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MT001490

UniProt Annotations

Entry Information

Gene Name	autophagy related 4A, cysteine peptidase
Protein Entry	ATG4A_HUMAN
UniProt ID	Q8WYN0
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=4; Name=1; IsoId=Q8WYN0-1; Sequence=Displayed; Name=2; IsoId=Q8WYN0-2; Sequence=VSP_013025; Name=3; IsoId=Q8WYN0-3; Sequence=VSP_025902; Note=No experimental confirmation available.; Name=4; IsoId=Q8WYN0-5; Sequence=VSP_030499; Note=Gene prediction based on EST data.;
Biophysicochemical Properties	Kinetic parameters: KM=33.9 uM for MAP1LC3B {ECO:0000269\|PubMed:21177865, ECO:0000269\|PubMed:22302004}; KM=20.8 uM for GABARAP {ECO:0000269\|PubMed:21177865, ECO:0000269\|PubMed:22302004}; KM=36.7 uM for GABARAPL1 {ECO:0000269\|PubMed:21177865, ECO:0000269\|PubMed:22302004}; KM=15.7 uM for GABARAPL2 {ECO:0000269\|PubMed:21177865, ECO:0000269\|PubMed:22302004};
Enzyme Regulation	Inhibited by N-ethylmaleimide. Redox-regulated during autophagy since reducing conditions activate ATG4A whereas an oxidizing environment such as the presence of H(2)O(2) inhibits its activity. {ECO:0000269\|PubMed:12473658, ECO:0000269\|PubMed:17347651}.
Function	Cysteine protease required for the cytoplasm to vacuole transport (Cvt) and autophagy. Cleaves the C-terminal amino acid of ATG8 family proteins 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. Preferred substrate is GABARAPL2 followed by MAP1LC3A and GABARAP. Has also an activity of delipidating enzyme for the PE-conjugated forms. {ECO:0000269\|PubMed:12473658, ECO:0000269\|PubMed:15169837, ECO:0000269\|PubMed:17347651, ECO:0000269\|PubMed:21177865, ECO:0000269\|PubMed:21245471, ECO:0000269\|PubMed:22302004}.
Similarity	Belongs to the peptidase C54 family. {ECO:0000305}.
Subcellular Location	Cytoplasm {ECO:0000250}.
Tissue Specificity	Widely expressed, at a low level, and the highest expression is observed in skeletal muscle and brain. Also detected in fetal liver. {ECO:0000269\|PubMed:12446702, ECO:0000269\|PubMed:15169837}.