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O94817 (ATG12_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ubiquitin-like protein ATG12
Alternative name(s):
Autophagy-related protein 12
Short name=APG12-like
Gene names
Name:ATG12
Synonyms:APG12, APG12L
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length140 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Ubiquitin-like protein involved in autophagy vesicles formation. 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 family proteins and their association to the vesicle membranes. The ATG12-ATG5 conjugate also regulates negatively the innate antiviral immune response by blocking the type I IFN production pathway through direct association with RARRES3 and MAVS. Plays also a role in translation or delivery of incoming viral RNA to the translation apparatus. Ref.5 Ref.9 Ref.11 Ref.12 Ref.14 Ref.16 Ref.19

Subunit structure

Forms a conjugate with ATG5. The ATG12-ATG5 conjugate forms a complex with several units of ATG16L. Interacts with ATG3, ATG7 and ATG10. ATG12-ATG5 also interacts with MAVS, MGA, RARRES3 and TECPR1. Ref.4 Ref.5 Ref.6 Ref.9 Ref.18 Ref.19

Subcellular location

Cytoplasm By similarity. Preautophagosomal structure membrane; Peripheral membrane protein. Note: TECPR1 recruits the ATG12-ATG5 conjugate to the autolysosomal membrane. Ref.18

Tissue specificity

Ubiquitous. Ref.1

Induction

Expression is induced by mitochondrial DNA deletions, chloramphenicol and nicotinamide. Ref.8 Ref.13

Domain

Shares weak sequence similarity with ubiquitin family, but contains an 'ubiquitin superfold' and the C-terminal Gly is required for isopeptide linkage. Ref.10

Post-translational modification

Acetylated by EP300. Ref.15

Miscellaneous

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

Sequence similarities

Belongs to the ATG12 family.

Sequence caution

The sequence AAH12266.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O94817-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O94817-4)

The sequence of this isoform differs from the canonical sequence as follows:
     56-74: DILLKAVGDTPIMKTKKWA → YLCESVLCSFPRPRSWNSL
     75-140: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 140140Ubiquitin-like protein ATG12
PRO_0000212471

Amino acid modifications

Cross-link140Glycyl lysine isopeptide (Gly-Lys) (interchain with K-? in acceptor protein)

Natural variations

Alternative sequence56 – 7419DILLK…TKKWA → YLCESVLCSFPRPRSWNSL in isoform 2.
VSP_018104
Alternative sequence75 – 14066Missing in isoform 2.
VSP_018105

Experimental info

Mutagenesis541K → D: Impairs E3 activity of the ATG12-ATG5 conjugate. Ref.19
Mutagenesis621V → R: Impairs E3 activity of the ATG12-ATG5 conjugate. Ref.19
Mutagenesis631G → D: Impairs E3 activity of the ATG12-ATG5 conjugate. Ref.19
Mutagenesis721K → D: Impairs E3 activity of the ATG12-ATG5 conjugate. Ref.19
Mutagenesis731W → A: Impairs E3 activity of the ATG12-ATG5 conjugate. Ref.19
Mutagenesis1081F → A, D or R: Impairs ATG12 stability. Ref.19
Mutagenesis1131D → V: Impairs E3 activity of the ATG12-ATG5 conjugate. Ref.19
Mutagenesis1221C → W: Impairs E3 activity of the ATG12-ATG5 conjugate. Ref.19
Mutagenesis1231F → D: Impairs ATG12 stability. Ref.19
Mutagenesis1381A → R: Impairs E3 activity of the ATG12-ATG5 conjugate. Ref.19
Mutagenesis1391W → F or Y: Impairs E3 activity of the ATG12-ATG5 conjugate. Ref.19

Secondary structure

.................. 140
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: 109258521C2D194F

FASTA14015,113
        10         20         30         40         50         60 
MAEEPQSVLQ LPTSIAAGGE GLTDVSPETT TPEPPSSAAV SPGTEEPAGD TKKKIDILLK 

        70         80         90        100        110        120 
AVGDTPIMKT KKWAVERTRT IQGLIDFIKK FLKLVASEQL FIYVNQSFAP SPDQEVGTLY 

       130        140 
ECFGSDGKLV LHYCKSQAWG 

« Hide

Isoform 2 [UniParc].

