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P19525

- E2AK2_HUMAN

UniProt

P19525 - E2AK2_HUMAN

Protein

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

Gene

EIF2AK2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 177 (01 Oct 2014)
      Sequence version 2 (01 May 1991)
      Previous versions | rss
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    Functioni

    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.24 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.
    ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

    Enzyme regulationi

    Initially produced in an inactive form and is activated by binding to viral dsRNA, which causes dimerization and autophosphorylation in the activation loop and stimulation of function. ISGylation can activate it in the absence of viral infection. Can also be activated by heparin, proinflammatory stimuli, growth factors, cytokines, oxidative stress and the cellular protein PRKRA. Activity is markedly stimulated by manganese ions. Activation is blocked by the viral components HIV-1 Tat protein and large amounts of HIV-1 trans-activation response (TAR) RNA element as well as by the cellular proteins TARBP2, DUS2L, NPM1, NCK1 and ADAR. Down-regulated by Toscana virus (TOS) and Rift valley fever virus (RVFV) NSS which promote its proteasomal degradation. Inhibited by vaccinia virus protein E3, probably via dsRNA sequestering.5 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei296 – 2961ATP
    Active sitei414 – 4141Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi273 – 2819ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. double-stranded RNA binding Source: MGI
    3. eukaryotic translation initiation factor 2alpha kinase activity Source: ProtInc
    4. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC
    5. poly(A) RNA binding Source: UniProtKB
    6. protein binding Source: UniProtKB
    7. protein kinase activity Source: UniProtKB
    8. protein phosphatase type 2A regulator activity Source: ProtInc
    9. protein serine/threonine kinase activity Source: ProtInc

    GO - Biological processi

    1. activation of MAPKK activity Source: UniProtKB
    2. defense response to virus Source: UniProtKB-KW
    3. endoplasmic reticulum unfolded protein response Source: Ensembl
    4. evasion or tolerance by virus of host immune response Source: Reactome
    5. innate immune response Source: UniProtKB-KW
    6. modulation by virus of host morphology or physiology Source: Reactome
    7. modulation by virus of host process Source: Reactome
    8. negative regulation of cell proliferation Source: ProtInc
    9. negative regulation of osteoblast proliferation Source: UniProtKB
    10. negative regulation of translation Source: UniProtKB
    11. negative regulation of viral genome replication Source: UniProtKB
    12. positive regulation of chemokine production Source: UniProtKB
    13. positive regulation of cytokine production Source: UniProtKB
    14. positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
    15. positive regulation of NIK/NF-kappaB signaling Source: UniProtKB
    16. positive regulation of stress-activated MAPK cascade Source: UniProtKB
    17. protein autophosphorylation Source: UniProtKB
    18. protein phosphorylation Source: UniProtKB
    19. regulation of hematopoietic progenitor cell differentiation Source: UniProtKB
    20. regulation of hematopoietic stem cell differentiation Source: UniProtKB
    21. regulation of hematopoietic stem cell proliferation Source: UniProtKB
    22. regulation of NLRP3 inflammasome complex assembly Source: UniProtKB
    23. response to interferon-alpha Source: UniProtKB
    24. response to virus Source: UniProtKB
    25. transcription, DNA-templated Source: UniProtKB-KW
    26. translation Source: Ensembl
    27. viral life cycle Source: Reactome

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase

    Keywords - Biological processi

    Antiviral defense, Host-virus interaction, Immunity, Innate immunity, Transcription, Transcription regulation

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding, RNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_115831. ISG15 antiviral mechanism.
    REACT_6350. Inhibition of PKR.
    SignaLinkiP19525.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Interferon-induced, double-stranded RNA-activated protein kinase (EC:2.7.11.1)
    Alternative name(s):
    Eukaryotic translation initiation factor 2-alpha kinase 2
    Short name:
    eIF-2A protein kinase 2
    Interferon-inducible RNA-dependent protein kinase
    P1/eIF-2A protein kinase
    Protein kinase RNA-activated
    Short name:
    PKR
    Tyrosine-protein kinase EIF2AK2 (EC:2.7.10.2)
    p68 kinase
    Gene namesi
    Name:EIF2AK2
    Synonyms:PKR, PRKR
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:9437. EIF2AK2.

    Subcellular locationi

    Cytoplasm. Nucleus. Cytoplasmperinuclear region
    Note: Nuclear localization is elevated in acute leukemia, myelodysplastic syndrome (MDS), melanoma, breast, colon, prostate and lung cancer patient samples or cell lines as well as neurocytes from advanced Creutzfeldt-Jakob disease patients.

