ATG4B (Autophagy Related 4B Cysteine Peptidase)
A key protease in the autophagy pathway, regulating LC3/GABARAP lipidation and autophagosome formation.
Gene Information Card
| Symbol | ATG4B |
|---|---|
| Full Name | Autophagy Related 4B Cysteine Peptidase |
| Gene Type | Protein coding |
| Chromosomal Location | 2q37.3 |
| NCBI Gene ID | 23192 ncbi.nlm.nih.gov/gene/23192 |
| Ensembl ID | ENSG00000168397 |
| UniProt ID | Q9Y4P1 |
| OMIM ID | 611338 |
| HGNC ID | 20790 |
| Aliases | APG4B, AUTL1, DKFZp686B15176 |
Description
ATG4B encodes a cysteine protease that is essential for autophagy. It cleaves the C-terminal of LC3 (MAP1LC3) and GABARAP family members to expose a glycine residue for lipidation with phosphatidylethanolamine, and also deconjugates LC3 from autophagosomal membranes. This dual activity is critical for autophagosome biogenesis and maturation. ATG4B is widely expressed and its dysregulation is implicated in various cancers and neurodegenerative disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Overexpression or altered splicing of ATG4B can enhance autophagy, promoting tumor cell survival under stress. In some contexts, reduced ATG4B activity may limit autophagy and sensitize cells to apoptosis. | COSMIC and literature (e.g., increased expression in colorectal and breast cancer). |
| Neurodegenerative diseases (e.g., Alzheimer's, Parkinson's) | Impaired autophagy due to ATG4B dysfunction leads to accumulation of protein aggregates and damaged organelles, contributing to neurodegeneration. | ClinVar and literature (e.g., association with Alzheimer's disease). |
| Inflammatory bowel disease (IBD) | Genetic variants in ATG4B may affect autophagy in intestinal epithelium, influencing inflammation and barrier function. | ClinVar and GWAS studies. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Liver | 15.7 | Medium |
| Kidney | 10.2 | Medium |
| Heart | 8.5 | Low |
| Skeletal Muscle | 6.1 | Low |
| Lung | 9.8 | Low |
| Colon | 11.4 | Medium |
| Breast | 7.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 18.5 | High expression; commonly used in autophagy studies. |
| HepG2 | 14.2 | Moderate expression; liver cancer cell line. |
| MCF7 | 12.8 | Moderate expression; breast cancer cell line. |
| A549 | 10.5 | Low-moderate expression; lung cancer cell line. |
| SH-SY5Y | 9.3 | Low expression; neuroblastoma cell line. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1Val) | Missense | Rare (ClinVar) | Potential loss of function due to start codon loss; may impair autophagy. |
| c.457C>T (p.Arg153Cys) | Missense | Rare (ClinVar) | Unknown significance; may affect protease activity. |
| c.1003G>A (p.Gly335Ser) | Missense | Rare (ClinVar) | Unknown significance; possibly damaging. |
| c.1246C>T (p.Arg416Trp) | Missense | Rare (ClinVar) | Unknown significance; may affect substrate binding. |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce or abolish ATG4B protease activity, leading to impaired LC3 processing and autophagy. Examples include start codon loss and catalytic site mutations.
Gain of Function (GOF)
Amplification or overexpression of ATG4B in certain cancers, enhancing autophagy and promoting tumor survival. No specific gain-of-function mutations are well-documented.
Dominant Negative (DN)
Some missense mutations may produce a protein that interferes with wild-type ATG4B function, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • cysteine-type peptidase activity | • autophagy |
| • proteolysis | • autophagosome assembly |
| • protein homodimerization activity | • microtubule-associated protein 1 light chain 3 binding |
Pathways
• Autophagy - animal
• Mitophagy
• Selective autophagy
• LC3/GABARAP conjugation pathway
Protein Summary
ATG4B is a 393-amino acid cysteine protease with a catalytic triad (Cys74, Asp278, His281). It processes pro-LC3 to mature LC3-I and deconjugates LC3-II from autophagosomal membranes. The protein contains an LIR (LC3-interacting region) motif that facilitates substrate recognition. ATG4B is regulated by oxidation and phosphorylation, and its activity is essential for autophagy flux.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ATG4B Knockout HEK293 Cell Line | EDJ-KQ2550 | Human | 23192 | Details Get a Quote |
| ATG4B Knockout A-549 Cell Line | EDJ-KQ23197 | Human | 23192 | Details Get a Quote |
| ATG4B Knockout HCT 116 Cell Line | EDJ-KQ23198 | Human | 23192 | Details Get a Quote |
| ATG4B Knockout HeLa Cell Line | EDJ-KQ21835 | Human | 23192 | Details Get a Quote |
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