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Identification
HMDB Protein ID HMDBP08840
Secondary Accession Numbers
  • 14567
Name Interferon-induced, double-stranded RNA-activated protein kinase
Synonyms
  1. Eukaryotic translation initiation factor 2-alpha kinase 2
  2. Interferon-inducible RNA-dependent protein kinase
  3. P1/eIF-2A protein kinase
  4. PKR
  5. Protein kinase RNA-activated
  6. eIF-2A protein kinase 2
  7. p68 kinase
Gene Name EIF2AK2
Protein Type Unknown
Biological Properties
General Function Involved in double-stranded RNA binding
Specific Function Following activation by double-stranded RNA in the presence of ATP, the kinase becomes autophosphorylated and can catalyze the phosphorylation of the translation initiation factor EIF2S1, which leads to an inhibition of the initiation of protein synthesis. Double-stranded RNA is generated during the course of a viral infection
Pathways Not Available
Reactions Not Available
GO Classification
Component
cell part
intracellular
Function
binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
nucleic acid binding
protein kinase activity
protein serine/threonine kinase activity
rna binding
double-stranded rna binding
Process
phosphorus metabolic process
phosphate metabolic process
metabolic process
cellular metabolic process
protein amino acid phosphorylation
phosphorylation
Cellular Location
  1. Cytoplasmic
Gene Properties
Chromosome Location Chromosome:2
Locus 2p22-p21
SNPs EIF2AK2
Gene Sequence
>1656 bp
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
Protein Properties
Number of Residues 551
Molecular Weight 62093.7
Theoretical pI 8.63
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Interferon-induced, double-stranded RNA-activated protein kinase
MAGDLSAGFFMEELNTYRQKQGVVLKYQELPNSGPPHDRRFTFQVIIDGREFPEGEGRSK
KEAKNAAAKLAVEILNKEKKAVSPLLLTTTNSSEGLSMGNYIGLINRIAQKKRLTVNYEQ
CASGVHGPEGFHYKCKMGQKEYSIGTGSTKQEAKQLAAKLAYLQILSEETSVKSDYLSSG
SFATTCESQSNSLVTSTLASESSSEGDFSADTSEINSNSDSLNSSSLLMNGLRNNQRKAK
RSLAPRFDLPDMKETKYTVDKRFGMDFKEIELIGSGGFGQVFKAKHRIDGKTYVIKRVKY
NNEKAEREVKALAKLDHVNIVHYNGCWDGFDYDPETSDDSLESSDYDPENSKNSSRSKTK
CLFIQMEFCDKGTLEQWIEKRRGEKLDKVLALELFEQITKGVDYIHSKKLIHRDLKPSNI
FLVDTKQVKIGDFGLVTSLKNDGKRTRSKGTLRYMSPEQISSQDYGKEVDLYALGLILAE
LLHVCDTAFETSKFFTDLRDGIISDIFDKKEKTLLQKLLSKKPEDRPNTSEILRTLTVWK
KSPEKNERHTC
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P19525
UniProtKB/Swiss-Prot Entry Name E2AK2_HUMAN
PDB IDs
GenBank Gene ID M35663
GeneCard ID EIF2AK2
GenAtlas ID EIF2AK2
HGNC ID HGNC:9437
References
General References
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  4. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  5. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332 ]
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  7. Langland JO, Jacobs BL: Inhibition of PKR by vaccinia virus: role of the N- and C-terminal domains of E3L. Virology. 2004 Jul 1;324(2):419-29. [PubMed:15207627 ]
  8. Meurs E, Chong K, Galabru J, Thomas NS, Kerr IM, Williams BR, Hovanessian AG: Molecular cloning and characterization of the human double-stranded RNA-activated protein kinase induced by interferon. Cell. 1990 Jul 27;62(2):379-90. [PubMed:1695551 ]
  9. Thomis DC, Doohan JP, Samuel CE: Mechanism of interferon action: cDNA structure, expression, and regulation of the interferon-induced, RNA-dependent P1/eIF-2 alpha protein kinase from human cells. Virology. 1992 May;188(1):33-46. [PubMed:1373553 ]
  10. Kuhen KL, Shen X, Samuel CE: Mechanism of interferon action sequence of the human interferon-inducible RNA-dependent protein kinase (PKR) deduced from genomic clones. Gene. 1996 Oct 31;178(1-2):191-3. [PubMed:8921913 ]
  11. Kuhen KL, Shen X, Carlisle ER, Richardson AL, Weier HU, Tanaka H, Samuel CE: Structural organization of the human gene (PKR) encoding an interferon-inducible RNA-dependent protein kinase (PKR) and differences from its mouse homolog. Genomics. 1996 Aug 15;36(1):197-201. [PubMed:8812437 ]
  12. Xu Z, Williams BR: Genomic features of human PKR: alternative splicing and a polymorphic CGG repeat in the 5'-untranslated region. J Interferon Cytokine Res. 1998 Aug;18(8):609-16. [PubMed:9726442 ]
  13. Polyak SJ, Tang N, Wambach M, Barber GN, Katze MG: The P58 cellular inhibitor complexes with the interferon-induced, double-stranded RNA-dependent protein kinase, PKR, to regulate its autophosphorylation and activity. J Biol Chem. 1996 Jan 19;271(3):1702-7. [PubMed:8576172 ]
  14. Brand SR, Kobayashi R, Mathews MB: The Tat protein of human immunodeficiency virus type 1 is a substrate and inhibitor of the interferon-induced, virally activated protein kinase, PKR. J Biol Chem. 1997 Mar 28;272(13):8388-95. [PubMed:9079663 ]
  15. Gale MJ Jr, Korth MJ, Tang NM, Tan SL, Hopkins DA, Dever TE, Polyak SJ, Gretch DR, Katze MG: Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural 5A protein. Virology. 1997 Apr 14;230(2):217-27. [PubMed:9143277 ]
  16. Tan SL, Katze MG: Biochemical and genetic evidence for complex formation between the influenza A virus NS1 protein and the interferon-induced PKR protein kinase. J Interferon Cytokine Res. 1998 Sep;18(9):757-66. [PubMed:9781815 ]
  17. Taylor DR, Shi ST, Romano PR, Barber GN, Lai MM: Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein. Science. 1999 Jul 2;285(5424):107-10. [PubMed:10390359 ]
  18. Taylor DR, Tian B, Romano PR, Hinnebusch AG, Lai MM, Mathews MB: Hepatitis C virus envelope protein E2 does not inhibit PKR by simple competition with autophosphorylation sites in the RNA-binding domain. J Virol. 2001 Feb;75(3):1265-73. [PubMed:11152499 ]
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