Eif2ak2
entrez
19106
canonical
uniprot
Q03963
canonical
ensembl
ENSMUSG00000024079
resolver
ensp
ENSMUSP00000024884
resolver
enst
ENSMUST00000024884
resolver
genesymbol
Eif2ak2
resolver
genesymbol_syn
Pkr
resolver
genesymbol_syn
Prkr
resolver
genesymbol_syn
Tik
resolver
uniprot
Q61742
resolver
uniprot
Q62026
resolver
uniprot_entry
E2AK2_MOUSE
resolver
uniprot_sec
Q61742
resolver
uniprot_sec
Q62026
resolver
activity_regulation
ACTIVITY 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, pro-inflammatory stimuli, growth factors, cytokines, oxidative stress and the cellular protein PRKRA. Activity is markedly stimulated by manganese ions. Activation is blocked by the cellular proteins TARBP2, DUS2L, NPM1, NCK1 and ADAR (By similarity). {ECO:0000250|UniProtKB:P19525}.
uniprot
proteins
amino_acid_sequence
MASDTPGFYMDKLNKYRQMHGVAITYKELSTSGPPHDRRFTFQVLIDEKEFPEAKGRSKQEARNAAAKLAVDILDNENKVDCHTSASEQGLFVGNYIGLVNSFAQKKKLSVNYEQCEPNSELPQRFICKCKIGQTMYGTGSGVTKQEAKQLAAKEAYQKLLKSPPKTAGTSSSVVTSTFSGFSSSSSMTSNGVSQSAPGSFSSENVFTNGLGENKRKSGVKVSPDDVQRNKYTLDARFNSDFEDIEEIGLGGFGQVFKAKHRIDGKRYAIKRVKYNTEKAEHEVQALAELNHVNIVQYHSCWEGVDYDPEHSMSDTSRYKTRCLFIQMEFCDKGTLEQWMRNRNQSKVDKALILDLYEQIVTGVEYIHSKGLIHRDLKPGNIFLVDERHIKIGDFGLATALENDGKSRTRRTGTLQYMSPEQLFLKHYGKEVDIFALGLILAELLHTCFTESEKIKFFESLRKGDFSNDIFDNKEKSLLKKLLSEKPKDRPETSEILKTLAEWRNISEKKKRNTC
uniprot
proteins
ec_number
2.7.10.2
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
FUNCTION: 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 (PubMed:20038207, PubMed:20478537, PubMed:21123651). 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 (PubMed:20631127, PubMed:21123651). Exerts its antiviral activity on a wide range of DNA and RNA viruses including west nile virus (WNV), sindbis virus (SV), foot-and-mouth virus (FMDV), semliki Forest virus (SFV) and lymphocytic choriomeningitis virus (LCMV) (PubMed:19264662, PubMed:20585572, PubMed:20631127, PubMed:21994357). Also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation: phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, and IRS1 (PubMed:19229320, PubMed:23403623). 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 proteasomal 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 pro-inflammatory cytokines and IFNs (PubMed:22948222, PubMed:23392680). 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 (PubMed:22801494, PubMed:23401008). Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin (PubMed:22633459). {ECO:0000250|UniProtKB:P19525, ECO:0000269|PubMed:19229320, ECO:0000269|PubMed:19264662, ECO:0000269|PubMed:20038207, ECO:0000269|PubMed:20478537, ECO:0000269|PubMed:20585572, ECO:0000269|PubMed:20631127, ECO:0000269|PubMed:21123651, ECO:0000269|PubMed:21994357, ECO:0000269|PubMed:22633459, ECO:0000269|PubMed:22801494, ECO:0000269|PubMed:22948222, ECO:0000269|PubMed:23392680, ECO:0000269|PubMed:23401008, ECO:0000269|PubMed:23403623}.
uniprot
proteins
mass_dalton
58280
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated on several Ser, Thr and Tyr residues. Autophosphorylation of Thr-414 is dependent on Thr-409 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. Autophosphorylation is inhibited by the concerted action of ATAC complex subunit MBIP and molybdopterin synthase complex subunit MOCS2B (By similarity). {ECO:0000250|UniProtKB:P19525}.
uniprot
proteins
protein_family
GCN2 subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
Ser/Thr protein kinase family
uniprot
proteins
pubmed
10848580
uniprot
proteins
pubmed
12882984
uniprot
proteins
pubmed
1351683
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
17079286
uniprot
proteins
pubmed
1714905
uniprot
proteins
pubmed
19229320
uniprot
proteins
pubmed
19264662
uniprot
proteins
pubmed
20038207
uniprot
proteins
pubmed
20478537
uniprot
proteins
pubmed
20585572
uniprot
proteins
pubmed
20631127
uniprot
proteins
pubmed
21123651
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21300116
uniprot
proteins
pubmed
21994357
uniprot
proteins
pubmed
22633459
uniprot
proteins
pubmed
22801494
uniprot
proteins
pubmed
22948222
uniprot
proteins
pubmed
23229543
uniprot
proteins
pubmed
23392680
uniprot
proteins
pubmed
23401008
uniprot
proteins
pubmed
23403623
uniprot
proteins
pubmed
7533117
uniprot
proteins
pubmed
7914700
uniprot
proteins
sequence_length
515
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P19525}. Nucleus {ECO:0000250|UniProtKB:P19525}. Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:P19525}.
uniprot
proteins