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P43601

- ATG18_YEAST

UniProt

P43601 - ATG18_YEAST

Protein

Autophagy-related protein 18

Gene

ATG18

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 131 (01 Oct 2014)
      Sequence version 1 (01 Nov 1995)
      Previous versions | rss
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    Functioni

    The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). May negatively regulate FAB1 activity by sequestering or masking VAC7 from FAB1. Necessary for proper vacuole morphology. Plays an important role in osmotically-induced vacuole fragmentation. Required for cytoplasm to vacuole transport (Cvt) vesicle formation, pexophagy and starvation-induced autophagy. Involved in correct ATG9 trafficking to the pre-autophagosomal structure. Might also be involved in premeiotic DNA replication. With ATG2, protects ATG8 from ARG4-mediated cleavage.16 Publications

    GO - Molecular functioni

    1. phosphatidylinositol-3,5-bisphosphate binding Source: SGD
    2. protein binding Source: UniProtKB
    3. ubiquitin binding Source: SGD

    GO - Biological processi

    1. CVT pathway Source: SGD
    2. late endosome to vacuole transport Source: SGD
    3. late nucleophagy Source: SGD
    4. macroautophagy Source: SGD
    5. peroxisome degradation Source: SGD
    6. piecemeal microautophagy of nucleus Source: SGD
    7. vacuolar protein processing Source: SGD

    Keywords - Biological processi

    Autophagy, Protein transport, Transport

    Enzyme and pathway databases

    BioCyciYEAST:G3O-30472-MONOMER.
    ReactomeiREACT_188969. XBP1(S) activates chaperone genes.

    Protein family/group databases

    TCDBi9.A.15.1.1. the autophagy-related phagophore-formation transporter (apt) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Autophagy-related protein 18
    Alternative name(s):
    Cytoplasm to vacuole targeting protein 18
    Needed for premeiotic replication protein 1
    Swollen vacuole phenotype protein 1
    Gene namesi
    Name:ATG18
    Synonyms:AUT10, CVT18, NMR1, SVP1
    Ordered Locus Names:YFR021W
    OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
    Taxonomic identifieri559292 [NCBI]
    Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
    ProteomesiUP000002311: Chromosome VI

    Organism-specific databases

    CYGDiYFR021w.
    SGDiS000001917. ATG18.

    Subcellular locationi

    Preautophagosomal structure membrane; Peripheral membrane protein. Vacuole membrane; Peripheral membrane protein. Endosome membrane; Peripheral membrane protein
    Note: Requires VAC7 for vacuole membrane localization. Under mid-log phase growth, localizes to the vacuolar membrane; but when cells are starved, is almost completely released from the vacuole membrane.

    GO - Cellular componenti

    1. cytosol Source: SGD
    2. endosome Source: SGD
    3. endosome membrane Source: UniProtKB-SubCell
    4. fungal-type vacuole membrane Source: SGD
    5. PAS complex Source: SGD
    6. pre-autophagosomal structure Source: SGD
    7. pre-autophagosomal structure membrane Source: UniProtKB-SubCell
    8. vacuolar membrane Source: UniProtKB

    Keywords - Cellular componenti

    Endosome, Membrane, Vacuole

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi73 – 764RRLR → SSLS: Slight reduction of PIP2 binding.
    Mutagenesisi264 – 2641S → A: Impairs membrane-association. 1 Publication
    Mutagenesisi268 – 2681T → A: Impairs membrane-association. 1 Publication
    Mutagenesisi271 – 2711R → A: Impairs membrane-association. 1 Publication
    Mutagenesisi285 – 2862RR → GG: Loss of recruitment to vacuole membrane. 1 Publication
    Mutagenesisi285 – 2862RR → TT: 40-fold decrease of affinity to PIP2. 1 Publication
    Mutagenesisi285 – 2851R → A: Impairs membrane-association. 1 Publication
    Mutagenesisi286 – 2861R → A: Impairs membrane-association. 1 Publication
    Mutagenesisi311 – 3111S → A: Impairs membrane-association. 1 Publication
    Mutagenesisi313 – 3131T → A: Impairs membrane-association. 1 Publication
    Mutagenesisi315 – 3151H → A: Impairs membrane-association. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 500500Autophagy-related protein 18PRO_0000050874Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei354 – 3541Phosphoserine1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiP43601.
    PaxDbiP43601.

    Expressioni

    Gene expression databases

    GenevestigatoriP43601.

