P19525 (E2AK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	EIF2AK2
Synonyms:	PKR, PRKR

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	551 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.
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.
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. Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.26 Ref.31
Subcellular location	Cytoplasm. Nucleus. Cytoplasm › perinuclear 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.
Tissue specificity	Highly expressed in thymus, spleen and bone marrow compared to non-hematopoietic tissues such as small intestine, liver, or kidney tissues. Co-localizes with GSK3B and TAU in the Alzheimer's disease (AD) brain. Elevated levels seen in breast and colon carcinomas,and which correlates with tumor progression and invasiveness or risk of progression.
Induction	By type I interferons.
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.30 Ref.68
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 process	Antiviral defense Host-virus interaction Immunity Innate immunity Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat
Ligand	ATP-binding Nucleotide-binding RNA-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase Tyrosine-protein kinase
PTM	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	defense response to virus Inferred from electronic annotation. Source: UniProtKB-KW endoplasmic reticulum unfolded protein response Inferred from electronic annotation. Source: Compara evasion or tolerance by virus of host immune response Traceable author statement. Source: Reactome modulation by virus of host cellular process Traceable author statement. Source: Reactome negative regulation of osteoblast proliferation Inferred from mutant phenotype PubMed 16216244. Source: UniProtKB protein autophosphorylation Inferred from mutant phenotype PubMed 16216244. Source: UniProtKB translation Inferred from electronic annotation. Source: Compara viral infectious cycle Traceable author statement. Source: Reactome virus-infected cell apoptotic process Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW double-stranded RNA binding Traceable author statement PubMed 1351683. Source: ProtInc 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: EC protein phosphatase type 2A regulator activity Traceable author statement PubMed 10866685. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DHX30	Q7L2E3	3	EBI-640775,EBI-1211456
DHX58	Q96C10	2	EBI-640775,EBI-744193
DHX9	Q08211	2	EBI-640775,EBI-352022
DICER1	Q9UPY3	2	EBI-640775,EBI-395506
DNAJC3	Q27968	5	EBI-640775,EBI-640793	From a different organism.
EDC4	Q6P2E9	2	EBI-640775,EBI-1006038
EIF6	P56537	2	EBI-640775,EBI-372243
FTSJ3	Q8IY81	2	EBI-640775,EBI-744088
MOV10	Q9HCE1	2	EBI-640775,EBI-1055820
STAU2	Q9NUL3	2	EBI-640775,EBI-722938
TARBP2	Q15633	2	EBI-640775,EBI-978581
TOLLIP	Q9H0E2	2	EBI-640775,EBI-74615
ZNF346	Q9UL40	2	EBI-640775,EBI-2462313

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.13

Chain

2 – 551

550

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

PRO_0000085945

Regions

Domain

9 – 77

69

DRBM 1

Domain

100 – 167

68

DRBM 2

Domain

267 – 538

272

Protein kinase

Repeat

331 – 343

13

1

Repeat

345 – 357

13

2

Nucleotide binding

273 – 281

9

ATP By similarity

Region

266 – 551

286

Interaction with TRAF5

Region

331 – 357

27

2 X 13 AA approximate repeats

Sites

Active site

414

1

Proton acceptor By similarity

Binding site

296

1

ATP

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.13

Modified residue

83

1

Phosphoserine Ref.21 Ref.35 Ref.38 Ref.45

Modified residue

88

1

Phosphothreonine; by autocatalysis Probable

Modified residue

89

1

Phosphothreonine; by autocatalysis Probable

Modified residue

90

1

Phosphothreonine; by autocatalysis Probable

Modified residue

101

1

Phosphotyrosine; by autocatalysis Ref.30

Modified residue

162

1

Phosphotyrosine; by autocatalysis Ref.30

Modified residue

242

1

Phosphoserine; by autocatalysis Probable

Modified residue

255

1

Phosphothreonine; by autocatalysis Probable

Modified residue

258

1

Phosphothreonine; by autocatalysis Probable

Modified residue

293

1

Phosphotyrosine; by autocatalysis Ref.30

Modified residue

446

1

Phosphothreonine; by autocatalysis Ref.22 Ref.68

Modified residue

451

1

Phosphothreonine; by autocatalysis Ref.22

Modified residue

456

1

Phosphoserine Ref.35

Cross-link

69

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)

Cross-link

159

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)

Natural variations

Alternative sequence

263 – 303

41

Missing in isoform 2.

VSP_046177

Natural variant

428

1

V → E. Ref.69
Corresponds to variant rs56219559 [ dbSNP | Ensembl ].

VAR_040474

Natural variant

439

1

L → V in a lung adenocarcinoma sample; somatic mutation. Ref.69

VAR_040475

Natural variant

506

1

I → V. Ref.69
Corresponds to variant rs34821155 [ dbSNP | Ensembl ].

VAR_040476

Experimental info

Mutagenesis

59 – 60

2

SK → AA in FL-PKR-2AI; moderate loss of activity but no effect on dsRNA binding.

Mutagenesis

60

1

K → A: Impairs dsRNA binding but not dimerization or activity.

Mutagenesis

67

1

A → E: Significant loss of activity; loss of dsRNA binding and dimerization.

Mutagenesis

83

1

S → A: No effect on enzymatic activity; when associated with A-88; A-89 and A-90. Ref.21

Mutagenesis

88

1

T → A: No effect on enzymatic activity; when associated with A-83; A-89 and A-90. Ref.21

Mutagenesis

89

1

T → A: No effect on enzymatic activity; when associated with A-83; A-88 and A-90. Ref.21

Mutagenesis

90

1

T → A: No effect on enzymatic activity; when associated with A-83; A-88 and A-89. Ref.21

Mutagenesis

149 – 150

2

TK → AA in FL-PKR-2AII; no effect on activity.

Mutagenesis

242

1

S → A: Moderate loss of activity; when associated with A-255 and A-258. Ref.21

Mutagenesis

244 – 296

53

Missing: Loss of activity. Ref.21

Mutagenesis

255

1

T → A: Moderate loss of activity; when associated with A-242 and A-255. Ref.21

Mutagenesis

258

1

T → A: Moderate loss of activity. Ref.21

Mutagenesis

296

1

K → R: Loss of activity. Ref.21

Mutagenesis

446

1

T → A: Significant loss of activity and impairs autophosphorylation of T-451.

Mutagenesis

451

1

T → A: Loss of activity.

Sequence conflict

102

1

I → M in AAP57628. Ref.7

Sequence conflict

224

1

S → R in AAP57628. Ref.7

Sequence conflict

512

1

K → E in AAF13156. Ref.6

Secondary structure

1

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551

Helix Strand Turn

Details...

Beta strand

5 – 7

3

Helix

10 – 21

12

Beta strand

26 – 32

7

Turn

35 – 37

3

Beta strand

41 – 50

10

Beta strand

54 – 56

3

Helix

61 – 76

16

Helix

102 – 111

10

Beta strand

115 – 123

9

Beta strand

125 – 138

14

Beta strand

144 – 149

6

Helix

150 – 167

18

Helix

261 – 266

6

Beta strand

267 – 274

8

Beta strand

276 – 278

3

Beta strand

281 – 286

6

Turn

287 – 289

3

Beta strand

292 – 299

8

Helix

303 – 305

3

Helix

306 – 314

9

Beta strand

323 – 332

10

Beta strand

358 – 366

9

Helix

374 – 380

7

Helix

381 – 383

3

Helix

388 – 407

20

Beta strand

410 – 412

3

Helix

417 – 419

3

Beta strand

420 – 424

5

Beta strand

427 – 430

4

Beta strand

437 – 440

4

Helix

457 – 461

5

Helix

468 – 482

15

Helix

488 – 499

12

Beta strand

505 – 507

3

Helix

509 – 518

10

Helix

523 – 525

3

Helix

529 – 539

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1991. Version 2. Checksum: 815AD83ACAB45DA3	FASTA	551	62,094
	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
	Isoform 2 [UniParc]. Checksum: 6EC61AFC54DEFCA4	FASTA	510	57,391
	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 KRKAEREVKA LAKLDHVNIV HYNGCWDGFD YDPETSDDSL 310 320 330 340 350 360 ESSDYDPENS KNSSRSKTKC LFIQMEFCDK GTLEQWIEKR RGEKLDKVLA LELFEQITKG 370 380 390 400 410 420 VDYIHSKKLI HRDLKPSNIF LVDTKQVKIG DFGLVTSLKN DGKRTRSKGT LRYMSPEQIS 430 440 450 460 470 480 SQDYGKEVDL YALGLILAEL LHVCDTAFET SKFFTDLRDG IISDIFDKKE KTLLQKLLSK 490 500 510 KPEDRPNTSE ILRTLTVWKK SPEKNERHTC

References

	« Hide 'large scale' referencesShow '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. , 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]	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. , 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, 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]	"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.
[24]	"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.
[25]	"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.
[26]	"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.
[27]	"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.
[28]	"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.
[29]	"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.
[30]	"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.
[31]	"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.
[32]	"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.
[33]	"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.
[34]	"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.
[35]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[36]	"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.
[37]	"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.
[38]	"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, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[39]	"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.
[40]	"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.
[41]	"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.
[42]	"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.
[43]	"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.
[44]	"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.
[45]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[46]	"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].
[47]	"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.
[48]	"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.
[49]	"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.
[50]	"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.
[51]	"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.
[52]	"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.
[53]	"Penetration resistance: PKR's other talent." Lacy-Hulbert A., Stuart L.M. Immunity 36:695-696(2012) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[54]	"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.
[55]	"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.
[56]	"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.
[57]	"PKR-dependent inflammatory signals." Kang R., Tang D. Sci. Signal. 5:PE47-PE47(2012) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[58]	"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.
[59]	"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.
[60]	"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 0:0-0(2013) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[61]	"The eIF2alpha kinases: their structures and functions." Donnelly N., Gorman A.M., Gupta S., Samali A. Cell. Mol. Life Sci. 0:0-0(2013) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[62]	"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.
[63]	"Toscana virus NSs protein promoftes degradation of double-stranded RNA-dependent protein kinase." Kalveram B., Ikegami T. J. Virol. 0:0-0(2013) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TOS NSS, ENZYME REGULATION.
[64]	"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.
[65]	"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.
[66]	"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.
[67]	"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.
[68]	"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.
[69]	"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.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00019463.
IPI00385404.

PIR

JC5225.

RefSeq

NP_001129123.1. NM_001135651.2.
NP_001129124.1. NM_001135652.2.
NP_002750.1. NM_002759.3.

UniGene

Hs.131431.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1QU6	NMR	-	A	1-170	[»]
2A19	X-ray	2.50	B/C	258-550	[»]
2A1A	X-ray	2.80	B	258-550	[»]
3UIU	X-ray	2.90	A/B	254-551	[»]

ProteinModelPortal

P19525.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-2657N.

IntAct

P19525. 45 interactions.

MINT

MINT-92415.

STRING

9606.ENSP00000233057.

PTM databases

PhosphoSite

P19525.

Polymorphism databases

DMDM

125527.

Proteomic databases

PaxDb

P19525.

PRIDE

P19525.

Protocols and materials databases

DNASU

5610.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000233057; ENSP00000233057; ENSG00000055332.
ENST00000395127; ENSP00000378559; ENSG00000055332.
ENST00000405334; ENSP00000385014; ENSG00000055332.

GeneID

5610.

KEGG

hsa:5610.

UCSC

uc010fab.2. human.
uc010fac.3. human.

Organism-specific databases

CTD

5610.

GeneCards

GC02M037326.

HGNC

HGNC:9437. EIF2AK2.

HPA

CAB003845.
HPA019795.

MIM

176871. gene.

neXtProt

NX_P19525.

PharmGKB

PA33779.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000234351.

HOVERGEN

HBG051430.

InParanoid

P19525.

KO

K16195.

OMA

MNGLRNN.

OrthoDB

EOG4548ZD.

PhylomeDB

P19525.

Enzyme and pathway databases

Reactome

REACT_116125. Disease.
REACT_6900. Immune System.

SignaLink

P19525.

Gene expression databases

ArrayExpress

P19525.

Bgee

P19525.

CleanEx

HS_EIF2AK2.

Genevestigator

P19525.

GermOnline

ENSG00000055332. Homo sapiens.

Family and domain databases

Gene3D

3.30.160.20. 2 hits.

InterPro

IPR001159. Ds-RNA-bd.
IPR014720. dsRNA-bd-like_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

PF00035. dsrm. 2 hits.
PF00069. Pkinase. 1 hit.
[Graphical view]

SMART

SM00358. DSRM. 2 hits.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

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]

ProtoNet

Search...

Other

BindingDB

P19525.

ChEMBL

CHEMBL5785.

ChiTaRS

EIF2AK2. human.

EvolutionaryTrace

P19525.

GenomeRNAi

5610.

NextBio

13635839.

PMAP-CutDB

P19525.

SOURCE

Search...

Entry information

Entry name

E2AK2_HUMAN

Accession

Primary (citable) accession number: P19525
Secondary accession number(s): A8K3P0 , D6W584, E9PC80, Q52M43, Q7Z6F6, Q9UIR4

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	May 1, 1991
Last modified:	May 29, 2013
This is version 162 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.