Recombinant Human Interferon-induced, double-stranded RNA-activated protein kinase(EIF2AK2)

Code CSB-EP007511HU
Size US$1726Purchase it in Cusabio online store
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  • (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
  • Based on the SEQUEST from database of E.coli host and target protein, the LC-MS/MS Analysis result of CSB-EP007511HU could indicate that this peptide derived from E.coli-expressed Homo sapiens (Human) EIF2AK2.
  • Based on the SEQUEST from database of E.coli host and target protein, the LC-MS/MS Analysis result of CSB-EP007511HU could indicate that this peptide derived from E.coli-expressed Homo sapiens (Human) EIF2AK2.
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Product Details

Description

Full-length of mature human interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2 cDNA carrying an N-terminal 6xHis-SUMO-tag was expressed in E.coli. The resulting protein is the recombinant fusion protein consisting of 2-551aa of human EIF2AK2. It was validated by both SDS-PAGE and LC-MS/MS analyses. The SDS-PAGE showed an about 75-85 kDa molecular mass of this protein and determines the purity of over 90%. In addition to being an immunogen for specific antibody synthesis, this recombinant protein also may be used in the studies of EIF2AK2-mediated signal transduction.

EIF2AK2, also called PKR, is activated by double-stranded RNA (dsRNA) and blocks the translation of viral mRNA in response to infection and physiologic stress conditions. It is also involved in innate immune response and the modulation of signal transduction, apoptosis, cell proliferation, and differentiation. Dongxue Mao etc. demonstrated that EIF2AK2 missense variants lead to a neurodevelopmental syndrome that may share phenotypic and pathogenic mechanisms with childhood ataxia with central nervous system hypomyelination/vanishing white matter disease (CACH/VWM).

Purity Greater than 90% as determined by SDS-PAGE.
Target Names EIF2AK2
Uniprot No. P19525
Research Area Signal Transduction
Alternative Names Double stranded RNA activated protein kinase; E2AK2_HUMAN; eIF-2A protein kinase 2; EIF2AK1; EIF2AK2; Eukaryotic translation initiation factor 2 alpha kinase 2; Eukaryotic translation initiation factor 2-alpha kinase 2; HGNC:9437; Interferon induced double stranded RNA activated protein kinase; Interferon inducible elF2 alpha kinase ; Interferon inducible RNA dependent protein kinase; Interferon-induced; double-stranded RNA-activated protein kinase; Interferon-inducible RNA-dependent protein kinase; MGC126524; P1/eIF-2A protein kinase; P1/eIF2A protein kinase ; p68 kinase; PKR; PPP1R83; PRKR; Protein kinase interferon inducible double stranded RNA dependent; Protein kinase RNA activated; Protein kinase RNA-activated; Protein phosphatase 1 regulatory subunit 83; Serine/threonine protein kinase TIK ; Tyrosine protein kinase EIF2AK2
Species Homo sapiens (Human)
Source E.coli
Expression Region 2-551aa
Target Protein Sequence AGDLSAGFFMEELNTYRQKQGVVLKYQELPNSGPPHDRRFTFQVIIDGREFPEGEGRSKKEAKNAAAKLAVEILNKEKKAVSPLLLTTTNSSEGLSMGNYIGLINRIAQKKRLTVNYEQCASGVHGPEGFHYKCKMGQKEYSIGTGSTKQEAKQLAAKLAYLQILSEETSVKSDYLSSGSFATTCESQSNSLVTSTLASESSSEGDFSADTSEINSNSDSLNSSSLLMNGLRNNQRKAKRSLAPRFDLPDMKETKYTVDKRFGMDFKEIELIGSGGFGQVFKAKHRIDGKTYVIKRVKYNNEKAEREVKALAKLDHVNIVHYNGCWDGFDYDPETSDDSLESSDYDPENSKNSSRSKTKCLFIQMEFCDKGTLEQWIEKRRGEKLDKVLALELFEQITKGVDYIHSKKLIHRDLKPSNIFLVDTKQVKIGDFGLVTSLKNDGKRTRSKGTLRYMSPEQISSQDYGKEVDLYALGLILAELLHVCDTAFETSKFFTDLRDGIISDIFDKKEKTLLQKLLSKKPEDRPNTSEILRTLTVWKKSPEKNERHTC
Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.
Mol. Weight 78.0kDa
Protein Length Full Length of Mature Protein
Tag Info N-terminal 6xHis-SUMO-tagged
Form Liquid or Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.
Buffer If the delivery form is liquid, the default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol.
Note: If you have any special requirement for the glycerol content, please remark when you place the order.
If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Reconstitution We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. Our default final concentration of glycerol is 50%. Customers could use it as reference.
Troubleshooting
and FAQs
Protein FAQs
Storage Condition Store at -20°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
Shelf Life The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Lead Time Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
Notes Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Datasheet & COA Please contact us to get it.

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Target Data

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.
Gene References into Functions
  1. We demonstrated the activation of PKR pathway in CADASIL PMID: 30073405
  2. These results establish that PKR regulation through stress-induced TRBP phosphorylation is an important mechanism ensuring cellular recovery and preventing apoptosis due to sustained PKR activation. PMID: 29348664
  3. Auto-phosphorylation represses PKR activity. PMID: 28281686
  4. The finding that zebularine upregulates CYP gene expression through DNMT1 and PKR modulation sheds light on the mechanisms controlling hepatocyte function and thus may aid in the development of new in-vitro systems using high-functioning hepatocytes PMID: 28112215
  5. Multiples studies identified PKR as a crucial component of the host defense mechanism against viruses. The dynamic nature of PKR's structure allows it to interact with viral and many cellular molecules that ultimately affect the function of target molecules and downstream components of their pathways. [review] PMID: 29716441
  6. High PKR expression is associated with Colorectal Cancer Cell Invasiveness. PMID: 30275201
  7. The data demonstrate that E3 promotes F1 expression by blocking activation of the double-stranded RNA-activated protein kinase R (PKR). PMID: 29997208
  8. findings indicate that MSI1 plays a leading role in stress granule formation that grants cancer stem cell properties and chemoresistant stress granules in GBM, in response to stressful conditions via the PKR/eIF2alpha signalling cascade. PMID: 29486283
  9. Here, the authors report that LRP16 selectively interacts and activates double-stranded RNA-dependent kinase (PKR), and also acts as scaffolds to assist the formation of a ternary complex of PKR and IKKbeta, prolonging the polymers of ADP-ribose (PAR)-dependent nuclear factor kappa B (NF-kappaB) transactivation caused by DNA-damaging agents and confers acquired chemoresistance. PMID: 28820388
  10. These data suggest that even a modest increase in expression of this weak PKR antagonist is sufficient to enable RhCMV replication in human cells. PMID: 29263260
  11. Activation of PKR by TNF-alpha mRNA element enables PKR phosphorylation. PKR phosphorylation on Ser51 is necessary and sufficient for efficient splicing of TNF-alpha mRNA. PMID: 28683312
  12. PKR is co-opted by EV-A71 via viral protease 3C-mediated proteolytic activation to facilitate viral replication. PMID: 28702377
  13. Findings suggest a novel role for PKR in lung cancer cells as a mediator of radiation resistance possibly through translocation of the protein product to the nucleus. PMID: 27203671
  14. a novel, positive role for PKR activation and eIF2alpha phosphorylation in human globin mRNA splicing, is reported. PMID: 28374749
  15. Clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-mediated ablation of double-stranded RNA (dsRNA)-activated protein kinase R (PKR) restored p53 responses while boosting hepatitis C virus replication, showing that p53 inhibition results directly from viral activation of PKR. PMID: 28442604
  16. Gene silencing studies showed that the suppression of immunoproteasome induction is essentially dependent on protein kinase R (PKR). Indeed, the generation of a strictly immunoproteasome-dependent cytotoxic T lymphocyte epitope was impaired in in vitro processing experiments using isolated 20S proteasomes from HCV-infected cells and was restored by the silencing of PKR expression. PMID: 27833096
  17. data provide the first evidence that KSHV ORF57 plays a role in modulating PKR/eIF2alpha/SG axis and enhances virus production during virus lytic infection. PMID: 29084250
  18. The PKR is a key constituent of the metaflammasome and interacts directly with several inflammatory kinases, such as inhibitor kappaB (IkappaB) kinase (IKK) and c-Jun N-terminal kinase (JNK), insulin receptor substrate 1 (IRS1), and component of the translational machinery such as eIF2alpha. PMID: 26831644
  19. infection with New World arenaviruses JUNV and MACV, but not OW LASV, activated PKR, concomitant with elevated phosphorylation of the translation initiation factor alpha subunit of eukaryotic initiation factor 2 PMID: 28794024
  20. The stem-loop of noncoding RNA 886 is structural feature not only critical for inhibiting PKR autophosphorylation, but also the phosphorylation of its cellular substrate, EIF-2alpha. PMID: 28069888
  21. Protein kinase R (PKR) was required for induction of stress granules (SGs) by mumps virus (MuV) infection and regulated type III IFN (IFN-lambda1) mRNA stability. PMID: 27560627
  22. data establish a model in which the Influenza A virus NS1 N-terminal domain engages in a binding interaction to inhibit activation of PKR and ensure efficient viral propagation and virulence PMID: 28250123
  23. It was established in this report that interactions between PACT, ADAR1 and HIV-1-encoded Tat protein diminish the activation of PKR in response to HIV-1 infection. PMID: 28167698
  24. In insulitic islets from living patients with recent-onset T1D, most of the overexpressed ISGs, including GBP1, TLR3, OAS1, EIF2AK2, HLA-E, IFI6, and STAT1, showed higher expression in the islet core compared with the peri-islet area containing the surrounding immune cells PMID: 27422384
  25. NF90 exerts its antiviral activity by antagonizing the inhibitory role of NS1 on PKR phosphorylation PMID: 27423063
  26. Crucially, Chlamydia trachomatis infection resulted in robust IRE1alpha RNAse activity that was dependent on TLR4 signalling and inhibition of IRE1alpha RNAse activity prevented PKR activation. PMID: 27021640
  27. the expression of a Tat construct containing mutations in the basic region (49-57aa), which is responsible for the interaction with PKR, favored neither parasite growth nor IL-10 expression in infected macrophages. PMID: 26608746
  28. This study provides insight into the molecular pathology of Cornelia de Lange syndrome by establishing a relationship between NIPBL and HDAC8 mutations and PKR activation. PMID: 26725122
  29. The Newcastle disease virus-induced translation shutoff at late infection times was attributed to sustaining phosphorylation of eIF2a, which is mediated by continual activation of PKR and degradation of PP1. PMID: 26869028
  30. The sole essential function of cytomegalovirus TRS1 is to antagonize host PKR. PMID: 26716879
  31. results show that ceramide acts at two distinct levels of the insulin signaling pathway (IRS1 and Akt). PKR, which is induced by both inflammation signals and ceramide, could play a major role in the development of insulin resistance in muscle cells. PMID: 26698173
  32. Classical swine fever virus (CSFV) infection increased the phosphorylation of eukaryotic translation initiation factor (eIF)2alpha and its kinase PKR. The activation of PKR during CSFV infection is beneficial to the virus. PMID: 25899421
  33. these data indicate a pivotal role for PKR's protein-binding function on the proliferation of pancreatic beta cells through TRAF2/RIP1/NF-kappaB/c-Myc pathways. PMID: 25715336
  34. The results from this study indicate an important role of RAX/PKR association in regulating PKR activity as well as ethanol neurotoxicity PMID: 25592072
  35. The G3BP1-Caprin1-PKR complex represents a new mode of PKR activation and is important for antiviral activity of G3BP1 and PKR during infection with mengovirus. PMID: 25784705
  36. The data support a model in which activating RNAs induce formation of a back-to-back parallel PKR kinase dimer whereas nonactivating RNAs either fail to induce dimerization or produce an alternative, inactive dimer configuration. PMID: 26488609
  37. Tyrosine phosphorylated EIF2AK2 plays a role in the regulation of insulin induced protein synthesis and in maintaining insulin sensitivity. PMID: 26321373
  38. PKR expression correlates with inferior survival and shorter remission duration for acute myeloid leukemia patients. PMID: 26202421
  39. No significant association was determined between the rs2254958 EIF2AK2 polymorphism and the development of IBD, or clinical outcome. PMID: 25607115
  40. the affinity of PACT-PACT and PACT-PKR interactions is enhanced in dystonia patient lymphoblasts, thereby leading to intensified PKR activation and enhanced cellular death. PMID: 26231208
  41. Protein levels of PRKR were significantly increased in prefrontal cortex in chronic excessive alcohol use. PMID: 25704249
  42. Mechanism by which PK2 inhibits the model eIF2alpha kinase human RNA-dependent protein kinase (PKR) as well as native insect eIF2alpha kinases, is reported. PMID: 26216977
  43. G3BP1, G3BP2 and CAPRIN1 are required for translation of interferon stimulated mRNAs and are targeted by a dengue virus non-coding RNA. PMID: 24992036
  44. This study demonstrates that two interferon stimulated genes, i.e. PKR and ADAR1 have opposite effects on HTLV replication in vivo. PMID: 25389016
  45. PKR directly interacts with HIV-1 Tat and phosphorylates the first exon of Tat exclusively at five Ser/Thr residues, which inhibits Tat-mediated provirus transcription. PMID: 25653431
  46. Authors show that the PXXP domain within G3BP1 is essential for the recruitment of PKR to stress granules, for eIF2alpha phosphorylation driven by PKR, and for nucleating stress granules of normal composition. PMID: 25520508
  47. Further studies revealed that Andes virus nucleocapsid protein inhibited PKR dimerization, a critical step required for PKR autophosphorylation to attain activity. PMID: 25410857
  48. SUMO potentiates the inhibition of protein synthesis induced by PKR in response to dsRNA. PMID: 25074923
  49. Early dsRNA induced transient activation of the cellular dsRNA sensor protein kinase R (PKR), resulting in enhanced production of interferons and cytokines in cells and mice. PMID: 25297997
  50. Cyclophilin inhibitors reduce phosphorylation of PKR and eIF2alpha during HCV infection to allow for translation of ISG products. PMID: 24786893

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Subcellular Location Cytoplasm, Nucleus, Cytoplasm, perinuclear region
Protein Families Protein kinase superfamily, Ser/Thr protein kinase family, GCN2 subfamily
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 carcin
Database Links

HGNC: 9437

OMIM: 176871

KEGG: hsa:5610

STRING: 9606.ENSP00000233057

UniGene: Hs.131431

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