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P22543

- VPS34_YEAST

UniProt

P22543 - VPS34_YEAST

Protein

Phosphatidylinositol 3-kinase VPS34

Gene

VPS34

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 140 (01 Oct 2014)
      Sequence version 1 (01 Aug 1991)
      Previous versions | rss
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    Functioni

    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.10 Publications

    Catalytic activityi

    ATP + 1-phosphatidyl-1D-myo-inositol = ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate.

    Enzyme regulationi

    Phosphatidylinositol 3-kinase activity is directly dependent on VPS15 protein kinase activity.

    GO - Molecular functioni

    1. 1-phosphatidylinositol-3-kinase activity Source: SGD
    2. ATP binding Source: UniProtKB-KW
    3. protein binding Source: IntAct
    4. protein kinase activity Source: SGD

    GO - Biological processi

    1. peroxisome degradation Source: SGD
    2. phosphatidylinositol-3-phosphate biosynthetic process Source: GOC
    3. phosphatidylinositol-mediated signaling Source: InterPro
    4. phosphatidylinositol phosphorylation Source: SGD
    5. positive regulation of transcription elongation from RNA polymerase II promoter Source: SGD
    6. protein phosphorylation Source: SGD
    7. protein transport Source: UniProtKB-KW

    Keywords - Molecular functioni

    Kinase, Transferase

    Keywords - Biological processi

    Autophagy, Protein transport, Transport

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BioCyciYEAST:YLR240W-MONOMER.
    BRENDAi2.7.1.137. 984.
    ReactomeiREACT_188955. Synthesis of PIPs at the Golgi membrane.
    REACT_188958. Synthesis of PIPs at the late endosome membrane.
    REACT_188968. Synthesis of PIPs at the early endosome membrane.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Phosphatidylinositol 3-kinase VPS34 (EC:2.7.1.137)
    Short name:
    PI3-kinase VPS34
    Short name:
    PI3K VPS34
    Short name:
    PtdIns-3-kinase VPS34
    Alternative name(s):
    Carboxypeptidase Y-deficient protein 15
    Vacuolar protein sorting-associated protein 34
    Vacuolar protein-targeting protein 29
    Gene namesi
    Name:VPS34
    Synonyms:END12, PEP15, VPL7, VPT29
    Ordered Locus Names:YLR240W
    ORF Names:L9672.10
    OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
    Taxonomic identifieri559292 [NCBI]
    Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
    ProteomesiUP000002311: Chromosome XII

    Organism-specific databases

    CYGDiYLR240w.
    SGDiS000004230. VPS34.

    Subcellular locationi

    GO - Cellular componenti

    1. endosome Source: SGD
    2. endosome membrane Source: UniProtKB-SubCell
    3. fungal-type vacuole membrane Source: SGD
    4. Golgi apparatus Source: UniProtKB-SubCell
    5. nucleus-vacuole junction Source: SGD
    6. peroxisome Source: SGD
    7. phosphatidylinositol 3-kinase complex I Source: SGD
    8. phosphatidylinositol 3-kinase complex II Source: SGD
    9. pre-autophagosomal structure Source: SGD

    Keywords - Cellular componenti

    Endosome, Golgi apparatus, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi731 – 7311D → A: Loss of kinase activity and no vacuolar carboxypeptidase Y (PCR1) sorting to the vacuole. 1 Publication
    Mutagenesisi736 – 7361N → K: Loss of kinase activity and no vacuolar carboxypeptidase Y (PCR1) sorting to the vacuole. 1 Publication
    Mutagenesisi749 – 7491D → E: Loss of kinase activity and no vacuolar carboxypeptidase Y (PCR1) sorting to the vacuole. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 875875Phosphatidylinositol 3-kinase VPS34PRO_0000088818Add
    BLAST

    Post-translational modificationi

    Autophosphorylated. Might also be phosphorylated by VPS15.

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiP22543.
    PaxDbiP22543.
    PeptideAtlasiP22543.
    PRIDEiP22543.

    Expressioni

    Gene expression databases

    GenevestigatoriP22543.

    Interactioni

    Subunit structurei

    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. Interacts directly with ATG38.3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    GPA1P085393EBI-20405,EBI-7376

    Protein-protein interaction databases

    BioGridi31507. 46 interactions.
    DIPiDIP-97N.
    IntActiP22543. 5 interactions.
    MINTiMINT-2780608.
    STRINGi4932.YLR240W.

