Protein: Cysteine protease ATG4B (EC 3.4.22.-) (Autophagy-related protein 4 homolog B) (A0A0G2QC33)
Organism: Rattus norvegicus (Rat)
Function: Cysteine protease that plays a key role in autophagy by mediating both proteolytic activation and delipidation of ATG8 family proteins. Required for canonical autophagy (macroautophagy), non-canonical autophagy as well as for mitophagy. The protease activity is required for proteolytic activation of ATG8 family proteins: cleaves the C-terminal amino acid of ATG8 proteins MAP1LC3A, MAP1LC3B, MAP1LC3C, GABARAPL1, GABARAPL2 and GABARAP, 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. Protease activity is also required to counteract formation of high-molecular weight conjugates of ATG8 proteins (ATG8ylation): acts as a deubiquitinating-like enzyme that removes ATG8 conjugated to other proteins, such as ATG3. In addition to the protease activity, also mediates delipidation of ATG8 family proteins. Catalyzes delipidation of PE-conjugated forms of ATG8 proteins during macroautophagy. Also involved in non-canonical autophagy, a parallel pathway involving conjugation of ATG8 proteins to single membranes at endolysosomal compartments, by catalyzing delipidation of ATG8 proteins conjugated to phosphatidylserine (PS). Compared to other members of the family (ATG4A, ATG4C or ATG4C), constitutes the major protein for proteolytic activation of ATG8 proteins, while it displays weaker delipidation activity than other ATG4 paralogs. Involved in phagophore growth during mitophagy independently of its protease activity and of ATG8 proteins: acts by regulating ATG9A trafficking to mitochondria and promoting phagophore-endoplasmic reticulum contacts during the lipid transfer phase of mitophagy.
Subcellular location: Cytoplasm {ECO:0000250|UniProtKB:Q9Y4P1}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q9Y4P1}. Cytoplasmic vesicle, autophagosome {ECO:0000250|UniProtKB:Q9Y4P1}. Endoplasmic reticulum {ECO:0000250|UniProtKB:Q9Y4P1}. Mitochondrion {ECO:0000250|UniProtKB:Q9Y4P1}. Note=Mainly localizes to the cytoplasm, including cytosol. A samll potion localizes to mitochondria; phosphorylation at Ser-34 promotes localization to mitochondria. {ECO:0000250|UniProtKB:Q9Y4P1}.
Sequence: MDAATLTYDTLRFAEFEDFPETSEPVWILGRKYSIFTEKDEILSDVASRLWFTYRRNFPAIGGTGPTSDTGWGCMLRCGQMIFAQALVCRHLGRDWRWTQRKRQPDSYFSVLNAFLDRKDSYYSIHQIAQMGVGEGKSIGQWYGPNTVAQVLKKLAVFDTWSSLAVHIAMDNTVVMEEIRRLCRASLPCAGAAALSMESERHCNGLPAGAEVTNRPLAWRPLVLLIPLRLGLTDINEAYVETLKHCFMMPQSLGVIGGKPNSAHYFIGYVGEELIYLDPHTTQPAVELTDSCFIPDESFHCQHPPCRMGIGELDPSIAVGFFCKTEEDFNDWCQQVKKLSQLGGALPMFELVEQQPSHLACQDVLNLSLDSSDVERLERFFDSEDEDFEILSL
InterPro domains: - IPR005078: Peptidase C54 (family) [8-373]
- IPR046793: Cysteine protease ATG4, F-type LIR motif (conserved_site) [363-391]
- IPR038765: Papain-like cysteine peptidase superfamily (homologous_superfamily) [7-353]
- IPR046792: Peptidase C54, catalytic domain (domain) [40-335]
Interaction partners: - Gamma-aminobutyric acid receptor-associated protein
- Gamma-aminobutyric acid receptor-associated protein-like 1
- Gamma-aminobutyric acid receptor-associated protein-like 2
- Microtubule-associated protein 1 light chain 3 beta
- Microtubule-associated protein 1 light chain 3 alpha
- Cysteine protease
- Cysteine protease
- Ubiquitin-like-conjugating enzyme ATG3
- Ubiquitin-like modifier-activating enzyme ATG7
- non-specific serine/threonine protein kinase
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0016787 (hydrolase activity), GO:0140096 (catalytic activity, acting on a protein), GO:0005515 (protein binding), GO:0008233 (peptidase activity), GO:0008234 (cysteine-type peptidase activity), GO:0004175 (endopeptidase activity), GO:0019783 (ubiquitin-like protein peptidase activity), GO:0004197 (cysteine-type endopeptidase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0044238 (primary metabolic process), GO:0044237 (cellular metabolic process), GO:0061919 (process utilizing autophagic mechanism), GO:0071704 (organic substance metabolic process), GO:0009056 (catabolic process), GO:0006807 (nitrogen compound metabolic process), GO:1901564 (organonitrogen compound metabolic process), GO:0043170 (macromolecule metabolic process), GO:0044248 (cellular catabolic process), GO:0019538 (protein metabolic process), GO:0006914 (autophagy), GO:0036211 (protein modification process), GO:0043412 (macromolecule modification), GO:0006508 (proteolysis)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005737 (cytoplasm), GO:0005829 (cytosol), GO:0005622 (intracellular anatomical structure)