APG5L/ATG5

Function

Involved in autophagic vesicle formation. Conjugation with ATG12, through a ubiquitin-like conjugating system involving ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes. Involved in mitochondrial quality control after oxidative damage, and in subsequent cellular longevity. Plays a critical role in multiple aspects of lymphocyte development and is essential for both B and T lymphocyte survival and proliferation. Required for optimal processing and presentation of antigens for MHC II. Involved in the maintenance of axon morphology and membrane structures, as well as in normal adipocyte differentiation. Promotes primary ciliogenesis through removal of OFD1 from centriolar satellites and degradation of IFT20 via the autophagic pathway.

May play an important role in the apoptotic process, possibly within the modified cytoskeleton. Its expression is a relatively late event in the apoptotic process, occurring downstream of caspase activity. Plays a crucial role in IFN-gamma-induced autophagic cell death by interacting with FADD.

(Microbial infection) May act as a proviral factor. In association with ATG12, negatively regulates the innate antiviral immune response by impairing the type I IFN production pathway upon vesicular stomatitis virus (VSV) infection (PubMed:17709747). Required for the translation of incoming hepatitis C virus (HCV) RNA and, thereby, for initiation of HCV replication, but not required once infection is established (PubMed:19666601).

Involvement in disease

Spinocerebellar ataxia, autosomal recessive, 25

SCAR25

A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR25 patients manifest delayed psychomotor development with delayed walking, truncal ataxia, dysmetria, and nystagmus, Cerebellar hypoplasia is seen on brain imaging.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Conjugated to ATG12; which is essential for autophagy, but is not required for association with isolation membrane.

Acetylated by EP300.

Sequence similarities

Belongs to the ATG5 family.

Tissue specificity

Ubiquitous. The mRNA is present at similar levels in viable and apoptotic cells, whereas the protein is dramatically highly expressed in apoptotic cells.

Cellular localization

• Cytoplasm
• Preautophagosomal structure membrane
• Peripheral membrane protein
• Colocalizes with nonmuscle actin. The conjugate detaches from the membrane immediately before or after autophagosome formation is completed (By similarity). Localizes also to discrete punctae along the ciliary axoneme and to the base of the ciliary axoneme.

Alternative names

• Autophagy protein 5
• APG5-like
• Apoptosis-specific protein
• ATG5
• APG5L
• ASP

Database links

• entrezGene:9474
• omim:604261
• swissprot:Q9H1Y0

Target type

Proteins

Primary research area

Oncology

Other research areas

• Neuroscience

Molecular weight

32447Da