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O94817

- ATG12_HUMAN

UniProt

O94817 - ATG12_HUMAN

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Protein

Ubiquitin-like protein ATG12

Gene

ATG12

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.7 Publications

GO - Molecular functioni

  1. Atg8 ligase activity Source: RefGenome

GO - Biological processi

  1. autophagic vacuole assembly Source: UniProtKB
  2. cellular response to nitrogen starvation Source: RefGenome
  3. C-terminal protein lipidation Source: RefGenome
  4. innate immune response Source: Reactome
  5. mitochondrion degradation Source: RefGenome
  6. negative regulation of type I interferon production Source: Reactome
  7. nucleophagy Source: RefGenome
Complete GO annotation...

Keywords - Biological processi

Autophagy, Immunity, Innate immunity, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiREACT_25271. Negative regulators of RIG-I/MDA5 signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin-like protein ATG12
Alternative name(s):
Autophagy-related protein 12
Short name:
APG12-like
Gene namesi
Name:ATG12
Synonyms:APG12, APG12L
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 5

Organism-specific databases

HGNCiHGNC:588. ATG12.

Subcellular locationi

Cytoplasm By similarity. Preautophagosomal structure membrane 1 Publication; Peripheral membrane protein 1 Publication
Note: TECPR1 recruits the ATG12-ATG5 conjugate to the autolysosomal membrane.

GO - Cellular componenti

  1. Atg12-Atg5-Atg16 complex Source: RefGenome
  2. pre-autophagosomal structure membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi54 – 541K → D: Impairs E3 activity of the ATG12-ATG5 conjugate. 1 Publication
Mutagenesisi62 – 621V → R: Impairs E3 activity of the ATG12-ATG5 conjugate. 1 Publication
Mutagenesisi63 – 631G → D: Impairs E3 activity of the ATG12-ATG5 conjugate. 1 Publication
Mutagenesisi72 – 721K → D: Impairs E3 activity of the ATG12-ATG5 conjugate. 1 Publication
Mutagenesisi73 – 731W → A: Impairs E3 activity of the ATG12-ATG5 conjugate. 1 Publication
Mutagenesisi108 – 1081F → A, D or R: Impairs ATG12 stability. 1 Publication
Mutagenesisi113 – 1131D → V: Impairs E3 activity of the ATG12-ATG5 conjugate. 1 Publication
Mutagenesisi122 – 1221C → W: Impairs E3 activity of the ATG12-ATG5 conjugate. 1 Publication
Mutagenesisi123 – 1231F → D: Impairs ATG12 stability. 1 Publication
Mutagenesisi138 – 1381A → R: Impairs E3 activity of the ATG12-ATG5 conjugate. 1 Publication
Mutagenesisi139 – 1391W → F or Y: Impairs E3 activity of the ATG12-ATG5 conjugate. 1 Publication

Organism-specific databases

PharmGKBiPA24879.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 140140Ubiquitin-like protein ATG12PRO_0000212471Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki140 – 140Glycyl lysine isopeptide (Gly-Lys) (interchain with K-? in acceptor protein)

Post-translational modificationi

Acetylated by EP300.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond

Proteomic databases

MaxQBiO94817.
PaxDbiO94817.
PRIDEiO94817.

PTM databases

PhosphoSiteiO94817.

Expressioni

Tissue specificityi

Ubiquitous.1 Publication

Inductioni

Expression is induced by mitochondrial DNA deletions, chloramphenicol and nicotinamide.2 Publications

Gene expression databases

BgeeiO94817.
CleanExiHS_ATG12.
ExpressionAtlasiO94817. baseline and differential.
GenevestigatoriO94817.

Organism-specific databases

HPAiCAB013272.

Interactioni

Subunit structurei

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 TECPR1.6 Publications

Protein-protein interaction databases

BioGridi114587. 28 interactions.
DIPiDIP-46466N.
IntActiO94817. 17 interactions.
MINTiMINT-1434758.
STRINGi9606.ENSP00000274459.

Structurei

Secondary structure

1
140
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi55 – 617
Beta strandi63 – 653
Beta strandi72 – 754
Helixi81 – 9111
Beta strandi96 – 983
Beta strandi101 – 1044
Turni105 – 1073
Helixi116 – 1238
Beta strandi128 – 1369

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4GDKX-ray2.70A/D52-140[»]
4GDLX-ray2.88A52-140[»]
4NAWX-ray2.20A/E/I/M52-140[»]
ProteinModelPortaliO94817.
SMRiO94817. Positions 53-140.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

Shares weak sequence similarity with ubiquitin family, but contains an 'ubiquitin superfold' and the C-terminal Gly is required for isopeptide linkage.1 Publication

Sequence similaritiesi

Belongs to the ATG12 family.Curated

Phylogenomic databases

eggNOGiNOG236266.
GeneTreeiENSGT00390000016654.
HOVERGENiHBG080875.
InParanoidiO94817.
KOiK08336.
OrthoDBiEOG7XPZ7X.
PhylomeDBiO94817.
TreeFamiTF325131.