    Structurei

    3D structure databases

    ProteinModelPortaliP22543.
    SMRiP22543. Positions 268-874.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini14 – 188175C2 PI3K-typePROSITE-ProRule annotationAdd
    BLAST
    Domaini293 – 526234PIK helicalPROSITE-ProRule annotationAdd
    BLAST
    Domaini619 – 873255PI3K/PI4KPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the PI3/PI4-kinase family.PROSITE-ProRule annotation
    Contains 1 C2 PI3K-type domain.PROSITE-ProRule annotation
    Contains 1 PI3K/PI4K domain.PROSITE-ProRule annotation
    Contains 1 PIK helical domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG5032.
    GeneTreeiENSGT00620000087805.
    HOGENOMiHOG000174003.
    KOiK00914.
    OMAiSAMTRRI.
    OrthoDBiEOG7WHHK2.

    Family and domain databases

    Gene3Di1.10.1070.11. 1 hit.
    1.25.40.70. 2 hits.
    2.60.40.150. 1 hit.
    InterProiIPR016024. ARM-type_fold.
    IPR000008. C2_dom.
    IPR011009. Kinase-like_dom.
    IPR000403. PI3/4_kinase_cat_dom.
    IPR018936. PI3/4_kinase_CS.
    IPR002420. PI3K_C2_dom.
    IPR008290. PI3K_Vps34.
    IPR015433. PI_Kinase.
    IPR001263. PInositide-3_kin_accessory_dom.
    [Graphical view]
    PANTHERiPTHR10048. PTHR10048. 1 hit.
    PfamiPF00454. PI3_PI4_kinase. 1 hit.
    PF00792. PI3K_C2. 1 hit.
    PF00613. PI3Ka. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000587. PI3K_Vps34. 1 hit.
    SMARTiSM00142. PI3K_C2. 1 hit.
    SM00145. PI3Ka. 1 hit.
    SM00146. PI3Kc. 1 hit.
    [Graphical view]
    SUPFAMiSSF48371. SSF48371. 2 hits.
    SSF49562. SSF49562. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEiPS00915. PI3_4_KINASE_1. 1 hit.
    PS00916. PI3_4_KINASE_2. 1 hit.
    PS50290. PI3_4_KINASE_3. 1 hit.
    PS51547. PI3K_C2. 1 hit.
    PS51545. PIK_HELICAL. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P22543-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSLNNITFCV SQDLDVPLKV KIKSLEGHKP LLKPSQKILN PELMLIGSNV    50
    FPSSDLIVSL QVFDKERNRN LTLPIYTPYI PFRNSRTWDY WLTLPIRIKQ 100
    LTFSSHLRII LWEYNGSKQI PFFNLETSIF NLKDCTLKRG FESLKFRYDV 150
    IDHCEVVTDN KDQENLNKYF QGEFTRLPWL DEITISKLRK QRENRTWPQG 200
    TFVLNLEFPM LELPVVFIER EIMNTQMNIP TLKNNPGLST DLREPNRNDP 250
    QIKISLGDKY HSTLKFYDPD QPNNDPIEEK YRRLERASKN ANLDKQVKPD 300
    IKKRDYLNKI INYPPGTKLT AHEKGSIWKY RYYLMNNKKA LTKLLQSTNL 350
    REESERVEVL ELMDSWAEID IDDALELLGS TFKNLSVRSY AVNRLKKASD 400
    KELELYLLQL VEAVCFENLS TFSDKSNSEF TIVDAVSSQK LSGDSMLLST 450
    SHANQKLLKS ISSESETSGT ESLPIVISPL AEFLIRRALV NPRLGSFFYW 500
    YLKSESEDKP YLDQILSSFW SRLDKKSRNI LNDQVRLINV LRECCETIKR 550
    LKDTTAKKME LLVHLLETKV RPLVKVRPIA LPLDPDVLIC DVCPETSKVF 600
    KSSLSPLKIT FKTTLNQPYH LMFKVGDDLR QDQLVVQIIS LMNELLKNEN 650
    VDLKLTPYKI LATGPQEGAI EFIPNDTLAS ILSKYHGILG YLKLHYPDEN 700
    ATLGVQGWVL DNFVKSCAGY CVITYILGVG DRHLDNLLVT PDGHFFHADF 750
    GYILGQDPKP FPPLMKLPPQ IIEAFGGAES SNYDKFRSYC FVAYSILRRN 800
    AGLILNLFEL MKTSNIPDIR IDPNGAILRV RERFNLNMSE EDATVHFQNL 850
    INDSVNALLP IVIDHLHNLA QYWRT 875
    Length:875
    Mass (Da):100,921
    Last modified:August 1, 1991 - v1
    Checksum:i806E3404EF260287
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X53531 Genomic DNA. Translation: CAA37610.1.
    U20865 Genomic DNA. Translation: AAB67396.1.
    U19027 Genomic DNA. Translation: AAB67422.2.
    BK006945 Genomic DNA. Translation: DAA09554.1.
    PIRiA36369.
    RefSeqiNP_013341.1. NM_001182127.1.