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. cytosol Source: Reactome
    3. membrane Source: UniProtKB
    4. nucleus Source: UniProtKB-SubCell
    5. perinuclear region of cytoplasm Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi59 – 602SK → AA in FL-PKR-2AI; moderate loss of activity but no effect on dsRNA binding. 1 Publication
    Mutagenesisi60 – 601K → A: Impairs dsRNA binding but not dimerization or activity. 1 Publication
    Mutagenesisi67 – 671A → E: Significant loss of activity; loss of dsRNA binding and dimerization. 1 Publication
    Mutagenesisi83 – 831S → A: No effect on enzymatic activity; when associated with A-88; A-89 and A-90. 2 Publications
    Mutagenesisi88 – 881T → A: No effect on enzymatic activity; when associated with A-83; A-89 and A-90. 2 Publications
    Mutagenesisi89 – 891T → A: No effect on enzymatic activity; when associated with A-83; A-88 and A-90. 2 Publications
    Mutagenesisi90 – 901T → A: No effect on enzymatic activity; when associated with A-83; A-88 and A-89. 2 Publications
    Mutagenesisi149 – 1502TK → AA in FL-PKR-2AII; no effect on activity. 1 Publication
    Mutagenesisi242 – 2421S → A: Moderate loss of activity; when associated with A-255 and A-258. 2 Publications
    Mutagenesisi244 – 29653Missing: Loss of activity. 1 PublicationAdd
    BLAST
    Mutagenesisi255 – 2551T → A: Moderate loss of activity; when associated with A-242 and A-255. 2 Publications
    Mutagenesisi258 – 2581T → A: Moderate loss of activity. 2 Publications
    Mutagenesisi296 – 2961K → R: Loss of activity. 2 Publications
    Mutagenesisi446 – 4461T → A: Significant loss of activity and impairs autophosphorylation of T-451. 1 Publication
    Mutagenesisi451 – 4511T → A: Loss of activity. 1 Publication

    Organism-specific databases

    PharmGKBiPA33779.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed3 Publications
    Chaini2 – 551550Interferon-induced, double-stranded RNA-activated protein kinasePRO_0000085945Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanine3 Publications
    Cross-linki69 – 69Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)
    Modified residuei83 – 831Phosphoserine4 Publications
    Modified residuei88 – 881Phosphothreonine; by autocatalysis1 Publication
    Modified residuei89 – 891Phosphothreonine; by autocatalysis1 Publication
    Modified residuei90 – 901Phosphothreonine; by autocatalysis1 Publication
    Modified residuei101 – 1011Phosphotyrosine; by autocatalysis1 Publication
    Cross-linki159 – 159Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)
    Modified residuei162 – 1621Phosphotyrosine; by autocatalysis1 Publication
    Modified residuei242 – 2421Phosphoserine; by autocatalysis1 Publication
    Modified residuei255 – 2551Phosphothreonine; by autocatalysis1 Publication
    Modified residuei258 – 2581Phosphothreonine; by autocatalysis1 Publication
    Modified residuei293 – 2931Phosphotyrosine; by autocatalysis1 Publication
    Modified residuei446 – 4461Phosphothreonine; by autocatalysis2 Publications
    Modified residuei451 – 4511Phosphothreonine; by autocatalysis2 Publications
    Modified residuei456 – 4561Phosphoserine1 Publication

    Post-translational modificationi

    Autophosphorylated on several Ser, Thr and Tyr residues. Autophosphorylation of Thr-451 is dependent on Thr-446 and is stimulated by dsRNA binding and dimerization. Autophosphorylation apparently leads to the activation of the kinase. Tyrosine autophosphorylation is essential for efficient dsRNA-binding, dimerization, and kinase activation.10 Publications

    Keywords - PTMi

    Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP19525.
    PaxDbiP19525.
    PRIDEiP19525.

    PTM databases

    PhosphoSiteiP19525.

    Miscellaneous databases

    PMAP-CutDBP19525.

    Expressioni

    Tissue specificityi

    Highly expressed in thymus, spleen and bone marrow compared to non-hematopoietic tissues such as small intestine, liver, or kidney tissues. Colocalizes with GSK3B and TAU in the Alzheimer disease (AD) brain. Elevated levels seen in breast and colon carcinomas,and which correlates with tumor progression and invasiveness or risk of progression.2 Publications

    Inductioni

    By type I interferons.1 Publication

    Gene expression databases

    ArrayExpressiP19525.
    BgeeiP19525.
    CleanExiHS_EIF2AK2.
    GenevestigatoriP19525.

    Organism-specific databases

    HPAiCAB003845.
    HPA019795.

