ATG3 (Autophagy Related 3)
A key E2-like enzyme in the autophagy conjugation system, essential for autophagosome formation and lysosomal degradation.
Gene Information Card
| Symbol | ATG3 |
|---|---|
| Full Name | Autophagy Related 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 3q13.2 |
| NCBI Gene ID | 64422 ncbi.nlm.nih.gov/gene/64422 |
| Ensembl ID | ENSG00000114349 |
| UniProt ID | Q9NT62 |
| OMIM ID | 609606 |
| HGNC ID | 20962 |
| Aliases | APG3, APG3-LIKE, hApg3, PC3-96 |
Description
ATG3 (Autophagy Related 3) encodes an E2-like enzyme essential for autophagy. It conjugates ATG8 family proteins (e.g., LC3, GABARAP) to phosphatidylethanolamine (PE) and mediates ATG12 conjugation to ATG3 itself, both critical steps in autophagosome membrane expansion and closure. The protein is ubiquitously expressed and its dysfunction is linked to cancer, neurodegenerative disorders, and infectious diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Altered ATG3 expression disrupts autophagy-mediated tumor suppression; overexpression correlates with poor prognosis. | PMID: 25609832 |
| Hepatocellular carcinoma | ATG3 downregulation impairs autophagic flux, promoting tumorigenesis. | PMID: 27846390 |
| Neurodegeneration (Alzheimer disease) | Reduced ATG3 activity leads to accumulation of damaged organelles and protein aggregates. | PMID: 29127255 |
| Crohn disease | ATG3 variants may impair autophagy of intracellular bacteria, contributing to chronic inflammation. | PMID: 21102463 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Brain | 8.3 | Medium |
| Heart | 7.1 | Medium |
| Skeletal muscle | 6.9 | Medium |
| Kidney | 10.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.2 | High expression; commonly used in autophagy studies |
| HEK293 | 11.8 | High expression |
| MCF7 | 9.5 | Medium expression |
| HepG2 | 13.1 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.01% | Likely loss of start codon; predicted loss of function |
| c.472C>T (p.Arg158Trp) | Missense | <0.01% | May disrupt E2 catalytic activity |
| c.839G>A (p.Arg280His) | Missense | <0.01% | Unknown functional impact |
Mutation functional classification
Loss of Function (LOF)
Mutations affecting the catalytic cysteine (Cys264) or conserved residues in the E2 core domain impair ATG8-PE conjugation and autophagosome formation.
Gain of Function (GOF)
No gain-of-function mutations reported in ATG3.
Dominant Negative (DN)
Truncated or misfolded ATG3 variants may interfere with wild-type protein function in the conjugation complex.
View complete mutation data：
Gene Ontology (GO)
| • post-embryonic development (GO:0009886) | • macroautophagy (GO:0016236) |
| • antigen processing and presentation of exogenous peptide antigen via MHC class II (GO:0019886) | • autophagosome maturation (GO:0030242) |
| • pre-autophagosomal structure membrane (GO:0034045) | • ATG8 family conjugation pathway (GO:0043044) |
| • reticulophagy (GO:0061709) | • autophagosome maturation (GO:0097352) |
Pathways
• Autophagy - animal (KEGG: hsa04140)
• Mitophagy (Reactome: R-HSA-5205647)
• LC3/GABARAP conjugation (Reactome: R-HSA-5672003)
• ATG12-ATG5 conjugation (Reactome: R-HSA-5672004)
Protein Summary
ATG3 is a 314-amino acid E2-like enzyme (UniProt Q9NT62) with a conserved catalytic cysteine (Cys264) that forms a thioester intermediate with ATG8 family proteins. It also mediates ATG12 conjugation to ATG3 itself, a non-canonical E2-E3 hybrid function. The protein localizes to the phagophore assembly site (PAS) and is essential for autophagosome biogenesis. Its activity is regulated by phosphorylation and interaction with ATG7 (E1) and ATG12-ATG5 (E3).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ATG3 Knockout HEK293 Cell Line | EDJ-KQ12466 | Human | 64422 | Details Get a Quote |
| ATG3 Knockout A-549 Cell Line | EDJ-KQ41409 | Human | 64422 | Details Get a Quote |
| ATG3 Knockout HCT 116 Cell Line | EDJ-KQ41410 | Human | 64422 | Details Get a Quote |
| ATG3 Knockout HeLa Cell Line | EDJ-KQ41411 | Human | 64422 | Details Get a Quote |
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