DELE1
entrez
9812
canonical
uniprot
Q14154
canonical
ensembl
ENSG00000081791
resolver
ensp
ENSP00000194118
resolver
ensp
ENSP00000396225
resolver
ensp
ENSP00000426138
resolver
ensp
ENSP00000565988
resolver
ensp
ENSP00000565989
resolver
ensp
ENSP00000565990
resolver
ensp
ENSP00000693766
resolver
ensp
ENSP00000766054
resolver
ensp
ENSP00000793839
resolver
enst
ENST00000194118
resolver
enst
ENST00000432126
resolver
enst
ENST00000895929
resolver
enst
ENST00000895930
resolver
enst
ENST00000895931
resolver
genesymbol
DELE1
resolver
genesymbol_syn
DELE
resolver
genesymbol_syn
KIAA0141
resolver
hgnc
HGNC:28969
resolver
uniprot
Q969R4
resolver
uniprot
Q96EU9
resolver
uniprot_entry
DELE1_HUMAN
resolver
uniprot_sec
Q969R4
resolver
uniprot_sec
Q96EU9
resolver
amino_acid_sequence
MWRLPGLLGRALPRTLGPSLWRVTPKSTSPDGPQTTSSTLLVPVPNLDRSGPHGPGTSGGPRSHGWKDAFQWMSSRVSPNTLWDAISWGTLAVLALQLARQIHFQASLPAGPQRVEHCSWHSPLDRFFSSPLWHPCSSLRQHILPSPDGPAPRHTGLREPRLGQEEASAQPRNFSHNSLRGARPQDPSEEGPGDFGFLHASSSIESEAKPAQPQPTGEKEQDKSKTLSLEEAVTSIQQLFQLSVSIAFNFLGTENMKSGDHTAAFSYFQKAAARGYSKAQYNAGLCHEHGRGTPRDISKAVLYYQLAASQGHSLAQYRYARCLLRDPASSWNPERQRAVSLLKQAADSGLREAQAFLGVLFTKEPYLDEQRAVKYLWLAANNGDSQSRYHLGICYEKGLGVQRNLGEALRCYQQSAALGNEAAQERLRALFSMGAAAPGPSDLTVTGLKSFSSPSLCSLNTLLAGTSRLPHASSTGNLGLLCRSGHLGASLEASSRAIPPHPYPLERSVVRLGFG
uniprot
proteins
function
FUNCTION: Protein kinase activator that acts as a key activator of the integrated stress response (ISR) following various stresses, such as iron deficiency, mitochondrial stress or mitochondrial DNA breaks (PubMed:32132706, PubMed:32132707, PubMed:35388015, PubMed:37327776, PubMed:37550454, PubMed:37832546, PubMed:38340717). Detects impaired protein import and processing in mitochondria, activating the ISR (PubMed:35388015). May also required 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, ECO:0000269|PubMed:35388015, ECO:0000269|PubMed:37327776, ECO:0000269|PubMed:37550454, ECO:0000269|PubMed:37832546, ECO:0000269|PubMed:38340717}.; FUNCTION: [DAP3-binding cell death enhancer 1]: Protein kinase activator that activates the ISR in response to iron deficiency: iron deficiency impairs mitochondrial import, promoting DELE1 localization at the mitochondrial surface, where it binds and activates EIF2AK1/HRI to trigger the ISR. {ECO:0000269|PubMed:37327776}.; 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, PubMed:37327776, PubMed:37550454, PubMed:37832546, PubMed:38340717). 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, PubMed:37327776, PubMed:37550454, PubMed:37832546). Also acts as an activator of PRKN-independent mitophagy: activates the protein kinase activity of EIF2AK1/HRI in response to mitochondrial damage, promoting eIF-2-alpha (EIF2S1) phosphorylation, leading to mitochondrial localization of EIF2S1 followed by induction of mitophagy (PubMed:38340717). {ECO:0000269|PubMed:32132706, ECO:0000269|PubMed:32132707, ECO:0000269|PubMed:37327776, ECO:0000269|PubMed:37550454, ECO:0000269|PubMed:37832546, ECO:0000269|PubMed:38340717}.
