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Q03963 (E2AK2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Eif2ak2
Synonyms:Pkr, Prkr, Tik
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length515 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

IFN-induced dsRNA-dependent serine/threonine-protein kinase which plays a key role in the innate immune response to viral infection and is also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation. Exerts its antiviral activity on a wide range of DNA and RNA viruses including 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. Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.24

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Enzyme regulation

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.

Subunit structure

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. Ref.6 Ref.7 Ref.8 Ref.10 Ref.18 Ref.19 Ref.20

Subcellular location

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

Tissue specificity

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

Induction

By type I interferons By similarity.

Post-translational modification

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. Ref.20

Disruption phenotype

Mice have significantly elevated numbers of bone marrow derived hematopoietic stem/progenitor cells (HSPCs) and which are more actively proliferating and resistant to stress. Ref.21

Sequence similarities

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily.

Contains 2 DRBM (double-stranded RNA-binding) domains.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processAntiviral defense
Immunity
Innate immunity
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   DomainRepeat
   LigandATP-binding
Nucleotide-binding
RNA-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
Tyrosine-protein kinase
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of MAPKK activity

Inferred from sequence or structural similarity. Source: UniProtKB

defense response to virus

Inferred from electronic annotation. Source: UniProtKB-KW

endoplasmic reticulum unfolded protein response

Inferred from direct assay PubMed 15542627. Source: MGI

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of apoptotic process

Inferred from genetic interaction PubMed 15542627. Source: MGI

negative regulation of osteoblast proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of translation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of viral genome replication

Inferred from mutant phenotype Ref.13. Source: UniProtKB

positive regulation of NF-kappaB transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of NIK/NF-kappaB signaling

Inferred from mutant phenotype Ref.13. Source: UniProtKB

positive regulation of chemokine production

Inferred from mutant phenotype Ref.13. Source: UniProtKB

positive regulation of cytokine production

Inferred from mutant phenotype Ref.13. Source: UniProtKB

positive regulation of stress-activated MAPK cascade

Inferred from mutant phenotype Ref.13. Source: UniProtKB

protein autophosphorylation

Inferred from direct assay Ref.20. Source: UniProtKB

protein phosphorylation

Inferred from direct assay PubMed 15542627PubMed 7519779. Source: MGI

regulation of NLRP3 inflammasome complex assembly

Inferred from mutant phenotype Ref.20. Source: UniProtKB

regulation of hematopoietic progenitor cell differentiation

Inferred from mutant phenotype Ref.21. Source: UniProtKB

regulation of hematopoietic stem cell differentiation

Inferred from mutant phenotype Ref.21. Source: UniProtKB

regulation of hematopoietic stem cell proliferation

Inferred from mutant phenotype Ref.21. Source: UniProtKB

response to interferon-alpha

Inferred from sequence or structural similarity. Source: UniProtKB

response to virus

Inferred from sequence or structural similarity. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

translation

Inferred from direct assay PubMed 7519779. Source: MGI

   Cellular_componentcytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

perinuclear region of cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

double-stranded RNA binding

Inferred from direct assay PubMed 21703541. Source: MGI

non-membrane spanning protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein kinase activity

Inferred from mutant phenotype Ref.12. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Irs1P355692EBI-2603444,EBI-400825

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 515514Interferon-induced, double-stranded RNA-activated protein kinase
PRO_0000085946

Regions

Domain8 – 7669DRBM 1
Domain95 – 16268DRBM 2
Domain242 – 504263Protein kinase
Nucleotide binding248 – 2569ATP By similarity
Region241 – 515275Interaction with TRAF5 By similarity
Compositional bias183 – 1875Poly-Ser
Compositional bias241 – 2477Asp/Glu-rich (acidic)

Sites

Active site3761Proton acceptor By similarity
Binding site2711ATP By similarity

Amino acid modifications

Modified residue21N-acetylalanine By similarity
Modified residue961Phosphotyrosine; by autocatalysis By similarity
Modified residue1571Phosphotyrosine; by autocatalysis By similarity
Modified residue2681Phosphotyrosine; by autocatalysis By similarity
Modified residue4091Phosphothreonine; by autocatalysis By similarity
Modified residue4141Phosphothreonine; by autocatalysis By similarity
Modified residue4191Phosphoserine By similarity
Cross-link68Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15) By similarity
Cross-link154Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15) By similarity

Experimental info

Sequence conflict521P → G in AAA40150. Ref.1
Sequence conflict601Q → T in AAA40150. Ref.1
Sequence conflict871S → C in AAA40150. Ref.1
Sequence conflict1441T → I in AAA39885. Ref.2
Sequence conflict281 – 2822EH → DR in AAA39885. Ref.2
Sequence conflict5101K → E in AAA40150. Ref.1
Sequence conflict512 – 5154RNTC → KHMLGPF in AAA40150. Ref.1

Secondary structure

....................... 515
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q03963 [UniParc].

