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Q03963

- E2AK2_MOUSE

UniProt

Q03963 - E2AK2_MOUSE

Protein

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

Gene

Eif2ak2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 144 (01 Oct 2014)
      Sequence version 2 (01 Nov 1997)
      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 west nile virus (WNV), sindbis virus (SV), foot-and-mouth virus (FMDV), semliki Forest virus (SFV) and lymphocytic choriomeningitis virus (LCMV). 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 and IRS1. 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. Regulates proliferation, differentiation and survival of hematopoietic stem/progenitor cells, induction of cytokines and chemokines and plays a role in cortex-dependent memory consolidation.14 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 cellular proteins TARBP2, DUS2L, NPM1, NCK1 and ADAR By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei271 – 2711ATPPROSITE-ProRule annotation
    Active sitei376 – 3761Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi248 – 2569ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. double-stranded RNA binding Source: MGI
    3. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC
    4. protein binding Source: UniProtKB
    5. protein kinase activity Source: UniProtKB
    6. protein serine/threonine kinase activity Source: UniProtKB-KW

    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: MGI
    4. innate immune response Source: UniProtKB-KW
    5. negative regulation of apoptotic process Source: MGI
    6. negative regulation of osteoblast proliferation Source: UniProtKB
    7. negative regulation of translation Source: UniProtKB
    8. negative regulation of viral genome replication Source: UniProtKB
    9. positive regulation of chemokine production Source: UniProtKB
    10. positive regulation of cytokine production Source: UniProtKB
    11. positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
    12. positive regulation of NIK/NF-kappaB signaling Source: UniProtKB
    13. positive regulation of stress-activated MAPK cascade Source: UniProtKB
    14. protein autophosphorylation Source: UniProtKB
    15. protein phosphorylation Source: MGI
    16. regulation of hematopoietic progenitor cell differentiation Source: UniProtKB
    17. regulation of hematopoietic stem cell differentiation Source: UniProtKB
    18. regulation of hematopoietic stem cell proliferation Source: UniProtKB
    19. regulation of NLRP3 inflammasome complex assembly Source: UniProtKB
    20. response to interferon-alpha Source: UniProtKB
    21. response to virus Source: UniProtKB
    22. transcription, DNA-templated Source: UniProtKB-KW
    23. translation Source: MGI

    Keywords - Molecular functioni

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

    Keywords - Biological processi

    Antiviral defense, Immunity, Innate immunity, Transcription, Transcription regulation

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding, RNA-binding

    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
    Serine/threonine-protein kinase TIK
    Tyrosine-protein kinase EIF2AK2 (EC:2.7.10.2)
    p68 kinase
    Gene namesi
    Name:Eif2ak2
    Synonyms:Pkr, Prkr, Tik
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 17

    Organism-specific databases

    MGIiMGI:1353449. Eif2ak2.

    Subcellular locationi

    Cytoplasm By similarity. Nucleus By similarity. Cytoplasmperinuclear region By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. nucleus Source: UniProtKB-SubCell
    3. perinuclear region of cytoplasm Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    Mice have significantly elevated numbers of bone marrow derived hematopoietic stem/progenitor cells (HSPCs) and which are more actively proliferating and resistant to stress.1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 515514Interferon-induced, double-stranded RNA-activated protein kinasePRO_0000085946Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanineBy similarity
    Cross-linki68 – 68Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)By similarity
    Modified residuei96 – 961Phosphotyrosine; by autocatalysisBy similarity
    Cross-linki154 – 154Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)By similarity
    Modified residuei157 – 1571Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei268 – 2681Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei409 – 4091Phosphothreonine; by autocatalysisBy similarity
    Modified residuei414 – 4141Phosphothreonine; by autocatalysisBy similarity
    Modified residuei419 – 4191PhosphoserineBy similarity

    Post-translational modificationi

    Autophosphorylated on several Ser, Thr and Tyr residues. Autophosphorylation of Thr-414 is dependent on Thr-409 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 By similarity.By similarity

    Keywords - PTMi

    Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiQ03963.
    PaxDbiQ03963.
    PRIDEiQ03963.

    PTM databases

    PhosphoSiteiQ03963.

    Expressioni

    Tissue specificityi

    Expressed in heart, lung, brain, kidney, testes, thymus and bone marrow.

