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P38316

- ATG12_YEAST

UniProt

P38316 - ATG12_YEAST

Protein

Ubiquitin-like protein ATG12

Gene

ATG12

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 122 (01 Oct 2014)
      Sequence version 1 (01 Oct 1994)
      Previous versions | rss
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    Functioni

    Ubiquitin-like protein involved in cytoplasm to vacuole transport (Cvt), autophagy vesicles formation, mitophagy, and nucleophagy. Conjugation with ATG5 through a ubiquitin-like conjugating system involving also ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 and ATG8 association to the vesicle membranes. ATG12-ATG5 rearranges the ATG3 catalytic center and enhances its E2 activity.14 Publications

    GO - Molecular functioni

    1. protein binding Source: IntAct
    2. protein tag Source: SGD

    GO - Biological processi

    1. autophagic vacuole assembly Source: SGD
    2. C-terminal protein lipidation Source: SGD
    3. CVT pathway Source: SGD
    4. late nucleophagy Source: SGD
    5. mitochondrion degradation Source: SGD
    6. piecemeal microautophagy of nucleus Source: SGD

    Keywords - Biological processi

    Autophagy, Protein transport, Transport, Ubl conjugation pathway

    Enzyme and pathway databases

    BioCyciYEAST:G3O-29154-MONOMER.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Ubiquitin-like protein ATG12
    Alternative name(s):
    Autophagy-related protein 12
    Gene namesi
    Name:ATG12
    Synonyms:APG12
    Ordered Locus Names:YBR217W
    ORF Names:YBR1506
    OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
    Taxonomic identifieri559292 [NCBI]
    Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
    ProteomesiUP000002311: Chromosome II

    Organism-specific databases

    CYGDiYBR217w.
    SGDiS000000421. ATG12.

    Subcellular locationi

    Preautophagosomal structure membrane 5 Publications; Peripheral membrane protein 5 Publications
    Note: Localizes to the isolation membrane (IM), a membrane sac which is generated from the pre-autophagosomal structure (PAS). Ultimately, the IM expands to become a mature autophagosome. Localizes also to a dot at the junction between the IM and the vacuolar membrane, termed the vacuole-IM contact site (VICS).

    GO - Cellular componenti

    1. Atg12-Atg5-Atg16 complex Source: SGD
    2. pre-autophagosomal structure Source: SGD
    3. pre-autophagosomal structure membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi106 – 1061I → A: Decreases protein stability. 1 Publication
    Mutagenesisi108 – 1081F → A: Decreases protein stability. 1 Publication
    Mutagenesisi149 – 1491Y → A: Impairs conjugation to ATG5 and autophagic activity. 1 Publication
    Mutagenesisi154 – 1541F → A: Impairs conjugation to ATG5 and autophagic activity. 1 Publication
    Mutagenesisi186 – 1861G → A: Strong decrease of conjugation with ATG5. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 186186Ubiquitin-like protein ATG12PRO_0000212485Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Cross-linki186 – 186Glycyl lysine isopeptide (Gly-Lys) (interchain with K-149 in ATG5)

    Keywords - PTMi

    Isopeptide bond, Phosphoprotein

    Expressioni

    Gene expression databases

    GenevestigatoriP38316.

    Interactioni

    Subunit structurei

    Forms a conjugate with ATG5. Forms a thioester bond with the 'Cys-133' of ATG10. Interacts with the ATG7 C-terminal 40 amino acids domain. The ATG12-ATG5 conjugate forms a complex with several units of ATG16. The ATG12-ATG5 conjugate associates also with ATG3. Interacts with COG2.7 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ATG16Q0381811EBI-2692,EBI-27344
    ATG5Q1238010EBI-2692,EBI-2664
    ATG7P388623EBI-2692,EBI-2677

    Protein-protein interaction databases

    BioGridi32914. 72 interactions.
    DIPiDIP-1189N.
    IntActiP38316. 62 interactions.
    MINTiMINT-388309.
    STRINGi4932.YBR217W.

    Structurei

    Secondary structure

    1
    186
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi103 – 1108
    Beta strandi121 – 1255
    Helixi130 – 14112
    Beta strandi147 – 1504
    Turni151 – 1533
    Helixi162 – 1698
    Beta strandi174 – 1807

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3W1SX-ray2.60C100-186[»]
    ProteinModelPortaliP38316.
    SMRiP38316. Positions 101-181.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the ATG12 family.Curated

    Phylogenomic databases

    eggNOGiNOG236266.
    HOGENOMiHOG000234863.
    KOiK08336.
    OMAiELIVSYC.
    OrthoDBiEOG7ZSJ5R.

