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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: -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

Miscellaneous

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

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-phosphatidylinositol-3-kinase activity Source: SGD
  • ATP binding Source: UniProtKB-KW
  • protein kinase activity Source: SGD

GO - Biological processi

  • autophagosome assembly Source: GO_Central
  • autophagy of peroxisome Source: SGD
  • endocytosis Source: GO_Central
  • endosomal transport Source: GO_Central
  • phosphatidylinositol-mediated signaling Source: GO_Central
  • phosphatidylinositol phosphorylation Source: SGD
  • positive regulation of macroautophagy Source: SGD
  • positive regulation of transcription elongation from RNA polymerase II promoter Source: SGD
  • protein phosphorylation Source: SGD
  • protein transport Source: UniProtKB-KW
  • regulation of protein localization by the Cvt pathway Source: SGD

Keywordsi

Molecular functionKinase, Transferase
Biological processAutophagy, Protein transport, Transport
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciYEAST:YLR240W-MONOMER
BRENDAi2.7.1.137 984
ReactomeiR-SCE-1632852 Macroautophagy
R-SCE-1660499 Synthesis of PIPs at the plasma membrane
R-SCE-1660514 Synthesis of PIPs at the Golgi membrane
R-SCE-1660516 Synthesis of PIPs at the early endosome membrane
R-SCE-1660517 Synthesis of PIPs at the late endosome membrane
R-SCE-5668599 RHO GTPases Activate NADPH Oxidases

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
Proteomesi
  • UP000002311 Componenti: Chromosome XII

Organism-specific databases

EuPathDBiFungiDB:YLR240W
SGDiS000004230 VPS34

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cell wall Cytoskeleton Vacuole Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Endosome, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi731D → A: Loss of kinase activity and no vacuolar carboxypeptidase Y (PCR1) sorting to the vacuole. 1 Publication1
Mutagenesisi736N → K: Loss of kinase activity and no vacuolar carboxypeptidase Y (PCR1) sorting to the vacuole. 1 Publication1
Mutagenesisi749D → E: Loss of kinase activity and no vacuolar carboxypeptidase Y (PCR1) sorting to the vacuole. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000888181 – 875Phosphatidylinositol 3-kinase VPS34Add BLAST875

Post-translational modificationi

Autophosphorylated. Might also be phosphorylated by VPS15.

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP22543
PaxDbiP22543
PRIDEiP22543

PTM databases

iPTMnetiP22543

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

Show more details

Protein-protein interaction databases

BioGridi31507, 114 interactors
DIPiDIP-97N
IntActiP22543, 6 interactors
MINTiP22543
STRINGi4932.YLR240W

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5DFZX-ray4.40C1-875[»]
5KC2electron microscopy28.00C1-875[»]
ProteinModelPortaliP22543
SMRiP22543
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini14 – 188C2 PI3K-typePROSITE-ProRule annotationAdd BLAST175
Domaini293 – 526PIK helicalPROSITE-ProRule annotationAdd BLAST234
Domaini619 – 873PI3K/PI4KPROSITE-ProRule annotationAdd BLAST255

Sequence similaritiesi

Belongs to the PI3/PI4-kinase family.PROSITE-ProRule annotation

Phylogenomic databases

GeneTreeiENSGT00760000119110
HOGENOMiHOG000174003
InParanoidiP22543
KOiK00914
OMAiFKKHEMG
OrthoDBiEOG092C13UM

Family and domain databases

Gene3Di1.10.1070.11, 1 hit
InterProiView protein in InterPro
IPR016024 ARM-type_fold
IPR011009 Kinase-like_dom_sf
IPR000403 PI3/4_kinase_cat_dom
IPR036940 PI3/4_kinase_cat_sf
IPR018936 PI3/4_kinase_CS
IPR002420 PI3K_C2_dom
IPR008290 PI3K_Vps34
IPR015433 PI_Kinase
IPR001263 PInositide-3_kin_accessory_dom
PANTHERiPTHR10048 PTHR10048, 1 hit
PfamiView protein in Pfam
PF00454 PI3_PI4_kinase, 1 hit
PF00792 PI3K_C2, 1 hit
PF00613 PI3Ka, 1 hit
PIRSFiPIRSF000587 PI3K_Vps34, 1 hit
SMARTiView protein in SMART
SM00142 PI3K_C2, 1 hit
SM00145 PI3Ka, 1 hit
SM00146 PI3Kc, 1 hit
SUPFAMiSSF48371 SSF48371, 2 hits
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
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

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:
EMBLi
GenBanki
DDBJi
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

Similar proteinsi

Entry informationi

Entry nameiVPS34_YEAST
AccessioniPrimary (citable) accession number: P22543
Secondary accession number(s): D6VYN8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1991
Last modified: May 23, 2018
This is version 177 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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