Target intelligence / Profile preview

Autophagy protein 5 (ATG5)

Target
ATG5
Molecular classification
Other (ATG5 does not belong to receptor, ion channel, enzyme, transporter, or transcription factor classes; it is a ubiquitin-like autophagy protein forming multiprotein complexes)
01

Overview

Autophagy protein 5 (ATG5) is a ubiquitin-like protein encoded by the *ATG5* gene on human chromosome 6. It forms a covalent complex with ATG12, which then associates with ATG16L1, creating the ATG12–ATG5–ATG16L1 complex crucial for autophagosome membrane elongation. ATG5 is activated by various protein kinases and transcription factors under cellular stress. Beyond its canonical autophagic functions, ATG5 can regulate apoptosis through calpain-mediated cleavage and mitochondrial translocation, participate in cell cycle arrest after DNA damage (G2/M arrest and mitotic catastrophe), and is involved in immune cell functions such as macrophage polarization and T-cell survival. ATG5 dysregulation is implicated in diverse human diseases, including cancer, neurodegenerative conditions, autoimmune and inflammatory diseases, and it serves as a key biomarker for autophagy-related cellular activity[1][2][3][4][5].

Other names
Autophagy protein 5ATG5APG5LASPSCAR25hAPG5APG5-likeApoptosis-specific protein
02

Mechanism of action

Activation or inhibition of autophagy by modulating ATG5 complex formation (either via upstream regulators, direct protein modulation, or mimicking cleavage-induced pro-apoptotic actions); Induction of apoptosis via calpain-mediated cleavage and mitochondrial targeting.

03

Biological functions

Autophagy (initiates and regulates autophagosome membrane formation)Apoptosis (can act as a pro-apoptotic factor in response to stress)Cell cycle regulation / Mitotic catastrophe (promotes G2/M arrest and can cause mitotic cell death after DNA damage)Immune response (regulates macrophage polarization, cytokine secretion, antigen presentation, and T-cell survival)
04

Disease associations

Cancer (essential in tumor cell autophagy and apoptosis; involved in hepatocellular carcinoma, colon, and breast cancer progression)Neurodegenerative disease (plays a key role in neuronal survival; altered ATG5 linked to Huntington, Parkinson disease)Autoimmune disease (implicated in multiple sclerosis, systemic lupus erythematosus, Crohn's disease)Inflammation (involved in inflammatory demyelination)Metabolic disorders (associated with type 2 diabetes mellitus)
05

Safety considerations

Non-specific modulation risk (autophagy is a fundamental cellular process; systemic inhibition/activation may impair tissue homeostasis)Risk of unwanted apoptosis or immune dysregulation when targeting ATG5 in therapeutic contexts
06

Interacting drugs

Trichokonin VI (antimicrobial peptide triggers ATG5-dependent autophagy)

1 more in the full profile.

07

Biomarkers

ATG5 expression levels (used as biomarkers of autophagy activity in cancer, neurodegeneration, and autoimmune disease; potential indicator in patient stratification and disease progression)

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