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P19525

- E2AK2_HUMAN

UniProt

P19525 - E2AK2_HUMAN

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Protein

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

Gene
EIF2AK2, PKR, PRKR
Organism
Homo sapiens (Human)
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 hepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV) and herpes simplex virus 1 (HHV-1). Inhibits viral replication via phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (EIF2S1), this phosphorylation impairs the recycling of EIF2S1 between successive rounds of initiation leading to inhibition of translation which eventually results in shutdown of cellular and viral protein synthesis. Also phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1 and the HHV-1 viral protein US11. In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity and phosphorylates CDK1 at 'Tyr-4' upon DNA damage, facilitating its ubiquitination and proteosomal degradation. Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding proinflammatory cytokines and IFNs. Activates the NF-kappa-B pathway via interaction with IKBKB and TRAF family of proteins and activates the p38 MAP kinase pathway via interaction with MAP2K6. Can act as both a positive and negative regulator of the insulin signaling pathway (ISP). Negatively regulates ISP by inducing the inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at 'Ser-312' and positively regulates ISP via phosphorylation of PPP2R5A which activates FOXO1, which in turn up-regulates the expression of insulin receptor substrate 2 (IRS2). Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes. Can trigger apoptosis via FADD-mediated activation of CASP8. Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin.24 Publications

Catalytic activityi

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

Enzyme regulationi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei296 – 2961ATP
Active sitei414 – 4141Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi273 – 2819ATP By similarity

GO - Molecular functioni

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

GO - Biological processi

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

Keywords - Molecular functioni

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

Keywords - Biological processi

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

Keywords - Ligandi

ATP-binding, Nucleotide-binding, RNA-binding

Enzyme and pathway databases

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

Names & Taxonomyi

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

Organism-specific databases

HGNCiHGNC:9437. EIF2AK2.

Subcellular locationi

Cytoplasm. Nucleus. Cytoplasmperinuclear region
Note: Nuclear localization is elevated in acute leukemia, myelodysplastic syndrome (MDS), melanoma, breast, colon, prostate and lung cancer patient samples or cell lines as well as neurocytes from advanced Creutzfeldt-Jakob disease patients.4 Publications

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytosol Source: Reactome
  3. nucleus Source: UniProtKB-SubCell
  4. perinuclear region of cytoplasm Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

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

Organism-specific databases

PharmGKBiPA33779.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 551550Interferon-induced, double-stranded RNA-activated protein kinasePRO_0000085945Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine3 Publications
Cross-linki69 – 69Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)1 Publication
Modified residuei83 – 831Phosphoserine4 Publications
Modified residuei88 – 881Phosphothreonine; by autocatalysis Inferred
Modified residuei89 – 891Phosphothreonine; by autocatalysis Inferred
Modified residuei90 – 901Phosphothreonine; by autocatalysis Inferred
Modified residuei101 – 1011Phosphotyrosine; by autocatalysis1 Publication
Cross-linki159 – 159Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)1 Publication
Modified residuei162 – 1621Phosphotyrosine; by autocatalysis1 Publication
Modified residuei242 – 2421Phosphoserine; by autocatalysis Inferred
Modified residuei255 – 2551Phosphothreonine; by autocatalysis Inferred
Modified residuei258 – 2581Phosphothreonine; by autocatalysis Inferred
Modified residuei293 – 2931Phosphotyrosine; by autocatalysis1 Publication
Modified residuei446 – 4461Phosphothreonine; by autocatalysis2 Publications
Modified residuei451 – 4511Phosphothreonine; by autocatalysis2 Publications
Modified residuei456 – 4561Phosphoserine1 Publication

Post-translational modificationi

Autophosphorylated on several Ser, Thr and Tyr residues. Autophosphorylation of Thr-451 is dependent on Thr-446 and is stimulated by dsRNA binding and dimerization. Autophosphorylation apparently leads to the activation of the kinase. Tyrosine autophosphorylation is essential for efficient dsRNA-binding, dimerization, and kinase activation.8 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP19525.
PaxDbiP19525.
PRIDEiP19525.

PTM databases

PhosphoSiteiP19525.

Miscellaneous databases

PMAP-CutDBP19525.

Expressioni

Tissue specificityi

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

Inductioni

By type I interferons.6 Publications

Gene expression databases

ArrayExpressiP19525.
BgeeiP19525.
CleanExiHS_EIF2AK2.
GenevestigatoriP19525.

Organism-specific databases

HPAiCAB003845.
HPA019795.

Interactioni

Subunit structurei

Homodimer. Interacts with STRBP By similarity. Interacts with DNAJC3. Inhibited by direct interaction with viral proteins such as HCV E2, HCV NS5A and influenza A NS1. Activated by the interaction with HIV-1 Tat By similarity. Forms a complex with FANCA, FANCC, FANCG and HSP70. Interacts with ADAR/ADAR1. Interacts with IRS1 By similarity. The inactive form interacts with NCK1 and GSN. Interacts (via the kinase catalytic domain) with STAT3 (via SH2 domain), TRAF2 (C-terminus), TRAF5 (C-terminus) and TRAF6 (C-terminus). Interacts with MAP2K6, IKBKB/IKKB, NPM1, TARBP2, NLRP1, NLRP3, NLRC4 and AIM2. Interacts (via DRBM 1 domain) with DUS2L (via DRBM domain). Interacts with DHX9 (via N-terminus) and this interaction is dependent upon activation of the kinase. Interacts with human herpes simplex virus 1 (HHV-1) protein US11 in an RNA-dependent manner. The inactive form interacts with Toscana virus (TOS) NSS. Interacts with herpes virus 8 protein v-IRF2; this interaction inhibits EIF2AK2 activation.20 Publications

Binary interactionsi

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

Protein-protein interaction databases

BioGridi111596. 78 interactions.
DIPiDIP-2657N.
IntActiP19525. 53 interactions.
MINTiMINT-92415.
STRINGi9606.ENSP00000233057.

Structurei

Secondary structure

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

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiP19525.

Family & Domainsi

Domains and Repeats

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

Region

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

Sequence similaritiesi

Keywords - Domaini

Repeat

Phylogenomic databases

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

Family and domain databases

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

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. Align

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

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

« Hide

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

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

Note: No experimental confirmation available.

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

Natural variant

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

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei263 – 30341Missing in isoform 2. VSP_046177Add
BLAST

Sequence conflict

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

Sequence databases

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

Genome annotation databases

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

Polymorphism databases

DMDMi125527.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

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

Sequence databases

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

3D structure databases

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

Protein-protein interaction databases

BioGridi 111596. 78 interactions.
DIPi DIP-2657N.
IntActi P19525. 53 interactions.
MINTi MINT-92415.
STRINGi 9606.ENSP00000233057.

Chemistry

BindingDBi P19525.
ChEMBLi CHEMBL5785.
GuidetoPHARMACOLOGYi 2016.

PTM databases

PhosphoSitei P19525.

Polymorphism databases

DMDMi 125527.

Proteomic databases

MaxQBi P19525.
PaxDbi P19525.
PRIDEi P19525.

Protocols and materials databases

DNASUi 5610.
Structural Biology Knowledgebase Search...

Genome annotation databases

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

Organism-specific databases

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

Phylogenomic databases

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

Enzyme and pathway databases

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

Miscellaneous databases

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

Gene expression databases

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

Family and domain databases

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

Publicationsi

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

Entry informationi

Entry nameiE2AK2_HUMAN
AccessioniPrimary (citable) accession number: P19525
Secondary accession number(s): A8K3P0
, D6W584, E9PC80, Q52M43, Q7Z6F6, Q9UIR4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: May 1, 1991
Last modified: September 3, 2014
This is version 176 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

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

Documents

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

External Data

Dasty 3

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