Eukaryotic translation initiation factor 2-alpha kinase 3 (EC 2.7.11.1) (PRKR-like endoplasmic reticulum kinase) (Pancreatic eIF2-alpha kinase) (HsPEK)
1_MERAI 6_ SPGLL 11_ VRALL 16_ LLLLL 21_ LGLAA 26_ RTVAA 31_ GRARG 36_ LPAPT 41_ AEAAF 46_ GLGAA 51_ AAPTS 56_ ATRVP 61_ AAGAV 66_ AAAEV 71_ TVEDA 76_ EALPA 81_ AAGEQ 86_ EPRGP 91_ EPDDE 96_ TELRP 101_ RGRSL 106_ VIIST 111_ LDGRI 116_ AALDP 121_ ENHGK 126_ KQWDL 131_ DVGSG 136_ SLVSS 141_ SLSKP 146_ EVFGN 151_ KMIIP 156_ SLDGA 161_ LFQWD 166_ QDRES 171_ METVP 176_ FTVES 181_ LLESS 186_ YKFGD 191_ DVVLV 196_ GGKSL 201_ TTYGL 206_ SAYSG 211_ KVRYI 216_ CSALG 221_ CRQWD 226_ SDEME 231_ QEEDI 236_ LLLQR 241_ TQKTV 246_ RAVGP 251_ RSGNE 256_ KWNFS 261_ VGHFE 266_ LRYIP 271_ DMETR 276_ AGFIE 281_ STFKP 286_ NENTE 291_ ESKII 296_ SDVEE 301_ QEAAI 306_ MDIVI 311_ KVSVA 316_ DWKVM 321_ AFSKK 326_ GGHLE 331_ WEYQF 336_ CTPIA 341_ SAWLL 346_ KDGKV 351_ IPISL 356_ FDDTS 361_ YTSND 366_ DVLED 371_ EEDIV 376_ EAARG 381_ ATENS 386_ VYLGM 391_ YRGQL 396_ YLQSS 401_ VRISE 406_ KFPSS 411_ PKALE 416_ SVTNE 421_ NAIIP 426_ LPTIK 431_ WKPLI 436_ HSPSR 441_ TPVLV 446_ GSDEF 451_ DKCLS 456_ NDKFS 461_ HEEYS 466_ NGALS 471_ ILQYP 476_ YDNGY 481_ YLPYY 486_ KRERN 491_ KRSTQ 496_ ITVRF 501_ LDNPH 506_ YNKNI 511_ RKKDP 516_ VLLLH 521_ WWKEI 526_ VATIL 531_ FCIIA 536_ TTFIV 541_ RRLFH 546_ PHPHR 551_ QRKES 556_ ETQCQ 561_ TENKY 566_ DSVSG 571_ EANDS 576_ SWNDI 581_ KNSGY 586_ ISRYL 591_ TDFEP 596_ IQCLG 601_ RGGFG 606_ VVFEA 611_ KNKVD 616_ DCNYA 621_ IKRIR 626_ LPNRE 631_ LAREK 636_ VMREV 641_ KALAK 646_ LEHPG 651_ IVRYF 656_ NAWLE 661_ APPEK 666_ WQEKM 671_ DEIWL 676_ KDEST 681_ DWPLS 686_ SPSPM 691_ DAPSV 696_ KIRRM 701_ DPFAT 706_ KEHIE 711_ IIAPS 716_ PQRSR 721_ SFSVG 726_ ISCDQ 731_ TSSSE 736_ SQFSP 741_ LEFSG 746_ MDHED 751_ ISESV 756_ DAAYN 761_ LQDSC 766_ LTDCD 771_ VEDGT 776_ MDGND 781_ EGHSF 786_ ELCPS 791_ EASPY 796_ VRSRE 801_ RTSSS 806_ IVFED 811_ SGCDN 816_ ASSKE 821_ EPKTN 826_ RLHIG 831_ NHCAN 836_ KLTAF 841_ KPTSS 846_ KSSSE 851_ ATLSI 856_ SPPRP 861_ TTLSL 866_ DLTKN 871_ TTEKL 876_ QPSSP 881_ KVYLY 886_ IQMQL 891_ CRKEN 896_ LKDWM 901_ NGRCT 906_ IEERE 911_ RSVCL 916_ HIFLQ 921_ IAEAV 926_ EFLHS 931_ KGLMH 936_ RDLKP 941_ SNIFF 946_ TMDDV 951_ VKVGD 956_ FGLVT 961_ AMDQD 966_ EEEQT 971_ VLTPM 976_ PAYAR 981_ HTGQV 986_ GTKLY 991_ MSPEQ 996_ IHGNS 1001_ YSHKV 1006_ DIFSL 1011_ GLILF 1016_ ELLYP 1021_ FSTQM 1026_ ERVRT 1031_ LTDVR 1036_ NLKFP 1041_ PLFTQ 1046_ KYPCE 1051_ YVMVQ 1056_ DMLSP 1061_ SPMER 1066_ PEAIN 1071_ IIENA 1076_ VFEDL 1081_ DFPGK 1086_ TVLRQ 1091_ RSRSL 1096_ SSSGT 1101_ KHSRQ 1106_ SNNSH 1111_SPLPS
1: Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to various stress, such as unfolded protein response (UPR) (PubMed:10026192, PubMed:10677345, PubMed:11907036, PubMed:12086964, PubMed:25925385, PubMed:31023583). Key effector of the integrated stress response (ISR) to unfolded proteins: EIF2AK3/PERK specifically recognizes and binds misfolded proteins, leading to its activation and EIF2S1/eIF-2-alpha phosphorylation (PubMed:10677345, PubMed:27917829, PubMed:31023583). EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activators ATF4 and QRICH1, and hence allowing ATF4- and QRICH1-mediated reprogramming (PubMed:10026192, PubMed:10677345, PubMed:31023583, PubMed:33384352). The EIF2AK3/PERK-mediated unfolded protein response increases mitochondrial oxidative phosphorylation by promoting ATF4-mediated expression of COX7A2L/SCAF1, thereby increasing formation of respiratory chain supercomplexes (PubMed:31023583). In contrast to most subcellular compartments, mitochondria are protected from the EIF2AK3/PERK-mediated unfolded protein response due to EIF2AK3/PERK inhibition by ATAD3A at mitochondria-endoplasmic reticulum contact sites (PubMed:39116259). In addition to EIF2S1/eIF-2-alpha, also phosphorylates NFE2L2/NRF2 in response to stress, promoting release of NFE2L2/NRF2 from the BCR(KEAP1) complex, leading to nuclear accumulation and activation of NFE2L2/NRF2 (By similarity). Serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin-D1 (CCND1) (By similarity). Involved in control of mitochondrial morphology and function (By similarity)