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MitoProteome Human Mitochondrial Protein Database
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Related Proteins
MT001438
UniProt Annotations
Entry Information
Gene Name
autophagy related 4D, cysteine peptidase
Protein Entry
ATG4D_HUMAN
UniProt ID
Q86TL0
Species
Human
Comments
Comment type
Description
Alternative Products
Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q86TL0-1; Sequence=Displayed; Name=2; IsoId=Q86TL0-2; Sequence=VSP_056671; Note=No experimental confirmation available.;
Biophysicochemical Properties
Kinetic parameters: KM=13.1 uM for MAP1LC3B {ECO:0000269|PubMed:21177865}; KM=7.2 uM for GABARAPL2 {ECO:0000269|PubMed:21177865};
Domain
Residues 64 to 103 constitute a cryptic mitochondrial transit peptide which is revealed after cleavage by caspase of residues 1 to 63 upon oxidative stress and cell death. It acts then as a functional transit peptide, and allows the import of the cleaved protein into the mitochondria (PubMed:22441018). {ECO:0000269|PubMed:22441018}.
Enzyme Regulation
Inhibited by N-ethylmaleimide.
Function
Cysteine protease ATG4D: Cysteine protease required for the cytoplasm to vacuole transport (Cvt) and autophagy. Cleaves the C-terminal amino acid of ATG8 family proteins MAP1LC3 and GABARAPL2, to reveal a C-terminal glycine. Exposure of the glycine at the C-terminus 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.
Function
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.
Ptm
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. {ECO:0000269|PubMed:19549685, ECO:0000269|PubMed:22441018}.
Similarity
Belongs to the peptidase C54 family. {ECO:0000305}.
Subcellular Location
Cysteine protease ATG4D: Cytoplasm.
Subcellular Location
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. {ECO:0000269|PubMed:12446702}.
MitoProteome Human Mitochondrial Protein Database
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