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)]
1_MWRLP 6_ GLLGR 11_ ALPRT 16_ LGPSL 21_ WRVTP 26_ KSTSP 31_ DGPQT 36_ TSSTL 41_ LVPVP 46_ NLDRS 51_ GPHGP 56_ GTSGG 61_ PRSHG 66_ WKDAF 71_ QWMSS 76_ RVSPN 81_ TLWDA 86_ ISWGT 91_ LAVLA 96_ LQLAR 101_ QIHFQ 106_ ASLPA 111_ GPQRV 116_ EHCSW 121_ HSPLD 126_ RFFSS 131_ PLWHP 136_ CSSLR 141_ QHILP 146_ SPDGP 151_ APRHT 156_ GLREP 161_ RLGQE 166_ EASAQ 171_ PRNFS 176_ HNSLR 181_ GARPQ 186_ DPSEE 191_ GPGDF 196_ GFLHA 201_ SSSIE 206_ SEAKP 211_ AQPQP 216_ TGEKE 221_ QDKSK 226_ TLSLE 231_ EAVTS 236_ IQQLF 241_ QLSVS 246_ IAFNF 251_ LGTEN 256_ MKSGD 261_ HTAAF 266_ SYFQK 271_ AAARG 276_ YSKAQ 281_ YNAGL 286_ CHEHG 291_ RGTPR 296_ DISKA 301_ VLYYQ 306_ LAASQ 311_ GHSLA 316_ QYRYA 321_ RCLLR 326_ DPASS 331_ WNPER 336_ QRAVS 341_ LLKQA 346_ ADSGL 351_ REAQA 356_ FLGVL 361_ FTKEP 366_ YLDEQ 371_ RAVKY 376_ LWLAA 381_ NNGDS 386_ QSRYH 391_ LGICY 396_ EKGLG 401_ VQRNL 406_ GEALR 411_ CYQQS 416_ AALGN 421_ EAAQE 426_ RLRAL 431_ FSMGA 436_ AAPGP 441_ SDLTV 446_ TGLKS 451_ FSSPS 456_ LCSLN 461_ TLLAG 466_ TSRLP 471_ HASST 476_ GNLGL 481_ LCRSG 486_ HLGAS 491_ LEASS 496_ RAIPP 501_ HPYPL 506_ERSVV
1: 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)
2: 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
3: 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)