    Inductioni

    By type I interferons.By similarity

    Gene expression databases

    BgeeiQ03963.
    GenevestigatoriQ03963.

    Interactioni

    Subunit structurei

    Homodimer. Interacts with DNAJC3 and STRBP By similarity. Forms a complex with FANCA, FANCC, FANCG and HSP70 By similarity. Interacts with ADAR/ADAR1. The inactive form interacts with NCK1. Interacts (via the kinase catalytic domain) with STAT3 (via SH2 domain), TRAF2 (C-terminus), TRAF5 (C-terminus) and TRAF6 (C-terminus). Interacts with MAP2K6, TARBP2, NLRP1, NLRC4 and AIM2. Interacts (via DRBM 1 domain) with DUS2L (via DRBM domain) By similarity. Interacts with DHX9 (via N-terminus) and this interaction is dependent upon activation of the kinase. The inactive form interacts with GSN. Interacts with IKBKB/IKKB, NPM1, NLRP3 and IRS1.By similarity7 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Irs1P355692EBI-2603444,EBI-400825

    Protein-protein interaction databases

    DIPiDIP-41411N.
    IntActiQ03963. 2 interactions.
    MINTiMINT-270896.

    Structurei

    Secondary structure

    1
    515
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi8 – 2013
    Beta strandi24 – 3310
    Beta strandi35 – 373
    Beta strandi39 – 4810
    Beta strandi54 – 585
    Helixi59 – 7416
    Helixi96 – 10611
    Beta strandi111 – 1155
    Beta strandi119 – 1235
    Beta strandi126 – 1349
    Beta strandi136 – 1449
    Helixi145 – 16218

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1X48NMR-A96-170[»]
    1X49NMR-A1-84[»]
    ProteinModelPortaliQ03963.
    SMRiQ03963. Positions 1-171, 190-504.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ03963.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini8 – 7669DRBM 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini95 – 16268DRBM 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini242 – 504263Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni241 – 515275Interaction with TRAF5By similarityAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi183 – 1875Poly-Ser
    Compositional biasi241 – 2477Asp/Glu-rich (acidic)

    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.
    GeneTreeiENSGT00530000062984.
    HOGENOMiHOG000234351.
    HOVERGENiHBG051430.
    InParanoidiQ03963.
    KOiK16195.
    OMAiRFTFQVI.
    OrthoDBiEOG71VSSK.
    PhylomeDBiQ03963.
    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]

    Sequencei

    Sequence statusi: Complete.

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

    Q03963-1 [UniParc]FASTAAdd to Basket

    « Hide

    MASDTPGFYM DKLNKYRQMH GVAITYKELS TSGPPHDRRF TFQVLIDEKE    50
    FPEAKGRSKQ EARNAAAKLA VDILDNENKV DCHTSASEQG LFVGNYIGLV 100
    NSFAQKKKLS VNYEQCEPNS ELPQRFICKC KIGQTMYGTG SGVTKQEAKQ 150
    LAAKEAYQKL LKSPPKTAGT SSSVVTSTFS GFSSSSSMTS NGVSQSAPGS 200
    FSSENVFTNG LGENKRKSGV KVSPDDVQRN KYTLDARFNS DFEDIEEIGL 250
    GGFGQVFKAK HRIDGKRYAI KRVKYNTEKA EHEVQALAEL NHVNIVQYHS 300
    CWEGVDYDPE HSMSDTSRYK TRCLFIQMEF CDKGTLEQWM RNRNQSKVDK 350
    ALILDLYEQI VTGVEYIHSK GLIHRDLKPG NIFLVDERHI KIGDFGLATA 400
    LENDGKSRTR RTGTLQYMSP EQLFLKHYGK EVDIFALGLI LAELLHTCFT 450
    ESEKIKFFES LRKGDFSNDI FDNKEKSLLK KLLSEKPKDR PETSEILKTL 500
    AEWRNISEKK KRNTC 515
    Length:515
    Mass (Da):58,280
    Last modified:November 1, 1997 - v2
    Checksum:i7A116F7D8DB9B847
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti52 – 521P → G in AAA40150. (PubMed:1714905)Curated
    Sequence conflicti60 – 601Q → T in AAA40150. (PubMed:1714905)Curated
    Sequence conflicti87 – 871S → C in AAA40150. (PubMed:1714905)Curated
    Sequence conflicti144 – 1441T → I in AAA39885. (PubMed:1351683)Curated
    Sequence conflicti281 – 2822EH → DR in AAA39885. (PubMed:1351683)Curated
    Sequence conflicti510 – 5101K → E in AAA40150. (PubMed:1714905)Curated
    Sequence conflicti512 – 5154RNTC → KHMLGPF in AAA40150. (PubMed:1714905)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M65029 mRNA. Translation: AAA40150.1.
    M93567 mRNA. Translation: AAA39885.1.
    U09928
    , U09914, U09915, U09916, U09917, U09918, U09919, U09920, U09921, U09922, U09923, U09924, U09925, U09926, U09927 Genomic DNA. Translation: AAC24729.1.
    AK028602 mRNA. Translation: BAC26027.1.
    CCDSiCCDS28980.1.
    PIRiA59309.
    RefSeqiNP_035293.1. NM_011163.4.
    UniGeneiMm.378990.