    Interactioni

    Subunit structurei

    Component of the PI(3,5)P2 regulatory complex, composed of ATG18, FIG4, FAB1, VAC14 and VAC7. VAC14 nucleates the assembly of the complex and serves as a scaffold. Interacts with ATG2, ATG9 and VAC17. The ATG2-ATG18 complex is essential for autophagosome formation.7 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    VAC14Q067085EBI-22968,EBI-27189

    Protein-protein interaction databases

    BioGridi31174. 64 interactions.
    DIPiDIP-5185N.
    IntActiP43601. 16 interactions.
    MINTiMINT-541235.
    STRINGi4932.YFR021W.

    Structurei

    3D structure databases

    ProteinModelPortaliP43601.
    SMRiP43601. Positions 112-152, 231-331, 455-485.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati243 – 28341WD 1Add
    BLAST
    Repeati288 – 32740WD 2Add
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni284 – 2874Necessary for proper localization to vacuole membrane

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi284 – 2885FRRGT-motif

    Domaini

    The 377 first amino acids might form a beta-propeller domain involved in specific binding to phosphatidylinositol 3,5-bisphosphate (PIP2), leading to the association of the protein to the membrane. Association to the membrane can also occur through binding to phosphatidylinositol 3-monophosphate (PI3P).
    The FRRGT-motif is essential for the cytoplasm to vacuole transport (Cvt) pathway, for the recruitment of ATG8 and ATG16 to the PAS in nutrient-rich medium, and for its recruitment to and dissociation from the PAS under starvation conditions.

    Sequence similaritiesi

    Belongs to the WD repeat SVP1 family.Curated
    Contains 2 WD repeats.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, WD repeat

    Phylogenomic databases

    eggNOGiNOG317564.
    GeneTreeiENSGT00730000110845.
    HOGENOMiHOG000217543.
    KOiK17908.
    OMAiYPTKIYS.
    OrthoDBiEOG7BW0V3.

    Family and domain databases

    Gene3Di2.130.10.10. 2 hits.
    InterProiIPR015943. WD40/YVTN_repeat-like_dom.
    IPR001680. WD40_repeat.
    IPR017986. WD40_repeat_dom.
    [Graphical view]
    PfamiPF00400. WD40. 2 hits.
    [Graphical view]
    SMARTiSM00320. WD40. 2 hits.
    [Graphical view]
    SUPFAMiSSF50978. SSF50978. 2 hits.
    PROSITEiPS50294. WD_REPEATS_REGION. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P43601-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSDSSPTINF INFNQTGTCI SLGTSKGFKI FNCEPFGKFY SEDSGGYAIV    50
    EMLFSTSLLA LVGIGDQPAL SPRRLRIINT KKHSIICEVT FPTSILSVKM 100
    NKSRLVVLLQ EQIYIYDINT MRLLHTIETN PNPRGLMAMS PSVANSYLVY 150
    PSPPKVINSE IKAHATTNNI TLSVGGNTET SFKRDQQDAG HSDISDLDQY 200
    SSFTKRDDAD PTSSNGGNSS IIKNGDVIVF NLETLQPTMV IEAHKGEIAA 250
    MAISFDGTLM ATASDKGTII RVFDIETGDK IYQFRRGTYA TRIYSISFSE 300
    DSQYLAVTGS SKTVHIFKLG HSMSNNKLDS DDSNMEEAAA DDSSLDTTSI 350
    DALSDEENPT RLAREPYVDA SRKTMGRMIR YSSQKLSRRA ARTLGQIFPI 400
    KVTSLLESSR HFASLKLPVE TNSHVMTISS IGSPIDIDTS EYPELFETGN 450
    SASTESYHEP VMKMVPIRVV SSDGYLYNFV MDPERGGDCL ILSQYSILMD 500
    Length:500
    Mass (Da):55,102
    Last modified:November 1, 1995 - v1
    Checksum:i06B2DFAF842AE933
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D50617 Genomic DNA. Translation: BAA09260.1.
    BK006940 Genomic DNA. Translation: DAA12461.1.
    PIRiS56276.
    RefSeqiNP_444297.1. NM_001179986.1.

    Genome annotation databases

    EnsemblFungiiYFR021W; YFR021W; YFR021W.
    GeneIDi850577.
    KEGGisce:YFR021W.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D50617 Genomic DNA. Translation: BAA09260.1 .
    BK006940 Genomic DNA. Translation: DAA12461.1 .
    PIRi S56276.
    RefSeqi NP_444297.1. NM_001179986.1.

