Phosphatidylinositol 3-kinase VPS34 - Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)

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P22543 (VPS34_YEAST) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 127. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Phosphatidylinositol 3-kinase VPS34
Short name=PI3-kinase VPS34
Short name=PI3K VPS34
Short name=PtdIns-3-kinase VPS34
EC=2.7.1.137

Alternative name(s):
Carboxypeptidase Y-deficient protein 15
Vacuolar protein sorting-associated protein 34
Vacuolar protein-targeting protein 29

Gene names

Name:	VPS34
Synonyms:	END12, PEP15, VPL7, VPT29
Ordered Locus Names:	YLR240W
ORF Names:	L9672.10

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces ›

Protein attributes

Sequence length	875 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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. Ref.1 Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12
Catalytic activity	ATP + 1-phosphatidyl-1D-myo-inositol = ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate.
Enzyme regulation	Phosphatidylinositol 3-kinase activity is directly dependent on VPS15 protein kinase activity.
Subunit structure	Component of the autophagy-specific VPS34 PI3-kinase complex I composed of VPS15, VPS30, VPS34 and ATG14; and of the VPS34 PI3-kinase complex II composed of VPS15, VPS30, VPS34 and VPS38.
Subcellular location	Golgi apparatus › trans-Golgi network membrane; Peripheral membrane protein. Endosome membrane; Peripheral membrane protein Ref.10 Ref.13.
Post-translational modification	Autophosphorylated. Might also be phosphorylated by VPS15. Ref.8
Miscellaneous	Present with 1080 molecules/cell in log phase SD medium.
Sequence similarities	Belongs to the PI3/PI4-kinase family. Contains 1 C2 PI3K-type domain. Contains 1 PI3K/PI4K domain. Contains 1 PIK helical domain.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Endosome Golgi apparatus Membrane
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	peroxisome degradation Inferred from mutant phenotype PubMed 21121900. Source: SGD phosphatidylinositol-mediated signaling Inferred from electronic annotation. Source: InterPro positive regulation of transcription elongation from RNA polymerase II promoter Inferred from mutant phenotype PubMed 23335340. Source: SGD protein transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell endosome Inferred from direct assay PubMed 16421251. Source: SGD endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell fungal-type vacuole membrane Inferred from direct assay PubMed 16421251. Source: SGD nucleus-vacuole junction Inferred from direct assay PubMed 23335340. Source: SGD peroxisome Inferred from direct assay PubMed 21121900. Source: SGD phosphatidylinositol 3-kinase complex I Inferred from direct assay Ref.10. Source: SGD phosphatidylinositol 3-kinase complex II Inferred from direct assay Ref.10. Source: SGD pre-autophagosomal structure Inferred from direct assay PubMed 16421251. Source: SGD
Molecular_function	1-phosphatidylinositol-3-kinase activity Inferred from direct assay Ref.8 Ref.7. Source: SGD ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein kinase activity Inferred from direct assay Ref.8. Source: SGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GPA1	P08539	3	EBI-20405,EBI-7376

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 875

875

Phosphatidylinositol 3-kinase VPS34

PRO_0000088818

Regions

Domain

14 – 188

175

C2 PI3K-type

Domain

293 – 526

234

PIK helical

Domain

619 – 873

255

PI3K/PI4K

Experimental info

Mutagenesis

731

D → A: Loss of kinase activity and no vacuolar carboxypeptidase Y (PCR1) sorting to the vacuole. Ref.7

Mutagenesis

736

N → K: Loss of kinase activity and no vacuolar carboxypeptidase Y (PCR1) sorting to the vacuole. Ref.7

Mutagenesis

749

D → E: Loss of kinase activity and no vacuolar carboxypeptidase Y (PCR1) sorting to the vacuole. Ref.7

Sequences

Sequence

Length

Mass (Da)

Tools

P22543 [UniParc].

Last modified August 1, 1991. Version 1.
Checksum: 806E3404EF260287
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FASTA

875

100,921

        10         20         30         40         50         60 
MSLNNITFCV SQDLDVPLKV KIKSLEGHKP LLKPSQKILN PELMLIGSNV FPSSDLIVSL 

        70         80         90        100        110        120 
QVFDKERNRN LTLPIYTPYI PFRNSRTWDY WLTLPIRIKQ LTFSSHLRII LWEYNGSKQI 

       130        140        150        160        170        180 
PFFNLETSIF NLKDCTLKRG FESLKFRYDV IDHCEVVTDN KDQENLNKYF QGEFTRLPWL 

       190        200        210        220        230        240 
DEITISKLRK QRENRTWPQG TFVLNLEFPM LELPVVFIER EIMNTQMNIP TLKNNPGLST 