    Interactioni

    Subunit structurei

    Homodimer. Interacts with STRBP By similarity. Interacts with DNAJC3. Inhibited by direct interaction with viral proteins such as HCV E2, HCV NS5A and influenza A NS1. Activated by the interaction with HIV-1 Tat By similarity. Forms a complex with FANCA, FANCC, FANCG and HSP70. Interacts with ADAR/ADAR1. Interacts with IRS1 By similarity. The inactive form interacts with NCK1 and GSN. Interacts (via the kinase catalytic domain) with STAT3 (via SH2 domain), TRAF2 (C-terminus), TRAF5 (C-terminus) and TRAF6 (C-terminus). Interacts with MAP2K6, IKBKB/IKKB, NPM1, TARBP2, NLRP1, NLRP3, NLRC4 and AIM2. Interacts (via DRBM 1 domain) with DUS2L (via DRBM domain). Interacts with DHX9 (via N-terminus) and this interaction is dependent upon activation of the kinase. Interacts with human herpes simplex virus 1 (HHV-1) protein US11 in an RNA-dependent manner. The inactive form interacts with Toscana virus (TOS) NSS. Interacts with herpes virus 8 protein v-IRF2; this interaction inhibits EIF2AK2 activation.By similarity21 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    O929722EBI-640775,EBI-6918883From a different organism.
    P279585EBI-640775,EBI-8753518From a different organism.
    CDK1P064934EBI-640775,EBI-444308
    DHX30Q7L2E33EBI-640775,EBI-1211456
    DHX58Q96C102EBI-640775,EBI-744193
    DHX9Q082112EBI-640775,EBI-352022
    DICER1Q9UPY32EBI-640775,EBI-395506
    DNAJC3Q279685EBI-640775,EBI-640793From a different organism.
    EDC4Q6P2E92EBI-640775,EBI-1006038
    EIF2S1P051984EBI-640775,EBI-1056162
    EIF6P565372EBI-640775,EBI-372243
    FTSJ3Q8IY812EBI-640775,EBI-744088
    K3LP206392EBI-640775,EBI-8674942From a different organism.
    MOV10Q9HCE12EBI-640775,EBI-1055820
    NPM1P067483EBI-640775,EBI-78579
    STAU2Q9NUL32EBI-640775,EBI-722938
    TARBP2Q156332EBI-640775,EBI-978581
    TOLLIPQ9H0E22EBI-640775,EBI-74615
    US11P044873EBI-640775,EBI-6150681From a different organism.
    vIRF-2Q2HR712EBI-640775,EBI-8876177From a different organism.
    ZNF346Q9UL402EBI-640775,EBI-2462313

    Protein-protein interaction databases

    BioGridi111596. 79 interactions.
    DIPiDIP-2657N.
    IntActiP19525. 53 interactions.
    MINTiMINT-92415.
    STRINGi9606.ENSP00000233057.

    Structurei

    Secondary structure

    1
    551
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi5 – 73
    Helixi10 – 2112
    Beta strandi26 – 327
    Turni35 – 373
    Beta strandi41 – 5010
    Beta strandi54 – 563
    Helixi61 – 7616
    Helixi102 – 11110
    Beta strandi115 – 1239
    Beta strandi125 – 13814
    Beta strandi144 – 1496
    Helixi150 – 16718
    Helixi261 – 2666
    Beta strandi267 – 2748
    Beta strandi276 – 2783
    Beta strandi281 – 2866
    Turni287 – 2893
    Beta strandi292 – 2998
    Helixi303 – 3053
    Helixi306 – 3149
    Beta strandi323 – 33210
    Beta strandi358 – 3669
    Helixi374 – 3807
    Helixi381 – 3833
    Helixi388 – 40720
    Beta strandi410 – 4123
    Helixi417 – 4193
    Beta strandi420 – 4245
    Beta strandi427 – 4304
    Beta strandi437 – 4404
    Helixi457 – 4615
    Helixi468 – 48215
    Helixi488 – 49912
    Beta strandi505 – 5073
    Helixi509 – 51810
    Helixi523 – 5253
    Helixi529 – 53810

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1QU6NMR-A1-170[»]
    2A19X-ray2.50B/C258-538[»]
    2A1AX-ray2.80B258-538[»]
    3UIUX-ray2.90A/B254-551[»]
    ProteinModelPortaliP19525.
    SMRiP19525. Positions 1-170, 257-541.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP19525.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini9 – 7769DRBM 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini100 – 16768DRBM 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini267 – 538272Protein kinasePROSITE-ProRule annotationAdd
    BLAST
    Repeati331 – 343131Add
    BLAST
    Repeati345 – 357132Add
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni266 – 551286Interaction with TRAF5Add
    BLAST
    Regioni331 – 357272 X 13 AA approximate repeatsAdd
    BLAST

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily.PROSITE-ProRule annotation
    Contains 2 DRBM (double-stranded RNA-binding) domains.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000234351.
    HOVERGENiHBG051430.
    InParanoidiP19525.
    KOiK16195.
    OMAiRFTFQVI.
    OrthoDBiEOG71VSSK.
    PhylomeDBiP19525.
    TreeFamiTF317576.

