Ser172
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Home > Phosphorylation Site Page: > Ser172  -  TBK1 (human)

Site Information
EDDEQFVsLyGTEEy   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447732

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 67 ) , electrophoretic mobility shift ( 7 ) , immunoprecipitation ( 4 , 5 , 7 , 9 , 12 ) , mass spectrometry ( 4 , 5 , 8 , 17 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ) , mutation of modification site ( 4 , 5 , 6 , 7 , 9 , 10 , 12 , 18 , 39 , 67 ) , phospho-antibody ( 1 , 5 , 6 , 7 , 9 , 10 , 12 , 13 , 14 , 19 , 39 , 66 ) , phosphopeptide mapping ( 67 ) , western blotting ( 1 , 4 , 5 , 6 , 7 , 9 , 10 , 12 , 13 , 18 , 19 , 39 , 66 )
Disease tissue studied:
brain cancer ( 19 , 66 ) , glioblastoma ( 19 , 66 ) , glioblastoma multiforme ( 66 ) , glioma ( 19 , 66 ) , HER2 positive breast cancer ( 8 ) , luminal A breast cancer ( 8 ) , luminal B breast cancer ( 8 ) , breast cancer, triple negative ( 8 ) , gastric cancer ( 24 , 33 ) , gastric carcinoma ( 24 , 33 ) , liver cancer ( 40 , 42 , 43 , 47 , 48 , 50 , 51 , 57 , 58 , 59 ) , liver cancer, surrounding tissue ( 41 , 45 , 49 , 60 , 61 ) , lung cancer ( 54 , 55 , 56 ) , non-small cell lung cancer ( 54 , 55 , 56 ) , melanoma skin cancer ( 52 , 53 ) , fibrosarcoma of soft tissue ( 1 , 6 ) , teratoma, surrounding tissue ( 44 ) , thyroid cancer, surrounding tissue ( 46 )
Relevant cell line - cell type - tissue:
'3T3-L1, differentiated' (adipocyte) ( 5 ) , 293 (epithelial) ( 9 , 39 ) , breast ( 8 ) , BTI-Tn-5B1-4 ( 18 ) , COS (fibroblast) ( 5 ) , dendritic cell ( 6 ) , germ cell-teratoma ( 44 ) , HCT116 (intestinal) ( 62 ) , HEK293T (epithelial) ( 4 , 5 , 7 , 10 , 13 , 18 ) , HeLa (cervical) ( 10 , 12 , 13 ) , HT1080 (fibroblast) ( 1 ) , Jurkat (T lymphocyte) ( 17 , 21 , 22 , 23 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 34 , 35 , 36 , 37 , 38 , 63 , 64 , 65 , 67 ) , L929 (fibroblast) ( 6 ) , liver ( 40 , 41 , 42 , 43 , 45 , 47 , 48 , 49 , 50 , 51 , 57 , 58 , 59 , 60 , 61 ) , lung ( 54 , 55 , 56 ) , macrophage-bone marrow ( 6 , 7 ) , macrophage-peritoneum ( 6 , 7 ) , MEF (fibroblast) ( 19 ) , MKN-45 (gastric) ( 24 ) , mononuclear ( 66 ) , MV4-11 (macrophage) ( 62 ) , RAW 264.7 (macrophage) ( 6 , 7 ) , SF9 ( 67 ) , skin ( 52 , 53 ) , stomach ( 33 ) , thyroid ( 46 ) , U373 MG (glial) [CD14 (human), transfection] ( 66 ) , U87MG (glial) ( 19 )

Upstream Regulation
Regulatory protein:
GSK3B (human) ( 39 ) , MST1 (human) ( 9 ) , Src (mouse) ( 6 ) , TRAF6 (mouse) ( 19 )
Putative in vivo kinases:
TBK1 (human) ( 39 )
Kinases, in vitro:
TBK1 (human) ( 7 )
Treatments:
depolarization ( 12 ) , dexamethasone ( 66 ) , dsDNA ( 1 ) , IL-17A ( 19 ) , insulin ( 5 ) , LPS ( 5 , 6 , 66 ) , oligomycin ( 12 ) , poly(I-C) ( 6 , 66 ) , RO-3306 ( 1 ) , saracatinib ( 6 ) , virus infection ( 6 , 9 )