    3D structure databases

    ProteinModelPortali P43601.
    SMRi P43601. Positions 112-152, 231-331, 455-485.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 31174. 64 interactions.
    DIPi DIP-5185N.
    IntActi P43601. 16 interactions.
    MINTi MINT-541235.
    STRINGi 4932.YFR021W.

    Protein family/group databases

    TCDBi 9.A.15.1.1. the autophagy-related phagophore-formation transporter (apt) family.

    Proteomic databases

    MaxQBi P43601.
    PaxDbi P43601.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    EnsemblFungii YFR021W ; YFR021W ; YFR021W .
    GeneIDi 850577.
    KEGGi sce:YFR021W.

    Organism-specific databases

    CYGDi YFR021w.
    SGDi S000001917. ATG18.

    Phylogenomic databases

    eggNOGi NOG317564.
    GeneTreei ENSGT00730000110845.
    HOGENOMi HOG000217543.
    KOi K17908.
    OMAi YPTKIYS.
    OrthoDBi EOG7BW0V3.

    Enzyme and pathway databases

    BioCyci YEAST:G3O-30472-MONOMER.
    Reactomei REACT_188969. XBP1(S) activates chaperone genes.

    Miscellaneous databases

    NextBioi 966400.

    Gene expression databases

    Genevestigatori P43601.

