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P43601 (ATG18_YEAST) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:ATG18
Synonyms:AUT10, CVT18, NMR1, SVP1
Ordered Locus Names:YFR021W
OrganismSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]
Taxonomic identifier559292 [NCBI]
Taxonomic lineageEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces

Protein attributes

Sequence length500 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.3 Ref.4 Ref.5 Ref.6 Ref.9 Ref.11 Ref.12 Ref.13 Ref.14 Ref.16 Ref.17 Ref.18 Ref.21 Ref.22 Ref.25 Ref.27

Subunit structure

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. Ref.9 Ref.10 Ref.12 Ref.14 Ref.17 Ref.18 Ref.19

Subcellular location

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. Ref.9 Ref.10 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.24 Ref.26 Ref.28

Domain

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). Ref.13 Ref.21

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. Ref.13 Ref.21

Miscellaneous

Present with 1560 molecules/cell in log phase SD medium.

Sequence similarities

Belongs to the WD repeat SVP1 family.

Contains 2 WD repeats.

Ontologies

Keywords
   Biological processAutophagy
Protein transport
Transport
   Cellular componentEndosome
Membrane
Vacuole
   DomainRepeat
WD repeat
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processCVT pathway

Inferred from direct assay Ref.4. Source: SGD

late endosome to vacuole transport

Inferred from mutant phenotype Ref.10. Source: SGD

late nucleophagy

Inferred from mutant phenotype PubMed 22768199. Source: SGD

macroautophagy

Inferred from direct assay Ref.4. Source: SGD

peroxisome degradation

Inferred from mutant phenotype Ref.5. Source: SGD

piecemeal microautophagy of nucleus

Inferred from mutant phenotype PubMed 18701704. Source: SGD

vacuolar protein processing

Inferred from direct assay Ref.4. Source: SGD

   Cellular_componentPAS complex

Inferred from direct assay Ref.17. Source: SGD

cytosol

Inferred from direct assay Ref.4. Source: SGD

endosome

Inferred from direct assay Ref.16. Source: SGD

endosome membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

fungal-type vacuole membrane

Inferred from direct assay Ref.10. Source: SGD

pre-autophagosomal structure

Inferred from direct assay Ref.15. Source: SGD

pre-autophagosomal structure membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

vacuolar membrane

Inferred from direct assay Ref.14. Source: UniProtKB

   Molecular_functionphosphatidylinositol-3,5-bisphosphate binding

Inferred from direct assay Ref.10. Source: SGD

protein binding

Inferred from physical interaction Ref.14. Source: UniProtKB

ubiquitin binding

Inferred from direct assay PubMed 21070969. Source: SGD

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

VAC14Q067085EBI-22968,EBI-27189

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 500500Autophagy-related protein 18
PRO_0000050874

Regions

Repeat243 – 28341WD 1
Repeat288 – 32740WD 2
Region284 – 2874Necessary for proper localization to vacuole membrane
Motif284 – 2885FRRGT-motif

Amino acid modifications

Modified residue3541Phosphoserine Ref.20

Experimental info

Mutagenesis73 – 764RRLR → SSLS: Slight reduction of PIP2 binding. Ref.10
Mutagenesis2641S → A: Impairs membrane-association. Ref.28
Mutagenesis2681T → A: Impairs membrane-association. Ref.28
Mutagenesis2711R → A: Impairs membrane-association. Ref.28
Mutagenesis285 – 2862RR → GG: Loss of recruitment to vacuole membrane. Ref.14 Ref.28
Mutagenesis285 – 2862RR → TT: 40-fold decrease of affinity to PIP2. Ref.14 Ref.28
Mutagenesis2851R → A: Impairs membrane-association. Ref.28
Mutagenesis2861R → A: Impairs membrane-association. Ref.28
Mutagenesis3111S → A: Impairs membrane-association. Ref.28
Mutagenesis3131T → A: Impairs membrane-association. Ref.28
Mutagenesis3151H → A: Impairs membrane-association. Ref.28

Sequences

Sequence LengthMass (Da)Tools
P43601 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: 06B2DFAF842AE933

FASTA50055,102
        10         20         30         40         50         60 
MSDSSPTINF INFNQTGTCI SLGTSKGFKI FNCEPFGKFY SEDSGGYAIV EMLFSTSLLA 

        70         80         90        100        110        120 
LVGIGDQPAL SPRRLRIINT KKHSIICEVT FPTSILSVKM NKSRLVVLLQ EQIYIYDINT 

       130        140        150        160        170        180 
MRLLHTIETN PNPRGLMAMS PSVANSYLVY PSPPKVINSE IKAHATTNNI TLSVGGNTET 