    Genome annotation databases

    EnsembliENSMUST00000024884; ENSMUSP00000024884; ENSMUSG00000024079.
    GeneIDi19106.
    KEGGimmu:19106.
    UCSCiuc008dph.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M65029 mRNA. Translation: AAA40150.1 .
    M93567 mRNA. Translation: AAA39885.1 .
    U09928
    , U09914 , U09915 , U09916 , U09917 , U09918 , U09919 , U09920 , U09921 , U09922 , U09923 , U09924 , U09925 , U09926 , U09927 Genomic DNA. Translation: AAC24729.1 .
    AK028602 mRNA. Translation: BAC26027.1 .
    CCDSi CCDS28980.1.
    PIRi A59309.
    RefSeqi NP_035293.1. NM_011163.4.
    UniGenei Mm.378990.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1X48 NMR - A 96-170 [» ]
    1X49 NMR - A 1-84 [» ]
    ProteinModelPortali Q03963.
    SMRi Q03963. Positions 1-171, 190-504.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-41411N.
    IntActi Q03963. 2 interactions.
    MINTi MINT-270896.

    Chemistry

    ChEMBLi CHEMBL1795121.

    PTM databases

    PhosphoSitei Q03963.

    Proteomic databases

    MaxQBi Q03963.
    PaxDbi Q03963.
    PRIDEi Q03963.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000024884 ; ENSMUSP00000024884 ; ENSMUSG00000024079 .
    GeneIDi 19106.
    KEGGi mmu:19106.
    UCSCi uc008dph.2. mouse.

    Organism-specific databases

    CTDi 5610.
    MGIi MGI:1353449. Eif2ak2.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00530000062984.
    HOGENOMi HOG000234351.
    HOVERGENi HBG051430.
    InParanoidi Q03963.
    KOi K16195.
    OMAi RFTFQVI.
    OrthoDBi EOG71VSSK.
    PhylomeDBi Q03963.
    TreeFami TF317576.

    Miscellaneous databases

    EvolutionaryTracei Q03963.
    NextBioi 295666.
    PROi Q03963.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q03963.
    Genevestigatori Q03963.

