Phosphatidylinositol 3-kinase VPS34 (P22543)

Identification
NamePhosphatidylinositol 3-kinase VPS34
Synonyms
  • PI3-kinase VPS34
  • PI3K VPS34
  • PtdIns-3-kinase VPS34
  • Carboxypeptidase Y-deficient protein 15
  • Vacuolar protein sorting-associated protein 34
  • Vacuolar protein-targeting protein 29
Gene NameVPS34
Enzyme Class
Biological Properties
General FunctionInvolved in binding
Specific FunctionPhosphatidylinositol 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
Cellular LocationGolgi apparatus, trans-Golgi network membrane; Peripheral membrane protein. Endosome membrane; Peripheral membrane protein
SMPDB Pathways
Inositol MetabolismPW002498 ThumbThumb?image type=greyscaleThumb?image type=simple
Inositol phosphate metabolismPW002495 ThumbThumb?image type=greyscaleThumb?image type=simple
KEGG Pathways
Inositol phosphate metabolismec00562 Map00562
SMPDB Reactions
1-Phosphatidyl-D-myo-inositol + Adenosine triphosphate → 1-phosphatidyl-1D-myo-inositol 4-phosphate + ADP
KEGG Reactions
Adenosine triphosphate + 1-Phosphatidyl-D-myo-inositol → 1-phosphatidyl-1D-myo-inositol 3-phosphate + ADP
Metabolites
YMDB IDNameView
YMDB00109Adenosine triphosphateShow
YMDB002301-Phosphatidyl-D-myo-inositolShow
YMDB00914ADPShow
YMDB162491-phosphatidyl-1D-myo-inositol 4-phosphate Show
GO Classification
Component
phosphoinositide 3-kinase complex
macromolecular complex
protein complex
Function
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
binding
kinase activity
lipid kinase activity
phosphotransferase activity, alcohol group as acceptor
phosphoinositide 3-kinase activity
inositol or phosphatidylinositol kinase activity
1-phosphatidylinositol-3-kinase activity
Process
intracellular signal transduction
second-messenger-mediated signaling
metabolic process
phosphoinositide-mediated signaling
glycerophospholipid metabolic process
phosphoinositide metabolic process
phosphoinositide phosphorylation
biological regulation
regulation of biological process
regulation of cellular process
signal transduction
organophosphate metabolic process
phospholipid metabolic process
Gene Properties
Chromosome Locationchromosome 12
LocusYLR240W
Gene Sequence>2628 bp ATGTCACTGAACAACATAACATTCTGTGTCTCACAGGATCTGGATGTTCCCCTGAAAGTG AAAATCAAGTCATTGGAAGGACATAAGCCACTGTTGAAGCCATCTCAAAAAATCCTGAAC CCTGAATTAATGCTGATAGGGTCAAATGTATTCCCTTCTAGTGATCTAATTGTATCCTTA CAGGTATTTGATAAAGAGAGAAACAGAAATTTAACTCTTCCGATATACACGCCGTATATT CCTTTCAGAAACTCTAGAACCTGGGATTATTGGTTGACTTTGCCCATACGTATCAAACAG CTTACCTTTAGCAGTCATTTACGCATTATTTTGTGGGAATACAATGGATCCAAGCAAATT CCCTTTTTCAATCTAGAAACGAGCATCTTTAACTTAAAAGACTGTACTTTAAAAAGAGGG TTTGAATCCTTAAAATTTCGTTATGATGTGATTGACCACTGTGAAGTGGTCACTGATAAC AAAGATCAAGAAAATTTGAATAAATATTTTCAGGGTGAATTCACGAGACTCCCTTGGCTT GACGAAATCACTATAAGCAAATTAAGGAAACAACGGGAAAATAGGACTTGGCCTCAGGGC ACCTTTGTCTTAAACTTAGAATTTCCAATGTTAGAGCTTCCTGTTGTGTTCATCGAAAGG GAAATTATGAATACTCAAATGAATATTCCAACTTTGAAGAACAATCCTGGACTAAGCACA GACTTACGAGAACCGAATAGGAATGATCCTCAAATCAAAATTTCTTTGGGGGACAAATAT CACTCCACATTGAAGTTTTACGATCCTGACCAACCAAACAATGATCCAATAGAGGAAAAG