       190        200        210        220        230        240 
SFKRDQQDAG HSDISDLDQY SSFTKRDDAD PTSSNGGNSS IIKNGDVIVF NLETLQPTMV 

       250        260        270        280        290        300 
IEAHKGEIAA MAISFDGTLM ATASDKGTII RVFDIETGDK IYQFRRGTYA TRIYSISFSE 

       310        320        330        340        350        360 
DSQYLAVTGS SKTVHIFKLG HSMSNNKLDS DDSNMEEAAA DDSSLDTTSI DALSDEENPT 

       370        380        390        400        410        420 
RLAREPYVDA SRKTMGRMIR YSSQKLSRRA ARTLGQIFPI KVTSLLESSR HFASLKLPVE 

       430        440        450        460        470        480 
TNSHVMTISS IGSPIDIDTS EYPELFETGN SASTESYHEP VMKMVPIRVV SSDGYLYNFV 

       490        500 
MDPERGGDCL ILSQYSILMD 

« Hide

References

« Hide 'large scale' references
[1]"Analysis of the nucleotide sequence of chromosome VI from Saccharomyces cerevisiae."
Murakami Y., Naitou M., Hagiwara H., Shibata T., Ozawa M., Sasanuma S., Sasanuma M., Tsuchiya Y., Soeda E., Yokoyama K., Yamazaki M., Tashiro H., Eki T.
Nat. Genet. 10:261-268(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: ATCC 204508 / S288c.
[2]"The reference genome sequence of Saccharomyces cerevisiae: Then and now."
Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.
G3 (Bethesda) 4:389-398(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: GENOME REANNOTATION.
Strain: ATCC 204508 / S288c.
[3]"A screen for genes required for meiosis and spore formation based on whole-genome expression."
Rabitsch K.P., Toth A., Galova M., Schleiffer A., Schaffner G., Aigner E., Rupp C., Penkner A.M., Moreno-Borchart A.C., Primig M., Esposito R.E., Klein F., Knop M., Nasmyth K.
Curr. Biol. 11:1001-1009(2001) [PubMed] [Europe PMC] [Abstract]
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]"A unified nomenclature for yeast autophagy-related genes."
Klionsky D.J., Cregg J.M., Dunn W.A. Jr., Emr S.D., Sakai Y., Sandoval I.V., Sibirny A., Subramani S., Thumm M., Veenhuis M., Ohsumi Y.
Dev. Cell 5:539-545(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NOMENCLATURE.
[8]"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].
[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]"Svp1p defines a family of phosphatidylinositol 3,5-bisphosphate effectors."
Dove S.K., Piper R.C., McEwen R.K., Yu J.W., King M.C., Hughes D.C., Thuring J., Holmes A.B., Cooke F.T., Michell R.H., Parker P.J., Lemmon M.A.
EMBO J. 23:1922-1933(2004) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D50617 Genomic DNA. Translation: BAA09260.1.
BK006940 Genomic DNA. Translation: DAA12461.1.
PIRS56276.
RefSeqNP_444297.1. NM_001179986.1.

3D structure databases

ProteinModelPortalP43601.
SMRP43601. Positions 112-152, 231-331, 455-485.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid31174. 64 interactions.
DIPDIP-5185N.
IntActP43601. 16 interactions.
MINTMINT-541235.
STRING4932.YFR021W.

Protein family/group databases

TCDB9.A.15.1.1. the autophagy-related phagophore-formation transporter (apt) family.

Proteomic databases

MaxQBP43601.
PaxDbP43601.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblFungiYFR021W; YFR021W; YFR021W.
GeneID850577.
KEGGsce:YFR021W.

Organism-specific databases

CYGDYFR021w.
SGDS000001917. ATG18.

Phylogenomic databases

eggNOGNOG317564.
GeneTreeENSGT00730000110845.
HOGENOMHOG000217543.
KOK17908.
OMAYPTKIYS.
OrthoDBEOG7BW0V3.

Enzyme and pathway databases

BioCycYEAST:G3O-30472-MONOMER.

Gene expression databases

GenevestigatorP43601.

Family and domain databases

Gene3D2.130.10.10. 2 hits.
InterProIPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamPF00400. WD40. 2 hits.
[Graphical view]
SMARTSM00320. WD40. 2 hits.
[Graphical view]
SUPFAMSSF50978. SSF50978. 2 hits.
PROSITEPS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio966400.

Entry information

Entry nameATG18_YEAST
AccessionPrimary (citable) accession number: P43601
Secondary accession number(s): D6VTQ1
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: June 11, 2014
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Relevant documents

Yeast chromosome VI

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

Yeast

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

SIMILARITY comments

Index of protein domains and families