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Protein

Ubiquitin-like-conjugating enzyme ATG3

Gene

Atg3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

E2 conjugating enzyme required for the cytoplasm to vacuole transport (Cvt), autophagy, and mitochondrial homeostasis. Responsible for the E2-like covalent binding of phosphatidylethanolamine to the C-terminal Gly of ATG8-like proteins (GABARAP, GABARAPL1, GABARAPL2 or MAP1LC3A). The ATG12-ATG5 conjugate plays a role of an E3 and promotes the transfer of ATG8-like proteins from ATG3 to phosphatidylethanolamine (PE). This step is required for the membrane association of ATG8-like proteins. The formation of the ATG8-phosphatidylethanolamine conjugates is essential for autophagy and for the cytoplasm to vacuole transport (Cvt). Preferred substrate is MAP1LC3A. Also acts as an autocatalytic E2-like enzyme, catalyzing the conjugation of ATG12 to itself, ATG12 conjugation to ATG3 playing a role in mitochondrial homeostasis but not in autophagy. ATG7 (E1-like enzyme) facilitates this reaction by forming an E1-E2 complex with ATG3. ATG12-ATG3 conjugate is also formed upon viccina virus infection, leading to the disruption the cellular autophagy which is not necessary for vaccinia survival and proliferation. Promotes primary ciliogenesis by removing OFD1 from centriolar satellites via the autophagic pathway.4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei264Glycyl thioester intermediateCurated1

GO - Molecular functioni

  • Atg12 transferase activity Source: UniProtKB
  • Atg8 ligase activity Source: UniProtKB
  • enzyme binding Source: MGI
  • ligase activity Source: UniProtKB-KW
  • ubiquitin-like protein transferase activity Source: MGI

GO - Biological processi

  • autophagosome assembly Source: UniProtKB
  • cellular protein modification process Source: MGI
  • macroautophagy Source: MGI
  • mitochondrial fragmentation involved in apoptotic process Source: UniProtKB
  • mitophagy Source: GO_Central
  • negative regulation of phagocytosis Source: MGI
  • nucleophagy Source: GO_Central
  • protein transport Source: UniProtKB-KW
  • protein ubiquitination Source: MGI
  • regulation of cilium assembly Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Autophagy, Protein transport, Transport, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-MMU-1632852. Macroautophagy.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin-like-conjugating enzyme ATG3 (EC:6.3.2.-)
Alternative name(s):
Autophagy-related protein 3
Short name:
APG3-like
Gene namesi
Name:Atg3
Synonyms:Apg3l
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:1915091. Atg3.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi71K → R: Does not affect ATG12 conjugation. 1 Publication1
Mutagenesisi83K → R: Does not affect ATG12 conjugation. 1 Publication1
Mutagenesisi243K → R: Abolishes ATG12 conjugation, leading to an expansion in mitochondrial mass and fragmented mitochondrial morphology. Does not affect PE-conjugation to ATG8-like proteins. 1 Publication1
Mutagenesisi264C → A: Abolishes E2-like activity. 1 Publication1
Mutagenesisi271K → R: Does not affect ATG12 conjugation. 1 Publication1
Mutagenesisi295K → R: Does not affect ATG12 conjugation. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002135701 – 314Ubiquitin-like-conjugating enzyme ATG3Add BLAST314

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Cross-linki243Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ATG12)

Post-translational modificationi

Conjugated to ATG12 at Lys-243. ATG12-conjugation plays a role in regulation of mitochondrial homeostasis and cell death, while it is not involved in PE-conjugation to ATG8-like proteins and autophagy.
Cleaved by CASP8 upon death ligand binding such as tumor necrosis factor-alpha. CASP8 cleavage blocks survival-related autophagy and favors apoptosis (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei169 – 170Cleavage; by CASP82

Keywords - PTMi

Acetylation, Isopeptide bond, Ubl conjugation

Proteomic databases

EPDiQ9CPX6.
MaxQBiQ9CPX6.
PaxDbiQ9CPX6.
PeptideAtlasiQ9CPX6.
PRIDEiQ9CPX6.

PTM databases

iPTMnetiQ9CPX6.
PhosphoSitePlusiQ9CPX6.
SwissPalmiQ9CPX6.

Expressioni

Gene expression databases

BgeeiENSMUSG00000022663.
CleanExiMM_ATG3.
GenevisibleiQ9CPX6. MM.

Interactioni

Subunit structurei

Interacts with ATG7 and ATG12. The complex composed of ATG3 and ATG7 plays a role in the conjugation of ATG12 to ATG5. Interacts with FNBP1L (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Atg12Q9CQY13EBI-2911810,EBI-2911788

GO - Molecular functioni

Protein-protein interaction databases

BioGridi212471. 4 interactors.
DIPiDIP-60109N.
IntActiQ9CPX6. 3 interactors.
MINTiMINT-4124733.
STRINGi10090.ENSMUSP00000023343.