    Family and domain databases

    InterProiIPR007242. Atg12.
    IPR029071. Ubiquitin-rel_dom.
    [Graphical view]
    PANTHERiPTHR13385. PTHR13385. 1 hit.
    PfamiPF04110. APG12. 1 hit.
    [Graphical view]
    SUPFAMiSSF54236. SSF54236. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    P38316-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSRILESENE TESDESSIIS TNNGTAMERS RNNQELRSSP HTVQNRLELF    50
    SRRLSQLGLA SDISVDQQVE DSSSGTYEQE ETIKTNAQTS KQKSHKDEKN 100
    IQKIQIKFQP IGSIGQLKPS VCKISMSQSF AMVILFLKRR LKMDHVYCYI 150
    NNSFAPSPQQ NIGELWMQFK TNDELIVSYC ASVAFG 186
    Length:186
    Mass (Da):21,106
    Last modified:October 1, 1994 - v1
    Checksum:i74B3C9FD3CEA9265
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB017924 Genomic DNA. Translation: BAA33473.1.
    Z36086 Genomic DNA. Translation: CAA85181.1.
    AY557706 Genomic DNA. Translation: AAS56032.1.
    BK006936 Genomic DNA. Translation: DAA07333.1.
    PIRiS46093.
    RefSeqiNP_009776.1. NM_001178565.1.

    Genome annotation databases

    EnsemblFungiiYBR217W; YBR217W; YBR217W.
    GeneIDi852518.
    KEGGisce:YBR217W.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB017924 Genomic DNA. Translation: BAA33473.1 .
    Z36086 Genomic DNA. Translation: CAA85181.1 .
    AY557706 Genomic DNA. Translation: AAS56032.1 .
    BK006936 Genomic DNA. Translation: DAA07333.1 .
    PIRi S46093.
    RefSeqi NP_009776.1. NM_001178565.1.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3W1S X-ray 2.60 C 100-186 [» ]
    ProteinModelPortali P38316.
    SMRi P38316. Positions 101-181.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 32914. 72 interactions.
    DIPi DIP-1189N.
    IntActi P38316. 62 interactions.
    MINTi MINT-388309.
    STRINGi 4932.YBR217W.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    EnsemblFungii YBR217W ; YBR217W ; YBR217W .
    GeneIDi 852518.
    KEGGi sce:YBR217W.

    Organism-specific databases

    CYGDi YBR217w.
    SGDi S000000421. ATG12.

    Phylogenomic databases

    eggNOGi NOG236266.
    HOGENOMi HOG000234863.
    KOi K08336.
    OMAi ELIVSYC.
    OrthoDBi EOG7ZSJ5R.

    Enzyme and pathway databases

    BioCyci YEAST:G3O-29154-MONOMER.

    Miscellaneous databases

    NextBioi 971550.
    PROi P38316.

    Gene expression databases

    Genevestigatori P38316.

