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Protein

Ubiquitin-like protein ATG12

Gene

ATG12

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.5 Publications
(Microbial infection) May act as a proviral factor. In association with ATG5, negatively regulates the innate antiviral immune response by impairing the type I IFN production pathway upon vesicular stomatitis virus (VSV) infection (PubMed:17709747). Required for the translation of incoming hepatitis C virus (HCV) RNA and, thereby, for the initiation of HCV replication, but not required once infection is established (PubMed:19666601).2 Publications

Miscellaneous

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

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processAutophagy, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-1632852 Macroautophagy
R-HSA-5205685 Pink/Parkin Mediated Mitophagy
R-HSA-8934903 Receptor Mediated Mitophagy
R-HSA-936440 Negative regulators of DDX58/IFIH1 signaling
SIGNORiO94817

Protein family/group databases

TCDBi9.A.15.2.1 the autophagy-related phagophore-formation transporter (apt) family

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
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000145782.12
HGNCiHGNC:588 ATG12
MIMi609608 gene
neXtProtiNX_O94817

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi54K → D: Impairs E3 activity of the ATG12-ATG5 conjugate. 1 Publication1
Mutagenesisi62V → R: Impairs E3 activity of the ATG12-ATG5 conjugate. 1 Publication1
Mutagenesisi63G → D: Impairs E3 activity of the ATG12-ATG5 conjugate. 1 Publication1
Mutagenesisi72K → D: Impairs E3 activity of the ATG12-ATG5 conjugate. 1 Publication1
Mutagenesisi73W → A: Impairs E3 activity of the ATG12-ATG5 conjugate. 1 Publication1
Mutagenesisi108F → A, D or R: Impairs ATG12 stability. 1 Publication1
Mutagenesisi113D → V: Impairs E3 activity of the ATG12-ATG5 conjugate. 1 Publication1
Mutagenesisi122C → W: Impairs E3 activity of the ATG12-ATG5 conjugate. 1 Publication1
Mutagenesisi123F → D: Impairs ATG12 stability. 1 Publication1
Mutagenesisi138A → R: Impairs E3 activity of the ATG12-ATG5 conjugate. 1 Publication1
Mutagenesisi139W → F or Y: Impairs E3 activity of the ATG12-ATG5 conjugate. 1 Publication1

Organism-specific databases

DisGeNETi9140
OpenTargetsiENSG00000145782
PharmGKBiPA24879

Polymorphism and mutation databases

BioMutaiATG12

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002124711 – 140Ubiquitin-like protein ATG12Add BLAST140

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki140Glycyl 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

EPDiO94817
MaxQBiO94817
PaxDbiO94817
PeptideAtlasiO94817
PRIDEiO94817
ProteomicsDBi50457
50458 [O94817-4]

PTM databases

iPTMnetiO94817
PhosphoSitePlusiO94817
SwissPalmiO94817

Expressioni

Tissue specificityi

Ubiquitous.1 Publication

Inductioni

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

Gene expression databases

BgeeiENSG00000145782 Expressed in 242 organ(s), highest expression level in corpus callosum
CleanExiHS_ATG12
ExpressionAtlasiO94817 baseline and differential
GenevisibleiO94817 HS

Organism-specific databases

HPAiCAB013272

Interactioni

Subunit structurei

Forms a conjugate with ATG5 (PubMed:11096062, PubMed:12207896, PubMed:11825910, PubMed:17709747, PubMed:26812546, PubMed:23202584). The ATG12-ATG5 conjugate forms a complex with several units of ATG16L (PubMed:23202584). Interacts with DHX58/RIG-1, IFIH1/MDA5 and MAVS/IPS-1 in monomeric form as well as in ATG12-ATG5 conjugate. The interaction with MAVS is further enhanced upon vesicular stomatitis virus (VSV) infection (PubMed:17709747). Interacts with ATG3 and ATG7 (PubMed:11096062, PubMed:12207896, PubMed:11825910, PubMed:23202584). Interacts with ATG10 (By similarity). Interacts with TECPR1 (PubMed:22342342).By similarity7 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi114587, 32 interactors
ComplexPortaliCPX-200 ATG12-ATG5-ATG16L1 complex
CPX-354 ATG12-ATG5-ATG16L2 complex
CPX-356 ATG5-ATG12 complex
CPX-358 ATG5-ATG12-TECPR1 complex
DIPiDIP-46466N
IntActiO94817, 29 interactors
STRINGi9606.ENSP00000425107

Structurei

Secondary structure

1140
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO94817
SMRiO94817
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

eggNOGiKOG3439 Eukaryota
ENOG4111ND7 LUCA
GeneTreeiENSGT00390000016654
HOVERGENiHBG080875
InParanoidiO94817
KOiK08336
OMAiIHYCKSQ
OrthoDBiEOG091G0XR8
PhylomeDBiO94817
TreeFamiTF325131

Family and domain databases

CDDicd01612 APG12_C, 1 hit
InterProiView protein in InterPro
IPR007242 Atg12
IPR029071 Ubiquitin-like_domsf
PANTHERiPTHR13385 PTHR13385, 1 hit
PfamiView protein in Pfam
PF04110 APG12, 1 hit
SUPFAMiSSF54236 SSF54236, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.iShow all

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

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RB14D6RB14_HUMAN
Ubiquitin-like protein ATG12
ATG12
56Annotation score:
H0Y9W4H0Y9W4_HUMAN
Ubiquitin-like protein ATG12
ATG12
59Annotation score:
H0YA29H0YA29_HUMAN
Ubiquitin-like protein ATG12
ATG12
66Annotation score:
H7BYD7H7BYD7_HUMAN
Ubiquitin-like protein ATG12
ATG12
75Annotation score:

Sequence cautioni

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

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01810456 – 74DILLK…TKKWA → YLCESVLCSFPRPRSWNSL in isoform 2. 1 PublicationAdd BLAST19
Alternative sequenceiVSP_01810575 – 140Missing in isoform 2. 1 PublicationAdd BLAST66

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.4 human [O94817-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiATG12_HUMAN
AccessioniPrimary (citable) accession number: O94817
Secondary accession number(s): Q6PJV2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: May 1, 1999
Last modified: September 12, 2018
This is version 158 of the entry and version 1 of the sequence. See 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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