Downstream Regulation
Effects of modification on TBK1:
enzymatic activity, induced ( 6 , 9 , 14 , 18 , 67 ) , phosphorylation ( 6 , 19 )
Effects of modification on biological processes:
transcription, induced ( 39 )

References 

1

Zhong L, et al. (2020) Phosphorylation of cGAS by CDK1 impairs self-DNA sensing in mitosis. Cell Discov 6, 26
32351706   Curated Info

2

Zhu L, et al. (2019) TBKBP1 and TBK1 form a growth factor signalling axis mediating immunosuppression and tumourigenesis. Nat Cell Biol 21, 1604-1614
31792381   Curated Info

3

Wu S, et al. (2019) HER2 recruits AKT1 to disrupt STING signalling and suppress antiviral defence and antitumour immunity. Nat Cell Biol 21, 1027-1040
31332347   Curated Info

4

Liu S, et al. (2017) Lck/Hck/Fgr-Mediated Tyrosine Phosphorylation Negatively Regulates TBK1 to Restrain Innate Antiviral Responses. Cell Host Microbe 21, 754-768.e5
28618271   Curated Info

5

Uhm M, et al. (2017) Phosphorylation of the exocyst protein Exo84 by TBK1 promotes insulin-stimulated GLUT4 trafficking. Sci Signal 10
28325821   Curated Info

6

Li X, et al. (2017) The tyrosine kinase Src promotes phosphorylation of the kinase TBK1 to facilitate type I interferon production after viral infection. Sci Signal 10
28049762   Curated Info

7

Gu M, et al. (2016) RKIP and TBK1 form a positive feedback loop to promote type I interferon production in innate immunity. EMBO J 35, 2553-2565
27753621   Curated Info

8

Mertins P, et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534, 55-62
27251275   Curated Info

9

Meng F, et al. (2016) Mst1 shuts off cytosolic antiviral defense through IRF3 phosphorylation. Genes Dev 30, 1086-100
27125670   Curated Info

10

Richter B, et al. (2016) Phosphorylation of OPTN by TBK1 enhances its binding to Ub chains and promotes selective autophagy of damaged mitochondria. Proc Natl Acad Sci U S A 113, 4039-44
27035970   Curated Info

11

Pourcelot M, et al. (2016) The Golgi apparatus acts as a platform for TBK1 activation after viral RNA sensing. BMC Biol 14, 69
27538435   Curated Info

12

Heo JM, et al. (2015) The PINK1-PARKIN Mitochondrial Ubiquitylation Pathway Drives a Program of OPTN/NDP52 Recruitment and TBK1 Activation to Promote Mitophagy. Mol Cell 60, 7-20
26365381   Curated Info

13

Lazarou M, et al. (2015) The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature 524, 309-14
26266977   Curated Info

14

Sirohi K, Kumari A, Radha V, Swarup G (2015) A Glaucoma-Associated Variant of Optineurin, M98K, Activates Tbk1 to Enhance Autophagosome Formation and Retinal Cell Death Dependent on Ser177 Phosphorylation of Optineurin. PLoS One 10, e0138289
26376340   Curated Info

15

Mertins P, et al. (2014) Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels. Mol Cell Proteomics 13, 1690-704
24719451   Curated Info

16

Simicek M, et al. (2013) The deubiquitylase USP33 discriminates between RALB functions in autophagy and innate immune response. Nat Cell Biol 15, 1220-30
24056301   Curated Info

17

Mertins P, et al. (2013) Integrated proteomic analysis of post-translational modifications by serial enrichment. Nat Methods 10, 634-7
23749302   Curated Info

