Relation Results

Identifier	Residue	Sequence
SIGNOR-275733	Ser122	KPPSSGTsSEFEVVT
pmid	sentence
36574265	TBK1 phosphorylation activates LIR-dependent degradation of the inflammation repressor TNIP1

Identifier	Residue	Sequence
SIGNOR-275734	Ser123	PPSSGTSsEFEVVTP
pmid	sentence
36574265	TBK1 phosphorylation activates LIR-dependent degradation of the inflammation repressor TNIP1

Publications:

2

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-270350	Ser13	KLMKAFEsLKSFQQQ	Homo sapiens	HEK-293 Cell
pmid	sentence
32757223	Herein, we report the discovery and validation of a kinase, TANK-binding kinase 1 (TBK1), that efficiently phosphorylates full-length and N-terminal HTT fragments in vitro (at S13/S16), in cells (at S13) and in vivo. TBK1 expression in HD models (cells, primary neurons, and Caenorhabditis elegans) increases mutant HTT exon 1 phosphorylation and reduces its aggregation and cytotoxicity.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-273815	Ser133	PVLKAHQsHSAEIES	Homo sapiens	HEK-293 Cell
pmid	sentence
23649622	TBK1 phosphorylates SIKE on six serine residues that mimic the IRF3 phosphorylation sequence.Serines are listed from left to right: 133, 185, 187, 188, 190, and 198.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-273813	Ser185	KELRELLsISSESLQ	Homo sapiens	HEK-293 Cell
pmid	sentence
23649622	TBK1 phosphorylates SIKE on six serine residues that mimic the IRF3 phosphorylation sequence.TBK1-SIKE interactions were modulated by SIKE phosphorylation, clustered in the C-terminal portion of SIKE (Ser-133, -185, -187, -188, -190, and -198). Here, we describe the mechanism by which suppressor of IKKε (SIKE) inhibits TBK1-mediated phosphorylation of interferon regulatory factor 3 (IRF3), which is essential to type I interferon production. Kinetic analyses showed that SIKE not only inhibits IRF3 phosphorylation but is also a high affinity TBK1 substrate.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-273814	Ser187	LRELLSIsSESLQAR	Homo sapiens	HEK-293 Cell
pmid	sentence
23649622	TBK1 phosphorylates SIKE on six serine residues that mimic the IRF3 phosphorylation sequence.Serines are listed from left to right: 133, 185, 187, 188, 190, and 198.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-273816	Ser188	RELLSISsESLQARK	Homo sapiens	HEK-293 Cell
pmid	sentence
23649622	TBK1 phosphorylates SIKE on six serine residues that mimic the IRF3 phosphorylation sequence.Serines are listed from left to right: 133, 185, 187, 188, 190, and 198.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-273817	Ser190	LLSISSEsLQARKEN	Homo sapiens	HEK-293 Cell
pmid	sentence
23649622	TBK1 phosphorylates SIKE on six serine residues that mimic the IRF3 phosphorylation sequence.Serines are listed from left to right: 133, 185, 187, 188, 190, and 198.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-273818	Ser198	LQARKENsMDTASQA	Homo sapiens	HEK-293 Cell
pmid	sentence
23649622	TBK1 phosphorylates SIKE on six serine residues that mimic the IRF3 phosphorylation sequence.Serines are listed from left to right: 133, 185, 187, 188, 190, and 198.

Publications:

6

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-273811	Ser147	REEGRCSsSDDDTDV	Homo sapiens	HEK-293 Cell
pmid	sentence
24488098	MDM2-dependent HPIP degradation occurs in breast cancer cells on its phosphorylation by the estrogen-activated kinase TBK1. Phosphorylation of HPIP on serine 147 by TBK1 promotes E2-mediated GREB1 expression.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-273643	Ser147	REEGRCSsSDDDTDV	Homo sapiens	HEK-293 Cell
pmid	sentence
24488098	Phosphorylation of HPIP on serine 147 by TBK1 promotes E2-mediated GREB1 expression. Accordingly, we identified the microtubule-associated HPIP, a positive regulator of oncogenic AKT signaling, as a novel MDM2 substrate. MDM2-dependent HPIP degradation occurs in breast cancer cells on its phosphorylation by the estrogen-activated kinase TBK1.

Publications:

2

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-196528	Ser158	QRMLPSLsLTEDVKW	Homo sapiens
pmid	sentence
22412986	Activation of interferon regulatory factor 5 by site specific phosphorylation. Although the gene induction by irf5 in the presence of tbk-1 was modest, phosphorylation by tbk-1 produced a significant shift in the mobility of irf5 in sds-page. For this reason we identified the residues that are phosphorylated on irf5 by tbk-1 with mass spectrometry. Ser-158 and ser-309 were found to be phosphorylated

Identifier	Residue	Sequence	Organism
SIGNOR-196532	Ser293	VELFGPIsLEQVRFP	Homo sapiens
pmid	sentence
22412986	Activation of interferon regulatory factor 5 by site specific phosphorylation. Although the gene induction by irf5 in the presence of tbk-1 was modest, phosphorylation by tbk-1 produced a significant shift in the mobility of irf5 in sds-page. For this reason we identified the residues that are phosphorylated on irf5 by tbk-1 with mass spectrometry. Ser-158 and ser-309 were found to be phosphorylated

Publications:

2

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-276966	Ser172	EDDEQFVsLYGTEEY	Homo sapiens
pmid	sentence
27419230	Furthermore, PPM1A, but not PPM1B, serves as an efficient phosphatase to dephosphorylate Ser 172 residue of both TBK1 and IKKepsilon kinases, which is critical for their kinase activities.\|In a similar in vitro phosphatase assay, incubation of PPM1A also eliminated TBK1 and IKKepsilon phosphorylation at Ser 172 residue, evidenced by phospho-S172 immunoblotting (XREF_FIG, F and G).\|These observations suggest that PPM1A may block kinase activities of TBK1 and IKKepsilon.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-273812	Ser202	SQQEKIDsIADHVNS	Homo sapiens	HEK-293 Cell
pmid	sentence
30827897	Stx17 is phosphorylated by TBK1 whereby phospho-Stx17 controls the formation of the ATG13+FIP200+ mammalian pre-autophagosomal structure (mPAS) in response to induction of autophagy. TBK1 phosphorylates Stx17 at S202.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence
SIGNOR-275648	Ser245	GGGDLPNsQEALQKL
pmid	sentence
33850055	TANK-binding kinase 1 (TBK1), a kinase downstream of MAVS, inhibited DDAH2 by phosphorylating DDAH2 at multiple sites. \|The T203D, T211D, S245D, and S253D mutations significantly reduced the inhibitory effect of DDAH2 on RLR signaling, suggesting that phosphorylation of these residues was critical for DDAH2 to inhibit activation o

Identifier	Residue	Sequence
SIGNOR-275646	Ser253	QEALQKLsDVTLVPV
pmid	sentence
33850055	TANK-binding kinase 1 (TBK1), a kinase downstream of MAVS, inhibited DDAH2 by phosphorylating DDAH2 at multiple sites. \|The T203D, T211D, S245D, and S253D mutations significantly reduced the inhibitory effect of DDAH2 on RLR signaling, suggesting that phosphorylation of these residues was critical for DDAH2 to inhibit activation o

Identifier	Residue	Sequence
SIGNOR-275645	Thr203	VRAMAVLtDHPYASL
pmid	sentence
33850055	TANK-binding kinase 1 (TBK1), a kinase downstream of MAVS, inhibited DDAH2 by phosphorylating DDAH2 at multiple sites. \|The T203D, T211D, S245D, and S253D mutations significantly reduced the inhibitory effect of DDAH2 on RLR signaling, suggesting that phosphorylation of these residues was critical for DDAH2 to inhibit activation o

Identifier	Residue	Sequence
SIGNOR-275647	Thr211	DHPYASLtLPDDAAA
pmid	sentence
33850055	TANK-binding kinase 1 (TBK1), a kinase downstream of MAVS, inhibited DDAH2 by phosphorylating DDAH2 at multiple sites. \|The T203D, T211D, S245D, and S253D mutations significantly reduced the inhibitory effect of DDAH2 on RLR signaling, suggesting that phosphorylation of these residues was critical for DDAH2 to inhibit activation o

Publications:

4

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-263136	Ser358	VPSTSTMsQEPELLI	Homo sapiens	HEK-293 Cell
pmid	sentence
18818105	MITA was phosphorylated by TBK1, which is required for MITA-mediated activation of IRF3. Our results suggest that MITA is a critical mediator of virus-triggered IRF3 activation and IFN expression and further demonstrate the importance of certain mitochondrial proteins in innate antiviral immunity. Consistent with its inability to activate IRF-E, the mutation of S358 to alanine impaired the ability of MITA to interact with TBK1 and to enhance the interaction between TBK1 and IRF3

Publications:

1

Organism:

Homo Sapiens

Pathways:

COVID-19 Causal Network, Innate Immune Response, SARS-CoV INNATE RESPONSE TO dsRNA

Identifier	Residue	Sequence	Organism
SIGNOR-246643	Ser36	RHDSGLDsMKDEEYE	Homo sapiens
pmid	sentence
11815618	Nuclear factor-kappaB activation depends on phosphorylation and degradation of its inhibitor protein, IkapapB. TBK-1 and IKK-i phosphorylate Ser36 of IkappaBalpha.

Publications:

1

Organism:

Homo Sapiens

Pathways:

COVID-19 Causal Network, EBV infection, Toll like receptors

Identifier	Residue	Sequence	Organism
SIGNOR-178391	Ser385	MARVGGAsSLENTVD	in vitro
pmid	sentence
18440553	Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404.

Identifier	Residue	Sequence	Organism
SIGNOR-178395	Ser386	ARVGGASsLENTVDL	in vitro
pmid	sentence
18440553	Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404.

Identifier	Residue	Sequence	Organism
SIGNOR-178399	Ser396	NTVDLHIsNSHPLSL	in vitro
pmid	sentence
18440553	Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404.

Identifier	Residue	Sequence	Organism
SIGNOR-178403	Ser398	VDLHISNsHPLSLTS	in vitro
pmid	sentence
18440553	Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404.

Identifier	Residue	Sequence	Organism
SIGNOR-178407	Ser402	ISNSHPLsLTSDQYK	in vitro
pmid	sentence
18440553	Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404.

Identifier	Residue	Sequence	Organism
SIGNOR-178411	Ser405	SHPLSLTsDQYKAYL	in vitro
pmid	sentence
18440553	Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404.

Identifier	Residue	Sequence	Organism
SIGNOR-178420	Thr404	NSHPLSLtSDQYKAY	in vitro
pmid	sentence
18440553	Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404.

Identifier	Residue	Organism	Cell Line
SIGNOR-120355		Homo sapiens	T-lymphocyte
pmid	sentence
14679297	We show that purified recombinant ikk-epsilon and tbk1 directly phosphorylate the critical serine residues in irf3 allowing its translocation into the nucleus and production of interferon type i.

Identifier	Residue	Organism
SIGNOR-260154		Homo sapiens
pmid	sentence
24622840	STING recruits TBK1 and IKKε and forms the TBK1-IKKε complex via the association with TRAF3. The TBK1 complex induces the phosphorylation, dimerization, and nuclear translocation of IRF3.

Publications:

9

Organism:

In Vitro, Homo Sapiens

Pathways:

COVID-19 Causal Network, EBV infection, Innate Immune Response, Inflammosome Activation, SARS-CoV INFLAMMATORY RESPONSE, SARS-CoV INNATE RESPONSE TO dsRNA, Toll like receptors

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-191944	Ser403	ESLSQMLsMGFSDEG	Homo sapiens	Macrophage
pmid	sentence
22921120	Tbk-1 coordinated assembly and function of the autophagic machinery and phosphorylated the autophagic adaptor p62 (sequestosome 1) on ser-403, a residue essential for its role in autophagic clearance.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-176771	Ser407	PIQLQALsLPLVVIV	Homo sapiens
pmid	sentence
22000020	We now show that stat6 is required for innate immune signaling in response to virus infection. Viruses or cytoplasmic nucleic acids trigger sting (also named mita/eris) to recruit stat6 to the endoplasmic reticulum, leading to stat6 phosphorylation on ser(407) by tbk1 and tyr(641), independent of jaks. Phosphorylated stat6 then dimerizes and translocates to the nucleus to induce specific target genes responsible for immune cell homing.

Identifier	Residue	Sequence	Organism
SIGNOR-176775	Tyr641	MGKDGRGyVPATIKM	Homo sapiens
pmid	sentence
22000020	We now show that stat6 is required for innate immune signaling in response to virus infection. Viruses or cytoplasmic nucleic acids trigger sting (also named mita/eris) to recruit stat6 to the endoplasmic reticulum, leading to stat6 phosphorylation on ser(407) by tbk1 and tyr(641), independent of jaks. Phosphorylated stat6 then dimerizes and translocates to the nucleus to induce specific target genes responsible for immune cell homing.

Publications:

2

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-252608	Ser473	RPHFPQFsYSASGTA	Homo sapiens
pmid	sentence
21329883	Upon mitogen stimulation, triggering of the innate immune response, re-exposure to glucose, or oncogene activation, tbk1 is recruited to the exocyst, where it activates akt. Akt is a direct tbk1 substrate that connects tbk1 to prosurvival signaling.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-172132	Ser473	RPHFPQFsYSASGTA	Homo sapiens
pmid	sentence
21329883	Upon mitogen stimulation, triggering of the innate immune response, re-exposure to glucose, or oncogene activation, tbk1 is recruited to the exocyst, where it activates akt. Akt is a direct tbk1 substrate that connects tbk1 to prosurvival signaling.

Publications:

1

Organism:

Homo Sapiens

Pathways:

COVID-19 Causal Network, EBV infection, Inflammosome Activation, SARS-CoV INFLAMMATORY RESPONSE

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-276939	Ser527	QDIDSRLsPGGSLAD	Homo sapiens	HEK-293 Cell
pmid	sentence
26407194	We further found that DYRK2 phosphorylated Ser527 of TBK1, which is essential for the recruitment of NLRP4 and for the E3 ubiquitin ligase DTX4 to degrade TBK1.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-129951	Ser536	SGDEDFSsIADMDFS	Homo sapiens
pmid	sentence
15489227	Chromatographic fractionation of cell extracts allowed the identification of two distinct enzymatic activities phosphorylating ser-536. Peak 1 represents an unknown kinase, whereas peak 2 contained ikkalpha, ikkbeta, ikkepsilon, and tbk1. collectively, our results provide evidence for at least five kinases that converge on ser-536 of p65 and a novel function for this phosphorylation site in the recruitment of components of the basal transcriptional machinery to the interleukin-8 promoter.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-272472	Ser716	HILERFGsLTMDGGL	Homo sapiens
pmid	sentence
31792381	TBKBP1 recruits TBK1 to protein kinase C-theta (PKCθ) through a scaffold protein, CARD10. This enables PKCθ to phosphorylate TBK1 at Ser 716, a crucial step for TBK1 activation

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
SIGNOR-277317	Thr228	DMADTCGtICHAADK	in vitro
pmid	sentence
34343500	Here, we show that ionizing radiation results in TBK1-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase (PRPS)1/2 at T228, thereby enhancing PRPS1/2 catalytic activity and promoting deoxyribonucleotide synthesis.

Publications:

1

Organism:

In Vitro

Identifier	Residue	Sequence	Organism
SIGNOR-277316	Thr228	DMADTCGtICHAADK	in vitro
pmid	sentence
34343500	Here, we show that ionizing radiation results in TBK1-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase (PRPS)1/2 at T228, thereby enhancing PRPS1/2 catalytic activity and promoting deoxyribonucleotide synthesis.

Publications:

1

Organism:

In Vitro

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-276724	Tyr354	SSNQELIyEGRRLVL	Homo sapiens	HEK-293T Cell
pmid	sentence
28618271	The Src family kinases (SFKs) Lck, Hck, and Fgr directly phosphorylate TBK1 at Tyr354/394, to prevent TBK1 dimerization and activation.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-276723	Tyr394	LNTIGLIyEKISLPK	Homo sapiens	HEK-293T Cell
pmid	sentence
28618271	The Src family kinases (SFKs) Lck, Hck, and Fgr directly phosphorylate TBK1 at Tyr354/394, to prevent TBK1 dimerization and activation.

Publications:

2

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-276726	Tyr354	SSNQELIyEGRRLVL	Homo sapiens	HEK-293T Cell
pmid	sentence
28618271	The Src family kinases (SFKs) Lck, Hck, and Fgr directly phosphorylate TBK1 at Tyr354/394, to prevent TBK1 dimerization and activation.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-276727	Tyr394	LNTIGLIyEKISLPK	Homo sapiens	HEK-293T Cell
pmid	sentence
28618271	The Src family kinases (SFKs) Lck, Hck, and Fgr directly phosphorylate TBK1 at Tyr354/394, to prevent TBK1 dimerization and activation.

Publications:

2

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-276725	Tyr354	SSNQELIyEGRRLVL	Homo sapiens	HEK-293T Cell
pmid	sentence
28618271	The Src family kinases (SFKs) Lck, Hck, and Fgr directly phosphorylate TBK1 at Tyr354/394, to prevent TBK1 dimerization and activation.

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-276722	Tyr394	LNTIGLIyEKISLPK	Homo sapiens	HEK-293T Cell
pmid	sentence
28618271	The Src family kinases (SFKs) Lck, Hck, and Fgr directly phosphorylate TBK1 at Tyr354/394, to prevent TBK1 dimerization and activation.

Publications:

2

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-260156		Homo sapiens
pmid	sentence
24622840	MAVS also interacts with STING that locates at the ER (endoplasmic reticulum), and induces the ubiquitination and dimerization of STING. The activated STING recruits TBK1 and IRF3 and contributes to the phosphorylation of IRF3 mediated by TBK1.

Publications:

1

Organism:

Homo Sapiens

Pathways:

COVID-19 Causal Network, Innate Immune Response, Inflammosome Activation, SARS-CoV INFLAMMATORY RESPONSE

Identifier	Residue	Organism
SIGNOR-272469		Homo sapiens
pmid	sentence
31792381	TBKBP1 recruits TBK1 to protein kinase C-theta (PKCθ) through a scaffold protein, CARD10. This enables PKCθ to phosphorylate TBK1 at Ser 716, a crucial step for TBK1 activation

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-262510		Homo sapiens
pmid	sentence
32979938	We use unbiased screening to identify SARS-CoV-2 proteins that antagonize type I interferon (IFN-I) response. We found three proteins that antagonize IFN-I production via distinct mechanisms: nonstructural protein 6 (nsp6) binds TANK binding kinase 1 (TBK1) to suppress interferon regulatory factor 3 (IRF3) phosphorylation, nsp13 binds and blocks TBK1 phosphorylation, and open reading frame 6 (ORF6) binds importin Karyopherin α 2 (KPNA2) to inhibit IRF3 nuclear translocation. the results indicate that (1) nsp6 binds to TBK1 without affecting TBK1 phosphorylation, but the nsp6/TBK1 interaction decreases IRF3 phosphorylation, which leads to reduced IFN-β production; and (2) nsp13 binds and inhibits TBK1 phosphorylation, resulting in decreased IRF3 activation and IFN-β production (Figure 2F).

Publications:

1

Organism:

Homo Sapiens

Pathways:

SARS-CoV INFLAMMATORY RESPONSE, SARS-CoV INNATE RESPONSE TO dsRNA

Identifier	Residue	Organism
SIGNOR-276985		in vitro
pmid	sentence
22750291	PPM1B dephosphorylates TBK1 in vivo and in vitro.\|These results demonstrate that PPM1B inhibits TBK1 mediated antiviral signaling by directly dephosphorylating TBK1 at Ser172.

Publications:

1

Organism:

In Vitro

Identifier	Residue	Organism	Cell Line
SIGNOR-262511		Homo sapiens	HEK-293 Cell
pmid	sentence
32979938	We use unbiased screening to identify SARS-CoV-2 proteins that antagonize type I interferon (IFN-I) response. We found three proteins that antagonize IFN-I production via distinct mechanisms: nonstructural protein 6 (nsp6) binds TANK binding kinase 1 (TBK1) to suppress interferon regulatory factor 3 (IRF3) phosphorylation, nsp13 binds and blocks TBK1 phosphorylation, and open reading frame 6 (ORF6) binds importin Karyopherin α 2 (KPNA2) to inhibit IRF3 nuclear translocation. the results indicate that (1) nsp6 binds to TBK1 without affecting TBK1 phosphorylation, but the nsp6/TBK1 interaction decreases IRF3 phosphorylation, which leads to reduced IFN-β production; and (2) nsp13 binds and inhibits TBK1 phosphorylation, resulting in decreased IRF3 activation and IFN-β production (Figure 2F).

Identifier	Residue	Organism	Cell Line
SIGNOR-262512		Homo sapiens	HEK-293 Cell
pmid	sentence
32979938	We use unbiased screening to identify SARS-CoV-2 proteins that antagonize type I interferon (IFN-I) response. We found three proteins that antagonize IFN-I production via distinct mechanisms: nonstructural protein 6 (nsp6) binds TANK binding kinase 1 (TBK1) to suppress interferon regulatory factor 3 (IRF3) phosphorylation, nsp13 binds and blocks TBK1 phosphorylation, and open reading frame 6 (ORF6) binds importin Karyopherin α 2 (KPNA2) to inhibit IRF3 nuclear translocation. the results indicate that (1) nsp6 binds to TBK1 without affecting TBK1 phosphorylation, but the nsp6/TBK1 interaction decreases IRF3 phosphorylation, which leads to reduced IFN-β production; and (2) nsp13 binds and inhibits TBK1 phosphorylation, resulting in decreased IRF3 activation and IFN-β production (Figure 2F).

Publications:

2

Organism:

Homo Sapiens

Pathways:

SARS-CoV INFLAMMATORY RESPONSE, SARS-CoV INNATE RESPONSE TO dsRNA

Identifier	Residue	Organism
SIGNOR-217667		Homo sapiens
pmid	sentence
16888014	The present results demonstrate that ikkepsilon- and tbk1-mediated phosphorylation of crel in the c-terminal td leads to cytoplasmic dissociation of a crel-ikb_ complex and nuclear accumulation of crel.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-148623		Homo sapiens
pmid	sentence
16888014	The present results demonstrate that ikkepsilon- and tbk1-mediated phosphorylation of crel in the c-terminal td leads to cytoplasmic dissociation of a crel-ikb_ complex and nuclear accumulation of crel.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism	Cell Line
SIGNOR-260593		Homo sapiens	HEK-293 Cell
pmid	sentence
26631542	Previous studies have shown that MERS-CoV ORF4b antagonizes the early antiviral alpha/beta interferon (IFN-α/β) response, which may significantly contribute to MERS-CoV pathogenesis; however, the underlying mechanism is poorly understood. Here, we found that ORF4b in the cytoplasm could specifically bind to TANK binding kinase 1 (TBK1) and IκB kinase epsilon (IKKε), suppress the molecular interaction between mitochondrial antiviral signaling protein (MAVS) and IKKε, and inhibit IFN regulatory factor 3 (IRF3) phosphorylation and subsequent IFN-β production. these results indicate that MERS-CoV ORF4b inhibits the induction of type I IFN through a direct interaction with IKKε/TBK1 in the cytoplasm

Publications:

1

Organism:

Homo Sapiens

Pathways:

COVID-19 Causal Network, SARS-CoV INNATE RESPONSE TO dsRNA

Identifier	Residue	Organism
SIGNOR-190795		Homo sapiens
pmid	sentence
Other

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism	Cell Line
SIGNOR-262276		Homo sapiens	HEK-293 Cell
pmid	sentence
20174559	Using biochemical experiments we showed that optineurin interacts with the protein kinase TBK1 and the ubiquitin ligase TRAF3. Furthermore, a mutation in optineurin that prevents the interaction with the small protein modifier ubiquitin (D474N) ablated the negative regulatory function of optineurin.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism	Cell Line
SIGNOR-276802
pmid	sentence
30145926	Inhibition of DNM or dynein-mediated endocytic trafficking for up to 1 h resulted in translocation of TFEB-GFP to the nucleus in P8B11-HeLa cells (Figure 5(a-c) and a correlated increase in transcription of TFEB-target genes, including MAP1LC3/LC3, SQSTM1, MCOLN1, CTSB, CTSF, and TFEB

Publications:

1

Identifier	Residue	Organism
SIGNOR-178053		Homo sapiens
pmid	sentence
18353649	Whereas nemo assembles some but not all ikk complexes [12,13], recent reports provide strong experimental evidence for a role of tank [also called traf-interacting protein (i-traf)], nak-associated protein (nap1) and similar to nap1 tbk1 adaptor (sintbad) in the assembly of tbk1 and ikk-e kinase complexes that phosphorylate irf3 and irf7 and promote type i ifn gene induction

Publications:

1

Organism:

Homo Sapiens

Pathways:

COVID-19 Causal Network, Innate Immune Response, SARS-CoV INNATE RESPONSE TO dsRNA, Toll like receptors

Identifier	Residue	Organism
SIGNOR-260145		Homo sapiens
pmid	sentence
25636800	After ligand binding, cGAS and RIG-I signal through respective adaptor proteins STING and MAVS to recruit the kinases IKK and TBK1, which then activate the transcription factors NF-κB and interferon regulatory factor 3 (IRF3), respectively.

Publications:

1

Organism:

Homo Sapiens

Pathways:

COVID-19 Causal Network, Innate Immune Response, SARS-CoV INNATE RESPONSE TO dsRNA

Identifier	Residue	Organism
SIGNOR-260153		Homo sapiens
pmid	sentence
24622840	MAVS also interacts with STING that locates at the ER (endoplasmic reticulum), and induces the ubiquitination and dimerization of STING. The activated STING recruits TBK1 and IRF3 and contributes to the phosphorylation of IRF3 mediated by TBK1.

Publications:

1

Organism:

Homo Sapiens

Pathways:

COVID-19 Causal Network, Innate Immune Response, SARS-CoV INNATE RESPONSE TO dsRNA

Identifier	Residue	Organism
SIGNOR-121576		Homo sapiens
pmid	sentence
14743216	A physical and functional map of the human tnf-alpha/nf-kappa b signal transduction pathway.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism	Cell Line
SIGNOR-266654		Homo sapiens	HEK-293 Cell
pmid	sentence
28871090	TRIM23 interacts with TBK1 and p62. TRIM23 GTPase activates TBK1 to phosphorylate p62. Biochemical characterization showed that TRIM23 binds with its C-terminal ARF domain to the N-terminal KD of TBK1, and that GTP hydrolysis activity of the ARF stimulates TBK1-mediated phosphorylation of p62 at S403 in its ubiquitin-associated (UBA) domain, which was shown to promote cargo recruitment and autophagic flux

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism	Cell Line
SIGNOR-71565		Homo sapiens	Neuron
pmid	sentence
10531053	Nlrp4 negatively regulates type i interferon signaling by targeting the kinase tbk1 for degradation via the ubiquitin ligase dtx4

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism	Cell Line
SIGNOR-261109		Mus musculus	Primary Cell
pmid	sentence
23099093	We herein describe the development of a novel series of 2,4-diamino-5-cyclopropyl pyrimidines as potent inhibitors of TBK1/IKKɛ, with improved kinase selectivity and drug-like properties.

Publications:

1

Organism:

Mus Musculus

Identifier	Residue	Organism	Cell Line
SIGNOR-118458		Homo sapiens	HEK-293 Cell
pmid	sentence
14530355	Toll/il-1 receptor domain-containing adaptor inducing ifn-beta (trif) associates with tnf receptor-associated factor 6 and tank-binding kinase 1, and activates two distinct transcription factors, nf-kappa b and ifn-regulatory factor-3, in the toll-like receptor signaling

Publications:

1

Organism:

Homo Sapiens

Pathways:

COVID-19 Causal Network, EBV infection, Innate Immune Response, Inflammosome Activation, SARS-CoV INFLAMMATORY RESPONSE, SARS-CoV INNATE RESPONSE TO dsRNA, Toll like receptors

Identifier	Residue	Organism
SIGNOR-260157		Homo sapiens
pmid	sentence
15489227	Constitutive and interleukin-1-inducible Phosphorylation of p65 NF-{kappa}B at Serine 536 Is Mediated by Multiple Protein Kinases Including I{kappa}B Kinase (IKK)-{alpha}, IKK{beta}, IKK{epsilon}, TRAF Family Member-Associated (TANK)-binding Kinase 1 (TBK1). Overexpressed ikkepsilon and tbk1 phosphorylate ser-536 in vivo and in vitro.

Publications:

1

Organism:

Homo Sapiens

Pathways:

COVID-19 Causal Network, EBV infection, Innate Immune Response, Inflammosome Activation, SARS-CoV INFLAMMATORY RESPONSE, SARS-CoV INNATE RESPONSE TO dsRNA, Toll like receptors

Identifier	Residue	Organism	Cell Line
SIGNOR-273664		Mus musculus	MEF Cell
pmid	sentence
28704656	Here we report that viral infection induced upregulation of INKIT, an inhibitor for NF-κB and IRF3 that restricted innate antiviral responses by blocking phosphorylation of p65 and IRF3. Viral infection induced IKK-mediated phosphorylation of INKIT at Ser58, resulting in its dissociation from the IKKs. INKIT is associated with IKKα/β and TBK1/IKKɛ and inhibits the recruitment and phosphorylation of p65 and IRF3, respectively. IKKα and TBK1 phosphorylate INKIT at Ser58, which results in disassociation of INKIT from IKKα or TBK1 and thereby allows for the subsequent recruitment and phosphorylation of p65 and IRF3

Publications:

1

Organism:

Mus Musculus

Identifier	Residue	Organism
SIGNOR-260155		Homo sapiens
pmid	sentence
24622840	STING recruits TBK1 and IKKε and forms the TBK1-IKKε complex via the association with TRAF3. The TBK1 complex induces the phosphorylation, dimerization, and nuclear translocation of IRF3.

Publications:

1

Organism:

Homo Sapiens

Pathways:

COVID-19 Causal Network, Innate Immune Response, SARS-CoV INNATE RESPONSE TO dsRNA, Toll like receptors

Name	TBK1 View Modifications
Full Name	Serine/threonine-protein kinase TBK1
Synonyms	NF-kappa-B-activating kinase, T2K, TANK-binding kinase 1 \| NAK
Primary ID	Q9UHD2
Links	- -
Type	protein
Relations	69
Pathways	COVID-19 Causal Network, EBV infection, Innate Immune Response, Inflammosome Activation, SARS-CoV INFLAMMATORY RESPONSE, SARS-CoV INNATE RESPONSE TO dsRNA, Toll like receptors
Inhibitors	N-[3-[[5-iodo-4-[3-[[oxo(thiophen-2-yl)methyl]amino]propylamino]-2-pyrimidinyl]amino]phenyl]-1-pyrrolidinecarboxamide
Function	Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents (PubMed:12692549, PubMed:14703513, PubMed:18583960, PubMed:12702806, PubMed:15367631, PubMed:10581243, PubMed:11839743, PubMed:15485837, PubMed:21138416, PubMed:25636800, PubMed:23453971, PubMed:23453972, PubMed:23746807, PubMed:26611359, PubMed:32404352). 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:14703513, PubMed:18583960, PubMed:12702806, PubMed:15367631, 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

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