    Family and domain databases

    Gene3Di3.30.160.20. 2 hits.
    InterProiIPR014720. dsRNA-bd_dom.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view]
    PfamiPF00035. dsrm. 2 hits.
    PF00069. Pkinase. 1 hit.
    [Graphical view]
    SMARTiSM00358. DSRM. 2 hits.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS50137. DS_RBD. 2 hits.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P19525-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MAGDLSAGFF MEELNTYRQK QGVVLKYQEL PNSGPPHDRR FTFQVIIDGR    50
    EFPEGEGRSK KEAKNAAAKL AVEILNKEKK AVSPLLLTTT NSSEGLSMGN 100
    YIGLINRIAQ KKRLTVNYEQ CASGVHGPEG FHYKCKMGQK EYSIGTGSTK 150
    QEAKQLAAKL AYLQILSEET SVKSDYLSSG SFATTCESQS NSLVTSTLAS 200
    ESSSEGDFSA DTSEINSNSD SLNSSSLLMN GLRNNQRKAK RSLAPRFDLP 250
    DMKETKYTVD KRFGMDFKEI ELIGSGGFGQ VFKAKHRIDG KTYVIKRVKY 300
    NNEKAEREVK ALAKLDHVNI VHYNGCWDGF DYDPETSDDS LESSDYDPEN 350
    SKNSSRSKTK CLFIQMEFCD KGTLEQWIEK RRGEKLDKVL ALELFEQITK 400
    GVDYIHSKKL IHRDLKPSNI FLVDTKQVKI GDFGLVTSLK NDGKRTRSKG 450
    TLRYMSPEQI SSQDYGKEVD LYALGLILAE LLHVCDTAFE TSKFFTDLRD 500
    GIISDIFDKK EKTLLQKLLS KKPEDRPNTS EILRTLTVWK KSPEKNERHT 550
    C 551
    Length:551
    Mass (Da):62,094
    Last modified:May 1, 1991 - v2
    Checksum:i815AD83ACAB45DA3
    GO
    Isoform 2 (identifier: P19525-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         263-303: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:510
    Mass (Da):57,391
    Checksum:i6EC61AFC54DEFCA4
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti102 – 1021I → M in AAP57628. 1 PublicationCurated
    Sequence conflicti224 – 2241S → R in AAP57628. 1 PublicationCurated
    Sequence conflicti512 – 5121K → E in AAF13156. (PubMed:9726442)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti428 – 4281V → E.1 Publication
    Corresponds to variant rs56219559 [ dbSNP | Ensembl ].
    VAR_040474
    Natural varianti439 – 4391L → V in a lung adenocarcinoma sample; somatic mutation. 1 Publication
    VAR_040475
    Natural varianti506 – 5061I → V.1 Publication
    Corresponds to variant rs34821155 [ dbSNP | Ensembl ].
    VAR_040476

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei263 – 30341Missing in isoform 2. 1 PublicationVSP_046177Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M35663 mRNA. Translation: AAA36409.1.
    M85294 mRNA. Translation: AAA18253.1.
    U50648
    , U50634, U50635, U50636, U50637, U50638, U50639, U50640, U50641, U50642, U50643, U50644, U50645, U50646, U50647 Genomic DNA. Translation: AAC50768.1.
    AF167472
    , AF167460, AF167462, AF167463, AF167464, AF167465, AF167466, AF167468, AF167470 Genomic DNA. Translation: AAF13156.1.
    AY302136 mRNA. Translation: AAP57628.1.
    AK290655 mRNA. Translation: BAF83344.1.
    AK313818 mRNA. Translation: BAG36554.1.
    AY228338 Genomic DNA. Translation: AAO38055.1.
    AC007899 Genomic DNA. Translation: AAY24317.1.
    CH471053 Genomic DNA. Translation: EAX00407.1.
    CH471053 Genomic DNA. Translation: EAX00408.1.
    CH471053 Genomic DNA. Translation: EAX00409.1.
    BC093676 mRNA. Translation: AAH93676.1.
    BC101475 mRNA. Translation: AAI01476.1.
    CCDSiCCDS1786.1. [P19525-1]
    CCDS46259.1. [P19525-2]
    PIRiJC5225.
    RefSeqiNP_001129123.1. NM_001135651.2. [P19525-1]
    NP_001129124.1. NM_001135652.2. [P19525-2]
    NP_002750.1. NM_002759.3. [P19525-1]
    UniGeneiHs.131431.

    Genome annotation databases

    EnsembliENST00000233057; ENSP00000233057; ENSG00000055332. [P19525-1]
    ENST00000395127; ENSP00000378559; ENSG00000055332. [P19525-1]
    ENST00000405334; ENSP00000385014; ENSG00000055332. [P19525-2]
    GeneIDi5610.
    KEGGihsa:5610.
    UCSCiuc010fac.3. human. [P19525-1]

    Polymorphism databases

    DMDMi125527.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs
    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M35663 mRNA. Translation: AAA36409.1 .
    M85294 mRNA. Translation: AAA18253.1 .
    U50648
    , U50634 , U50635 , U50636 , U50637 , U50638 , U50639 , U50640 , U50641 , U50642 , U50643 , U50644 , U50645 , U50646 , U50647 Genomic DNA. Translation: AAC50768.1 .
    AF167472
    , AF167460 , AF167462 , AF167463 , AF167464 , AF167465 , AF167466 , AF167468 , AF167470 Genomic DNA. Translation: AAF13156.1 .
    AY302136 mRNA. Translation: AAP57628.1 .
    AK290655 mRNA. Translation: BAF83344.1 .
    AK313818 mRNA. Translation: BAG36554.1 .
    AY228338 Genomic DNA. Translation: AAO38055.1 .
    AC007899 Genomic DNA. Translation: AAY24317.1 .
    CH471053 Genomic DNA. Translation: EAX00407.1 .
    CH471053 Genomic DNA. Translation: EAX00408.1 .
    CH471053 Genomic DNA. Translation: EAX00409.1 .
    BC093676 mRNA. Translation: AAH93676.1 .
    BC101475 mRNA. Translation: AAI01476.1 .
    CCDSi CCDS1786.1. [P19525-1 ]
    CCDS46259.1. [P19525-2 ]
    PIRi JC5225.
    RefSeqi NP_001129123.1. NM_001135651.2. [P19525-1 ]
    NP_001129124.1. NM_001135652.2. [P19525-2 ]
    NP_002750.1. NM_002759.3. [P19525-1 ]
    UniGenei Hs.131431.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1QU6 NMR - A 1-170 [» ]
    2A19 X-ray 2.50 B/C 258-538 [» ]
    2A1A X-ray 2.80 B 258-538 [» ]
    3UIU X-ray 2.90 A/B 254-551 [» ]
    ProteinModelPortali P19525.
    SMRi P19525. Positions 1-170, 257-541.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111596. 79 interactions.
    DIPi DIP-2657N.
    IntActi P19525. 53 interactions.
    MINTi MINT-92415.
    STRINGi 9606.ENSP00000233057.

