UniProtKB - Q63184 (E2AK2_RAT)
Interferon-induced, double-stranded RNA-activated protein kinase
Eif2ak2
Functioni
IFN-induced dsRNA-dependent serine/threonine-protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) and plays a key role in the innate immune response to viral infection (By similarity).
Inhibits viral replication via the integrated stress response (ISR): EIF2S1/eIF-2-alpha phosphorylation in response to viral infection converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, resulting to a shutdown of cellular and viral protein synthesis, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4 (By similarity).
Exerts its antiviral activity on a wide range of DNA and RNA viruses (By similarity).
Also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation: phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3 and IRS1 (By similarity).
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 (By similarity).
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 (By similarity).
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 (By similarity).
Can act as both a positive and negative regulator of the insulin signaling pathway (ISP) (By similarity).
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) (By similarity).
Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes (By similarity).
Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin (By similarity).
By similarityCatalytic activityi
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 265 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 373 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 242 – 250 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- double-stranded RNA binding Source: RGD
- eukaryotic translation initiation factor 2alpha kinase activity Source: RGD
- identical protein binding Source: RGD
- non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC
- protein kinase activity Source: UniProtKB
- protein serine/threonine/tyrosine kinase activity Source: RHEA
- protein serine kinase activity Source: RHEA
GO - Biological processi
- cellular response to amino acid starvation Source: RGD
- defense response to virus Source: RGD
- endoplasmic reticulum unfolded protein response Source: RGD
- innate immune response Source: UniProtKB-KW
- negative regulation of apoptotic process Source: RGD
- negative regulation of osteoblast proliferation Source: UniProtKB
- negative regulation of translation Source: UniProtKB
- negative regulation of viral genome replication Source: UniProtKB
- positive regulation of apoptotic process Source: RGD
- positive regulation of chemokine production Source: UniProtKB
- positive regulation of cytokine production Source: UniProtKB
- positive regulation of MAPK cascade Source: UniProtKB
- positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
- positive regulation of NIK/NF-kappaB signaling Source: UniProtKB
- positive regulation of stress-activated MAPK cascade Source: UniProtKB
- protein autophosphorylation Source: UniProtKB
- protein phosphorylation Source: UniProtKB
- regulation of hematopoietic progenitor cell differentiation Source: UniProtKB
- regulation of hematopoietic stem cell differentiation Source: UniProtKB
- regulation of hematopoietic stem cell proliferation Source: UniProtKB
- regulation of NLRP3 inflammasome complex assembly Source: UniProtKB
- response to exogenous dsRNA Source: RGD
- response to interferon-alpha Source: UniProtKB
- response to lipopolysaccharide Source: RGD
- response to mechanical stimulus Source: RGD
- response to organic substance Source: RGD
- response to toxic substance Source: RGD
- response to virus Source: UniProtKB
- response to vitamin E Source: RGD
- translation Source: RGD
Keywordsi
Molecular function | Kinase, RNA-binding, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase |
Biological process | Antiviral defense, Immunity, Innate immunity, Transcription, Transcription regulation |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-RNO-1169408, ISG15 antiviral mechanism |
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 Protein kinase RNA-activated Short name: PKR Short name: Protein kinase RCurated Tyrosine-protein kinase EIF2AK2 (EC:2.7.10.2) |
Gene namesi | Name:Eif2ak2 Synonyms:Prkr |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 3402, Eif2ak2 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm By similarity
Nucleus
- Nucleus By similarity
Other locations
- perinuclear region By similarity
Cytosol
- cytosol Source: GO_Central
Nucleus
- nucleus Source: RGD
Other locations
- cytoplasm Source: UniProtKB
- perinuclear region of cytoplasm Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedBy similarity | |||
ChainiPRO_0000274915 | 2 – 513 | Interferon-induced, double-stranded RNA-activated protein kinaseAdd BLAST | 512 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineBy similarity | 1 | |
Cross-linki | 68 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)By similarity | ||
Modified residuei | 82 | PhosphoserineBy similarity | 1 | |
Modified residuei | 84 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 96 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Cross-linki | 154 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)By similarity | ||
Modified residuei | 157 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 227 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 262 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 406 | Phosphothreonine; by autocatalysisBy similarity | 1 | |
Modified residuei | 411 | Phosphothreonine; by autocatalysisBy similarity | 1 | |
Modified residuei | 416 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
jPOSTi | Q63184 |
PaxDbi | Q63184 |
PRIDEi | Q63184 |
Interactioni
Subunit structurei
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). 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, IRS1, 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 (By similarity).
By similarityGO - Molecular functioni
- identical protein binding Source: RGD
Protein-protein interaction databases
BioGRIDi | 248507, 3 interactors |
STRINGi | 10116.ENSRNOP00000067694 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 8 – 76 | DRBM 1PROSITE-ProRule annotationAdd BLAST | 69 | |
Domaini | 95 – 162 | DRBM 2PROSITE-ProRule annotationAdd BLAST | 68 | |
Domaini | 236 – 502 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 267 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 235 – 513 | Interaction with TRAF5By similarityAdd BLAST | 279 |
Sequence similaritiesi
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | KOG1033, Eukaryota |
InParanoidi | Q63184 |
OrthoDBi | 1195366at2759 |
PhylomeDBi | Q63184 |
Family and domain databases
CDDi | cd19903, DSRM_EIF2AK2_rpt1, 1 hit |
InterProi | View protein in InterPro IPR014720, dsRBD_dom IPR044452, EIF2AK2_DSRM_1 IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00035, dsrm, 2 hits PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00358, DSRM, 2 hits SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS50137, DS_RBD, 2 hits PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
10 20 30 40 50
MASDTPGFYV DKLNKYSQIH KVKIIYKEIS VTGPPHDRRF TFQVIIEERE
60 70 80 90 100
FPEGEGRSKQ EAKNNAAKLA VEILDNENKV DSHTDASEQG LIEGNYIGLV
110 120 130 140 150
NSFAQKENLP VNFELCDPDS QLPHRFICKC KIGQTTYGTG FGANKKEAKQ
160 170 180 190 200
LAAKNAYQKL SEKSPSKTGF VTSLSSDFSS SSSITSNSAS QSASGRDFED
210 220 230 240 250
IFMNGLREKR KSGVKVPSDD VLRNKYTLDD RFSKDFEDIE EIGSGGFGQV
260 270 280 290 300
FKAKHRIDGK TYAIKRITYN TKKAKREVQA LAELNHANIV QYRVCWEGED
310 320 330 340 350
YDYDPENSTN GDTSRYKTRC LFIQMEFCDK GTLQQWLEKR NRSQEDKALV
360 370 380 390 400
LELFEQIVTG VDYIHSKGLI HRDLKPGNIF LVDEKHIKIG DFGLATALEN
410 420 430 440 450
DGNPRTKYTG TPQYMSPEQK SSLVEYGKEV DIFALGLILA ELLHICKTDS
460 470 480 490 500
EKIEFFQLLR NGIFSDDIFD NKEKSLLQKL LSSKPRERPN TSEILKTLAE
510
WKNISEKKKR NTC
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketM0RDJ3 | M0RDJ3_RAT | Interferon-induced, double-stranded... | Eif2ak2 rCG_61784 | 513 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L29281 mRNA Translation: AAA61926.1 |
PIRi | S50216 |
RefSeqi | NP_062208.1, NM_019335.1 |
Genome annotation databases
GeneIDi | 54287 |
KEGGi | rno:54287 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L29281 mRNA Translation: AAA61926.1 |
PIRi | S50216 |
RefSeqi | NP_062208.1, NM_019335.1 |
3D structure databases
SMRi | Q63184 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 248507, 3 interactors |
STRINGi | 10116.ENSRNOP00000067694 |
Proteomic databases
jPOSTi | Q63184 |
PaxDbi | Q63184 |
PRIDEi | Q63184 |
Genome annotation databases
GeneIDi | 54287 |
KEGGi | rno:54287 |
Organism-specific databases
CTDi | 5610 |
RGDi | 3402, Eif2ak2 |
Phylogenomic databases
eggNOGi | KOG1033, Eukaryota |
InParanoidi | Q63184 |
OrthoDBi | 1195366at2759 |
PhylomeDBi | Q63184 |
Enzyme and pathway databases
Reactomei | R-RNO-1169408, ISG15 antiviral mechanism |
Miscellaneous databases
PROi | PR:Q63184 |
Family and domain databases
CDDi | cd19903, DSRM_EIF2AK2_rpt1, 1 hit |
InterProi | View protein in InterPro IPR014720, dsRBD_dom IPR044452, EIF2AK2_DSRM_1 IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00035, dsrm, 2 hits PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00358, DSRM, 2 hits SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS50137, DS_RBD, 2 hits PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | E2AK2_RAT | |
Accessioni | Q63184Primary (citable) accession number: Q63184 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 6, 2007 |
Last sequence update: | November 1, 1996 | |
Last modified: | February 23, 2022 | |
This is version 140 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families