ATG4A
ATG4A (autophagy related 4A cysteine peptidase, also known as AUTL2 and APG4A) is a cytoplasmic cysteine protease of the peptidase C54 family. It activates and delipidates ATG8 family proteins, two steps that underpin autophagy. Browse Assay Genie's current range of ATG4A research reagents below, or read on for the biology behind the target.
ATG4A is a cysteine protease that plays a key role in autophagy by mediating both proteolytic activation and delipidation of ATG8 family proteins. Its protease activity cleaves the C-terminal amino acid of ATG8 proteins to reveal a C-terminal glycine. Exposing this glycine is essential for conjugation of ATG8 proteins to phosphatidylethanolamine (PE) and their insertion into membranes, which is necessary for autophagy. The preferred substrate is GABARAPL2, followed by MAP1LC3A and GABARAP.
The enzyme also counteracts the formation of high-molecular weight ATG8 conjugates (ATG8ylation). It acts as a deubiquitinating-like enzyme that removes ATG8 conjugated to other proteins, such as ATG3. In addition, it catalyses delipidation of PE-conjugated ATG8 proteins during macroautophagy. Compared with ATG4B, the major protein for proteolytic activation of ATG8 proteins, ATG4A cleaves the C-terminal amino acid less efficiently but shows stronger delipidation activity. 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 during the lipid transfer phase.
The human ATG4A gene encodes a member of the autophagin protein family and of the C-54 family of cysteine proteases. HGNC places it in the autophagy related group and the autophagy related 4 family of cysteine peptidases. Earlier names include AUT-like 2 and APG4 autophagy 4 homolog A, after the yeast genes. Autophagy destroys endogenous proteins and damaged organelles within the cell. It is thought to be essential for cell homeostasis and remodelling during differentiation, metamorphosis, non-apoptotic cell death and ageing. Reduced autophagy has been described in some malignant tumours, and a role in controlling the unregulated cell growth linked to cancer has been proposed. A mouse ortholog, Atg4a, is recognised.
ATG4A processes and delipidates ATG8 family proteins, steps required for their membrane insertion and for autophagy.
ATG4A supports phagophore growth in mitophagy by regulating ATG9A trafficking to mitochondria and promoting phagophore-endoplasmic reticulum contacts.
ATG4A shows stronger delipidation but weaker C-terminal cleavage activity than ATG4B, making it useful for comparing ATG4 paralogues.
Reduced autophagy has been described in some malignant tumours, and autophagy is proposed to help control unregulated cell growth.
ATG4A is a cysteine protease that activates ATG8 family proteins by cleaving their C-terminal amino acid to expose a glycine needed for PE conjugation. It also delipidates PE-conjugated ATG8 proteins and removes ATG8 from other proteins such as ATG3.
ATG4A is also called AUTL2 and APG4A. Earlier names include AUT-like 2 cysteine endopeptidase and APG4 autophagy 4 homolog A, reflecting its yeast homologues. UniProt lists the protein as cysteine protease ATG4A, and it is a member of the autophagin family.
ATG4B is the major protein for proteolytic activation of ATG8 proteins. ATG4A cleaves the C-terminal amino acid more weakly but shows stronger delipidation activity. Mouse Atg4a is the ortholog; check the datasheet of any product for its validated reactivity.
Other ATG4 proteases, ATG8 conjugation machinery and autophagy-related proteins with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q8WYN0; product specifications from Assay Genie datasheets.