| IED ID | IndEnz0002014425 |
| Enzyme Type ID | protease014425 |
| Protein Name |
Probable cysteine protease ATG4 EC 3.4.22.- Autophagy-related protein 4 |
| Gene Name | ATG4 CIMG_02134 |
| Organism | Coccidioides immitis (strain RS) (Valley fever fungus) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Fungi Dikarya Ascomycota saccharomyceta Pezizomycotina leotiomyceta Eurotiomycetes Eurotiomycetidae Onygenales Onygenales incertae sedis Coccidioides Coccidioides immitis (Valley fever fungus) Coccidioides immitis (strain RS) (Valley fever fungus) |
| Enzyme Sequence | MNTVDIGQKYKRIVEYLWDPEPKNDDDIIEPVWCLGKEYKTSIPRDSEGAEAPESCNMPGMPFLSPMNQMSLSSRDTQAALSKPATPPHQLGIQRSKSREWPTSFLDDFESKFWFTYRSNFPAIPKSRDPDTPLALTLSVRLRSQFLDTHGFTADTGWGCMIRSGQSLLANALSILNLGRDWRRGSKIKEECELLSLFADNPQAPFSIHRFVDYGASACGKHPGEWFGPSATARCIEALSNECKHTDLNVYVMSDGSDVHEDQFRQIAGPDGIRPTLILLGVRLGIESVTPVYWEALRAIIRYPQSVGIAGGRPSSSLYFIGVQGPYFFYLDPHHTRPAVSWNPDSTLSPENLDTYHTRRLRRLHIREMDPSMLIGFLIKDDDDWKDWKRRLRSVTGNPIIHIFDLERPNFGRHLEREEAVDEVEALDDDSN |
| Enzyme Length | 432 |
| Uniprot Accession Number | Q1E5M9 |
| Absorption | |
| Active Site | ACT_SITE 160; /note=Nucleophile; /evidence=ECO:0000250|UniProtKB:Q9Y4P1; ACT_SITE 332; /evidence=ECO:0000250|UniProtKB:Q9Y4P1; ACT_SITE 334; /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. 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. The protease activity is required for proteolytic activation of ATG8: cleaves the C-terminal amino acid of ATG8 to reveal a C-terminal glycine. 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. {ECO:0000250|UniProtKB:P53867}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Chain (1); Region (1) |
| Keywords | Autophagy;Cytoplasm;Hydrolase;Nucleus;Protease;Protein transport;Reference proteome;Thiol protease;Transport |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P53867}. Nucleus {ECO:0000250|UniProtKB:P53867}. Preautophagosomal structure {ECO:0000250|UniProtKB:P53867}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 49,088 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:67548; RHEA:67549 |
| Cross Reference Brenda |