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Protein

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

Gene

EIF2AK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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.PROSITE-ProRule annotation

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)DescriptionActionsGraphical viewLength
Binding sitei296ATP1
Active sitei414Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi273 – 281ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • double-stranded RNA binding Source: MGI
  • eukaryotic translation initiation factor 2alpha kinase activity Source: UniProtKB
  • non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC
  • poly(A) RNA binding Source: UniProtKB
  • protein kinase activity Source: UniProtKB
  • protein phosphatase type 2A regulator activity Source: ProtInc
  • protein serine/threonine kinase activity Source: ProtInc

GO - Biological processi

  • activation of MAPKK activity Source: UniProtKB
  • cellular response to amino acid starvation Source: UniProtKB
  • defense response to virus Source: UniProtKB-KW
  • endoplasmic reticulum unfolded protein response Source: Ensembl
  • evasion or tolerance by virus of host immune response Source: Reactome
  • innate immune response Source: UniProtKB-KW
  • negative regulation of apoptotic process Source: Ensembl
  • negative regulation of cell proliferation Source: ProtInc
  • negative regulation of osteoblast proliferation Source: UniProtKB
  • negative regulation of translation Source: UniProtKB
  • negative regulation of viral genome replication Source: UniProtKB
  • positive regulation of chemokine production Source: UniProtKB
  • positive regulation of cytokine production 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 interferon-alpha Source: UniProtKB
  • response to toxic substance Source: InterPro
  • response to virus Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
  • translation Source: Ensembl
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

BioCyciZFISH:HS00683-MONOMER.
ReactomeiR-HSA-1169408. ISG15 antiviral mechanism.
R-HSA-169131. Inhibition of PKR.
SignaLinkiP19525.
SIGNORiP19525.

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
Short name:
Protein kinase R1 Publication
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
Proteomesi
  • UP000005640 Componenti: 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.

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • membrane Source: UniProtKB
  • nucleus Source: UniProtKB-SubCell
  • perinuclear region of cytoplasm Source: UniProtKB
  • ribosome Source: AgBase
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi59 – 60SK → AA in FL-PKR-2AI; moderate loss of activity but no effect on dsRNA binding. 1 Publication2
Mutagenesisi60K → A: Impairs dsRNA binding but not dimerization or activity. 1 Publication1
Mutagenesisi67A → E: Significant loss of activity; loss of dsRNA binding and dimerization. 1 Publication1
Mutagenesisi83S → A: No effect on enzymatic activity; when associated with A-88; A-89 and A-90. 1 Publication1
Mutagenesisi88T → A: No effect on enzymatic activity; when associated with A-83; A-89 and A-90. 1 Publication1
Mutagenesisi89T → A: No effect on enzymatic activity; when associated with A-83; A-88 and A-90. 1 Publication1
Mutagenesisi90T → A: No effect on enzymatic activity; when associated with A-83; A-88 and A-89. 1 Publication1
Mutagenesisi149 – 150TK → AA in FL-PKR-2AII; no effect on activity. 1 Publication2
Mutagenesisi242S → A: Moderate loss of activity; when associated with A-255 and A-258. 1 Publication1
Mutagenesisi244 – 296Missing : Loss of activity. 1 PublicationAdd BLAST53
Mutagenesisi255T → A: Moderate loss of activity; when associated with A-242 and A-255. 1 Publication1
Mutagenesisi258T → A: Moderate loss of activity. 1 Publication1
Mutagenesisi296K → R: Loss of activity. 1 Publication1
Mutagenesisi446T → A: Significant loss of activity and impairs autophosphorylation of T-451. 1 Publication1
Mutagenesisi451T → A: Loss of activity. 1 Publication1

Organism-specific databases

DisGeNETi5610.
OpenTargetsiENSG00000055332.
PharmGKBiPA33779.

Chemistry databases

ChEMBLiCHEMBL5785.
GuidetoPHARMACOLOGYi2016.

Polymorphism and mutation databases

BioMutaiEIF2AK2.
DMDMi125527.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00000859452 – 551Interferon-induced, double-stranded RNA-activated protein kinaseAdd BLAST550

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1 Publication1
Cross-linki69Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)1 Publication
Modified residuei83PhosphoserineCombined sources1 Publication1
Modified residuei88Phosphothreonine; by autocatalysis1 Publication1
Modified residuei89Phosphothreonine; by autocatalysis1 Publication1
Modified residuei90Phosphothreonine; by autocatalysis1 Publication1
Modified residuei101Phosphotyrosine; by autocatalysis1 Publication1
Cross-linki159Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)1 Publication
Modified residuei162Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei242Phosphoserine; by autocatalysis1 Publication1
Modified residuei255Phosphothreonine; by autocatalysis1 Publication1
Modified residuei258Phosphothreonine; by autocatalysis1 Publication1
Modified residuei293Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei446Phosphothreonine; by autocatalysis2 Publications1
Modified residuei451Phosphothreonine; by autocatalysis2 Publications1
Modified residuei456PhosphoserineCombined sources1
Modified residuei542PhosphoserineCombined sources1

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.7 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP19525.
MaxQBiP19525.
PaxDbiP19525.
PeptideAtlasiP19525.
PRIDEiP19525.
TopDownProteomicsiP19525-1. [P19525-1]

PTM databases

iPTMnetiP19525.
PhosphoSitePlusiP19525.
SwissPalmiP19525.

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.1 Publication

Gene expression databases

BgeeiENSG00000055332.
CleanExiHS_EIF2AK2.
ExpressionAtlasiP19525. baseline and differential.
GenevisibleiP19525. HS.

Organism-specific databases

HPAiCAB003845.
HPA019795.
HPA063893.

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.By similarity21 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
PRKRAO755694EBI-640775,EBI-713955
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. 97 interactors.
DIPiDIP-2657N.
IntActiP19525. 61 interactors.
MINTiMINT-92415.
STRINGi9606.ENSP00000233057.

Chemistry databases

BindingDBiP19525.

Structurei

Secondary structure

1551
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi5 – 7Combined sources3
Helixi10 – 21Combined sources12
Beta strandi26 – 32Combined sources7
Turni35 – 37Combined sources3
Beta strandi41 – 50Combined sources10
Beta strandi54 – 56Combined sources3
Helixi61 – 76Combined sources16
Helixi102 – 111Combined sources10
Beta strandi115 – 123Combined sources9
Beta strandi125 – 138Combined sources14
Beta strandi144 – 149Combined sources6
Helixi150 – 167Combined sources18
Helixi261 – 266Combined sources6
Beta strandi267 – 274Combined sources8
Beta strandi276 – 278Combined sources3
Beta strandi281 – 286Combined sources6
Turni287 – 289Combined sources3
Beta strandi292 – 299Combined sources8
Helixi303 – 305Combined sources3
Helixi306 – 314Combined sources9
Beta strandi323 – 332Combined sources10
Beta strandi358 – 366Combined sources9
Helixi374 – 380Combined sources7
Helixi381 – 383Combined sources3
Helixi388 – 407Combined sources20
Beta strandi410 – 412Combined sources3
Helixi417 – 419Combined sources3
Beta strandi420 – 424Combined sources5
Beta strandi427 – 430Combined sources4
Beta strandi437 – 440Combined sources4
Helixi457 – 461Combined sources5
Helixi468 – 482Combined sources15
Helixi488 – 499Combined sources12
Beta strandi505 – 507Combined sources3
Helixi509 – 518Combined sources10
Helixi523 – 525Combined sources3
Helixi529 – 538Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1QU6NMR-A1-170[»]
2A19X-ray2.50B/C258-538[»]
2A1AX-ray2.80B258-538[»]
3UIUX-ray2.90A/B254-551[»]
ProteinModelPortaliP19525.
SMRiP19525.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP19525.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini9 – 77DRBM 1PROSITE-ProRule annotationAdd BLAST69
Domaini100 – 167DRBM 2PROSITE-ProRule annotationAdd BLAST68
Domaini267 – 538Protein kinasePROSITE-ProRule annotationAdd BLAST272
Repeati331 – 3431Add BLAST13
Repeati345 – 3572Add BLAST13

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni266 – 551Interaction with TRAF51 PublicationAdd BLAST286
Regioni331 – 3572 X 13 AA approximate repeatsAdd BLAST27

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily.PROSITE-ProRule annotation
Contains 2 DRBM (double-stranded RNA-binding) domains.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG1033. Eukaryota.
ENOG410XS0B. LUCA.
GeneTreeiENSGT00530000062984.
HOGENOMiHOG000234351.
HOVERGENiHBG051430.
InParanoidiP19525.
KOiK16195.
OMAiELLYICP.
OrthoDBiEOG091G088F.
PhylomeDBiP19525.
TreeFamiTF317576.

Family and domain databases

Gene3Di3.30.160.20. 2 hits.
InterProiIPR014720. dsRBD_dom.
IPR011009. Kinase-like_dom.
IPR033366. PKR.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR11042:SF102. PTHR11042:SF102. 1 hit.
PfamiPF00035. dsrm. 2 hits.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00358. DSRM. 2 hits.
SM00220. S_TKc. 1 hit.
[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. AlignAdd to basket

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

        10         20         30         40         50
MAGDLSAGFF MEELNTYRQK QGVVLKYQEL PNSGPPHDRR FTFQVIIDGR
60 70 80 90 100
EFPEGEGRSK KEAKNAAAKL AVEILNKEKK AVSPLLLTTT NSSEGLSMGN
110 120 130 140 150
YIGLINRIAQ KKRLTVNYEQ CASGVHGPEG FHYKCKMGQK EYSIGTGSTK
160 170 180 190 200
QEAKQLAAKL AYLQILSEET SVKSDYLSSG SFATTCESQS NSLVTSTLAS
210 220 230 240 250
ESSSEGDFSA DTSEINSNSD SLNSSSLLMN GLRNNQRKAK RSLAPRFDLP
260 270 280 290 300
DMKETKYTVD KRFGMDFKEI ELIGSGGFGQ VFKAKHRIDG KTYVIKRVKY
310 320 330 340 350
NNEKAEREVK ALAKLDHVNI VHYNGCWDGF DYDPETSDDS LESSDYDPEN
360 370 380 390 400
SKNSSRSKTK CLFIQMEFCD KGTLEQWIEK RRGEKLDKVL ALELFEQITK
410 420 430 440 450
GVDYIHSKKL IHRDLKPSNI FLVDTKQVKI GDFGLVTSLK NDGKRTRSKG
460 470 480 490 500
TLRYMSPEQI SSQDYGKEVD LYALGLILAE LLHVCDTAFE TSKFFTDLRD
510 520 530 540 550
GIISDIFDKK EKTLLQKLLS KKPEDRPNTS EILRTLTVWK KSPEKNERHT

C
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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti102I → M in AAP57628 (Ref. 7) Curated1
Sequence conflicti224S → R in AAP57628 (Ref. 7) Curated1
Sequence conflicti512K → E in AAF13156 (PubMed:9726442).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040474428V → E.1 PublicationCorresponds to variant rs56219559dbSNPEnsembl.1
Natural variantiVAR_040475439L → V in a lung adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_040476506I → V.1 PublicationCorresponds to variant rs34821155dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_046177263 – 303Missing in isoform 2. 1 PublicationAdd BLAST41

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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]
XP_011531289.1. XM_011532987.2. [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.
UCSCiuc010fab.3. human. [P19525-1]

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:
EMBLi
GenBanki
DDBJi
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]
XP_011531289.1. XM_011532987.2. [P19525-1]
UniGeneiHs.131431.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1QU6NMR-A1-170[»]
2A19X-ray2.50B/C258-538[»]
2A1AX-ray2.80B258-538[»]
3UIUX-ray2.90A/B254-551[»]
ProteinModelPortaliP19525.
SMRiP19525.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111596. 97 interactors.
DIPiDIP-2657N.
IntActiP19525. 61 interactors.
MINTiMINT-92415.
STRINGi9606.ENSP00000233057.

Chemistry databases

BindingDBiP19525.
ChEMBLiCHEMBL5785.
GuidetoPHARMACOLOGYi2016.

PTM databases

iPTMnetiP19525.
PhosphoSitePlusiP19525.
SwissPalmiP19525.

Polymorphism and mutation databases

BioMutaiEIF2AK2.
DMDMi125527.

Proteomic databases

EPDiP19525.
MaxQBiP19525.
PaxDbiP19525.
PeptideAtlasiP19525.
PRIDEiP19525.
TopDownProteomicsiP19525-1. [P19525-1]

Protocols and materials databases

DNASUi5610.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000233057; ENSP00000233057; ENSG00000055332. [P19525-1]
ENST00000395127; ENSP00000378559; ENSG00000055332. [P19525-1]
ENST00000405334; ENSP00000385014; ENSG00000055332. [P19525-2]
GeneIDi5610.
KEGGihsa:5610.
UCSCiuc010fab.3. human. [P19525-1]

Organism-specific databases

CTDi5610.
DisGeNETi5610.
GeneCardsiEIF2AK2.
HGNCiHGNC:9437. EIF2AK2.
HPAiCAB003845.
HPA019795.
HPA063893.
MIMi176871. gene.
neXtProtiNX_P19525.
OpenTargetsiENSG00000055332.
PharmGKBiPA33779.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1033. Eukaryota.
ENOG410XS0B. LUCA.
GeneTreeiENSGT00530000062984.
HOGENOMiHOG000234351.
HOVERGENiHBG051430.
InParanoidiP19525.
KOiK16195.
OMAiELLYICP.
OrthoDBiEOG091G088F.
PhylomeDBiP19525.
TreeFamiTF317576.

Enzyme and pathway databases

BioCyciZFISH:HS00683-MONOMER.
ReactomeiR-HSA-1169408. ISG15 antiviral mechanism.
R-HSA-169131. Inhibition of PKR.
SignaLinkiP19525.
SIGNORiP19525.

Miscellaneous databases

ChiTaRSiEIF2AK2. human.
EvolutionaryTraceiP19525.
GeneWikiiProtein_kinase_R.
GenomeRNAii5610.
PMAP-CutDBP19525.
PROiP19525.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000055332.
CleanExiHS_EIF2AK2.
ExpressionAtlasiP19525. baseline and differential.
GenevisibleiP19525. HS.

Family and domain databases

Gene3Di3.30.160.20. 2 hits.
InterProiIPR014720. dsRBD_dom.
IPR011009. Kinase-like_dom.
IPR033366. PKR.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR11042:SF102. PTHR11042:SF102. 1 hit.
PfamiPF00035. dsrm. 2 hits.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00358. DSRM. 2 hits.
SM00220. S_TKc. 1 hit.
[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]
ProtoNetiSearch...

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: November 30, 2016
This is version 201 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.