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Q03963

- E2AK2_MOUSE

UniProt

Q03963 - E2AK2_MOUSE

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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

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. poly(A) RNA binding Source: Ensembl
  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
Complete GO annotation...

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-KW
  3. perinuclear region of cytoplasm Source: UniProtKB
Complete GO annotation...

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 – 2013Combined sources
Beta strandi24 – 3310Combined sources
Beta strandi35 – 373Combined sources
Beta strandi39 – 4810Combined sources
Beta strandi54 – 585Combined sources
Helixi59 – 7416Combined sources
Helixi96 – 10611Combined sources
Beta strandi111 – 1155Combined sources
Beta strandi119 – 1235Combined sources
Beta strandi126 – 1349Combined sources
Beta strandi136 – 1449Combined sources
Helixi145 – 16218Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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

        10         20         30         40         50
MASDTPGFYM DKLNKYRQMH GVAITYKELS TSGPPHDRRF TFQVLIDEKE
60 70 80 90 100
FPEAKGRSKQ EARNAAAKLA VDILDNENKV DCHTSASEQG LFVGNYIGLV
110 120 130 140 150
NSFAQKKKLS VNYEQCEPNS ELPQRFICKC KIGQTMYGTG SGVTKQEAKQ
160 170 180 190 200
LAAKEAYQKL LKSPPKTAGT SSSVVTSTFS GFSSSSSMTS NGVSQSAPGS
210 220 230 240 250
FSSENVFTNG LGENKRKSGV KVSPDDVQRN KYTLDARFNS DFEDIEEIGL
260 270 280 290 300
GGFGQVFKAK HRIDGKRYAI KRVKYNTEKA EHEVQALAEL NHVNIVQYHS
310 320 330 340 350
CWEGVDYDPE HSMSDTSRYK TRCLFIQMEF CDKGTLEQWM RNRNQSKVDK
360 370 380 390 400
ALILDLYEQI VTGVEYIHSK GLIHRDLKPG NIFLVDERHI KIGDFGLATA
410 420 430 440 450
LENDGKSRTR RTGTLQYMSP EQLFLKHYGK EVDIFALGLI LAELLHTCFT
460 470 480 490 500
ESEKIKFFES LRKGDFSNDI FDNKEKSLLK KLLSEKPKDR PETSEILKTL
510
AEWRNISEKK KRNTC
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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:
PDBei
RCSB PDBi
PDBji
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 146 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