    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. "TIK, a novel serine/threonine kinase, is recognized by antibodies directed against phosphotyrosine."
      Icely P.L., Gros P., Bergeron J.J.M., Devault A., Afar D.E.H., Bell J.C.
      J. Biol. Chem. 266:16073-16077(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Identification of double-stranded RNA-binding domains in the interferon-induced double-stranded RNA-activated p68 kinase."
      Feng G.S., Chong K., Kumar A., Williams B.R.G.
      Proc. Natl. Acad. Sci. U.S.A. 89:5447-5451(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Mammary carcinoma.
    3. "Mechanism of interferon action: structure of the mouse PKR gene encoding the interferon-inducible RNA-dependent protein kinase."
      Tanaka H., Samuel C.E.
      Proc. Natl. Acad. Sci. U.S.A. 91:7995-7999(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: DBA/2J.
      Tissue: Liver.
    4. "Sequence of the murine interferon-inducible RNA-dependent protein kinase (PKR) deduced from genomic clones."
      Tanaka H., Samuel C.E.
      Gene 153:283-284(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: DBA/2J.
      Tissue: Liver.
    5. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J.
      Tissue: Skin.
    6. "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: INTERACTION WITH IKBKB.
    7. "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.
    8. "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.
    9. "PKR acts early in infection to suppress Semliki Forest virus production and strongly enhances the type I interferon response."
      Barry G., Breakwell L., Fragkoudis R., Attarzadeh-Yazdi G., Rodriguez-Andres J., Kohl A., Fazakerley J.K.
      J. Gen. Virol. 90:1382-1391(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN SFV RESTRICTION.
    10. "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.
    11. "Protein kinase R contributes to immunity against specific viruses by regulating interferon mRNA integrity."
      Schulz O., Pichlmair A., Rehwinkel J., Rogers N.C., Scheuner D., Kato H., Takeuchi O., Akira S., Kaufman R.J., Reis e Sousa C.
      Cell Host Microbe 7:354-361(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    12. "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.
    13. "Double-stranded RNA-activated protein kinase regulates early innate immune responses during respiratory syncytial virus infection."
      Minor R.A., Limmon G.V., Miller-DeGraff L., Dixon D., Andrews D.M., Kaufman R.J., Imani F.
      J. Interferon Cytokine Res. 30:263-272(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    14. "Protein kinase R is responsible for the phosphorylation of eIF2alpha in rotavirus infection."
      Rojas M., Arias C.F., Lopez S.
      J. Virol. 84:10457-10466(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    15. "Role of PKR and Type I IFNs in viral control during primary and secondary infection."
      Nakayama Y., Plisch E.H., Sullivan J., Thomas C., Czuprynski C.J., Williams B.R., Suresh M.
      PLoS Pathog. 6:E1000966-E1000966(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN LCMV RESTRICTION.
    16. "Protein kinase R is a novel mediator of CD40 signaling and plays a critical role in modulating immunoglobulin expression during respiratory syncytial virus infection."
      Thakur S.A., Zalinger Z.B., Johnson T.R., Imani F.
      Clin. Vaccine Immunol. 18:2060-2066(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    17. "Novel insights in the interplay between inflammation and metabolic diseases: a role for the pathogen sensing kinase PKR."
      Marsollier N., Ferre P., Foufelle F.
      J. Hepatol. 54:1307-1309(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    18. "Double-stranded RNA-activated protein kinase is a key modulator of insulin sensitivity in physiological conditions and in obesity in mice."
      Carvalho-Filho M.A., Carvalho B.M., Oliveira A.G., Guadagnini D., Ueno M., Dias M.M., Tsukumo D.M., Hirabara S.M., Reis L.F., Curi R., Carvalheira J.B., Saad M.J.
      Endocrinology 153:5261-5274(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH IRS1.
    19. "Regulation of actin dynamics by protein kinase R control of gelsolin enforces basal innate immune defense."
      Irving A.T., Wang D., Vasilevski O., Latchoumanin O., Kozer N., Clayton A.H., Szczepny A., Morimoto H., Xu D., Williams B.R., Sadler A.J.
      Immunity 36:795-806(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH GSN.
    20. Cited for: FUNCTION, INTERACTION WITH NLRP3, AUTOPHOSPHORYLATION.
    21. "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: FUNCTION, DISRUPTION PHENOTYPE.
    22. "The protein kinase PKR is critical for LPS-induced iNOS production but dispensable for inflammasome activation in macrophages."
      He Y., Franchi L., Nunez G.
      Eur. J. Immunol. 43:1147-1152(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    23. "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: ISGYLATION.
    24. "Blocking the eIF2? kinase (PKR) enhances positive and negative forms of cortex-dependent taste memory."
      Stern E., Chinnakkaruppan A., David O., Sonenberg N., Rosenblum K.
      J. Neurosci. 33:2517-2525(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    25. "Solution structure of the first and second DSRM domain in interferon-induced, double-stranded RNA-activated protein kinase."
      RIKEN structural genomics initiative (RSGI)
      Submitted (NOV-2005) to the PDB data bank
      Cited for: STRUCTURE BY NMR OF 1-171.

    Entry informationi

    Entry nameiE2AK2_MOUSE
    AccessioniPrimary (citable) accession number: Q03963
    Secondary accession number(s): Q61742, Q62026
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 1, 1994
    Last sequence update: November 1, 1997
    Last modified: October 1, 2014
    This is version 144 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3