    Family and domain databases

    InterProi IPR007242. Atg12.
    IPR029071. Ubiquitin-rel_dom.
    [Graphical view ]
    PANTHERi PTHR13385. PTHR13385. 1 hit.
    Pfami PF04110. APG12. 1 hit.
    [Graphical view ]
    SUPFAMi SSF54236. SSF54236. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, PHOSPHORYLATION, CONJUGATION TO ATG5, SUBCELLULAR LOCATION, MUTAGENESIS OF GLY-186.
      Strain: ATCC 26109 / X2180.
    2. "Complete DNA sequence of yeast chromosome II."
      Feldmann H., Aigle M., Aljinovic G., Andre B., Baclet M.C., Barthe C., Baur A., Becam A.-M., Biteau N., Boles E., Brandt T., Brendel M., Brueckner M., Bussereau F., Christiansen C., Contreras R., Crouzet M., Cziepluch C.
      , Demolis N., Delaveau T., Doignon F., Domdey H., Duesterhus S., Dubois E., Dujon B., El Bakkoury M., Entian K.-D., Feuermann M., Fiers W., Fobo G.M., Fritz C., Gassenhuber J., Glansdorff N., Goffeau A., Grivell L.A., de Haan M., Hein C., Herbert C.J., Hollenberg C.P., Holmstroem K., Jacq C., Jacquet M., Jauniaux J.-C., Jonniaux J.-L., Kallesoee T., Kiesau P., Kirchrath L., Koetter P., Korol S., Liebl S., Logghe M., Lohan A.J.E., Louis E.J., Li Z.Y., Maat M.J., Mallet L., Mannhaupt G., Messenguy F., Miosga T., Molemans F., Mueller S., Nasr F., Obermaier B., Perea J., Pierard A., Piravandi E., Pohl F.M., Pohl T.M., Potier S., Proft M., Purnelle B., Ramezani Rad M., Rieger M., Rose M., Schaaff-Gerstenschlaeger I., Scherens B., Schwarzlose C., Skala J., Slonimski P.P., Smits P.H.M., Souciet J.-L., Steensma H.Y., Stucka R., Urrestarazu L.A., van der Aart Q.J.M., Van Dyck L., Vassarotti A., Vetter I., Vierendeels F., Vissers S., Wagner G., de Wergifosse P., Wolfe K.H., Zagulski M., Zimmermann F.K., Mewes H.-W., Kleine K.
      EMBO J. 13:5795-5809(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: ATCC 204508 / S288c.
    3. Cited for: GENOME REANNOTATION.
      Strain: ATCC 204508 / S288c.
    4. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: ATCC 204508 / S288c.
    5. "Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae."
      Tsukada M., Ohsumi Y.
      FEBS Lett. 333:169-174(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    6. "Apg10p, a novel protein-conjugating enzyme essential for autophagy in yeast."
      Shintani T., Mizushima N., Ogawa Y., Matsuura A., Noda T., Ohsumi Y.
      EMBO J. 18:5234-5241(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ATG10.
    7. "Apg7p/Cvt2p: a novel protein-activating enzyme essential for autophagy."
      Tanida I., Mizushima N., Kiyooka M., Ohsumi M., Ueno T., Ohsumi Y., Kominami E.
      Mol. Biol. Cell 10:1367-1379(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ATG7.
    8. "Apg5p functions in the sequestration step in the cytoplasm-to-vacuole targeting and macroautophagy pathways."
      George M.D., Baba M., Scott S.V., Mizushima N., Garrison B.S., Ohsumi Y., Klionsky D.J.
      Mol. Biol. Cell 11:969-982(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ATG5, SUBCELLULAR LOCATION.
    9. "The pre-autophagosomal structure organized by concerted functions of APG genes is essential for autophagosome formation."
      Suzuki K., Kirisako T., Kamada Y., Mizushima N., Noda T., Ohsumi Y.
      EMBO J. 20:5971-5981(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    10. "The C-terminal region of an Apg7p/Cvt2p is required for homodimerization and is essential for its E1 activity and E1-E2 complex formation."
      Komatsu M., Tanida I., Ueno T., Ohsumi M., Ohsumi Y., Kominami E.
      J. Biol. Chem. 276:9846-9854(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ATG7.
    11. "Membrane recruitment of Aut7p in the autophagy and cytoplasm to vacuole targeting pathways requires Aut1p, Aut2p, and the autophagy conjugation complex."
      Kim J., Huang W.-P., Klionsky D.J.
      J. Cell Biol. 152:51-64(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    12. "Formation of the approximately 350-kDa Apg12-Apg5.Apg16 multimeric complex, mediated by Apg16 oligomerization, is essential for autophagy in yeast."
      Kuma A., Mizushima N., Ishihara N., Ohsumi Y.
      J. Biol. Chem. 277:18619-18625(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION IN A COMPLEX WITH ATG5 AND ATG16.
    13. Cited for: NOMENCLATURE.
    14. "The carboxyl terminal 17 amino acids within Apg7 are essential for Apg8 lipidation, but not for Apg12 conjugation."
      Yamazaki-Sato H., Tanida I., Ueno T., Kominami E.
      FEBS Lett. 551:71-77(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: CONJUGATION TO ATG5.