18

Tu D, et al. (2013) Structure and ubiquitination-dependent activation of TANK-binding kinase 1. Cell Rep 3, 747-58
23453972   Curated Info

19

Qu F, et al. (2012) TRAF6-Dependent Act1 Phosphorylation by the IκB Kinase-Related Kinases Suppresses Interleukin-17-Induced NF-κB Activation. Mol Cell Biol 32, 3925-37
22851696   Curated Info

20

Stokes MP, et al. (2012) PTMScan Direct: Identification and Quantification of Peptides from Critical Signaling Proteins by Immunoaffinity Enrichment Coupled with LC-MS/MS. Mol Cell Proteomics 11, 187-201
22322096   Curated Info

21

Mulhern D (2012) CST Curation Set: 13107; Year: 2012; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

22

Mulhern D (2012) CST Curation Set: 13108; Year: 2012; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

23

Mulhern D (2012) CST Curation Set: 13109; Year: 2012; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY]
Curated Info

24

Mulhern D (2012) CST Curation Set: 13402; Year: 2012; Biosample/Treatment: cell line, MKN-45/untreated; Disease: gastric carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY]
Curated Info

25

Mulhern D (2011) CST Curation Set: 12684; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (F/Y/M)Xp[ST](L/I/M)
Curated Info

26

Mulhern D (2011) CST Curation Set: 12685; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (F/Y/M)Xp[ST](L/I/M)
Curated Info

27

Mulhern D (2011) CST Curation Set: 12678; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (F/Y/M)Xp[ST](L/I/M)
Curated Info

28

Mulhern D (2011) CST Curation Set: 12679; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (F/Y/M)Xp[ST](L/I/M)
Curated Info

29

Mulhern D (2011) CST Curation Set: 12681; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (F/Y/M)Xp[ST](L/I/M)
Curated Info

30

Mulhern D (2011) CST Curation Set: 12682; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (F/Y/M)Xp[ST](L/I/M)
Curated Info

31

Guo A (2011) CST Curation Set: 12073; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (F/Y/M)Xp[ST](L/I/M)
Curated Info

32

Guo A (2011) CST Curation Set: 12074; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (F/Y/M)Xp[ST](L/I/M)
Curated Info

33

Rikova K (2011) CST Curation Set: 12176; Year: 2011; Biosample/Treatment: tissue, gastrointestinal tract/untreated; Disease: gastric carcinoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pY Antibodies Used to Purify Peptides prior to LCMS: Phospho-Tyrosine Mouse mAb (P-Tyr-100) Cat#: 9411, PTMScan(R) Phospho-Tyr Motif (Y*) Immunoaffinity Beads Cat#: 1991
Curated Info

34

Guo A (2011) CST Curation Set: 11884; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

35

Guo A (2011) CST Curation Set: 11885; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

36

Guo A (2011) CST Curation Set: 11889; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

37

Guo A (2011) CST Curation Set: 11890; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY]
Curated Info

38

Guo A (2011) CST Curation Set: 11893; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY]
Curated Info

39

Lei CQ, et al. (2010) Glycogen synthase kinase 3β regulates IRF3 transcription factor-mediated antiviral response via activation of the kinase TBK1. Immunity 33, 878-89
21145761   Curated Info

40

Tucker M (2010) CST Curation Set: 9834; Year: 2010; Biosample/Treatment: tissue, liver/untreated; Disease: liver cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

41

Tucker M (2010) CST Curation Set: 9831; Year: 2010; Biosample/Treatment: tissue, liver/untreated; Disease: liver cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

42

Tucker M (2010) CST Curation Set: 9842; Year: 2010; Biosample/Treatment: tissue, liver/untreated; Disease: liver cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

43

Tucker M (2010) CST Curation Set: 9832; Year: 2010; Biosample/Treatment: tissue, liver/untreated; Disease: liver cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

