DELE1_HUMAN
ID DELE1_HUMAN Reviewed; 515 AA.
AC Q14154; Q969R4; Q96EU9;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=DAP3-binding cell death enhancer 1 {ECO:0000305};
DE AltName: Full=DAP3-binding cell death enhancer 1, long form {ECO:0000303|PubMed:32132707};
DE Short=DELE1(L) {ECO:0000303|PubMed:32132707};
DE AltName: Full=Death ligand signal enhancer {ECO:0000303|PubMed:20563667};
DE Contains:
DE RecName: Full=DAP3-binding cell death enhancer 1 short form {ECO:0000303|PubMed:32132707};
DE Short=DELE1(S) {ECO:0000303|PubMed:32132707};
DE Short=S-DELE1 {ECO:0000303|PubMed:32132706};
DE Flags: Precursor;
GN Name=DELE1 {ECO:0000312|HGNC:HGNC:28969};
GN Synonyms=DELE {ECO:0000303|PubMed:20563667},
GN KIAA0141 {ECO:0000303|PubMed:8590280};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Bone marrow;
RX PubMed=8590280; DOI=10.1093/dnares/2.4.167;
RA Nagase T., Seki N., Tanaka A., Ishikawa K., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. IV. The
RT coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 2:167-174(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS THR-95 AND THR-247.
RC TISSUE=Brain, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH DAP3.
RX PubMed=20563667; DOI=10.1007/s10495-010-0519-3;
RA Harada T., Iwai A., Miyazaki T.;
RT "Identification of DELE, a novel DAP3-binding protein which is crucial for
RT death receptor-mediated apoptosis induction.";
RL Apoptosis 15:1247-1255(2010).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE, DOMAIN, AND
RP INTERACTION WITH EIF2AK1.
RX PubMed=32132706; DOI=10.1038/s41586-020-2076-4;
RA Fessler E., Eckl E.M., Schmitt S., Mancilla I.A., Meyer-Bender M.F.,
RA Hanf M., Philippou-Massier J., Krebs S., Zischka H., Jae L.T.;
RT "A pathway coordinated by DELE1 relays mitochondrial stress to the
RT cytosol.";
RL Nature 579:433-437(2020).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE, DOMAIN, AND
RP INTERACTION WITH EIF2AK1.
RX PubMed=32132707; DOI=10.1038/s41586-020-2078-2;
RA Guo X., Aviles G., Liu Y., Tian R., Unger B.A., Lin Y.T., Wiita A.P.,
RA Xu K., Correia M.A., Kampmann M.;
RT "Mitochondrial stress is relayed to the cytosol by an OMA1-DELE1-HRI
RT pathway.";
RL Nature 579:427-432(2020).
CC -!- FUNCTION: [DAP3-binding cell death enhancer 1]: Key activator of the
CC integrated stress response (ISR) following mitochondrial stress
CC (PubMed:32132706, PubMed:32132707). In response to mitochondrial
CC stress, cleaved by the protease OMA1, generating the DAP3-binding cell
CC death enhancer 1 short form (DELE1(S) or S-DELE1), which translocates
CC to the cytosol and activates EIF2AK1/HRI to trigger the ISR
CC (PubMed:32132706, PubMed:32132707). Essential for the induction of
CC death receptor-mediated apoptosis through the regulation of caspase
CC activation (PubMed:20563667). {ECO:0000269|PubMed:20563667,
CC ECO:0000269|PubMed:32132706, ECO:0000269|PubMed:32132707}.
CC -!- FUNCTION: [DAP3-binding cell death enhancer 1 short form]: Protein
CC kinase activator generated by protein cleavage in response to
CC mitochondrial stress, which accumulates in the cytosol and specifically
CC binds to and activates the protein kinase activity of EIF2AK1/HRI
CC (PubMed:32132706, PubMed:32132707). It thereby activates the integrated
CC stress response (ISR): EIF2AK1/HRI activation promotes eIF-2-alpha
CC (EIF2S1) phosphorylation, leading to a decrease in global protein
CC synthesis and the induction of selected genes, including the
CC transcription factor ATF4, the master transcriptional regulator of the
CC ISR (PubMed:32132706, PubMed:32132707). {ECO:0000269|PubMed:32132706,
CC ECO:0000269|PubMed:32132707}.
CC -!- SUBUNIT: Interacts with DAP3. {ECO:0000269|PubMed:20563667}.
CC -!- SUBUNIT: [DAP3-binding cell death enhancer 1 short form]: Interacts
CC (via TPR repeats) with EIF2AK1/HRI; activating the protein kinase
CC activity of EIF2AK1/HRI, thereby promoting the integrated stress
CC response (ISR). {ECO:0000269|PubMed:32132706,
CC ECO:0000269|PubMed:32132707}.
