| IED ID | IndEnz0002014407 |
| Enzyme Type ID | protease014407 |
| Protein Name |
Cysteine protease ATG4C EC 3.4.22.- AUT-like 3 cysteine endopeptidase Autophagy-related cysteine endopeptidase 3 Autophagin-3 Autophagy-related protein 4 homolog C HsAPG4C |
| Gene Name | ATG4C APG4C AUTL1 AUTL3 |
| Organism | Homo sapiens (Human) |
| 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 Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MEATGTDEVDKLKTKFISAWNNMKYSWVLKTKTYFSRNSPVLLLGKCYHFKYEDEDKTLPAESGCTIEDHVIAGNVEEFRKDFISRIWLTYREEFPQIEGSALTTDCGWGCTLRTGQMLLAQGLILHFLGRAWTWPDALNIENSDSESWTSHTVKKFTASFEASLSGEREFKTPTISLKETIGKYSDDHEMRNEVYHRKIISWFGDSPLALFGLHQLIEYGKKSGKKAGDWYGPAVVAHILRKAVEEARHPDLQGITIYVAQDCTVYNSDVIDKQSASMTSDNADDKAVIILVPVRLGGERTNTDYLEFVKGILSLEYCVGIIGGKPKQSYYFAGFQDDSLIYMDPHYCQSFVDVSIKDFPLETFHCPSPKKMSFRKMDPSCTIGFYCRNVQDFKRASEEITKMLKFSSKEKYPLFTFVNGHSRDYDFTSTTTNEEDLFSEDEKKQLKRFSTEEFVLL |
| Enzyme Length | 458 |
| Uniprot Accession Number | Q96DT6 |
| Absorption | |
| Active Site | ACT_SITE 111; /note=Nucleophile; /evidence=ECO:0000250|UniProtKB:Q9Y4P1; ACT_SITE 345; /evidence=ECO:0000250|UniProtKB:Q9Y4P1; ACT_SITE 347; /evidence=ECO:0000250|UniProtKB:Q9Y4P1 |
| Activity Regulation | ACTIVITY REGULATION: Inhibited by N-ethylmaleimide. {ECO:0000269|PubMed:21177865}. |
| 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:0000269|PubMed:29458288, ECO:0000269|PubMed:33909989};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67549; Evidence={ECO:0000269|PubMed:29458288, ECO:0000269|PubMed:33909989}; |
| 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 (PubMed:21177865, PubMed:29458288, PubMed:30661429). The protease activity is required for proteolytic activation of ATG8 family proteins: cleaves the C-terminal amino acid of ATG8 proteins MAP1LC3 and GABARAPL2, to reveal a C-terminal glycine (PubMed:21177865). 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 (By similarity). In addition to the protease activity, also mediates delipidation of ATG8 family proteins (PubMed:29458288, PubMed:33909989). Catalyzes delipidation of PE-conjugated forms of ATG8 proteins during macroautophagy (PubMed:29458288, PubMed:33909989). 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 (PubMed:29458288). In contrast to other members of the family, weakly or not involved in phagophore growth during mitophagy (PubMed:33773106). {ECO:0000250|UniProtKB:Q9Y4P1, ECO:0000269|PubMed:21177865, ECO:0000269|PubMed:29458288, ECO:0000269|PubMed:30661429, ECO:0000269|PubMed:33773106, ECO:0000269|PubMed:33909989}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Chain (1); Frameshift (1); Modified residue (3) |
| Keywords | Acetylation;Autophagy;Cytoplasm;Hydrolase;Phosphoprotein;Protease;Protein transport;Reference proteome;Thiol protease;Transport;Ubl conjugation pathway |
| Interact With | P42858 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q8BGE6}. |
| Modified Residue | MOD_RES 1; /note=N-acetylmethionine; /evidence=ECO:0007744|PubMed:19413330; MOD_RES 451; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:23186163; MOD_RES 452; /note=Phosphothreonine; /evidence=ECO:0007744|PubMed:23186163 |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 15187094; 18193044; 19322194; 20562859; 22248718; 27742532; 28423511; 31291988; 32401768; |
| Motif | |
| Gene Encoded By | |
| Mass | 52,497 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=47.5 uM for MAP1LC3B {ECO:0000269|PubMed:21177865}; KM=12.4 uM for GABARAPL2 {ECO:0000269|PubMed:21177865}; |
| Metal Binding | |
| Rhea ID | RHEA:67548; RHEA:67549 |
| Cross Reference Brenda |