    Chemistry

    BindingDBi P19525.
    ChEMBLi CHEMBL5785.
    GuidetoPHARMACOLOGYi 2016.

    PTM databases

    PhosphoSitei P19525.

    Polymorphism databases

    DMDMi 125527.

    Proteomic databases

    MaxQBi P19525.
    PaxDbi P19525.
    PRIDEi P19525.

    Protocols and materials databases

    DNASUi 5610.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000233057 ; ENSP00000233057 ; ENSG00000055332 . [P19525-1 ]
    ENST00000395127 ; ENSP00000378559 ; ENSG00000055332 . [P19525-1 ]
    ENST00000405334 ; ENSP00000385014 ; ENSG00000055332 . [P19525-2 ]
    GeneIDi 5610.
    KEGGi hsa:5610.
    UCSCi uc010fac.3. human. [P19525-1 ]

    Organism-specific databases

    CTDi 5610.
    GeneCardsi GC02M037326.
    HGNCi HGNC:9437. EIF2AK2.
    HPAi CAB003845.
    HPA019795.
    MIMi 176871. gene.
    neXtProti NX_P19525.
    PharmGKBi PA33779.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000234351.
    HOVERGENi HBG051430.
    InParanoidi P19525.
    KOi K16195.
    OMAi RFTFQVI.
    OrthoDBi EOG71VSSK.
    PhylomeDBi P19525.
    TreeFami TF317576.

    Enzyme and pathway databases

    Reactomei REACT_115831. ISG15 antiviral mechanism.
    REACT_6350. Inhibition of PKR.
    SignaLinki P19525.

    Miscellaneous databases

    ChiTaRSi EIF2AK2. human.
    EvolutionaryTracei P19525.
    GeneWikii Protein_kinase_R.
    GenomeRNAii 5610.
    NextBioi 13635839.
    PMAP-CutDB P19525.
    PROi P19525.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P19525.
    Bgeei P19525.
    CleanExi HS_EIF2AK2.
    Genevestigatori P19525.

    Family and domain databases

    Gene3Di 3.30.160.20. 2 hits.
    InterProi IPR014720. dsRNA-bd_dom.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view ]
    Pfami PF00035. dsrm. 2 hits.
    PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SMARTi SM00358. DSRM. 2 hits.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS50137. DS_RBD. 2 hits.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Molecular cloning and characterization of the human double-stranded RNA-activated protein kinase induced by interferon."
      Meurs E., Chong K., Galabru J., Thomas N.S.B., Kerr I.M., Williams B.R.G., Hovanessian A.G.
      Cell 62:379-390(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 101-118 AND 309-325, INDUCTION.
    2. Meurs E.
      Submitted (AUG-1990) to the EMBL/GenBank/DDBJ databases
      Cited for: SEQUENCE REVISION.
    3. "Mechanism of interferon action: cDNA structure, expression, and regulation of the interferon-induced, RNA-dependent P1/eIF-2 alpha protein kinase from human cells."
      Thomis D.C., Doohan J.P., Samuel C.E.
      Virology 188:33-46(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    4. "Mechanism of interferon action sequence of the human interferon-inducible RNA-dependent protein kinase (PKR) deduced from genomic clones."
      Kuhen K.L., Shen X., Samuel C.E.
      Gene 178:191-193(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
    5. "Structural organization of the human gene (PKR) encoding an interferon-inducible RNA-dependent protein kinase (PKR) and differences from its mouse homolog."
      Kuhen K.L., Shen X., Carlisle E.R., Richardson A.L., Weier H.-U.G., Tanaka H., Samuel C.E.
      Genomics 36:197-201(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Tissue: Placenta.
    6. "Genomic features of human PKR: alternative splicing and a polymorphic CGG repeat in the 5'-untranslated region."
      Xu Z., Williams B.R.
      J. Interferon Cytokine Res. 18:609-616(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    7. Li H., Huang F., Shen C., Zhou G., Zheng G., Ke R., Lin L., Yang S.
      Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    8. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Brain and Embryo.
    9. NIEHS SNPs program
      Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    10. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
      Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
      , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
      Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    11. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    12. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Brain.
    13. Bienvenut W.V., Gao M., Leug H.
      Submitted (JUN-2009) to UniProtKB
      Cited for: PROTEIN SEQUENCE OF 2-18; 27-40; 70-77; 414-426 AND 430-440, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY.
      Tissue: Prostatic carcinoma.
    14. "The P58 cellular inhibitor complexes with the interferon-induced, double-stranded RNA-dependent protein kinase, PKR, to regulate its autophosphorylation and activity."
      Polyak S.J., Tang N., Wambach M., Barber G.N., Katze M.G.
      J. Biol. Chem. 271:1702-1707(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH DNAJC3.
    15. "The Tat protein of human immunodeficiency virus type 1 is a substrate and inhibitor of the interferon-induced, virally activated protein kinase, PKR."
      Brand S.R., Kobayashi R., Mathews M.B.
      J. Biol. Chem. 272:8388-8395(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HIV-1 TAT.
    16. "Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural 5A protein."
      Gale M.J. Jr., Korth M.J., Tang N.M., Tan S.-L., Hopkins D.A., Dever T.E., Polyak S.J., Gretch D.R., Katze M.G.
      Virology 230:217-227(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HCV NS5A.
    17. "Biochemical and genetic evidence for complex formation between the influenza A virus NS1 protein and the interferon-induced PKR protein kinase."
      Tan S.L., Katze M.G.
      J. Interferon Cytokine Res. 18:757-766(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH INFLUENZA A NS1 PROTEIN.
    18. "Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein."
      Taylor D.R., Shi S.T., Romano P.R., Barber G.N., Lai M.M.C.
      Science 285:107-110(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HCV E2 ENVELOPE PROTEIN.
    19. "PKR stimulates NF-kappaB irrespective of its kinase function by interacting with the IkappaB kinase complex."
      Bonnet M.C., Weil R., Dam E., Hovanessian A.G., Meurs E.F.
      Mol. Cell. Biol. 20:4532-4542(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH IKBKB.
    20. "Two dimerization domains in the trans-activation response RNA-binding protein (TRBP) individually reverse the protein kinase R inhibition of HIV-1 long terminal repeat expression."
      Daher A., Longuet M., Dorin D., Bois F., Segeral E., Bannwarth S., Battisti P.-L., Purcell D.F., Benarous R., Vaquero C., Meurs E.F., Gatignol A.
      J. Biol. Chem. 276:33899-33905(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TARBP2.
    21. "Hepatitis C virus envelope protein E2 does not inhibit PKR by simple competition with autophosphorylation sites in the RNA-binding domain."
      Taylor D.R., Tian B., Romano P.R., Hinnebusch A.G., Lai M.M.C., Mathews M.B.
      J. Virol. 75:1265-1273(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-83; THR-88; THR-89; THR-90; SER-242; THR-255 AND THR-258, MUTAGENESIS OF SER-83; THR-88; THR-89; THR-90; SER-242; THR-255; THR-258 AND LYS-296, INHIBITION BY HCV E2 ENVELOPE PROTEIN.
    22. "Binding of double-stranded RNA to protein kinase PKR is required for dimerization and promotes critical autophosphorylation events in the activation loop."
      Zhang F., Romano P.R., Nagamura-Inoue T., Tian B., Dever T.E., Mathews M.B., Ozato K., Hinnebusch A.G.
      J. Biol. Chem. 276:24946-24958(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS, PHOSPHORYLATION AT THR-446 AND THR-451.
    23. "Latently expressed human herpesvirus 8-encoded interferon regulatory factor 2 inhibits double-stranded RNA-activated protein kinase."
      Burysek L., Pitha P.M.
      J. Virol. 75:2345-2352(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HHV-8 PROTEIN VIRF2.
    24. "The herpes simplex virus type 1 U(S)11 protein interacts with protein kinase R in infected cells and requires a 30-amino-acid sequence adjacent to a kinase substrate domain."
      Cassady K.A., Gross M.
      J. Virol. 76:2029-2035(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH HHV-1 US11.
    25. "Nucleophosmin interacts with and inhibits the catalytic function of eukaryotic initiation factor 2 kinase PKR."
      Pang Q., Christianson T.A., Koretsky T., Carlson H., David L., Keeble W., Faulkner G.R., Speckhart A., Bagby G.C.
      J. Biol. Chem. 278:41709-41717(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NPM1, ENZYME REGULATION.
    26. "Protein kinase R (PKR) interacts with and activates mitogen-activated protein kinase kinase 6 (MKK6) in response to double-stranded RNA stimulation."
      Silva A.M., Whitmore M., Xu Z., Jiang Z., Li X., Williams B.R.
      J. Biol. Chem. 279:37670-37676(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH MAP2K6.
    27. "The Fanconi anemia proteins functionally interact with the protein kinase regulated by RNA (PKR)."
      Zhang X., Li J., Sejas D.P., Rathbun K.R., Bagby G.C., Pang Q.
      J. Biol. Chem. 279:43910-43919(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION IN A COMPLEX WITH FANCA; FANCC; FANCG AND HSP70.
    28. Cited for: FUNCTION, INTERACTION WITH TRAF2; TRAF5 AND TRAF6, SUBCELLULAR LOCATION.
    29. "Inhibition of PKR by vaccinia virus: role of the N- and C-terminal domains of E3L."
      Langland J.O., Jacobs B.L.
      Virology 324:419-429(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INHIBITION BY VACCINIA VIRUS PROTEIN E3.
    30. "Impact of protein kinase PKR in cell biology: from antiviral to antiproliferative action."
      Garcia M.A., Gil J., Ventoso I., Guerra S., Domingo E., Rivas C., Esteban M.
      Microbiol. Mol. Biol. Rev. 70:1032-1060(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    31. "Tyrosine phosphorylation acts as a molecular switch to full-scale activation of the eIF2alpha RNA-dependent protein kinase."
      Su Q., Wang S., Baltzis D., Qu L.K., Wong A.H., Koromilas A.E.
      Proc. Natl. Acad. Sci. U.S.A. 103:63-68(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT TYR-101; TYR-162 AND TYR-293.
    32. "Double-stranded RNA deaminase ADAR1 increases host susceptibility to virus infection."
      Nie Y., Hammond G.L., Yang J.H.
      J. Virol. 81:917-923(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ADAR.
    33. "Activation of PKR: an open and shut case?"
      Cole J.L.
      Trends Biochem. Sci. 32:57-62(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON ENZYME REGULATION.
    34. "Nck-1 interacts with PKR and modulates its activation by dsRNA."
      Cardin E., Larose L.
      Biochem. Biophys. Res. Commun. 377:231-235(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH NCK1, ENZYME REGULATION.
    35. "Interaction of human tRNA-dihydrouridine synthase-2 with interferon-induced protein kinase PKR."
      Mittelstadt M., Frump A., Khuu T., Fowlkes V., Handy I., Patel C.V., Patel R.C.
      Nucleic Acids Res. 36:998-1008(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH DUS2L, ENZYME REGULATION.
    36. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83 AND SER-456, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    37. "PKR activity is required for acute leukemic cell maintenance and growth: a role for PKR-mediated phosphatase activity to regulate GSK-3 phosphorylation."
      Blalock W.L., Grimaldi C., Fala F., Follo M., Horn S., Basecke J., Martinelli G., Cocco L., Martelli A.M.
      J. Cell. Physiol. 221:232-241(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    38. "An antiviral response directed by PKR phosphorylation of the RNA helicase A."
      Sadler A.J., Latchoumanin O., Hawkes D., Mak J., Williams B.R.
      PLoS Pathog. 5:E1000311-E1000311(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH DHX9.
    39. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
      Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
      Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Leukemic T-cell.
    40. "PKR protein kinase is activated by hepatitis C virus and inhibits viral replication through translational control."
      Kang J.I., Kwon S.N., Park S.H., Kim Y.K., Choi S.Y., Kim J.P., Ahn B.Y.
      Virus Res. 142:51-56(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN HCV RESTRICTION.
    41. "A role for protein kinase PKR in the mediation of Epstein-Barr virus latent membrane protein-1-induced IL-6 and IL-10 expression."
      Lin S.S., Lee D.C., Law A.H., Fang J.W., Chua D.T., Lau A.S.
      Cytokine 50:210-219(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    42. "New Cdc2 Tyr 4 phosphorylation by dsRNA-activated protein kinase triggers Cdc2 polyubiquitination and G2 arrest under genotoxic stresses."
      Yoon C.-H., Miah M.A., Kim K.P., Bae Y.-S.
      EMBO Rep. 11:393-399(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS CDK1 KINASE UPON DNA DAMAGE, FUNCTION AS TYROSINE-PROTEIN KINASE.
    43. "Phosphorylation of the NFAR proteins by the dsRNA-dependent protein kinase PKR constitutes a novel mechanism of translational regulation and cellular defense."
      Harashima A., Guettouche T., Barber G.N.
      Genes Dev. 24:2640-2653(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    44. "Double-stranded RNA-activated protein kinase inhibits hepatitis C virus replication but may be not essential in interferon treatment."
      Chang J.H., Kato N., Muroyama R., Taniguchi H., Guleng B., Dharel N., Shao R.X., Tateishi K., Jazag A., Kawabe T., Omata M.
      Liver Int. 30:311-318(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN HCV RESTRICTION.
    45. "The double-stranded RNA-dependent protein kinase differentially regulates insulin receptor substrates 1 and 2 in HepG2 cells."
      Yang X., Nath A., Opperman M.J., Chan C.
      Mol. Biol. Cell 21:3449-3458(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, PHOSPHORYLATION AT THR-451.
    46. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    47. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    48. "Modulation of tau phosphorylation by the kinase PKR: implications in Alzheimer's disease."