    Family and domain databases

    Gene3Di 2.130.10.10. 2 hits.
    InterProi IPR015943. WD40/YVTN_repeat-like_dom.
    IPR001680. WD40_repeat.
    IPR017986. WD40_repeat_dom.
    [Graphical view ]
    Pfami PF00400. WD40. 2 hits.
    [Graphical view ]
    SMARTi SM00320. WD40. 2 hits.
    [Graphical view ]
    SUPFAMi SSF50978. SSF50978. 2 hits.
    PROSITEi PS50294. WD_REPEATS_REGION. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: ATCC 204508 / S288c.
    2. Cited for: GENOME REANNOTATION.
      Strain: ATCC 204508 / S288c.
    3. Cited for: FUNCTION.
    4. "Autophagy and the cytoplasm to vacuole targeting pathway both require Aut10p."
      Barth H., Meiling-Wesse K., Epple U.D., Thumm M.
      FEBS Lett. 508:23-28(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    5. "Cvt18/Gsa12 is required for cytoplasm-to-vacuole transport, pexophagy, and autophagy in Saccharomyces cerevisiae and Pichia pastoris."
      Guan J., Stromhaug P.E., George M.D., Habibzadegah-Tari P., Bevan A., Dunn W.A. Jr., Klionsky D.J.
      Mol. Biol. Cell 12:3821-3838(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    6. "Functional analysis of the Saccharomyces cerevisiae YFR021w/YGR223c/YPL100w ORF family suggests relations to mitochondrial/peroxisomal functions and amino acid signalling pathways."
      Georgakopoulos T., Koutroubas G., Vakonakis I., Tzermia M., Prokova V., Voutsina A., Alexandraki D.
      Yeast 18:1155-1171(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    7. Cited for: NOMENCLATURE.
    8. Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
    9. "The Atg1-Atg13 complex regulates Atg9 and Atg23 retrieval transport from the pre-autophagosomal structure."
      Reggiori F., Tucker K.A., Stromhaug P.E., Klionsky D.J.
      Dev. Cell 6:79-90(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ATG9.
    10. Cited for: INTERACTION WITH PIP2, SUBCELLULAR LOCATION, MUTAGENESIS OF 73-ARG--ARG-76 AND 285-ARG-ARG-286.
    11. "Atg21 is required for effective recruitment of Atg8 to the preautophagosomal structure during the Cvt pathway."
      Meiling-Wesse K., Barth H., Voss C., Eskelinen E.-L., Epple U.D., Thumm M.
      J. Biol. Chem. 279:37741-37750(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    12. "Atg21 is a phosphoinositide binding protein required for efficient lipidation and localization of Atg8 during uptake of aminopeptidase I by selective autophagy."
      Stromhaug P.E., Reggiori F., Guan J., Wang C.-W., Klionsky D.J.
      Mol. Biol. Cell 15:3553-3566(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PIP2.
    13. "The relevance of the phosphatidylinositolphosphat-binding motif FRRGT of Atg18 and Atg21 for the Cvt pathway and autophagy."
      Krick R., Tolstrup J., Appelles A., Henke S., Thumm M.
      FEBS Lett. 580:4632-4638(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, DOMAIN.
    14. "Atg18 regulates organelle morphology and Fab1 kinase activity independent of its membrane recruitment by phosphatidylinositol 3,5-bisphosphate."
      Efe J.A., Botelho R.J., Emr S.D.
      Mol. Biol. Cell 18:4232-4244(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH VAC17, MUTAGENESIS OF 285-ARG--ARG-286.
    15. "Localization of autophagy-related proteins in yeast using a versatile plasmid-based resource of fluorescent protein fusions."
      Ma J., Bharucha N., Dobry C.J., Frisch R.L., Lawson S., Kumar A.
      Autophagy 4:792-800(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    16. "Dissecting the localization and function of Atg18, Atg21 and Ygr223c."
      Krick R., Henke S., Tolstrup J., Thumm M.
      Autophagy 4:896-910(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, FUNCTION.
    17. "VAC14 nucleates a protein complex essential for the acute interconversion of PI3P and PI(3,5)P(2) in yeast and mouse."
      Jin N., Chow C.Y., Liu L., Zolov S.N., Bronson R., Davisson M., Petersen J.L., Zhang Y., Park S., Duex J.E., Goldowitz D., Meisler M.H., Weisman L.S.
      EMBO J. 27:3221-3234(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION IN THE PI(3,5)P2 REGULATORY COMPLEX, FUNCTION, SUBCELLULAR LOCATION.
    18. "The Atg18-Atg2 complex is recruited to autophagic membranes via phosphatidylinositol 3-phosphate and exerts an essential function."
      Obara K., Sekito T., Niimi K., Ohsumi Y.
      J. Biol. Chem. 283:23972-23980(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH ATG2, PI3P-BINDING, SUBCELLULAR LOCATION.
    19. "Self-interaction is critical for Atg9 transport and function at the phagophore assembly site during autophagy."
      He C., Baba M., Cao Y., Klionsky D.J.
      Mol. Biol. Cell 19:5506-5516(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ATG9, SUBCELLULAR LOCATION.
    20. "A multidimensional chromatography technology for in-depth phosphoproteome analysis."
      Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.
      Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-354, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    21. "Roles of the lipid-binding motifs of Atg18 and Atg21 in the cytoplasm to vacuole targeting pathway and autophagy."
      Nair U., Cao Y., Xie Z., Klionsky D.J.
      J. Biol. Chem. 285:11476-11488(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DOMAIN.
    22. "GFP-Atg8 protease protection as a tool to monitor autophagosome biogenesis."
      Nair U., Thumm M., Klionsky D.J., Krick R.
      Autophagy 7:1546-1550(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    23. "Phosphoinositide [PI(3,5)P2] lipid-dependent regulation of the general transcriptional regulator Tup1."
      Han B.K., Emr S.D.
      Genes Dev. 25:984-995(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: PIP2-BINDING.
    24. "KCS1 deletion in Saccharomyces cerevisiae leads to a defect in translocation of autophagic proteins and reduces autophagosome formation."
      Taylor R. Jr., Chen P.H., Chou C.C., Patel J., Jin S.V.
      Autophagy 8:1300-1311(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    25. "Autophagosome formation can be achieved in the absence of Atg18 by expressing engineered PAS-targeted Atg2."
      Kobayashi T., Suzuki K., Ohsumi Y.
      FEBS Lett. 586:2473-2478(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION OF THE ATG2-ATG8 COMPLEX.
    26. "Two-site recognition of phosphatidylinositol 3-phosphate by PROPPINs in autophagy."
      Baskaran S., Ragusa M.J., Boura E., Hurley J.H.
      Mol. Cell 47:339-348(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    27. "Yeast vacuoles fragment in an asymmetrical two-phase process with distinct protein requirements."
      Zieger M., Mayer A.
      Mol. Biol. Cell 23:3438-3449(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    28. "Structural and functional characterization of the two phosphoinositide binding sites of PROPPINs, a beta-propeller protein family."
      Krick R., Busse R.A., Scacioc A., Stephan M., Janshoff A., Thumm M., Kuhnel K.
      Proc. Natl. Acad. Sci. U.S.A. 109:E2042-E2049(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF SER-264; THR-268; ARG-271; ARG-285; ARG-286; SER-311; THR-313 AND HIS-315.

    Entry informationi

    Entry nameiATG18_YEAST
    AccessioniPrimary (citable) accession number: P43601
    Secondary accession number(s): D6VTQ1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1995
    Last sequence update: November 1, 1995
    Last modified: October 1, 2014
    This is version 131 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 1560 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 VI
      Yeast (Saccharomyces cerevisiae) chromosome VI: entries and gene names

    External Data

    Dasty 3