uniprot
proteins
mass_dalton
55920
uniprot
proteins
mutagenesis
MUTAGEN 239..251; /note="LFQLSVSIAFNFL->EFQESVSIAFNAE: Impaired oligomerization and ability to activate EIF2AK1/HRI."; /evidence="ECO:0000269|PubMed:37550454"; MUTAGEN 239; /note="L->E: Impaired oligomerization."; /evidence="ECO:0000269|PubMed:37550454"; MUTAGEN 242..251; /note="LSVSIAFNFL->ESVSIAFNAE: Impaired oligomerization and ability to activate EIF2AK1/HRI."; /evidence="ECO:0000269|PubMed:37550454"; MUTAGEN 242; /note="L->E: Impaired oligomerization."; /evidence="ECO:0000269|PubMed:37550454"; MUTAGEN 244; /note="Missing: Impaired oligomerization and ability to activate EIF2AK1/HRI."; /evidence="ECO:0000269|PubMed:37550454"; MUTAGEN 250..251; /note="FL->AE: Impaired oligomerization and ability to activate EIF2AK1/HRI."; /evidence="ECO:0000269|PubMed:37550454"; MUTAGEN 403; /note="R->S: Impaired oligomerization; when associated with S-431."; /evidence="ECO:0000269|PubMed:37550454"; MUTAGEN 431; /note="F->S: Impaired oligomerization; when associated with S-403."; /evidence="ECO:0000269|PubMed:37550454
uniprot
proteins
post_translational_modification
PTM: [DAP3-binding cell death enhancer 1]: Unstable protein in absence of stress: imported in the mitochondrial matrix following processing by the mitochondrial-processing peptidase (MPP), where it is degraded by LONP1 (PubMed:37327776). Stabilized in response to iron deficiency: iron deficiency impairs mitochondrial import, promoting localization at the mitochondrial surface and stabilization (PubMed:37327776). 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, PubMed:37327776, PubMed:38340717). 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, ECO:0000269|PubMed:37327776, ECO:0000269|PubMed:38340717}.; PTM: [DAP3-binding cell death enhancer 1 short form]: Ubiquitinated and degraded by the SIFI complex once the mitochondrial stress has been resolved, thereby providing stress response silencing (PubMed:38297121). Within the SIFI complex, UBR4 initiates ubiquitin chain that are further elongated or branched by KCMF1 (PubMed:38297121). {ECO:0000269|PubMed:38297121}.
uniprot
proteins
protein_family
DELE1 family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
20563667
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
32132706
uniprot
proteins
pubmed
32132707
uniprot
proteins
pubmed
35388015
uniprot
proteins
pubmed
37327776
uniprot
proteins
pubmed
37550454
uniprot
proteins
pubmed
37832546
uniprot
proteins
pubmed
38297121
uniprot
proteins
pubmed
38340717
uniprot
proteins
pubmed
8590280
uniprot
proteins
sequence_length
515
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [DAP3-binding cell death enhancer 1]: Mitochondrion {ECO:0000269|PubMed:20563667, ECO:0000269|PubMed:32132706, ECO:0000269|PubMed:32132707, ECO:0000269|PubMed:37327776}. Mitochondrion outer membrane {ECO:0000269|PubMed:37327776}. Mitochondrion inner membrane {ECO:0000269|PubMed:32132707}. Note=Imported in the mitochondrial matrix in absence of stress, leading to its degradation by LONP1 (PubMed:37327776). Localizes at the mitochondrial surface in response to iron deficiency: iron deficiency impairs mitochondrial import, promoting localization at the mitochondrial surface and stabilization (PubMed:37327776). 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) (PubMed:32132707). {ECO:0000269|PubMed:32132707, ECO:0000269|PubMed:37327776}.; 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}.
uniprot
proteins