Checksum: 21346AAD91E00D16
Show »

FASTA747,746

References

« Hide 'large scale' references
[1]"A new protein conjugation system in human. The counterpart of the yeast Apg12p conjugation system essential for autophagy."
Mizushima N., Sugita H., Yoshimori T., Ohsumi Y.
J. Biol. Chem. 273:33889-33892(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CONJUGATION TO ATG5, TISSUE SPECIFICITY.
[2]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Brain and Ovary.
[4]"The human homolog of Saccharomyces cerevisiae Apg7p is a Protein-activating enzyme for multiple substrates including human Apg12p, GATE-16, GABARAP, and MAP-LC3."
Tanida I., Tanida-Miyake E., Ueno T., Kominami E.
J. Biol. Chem. 276:1701-1706(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ATG7, CONJUGATION TO ATG5.
[5]"Mammalian Apg12p, but not the Apg12p.Apg5p conjugate, facilitates LC3 processing."
Tanida I., Nishitani T., Nemoto T., Ueno T., Kominami E.
Biochem. Biophys. Res. Commun. 296:1164-1170(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ATG3, CONJUGATION TO ATG5, FUNCTION.
[6]"Human Apg3p/Aut1p homologue is an authentic E2 enzyme for multiple substrates, GATE-16, GABARAP, and MAP-LC3, and facilitates the conjugation of hApg12p to hApg5p."
Tanida I., Tanida-Miyake E., Komatsu M., Ueno T., Kominami E.
J. Biol. Chem. 277:13739-13744(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ATG3, CONJUGATION TO ATG5.
[7]"Stimulation of ATG12-ATG5 conjugation by ribonucleic acid."
Shao Y., Gao Z., Feldman T., Jiang X.
Autophagy 3:10-16(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: CONJUGATION TO ATG5.
[8]"Mitochondrial DNA deletions and chloramphenicol treatment stimulate the autophagic transcript ATG12."
Prigione A., Cortopassi G.
Autophagy 3:377-380(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[9]"The Atg5-Atg12 conjugate associates with innate antiviral immune responses."
Jounai N., Takeshita F., Kobiyama K., Sawano A., Miyawaki A., Xin K.Q., Ishii K.J., Kawai T., Akira S., Suzuki K., Okuda K.
Proc. Natl. Acad. Sci. U.S.A. 104:14050-14055(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN INNATE IMMUNE RESPONSE, INTERACTION WITH MAVS; MGA AND RARRES3.
[10]"The Atg8 and Atg12 ubiquitin-like conjugation systems in macroautophagy. 'Protein modifications: beyond the usual suspects' review series."
Geng J., Klionsky D.J.
EMBO Rep. 9:859-864(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN.
[11]"Ubiquitin signals autophagic degradation of cytosolic proteins and peroxisomes."
Kim P.K., Hailey D.W., Mullen R.T., Lippincott-Schwartz J.
Proc. Natl. Acad. Sci. U.S.A. 105:20567-20574(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"Induction of autophagy promotes fusion of multivesicular bodies with autophagic vacuoles in k562 cells."
Fader C.M., Sanchez D., Furlan M., Colombo M.I.
Traffic 9:230-250(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[13]"Nicotinamide enhances mitochondria quality through autophagy activation in human cells."
Kang H.T., Hwang E.S.
Aging Cell 8:426-438(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[14]"Effect of Helicobacter pylori's vacuolating cytotoxin on the autophagy pathway in gastric epithelial cells."
Terebiznik M.R., Raju D., Vazquez C.L., Torbricki K., Kulkarni R., Blanke S.R., Yoshimori T., Colombo M.I., Jones N.L.
Autophagy 5:370-379(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[15]"Regulation of autophagy by the p300 acetyltransferase."
Lee I.H., Finkel T.
J. Biol. Chem. 284:6322-6328(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION.
[16]"The autophagy machinery is required to initiate hepatitis C virus replication."
Dreux M., Gastaminza P., Wieland S.F., Chisari F.V.
Proc. Natl. Acad. Sci. U.S.A. 106:14046-14051(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN VIRAL REPLICATION.
[17]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]"A mammalian autophagosome maturation mechanism mediated by TECPR1 and the Atg12-Atg5 conjugate."
Chen D., Fan W., Lu Y., Ding X., Chen S., Zhong Q.
Mol. Cell 45:629-641(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TECPR1, SUBCELLULAR LOCATION.
[19]"Structure of the human ATG12-ATG5 conjugate required for LC3 lipidation in autophagy."
Otomo C., Metlagel Z., Takaesu G., Otomo T.
Nat. Struct. Mol. Biol. 20:59-66(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 52-140 IN COMPLEX WITH ATG5 AND ATG16L, INTERACTION WITH ATG3, FUNCTION, MUTAGENESIS OF LYS-54; VAL-62; GLY-63; LYS-72; TRP-73; PHE-108; ASP-113; CYS-122; PHE-123; ALA-138 AND TRP-139.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB017507 mRNA. Translation: BAA36493.1.
AC026449 Genomic DNA. No translation available.
BC011033 mRNA. Translation: AAH11033.1.
BC012266 mRNA. Translation: AAH12266.2. Different initiation.
CCDSCCDS4122.2. [O94817-1]
CCDS64222.1. [O94817-4]
RefSeqNP_001264712.1. NM_001277783.1. [O94817-4]
NP_004698.3. NM_004707.3. [O94817-1]
UniGeneHs.264482.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4GDKX-ray2.70A/D52-140[»]
4GDLX-ray2.88A52-140[»]
4NAWX-ray2.20A/E/I/M52-140[»]
ProteinModelPortalO94817.
SMRO94817. Positions 53-140.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114587. 27 interactions.
DIPDIP-46466N.
IntActO94817. 17 interactions.
MINTMINT-1434758.
STRING9606.ENSP00000274459.

