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P22543

- VPS34_YEAST

UniProt

P22543 - VPS34_YEAST

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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

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 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
Complete GO annotation...

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. fungal-type vacuole membrane Source: SGD
  3. Golgi apparatus Source: UniProtKB-KW
  4. nucleus-vacuole junction Source: SGD
  5. peroxisome Source: SGD
  6. phosphatidylinositol 3-kinase complex I Source: SGD
  7. phosphatidylinositol 3-kinase complex II Source: SGD
  8. pre-autophagosomal structure Source: SGD
Complete GO annotation...

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. 47 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.
GeneTreeiENSGT00760000119110.
HOGENOMiHOG000174003.
InParanoidiP22543.
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

        10         20         30         40         50
MSLNNITFCV SQDLDVPLKV KIKSLEGHKP LLKPSQKILN PELMLIGSNV
60 70 80 90 100
FPSSDLIVSL QVFDKERNRN LTLPIYTPYI PFRNSRTWDY WLTLPIRIKQ
110 120 130 140 150
LTFSSHLRII LWEYNGSKQI PFFNLETSIF NLKDCTLKRG FESLKFRYDV
160 170 180 190 200
IDHCEVVTDN KDQENLNKYF QGEFTRLPWL DEITISKLRK QRENRTWPQG
210 220 230 240 250
TFVLNLEFPM LELPVVFIER EIMNTQMNIP TLKNNPGLST DLREPNRNDP
260 270 280 290 300
QIKISLGDKY HSTLKFYDPD QPNNDPIEEK YRRLERASKN ANLDKQVKPD
310 320 330 340 350
IKKRDYLNKI INYPPGTKLT AHEKGSIWKY RYYLMNNKKA LTKLLQSTNL
360 370 380 390 400
REESERVEVL ELMDSWAEID IDDALELLGS TFKNLSVRSY AVNRLKKASD
410 420 430 440 450
KELELYLLQL VEAVCFENLS TFSDKSNSEF TIVDAVSSQK LSGDSMLLST
460 470 480 490 500
SHANQKLLKS ISSESETSGT ESLPIVISPL AEFLIRRALV NPRLGSFFYW
510 520 530 540 550
YLKSESEDKP YLDQILSSFW SRLDKKSRNI LNDQVRLINV LRECCETIKR
560 570 580 590 600
LKDTTAKKME LLVHLLETKV RPLVKVRPIA LPLDPDVLIC DVCPETSKVF
610 620 630 640 650
KSSLSPLKIT FKTTLNQPYH LMFKVGDDLR QDQLVVQIIS LMNELLKNEN
660 670 680 690 700
VDLKLTPYKI LATGPQEGAI EFIPNDTLAS ILSKYHGILG YLKLHYPDEN
710 720 730 740 750
ATLGVQGWVL DNFVKSCAGY CVITYILGVG DRHLDNLLVT PDGHFFHADF
760 770 780 790 800
GYILGQDPKP FPPLMKLPPQ IIEAFGGAES SNYDKFRSYC FVAYSILRRN
810 820 830 840 850
AGLILNLFEL MKTSNIPDIR IDPNGAILRV RERFNLNMSE EDATVHFQNL
860 870
INDSVNALLP IVIDHLHNLA QYWRT
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. 47 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 ENSGT00760000119110.
HOGENOMi HOG000174003.
InParanoidi P22543.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 141 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