| IED ID | IndEnz0002014391 |
| Enzyme Type ID | protease014391 |
| Protein Name |
Cysteine protease ATG4A EC 3.4.22.- AUT-like 2 cysteine endopeptidase Autophagy-related cysteine endopeptidase 2 Autophagin-2 Autophagy-related protein 4 homolog A |
| Gene Name | Atg4a Apg4a Autl2 |
| Organism | Mus musculus (Mouse) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MESVMSKYENQILIFPDYLEEFPDTDELVWILGKQHPLKTEKSKLLSDISARLWFTYRRKFSPIGGTGPSSDAGWGCMLRCGQMMLAQALICRHLGRDWNWERQKEQPKEYQRILQCFLDRKDCCYSIHQMAQMGVGEGKSIGEWFGPNTVAQVIKKLALFDEWNSLAVYVSMDNTVVIEDIKKMCCVLPVGAADPAGDFLTASNQSRDTSVPCSAWKPLLLIVPLRLGINQINPVYVEAFKECFKMPQSLGALGGKPNNAYYFIGFLGDELIFLDPHTTQTFVDIEESGLVDDQTFHCLQSPQRMSILNLDPSVALGFFCKEEKDFDNWCSLVQKEILKENLRMFELVQKHPSHWPPFVPPAKPEVTTTGAEFIESTEQLEDFELEEDFEILSVG |
| Enzyme Length | 396 |
| Uniprot Accession Number | Q8C9S8 |
| Absorption | |
| Active Site | ACT_SITE 77; /note=Nucleophile; /evidence=ECO:0000250|UniProtKB:Q9Y4P1; ACT_SITE 276; /evidence=ECO:0000250|UniProtKB:Q9Y4P1; ACT_SITE 278; /evidence=ECO:0000250|UniProtKB:Q9Y4P1 |
| Activity Regulation | ACTIVITY 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:0000250|UniProtKB:Q8WYN0}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=[protein]-C-terminal L-amino acid-glycyl-phosphatidylethanolamide + H2O = [protein]-C-terminal L-amino acid-glycine + a 1,2-diacyl-sn-glycero-3-phosphoethanolamine; Xref=Rhea:RHEA:67548, Rhea:RHEA-COMP:17323, Rhea:RHEA-COMP:17324, ChEBI:CHEBI:15377, ChEBI:CHEBI:64612, ChEBI:CHEBI:172940, ChEBI:CHEBI:172941; Evidence={ECO:0000250|UniProtKB:Q8WYN0};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67549; Evidence={ECO:0000250|UniProtKB:Q8WYN0}; |
| DNA Binding | |
| EC Number | 3.4.22.- |
| Enzyme Function | FUNCTION: Cysteine protease that plays a key role in autophagy by mediating both proteolytic activation and delipidation of ATG8 family proteins. The protease activity is required for proteolytic activation of ATG8 family proteins: cleaves the C-terminal amino acid of ATG8 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. 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. Compared to ATG4B, the major protein for proteolytic activation of ATG8 proteins, shows weaker ability to cleave the C-terminal amino acid of ATG8 proteins, while it displays stronger delipidation activity. 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. {ECO:0000250|UniProtKB:Q8WYN0}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Chain (1); Motif (1); Sequence conflict (4) |
| Keywords | Autophagy;Cytoplasm;Hydrolase;Lipid metabolism;Protease;Protein transport;Reference proteome;Thiol protease;Transport;Ubl conjugation pathway |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q8BGE6}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 16602821; 21267068; 25652854; 26805760; |
| Motif | MOTIF 390..393; /note=LIR; /evidence=ECO:0000250|UniProtKB:Q8WYN0 |
| Gene Encoded By | |
| Mass | 45,095 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:67548; RHEA:67549 |
| Cross Reference Brenda |