TATAGGAGATTGGAAAGAGCATCTAAAAATGCAAACTTGGACAAGCAAGTGAAGCCGGAC ATTAAAAAGAGGGACTACTTGAATAAAATCATCAACTACCCCCCTGGCACTAAATTAACA GCACATGAAAAGGGTTCAATATGGAAATATAGGTATTATTTGATGAACAATAAAAAAGCT CTTACAAAGTTATTACAGAGTACAAATTTGAGAGAAGAATCGGAAAGAGTAGAGGTTTTA GAACTAATGGACTCATGGGCAGAAATTGATATAGACGACGCATTAGAACTATTAGGCTCA ACTTTTAAAAACCTTTCAGTGAGATCGTACGCCGTAAATAGGCTGAAGAAGGCATCAGAC AAGGAGCTGGAATTGTACTTATTACAGTTGGTAGAAGCTGTCTGTTTTGAGAACCTGTCC ACTTTTTCCGACAAATCTAACAGTGAATTCACTATTGTGGATGCCGTATCTTCGCAAAAG CTTTCGGGTGATTCTATGTTACTATCTACATCGCATGCCAACCAAAAATTATTAAAGTCC ATCTCGAGTGAATCGGAAACTTCCGGGACAGAATCGCTACCAATCGTCATTTCTCCCTTG GCTGAGTTTTTGATTAGGAGAGCACTGGTCAACCCAAGGTTAGGAAGTTTTTTCTATTGG TATTTAAAGTCCGAGTCTGAGGACAAGCCATATTTAGACCAGATTTTAAGTTCCTTTTGG AGTAGACTGGATAAAAAATCTCGGAATATACTGAACGATCAAGTCAGGCTAATAAATGTG CTCAGGGAATGTTGTGAAACAATTAAGAGGCTGAAAGATACTACAGCCAAAAAGATGGAA TTACTAGTGCATTTATTGGAGACGAAAGTCAGGCCTCTTGTCAAAGTACGACCAATTGCT TTACCACTAGACCCTGATGTGTTGATATGCGACGTTTGTCCTGAAACTTCGAAGGTATTT AAAAGCTCTTTATCGCCACTAAAAATAACATTCAAAACGACCTTAAACCAACCATATCAC TTAATGTTTAAGGTTGGCGATGATTTGAGACAAGATCAACTGGTAGTACAGATCATAAGT TTAATGAATGAGTTATTAAAAAATGAAAACGTGGACTTGAAATTGACACCATACAAAATT TTGGCAACAGGACCACAAGAAGGTGCCATTGAATTTATCCCTAATGACACATTAGCTAGC ATACTAAGCAAATATCACGGTATTCTTGGCTACCTTAAACTCCACTATCCTGATGAGAAC GCGACATTAGGCGTACAAGGCTGGGTTTTAGATAATTTTGTCAAATCTTGTGCTGGCTAT TGTGTTATTACATACATCTTAGGTGTCGGCGATAGGCATTTAGACAACTTACTAGTCACG CCAGATGGGCACTTTTTTCACGCAGACTTTGGTTATATCTTGGGTCAGGACCCCAAACCT TTTCCGCCATTAATGAAATTGCCCCCTCAAATTATAGAGGCGTTTGGGGGTGCAGAATCA TCAAATTATGATAAATTTCGCAGCTACTGTTTTGTGGCATATTCGATTTTAAGAAGGAAT GCAGGCTTAATCTTAAACCTGTTTGAATTAATGAAGACTTCGAACATACCTGATATCAGA ATAGATCCCAATGGTGCTATATTACGTGTAAGAGAGAGATTTAATTTGAATATGTCCGAA GAAGATGCCACAGTGCATTTTCAGAATCTAATCAATGATAGTGTAAATGCTTTGCTGCCT ATCGTGATTGATCATTTACATAATCTGGCACAATACTGGCGGACCTGA
Protein Properties
Pfam Domain Function
Protein Residues875
Protein Molecular Weight100920.0
Protein Theoretical pI7.9
Signalling Regions
  • None
Transmembrane Regions
  • None
Protein Sequence>Phosphatidylinositol 3-kinase VPS34 MSLNNITFCVSQDLDVPLKVKIKSLEGHKPLLKPSQKILNPELMLIGSNVFPSSDLIVSL QVFDKERNRNLTLPIYTPYIPFRNSRTWDYWLTLPIRIKQLTFSSHLRIILWEYNGSKQI PFFNLETSIFNLKDCTLKRGFESLKFRYDVIDHCEVVTDNKDQENLNKYFQGEFTRLPWL DEITISKLRKQRENRTWPQGTFVLNLEFPMLELPVVFIEREIMNTQMNIPTLKNNPGLST DLREPNRNDPQIKISLGDKYHSTLKFYDPDQPNNDPIEEKYRRLERASKNANLDKQVKPD IKKRDYLNKIINYPPGTKLTAHEKGSIWKYRYYLMNNKKALTKLLQSTNLREESERVEVL ELMDSWAEIDIDDALELLGSTFKNLSVRSYAVNRLKKASDKELELYLLQLVEAVCFENLS TFSDKSNSEFTIVDAVSSQKLSGDSMLLSTSHANQKLLKSISSESETSGTESLPIVISPL AEFLIRRALVNPRLGSFFYWYLKSESEDKPYLDQILSSFWSRLDKKSRNILNDQVRLINV LRECCETIKRLKDTTAKKMELLVHLLETKVRPLVKVRPIALPLDPDVLICDVCPETSKVF KSSLSPLKITFKTTLNQPYHLMFKVGDDLRQDQLVVQIISLMNELLKNENVDLKLTPYKI LATGPQEGAIEFIPNDTLASILSKYHGILGYLKLHYPDENATLGVQGWVLDNFVKSCAGY CVITYILGVGDRHLDNLLVTPDGHFFHADFGYILGQDPKPFPPLMKLPPQIIEAFGGAES SNYDKFRSYCFVAYSILRRNAGLILNLFELMKTSNIPDIRIDPNGAILRVRERFNLNMSE EDATVHFQNLINDSVNALLPIVIDHLHNLAQYWRT
References
External Links
ResourceLink
Saccharomyces Genome Database VPS34
Uniprot IDP22543
Uniprot NameVPS34_YEAST
GenBank Gene IDU20865
