ATG3

ATG3

Target · Autophagy E2 enzyme

ATG3 Autophagy related 3 · Ubiquitin-like-conjugating enzyme ATG3

ATG3 (autophagy related 3) is an E2 ubiquitin-like-conjugating enzyme that lipidates ATG8-like proteins during autophagosome formation. It is also known as APG3L, PC3-96, FLJ22125, MGC15201 and DKFZp564M1178. Browse Assay Genie's current range of ATG3 research reagents below, or read on for the biology behind the target.

Cytoplasmic enzymeE2 conjugating enzymeLipidates LC3/GABARAP
314 aa
Protein length
~36 kDa
Molecular weight
3q13.2
Gene locus
EC 2.3.2.-
Enzyme class
Target information

What is ATG3 (autophagy related 3)?

ATG3 is an E2 conjugating enzyme that catalyses the covalent conjugation of the C-terminal glycine of ATG8-like proteins (GABARAP, GABARAPL1, GABARAPL2 or MAP1LC3A) to the amino group of phosphatidylethanolamine (PE)-containing lipids in membranes. The resulting membrane-bound ATG8-like proteins are a key step in the development of autophagic isolation membranes during autophagosome formation. ATG3 cycles between binding to ATG7, which loads it with ATG8-like proteins, and binding to the E3 enzyme complex of ATG12, ATG5 and ATG16L1, which promotes the lipidation reaction.

ATG3 also acts as a membrane curvature sensor. It detects local membrane stress arising from lipid-packing defects, such as those caused by high proportions of conical lipids or strong curvature, and interacts with negatively charged membranes to promote tethering and enhance LC3/GABARAP lipidation. In addition, ATG3 is an autocatalytic E2-like enzyme: in an ATG7-dependent manner it conjugates ATG12 to itself. This ATG12-ATG3 complex contributes to mitochondrial homeostasis rather than autophagy, and through its interaction with PDCD6IP it promotes late endosome to lysosome trafficking and basal autophagosome maturation. The conjugate is also formed during vaccinia virus infection, where it disrupts cellular autophagy. ATG3 further promotes primary ciliogenesis by removing OFD1 from centriolar satellites via the autophagic pathway.

The human ATG3 gene encodes a member of the ATG3 family and belongs to the HGNC groups for autophagy-related genes and autophagy-related E2 enzymes. It was previously named APG3 autophagy 3-like, after the yeast homologue. According to NCBI Gene, the protein is a component of ubiquitination-like systems in autophagy and plays a role in regulating autophagy during cell death. A pseudogene is located on chromosome 20, and alternative splicing yields multiple transcript variants encoding different isoforms. Mouse and rat orthologs are both named Atg3.

Autophagosome formation

ATG3 lipidates ATG8-like proteins with PE, a key step in building autophagic isolation membranes.

Membrane curvature sensing

ATG3 senses lipid-packing defects and membrane curvature to facilitate LC3/GABARAP lipidation.

Mitochondrial homeostasis

The ATG12-ATG3 conjugate plays a role in mitochondrial homeostasis independently of autophagy.

Ciliogenesis and trafficking

ATG3 promotes primary ciliogenesis via OFD1 removal and, as ATG12-ATG3, late endosome to lysosome trafficking.

Background

ATG3 frequently asked questions

What does ATG3 do?

ATG3 is an E2 conjugating enzyme that attaches ATG8-like proteins such as GABARAP and MAP1LC3A to phosphatidylethanolamine in membranes, a key step in autophagosome formation. It receives these proteins from ATG7 and works with the ATG12, ATG5 and ATG16L1 E3 complex.

What other names does ATG3 go by?

ATG3 is also known as APG3L, PC3-96, FLJ22125, MGC15201 and DKFZp564M1178. Earlier HGNC names were APG3 autophagy 3-like and ATG3 autophagy related 3 homolog, both referring to the S. cerevisiae counterpart. UniProt names the protein ubiquitin-like-conjugating enzyme ATG3.

Is ATG3 conserved across species?

Yes. Mouse and rat both carry an orthologous Atg3 gene, and the human gene was originally named after its yeast homologue. Check the datasheet of any product for its validated reactivity.

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Related targets

Other autophagy-related enzymes and components of the ATG12, ATG5 and ATG16L1 conjugation machinery with products at Assay Genie.

Gene and protein annotations from HGNC, NCBI Gene and UniProt Q9NT62; product specifications from Assay Genie datasheets.

ATG3 Product listing