44

Tucker M (2010) CST Curation Set: 9847; Year: 2010; Biosample/Treatment: cell line, xy3-145N/untreated; Disease: -; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

45

Tucker M (2010) CST Curation Set: 9843; Year: 2010; Biosample/Treatment: tissue, liver/untreated; Disease: liver cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

46

Tucker M (2010) CST Curation Set: 9849; Year: 2010; Biosample/Treatment: tissue, thyroid/untreated; Disease: thyroid cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

47

Tucker M (2010) CST Curation Set: 9838; Year: 2010; Biosample/Treatment: tissue, liver/untreated; Disease: liver cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

48

Tucker M (2010) CST Curation Set: 9830; Year: 2010; Biosample/Treatment: tissue, liver/untreated; Disease: liver cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

49

Tucker M (2010) CST Curation Set: 9841; Year: 2010; Biosample/Treatment: tissue, liver/untreated; Disease: liver cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

50

Tucker M (2010) CST Curation Set: 9840; Year: 2010; Biosample/Treatment: tissue, liver/untreated; Disease: liver cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

51

Tucker M (2010) CST Curation Set: 9844; Year: 2010; Biosample/Treatment: tissue, liver/untreated; Disease: liver cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

52

Tucker M (2010) CST Curation Set: 9778; Year: 2010; Biosample/Treatment: tissue, skin/untreated; Disease: melanoma skin cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

53

Tucker M (2010) CST Curation Set: 9784; Year: 2010; Biosample/Treatment: tissue, skin/untreated; Disease: melanoma skin cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

54

Rikova K (2010) CST Curation Set: 9470; Year: 2010; Biosample/Treatment: tissue, /untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

55

Rikova K (2010) CST Curation Set: 9456; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

56

Rikova K (2010) CST Curation Set: 9450; Year: 2010; Biosample/Treatment: tissue, lung/untreated; Disease: non-small cell lung cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
Curated Info

57

Tucker M (2010) CST Curation Set: 8912; Year: 2010; Biosample/Treatment: tissue, liver/untreated; Disease: liver cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

58

Tucker M (2010) CST Curation Set: 8910; Year: 2010; Biosample/Treatment: tissue, liver/untreated; Disease: liver cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

59

Tucker M (2010) CST Curation Set: 8914; Year: 2010; Biosample/Treatment: tissue, liver/untreated; Disease: liver cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

60

Tucker M (2010) CST Curation Set: 8911; Year: 2010; Biosample/Treatment: tissue, liver/untreated; Disease: liver cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

61

Tucker M (2010) CST Curation Set: 8909; Year: 2010; Biosample/Treatment: tissue, liver/untreated; Disease: liver cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

62

Oppermann FS, et al. (2009) Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics 8, 1751-64
19369195   Curated Info

63

Zhou J (2009) CST Curation Set: 6049; Year: 2009; Biosample/Treatment: cell line, Jurkat/TPA; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (F/Y/M)Xp[ST](L/I/M)
Curated Info

64

Zhou J (2009) CST Curation Set: 6050; Year: 2009; Biosample/Treatment: cell line, Jurkat/TPA; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (F/Y/M)Xp[ST](L/I/M)
Curated Info

65

Zhou J (2009) CST Curation Set: 6048; Year: 2009; Biosample/Treatment: cell line, Jurkat/untreated; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: (F/Y/M)Xp[ST](L/I/M)
Curated Info

66

McCoy CE, et al. (2008) Glucocorticoids inhibit IRF3 phosphorylation in response to Toll-like receptor-3 and -4 by targeting TBK1 activation. J Biol Chem 283, 14277-85
18356163   Curated Info

67

Kishore N, et al. (2002) IKK-i and TBK-1 are enzymatically distinct from the homologous enzyme IKK-2: comparative analysis of recombinant human IKK-i, TBK-1, and IKK-2. J Biol Chem 277, 13840-7
11839743   Curated Info