    Genome annotation databases

    EnsemblFungiiYLR240W; YLR240W; YLR240W.
    GeneIDi850941.
    KEGGisce:YLR240W.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X53531 Genomic DNA. Translation: CAA37610.1 .
    U20865 Genomic DNA. Translation: AAB67396.1 .
    U19027 Genomic DNA. Translation: AAB67422.2 .
    BK006945 Genomic DNA. Translation: DAA09554.1 .
    PIRi A36369.
    RefSeqi NP_013341.1. NM_001182127.1.

    3D structure databases

    ProteinModelPortali P22543.
    SMRi P22543. Positions 268-874.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 31507. 46 interactions.
    DIPi DIP-97N.
    IntActi P22543. 5 interactions.
    MINTi MINT-2780608.
    STRINGi 4932.YLR240W.

    Proteomic databases

    MaxQBi P22543.
    PaxDbi P22543.
    PeptideAtlasi P22543.
    PRIDEi P22543.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    EnsemblFungii YLR240W ; YLR240W ; YLR240W .
    GeneIDi 850941.
    KEGGi sce:YLR240W.

    Organism-specific databases

    CYGDi YLR240w.
    SGDi S000004230. VPS34.

    Phylogenomic databases

    eggNOGi COG5032.
    GeneTreei ENSGT00620000087805.
    HOGENOMi HOG000174003.
    KOi K00914.
    OMAi SAMTRRI.
    OrthoDBi EOG7WHHK2.

    Enzyme and pathway databases

    BioCyci YEAST:YLR240W-MONOMER.
    BRENDAi 2.7.1.137. 984.
    Reactomei REACT_188955. Synthesis of PIPs at the Golgi membrane.
    REACT_188958. Synthesis of PIPs at the late endosome membrane.
    REACT_188968. Synthesis of PIPs at the early endosome membrane.

    Miscellaneous databases

    NextBioi 967390.
    PROi P22543.

    Gene expression databases

    Genevestigatori P22543.

