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P38316

- ATG12_YEAST

UniProt

P38316 - ATG12_YEAST

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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

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 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
Complete GO annotation...

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. membrane Source: UniProtKB-KW
  3. pre-autophagosomal structure Source: SGD
Complete GO annotation...

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 – 1108Combined sources
Beta strandi121 – 1255Combined sources
Helixi130 – 14112Combined sources
Beta strandi147 – 1504Combined sources
Turni151 – 1533Combined sources
Helixi162 – 1698Combined sources
Beta strandi174 – 1807Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
InParanoidiP38316.
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

        10         20         30         40         50
MSRILESENE TESDESSIIS TNNGTAMERS RNNQELRSSP HTVQNRLELF
60 70 80 90 100
SRRLSQLGLA SDISVDQQVE DSSSGTYEQE ETIKTNAQTS KQKSHKDEKN
110 120 130 140 150
IQKIQIKFQP IGSIGQLKPS VCKISMSQSF AMVILFLKRR LKMDHVYCYI
160 170 180
NNSFAPSPQQ NIGELWMQFK TNDELIVSYC ASVAFG
Length:186
Mass (Da):21,106
Last modified:October 1, 1994 - v1
Checksum:i74B3C9FD3CEA9265
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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:
PDBei
RCSB PDBi
PDBji
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.
InParanoidi P38316.
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 124 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