background:
Autophagy is the process by which endogenous proteins and damaged organelles are destroyed intracellularly. Autophagy is postulated to be essential for cell homeostasis and cell remodeling during differentiation, metamorphosis, non-apoptotic cell death, and aging. Reduced levels of autophagy have been described in some malignant tumors, and a role for autophagy in controlling the unregulated cell growth linked to cancer has been proposed. This gene belongs to the autophagy-related protein 4 (Atg4) family of C54 endopeptidases. Members of this family encode proteins that play a role in the biogenesis of autophagosomes, which sequester the cytosol and organelles for degradation by lysosomes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
Function:
Cysteine protease ATG4D: Cysteine protease required for the cytoplasm to vacuole transport (Cvt) and autophagy. Cleaves the SLCterminal amino acid of ATG8 family proteins MAP1LC3 and GABARAPL2, to reveal a SLCterminal glycine. Exposure of the glycine at the SLCterminus is essential for ATG8 proteins conjugation to phosphatidylethanolamine (PE) and insertion to membranes, which is necessary for autophagy. Has also an activity of delipidating enzyme for the PE-conjugated forms.
Cysteine protease ATG4D, mitochondrial: Plays a role as an autophagy regulator that links mitochondrial dysfunction with apoptosis. The mitochondrial import of ATG4D during cellular stress and differentiation may play important roles in the regulation of mitochondrial physiology, ROS, mitophagy and cell viability.
Subcellular Location:
Cysteine protease ATG4D: Cytoplasm.
Cysteine protease ATG4D, mitochondrial: Cytoplasm. Mitochondrion matrix. Note=Imported into mitochondrial matrix after cleavage by CASP3 during oxidative stress and cell death.
Tissue Specificity:
Mainly expressed in skeletal muscle and, to a lower extent, in testis.
Post-translational modifications:
Cleaved by CASP3 during apoptosis which leads to increased activity. The cleavage by CASP3 reveals a cryptic mitochondrial targeting sequence immediately downstream of their canonical caspase cleavage sites which leads to mitochondroal import of the protein.
Similarity:
Belongs to the peptidase C54 family.
Database links:
Entrez Gene: 84971 Human
Entrez Gene: 235040 Mouse
Entrez Gene: 100141400 Pig
Entrez Gene: 686505 Rat
Omim: 611340 Human
SwissProt: Q86TL0 Human
SwissProt: Q8BGV9 Mouse
SwissProt: Q684M2 Pig
Unigene: 512799 Human
Unigene: 88165 Mouse
Unigene: 202643 Rat
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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