Q63184 (E2AK2_RAT) 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
Protein kinase RNA-activated
Short name=PKR
Tyrosine-protein kinase EIF2AK2
EC=2.7.10.2

Gene names

Name:	Eif2ak2
Synonyms:	Prkr

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	513 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	Following activation by double-stranded RNA in the presence of ATP, the kinase becomes autophosphorylated and can catalyze the phosphorylation of the translation initiation factor EIF2S1, which leads to an inhibition of the initiation of protein synthesis. Double-stranded RNA is generated during the course of a viral infection. In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity: phosphorylates CDK1 upon DNA damage. CDK1 phosphorylation triggers CDK1 polyubiquitination and subsequent proteolysis, thus leading to G2 arrest By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Enzyme regulation	Activity is markedly stimulated by manganese ions. Besides dsRNA, heparin is a potent activator of the kinase By similarity.
Subunit structure	Homodimer By similarity. Interacts with DNAJC3 By similarity. Interacts with STRBP. Forms a complex with FANCA, FANCC, FANCG and HSP70 By similarity. Interacts with ADAR/ADAR1 By similarity. Ref.2
Induction	By interferon By similarity.
Post-translational modification	Autophosphorylated on several Ser, Thr and Tyr residues. Autophosphorylation of Thr-411 is dependent on Thr-406 and is stimulated by dsRNA binding and dimerization. Autophosphorylation apparently leads to the activation of the kinase. Tyrosine autophosphorylation is essential for efficient dsRNA-binding, dimerization, and kinase activation By similarity.
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
Domain	Repeat
Ligand	ATP-binding Nucleotide-binding RNA-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase Tyrosine-protein kinase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	defense response to virus Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of osteoblast proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of apoptotic process Inferred from mutant phenotype PubMed 18535002. Source: RGD response to exogenous dsRNA Inferred from expression pattern PubMed 15920723. Source: RGD response to lipopolysaccharide Inferred from mutant phenotype PubMed 15630703. Source: RGD response to mechanical stimulus Inferred from expression pattern PubMed 15781241. Source: RGD response to toxin Inferred from mutant phenotype PubMed 18535002. Source: RGD response to vitamin E Inferred from physical interaction PubMed 17953670. Source: RGD
Cellular_component	nucleus Inferred from direct assay PubMed 17953670. Source: RGD
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW double-stranded RNA binding Inferred from electronic annotation. Source: InterPro non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 513	512	Interferon-induced, double-stranded RNA-activated protein kinase		PRO_0000274915
Regions
	Domain	8 – 76	69	DRBM 1
	Domain	95 – 162	68	DRBM 2
	Domain	236 – 502	267	Protein kinase
	Nucleotide binding	242 – 250	9	ATP By similarity
	Compositional bias	161 – 194	34	Ser-rich
Sites
	Active site	373	1	Proton acceptor By similarity
	Binding site	265	1	ATP By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylalanine By similarity
	Modified residue	82	1	Phosphoserine By similarity
	Modified residue	96	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	157	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	262	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	406	1	Phosphothreonine; by autocatalysis By similarity
	Modified residue	411	1	Phosphothreonine; by autocatalysis By similarity
	Modified residue	416	1	Phosphoserine By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q63184 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 716751E84B7FED88	FASTA	513	58,259
	10 20 30 40 50 60 MASDTPGFYV DKLNKYSQIH KVKIIYKEIS VTGPPHDRRF TFQVIIEERE FPEGEGRSKQ 70 80 90 100 110 120 EAKNNAAKLA VEILDNENKV DSHTDASEQG LIEGNYIGLV NSFAQKENLP VNFELCDPDS 130 140 150 160 170 180 QLPHRFICKC KIGQTTYGTG FGANKKEAKQ LAAKNAYQKL SEKSPSKTGF VTSLSSDFSS 190 200 210 220 230 240 SSSITSNSAS QSASGRDFED IFMNGLREKR KSGVKVPSDD VLRNKYTLDD RFSKDFEDIE 250 260 270 280 290 300 EIGSGGFGQV FKAKHRIDGK TYAIKRITYN TKKAKREVQA LAELNHANIV QYRVCWEGED 310 320 330 340 350 360 YDYDPENSTN GDTSRYKTRC LFIQMEFCDK GTLQQWLEKR NRSQEDKALV LELFEQIVTG 370 380 390 400 410 420 VDYIHSKGLI HRDLKPGNIF LVDEKHIKIG DFGLATALEN DGNPRTKYTG TPQYMSPEQK 430 440 450 460 470 480 SSLVEYGKEV DIFALGLILA ELLHICKTDS EKIEFFQLLR NGIFSDDIFD NKEKSLLQKL 490 500 510 LSSKPRERPN TSEILKTLAE WKNISEKKKR NTC

References

[1]	"Cloning and characterization of a cDNA encoding rat PKR, the double-stranded RNA-dependent eukaryotic initiation factor-2 kinase." Mellor H., Flowers K.M., Kimball S.R., Jefferson L.S. Biochim. Biophys. Acta 1219:693-696(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Brain.
[2]	"A new double-stranded RNA-binding protein that interacts with PKR." Coolidge C.J., Patton J.G. Nucleic Acids Res. 28:1407-1417(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH STRBP.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L29281 mRNA. Translation: AAA61926.1.
IPI	IPI00206017.
PIR	S50216.
RefSeq	NP_062208.1. NM_019335.1.
UniGene	Rn.10022. Rn.233226.
3D structure databases
HSSP	HSSP built from PDB template 2A19 based on UniProtKB P19525.
ProteinModelPortal	Q63184.
SMR	Q63184. Positions 1-176, 226-502.
ModBase	Search...
Proteomic databases
PRIDE	Q63184.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	54287.
KEGG	rno:54287.
Organism-specific databases
CTD	5610.
RGD	3402. Eif2ak2.
Phylogenomic databases
HOVERGEN	HBG051430.
KO	K16195.
Gene expression databases
Genevestigator	Q63184.
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
NextBio	610880.

Entry information

Entry name

E2AK2_RAT

Accession

Primary (citable) accession number: Q63184

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 6, 2007
Last sequence update:	November 1, 1996
Last modified:	April 3, 2013
This is version 89 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program