       250        260        270        280        290        300 
DLREPNRNDP QIKISLGDKY HSTLKFYDPD QPNNDPIEEK YRRLERASKN ANLDKQVKPD 

       310        320        330        340        350        360 
IKKRDYLNKI INYPPGTKLT AHEKGSIWKY RYYLMNNKKA LTKLLQSTNL REESERVEVL 

       370        380        390        400        410        420 
ELMDSWAEID IDDALELLGS TFKNLSVRSY AVNRLKKASD KELELYLLQL VEAVCFENLS 

       430        440        450        460        470        480 
TFSDKSNSEF TIVDAVSSQK LSGDSMLLST SHANQKLLKS ISSESETSGT ESLPIVISPL 

       490        500        510        520        530        540 
AEFLIRRALV NPRLGSFFYW YLKSESEDKP YLDQILSSFW SRLDKKSRNI LNDQVRLINV 

       550        560        570        580        590        600 
LRECCETIKR LKDTTAKKME LLVHLLETKV RPLVKVRPIA LPLDPDVLIC DVCPETSKVF 

       610        620        630        640        650        660 
KSSLSPLKIT FKTTLNQPYH LMFKVGDDLR QDQLVVQIIS LMNELLKNEN VDLKLTPYKI 

       670        680        690        700        710        720 
LATGPQEGAI EFIPNDTLAS ILSKYHGILG YLKLHYPDEN ATLGVQGWVL DNFVKSCAGY 

       730        740        750        760        770        780 
CVITYILGVG DRHLDNLLVT PDGHFFHADF GYILGQDPKP FPPLMKLPPQ IIEAFGGAES 

       790        800        810        820        830        840 
SNYDKFRSYC FVAYSILRRN AGLILNLFEL MKTSNIPDIR IDPNGAILRV RERFNLNMSE 

       850        860        870 
EDATVHFQNL INDSVNALLP IVIDHLHNLA QYWRT

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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. Hoheisel J.D. Nature 387:87-90(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204511 / S288c / AB972.
[3]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases 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]	"Global analysis of protein localization in budding yeast." Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., Weissman J.S., O'Shea E.K. Nature 425:686-691(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
[14]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed] [Europe PMC] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X53531 Genomic DNA. Translation: CAA37610.1. U20865 Genomic DNA. Translation: AAB67396.1. U19027 Genomic DNA. Translation: AAB67422.2. BK006945 Genomic DNA. Translation: DAA09554.1.
PIR	A36369.
RefSeq	NP_013341.1. NM_001182127.1.
3D structure databases
ProteinModelPortal	P22543.
SMR	P22543. Positions 268-874.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-97N.
IntAct	P22543. 5 interactions.
MINT	MINT-2780608.
STRING	4932.YLR240W.
Proteomic databases
PaxDb	P22543.
PeptideAtlas	P22543.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblFungi	YLR240W; YLR240W; YLR240W.
GeneID	850941.
KEGG	sce:YLR240W.
Organism-specific databases
CYGD	YLR240w.
SGD	S000004230. VPS34.
Phylogenomic databases
eggNOG	COG5032.
GeneTree	ENSGT00620000087805.
HOGENOM	HOG000174003.
KO	K00914.
OMA	SAMTRRI.
OrthoDB	EOG4PP1R1.
Enzyme and pathway databases
BRENDA	2.7.1.137. 984.
Gene expression databases
Genevestigator	P22543.
GermOnline	YLR240W. Saccharomyces cerevisiae.
Family and domain databases
Gene3D	1.10.1070.11. 1 hit. 1.25.40.70. 2 hits.
InterPro	IPR016024. ARM-type_fold. IPR008973. C2_Ca/lipid-bd_dom_CaLB. 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]
PANTHER	PTHR10048. PTHR10048. 1 hit.
Pfam	PF00454. PI3_PI4_kinase. 1 hit. PF00792. PI3K_C2. 1 hit. PF00613. PI3Ka. 1 hit. [Graphical view]
PIRSF	PIRSF000587. PI3K_Vps34. 1 hit.
SMART	SM00142. PI3K_C2. 1 hit. SM00145. PI3Ka. 1 hit. SM00146. PI3Kc. 1 hit. [Graphical view]
SUPFAM	SSF48371. ARM-type_fold. 1 hit. SSF49562. C2_CaLB. 1 hit. SSF56112. Kinase_like. 1 hit.
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. [Graphical view]
ProtoNet	Search...
Other
NextBio	967390.

Entry information

Entry name

VPS34_YEAST

Accession

Primary (citable) accession number: P22543
Secondary accession number(s): D6VYN8

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	August 1, 1991
Last modified:	May 1, 2013
This is version 127 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program

Relevant documents

Yeast

Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD

Yeast chromosome XII

Yeast (Saccharomyces cerevisiae) chromosome XII: entries and gene names

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents