Recombinant Human Serine/threonine-protein kinase TBK1(TBK1),partial

Code CSB-YP890690HU1
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Source Yeast
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Code CSB-EP890690HU1
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Source E.coli
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Code CSB-EP890690HU1-B
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Source E.coli
Conjugate Avi-tag Biotinylated
E. coli biotin ligase (BirA) is highly specific in covalently attaching biotin to the 15 amino acid AviTag peptide. This recombinant protein was biotinylated in vivo by AviTag-BirA technology, which method is BriA catalyzes amide linkage between the biotin and the specific lysine of the AviTag.
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Code CSB-BP890690HU1
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Source Baculovirus
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Code CSB-MP890690HU1
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Source Mammalian cell
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Product Details

Purity >85% (SDS-PAGE)
Target Names TBK1
Uniprot No. Q9UHD2
Alternative Names EC 2.7.11.1; FLJ11330; FTDALS4; NAK; NF kappa B activating kinase; NF kB activating kinase; NF-kappa-B-activating kinase; Serine/threonine protein kinase TBK 1; Serine/threonine protein kinase TBK1; Serine/threonine-protein kinase TBK1; T2K; TANK binding kinase 1; TANK-binding kinase 1; TBK 1; Tbk1; TBK1_HUMAN
Species Homo sapiens (Human)
Protein Length Partial
Tag Info The following tags are available.
N-terminal His-tagged
Tag-Free
The tag type will be determined during production process. If you have specified tag type, please tell us and we will develop the specified tag preferentially.
Form 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 before Lyophilization 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℃/-80℃. 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/-80°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.
Note: All of our proteins are default shipped with normal blue ice packs, if you request to ship with dry ice, please communicate with us in advance and extra fees will be charged.
Notes Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Datasheet Please contact us to get it.

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Target Background

Function
Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents. Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRFs leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNA and IFNB. In order to establish such an antiviral state, TBK1 form several different complexes whose composition depends on the type of cell and cellular stimuli. Plays a key role in IRF3 activation: acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1. Phosphorylated IRF3 dissociates from the adapter proteins, dimerizes, and then enters the nucleus to induce expression of interferons. Thus, several scaffolding molecules including FADD, TRADD, MAVS, AZI2, TANK or TBKBP1/SINTBAD can be recruited to the TBK1-containing-complexes. Under particular conditions, functions as a NF-kappa-B effector by phosphorylating NF-kappa-B inhibitor alpha/NFKBIA, IKBKB or RELA to translocate NF-Kappa-B to the nucleus. Restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin on 'Ser-177', thus enhancing LC3 binding affinity and antibacterial autophagy. Phosphorylates SMCR8 component of the C9orf72-SMCR8 complex, promoting autophagosome maturation. Phosphorylates and activates AKT1. Seems to play a role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, wich leads to a negative impact on insulin sensitivity. Attenuates retroviral budding by phosphorylating the endosomal sorting complex required for transport-I (ESCRT-I) subunit VPS37C. Phosphorylates Borna disease virus (BDV) P protein. Plays an essential role in the TLR3- and IFN-dependent control of herpes virus HSV-1 and HSV-2 infections in the central nervous system.
Gene References into Functions
  1. Of the whole cohort of patients with Motor Neuron Disease and Frontotemporal Dementia, 2 patients harboured a mutation in the TANK-binding kinase 1 (TBK1). PMID: 29886477
  2. TBK1 is not only a recurrent cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), but a cause of other neurodegenerative disorders like progressive cerebellar ataxia and cerebellar ataxia. PMID: 29137817
  3. It contributes to the etiology of sporadic amyotrophic lateral sclerosis in Japanese patients. PMID: 29398122
  4. TANK-binding kinase 1 (TBK1) loss-of-function (LoF) mutations are risk of Alzheimer's disease. PMID: 29146049
  5. Cdc25A negatively regulates the antiviral immune response by inhibiting TBK1 activity. PMID: 30021902
  6. Two-stage meta-analysis to investigate the frequency of TBK1 mutations in amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) patients and the association between the mutations and risk of ALS/FTD spectrum showed that TBK1 loss of function and missense mutations are not frequently found in ALS/FTD patients, and both of them are associated with an increased risk for ALS/FTD spectrum. PMID: 29349657
  7. Low TBK1 expression is associated with RNA virus infections. PMID: 29743353
  8. Loss of TBK1 by Us11 promotes HSV-1 infection through Formation of the Us11-Hsp90 Complex. PMID: 29743370
  9. This study supports the implication of TBK1 in Amyotrophic Lateral Sclerosis and Cognitive Decline pathogenesis in Italy. PMID: 29103041
  10. work identifies the TRIM23-TBK1-p62 axis as a key component of selective autophagy and further reveals a role for K27-linked ubiquitination in GTPase-dependent TBK1 activation PMID: 28871090
  11. we detected no statistical difference in age at diagnosis or maximum IOP when we compared patients with a TBK1 gene duplication and patients with a TBK1 gene triplication. PMID: 28984711
  12. Human T-lymphotropic virus 1 Tax protein impairs K63-linked ubiquitination of STING and disrupted the interactions between STING and TBK1 to evade host innate immunity. PMID: 28119118
  13. we investigated a large European study population of 2,538 European FTD-ALS spectrum patients to get a deeper appreciation of the mutation frequency, mutation spectrum, and the genotype-phenotype profile of TBK1 patient carriers. PMID: 28008748
  14. These results outline a novel mechanism for the control of TBK1 activity and suggest USP1-UAF1 complex as a potential target for the prevention of viral diseases. PMID: 29138248
  15. TRIM9s undergoes Lys-63-linked auto-polyubiquitination and serves as a platform to bridge GSK3beta to TBK1, leading to the activation of IRF3 signaling. PMID: 26915459
  16. YPEL5 silencing enhanced the induction of IFNB1 by pattern recognition receptors and phosphorylation of TBK1/IKBKE kinases, whereas co-immunoprecipitation experiments revealed that YPEL5 interacted physically with IKBKE. PMID: 27705791
  17. ZIKV infection of neuroepithelial stem cells and radial glial cells causes centrosomal depletion and mitochondrial sequestration of phospho-TBK1 during mitosis. PMID: 27568284
  18. High TBK1 expression is associated with Lung cancer. PMID: 28716898
  19. Our results highlight an unexpected role of the Golgi apparatus in innate immunity as a key subcellular gateway for TBK1 activation after RNA virus infection. PMID: 27538435
  20. The results of this study proposed that TBK1 is not a frequent causal gene in Chinese ALS patients. PMID: 27260353
  21. HERP Binds TBK1 To Activate Innate Immunity and Repress Virus Replication in Response to Endoplasmic Reticulum Stress PMID: 28954889
  22. these data suggest that HNSs, an antagonist of host innate immunity, interacts with TBK1 and thereby hinders the association of TBK1 with its substrate IRF3, thus blocking IRF3 activation and transcriptional induction of the cellular antiviral responses. PMID: 28848048
  23. Pathogenic variants in TBK1 are rare but could be responsible for sALS in a small number of Korean patients. PMID: 27939697
  24. High TBK1 expression is associated with normal tension glaucoma. PMID: 28025332
  25. We identified novel genomic TBK1 variants including two loss-of-function (LoF) (p.Leu59Phefs*16 and c.358+5G>A), two missense (p.Asp118Asn and p.Ile397Thr) and one intronic variant (c.1644-5_1644-2delAATA). PMID: 28822984
  26. Mutations in the TANK-binding kinase 1 (TBK1) gene were identified as a cause for amyotrophic lateral sclerosis (ALS) with or without comorbid frontotemporal dementia. PMID: 27156075
  27. The occurrence of TBK1 mutations in FTD and ALS underlines the fact that FTD and ALS are part of the same disease spectrum. For future therapeutic trials, characterization of TBK1 mutation carriers in presymptomatic cohorts, such as the genetic frontotemporal dementia initiative (GENFI), is of great importance. PMID: 27570907
  28. demonstrate a key role of TBK1/IKKepsilon in the survival and proliferation of HTLV-1-transformed T cells PMID: 27123832
  29. Data suggest that changes in inhibitor of nuclear factor kappa B kinase subunit epsilon (IKKepsilon) and TANK-binding kinase 1 (TBK1) expression may be involved in the development of intestinal-type gastric cancer. PMID: 27145266
  30. review of the role of TBK1 in the seemingly unrelated, yet allelic diseases amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), normal tension glaucoma (NTG) and childhood herpes simplex encephalitis and discuss the role of TBK1 in neuroinflammatory diseases PMID: 27211305
  31. Enrichment of qualifying variants toward glaucoma was present in all genes except WDR36, in which controls harbored more variants, and TBK1, in which no qualifying variants were detected in cases or controls. PMID: 28282485
  32. Human herpesvirus 1 ICP27 interacted with TBK1 and STING in a manner that was dependent on TBK1 activity and the RGG motif in ICP27 and inhibited type I IFN induction through the cGAS-STING-TBK1 pathway in human macrophages. PMID: 27234299
  33. Upon cytosolic DNA stimulation, STAT3 Ser(754) is directly phosphorylated by TBK1 in a STING-dependent manner. Moreover, Ser(754) phosphorylation inhibits cytosolic DNA-induced STAT3 transcriptional activity and selectively reduces STAT3 target genes that are up-regulated in response to cytosolic DNA PMID: 28188292
  34. TBK1 complexes required for the phosphorylation of IRF3 and the production of interferon-beta have been identified. PMID: 28159912
  35. This review suggested that haploinsufficiency of TBK1 is causative for ALS and FTD regardless of the type of mutation. PMID: 27892983
  36. Report establishes optineurin as a positive regulator TBK1 via a bipartite interaction between these molecules. PMID: 27086836
  37. TBK1 duplication is found in normal tension and not in high tension open-angle glaucoma patients of Indian origin. PMID: 27350692
  38. A broader phenotypic range may be associated with TBK1 copy-number variations, although mutations in this gene are most often detected in patients with normal-tension glaucoma. PMID: 27881886
  39. Autoubiquitination of TRIM26 links TBK1 to NEMO in RLR-mediated innate antiviral immune response PMID: 26611359
  40. Mutations in the TBK1 gene were identified to cause amyotrophic lateral sclerosis (ALS) PMID: 26804609
  41. TBK1 should thus also be sequenced, after exclusion of C9orf72 mutation, in patients presenting frontotemporal dementia, particularly in cases secondarily associated with amyotrophic lateral sclerosis PMID: 26476236
  42. Its frame-shift mutation results in familial amyotrophic lateral sclerosis of Chinese origin. PMID: 26350399
  43. TBK1 carriers with amyotrophic lateral sclerosis had shorter disease duration than carriers with frontotemporal dementia in a Belgian cohort. PMID: 26674655
  44. The expression of TBK1 in mammalian cell mitosis is reported, including localization of the protein during division and its binding properties. PMID: 26656453
  45. Optineurin and TANK-binding kinase 1 (TBK1) are transiently recruited to the polyubiquitinated mitochondria, and the activated TBK1 phosphorylates p62 at S403 PMID: 25972374
  46. TBK1 loss of function mutations are the third most frequent cause of clinical frontotemporal dementia in a Belgian cohort. PMID: 26581300
  47. Data suggest OPTN (optineurin) is involved in up-regulation of innate immunity in mitosis; mechanism involves phosphorylation/mitochondrial translocation of TBK1 and phosphorylation/nuclear translocation of CYLD (cylindromatosis protein). PMID: 25923723
  48. TBK1 has a role in regulating T-cell activation and migration PMID: 25606824
  49. findings demonstrate a novel regulatory circuit in which STING and TBK1 reciprocally regulate each other to enable efficient antiviral signaling activation, and PPM1A dephosphorylates STING and TBK1 PMID: 25815785
  50. Data indicate that suppressor of cytokine signaling 3 (SOCS3) knockdown markedly increases the abundance of TANK-binding kinase 1 (TBK1). PMID: 25939384

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Involvement in disease Glaucoma 1, open angle, P (GLC1P); Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 (FTDALS4)
Subcellular Location Cytoplasm.
Protein Families Protein kinase superfamily, Ser/Thr protein kinase family, I-kappa-B kinase subfamily
Tissue Specificity Ubiquitous with higher expression in testis. Expressed in the ganglion cells, nerve fiber layer and microvasculature of the retina.
Database Links

HGNC: 11584

OMIM: 177700

KEGG: hsa:29110

STRING: 9606.ENSP00000329967

UniGene: Hs.505874

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