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P19525 (E2AK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 175. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·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
Tyrosine-protein kinase EIF2AK2
EC=2.7.10.2
p68 kinase
Gene names
Name:EIF2AK2
Synonyms:PKR, PRKR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length551 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 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. Ref.19 Ref.24 Ref.26 Ref.28 Ref.34 Ref.37 Ref.38 Ref.40 Ref.41 Ref.42 Ref.43 Ref.44 Ref.45 Ref.51 Ref.52 Ref.53 Ref.55 Ref.56 Ref.58 Ref.61 Ref.65 Ref.67 Ref.68 Ref.69

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 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. Ref.25 Ref.34 Ref.35 Ref.65 Ref.66

Subunit structure

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. Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.32 Ref.34 Ref.35 Ref.38 Ref.56 Ref.58 Ref.66

Subcellular location

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. Ref.28 Ref.48 Ref.51 Ref.53

Tissue specificity

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. Ref.48 Ref.63

Induction

By type I interferons. Ref.1 Ref.25 Ref.34 Ref.35 Ref.65 Ref.66

Post-translational modification

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. Ref.21 Ref.22 Ref.31 Ref.45 Ref.48 Ref.51 Ref.58 Ref.71

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
Host-virus interaction
Immunity
Innate immunity
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   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
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of MAPKK activity

Inferred from mutant phenotype Ref.26. Source: UniProtKB

defense response to virus

Inferred from electronic annotation. Source: UniProtKB-KW

endoplasmic reticulum unfolded protein response

Inferred from electronic annotation. Source: Ensembl

evasion or tolerance by virus of host immune response

Traceable author statement. Source: Reactome

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

modulation by virus of host morphology or physiology

Traceable author statement. Source: Reactome

modulation by virus of host process

Traceable author statement. Source: Reactome

negative regulation of cell proliferation

Traceable author statement PubMed 1351683. Source: ProtInc

negative regulation of osteoblast proliferation

Inferred from mutant phenotype PubMed 16216244. Source: UniProtKB

negative regulation of translation

Inferred from direct assay Ref.25. Source: UniProtKB

negative regulation of viral genome replication

Inferred from mutant phenotype Ref.40Ref.44. Source: UniProtKB

positive regulation of NF-kappaB transcription factor activity

Inferred from direct assay Ref.28. Source: UniProtKB

positive regulation of NIK/NF-kappaB signaling

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of chemokine production

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cytokine production

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of stress-activated MAPK cascade

Inferred from sequence or structural similarity. Source: UniProtKB

protein autophosphorylation

Inferred from direct assay Ref.58. Source: UniProtKB

protein phosphorylation

Inferred from direct assay Ref.40. Source: UniProtKB

regulation of NLRP3 inflammasome complex assembly

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of hematopoietic progenitor cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of hematopoietic stem cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of hematopoietic stem cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

response to interferon-alpha

Inferred from direct assay Ref.44. Source: UniProtKB

response to virus

Inferred from mutant phenotype Ref.40. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

translation

Inferred from electronic annotation. Source: Ensembl

viral life cycle

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasm

Inferred from direct assay Ref.28. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

perinuclear region of cytoplasm

Inferred from direct assay Ref.28. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

double-stranded RNA binding

Inferred from direct assay PubMed 21266579. Source: MGI

eukaryotic translation initiation factor 2alpha kinase activity

Traceable author statement PubMed 10866685. Source: ProtInc

non-membrane spanning protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

poly(A) RNA binding

Inferred from direct assay PubMed 22681889. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.25Ref.28Ref.26Ref.35PubMed 18362360Ref.34Ref.58. Source: UniProtKB

protein kinase activity

Inferred from direct assay Ref.25Ref.26Ref.34. Source: UniProtKB

protein phosphatase type 2A regulator activity

Traceable author statement PubMed 10866685. Source: ProtInc

protein serine/threonine kinase activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P19525-1)

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.
Isoform 2 (identifier: P19525-2)

The sequence of this isoform differs from the canonical sequence as follows:
     263-303: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.13
Chain2 – 551550Interferon-induced, double-stranded RNA-activated protein kinase
PRO_0000085945

Regions

Domain9 – 7769DRBM 1
Domain100 – 16768DRBM 2
Domain267 – 538272Protein kinase
Repeat331 – 343131
Repeat345 – 357132
Nucleotide binding273 – 2819ATP By similarity
Region266 – 551286Interaction with TRAF5
Region331 – 357272 X 13 AA approximate repeats

