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Details on Person UniProt:Q14154 DELE1

Class:Id	ReferenceGeneProduct:67504
_chainChangeLog	transit peptide:1-101 added on Fri February 6 2015;chain:102-515 added on Fri February 6 2015;chain:143-515 for 67504 added on Wed August 26 2020;transit peptide:1-101 for 67504 removed on Mon Feb 26 2024;transit peptide:1-23 for 67504 added on Mon Feb 26 2024;propeptide:24-101 for 67504 added on Mon Feb 26 2024
_displayName	UniProt:Q14154 DELE1
_timestamp	2024-11-03 19:40:37
chain	transit peptide:1-23 propeptide:24-101 chain:102-515 chain:143-515
checksum	80818A18B6253BA8
comment	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).FUNCTION 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.FUNCTION 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).SUBUNIT Interacts with DAP3.SUBUNIT Interacts (via TPR repeats) with EIF2AK1/HRI; activating the protein kinase activity of EIF2AK1/HRI, thereby promoting the integrated stress response (ISR).SUBUNIT Homooctamer; oligomerization is required to activate EIF2AK1/HRI (PubMed:37550454). Interacts (via TPR repeats) with EIF2AK1/HRI; activating the protein kinase activity of EIF2AK1/HRI, thereby promoting the integrated stress response (ISR) (PubMed:32132706, PubMed:32132707, PubMed:37550454, PubMed:38340717).INTERACTION 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).SUBCELLULAR LOCATION This short form is generated by proteolytic processing by OMA1 in response to mitochondrial stress, leading to translocation to the cytosol.TISSUE SPECIFICITY Detected in liver, skeletal muscle, kidney, pancreas, spleen, thyroid, testis, ovary, small intestine and colon.DOMAIN The TPR repeats bind to and activate EIF2AK1/HRI.PTM 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).PTM 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).SIMILARITY Belongs to the DELE1 family.SEQUENCE CAUTION Extended N-terminus.ONLINE INFORMATION Stress - Issue 230 of November 2020
description	recommendedName: fullName evidence="19"DAP3-binding cell death enhancer 1 alternativeName: fullName evidence="16"DAP3-binding cell death enhancer 1, long form shortName evidence="16"DELE1(L) alternativeName: fullName evidence="14"Death ligand signal enhancer component recommendedName: fullName evidence="16"DAP3-binding cell death enhancer 1 short form shortName evidence="16"DELE1(S) shortName evidence="15"S-DELE1 shortName evidence="17"cDELE1 /component
geneName	DELE1 DELE KIAA0141
identifier	Q14154
isSequenceChanged	FALSE
keyword	3D-structure Apoptosis Cytoplasm DNA damage Membrane Mitochondrion Mitochondrion inner membrane Mitochondrion outer membrane Proteomics identification Reference proteome Repeat TPR repeat Transit peptide Ubl conjugation
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03
name	DELE1
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8990642] ENSEMBL:ENSG00000081791 DELE1 [Homo sapiens]
secondaryIdentifier	DELE1_HUMAN Q969R4 Q96EU9
sequenceLength	515
species	[Species:48887] Homo sapiens
(referenceEntity)	[EntityWithAccessionedSequence:9840377] DELE1 [mitochondrial inner membrane] [Homo sapiens] [EntityWithAccessionedSequence:9840380] DELE1(143-515) [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9840386] DELE1(143-515) [mitochondrial inner membrane] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:Q14154 DELE1 (67504)