      Bose A., Mouton-Liger F., Paquet C., Mazot P., Vigny M., Gray F., Hugon J.
      Brain Pathol. 21:189-200(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, PHOSPHORYLATION.
    49. "Protein kinase PKR and RNA adenosine deaminase ADAR1: new roles for old players as modulators of the interferon response."
      Pfaller C.K., Li Z., George C.X., Samuel C.E.
      Curr. Opin. Immunol. 23:573-582(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    50. "The role of protein kinase R in the interferon response."
      Pindel A., Sadler A.
      J. Interferon Cytokine Res. 31:59-70(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    51. "Multiple forms of PKR present in the nuclei of acute leukemia cells represent an active kinase that is responsive to stress."
      Blalock W.L., Bavelloni A., Piazzi M., Tagliavini F., Faenza I., Martelli A.M., Follo M.Y., Cocco L.
      Leukemia 25:236-245(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION.
    52. "PKR-dependent mechanisms of interferon-? for inhibiting hepatitis B virus replication."
      Park I.H., Baek K.W., Cho E.Y., Ahn B.Y.
      Mol. Cells 32:167-172(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN HBV RESTRICTION.
    53. "The RAX/PACT-PKR stress response pathway promotes p53 sumoylation and activation, leading to G(1) arrest."
      Bennett R.L., Pan Y., Christian J., Hui T., May W.S. Jr.
      Cell Cycle 11:407-417(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION.
    54. "Penetration resistance: PKR's other talent."
      Lacy-Hulbert A., Stuart L.M.
      Immunity 36:695-696(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    55. "Protein kinase PKR amplification of interferon beta induction occurs through initiation factor eIF-2alpha-mediated translational control."
      McAllister C.S., Taghavi N., Samuel C.E.
      J. Biol. Chem. 287:36384-36392(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    56. Cited for: FUNCTION, INTERACTION WITH STAT3.
    57. "Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
      Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
      Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    58. Cited for: FUNCTION, INTERACTION WITH NLRP1; NLRP3; NLRC4 AND AIM2, AUTOPHOSPHORYLATION.
    59. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    60. "PKR-dependent inflammatory signals."
      Kang R., Tang D.
      Sci. Signal. 5:PE47-PE47(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    61. "Protein kinase PKR catalytic activity is required for the PKR-dependent activation of mitogen-activated protein kinases and amplification of interferon beta induction following virus infection."
      Taghavi N., Samuel C.E.
      Virology 427:208-216(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    62. "dsRNA-dependent protein kinase PKR and its role in stress, signaling and HCV infection."
      Dabo S., Meurs E.F.
      Viruses 4:2598-2635(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    63. "PKR regulates proliferation, differentiation and survival of murine hematopoietic stem/progenitor cells."
      Liu X., Bennett R.L., Cheng X., Byrne M., Reinhard M.K., May W.S. Jr.
      Blood 121:3364-3374(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    64. "The eIF2alpha kinases: their structures and functions."
      Donnelly N., Gorman A.M., Gupta S., Samali A.
      Cell. Mol. Life Sci. 70:3493-3511(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    65. "Activation of double-stranded RNA-activated protein kinase (PKR) by interferon-stimulated gene 15 (ISG15) modification down-regulates protein translation."
      Okumura F., Okumura A.J., Uematsu K., Hatakeyama S., Zhang D.E., Kamura T.
      J. Biol. Chem. 288:2839-2847(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, ISGYLATION AT LYS-69 AND LYS-159, ENZYME REGULATION.
    66. "Toscana virus NSs protein promoftes degradation of double-stranded RNA-dependent protein kinase."
      Kalveram B., Ikegami T.
      J. Virol. 87:3710-3718(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TOS NSS, ENZYME REGULATION.
    67. "Stress granule formation induced by measles virus is protein kinase PKR dependent and impaired by RNA adenosine deaminase ADAR1."
      Okonski K.M., Samuel C.E.
      J. Virol. 87:756-766(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN MV RESTRICTION.
    68. "Protein kinase regulated by dsRNA downregulates the interferon production in dengue virus- and dsrna-stimulated human lung epithelial cells."
      Li Y., Xie J., Wu S., Xia J., Zhang P., Liu C., Zhang P., Huang X.
      PLoS ONE 8:E55108-E55108(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    69. "The modulation of hepatitis C virus 1a replication by PKR is dependent on NF-kB mediated interferon beta response in Huh7.5.1 cells."
      Zhang L., Alter H.J., Wang H., Jia S., Wang E., Marincola F.M., Shih J.W., Wang R.Y.
      Virology 438:28-36(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN HCV RESTRICTION.
    70. "Structure of the double-stranded RNA-binding domain of the protein kinase PKR reveals the molecular basis of its dsRNA-mediated activation."
      Nanduri S., Carpick B.W., Yang Y., Williams B.R.G., Qin J.
      EMBO J. 17:5458-5465(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 1-175.
    71. "Higher-order substrate recognition of eIF2alpha by the RNA-dependent protein kinase PKR."
      Dar A.C., Dever T.E., Sicheri F.
      Cell 122:887-900(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 258-550 IN COMPLEX WITH EIF2ALPHA, PHOSPHORYLATION AT THR-446.
    72. "Patterns of somatic mutation in human cancer genomes."
      Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
      , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
      Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLU-428; VAL-439 AND VAL-506.

    Entry informationi

    Entry nameiE2AK2_HUMAN
    AccessioniPrimary (citable) accession number: P19525
    Secondary accession number(s): A8K3P0
    , D6W584, E9PC80, Q52M43, Q7Z6F6, Q9UIR4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1991
    Last sequence update: May 1, 1991
    Last modified: October 1, 2014
    This is version 177 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3