Sites

Active site4141Proton acceptor By similarity
Binding site2961ATP

Amino acid modifications

Modified residue21N-acetylalanine Ref.13 Ref.57 Ref.59
Modified residue831Phosphoserine Ref.21 Ref.36 Ref.39 Ref.46
Modified residue881Phosphothreonine; by autocatalysis Probable
Modified residue891Phosphothreonine; by autocatalysis Probable
Modified residue901Phosphothreonine; by autocatalysis Probable
Modified residue1011Phosphotyrosine; by autocatalysis Ref.31
Modified residue1621Phosphotyrosine; by autocatalysis Ref.31
Modified residue2421Phosphoserine; by autocatalysis Probable
Modified residue2551Phosphothreonine; by autocatalysis Probable
Modified residue2581Phosphothreonine; by autocatalysis Probable
Modified residue2931Phosphotyrosine; by autocatalysis Ref.31
Modified residue4461Phosphothreonine; by autocatalysis Ref.22 Ref.71
Modified residue4511Phosphothreonine; by autocatalysis Ref.22 Ref.45
Modified residue4561Phosphoserine Ref.36
Cross-link69Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15) Ref.65
Cross-link159Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15) Ref.65

Natural variations

Alternative sequence263 – 30341Missing in isoform 2.
VSP_046177
Natural variant4281V → E. Ref.72
Corresponds to variant rs56219559 [ dbSNP | Ensembl ].
VAR_040474
Natural variant4391L → V in a lung adenocarcinoma sample; somatic mutation. Ref.72
VAR_040475
Natural variant5061I → V. Ref.72
Corresponds to variant rs34821155 [ dbSNP | Ensembl ].
VAR_040476

Experimental info

Mutagenesis59 – 602SK → AA in FL-PKR-2AI; moderate loss of activity but no effect on dsRNA binding.
Mutagenesis601K → A: Impairs dsRNA binding but not dimerization or activity.
Mutagenesis671A → E: Significant loss of activity; loss of dsRNA binding and dimerization.
Mutagenesis831S → A: No effect on enzymatic activity; when associated with A-88; A-89 and A-90. Ref.21
Mutagenesis881T → A: No effect on enzymatic activity; when associated with A-83; A-89 and A-90. Ref.21
Mutagenesis891T → A: No effect on enzymatic activity; when associated with A-83; A-88 and A-90. Ref.21
Mutagenesis901T → A: No effect on enzymatic activity; when associated with A-83; A-88 and A-89. Ref.21
Mutagenesis149 – 1502TK → AA in FL-PKR-2AII; no effect on activity.
Mutagenesis2421S → A: Moderate loss of activity; when associated with A-255 and A-258. Ref.21
Mutagenesis244 – 29653Missing: Loss of activity. Ref.21
Mutagenesis2551T → A: Moderate loss of activity; when associated with A-242 and A-255. Ref.21
Mutagenesis2581T → A: Moderate loss of activity. Ref.21
Mutagenesis2961K → R: Loss of activity. Ref.21
Mutagenesis4461T → A: Significant loss of activity and impairs autophosphorylation of T-451.
Mutagenesis4511T → A: Loss of activity.
Sequence conflict1021I → M in AAP57628. Ref.7
Sequence conflict2241S → R in AAP57628. Ref.7
Sequence conflict5121K → E in AAF13156. Ref.6

Secondary structure

..................................................................... 551
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 1991. Version 2.
Checksum: 815AD83ACAB45DA3

FASTA55162,094
        10         20         30         40         50         60 
MAGDLSAGFF MEELNTYRQK QGVVLKYQEL PNSGPPHDRR FTFQVIIDGR EFPEGEGRSK 

        70         80         90        100        110        120 
KEAKNAAAKL AVEILNKEKK AVSPLLLTTT NSSEGLSMGN YIGLINRIAQ KKRLTVNYEQ 

       130        140        150        160        170        180 
CASGVHGPEG FHYKCKMGQK EYSIGTGSTK QEAKQLAAKL AYLQILSEET SVKSDYLSSG 

       190        200        210        220        230        240 
SFATTCESQS NSLVTSTLAS ESSSEGDFSA DTSEINSNSD SLNSSSLLMN GLRNNQRKAK 

       250        260        270        280        290        300 
RSLAPRFDLP DMKETKYTVD KRFGMDFKEI ELIGSGGFGQ VFKAKHRIDG KTYVIKRVKY 

       310        320        330        340        350        360 
NNEKAEREVK ALAKLDHVNI VHYNGCWDGF DYDPETSDDS LESSDYDPEN SKNSSRSKTK 

       370        380        390        400        410        420 
CLFIQMEFCD KGTLEQWIEK RRGEKLDKVL ALELFEQITK GVDYIHSKKL IHRDLKPSNI 

       430        440        450        460        470        480 
FLVDTKQVKI GDFGLVTSLK NDGKRTRSKG TLRYMSPEQI SSQDYGKEVD LYALGLILAE 

       490        500        510        520        530        540 
LLHVCDTAFE TSKFFTDLRD GIISDIFDKK EKTLLQKLLS KKPEDRPNTS EILRTLTVWK 

       550 
KSPEKNERHT C 

« Hide

Isoform 2 [UniParc].

Checksum: 6EC61AFC54DEFCA4
Show »

FASTA51057,391

References

« Hide 'large scale' references
[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. expand/collapse author list , 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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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]"TRAF family proteins link PKR with NF-kappa B activation."
Gil J., Garcia M.A., Gomez-Puertas P., Guerra S., Rullas J., Nakano H., Alcami J., Esteban M.
Mol. Cell. Biol. 24:4502-4512(2004) [PubMed] [Europe PMC] [Abstract]
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]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
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]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
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]"Cytoplasmic STAT3 represses autophagy by inhibiting PKR activity."
Shen S., Niso-Santano M., Adjemian S., Takehara T., Malik S.A., Minoux H., Souquere S., Marino G., Lachkar S., Senovilla L., Galluzzi L., Kepp O., Pierron G., Maiuri M.C., Hikita H., Kroemer R., Kroemer G.
Mol. Cell 48:667-680(2012) [PubMed] [Europe PMC] [Abstract]
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]"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 NLRP1; NLRP3; NLRC4 AND AIM2, AUTOPHOSPHORYLATION.
[59]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M35663 mRNA. Translation: AAA36409.1.
M85294 mRNA. Translation: AAA18253.1.
U50648 expand/collapse EMBL AC list , U50634, U50635, U50636, U50637, U50638, U50639, U50640, U50641, U50642, U50643, U50644, U50645, U50646, U50647 Genomic DNA. Translation: AAC50768.1.
AF167472 expand/collapse EMBL AC list , 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.
CCDSCCDS1786.1. [P19525-1]
CCDS46259.1. [P19525-2]
PIRJC5225.
RefSeqNP_001129123.1. NM_001135651.2. [P19525-1]
NP_001129124.1. NM_001135652.2. [P19525-2]
NP_002750.1. NM_002759.3. [P19525-1]
UniGeneHs.131431.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1QU6NMR-A1-170[»]
2A19X-ray2.50B/C258-538[»]
2A1AX-ray2.80B258-538[»]
3UIUX-ray2.90A/B254-551[»]
ProteinModelPortalP19525.
SMRP19525. Positions 1-170, 257-541.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111596. 216 interactions.
DIPDIP-2657N.
IntActP19525. 53 interactions.
MINTMINT-92415.
STRING9606.ENSP00000233057.

Chemistry

BindingDBP19525.
ChEMBLCHEMBL5785.
GuidetoPHARMACOLOGY2016.

PTM databases

PhosphoSiteP19525.

Polymorphism databases

DMDM125527.

Proteomic databases

MaxQBP19525.
PaxDbP19525.
PRIDEP19525.

Protocols and materials databases

DNASU5610.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000233057; ENSP00000233057; ENSG00000055332. [P19525-1]
ENST00000395127; ENSP00000378559; ENSG00000055332. [P19525-1]
ENST00000405334; ENSP00000385014; ENSG00000055332. [P19525-2]
GeneID5610.
KEGGhsa:5610.
UCSCuc010fac.3. human. [P19525-1]

Organism-specific databases

CTD5610.
GeneCardsGC02M037326.
HGNCHGNC:9437. EIF2AK2.
HPACAB003845.
HPA019795.
MIM176871. gene.
neXtProtNX_P19525.
PharmGKBPA33779.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000234351.
HOVERGENHBG051430.
InParanoidP19525.
KOK16195.
OMARFTFQVI.
OrthoDBEOG71VSSK.
PhylomeDBP19525.
TreeFamTF317576.

Enzyme and pathway databases

ReactomeREACT_116125. Disease.
REACT_6900. Immune System.
SignaLinkP19525.

Gene expression databases

ArrayExpressP19525.
BgeeP19525.
CleanExHS_EIF2AK2.
GenevestigatorP19525.

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]
ProtoNetSearch...

Other

ChiTaRSEIF2AK2. human.
EvolutionaryTraceP19525.
GeneWikiProtein_kinase_R.
GenomeRNAi5610.
NextBio13635839.
PMAP-CutDBP19525.
PROP19525.
SOURCESearch...

Entry information

Entry nameE2AK2_HUMAN
AccessionPrimary (citable) accession number: P19525
Secondary accession number(s): A8K3P0 expand/collapse secondary AC list , D6W584, E9PC80, Q52M43, Q7Z6F6, Q9UIR4
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: May 1, 1991
Last modified: July 9, 2014
This is version 175 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

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SIMILARITY comments

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