saccharomycotina > Saccharomycetes > Saccharomycetales > Saccharomycetaceae > Saccharomyces
Accessions
- Primary accessionP22543
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Golgi apparatus, trans-Golgi network membrane ; Peripheral membrane protein
Endosome membrane ; Peripheral membrane protein
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Abnormal localization of the peripheral membrane protein PIB2 to the vacuolar membrane (PubMed:26510498, PubMed:29698392).
Decreases activation of TORC1 in response to glutamine (PubMed:28483912).
Decreases activation of TORC1 in response to glutamine (PubMed:28483912).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 731 | Loss of kinase activity and no vacuolar carboxypeptidase Y (PCR1) sorting to the vacuole. | ||||
Sequence: D → A | ||||||
Mutagenesis | 736 | Loss of kinase activity and no vacuolar carboxypeptidase Y (PCR1) sorting to the vacuole. | ||||
Sequence: N → K | ||||||
Mutagenesis | 749 | Loss of kinase activity and no vacuolar carboxypeptidase Y (PCR1) sorting to the vacuole. | ||||
Sequence: D → E |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 3 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000088818 | 1-875 | Phosphatidylinositol 3-kinase VPS34 | |||
Sequence: MSLNNITFCVSQDLDVPLKVKIKSLEGHKPLLKPSQKILNPELMLIGSNVFPSSDLIVSLQVFDKERNRNLTLPIYTPYIPFRNSRTWDYWLTLPIRIKQLTFSSHLRIILWEYNGSKQIPFFNLETSIFNLKDCTLKRGFESLKFRYDVIDHCEVVTDNKDQENLNKYFQGEFTRLPWLDEITISKLRKQRENRTWPQGTFVLNLEFPMLELPVVFIEREIMNTQMNIPTLKNNPGLSTDLREPNRNDPQIKISLGDKYHSTLKFYDPDQPNNDPIEEKYRRLERASKNANLDKQVKPDIKKRDYLNKIINYPPGTKLTAHEKGSIWKYRYYLMNNKKALTKLLQSTNLREESERVEVLELMDSWAEIDIDDALELLGSTFKNLSVRSYAVNRLKKASDKELELYLLQLVEAVCFENLSTFSDKSNSEFTIVDAVSSQKLSGDSMLLSTSHANQKLLKSISSESETSGTESLPIVISPLAEFLIRRALVNPRLGSFFYWYLKSESEDKPYLDQILSSFWSRLDKKSRNILNDQVRLINVLRECCETIKRLKDTTAKKMELLVHLLETKVRPLVKVRPIALPLDPDVLICDVCPETSKVFKSSLSPLKITFKTTLNQPYHLMFKVGDDLRQDQLVVQIISLMNELLKNENVDLKLTPYKILATGPQEGAIEFIPNDTLASILSKYHGILGYLKLHYPDENATLGVQGWVLDNFVKSCAGYCVITYILGVGDRHLDNLLVTPDGHFFHADFGYILGQDPKPFPPLMKLPPQIIEAFGGAESSNYDKFRSYCFVAYSILRRNAGLILNLFELMKTSNIPDIRIDPNGAILRVRERFNLNMSEEDATVHFQNLINDSVNALLPIVIDHLHNLAQYWRT |
Post-translational modification
Autophosphorylated. Might also be phosphorylated by VPS15.
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Component of the autophagy-specific VPS34 PI3-kinase complex I composed of VPS15, VPS30, VPS34, ATG14 and ATG38, and of the VPS34 PI3-kinase complex II composed of VPS15, VPS30, VPS34 and VPS38 (PubMed:11157979, PubMed:24165940, PubMed:26450213, PubMed:8387919).
Interacts directly with ATG38 (PubMed:24165940).
Interacts directly with VPS34 (PubMed:27630019).
Interacts directly with ATG38 (PubMed:24165940).
Interacts directly with VPS34 (PubMed:27630019).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P22543 | ATG38 Q05789 | 5 | EBI-20405, EBI-35873 | |
BINARY | P22543 | GPA1 P08539 | 3 | EBI-20405, EBI-7376 | |
BINARY | P22543 | VPS15 P22219 | 4 | EBI-20405, EBI-20347 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 14-188 | C2 PI3K-type | ||||
Sequence: LDVPLKVKIKSLEGHKPLLKPSQKILNPELMLIGSNVFPSSDLIVSLQVFDKERNRNLTLPIYTPYIPFRNSRTWDYWLTLPIRIKQLTFSSHLRIILWEYNGSKQIPFFNLETSIFNLKDCTLKRGFESLKFRYDVIDHCEVVTDNKDQENLNKYFQGEFTRLPWLDEITISKL | ||||||
Domain | 293-526 | PIK helical | ||||
Sequence: LDKQVKPDIKKRDYLNKIINYPPGTKLTAHEKGSIWKYRYYLMNNKKALTKLLQSTNLREESERVEVLELMDSWAEIDIDDALELLGSTFKNLSVRSYAVNRLKKASDKELELYLLQLVEAVCFENLSTFSDKSNSEFTIVDAVSSQKLSGDSMLLSTSHANQKLLKSISSESETSGTESLPIVISPLAEFLIRRALVNPRLGSFFYWYLKSESEDKPYLDQILSSFWSRLDKK | ||||||
Domain | 593-859 | PI3K/PI4K catalytic | ||||
Sequence: CPETSKVFKSSLSPLKITFKTTLNQPYHLMFKVGDDLRQDQLVVQIISLMNELLKNENVDLKLTPYKILATGPQEGAIEFIPNDTLASILSKYHGILGYLKLHYPDENATLGVQGWVLDNFVKSCAGYCVITYILGVGDRHLDNLLVTPDGHFFHADFGYILGQDPKPFPPLMKLPPQIIEAFGGAESSNYDKFRSYCFVAYSILRRNAGLILNLFELMKTSNIPDIRIDPNGAILRVRERFNLNMSEEDATVHFQNLINDSVNALL | ||||||
Region | 599-605 | G-loop | ||||
Sequence: VFKSSLS | ||||||
Region | 728-736 | Catalytic loop | ||||
Sequence: GVGDRHLDN | ||||||
Region | 747-768 | Activation loop | ||||
Sequence: HADFGYILGQDPKPFPPLMKLP |
Sequence similarities
Belongs to the PI3/PI4-kinase family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length875
- Mass (Da)100,921
- Last updated1991-08-01 v1
- Checksum806E3404EF260287
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X53531 EMBL· GenBank· DDBJ | CAA37610.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U20865 EMBL· GenBank· DDBJ | AAB67396.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U19027 EMBL· GenBank· DDBJ | AAB67422.2 EMBL· GenBank· DDBJ | Genomic DNA | ||
BK006945 EMBL· GenBank· DDBJ | DAA09554.1 EMBL· GenBank· DDBJ | Genomic DNA |