Last modified November 1, 1997. Version 2.
Checksum: 7A116F7D8DB9B847

FASTA51558,280
        10         20         30         40         50         60 
MASDTPGFYM DKLNKYRQMH GVAITYKELS TSGPPHDRRF TFQVLIDEKE FPEAKGRSKQ 

        70         80         90        100        110        120 
EARNAAAKLA VDILDNENKV DCHTSASEQG LFVGNYIGLV NSFAQKKKLS VNYEQCEPNS 

       130        140        150        160        170        180 
ELPQRFICKC KIGQTMYGTG SGVTKQEAKQ LAAKEAYQKL LKSPPKTAGT SSSVVTSTFS 

       190        200        210        220        230        240 
GFSSSSSMTS NGVSQSAPGS FSSENVFTNG LGENKRKSGV KVSPDDVQRN KYTLDARFNS 

       250        260        270        280        290        300 
DFEDIEEIGL GGFGQVFKAK HRIDGKRYAI KRVKYNTEKA EHEVQALAEL NHVNIVQYHS 

       310        320        330        340        350        360 
CWEGVDYDPE HSMSDTSRYK TRCLFIQMEF CDKGTLEQWM RNRNQSKVDK ALILDLYEQI 

       370        380        390        400        410        420 
VTGVEYIHSK GLIHRDLKPG NIFLVDERHI KIGDFGLATA LENDGKSRTR RTGTLQYMSP 

       430        440        450        460        470        480 
EQLFLKHYGK EVDIFALGLI LAELLHTCFT ESEKIKFFES LRKGDFSNDI FDNKEKSLLK 

       490        500        510 
KLLSEKPKDR PETSEILKTL AEWRNISEKK KRNTC 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Novel role of PKR in inflammasome activation and HMGB1 release."
Lu B., Nakamura T., Inouye K., Li J., Tang Y., Lundbaeck P., Valdes-Ferrer S.I., Olofsson P.S., Kalb T., Roth J., Zou Y., Erlandsson-Harris H., Yang H., Ting J.P., Wang H., Andersson U., Antoine D.J., Chavan S.S., Hotamisligil G.S., Tracey K.J.
Nature 488:670-674(2012) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M65029 mRNA. Translation: AAA40150.1.
M93567 mRNA. Translation: AAA39885.1.
U09928 expand/collapse EMBL AC list , U09914, U09915, U09916, U09917, U09918, U09919, U09920, U09921, U09922, U09923, U09924, U09925, U09926, U09927 Genomic DNA. Translation: AAC24729.1.
AK028602 mRNA. Translation: BAC26027.1.
PIRA59309.
RefSeqNP_035293.1. NM_011163.4.
UniGeneMm.378990.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1X48NMR-A96-171[»]
1X49NMR-A1-85[»]
ProteinModelPortalQ03963.
SMRQ03963. Positions 1-171, 190-504.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-41411N.
IntActQ03963. 2 interactions.
MINTMINT-270896.

Chemistry

ChEMBLCHEMBL1795121.

PTM databases

PhosphoSiteQ03963.

Proteomic databases

PaxDbQ03963.
PRIDEQ03963.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000024884; ENSMUSP00000024884; ENSMUSG00000024079.
GeneID19106.
KEGGmmu:19106.
UCSCuc008dph.2. mouse.

Organism-specific databases

CTD5610.
MGIMGI:1353449. Eif2ak2.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00530000062984.
HOGENOMHOG000234351.
HOVERGENHBG051430.
InParanoidQ03963.
KOK16195.
OMARFTFQVI.
OrthoDBEOG71VSSK.
PhylomeDBQ03963.
TreeFamTF317576.

Gene expression databases

BgeeQ03963.
GenevestigatorQ03963.

Family and domain databases

Gene3D3.30.160.20. 2 hits.
InterProIPR014720. dsRNA-bd_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00035. dsrm. 2 hits.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00358. DSRM. 2 hits.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS50137. DS_RBD. 2 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
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Other

EvolutionaryTraceQ03963.
NextBio295666.
PROQ03963.
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Entry information

Entry nameE2AK2_MOUSE
AccessionPrimary (citable) accession number: Q03963
Secondary accession number(s): Q61742, Q62026
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: November 1, 1997
Last modified: April 16, 2014
This is version 140 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot