Interferon-induced, double-stranded RNA-activated protein kinase (EC 2.7.11.1) (Eukaryotic translation initiation factor 2-alpha kinase 2) (eIF-2A protein kinase 2) (Interferon-inducible RNA-dependent protein kinase) (P1/eIF-2A protein kinase) (Protein kinase RNA-activated) (PKR) (Protein kinase R) (Tyrosine-protein kinase EIF2AK2) (EC 2.7.10.2) (p68 kinase)
1_MAGDL 6_ SAGFF 11_ MEELN 16_ TYRQK 21_ QGVVL 26_ KYQEL 31_ PNSGP 36_ PHDRR 41_ FTFQV 46_ IIDGR 51_ EFPEG 56_ EGRSK 61_ KEAKN 66_ AAAKL 71_ AVEIL 76_ NKEKK 81_ AVSPL 86_ LLTTT 91_ NSSEG 96_ LSMGN 101_ YIGLI 106_ NRIAQ 111_ KKRLT 116_ VNYEQ 121_ CASGV 126_ HGPEG 131_ FHYKC 136_ KMGQK 141_ EYSIG 146_ TGSTK 151_ QEAKQ 156_ LAAKL 161_ AYLQI 166_ LSEET 171_ SVKSD 176_ YLSSG 181_ SFATT 186_ CESQS 191_ NSLVT 196_ STLAS 201_ ESSSE 206_ GDFSA 211_ DTSEI 216_ NSNSD 221_ SLNSS 226_ SLLMN 231_ GLRNN 236_ QRKAK 241_ RSLAP 246_ RFDLP 251_ DMKET 256_ KYTVD 261_ KRFGM 266_ DFKEI 271_ ELIGS 276_ GGFGQ 281_ VFKAK 286_ HRIDG 291_ KTYVI 296_ KRVKY 301_ NNEKA 306_ EREVK 311_ ALAKL 316_ DHVNI 321_ VHYNG 326_ CWDGF 331_ DYDPE 336_ TSDDS 341_ LESSD 346_ YDPEN 351_ SKNSS 356_ RSKTK 361_ CLFIQ 366_ MEFCD 371_ KGTLE 376_ QWIEK 381_ RRGEK 386_ LDKVL 391_ ALELF 396_ EQITK 401_ GVDYI 406_ HSKKL 411_ IHRDL 416_ KPSNI 421_ FLVDT 426_ KQVKI 431_ GDFGL 436_ VTSLK 441_ NDGKR 446_ TRSKG 451_ TLRYM 456_ SPEQI 461_ SSQDY 466_ GKEVD 471_ LYALG 476_ LILAE 481_ LLHVC 486_ DTAFE 491_ TSKFF 496_ TDLRD 501_ GIISD 506_ IFDKK 511_ EKTLL 516_ QKLLS 521_ KKPED 526_ RPNTS 531_ EILRT 536_ LTVWK 541_ KSPEK 546_NERHT
1: IFN-induced dsRNA-dependent serine/threonine-protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) and plays a key role in the innate immune response to viral infection (PubMed:18835251, PubMed:19189853, PubMed:19507191, PubMed:21072047, PubMed:21123651, PubMed:22381929, PubMed:22948139, PubMed:23229543). Inhibits viral replication via the integrated stress response (ISR): EIF2S1/eIF-2-alpha phosphorylation in response to viral infection converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, resulting to a shutdown of cellular and viral protein synthesis, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4 (PubMed:19189853, PubMed:21123651, PubMed:22948139, PubMed:23229543). Exerts its antiviral activity on a wide range of DNA and RNA viruses including hepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV) and herpes simplex virus 1 (HHV-1) (PubMed:11836380, PubMed:19189853, PubMed:19840259, PubMed:20171114, PubMed:21710204, PubMed:23115276, PubMed:23399035). Also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation: phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1 and the HHV-1 viral protein US11 (PubMed:11836380, PubMed:19229320, PubMed:22214662). In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity and phosphorylates CDK1 at 'Tyr-4' upon DNA damage, facilitating its ubiquitination and proteasomal degradation (PubMed:20395957). Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding pro-inflammatory cytokines and IFNs (PubMed:22948139, PubMed:23084476, PubMed:23372823). Activates the NF-kappa-B pathway via interaction with IKBKB and TRAF family of proteins and activates the p38 MAP kinase pathway via interaction with MAP2K6 (PubMed:10848580, PubMed:15121867, PubMed:15229216). Can act as both a positive and negative regulator of the insulin signaling pathway (ISP) (PubMed:20685959). Negatively regulates ISP by inducing the inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at 'Ser-312' and positively regulates ISP via phosphorylation of PPP2R5A which activates FOXO1, which in turn up-regulates the expression of insulin receptor substrate 2 (IRS2) (PubMed:20685959). Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes (PubMed:22801494). Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin (By similarity)