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P43601

- ATG18_YEAST

UniProt

P43601 - ATG18_YEAST

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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

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 ATG4-mediated cleavage.17 Publications

GO - Molecular functioni

  1. phosphatidylinositol-3,5-bisphosphate binding Source: SGD
  2. 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
Complete GO annotation...

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 181 Publication
Alternative name(s):
Cytoplasm to vacuole targeting protein 181 Publication
Needed for premeiotic replication protein 11 Publication
Swollen vacuole phenotype protein 11 Publication
Gene namesi
Name:ATG181 Publication
Synonyms:AUT101 Publication, CVT181 Publication, NMR11 Publication, SVP11 Publication
Ordered Locus Names:YFR021WImported
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 5 Publications; Peripheral membrane protein 5 Publications. Vacuole membrane 6 Publications; Peripheral membrane protein 6 Publications. Endosome membrane 1 Publication; Peripheral membrane protein 1 Publication
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.1 Publication

GO - Cellular componenti

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

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.8 Publications

Binary interactionsi

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

Protein-protein interaction databases

BioGridi31174. 65 interactions.
DIPiDIP-5185N.
IntActiP43601. 16 interactions.
MINTiMINT-541235.
STRINGi4932.YFR021W.

Structurei

3D structure databases

ProteinModelPortaliP43601.
SMRiP43601. Positions 5-33, 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-motif1 Publication

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).1 Publication
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.1 Publication

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.
InParanoidiP43601.
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

        10         20         30         40         50
MSDSSPTINF INFNQTGTCI SLGTSKGFKI FNCEPFGKFY SEDSGGYAIV
60 70 80 90 100
EMLFSTSLLA LVGIGDQPAL SPRRLRIINT KKHSIICEVT FPTSILSVKM
110 120 130 140 150
NKSRLVVLLQ EQIYIYDINT MRLLHTIETN PNPRGLMAMS PSVANSYLVY
160 170 180 190 200
PSPPKVINSE IKAHATTNNI TLSVGGNTET SFKRDQQDAG HSDISDLDQY
210 220 230 240 250
SSFTKRDDAD PTSSNGGNSS IIKNGDVIVF NLETLQPTMV IEAHKGEIAA
260 270 280 290 300
MAISFDGTLM ATASDKGTII RVFDIETGDK IYQFRRGTYA TRIYSISFSE
310 320 330 340 350
DSQYLAVTGS SKTVHIFKLG HSMSNNKLDS DDSNMEEAAA DDSSLDTTSI
360 370 380 390 400
DALSDEENPT RLAREPYVDA SRKTMGRMIR YSSQKLSRRA ARTLGQIFPI
410 420 430 440 450
KVTSLLESSR HFASLKLPVE TNSHVMTISS IGSPIDIDTS EYPELFETGN
460 470 480 490 500
SASTESYHEP VMKMVPIRVV SSDGYLYNFV MDPERGGDCL ILSQYSILMD
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 5-33, 231-331, 455-485.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 31174. 65 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.
InParanoidi P43601.
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

« Hide 'large scale' publications
  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.
  29. "Atg1 kinase organizes autophagosome formation by phosphorylating Atg9."
    Papinski D., Kraft C.
    Autophagy 10:1338-1340(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH ATG9.

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 29, 2014
This is version 132 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