Structurei

3D structure databases

ProteinModelPortaliQ9CPX6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the ATG3 family.Curated

Phylogenomic databases

eggNOGiKOG2981. Eukaryota.
ENOG410Y3BC. LUCA.
GeneTreeiENSGT00390000010308.
HOGENOMiHOG000234613.
HOVERGENiHBG080876.
InParanoidiQ9CPX6.
KOiK08343.
OMAiETKEEMH.
OrthoDBiEOG091G0H8F.
PhylomeDBiQ9CPX6.
TreeFamiTF105903.

Family and domain databases

InterProiIPR007135. Autophagy-rel_prot_3.
IPR019461. Autophagy-rel_prot_3_C.
IPR007134. Autophagy-rel_prot_3_N.
[Graphical view]
PfamiPF03987. Autophagy_act_C. 1 hit.
PF10381. Autophagy_C. 1 hit.
PF03986. Autophagy_N. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9CPX6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQNVINTVKG KALEVAEYLT PVLKESKFKE TGVITPEEFV AAGDHLVHHC
60 70 80 90 100
PTWQWATGEE LKVKAYLPTD KQFLVTKNVP CYKRCKQMEY SDELEAIIEE
110 120 130 140 150
DDGDGGWVDT YHNTGITGIT EAVKEITLES KDSIKLQDCS ALCDEEDEED
160 170 180 190 200
EGEAADMEEY EESGLLETDE ATLDTRKIVE ACKAKADAGG EDAILQTRTY
210 220 230 240 250
DLYITYDKYY QTPRLWLFGY DEQRQPLTVE HMYEDISQDH VKKTVTIENH
260 270 280 290 300
PHLPPPPMCS VHPCRHAEVM KKIIETVAEG GGELGVHMYL LIFLKFVQAV
310
IPTIEYDYTR HFTM
Length:314
Mass (Da):35,796
Last modified:June 1, 2001 - v1
Checksum:iEC5ECACD3247ED66
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB079386 mRNA. Translation: BAC57452.1.
AK005266 mRNA. Translation: BAB23918.1.
AK011409 mRNA. Translation: BAB27600.1.
AK078877 mRNA. Translation: BAC37437.1.
AK150914 mRNA. Translation: BAE29952.1.
AK159231 mRNA. Translation: BAE34917.1.
BC010809 mRNA. Translation: AAH10809.1.
CCDSiCCDS28194.1.
RefSeqiNP_080678.1. NM_026402.3.
UniGeneiMm.41775.

Genome annotation databases

EnsembliENSMUST00000023343; ENSMUSP00000023343; ENSMUSG00000022663.
GeneIDi67841.
KEGGimmu:67841.
UCSCiuc007zii.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB079386 mRNA. Translation: BAC57452.1.
AK005266 mRNA. Translation: BAB23918.1.
AK011409 mRNA. Translation: BAB27600.1.
AK078877 mRNA. Translation: BAC37437.1.
AK150914 mRNA. Translation: BAE29952.1.
AK159231 mRNA. Translation: BAE34917.1.
BC010809 mRNA. Translation: AAH10809.1.
CCDSiCCDS28194.1.
RefSeqiNP_080678.1. NM_026402.3.
UniGeneiMm.41775.

3D structure databases

ProteinModelPortaliQ9CPX6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi212471. 4 interactors.
DIPiDIP-60109N.
IntActiQ9CPX6. 3 interactors.
MINTiMINT-4124733.
STRINGi10090.ENSMUSP00000023343.

PTM databases

iPTMnetiQ9CPX6.
PhosphoSitePlusiQ9CPX6.
SwissPalmiQ9CPX6.

Proteomic databases

EPDiQ9CPX6.
MaxQBiQ9CPX6.
PaxDbiQ9CPX6.
PeptideAtlasiQ9CPX6.
PRIDEiQ9CPX6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000023343; ENSMUSP00000023343; ENSMUSG00000022663.
GeneIDi67841.
KEGGimmu:67841.
UCSCiuc007zii.1. mouse.

Organism-specific databases

CTDi64422.
MGIiMGI:1915091. Atg3.

Phylogenomic databases

eggNOGiKOG2981. Eukaryota.
ENOG410Y3BC. LUCA.
GeneTreeiENSGT00390000010308.
HOGENOMiHOG000234613.
HOVERGENiHBG080876.
InParanoidiQ9CPX6.
KOiK08343.
OMAiETKEEMH.
OrthoDBiEOG091G0H8F.
PhylomeDBiQ9CPX6.
TreeFamiTF105903.

Enzyme and pathway databases

ReactomeiR-MMU-1632852. Macroautophagy.

Miscellaneous databases

ChiTaRSiAtg3. mouse.
PROiQ9CPX6.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000022663.
CleanExiMM_ATG3.
GenevisibleiQ9CPX6. MM.

Family and domain databases

InterProiIPR007135. Autophagy-rel_prot_3.
IPR019461. Autophagy-rel_prot_3_C.
IPR007134. Autophagy-rel_prot_3_N.
[Graphical view]
PfamiPF03987. Autophagy_act_C. 1 hit.
PF10381. Autophagy_C. 1 hit.
PF03986. Autophagy_N. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiATG3_MOUSE
AccessioniPrimary (citable) accession number: Q9CPX6
Secondary accession number(s): Q3TXJ9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: June 1, 2001
Last modified: November 2, 2016
This is version 109 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.