Genebank Protein ID662340
General Reference
  • Herman, P. K., Emr, S. D. (1990). "Characterization of VPS34, a gene required for vacuolar protein sorting and vacuole segregation in Saccharomyces cerevisiae." Mol Cell Biol 10:6742-6754.2247081
  • Johnston, M., Hillier, L., Riles, L., Albermann, K., Andre, B., Ansorge, W., Benes, V., Bruckner, M., Delius, H., Dubois, E., Dusterhoft, A., Entian, K. D., Floeth, M., Goffeau, A., Hebling, U., Heumann, K., Heuss-Neitzel, D., Hilbert, H., Hilger, F., Kleine, K., Kotter, P., Louis, E. J., Messenguy, F., Mewes, H. W., Hoheisel, J. D., et, a. l. .. (1997). "The nucleotide sequence of Saccharomyces cerevisiae chromosome XII." Nature 387:87-90.9169871
  • Robinson, J. S., Klionsky, D. J., Banta, L. M., Emr, S. D. (1988). "Protein sorting in Saccharomyces cerevisiae: isolation of mutants defective in the delivery and processing of multiple vacuolar hydrolases." Mol Cell Biol 8:4936-4948.3062374
  • Auger, K. R., Carpenter, C. L., Cantley, L. C., Varticovski, L. (1989). "Phosphatidylinositol 3-kinase and its novel product, phosphatidylinositol 3-phosphate, are present in Saccharomyces cerevisiae." J Biol Chem 264:20181-20184.2555343
  • Stack, J. H., Herman, P. K., Schu, P. V., Emr, S. D. (1993). "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." EMBO J 12:2195-2204.8387919
  • Schu, P. V., Takegawa, K., Fry, M. J., Stack, J. H., Waterfield, M. D., Emr, S. D. (1993). "Phosphatidylinositol 3-kinase encoded by yeast VPS34 gene essential for protein sorting." Science 260:88-91.8385367
  • Stack, J. H., Emr, S. D. (1994). "Vps34p required for yeast vacuolar protein sorting is a multiple specificity kinase that exhibits both protein kinase and phosphatidylinositol-specific PI 3-kinase activities." J Biol Chem 269:31552-31562.7989323
  • Munn, A. L., Riezman, H. (1994). "Endocytosis is required for the growth of vacuolar H(+)-ATPase-defective yeast: identification of six new END genes." J Cell Biol 127:373-386.7929582
  • Kihara, A., Noda, T., Ishihara, N., Ohsumi, Y. (2001). "Two distinct Vps34 phosphatidylinositol 3-kinase complexes function in autophagy and carboxypeptidase Y sorting in Saccharomyces cerevisiae." J Cell Biol 152:519-530.11157979
  • Takahashi, T., Shimoi, H., Ito, K. (2001). "Identification of genes required for growth under ethanol stress using transposon mutagenesis in Saccharomyces cerevisiae." Mol Genet Genomics 265:1112-1119.11523784
  • Burda, P., Padilla, S. M., Sarkar, S., Emr, S. D. (2002). "Retromer function in endosome-to-Golgi retrograde transport is regulated by the yeast Vps34 PtdIns 3-kinase." J Cell Sci 115:3889-3900.12244127
  • Huh, W. K., Falvo, J. V., Gerke, L. C., Carroll, A. S., Howson, R. W., Weissman, J. S., O'Shea, E. K. (2003). "Global analysis of protein localization in budding yeast." Nature 425:686-691.14562095
  • Ghaemmaghami, S., Huh, W. K., Bower, K., Howson, R. W., Belle, A., Dephoure, N., O'Shea, E. K., Weissman, J. S. (2003). "Global analysis of protein expression in yeast." Nature 425:737-741.14562106