ATG4B
ATG4B (autophagy related 4B cysteine peptidase, also known as Apg4B, AUTL1 or KIAA0943) is a cysteine protease of the peptidase C54 family. It activates and delipidates ATG8 family proteins, a role that makes it central to autophagy and mitophagy. Browse Assay Genie's current range of ATG4B research reagents below, or read on for the biology behind the target.
ATG4B is a cysteine protease that plays a key role in autophagy by mediating both proteolytic activation and delipidation of ATG8 family proteins. It is required for canonical autophagy (macroautophagy), non-canonical autophagy and mitophagy. Its protease activity cleaves the C-terminal amino acid of MAP1LC3A, MAP1LC3B, MAP1LC3C, GABARAP, GABARAPL1 and GABARAPL2, exposing a C-terminal glycine. This glycine is essential for conjugation of ATG8 proteins to phosphatidylethanolamine (PE) and their insertion into membranes, which autophagy requires.
The enzyme also counteracts the formation of high-molecular weight ATG8 conjugates (ATG8ylation), acting as a deubiquitinating-like enzyme that removes ATG8 from other proteins such as ATG3. It catalyses delipidation of PE-conjugated ATG8 proteins during macroautophagy. In non-canonical autophagy, which conjugates ATG8 proteins to single membranes at endolysosomal compartments, it delipidates ATG8 proteins linked to phosphatidylserine. Compared with other ATG4 paralogs, ATG4B is the major enzyme for proteolytic activation of ATG8 proteins, but its delipidation activity is weaker. During mitophagy it also supports phagophore growth independently of its protease activity and of ATG8 proteins, by regulating ATG9A trafficking to mitochondria and promoting phagophore-endoplasmic reticulum contacts.
The human ATG4B gene encodes a member of the autophagin protein family, which belongs to the autophagy related 4 family of cysteine peptidases. It was formerly named APG4 autophagy 4 homolog B (S. cerevisiae). Alternate splice variants encoding different isoforms have been characterised. UniProt places the protein in the cytosol, autophagosomes, endoplasmic reticulum and mitochondria. Autophagy removes damaged organelles and endogenous proteins and is thought to be essential for cell homeostasis. Reduced autophagy has been described in some malignant tumours.
ATG4B proteolytically activates ATG8 family proteins and removes their lipid conjugates, making it a key enzyme for studying autophagosome formation.
ATG4B supports phagophore growth in mitophagy by regulating ATG9A trafficking to mitochondria and promoting phagophore-endoplasmic reticulum contacts.
ATG4B delipidates phosphatidylserine-conjugated ATG8 proteins at endolysosomal compartments, linking it to this parallel autophagy pathway.
Autophagy is proposed to control unregulated cell growth, and reduced autophagy has been described in some malignant tumours, which motivates study of ATG4B.
ATG4B is a cysteine protease that cleaves the C-terminus of ATG8 family proteins to expose a glycine needed for lipid conjugation. It also delipidates ATG8 proteins and removes ATG8 from other proteins such as ATG3. It acts in macroautophagy, non-canonical autophagy and mitophagy.
ATG4B is also called Apg4B, APG4B, AUTL1, KIAA0943 and DKFZp586D1822. Earlier names include APG4 autophagy 4 homolog B (S. cerevisiae). The encoded protein is a member of the autophagin family and of the C-54 family of cysteine proteases. Alternate splice variants encode different isoforms.
Compared with other ATG4 paralogs, ATG4B is the major protein for proteolytic activation of ATG8 proteins, though it shows weaker delipidation activity. Orthologs exist in mouse and rat, both named Atg4b. Check the datasheet of any product for its validated reactivity.
Other ATG4 family proteases and autophagy pathway proteins, including ATG8 conjugation machinery and mitophagy partners.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q9Y4P1; product specifications from Assay Genie datasheets.