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.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: O94817-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MAEEPQSVLQ LPTSIAAGGE GLTDVSPETT TPEPPSSAAV SPGTEEPAGD
60 70 80 90 100
TKKKIDILLK AVGDTPIMKT KKWAVERTRT IQGLIDFIKK FLKLVASEQL
110 120 130 140
FIYVNQSFAP SPDQEVGTLY ECFGSDGKLV LHYCKSQAWG
Length:140
Mass (Da):15,113
Last modified:May 1, 1999 - v1
Checksum:i109258521C2D194F
GO
Isoform 2 (identifier: O94817-4) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     56-74: DILLKAVGDTPIMKTKKWA → YLCESVLCSFPRPRSWNSL
     75-140: Missing.

Note: No experimental confirmation available.

Show »
Length:74
Mass (Da):7,746
Checksum:i21346AAD91E00D16
GO

Sequence cautioni

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

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei56 – 7419DILLK…TKKWA → YLCESVLCSFPRPRSWNSL in isoform 2. 1 PublicationVSP_018104Add
BLAST
Alternative sequencei75 – 14066Missing in isoform 2. 1 PublicationVSP_018105Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB017507 mRNA. Translation: BAA36493.1.
AC026449 Genomic DNA. No translation available.
BC011033 mRNA. Translation: AAH11033.1.
BC012266 mRNA. Translation: AAH12266.2. Different initiation.
CCDSiCCDS4122.2. [O94817-1]
CCDS64222.1. [O94817-4]
RefSeqiNP_001264712.1. NM_001277783.1. [O94817-4]
NP_004698.3. NM_004707.3. [O94817-1]
UniGeneiHs.264482.

Genome annotation databases

EnsembliENST00000500945; ENSP00000425164; ENSG00000145782. [O94817-4]
ENST00000509910; ENSP00000425107; ENSG00000145782. [O94817-1]
GeneIDi9140.
KEGGihsa:9140.
UCSCiuc003krh.3. human. [O94817-1]
uc003kri.4. human. [O94817-4]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB017507 mRNA. Translation: BAA36493.1 .
AC026449 Genomic DNA. No translation available.
BC011033 mRNA. Translation: AAH11033.1 .
BC012266 mRNA. Translation: AAH12266.2 . Different initiation.
CCDSi CCDS4122.2. [O94817-1 ]
CCDS64222.1. [O94817-4 ]
RefSeqi NP_001264712.1. NM_001277783.1. [O94817-4 ]
NP_004698.3. NM_004707.3. [O94817-1 ]
UniGenei Hs.264482.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
4GDK X-ray 2.70 A/D 52-140 [» ]
4GDL X-ray 2.88 A 52-140 [» ]
4NAW X-ray 2.20 A/E/I/M 52-140 [» ]
ProteinModelPortali O94817.
SMRi O94817. Positions 53-140.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 114587. 28 interactions.
DIPi DIP-46466N.
IntActi O94817. 17 interactions.
MINTi MINT-1434758.
STRINGi 9606.ENSP00000274459.

PTM databases

PhosphoSitei O94817.

Proteomic databases

MaxQBi O94817.
PaxDbi O94817.
PRIDEi O94817.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000500945 ; ENSP00000425164 ; ENSG00000145782 . [O94817-4 ]
ENST00000509910 ; ENSP00000425107 ; ENSG00000145782 . [O94817-1 ]
GeneIDi 9140.
KEGGi hsa:9140.
UCSCi uc003krh.3. human. [O94817-1 ]
uc003kri.4. human. [O94817-4 ]

Organism-specific databases

CTDi 9140.
GeneCardsi GC05M115163.
HGNCi HGNC:588. ATG12.
HPAi CAB013272.
MIMi 609608. gene.
neXtProti NX_O94817.
PharmGKBi PA24879.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG236266.
GeneTreei ENSGT00390000016654.
HOVERGENi HBG080875.
InParanoidi O94817.
KOi K08336.
OrthoDBi EOG7XPZ7X.
PhylomeDBi O94817.
TreeFami TF325131.

Enzyme and pathway databases

Reactomei REACT_25271. Negative regulators of RIG-I/MDA5 signaling.

Miscellaneous databases

ChiTaRSi ATG12. human.
GeneWikii ATG12.
GenomeRNAii 9140.
NextBioi 34279.
PROi O94817.
SOURCEi Search...

Gene expression databases

Bgeei O94817.
CleanExi HS_ATG12.
ExpressionAtlasi O94817. baseline and differential.
Genevestigatori O94817.

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. "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.
    , 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. 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. 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.

Entry informationi

Entry nameiATG12_HUMAN
AccessioniPrimary (citable) accession number: O94817
Secondary accession number(s): Q6PJV2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: May 1, 1999
Last modified: October 29, 2014
This is version 120 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

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. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3