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

中文名稱：

人TBK1重組蛋白
品名簡稱：

Recombinant Human TBK1 protein, partial
貨號：

CSB-EP890690HU1
說明書：

MSDS Datasheet
規格：

￥1536
圖片：
(Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
其他：

產品詳情
產品評價
相關產品
靶點詳情

產品詳情

純度：

Greater than 90% as determined by SDS-PAGE.
生物活性：

Not Test
基因名：

TBK1
Uniprot No.：

Q9UHD2
別名：

NF-kappa-B-activating kinase;T2K;TANK-binding kinase 1
種屬：

Homo sapiens (Human)
蛋白長度：

Partial
來源：

E.coli
分子量：

23.2 kDa
表達區域：

590-729aa
氨基酸序列

LYYHATKAMTHFTDECVKKYEAFLNKSEEWIRKMLHLRKQLLSLTNQCFDIEEEVSKYQEYTNELQETLPQKMFTASSGIKHTMTPIYPSSNTLVEMTLGMKKLKEEMEGVVKELAENNHILERFGSLTMDGGLRNVDCL
Note: The complete sequence may include tag sequence, target protein sequence, linker sequence and extra sequence that is translated with the protein sequence for the purpose(s) of secretion, stability, solubility, etc.
If the exact amino acid sequence of this recombinant protein is critical to your application, please explicitly request the full and complete sequence of this protein before ordering.
蛋白標簽：

C-terminal 6xHis-tagged
產品提供形式：

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.
緩沖液：

If the delivery form is liquid, the default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol. If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose.
復溶：

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.
儲存條件：

Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
保質期：

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.
貨期：

Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
Datasheet & COA：

Please contact us to get it.

產品評價

靶點詳情

功能：

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.
基因功能參考文獻：
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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相關疾病：

Glaucoma 1, open angle, P (GLC1P); Frontotemporal dementia and/or amyotrophic lateral sclerosis 4 (FTDALS4)
亞細胞定位：

Cytoplasm.
蛋白家族：

Protein kinase superfamily, Ser/Thr protein kinase family, I-kappa-B kinase subfamily
組織特異性：

Ubiquitous with higher expression in testis. Expressed in the ganglion cells, nerve fiber layer and microvasculature of the retina.
數據庫鏈接：

HGNC: 11584

OMIM: 177700

KEGG: hsa:29110

STRING: 9606.ENSP00000329967

UniGene: Hs.505874