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Mouse Anti-EIF2AK2 Recombinant Antibody (1D11) (CBMAB-A2518-LY)

The product is antibody recognizes EIF2AK2. The antibody 1D11 immunoassay techniques such as: WB, ELISA.
See all EIF2AK2 antibodies

Summary

Host Animal
Mouse
Specificity
Human
Clone
1D11
Antibody Isotype
IgG1, κ
Application
WB, ELISA

Basic Information

Immunogen
EIF2AK2 (NP_002750, 1 a.a. ~ 100 a.a) partial recombinant protein with GST tag. MW of the GST tag alone is 26 KDa.
Specificity
Human
Antibody Isotype
IgG1, κ
Clonality
Monoclonal
Application Notes
The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.

Formulations & Storage [For reference only, actual COA shall prevail!]

Format
Liquid
Purity
> 95% Purity determined by SDS-PAGE.
Storage
Store at +4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freezethaw cycles.

Target

Full Name
eukaryotic translation initiation factor 2 alpha kinase 2
Entrez Gene ID
UniProt ID
Alternative Names
EIF2AK1; MGC126524; PKR; PRKR
Research Area
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:18835251, PubMed:19507191, PubMed:19189853, PubMed:21123651, PubMed:21072047, PubMed:22948139, PubMed:23229543, PubMed:22381929).

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:19189853, PubMed:21123651, PubMed:22948139, PubMed:23229543).

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) (PubMed:11836380, PubMed:19189853, PubMed:20171114, PubMed:19840259, PubMed:21710204, PubMed:23115276, PubMed:23399035).

Also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation: phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1 and the HHV-1 viral protein US11 (PubMed:11836380, PubMed:22214662, PubMed:19229320).

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 (PubMed:20395957).

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 (PubMed:22948139, PubMed:23084476, PubMed:23372823).

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 (PubMed:10848580, PubMed:15121867, PubMed:15229216).

Can act as both a positive and negative regulator of the insulin signaling pathway (ISP) (PubMed:20685959).

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) (PubMed:20685959).

Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes (PubMed:22801494).

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).
Biological Process
Activation of MAPKK activity Source: UniProtKB
Cellular response to amino acid starvation Source: UniProtKB
Defense response to virus Source: ARUK-UCL
Endoplasmic reticulum unfolded protein response Source: Ensembl
Innate immune response Source: UniProtKB-KW
Negative regulation of apoptotic process Source: Ensembl
Negative regulation of cell population 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 virus Source: UniProtKB
Translation Source: Ensembl
Cellular Location
Nucleus; Cytoplasm; Perinuclear region. 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.
Involvement in disease
Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome (LEUDEN):
An autosomal dominant disorder characterized by global developmental delay apparent in early childhood, cognitive impairment, ataxia, poor or absent speech with dysarthria, hypotonia, hypertonia, extrapyramidal signs, tremor, and abnormal involuntary movements. Affected individuals also exhibit neurological regression in the setting of febrile illness or infection. Many patients have seizures. Brain imaging shows diffuse white matter abnormalities with poor myelination.
PTM
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.

Waller, S. E., Morales‐Briceño, H., Williams, L., Mohammad, S. S., Fellner, A., Kumar, K. R., ... & Fung, V. S. (2022). Possible EIF2AK2‐Associated Stress‐Related Neurological Decompensation with Combined Dystonia and Striatal Lesions. Movement Disorders Clinical Practice, 9(2), 240-244.

Zhao, Y., Zhao, H., Zhang, D., Quan, Q., Ge, Y., Li, L., & Guo, L. (2022). YTHDF3 Facilitates eIF2AK2 and eIF3A Recruitment on mRNAs to Regulate Translational Processes in Oxaliplatin-Resistant Colorectal Cancer. ACS Chemical Biology, 17(7), 1778-1788.

Kuipers, D. J., Mandemakers, W., Lu, C. S., Olgiati, S., Breedveld, G. J., Fevga, C., ... & Bonifati, V. (2021). EIF2AK2 missense variants associated with early onset generalized dystonia. Annals of neurology, 89(3), 485-497.

Ge, L., Zhang, Y., Zhao, X., Wang, J., Zhang, Y., Wang, Q., ... & You, Y. (2021). EIF2AK2 selectively regulates the gene transcription in immune response and histones associated with systemic lupus erythematosus. Molecular Immunology, 132, 132-141.

Calame, D. G., Hainlen, M., Takacs, D., Ferrante, L., Pence, K., Emrick, L. T., & Chao, H. T. (2021). EIF2AK2-related neurodevelopmental disorder with leukoencephalopathy, developmental delay, and episodic neurologic regression mimics Pelizaeus-Merzbacher disease. Neurology Genetics, 7(1).

Mao, D., Reuter, C. M., Ruzhnikov, M. R., Beck, A. E., Farrow, E. G., Emrick, L. T., ... & Lanza, I. R. (2020). De novo EIF2AK1 and EIF2AK2 variants are associated with developmental delay, leukoencephalopathy, and neurologic decompensation. The American Journal of Human Genetics, 106(4), 570-583.

Assunção, C. B., de Aguiar, E. L., Al-Hatmi, A. M., Vieira, V. C. S., Machado, A. S., Junta, C., ... & Caligiorne, R. B. (2020). New molecular marker for phylogenetic reconstruction of black yeast-like fungi (Chaetothyriales) with hypothetical EIF2AK2 kinase gene. Fungal biology, 124(12), 1032-1038.

Meyer, C., Garzia, A., Mazzola, M., Gerstberger, S., Molina, H., & Tuschl, T. (2018). The TIA1 RNA-binding protein family regulates EIF2AK2-mediated stress response and cell cycle progression. Molecular cell, 69(4), 622-635.

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For research use only. Not intended for any clinical use.

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