Recombinant human NAK/TBK1 protein is a Human Full Length protein, in the 1 to 729 aa range, expressed in Baculovirus infected Sf9, with >70% purity and suitable for SDS-PAGE, WB, FuncS.
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- Journal of molecular cell biology 11:158-1692018Host HDAC4 regulates the antiviral response by inhibiting the phosphorylation of IRF3.Applications:Unspecified applicationReactive species:Unspecified reactive speciesQi Yang,Jielin Tang,Rongjuan Pei,XiaoXiao Gao,Jing Guo,Chonghui Xu,Yun Wang,Qian Wang,Chunchen Wu,Yuan Zhou,Xue Hu,He Zhao,Yanyi Wang,Xinwen Chen,Jizheng ChenPubMed 29800227
Key facts
- Purity
- >70%
- Expression system
- Baculovirus infected Sf9 cells
- Tags
- GST tag N-Terminus
- Applications
- SDS-PAGE, WB, FuncS
- Biologically active
- Yes
Amino acid sequence
M Q S T S N H L W L L S D I L G Q G A T A N V F R G R H K K T G D L F A I K V F N N I S F L R P V D V Q M R E F E V L K K L N H K N I V K L F A I E E E T T T R H K V L I M E F C P C G S L Y T V L E E P S N A Y G L P E S E F L I V L R D V V G G M N H L R E N G I V H R D I K P G N I M R V I G E D G Q S V Y K L T D F G A A R E L E D D E Q F V S L Y G T E E Y L H P D M Y E R A V L R K D H Q K K Y G A T V D L W S I G V T F Y H A A T G S L P F R P F E G P R R N K E V M Y K I I T G K P S G A I S G V Q K A E N G P I D W S G D M P V S C S L S R G L Q V L L T P V L A N I L E A D Q E K C W G F D Q F F A E T S D I L H R M V I H V F S L Q Q M T A H K I Y I H S Y N T A T I F H E L V Y K Q T K I I S S N Q E L I Y E G R R L V L E P G R L A Q H F P K T T E E N P I F V V S R E P L N T I G L I Y E K I S L P K V H P R Y D L D G D A S M A K A I T G V V C Y A C R I A S T L L L Y Q E L M R K G I R W L I E L I K D D Y N E T V H K K T E V V I T L D F C I R N I E K T V K V Y E K L M K I N L E A A E L G E I S D I H T K L L R L S S S Q G T I E T S L Q D I D S R L S P G G S L A D A W A H Q E G T H P K D R N V E K L Q V L L N C M T E I Y Y Q F K K D K A E R R L A Y N E E Q I H K F D K Q K L Y Y H A T K A M T H F T D E C V K K Y E A F L N K S E E W I R K M L H L R K Q L L S L T N Q C F D I E E E V S K Y Q E Y T N E L Q E T L P Q K M F T A S S G I K H T M T P I Y P S S N T L V E M T L G M K K L K E E M E G V V K E L A E N N H I L E R F G S L T M D G G L R N V D C L
Reactivity data
| Application | Reactivity | Dilution info | Notes |
|---|---|---|---|
Application SDS-PAGE | Reactivity Reacts | Dilution info - | Notes - |
Application WB | Reactivity Reacts | Dilution info - | Notes ab85276 can be used as a WB positive control in conjunction with ab75969. |
Application FuncS | Reactivity Reacts | Dilution info - | Notes - |
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Target data
Function
Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents (PubMed:10581243, PubMed:11839743, PubMed:12692549, PubMed:12702806, PubMed:14703513, PubMed:15367631, PubMed:15485837, PubMed:18583960, PubMed:21138416, PubMed:23453971, PubMed:23453972, PubMed:23746807, PubMed:25636800, PubMed:26611359, PubMed:32404352, PubMed:34363755). 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 (PubMed:12692549, PubMed:12702806, PubMed:14703513, PubMed:15367631, PubMed:18583960, PubMed:25636800). 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 (PubMed:12702806, PubMed:15367631, PubMed:25636800, PubMed:32972995). In order to establish such an antiviral state, TBK1 form several different complexes whose composition depends on the type of cell and cellular stimuli (PubMed:23453971, PubMed:23453972, PubMed:23746807). 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 (PubMed:25636800, PubMed:30842653). Phosphorylated IRF3 dissociates from the adapter proteins, dimerizes, and then enters the nucleus to induce expression of interferons (PubMed:25636800). Thus, several scaffolding molecules including FADD, TRADD, MAVS, AZI2, TANK or TBKBP1/SINTBAD can be recruited to the TBK1-containing-complexes (PubMed:21931631). 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 (PubMed:10783893, PubMed:15489227). Restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin on 'Ser-177', thus enhancing LC3 binding affinity and antibacterial autophagy (PubMed:21617041). Phosphorylates SMCR8 component of the C9orf72-SMCR8 complex, promoting autophagosome maturation (PubMed:27103069). Phosphorylates ATG8 proteins MAP1LC3C and GABARAPL2, thereby preventing their delipidation and premature removal from nascent autophagosomes (PubMed:31709703). Phosphorylates and activates AKT1 (PubMed:21464307). 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 (By similarity). Attenuates retroviral budding by phosphorylating the endosomal sorting complex required for transport-I (ESCRT-I) subunit VPS37C (PubMed:21270402). Phosphorylates Borna disease virus (BDV) P protein (PubMed:16155125). 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 (PubMed:22851595). Acts both as a positive and negative regulator of the mTORC1 complex, depending on the context: activates mTORC1 in response to growth factors by catalyzing phosphorylation of MTOR, while it limits the mTORC1 complex by promoting phosphorylation of RPTOR (PubMed:29150432, PubMed:31530866). Involved in the regulation of TNF-induced RIPK1-mediated cell death, probably acting via CYLD phosphorylation that in turn controls RIPK1 ubiquitination status (PubMed:34363755). Participates also in the differentiation of T follicular regulatory cells together with the receptor ICOS (PubMed:27135603).
Alternative names
NAK, TBK1, Serine/threonine-protein kinase TBK1, NF-kappa-B-activating kinase, T2K, TANK-binding kinase 1
Recommended products
Recombinant human NAK/TBK1 protein is a Human Full Length protein, in the 1 to 729 aa range, expressed in Baculovirus infected Sf9, with >70% purity and suitable for SDS-PAGE, WB, FuncS.
Key facts
- Purity
- >70%
- Expression system
- Baculovirus infected Sf9 cells
- Tags
- GST tag N-Terminus
- Applications
- SDS-PAGE, WB, FuncS
- Biologically active
- Yes
- Biological activity
- The Specific activity of ab85276 was determined to be 305 nmol/min/mg.
- Accession
- Q9UHD2-1
- Animal free
- No
- Species
- Human
- Concentration
- Storage buffer
pH: 7.5
Constituents: 25% Glycerol (glycerin, glycerine), 0.87% Sodium chloride, 0.79% Tris HCl, 0.00385% (R*,R*)-1,4-Dimercaptobutan-2,3-diol, 0.0038% EGTA, 0.00292% EDTA, 0.00174% PMSF
Sequence info
Amino acid sequence
- M Q S T S N H L W L L S D I L G Q G A T A N V F R G R H K K T G D L F A I K V F N N I S F L R P V D V Q M R E F E V L K K L N H K N I V K L F A I E E E T T T R H K V L I M E F C P C G S L Y T V L E E P S N A Y G L P E S E F L I V L R D V V G G M N H L R E N G I V H R D I K P G N I M R V I G E D G Q S V Y K L T D F G A A R E L E D D E Q F V S L Y G T E E Y L H P D M Y E R A V L R K D H Q K K Y G A T V D L W S I G V T F Y H A A T G S L P F R P F E G P R R N K E V M Y K I I T G K P S G A I S G V Q K A E N G P I D W S G D M P V S C S L S R G L Q V L L T P V L A N I L E A D Q E K C W G F D Q F F A E T S D I L H R M V I H V F S L Q Q M T A H K I Y I H S Y N T A T I F H E L V Y K Q T K I I S S N Q E L I Y E G R R L V L E P G R L A Q H F P K T T E E N P I F V V S R E P L N T I G L I Y E K I S L P K V H P R Y D L D G D A S M A K A I T G V V C Y A C R I A S T L L L Y Q E L M R K G I R W L I E L I K D D Y N E T V H K K T E V V I T L D F C I R N I E K T V K V Y E K L M K I N L E A A E L G E I S D I H T K L L R L S S S Q G T I E T S L Q D I D S R L S P G G S L A D A W A H Q E G T H P K D R N V E K L Q V L L N C M T E I Y Y Q F K K D K A E R R L A Y N E E Q I H K F D K Q K L Y Y H A T K A M T H F T D E C V K K Y E A F L N K S E E W I R K M L H L R K Q L L S L T N Q C F D I E E E V S K Y Q E Y T N E L Q E T L P Q K M F T A S S G I K H T M T P I Y P S S N T L V E M T L G M K K L K E E M E G V V K E L A E N N H I L E R F G S L T M D G G L R N V D C L
- Accession
- Q9UHD2
- Protein length
- Full Length
- Predicted molecular weight
- 105 kDa
- Amino acids
- 1 to 729
- Nature
- Recombinant
- Tags
- GST tag N-Terminus
Specifications
- Form
- Liquid
- Additional notes
Purified by affinity chromatography
General info
- Function
Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents (PubMed:10581243, PubMed:11839743, PubMed:12692549, PubMed:12702806, PubMed:14703513, PubMed:15367631, PubMed:15485837, PubMed:18583960, PubMed:21138416, PubMed:23453971, PubMed:23453972, PubMed:23746807, PubMed:25636800, PubMed:26611359, PubMed:32404352, PubMed:34363755). 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 (PubMed:12692549, PubMed:12702806, PubMed:14703513, PubMed:15367631, PubMed:18583960, PubMed:25636800). 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 (PubMed:12702806, PubMed:15367631, PubMed:25636800, PubMed:32972995). In order to establish such an antiviral state, TBK1 form several different complexes whose composition depends on the type of cell and cellular stimuli (PubMed:23453971, PubMed:23453972, PubMed:23746807). 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 (PubMed:25636800, PubMed:30842653). Phosphorylated IRF3 dissociates from the adapter proteins, dimerizes, and then enters the nucleus to induce expression of interferons (PubMed:25636800). Thus, several scaffolding molecules including FADD, TRADD, MAVS, AZI2, TANK or TBKBP1/SINTBAD can be recruited to the TBK1-containing-complexes (PubMed:21931631). 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 (PubMed:10783893, PubMed:15489227). Restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin on 'Ser-177', thus enhancing LC3 binding affinity and antibacterial autophagy (PubMed:21617041). Phosphorylates SMCR8 component of the C9orf72-SMCR8 complex, promoting autophagosome maturation (PubMed:27103069). Phosphorylates ATG8 proteins MAP1LC3C and GABARAPL2, thereby preventing their delipidation and premature removal from nascent autophagosomes (PubMed:31709703). Phosphorylates and activates AKT1 (PubMed:21464307). 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 (By similarity). Attenuates retroviral budding by phosphorylating the endosomal sorting complex required for transport-I (ESCRT-I) subunit VPS37C (PubMed:21270402). Phosphorylates Borna disease virus (BDV) P protein (PubMed:16155125). 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 (PubMed:22851595). Acts both as a positive and negative regulator of the mTORC1 complex, depending on the context: activates mTORC1 in response to growth factors by catalyzing phosphorylation of MTOR, while it limits the mTORC1 complex by promoting phosphorylation of RPTOR (PubMed:29150432, PubMed:31530866). Involved in the regulation of TNF-induced RIPK1-mediated cell death, probably acting via CYLD phosphorylation that in turn controls RIPK1 ubiquitination status (PubMed:34363755). Participates also in the differentiation of T follicular regulatory cells together with the receptor ICOS (PubMed:27135603).
- Sequence similarities
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily.
- Post-translational modifications
Autophosphorylation at Ser-172 activates the kinase, and is an essential step for virus-triggered signaling. Phosphorylated by IKBKB/IKKB at Ser-172. Phosphorylation requires homodimerization and ubiquitination at Lys-30 and Lys-401. Dephosphorylated at Ser-172 by PPM1B and this negatively regulates its role in mediating antiviral response.
Storage
- Shipped at conditions
- Dry Ice
- Appropriate short-term storage conditions
- -80°C
- Appropriate long-term storage conditions
- -80°C
- Aliquoting information
- Upon delivery aliquot
- Storage information
- Avoid freeze / thaw cycle
This product is an active protein and may elicit a biological response in vivo, handle with caution.
Notes
Native Pig Myelin Basic Protein ab64311 (Myelin Basic Protein protein) can be utilized as a substrate for assessing kinase activity
Supplementary info
- This supplementary information is collated from multiple sources and compiled automatically.
- Activity summary
The NAK/TBK1 also known as TANK-binding kinase 1 is a fundamental protein kinase in various cellular processes. It weighs approximately 84 kDa and is expressed in many tissues including lymphoid organs and the brain. NAK acts as a serine/threonine-protein kinase which transfers a phosphate group to specific substrates modulating their function and activity. Phosphorylation by TBK1 initiates several signaling events making it an important regulator in immune responses and inflammatory signaling pathways.
- Biological function summary
This kinase plays a significant role in antiviral defense and autophagy. NAK/TBK1 is also involved in innate immune signaling and cell survival. TBK1 forms part of a larger signaling complex interacting with adaptors like TRAF3 and TANK which are important for its proper localization and function. Phospho-NAK its phosphorylated form can activate other molecules driving various downstream immune and stress responses.
- Pathways
The protein is integral to the type I interferon signaling pathway and NF-kB pathway. NAK/TBK1 interacts closely with IRF3 a transcription factor important for antiviral activity and plays a role alongside other proteins like IKKε. These interactions permit activation of genes necessary for defense mechanisms against viral pathogens and control of inflammation. In the NF-kB pathway TBK1 helps regulate cellular responses to stress and inflammatory signals.
- Associated diseases and disorders
NAK/TBK1 has associations with amyotrophic lateral sclerosis (ALS) and various cancers. Research shows connections between TBK1 mutations and ALS indicating its importance in neuronal function and health. Additionally aberrations in TBK1 activity contribute to oncogenesis as it can affect cell proliferation and survival. The protein's relation with signaling proteins such as p62/SQSTM1 highlights its diverse role in disease mechanisms making it a potential therapeutic target.
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Functional Studies - Recombinant human NAK/TBK1 protein (ab85276)
The specific activity of NAK/TBK1 (ab85276) was determined to be 310 nmol/min/mg as per activity assay protocol
SDS-PAGE - Recombinant human NAK/TBK1 protein (ab85276)
SDS PAGE analysis of ab85276
Functional Studies - Recombinant human NAK/TBK1 protein (ab85276)
The Specific activity of ab85276 was determined to be 305 nmol/min/mg.
SDS-PAGE - Recombinant human NAK/TBK1 protein (ab85276)
SDS-PAGE showing ab85276 at approximately 105kDa.
Western blot - Recombinant human NAK/TBK1 protein (ab85276)
All lanes: Anti-NAK antibody (ab75969) at 1 µg/mL
All lanes: Western blot - Recombinant human NAK/TBK1 protein (ab85276) at 0.1 µg
SecondaryAll lanes: Western blot - Goat Anti-Rabbit IgG H&L (HRP) preadsorbed (Goat Anti-Rabbit IgG H&L (HRP) preadsorbed ab97080) at 1/5000 dilution
Developed using the ECL technique.
Performed under reducing conditions.
Exposure time: 1min
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