CC -!- INTERACTION:
CC Q14154; P24539: ATP5PB; NbExp=3; IntAct=EBI-2805660, EBI-1044810;
CC Q14154; O43186: CRX; NbExp=3; IntAct=EBI-2805660, EBI-748171;
CC Q14154; P50570-2: DNM2; NbExp=3; IntAct=EBI-2805660, EBI-10968534;
CC Q14154; P42858: HTT; NbExp=18; IntAct=EBI-2805660, EBI-466029;
CC Q14154; O14901: KLF11; NbExp=3; IntAct=EBI-2805660, EBI-948266;
CC Q14154; Q13449: LSAMP; NbExp=3; IntAct=EBI-2805660, EBI-4314821;
CC Q14154; P28331-2: NDUFS1; NbExp=3; IntAct=EBI-2805660, EBI-6190702;
CC Q14154; Q9BVL2: NUP58; NbExp=3; IntAct=EBI-2805660, EBI-2811583;
CC Q14154; O14656-2: TOR1A; NbExp=3; IntAct=EBI-2805660, EBI-25847109;
CC -!- SUBCELLULAR LOCATION: [DAP3-binding cell death enhancer 1]:
CC Mitochondrion {ECO:0000269|PubMed:20563667,
CC ECO:0000269|PubMed:32132706, ECO:0000269|PubMed:32132707}.
CC Mitochondrion inner membrane {ECO:0000269|PubMed:32132707}.
CC Note=Associates with the mitochondrion inner membrane in response to
CC mitochondrial stress, leading to its proteolytic processing by OMA1,
CC and generation of the AP3-binding cell death enhancer 1 short form
CC (DELE1(S) or S-DELE1). {ECO:0000269|PubMed:32132707}.
CC -!- SUBCELLULAR LOCATION: [DAP3-binding cell death enhancer 1 short form]:
CC Cytoplasm, cytosol {ECO:0000269|PubMed:32132706,
CC ECO:0000269|PubMed:32132707}. Note=This short form is generated by
CC proteolytic processing by OMA1 in response to mitochondrial stress,
CC leading to translocation to the cytosol. {ECO:0000269|PubMed:32132706,
CC ECO:0000269|PubMed:32132707}.
CC -!- TISSUE SPECIFICITY: Detected in liver, skeletal muscle, kidney,
CC pancreas, spleen, thyroid, testis, ovary, small intestine and colon.
CC {ECO:0000269|PubMed:8590280}.
CC -!- DOMAIN: [DAP3-binding cell death enhancer 1 short form]: The TPR
CC repeats bind to and activate EIF2AK1/HRI. {ECO:0000269|PubMed:32132706,
CC ECO:0000269|PubMed:32132707}.
CC -!- PTM: [DAP3-binding cell death enhancer 1]: Cleaved by OMA1 in response
CC to mitochondrial stress, generating the DAP3-binding cell death
CC enhancer 1 short form (DELE1(S) or S-DELE1) that accumulates in the
CC cytosol and activates the protein kinase activity of EIF2AK1/HRI
CC (PubMed:32132706, PubMed:32132707). Protein cleavage by OMA1 can take
CC place at different positions, and apparently does not require a
CC specific sequence motif (PubMed:32132707).
CC {ECO:0000269|PubMed:32132706, ECO:0000269|PubMed:32132707}.
CC -!- SIMILARITY: Belongs to the DELE1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA09490.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Stress - Issue 230 of
CC November 2020;
CC URL="https://web.expasy.org/spotlight/back_issues/230/";
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DR EMBL; D50931; BAA09490.2; ALT_INIT; mRNA.
DR EMBL; BC007855; AAH07855.1; -; mRNA.
DR EMBL; BC010452; AAH10452.1; -; mRNA.
DR EMBL; BC011269; AAH11269.1; -; mRNA.
DR EMBL; BC011926; AAH11926.1; -; mRNA.
DR CCDS; CCDS4268.1; -.
DR RefSeq; NP_001136075.1; NM_001142603.2.
DR RefSeq; NP_055588.3; NM_014773.4.
DR RefSeq; XP_005268604.1; XM_005268547.3.
DR RefSeq; XP_005268605.1; XM_005268548.3.
DR AlphaFoldDB; Q14154; -.
DR SMR; Q14154; -.
DR BioGRID; 115151; 13.
DR IntAct; Q14154; 16.
DR STRING; 9606.ENSP00000396225; -.
DR iPTMnet; Q14154; -.
DR PhosphoSitePlus; Q14154; -.
DR BioMuta; KIAA0141; -.
DR DMDM; 116242599; -.
DR MassIVE; Q14154; -.
DR MaxQB; Q14154; -.
DR PaxDb; Q14154; -.
DR PeptideAtlas; Q14154; -.
DR PRIDE; Q14154; -.
DR ProteomicsDB; 59857; -.
DR Antibodypedia; 27388; 66 antibodies from 25 providers.
DR DNASU; 9812; -.
DR Ensembl; ENST00000194118.8; ENSP00000194118.4; ENSG00000081791.9.
DR Ensembl; ENST00000432126.7; ENSP00000396225.2; ENSG00000081791.9.
DR GeneID; 9812; -.
DR KEGG; hsa:9812; -.
DR MANE-Select; ENST00000432126.7; ENSP00000396225.2; NM_014773.5; NP_055588.3.
DR UCSC; uc003lls.4; human.
DR CTD; 9812; -.
DR DisGeNET; 9812; -.
DR GeneCards; DELE1; -.