PTM databases

PhosphoSiteO94817.

Proteomic databases

MaxQBO94817.
PaxDbO94817.
PRIDEO94817.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000500945; ENSP00000425164; ENSG00000145782. [O94817-4]
ENST00000509910; ENSP00000425107; ENSG00000145782. [O94817-1]
GeneID9140.
KEGGhsa:9140.
UCSCuc003krh.3. human. [O94817-1]
uc003kri.4. human. [O94817-4]

Organism-specific databases

CTD9140.
GeneCardsGC05M115195.
HGNCHGNC:588. ATG12.
HPACAB013272.
MIM609608. gene.
neXtProtNX_O94817.
PharmGKBPA24879.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG236266.
HOVERGENHBG080875.
InParanoidO94817.
KOK08336.
OrthoDBEOG7XPZ7X.
PhylomeDBO94817.
TreeFamTF325131.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressO94817.
BgeeO94817.
CleanExHS_ATG12.
GenevestigatorO94817.

Family and domain databases

InterProIPR007242. Atg12.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PANTHERPTHR13385. PTHR13385. 1 hit.
PfamPF04110. APG12. 1 hit.
[Graphical view]
SUPFAMSSF54236. SSF54236. 1 hit.
ProtoNetSearch...

Other

ChiTaRSATG12. human.
GeneWikiATG12.
GenomeRNAi9140.
NextBio34279.
PROO94817.
SOURCESearch...

Entry information

Entry nameATG12_HUMAN
AccessionPrimary (citable) accession number: O94817
Secondary accession number(s): Q6PJV2
Entry history
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: May 1, 1999
Last modified: July 9, 2014
This is version 117 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM