ELISA/assay

Human Inhibitor of Kb Kinase Beta ELISA Kit

MBS009699

96 Strip Wells

600 USD

ELISA Kit

Human Inhibitor of Kb Kinase Beta ELISA Kit

Inhibitor of Kb Kinase Beta

Interferon-induced, double-stranded RNA-activated protein kinase; Interferon-induced, double-stranded RNA-activated protein kinase; interferon-induced, double-stranded RNA-activated protein kinase; p68 kinase; eIF-2A protein kinase 2; P1/eIF-2A protein kinase; tyrosine-protein kinase EIF2AK2; interferon-inducible elF2alpha kinase; double stranded RNA activated protein kinase; protein phosphatase 1, regulatory subunit 83; protein kinase, interferon-inducible double stranded RNA dependent; eukaryotic translation initiation factor 2-alpha kinase 2; Eukaryotic translation initiation factor 2-alpha kinase 2; eIF-2A protein kinase 2; Interferon-inducible RNA-dependent protein kinase; P1/eIF-2A protein kinase; Protein kinase RNA-activated; PKR; Tyrosine-protein kinase EIF2AK2 (EC:2.7.10.2); p68 kinase

IKKbeta

EIF2AK2; EIF2AK2; PKR; PRKR; EIF2AK1; PPP1R83; PKR; PRKR; eIF-2A protein kinase 2; PKR

E2AK2_HUMAN

Human

551

Store all reagents at 2-8 degree C

ELISA Type: Sandwich

125527

P19525.2

P19525

62,094 Da

Antiviral Mechanism By IFN-stimulated Genes Pathway 530760!!Ceramide Signaling Pathway 138023!!Cytokine Signaling In Immune System Pathway 366171!!Disease Pathway 530764!!Epstein-Barr Virus Infection Pathway 585562!!Epstein-Barr Virus Infection Pathway 587115!!Hepatitis C Pathway 173973!!Hepatitis C Pathway 173907!!Herpes Simplex Infection Pathway 377873!!Herpes Simplex Infection Pathway 377865

The protein encoded by this gene is a serine/threonine protein kinase that is activated by autophosphorylation after binding to dsRNA. The activated form of the encoded protein can phosphorylate translation initiation factor EIF2S1, which in turn inhibits protein synthesis. This protein is also activated by manganese ions and heparin. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

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. Ref.19 Ref.24 Ref.26 Ref.28 Ref.34 Ref.37 Ref.38 Ref.40 Ref.41 Ref.42 Ref.43 Ref.44 Ref.45 Ref.51 Ref.52 Ref.53 Ref.55 Ref.56 Ref.58 Ref.61 Ref.65 Ref.67 Ref.68 Ref.69. 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. Ref.25 Ref.34 Ref.35 Ref.65 Ref.66. 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. Interacts with herpes virus 8 protein v-IRF2; this interaction inhibits EIF2AK2 activation. Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.32 Ref.34 Ref.35 Ref.38 Ref.56 Ref.58 Ref.66. 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. Ref.28 Ref.48 Ref.51 Ref.53. Tissue specificity: 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. Ref.48 Ref.63. Induction: By type I interferons. Ref.1 Ref.25 Ref.34 Ref.35 Ref.65 Ref.66. 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.31 Ref.45 Ref.48 Ref.51 Ref.58 Ref.71. 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.

96 Strip Wells

600 USD