| IED ID | IndEnz0002014261 |
| Enzyme Type ID | protease014261 |
| Protein Name |
DAP3-binding cell death enhancer 1 DAP3-binding cell death enhancer 1, long form DELE1 L Death ligand signal enhancer Cleaved into: DAP3-binding cell death enhancer 1 short form DELE1 S S-DELE1 |
| Gene Name | DELE1 DELE KIAA0141 |
| 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 | MWRLPGLLGRALPRTLGPSLWRVTPKSTSPDGPQTTSSTLLVPVPNLDRSGPHGPGTSGGPRSHGWKDAFQWMSSRVSPNTLWDAISWGTLAVLALQLARQIHFQASLPAGPQRVEHCSWHSPLDRFFSSPLWHPCSSLRQHILPSPDGPAPRHTGLREPRLGQEEASAQPRNFSHNSLRGARPQDPSEEGPGDFGFLHASSSIESEAKPAQPQPTGEKEQDKSKTLSLEEAVTSIQQLFQLSVSIAFNFLGTENMKSGDHTAAFSYFQKAAARGYSKAQYNAGLCHEHGRGTPRDISKAVLYYQLAASQGHSLAQYRYARCLLRDPASSWNPERQRAVSLLKQAADSGLREAQAFLGVLFTKEPYLDEQRAVKYLWLAANNGDSQSRYHLGICYEKGLGVQRNLGEALRCYQQSAALGNEAAQERLRALFSMGAAAPGPSDLTVTGLKSFSSPSLCSLNTLLAGTSRLPHASSTGNLGLLCRSGHLGASLEASSRAIPPHPYPLERSVVRLGFG |
| Enzyme Length | 515 |
| Uniprot Accession Number | Q14154 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: [DAP3-binding cell death enhancer 1]: Key activator of the integrated stress response (ISR) following mitochondrial stress (PubMed:32132706, PubMed:32132707). In response to mitochondrial stress, cleaved by the protease OMA1, generating the DAP3-binding cell death enhancer 1 short form (DELE1(S) or S-DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to trigger the ISR (PubMed:32132706, PubMed:32132707). Essential for the induction of death receptor-mediated apoptosis through the regulation of caspase activation (PubMed:20563667). {ECO:0000269|PubMed:20563667, ECO:0000269|PubMed:32132706, ECO:0000269|PubMed:32132707}.; FUNCTION: [DAP3-binding cell death enhancer 1 short form]: Protein kinase activator generated by protein cleavage in response to mitochondrial stress, which accumulates in the cytosol and specifically binds to and activates the protein kinase activity of EIF2AK1/HRI (PubMed:32132706, PubMed:32132707). It thereby activates the integrated stress response (ISR): EIF2AK1/HRI activation promotes eIF-2-alpha (EIF2S1) phosphorylation, leading to a decrease in global protein synthesis and the induction of selected genes, including the transcription factor ATF4, the master transcriptional regulator of the ISR (PubMed:32132706, PubMed:32132707). {ECO:0000269|PubMed:32132706, ECO:0000269|PubMed:32132707}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Chain (2); Compositional bias (2); Erroneous initiation (1); Natural variant (5); Region (2); Repeat (7); Site (1); Transit peptide (1) |
| Keywords | Apoptosis;Cytoplasm;Membrane;Mitochondrion;Mitochondrion inner membrane;Reference proteome;Repeat;TPR repeat;Transit peptide |
| Interact With | P24539; O43186; P50570-2; P42858; O14901; Q13449; P28331-2; Q9BVL2; O14656-2 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [DAP3-binding cell death enhancer 1]: Mitochondrion {ECO:0000269|PubMed:20563667, ECO:0000269|PubMed:32132706, ECO:0000269|PubMed:32132707}. Mitochondrion inner membrane {ECO:0000269|PubMed:32132707}. Note=Associates with the mitochondrion inner membrane in response to mitochondrial stress, leading to its proteolytic processing by OMA1, and generation of the AP3-binding cell death enhancer 1 short form (DELE1(S) or S-DELE1). {ECO:0000269|PubMed:32132707}.; SUBCELLULAR LOCATION: [DAP3-binding cell death enhancer 1 short form]: Cytoplasm, cytosol {ECO:0000269|PubMed:32132706, ECO:0000269|PubMed:32132707}. Note=This short form is generated by proteolytic processing by OMA1 in response to mitochondrial stress, leading to translocation to the cytosol. {ECO:0000269|PubMed:32132706, ECO:0000269|PubMed:32132707}. |
| Modified Residue | |
| Post Translational Modification | PTM: [DAP3-binding cell death enhancer 1]: Cleaved by OMA1 in response to mitochondrial stress, generating the DAP3-binding cell death enhancer 1 short form (DELE1(S) or S-DELE1) that accumulates in the cytosol and activates the protein kinase activity of EIF2AK1/HRI (PubMed:32132706, PubMed:32132707). Protein cleavage by OMA1 can take place at different positions, and apparently does not require a specific sequence motif (PubMed:32132707). {ECO:0000269|PubMed:32132706, ECO:0000269|PubMed:32132707}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 20711500; 20877624; 24705354; 25416956; |
| Motif | |
| Gene Encoded By | |
| Mass | 55,920 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |