Interferon-induced, double-stranded RNA-activated protein kinase

Details

Name
Interferon-induced, double-stranded RNA-activated protein kinase
Synonyms
  • 2.7.11.1
  • eIF-2A protein kinase 2
  • Eukaryotic translation initiation factor 2-alpha kinase 2
  • Interferon-inducible RNA-dependent protein kinase
  • P1/eIF-2A protein kinase
  • p68 kinase
  • PKR
  • PRKR
  • Protein kinase R
  • Protein kinase RNA-activated
  • Tyrosine-protein kinase EIF2AK2
Gene Name
EIF2AK2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051746|Interferon-induced, double-stranded RNA-activated protein kinase
MAGDLSAGFFMEELNTYRQKQGVVLKYQELPNSGPPHDRRFTFQVIIDGREFPEGEGRSK
KEAKNAAAKLAVEILNKEKKAVSPLLLTTTNSSEGLSMGNYIGLINRIAQKKRLTVNYEQ
CASGVHGPEGFHYKCKMGQKEYSIGTGSTKQEAKQLAAKLAYLQILSEETSVKSDYLSSG
SFATTCESQSNSLVTSTLASESSSEGDFSADTSEINSNSDSLNSSSLLMNGLRNNQRKAK
RSLAPRFDLPDMKETKYTVDKRFGMDFKEIELIGSGGFGQVFKAKHRIDGKTYVIKRVKY
NNEKAEREVKALAKLDHVNIVHYNGCWDGFDYDPETSDDSLESSDYDPENSKNSSRSKTK
CLFIQMEFCDKGTLEQWIEKRRGEKLDKVLALELFEQITKGVDYIHSKKLIHRDLKPSNI
FLVDTKQVKIGDFGLVTSLKNDGKRTRSKGTLRYMSPEQISSQDYGKEVDLYALGLILAE
LLHVCDTAFETSKFFTDLRDGIISDIFDKKEKTLLQKLLSKKPEDRPNTSEILRTLTVWK
KSPEKNERHTC
Number of residues
551
Molecular Weight
62093.71
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / double-stranded RNA binding / eukaryotic translation initiation factor 2alpha kinase activity / identical protein binding / non-membrane spanning protein tyrosine kinase activity / protein kinase activity / protein phosphatase regulator activity / protein serine/threonine kinase activity / RNA binding
Processes
activation of MAPKK activity / cellular response to amino acid starvation / defense response to virus / endoplasmic reticulum unfolded protein response / evasion or tolerance by virus of host immune response / innate immune response / negative regulation of apoptotic process / negative regulation of cell proliferation / negative regulation of osteoblast proliferation / negative regulation of translation / negative regulation of viral genome replication / positive regulation of chemokine production / positive regulation of cytokine production / positive regulation of NF-kappaB transcription factor activity / positive regulation of NIK/NF-kappaB signaling / positive regulation of stress-activated MAPK cascade / protein autophosphorylation / protein phosphorylation / regulation of hematopoietic progenitor cell differentiation / regulation of hematopoietic stem cell differentiation / regulation of hematopoietic stem cell proliferation / regulation of NLRP3 inflammasome complex assembly / response to interferon-alpha / response to toxic substance / response to virus / transcription, DNA-templated / translation
Components
cytoplasm / cytosol / membrane / nucleus / perinuclear region of cytoplasm / ribosome
General Function
IFN-induced dsRNA-dependent serine/threonine-protein kinase which plays a key role in the innate immune response to viral infection and is also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation. 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). Inhibits viral replication via phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (EIF2S1), this phosphorylation impairs the recycling of EIF2S1 between successive rounds of initiation leading to inhibition of translation which eventually results in shutdown of cellular and viral protein synthesis. Also phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1 and the HHV-1 viral protein US11. 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 proteosomal degradation. 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 proinflammatory cytokines and IFNs. 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. Can act as both a positive and negative regulator of the insulin signaling pathway (ISP). 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). Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes. Can trigger apoptosis via FADD-mediated activation of CASP8. Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin.
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0051747|Interferon-induced, double-stranded RNA-activated protein kinase (EIF2AK2)
ATGGCTGGTGATCTTTCAGCAGGTTTCTTCATGGAGGAACTTAATACATACCGTCAGAAG
CAGGGAGTAGTACTTAAATATCAAGAACTGCCTAATTCAGGACCTCCACATGATAGGAGG
TTTACATTTCAAGTTATAATAGATGGAAGAGAATTTCCAGAAGGTGAAGGTAGATCAAAG
AAGGAAGCAAAAAATGCCGCAGCCAAATTAGCTGTTGAGATACTTAATAAGGAAAAGAAG
GCAGTTAGTCCTTTATTATTGACAACAACGAATTCTTCAGAAGGATTATCCATGGGGAAT
TACATAGGCCTTATCAATAGAATTGCCCAGAAGAAAAGACTAACTGTAAATTATGAACAG
TGTGCATCGGGGGTGCATGGGCCAGAAGGATTTCATTATAAATGCAAAATGGGACAGAAA
GAATATAGTATTGGTACAGGTTCTACTAAACAGGAAGCAAAACAATTGGCCGCTAAACTT
GCATATCTTCAGATATTATCAGAAGAAACCTCAGTGAAATCTGACTACCTGTCCTCTGGT
TCTTTTGCTACTACGTGTGAGTCCCAAAGCAACTCTTTAGTGACCAGCACACTCGCTTCT
GAATCATCATCTGAAGGTGACTTCTCAGCAGATACATCAGAGATAAATTCTAACAGTGAC
AGTTTAAACAGTTCTTCGTTGCTTATGAATGGTCTCAGAAATAATCAAAGGAAGGCAAAA
AGATCTTTGGCACCCAGATTTGACCTTCCTGACATGAAAGAAACAAAGTATACTGTGGAC
AAGAGGTTTGGCATGGATTTTAAAGAAATAGAATTAATTGGCTCAGGTGGATTTGGCCAA
GTTTTCAAAGCAAAACACAGAATTGACGGAAAGACTTACGTTATTAAACGTGTTAAATAT
AATAACGAGAAGGCGGAGCGTGAAGTAAAAGCATTGGCAAAACTTGATCATGTAAATATT
GTTCACTACAATGGCTGTTGGGATGGATTTGATTATGATCCTGAGACCAGTGATGATTCT
CTTGAGAGCAGTGATTATGATCCTGAGAACAGCAAAAATAGTTCAAGGTCAAAGACTAAG
TGCCTTTTCATCCAAATGGAATTCTGTGATAAAGGGACCTTGGAACAATGGATTGAAAAA
AGAAGAGGCGAGAAACTAGACAAAGTTTTGGCTTTGGAACTCTTTGAACAAATAACAAAA
GGGGTGGATTATATACATTCAAAAAAATTAATTCATAGAGATCTTAAGCCAAGTAATATA
TTCTTAGTAGATACAAAACAAGTAAAGATTGGAGACTTTGGACTTGTAACATCTCTGAAA
AATGATGGAAAGCGAACAAGGAGTAAGGGAACTTTGCGATACATGAGCCCAGAACAGATT
TCTTCGCAAGACTATGGAAAGGAAGTGGACCTCTACGCTTTGGGGCTAATTCTTGCTGAA
CTTCTTCATGTATGTGACACTGCTTTTGAAACATCAAAGTTTTTCACAGACCTACGGGAT
GGCATCATCTCAGATATATTTGATAAAAAAGAAAAAACTCTTCTACAGAAATTACTCTCA
AAGAAACCTGAGGATCGACCTAACACATCTGAAATACTAAGGACCTTGACTGTGTGGAAG
AAAAGCCCAGAGAAAAATGAACGACACACATGTTAG
Chromosome Location
2
Locus
2p22.2
External Identifiers
ResourceLink
UniProtKB IDP19525
UniProtKB Entry NameE2AK2_HUMAN
HGNC IDHGNC:9437
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB00328Indomethacinapproved, investigationalunknowninducerDetails
DB07995H-89experimentalunknowninhibitorDetails