| IED ID | IndEnz0002014446 |
| Enzyme Type ID | protease014446 |
| Protein Name |
Probable cysteine protease atg4 EC 3.4.22.- Autophagy-related protein 4 |
| Gene Name | atg4 SPAC19B12.08 |
| Organism | Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Fungi Dikarya Ascomycota Taphrinomycotina Schizosaccharomycetes Schizosaccharomycetales Schizosaccharomycetaceae Schizosaccharomyces Schizosaccharomyces pombe (Fission yeast) Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast) |
| Enzyme Sequence | MELMARFLERYLHFAPTNTEPPGTLIWFLGHSYKIEDSQWPEKFLYDSFSLITITYRSGIEGLENMTSDTGWGCMIRSTQTLLANCLRICYPEKQLKEILALFADEPSAPFSIHQFVTMGKTLCDINPGQWFGPTTSCSCVARLSDQNPDVPLHVYVARNGNAIYRDQLSKVSFPVLLLIPTRLGIDSINESYYDQLLQVFEIRSFVGITGGRPRSAHYFYARQNQYFFYLDPHCTHFAHTTTQPASEETFHSATLRRVAIQDLDPCMIFGFLIRDEEEWHSFEANQKYFADIVQIFDSEPQPVETHDDFVLDENVEDHL |
| Enzyme Length | 320 |
| Uniprot Accession Number | Q9P373 |
| Absorption | |
| Active Site | ACT_SITE 74; /note=Nucleophile; /evidence=ECO:0000250|UniProtKB:Q9Y4P1; ACT_SITE 232; /evidence=ECO:0000250|UniProtKB:Q9Y4P1; ACT_SITE 234; /evidence=ECO:0000250|UniProtKB:Q9Y4P1 |
| Activity Regulation | |
| 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:P53867};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67549; Evidence={ECO:0000250|UniProtKB:P53867}; |
| DNA Binding | |
| EC Number | 3.4.22.- |
| Enzyme Function | FUNCTION: Cysteine protease that plays a key role in cytoplasm to vacuole transport (Cvt) and autophagy by mediating both proteolytic activation and delipidation of atg8 (PubMed:23950735). Required for selective autophagic degradation of the nucleus (nucleophagy) as well as for mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production (By similarity). The protease activity is required for proteolytic activation of atg8: cleaves the C-terminal amino acid of atg8 to reveal a C-terminal glycine (PubMed:23950735). Atg8 ubiquitin-like activity requires the exposure of the glycine at the C-terminus for its conjugation to phosphatidylethanolamine (PE) and its insertion to membranes, which is necessary for autophagy. The atg8-PE conjugate mediates tethering between adjacent membranes and stimulates membrane hemifusion, leading to expansion of the autophagosomal membrane during autophagy. In addition to the protease activity, also catalyzes deconjugation of PE-conjugated forms of atg8 during macroautophagy: atg8 delipidation is required to release the protein from membranes, which facilitates multiple events during macroautophagy, and especially for efficient autophagosome biogenesis, the assembly of atg9-containing tubulovesicular clusters into phagophores/autophagosomes, and for the disassembly of PAS-associated ATG components. Atg8 delipidation by atg4 also recycles atg8-PE generated on inappropriate membranes to maintain a reservoir of unlipidated atg8 that is required for autophagosome formation at the PAS (By similarity). Plays a role in meiosis and sporulation (PubMed:19778961). {ECO:0000250|UniProtKB:P53867, ECO:0000269|PubMed:19778961, ECO:0000269|PubMed:23950735}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Chain (1) |
| Keywords | Autophagy;Cytoplasm;Hydrolase;Nucleus;Protease;Protein transport;Reference proteome;Thiol protease;Transport;Ubl conjugation pathway |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16823372}. Nucleus {ECO:0000269|PubMed:16823372}. Preautophagosomal structure {ECO:0000250|UniProtKB:P53867}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 16491466; 16802154; 20473289; 22252817; 23173672; 23697806; 34250083; |
| Motif | |
| Gene Encoded By | |
| Mass | 36,929 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:67548; RHEA:67549 |
| Cross Reference Brenda |