    Family and domain databases

    Gene3Di 1.10.1070.11. 1 hit.
    1.25.40.70. 2 hits.
    2.60.40.150. 1 hit.
    InterProi IPR016024. ARM-type_fold.
    IPR000008. C2_dom.
    IPR011009. Kinase-like_dom.
    IPR000403. PI3/4_kinase_cat_dom.
    IPR018936. PI3/4_kinase_CS.
    IPR002420. PI3K_C2_dom.
    IPR008290. PI3K_Vps34.
    IPR015433. PI_Kinase.
    IPR001263. PInositide-3_kin_accessory_dom.
    [Graphical view ]
    PANTHERi PTHR10048. PTHR10048. 1 hit.
    Pfami PF00454. PI3_PI4_kinase. 1 hit.
    PF00792. PI3K_C2. 1 hit.
    PF00613. PI3Ka. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF000587. PI3K_Vps34. 1 hit.
    SMARTi SM00142. PI3K_C2. 1 hit.
    SM00145. PI3Ka. 1 hit.
    SM00146. PI3Kc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48371. SSF48371. 2 hits.
    SSF49562. SSF49562. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEi PS00915. PI3_4_KINASE_1. 1 hit.
    PS00916. PI3_4_KINASE_2. 1 hit.
    PS50290. PI3_4_KINASE_3. 1 hit.
    PS51547. PI3K_C2. 1 hit.
    PS51545. PIK_HELICAL. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Characterization of VPS34, a gene required for vacuolar protein sorting and vacuole segregation in Saccharomyces cerevisiae."
      Herman P.K., Emr S.D.
      Mol. Cell. Biol. 10:6742-6754(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION.
    2. "The nucleotide sequence of Saccharomyces cerevisiae chromosome XII."
      Johnston M., Hillier L.W., Riles L., Albermann K., Andre B., Ansorge W., Benes V., Brueckner M., Delius H., Dubois E., Duesterhoeft A., Entian K.-D., Floeth M., Goffeau A., Hebling U., Heumann K., Heuss-Neitzel D., Hilbert H.
      , Hilger F., Kleine K., Koetter P., Louis E.J., Messenguy F., Mewes H.-W., Miosga T., Moestl D., Mueller-Auer S., Nentwich U., Obermaier B., Piravandi E., Pohl T.M., Portetelle D., Purnelle B., Rechmann S., Rieger M., Rinke M., Rose M., Scharfe M., Scherens B., Scholler P., Schwager C., Schwarz S., Underwood A.P., Urrestarazu L.A., Vandenbol M., Verhasselt P., Vierendeels F., Voet M., Volckaert G., Voss H., Wambutt R., Wedler E., Wedler H., Zimmermann F.K., Zollner A., Hani J., Hoheisel J.D.
      Nature 387:87-90(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: ATCC 204508 / S288c.
    3. Cited for: GENOME REANNOTATION.
      Strain: ATCC 204508 / S288c.
    4. "Protein sorting in Saccharomyces cerevisiae: isolation of mutants defective in the delivery and processing of multiple vacuolar hydrolases."
      Robinson J.S., Klionsky D.J., Banta L.M., Emr S.D.
      Mol. Cell. Biol. 8:4936-4948(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    5. "Phosphatidylinositol 3-kinase and its novel product, phosphatidylinositol 3-phosphate, are present in Saccharomyces cerevisiae."
      Auger K.R., Carpenter C.L., Cantley L.C., Varticovski L.
      J. Biol. Chem. 264:20181-20184(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    6. "A membrane-associated complex containing the Vps15 protein kinase and the Vps34 PI 3-kinase is essential for protein sorting to the yeast lysosome-like vacuole."
      Stack J.H., Herman P.K., Schu P.V., Emr S.D.
      EMBO J. 12:2195-2204(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH VPS15.
    7. "Phosphatidylinositol 3-kinase encoded by yeast VPS34 gene essential for protein sorting."
      Schu P.V., Takegawa K., Fry M.J., Stack J.H., Waterfield M.D., Emr S.D.
      Science 260:88-91(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF ASP-731; ASN-736 AND ASP-749.
    8. "Vps34p required for yeast vacuolar protein sorting is a multiple specificity kinase that exhibits both protein kinase and phosphatidylinositol-specific PI 3-kinase activities."
      Stack J.H., Emr S.D.
      J. Biol. Chem. 269:31552-31562(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, AUTOPHOSPHORYLATION.
    9. "Endocytosis is required for the growth of vacuolar H(+)-ATPase-defective yeast: identification of six new END genes."
      Munn A.L., Riezman H.
      J. Cell Biol. 127:373-386(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    10. "Two distinct Vps34 phosphatidylinositol 3-kinase complexes function in autophagy and carboxypeptidase Y sorting in Saccharomyces cerevisiae."
      Kihara A., Noda T., Ishihara N., Ohsumi Y.
      J. Cell Biol. 152:519-530(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH VPS15; VPS30; VPS38 AND ATG14.
    11. "Identification of genes required for growth under ethanol stress using transposon mutagenesis in Saccharomyces cerevisiae."
      Takahashi T., Shimoi H., Ito K.
      Mol. Genet. Genomics 265:1112-1119(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    12. "Retromer function in endosome-to-Golgi retrograde transport is regulated by the yeast Vps34 PtdIns 3-kinase."
      Burda P., Padilla S.M., Sarkar S., Emr S.D.
      J. Cell Sci. 115:3889-3900(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    13. Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
    14. Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
    15. "Atg38 is required for autophagy-specific phosphatidylinositol 3-kinase complex integrity."
      Araki Y., Ku W.C., Akioka M., May A.I., Hayashi Y., Arisaka F., Ishihama Y., Ohsumi Y.
      J. Cell Biol. 203:299-313(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE AUTOPHAGY-SPECIFIC VPS34 PI3-KINASE COMPLEX I, INTERACTION WITH ATG38.

    Entry informationi

    Entry nameiVPS34_YEAST
    AccessioniPrimary (citable) accession number: P22543
    Secondary accession number(s): D6VYN8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1991
    Last sequence update: August 1, 1991
    Last modified: October 1, 2014
    This is version 140 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programFungal Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Present with 1080 molecules/cell in log phase SD medium.1 Publication

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    2. Yeast
      Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
    3. Yeast chromosome XII
      Yeast (Saccharomyces cerevisiae) chromosome XII: entries and gene names

    External Data

    Dasty 3