    15. "Structure-function relationship of Atg12, a ubiquitin-like modifier essential for autophagy."
      Hanada T., Ohsumi Y.
      Autophagy 1:110-118(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CONJUGATION TO ATG5, MUTAGENESIS OF ILE-106; PHE-108; TYR-149 AND PHE-154.
    16. Cited for: FUNCTION.
    17. "The role of autophagy in mitochondria maintenance: characterization of mitochondrial functions in autophagy-deficient S. cerevisiae strains."
      Zhang Y., Qi H., Taylor R., Xu W., Liu L.F., Jin S.
      Autophagy 3:337-346(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    18. "Hierarchy of Atg proteins in pre-autophagosomal structure organization."
      Suzuki K., Kubota Y., Sekito T., Ohsumi Y.
      Genes Cells 12:209-218(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION.
    19. "The Atg12-Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy."
      Hanada T., Noda N.N., Satomi Y., Ichimura Y., Fujioka Y., Takao T., Inagaki F., Ohsumi Y.
      J. Biol. Chem. 282:37298-37302(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION OF THE ATG12-ATG5 CONJUGATE, INTERACTION WITH ATG3.
    20. "New insights into autophagy using a multiple knockout strain."
      Cao Y., Klionsky D.J.
      Autophagy 4:1073-1075(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    21. "In vivo reconstitution of autophagy in Saccharomyces cerevisiae."
      Cao Y., Cheong H., Song H., Klionsky D.J.
      J. Cell Biol. 182:703-713(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: CONJUGATION TO ATG5, FUNCTION OF THE ATG12-ATG5 CONJUGATE.
    22. "Crystallization of the Atg12-Atg5 conjugate bound to Atg16 by the free-interface diffusion method."
      Noda N.N., Fujioka Y., Ohsumi Y., Inagaki F.
      J. Synchrotron Radiat. 15:266-268(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: CRYSTALLIZATION OF THE ATG12-ATG5 CONJUGATE BOUND TO ATG16.
    23. "Piecemeal microautophagy of the nucleus requires the core macroautophagy genes."
      Krick R., Muehe Y., Prick T., Bremer S., Schlotterhose P., Eskelinen E.L., Millen J., Goldfarb D.S., Thumm M.
      Mol. Biol. Cell 19:4492-4505(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    24. "The conserved oligomeric Golgi complex is involved in double-membrane vesicle formation during autophagy."
      Yen W.L., Shintani T., Nair U., Cao Y., Richardson B.C., Li Z., Hughson F.M., Baba M., Klionsky D.J.
      J. Cell Biol. 188:101-114(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH COG2.
    25. "Sphingolipid synthesis is involved in autophagy in Saccharomyces cerevisiae."
      Yamagata M., Obara K., Kihara A.
      Biochem. Biophys. Res. Commun. 410:786-791(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: CONJUGATION TO ATG5.
    26. "Mechanism and functions of membrane binding by the Atg5-Atg12/Atg16 complex during autophagosome formation."
      Romanov J., Walczak M., Ibiricu I., Schuchner S., Ogris E., Kraft C., Martens S.
      EMBO J. 31:4304-4317(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, FUNCTION OF THE ATG5-ATG12/ATG16 COMPLEX.
    27. "A late form of nucleophagy in Saccharomyces cerevisiae."
      Mijaljica D., Prescott M., Devenish R.J.
      PLoS ONE 7:E40013-E40013(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    28. "Fine mapping of autophagy-related proteins during autophagosome formation in Saccharomyces cerevisiae."
      Suzuki K., Akioka M., Kondo-Kakuta C., Yamamoto H., Ohsumi Y.
      J. Cell Sci. 126:2534-2544(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    29. "Structure of the Atg12-Atg5 conjugate reveals a platform for stimulating Atg8-PE conjugation."
      Noda N.N., Fujioka Y., Hanada T., Ohsumi Y., Inagaki F.
      EMBO Rep. 14:206-211(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 100-186 IN CONJUGATION WITH ATG5.

    Entry informationi

    Entry nameiATG12_YEAST
    AccessioniPrimary (citable) accession number: P38316
    Secondary accession number(s): D6VQL3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1994
    Last sequence update: October 1, 1994
    Last modified: October 1, 2014
    This is version 122 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programFungal Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Small amount of ATG5-ATG12 conjugate is enough to perform normal autophagy.

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families
    3. Yeast
      Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
    4. Yeast chromosome II
      Yeast (Saccharomyces cerevisiae) chromosome II: entries and gene names

    External Data

    Dasty 3