DR HGNC; HGNC:28969; DELE1.
DR HPA; ENSG00000081791; Low tissue specificity.
DR MIM; 615741; gene.
DR neXtProt; NX_Q14154; -.
DR OpenTargets; ENSG00000081791; -.
DR PharmGKB; PA134992099; -.
DR VEuPathDB; HostDB:ENSG00000081791; -.
DR eggNOG; KOG1550; Eukaryota.
DR GeneTree; ENSGT00390000002137; -.
DR HOGENOM; CLU_039734_0_0_1; -.
DR InParanoid; Q14154; -.
DR OMA; HAWSTGN; -.
DR OrthoDB; 1039341at2759; -.
DR PhylomeDB; Q14154; -.
DR TreeFam; TF329996; -.
DR PathwayCommons; Q14154; -.
DR SignaLink; Q14154; -.
DR BioGRID-ORCS; 9812; 18 hits in 1082 CRISPR screens.
DR ChiTaRS; KIAA0141; human.
DR GenomeRNAi; 9812; -.
DR Pharos; Q14154; Tbio.
DR PRO; PR:Q14154; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q14154; protein.
DR Bgee; ENSG00000081791; Expressed in right hemisphere of cerebellum and 200 other tissues.
DR ExpressionAtlas; Q14154; baseline and differential.
DR Genevisible; Q14154; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; IDA:UniProtKB.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IDA:UniProtKB.
DR GO; GO:0140468; P:HRI-mediated signaling; IDA:UniProtKB.
DR GO; GO:0140467; P:integrated stress response signaling; IDA:UniProtKB.
DR GO; GO:0043281; P:regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
DR Gene3D; 1.25.40.10; -; 1.
DR InterPro; IPR006597; Sel1-like.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR Pfam; PF08238; Sel1; 5.
DR SMART; SM00671; SEL1; 5.
PE 1: Evidence at protein level;
KW Apoptosis; Cytoplasm; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Reference proteome; Repeat; TPR repeat;
KW Transit peptide.
FT TRANSIT 1..101
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 102..515
FT /note="DAP3-binding cell death enhancer 1"
FT /id="PRO_0000050721"
FT CHAIN ?143..515
FT /note="DAP3-binding cell death enhancer 1 short form"
FT /evidence="ECO:0000305|PubMed:32132707"
FT /id="PRO_0000450308"
FT REPEAT 213..244
FT /note="TPR 1"
FT /evidence="ECO:0000255"
FT REPEAT 245..277
FT /note="TPR 2"
FT /evidence="ECO:0000255"
FT REPEAT 278..312
FT /note="TPR 3"
FT /evidence="ECO:0000255"
FT REPEAT 313..350
FT /note="TPR 4"
FT /evidence="ECO:0000255"
FT REPEAT 351..384
FT /note="TPR 5"
FT /evidence="ECO:0000255"
FT REPEAT 385..422
FT /note="TPR 6"
FT /evidence="ECO:0000255"
FT REPEAT 472..504
FT /note="TPR 7"
FT /evidence="ECO:0000255"
FT REGION 19..65
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 144..226
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 21..44
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 168..182
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 142..143
FT /note="Cleavage; by OMA1"
FT /evidence="ECO:0000305|PubMed:32132707"
FT VARIANT 60
FT /note="G -> D (in dbSNP:rs34438707)"
FT /id="VAR_055940"
FT VARIANT 95
FT /note="A -> T (in dbSNP:rs17850821)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_028197"
FT VARIANT 128
FT /note="F -> L (in dbSNP:rs10036567)"
FT /id="VAR_018272"
FT VARIANT 247
FT /note="A -> T (in dbSNP:rs351260)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_018273"
FT VARIANT 468
FT /note="R -> C (in dbSNP:rs10056676)"
FT /id="VAR_028198"
SQ SEQUENCE 515 AA; 55920 MW; 80818A18B6253BA8 CRC64;
MWRLPGLLGR ALPRTLGPSL WRVTPKSTSP DGPQTTSSTL LVPVPNLDRS GPHGPGTSGG
PRSHGWKDAF QWMSSRVSPN TLWDAISWGT LAVLALQLAR QIHFQASLPA GPQRVEHCSW
HSPLDRFFSS PLWHPCSSLR QHILPSPDGP APRHTGLREP RLGQEEASAQ PRNFSHNSLR
GARPQDPSEE GPGDFGFLHA SSSIESEAKP AQPQPTGEKE QDKSKTLSLE EAVTSIQQLF
QLSVSIAFNF LGTENMKSGD HTAAFSYFQK AAARGYSKAQ YNAGLCHEHG RGTPRDISKA
VLYYQLAASQ GHSLAQYRYA RCLLRDPASS WNPERQRAVS LLKQAADSGL REAQAFLGVL
FTKEPYLDEQ RAVKYLWLAA NNGDSQSRYH LGICYEKGLG VQRNLGEALR CYQQSAALGN
EAAQERLRAL FSMGAAAPGP SDLTVTGLKS FSSPSLCSLN TLLAGTSRLP HASSTGNLGL
LCRSGHLGAS LEASSRAIPP HPYPLERSVV RLGFG
