Thr187

Site Information
CDIQtHMtNNKGsAA SwissProt Entrez-Gene
Blast this site against: NCBI SwissProt PDB
Site Group ID: 454704

In vivo Characterization
Methods used to characterize site in vivo:	immunoassay ( 12 ) , immunoprecipitation ( 8 ) , mutation of modification site ( 8 , 15 , 22 ) , peptide sequencing ( 14 ) , phospho-antibody ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ) , western blotting ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 )
Disease tissue studied:	colorectal cancer ( 1 ) , colorectal carcinoma ( 1 ) , gastric cancer ( 8 ) , gastric carcinoma ( 8 ) , leukemia ( 5 , 10 ) , acute myelogenous leukemia ( 5 ) , T cell leukemia ( 10 ) , liver cancer ( 14 ) , lung cancer ( 3 ) , non-small cell lung cancer ( 3 ) , non-small cell lung adenocarcinoma ( 3 ) , lymphoma ( 17 ) , B cell lymphoma ( 17 ) , oropharyngeal cancer ( 4 ) , squamous cell carcinoma of the oropharynx ( 4 ) , ovarian cancer ( 19 )
Relevant cell line - cell type - tissue:	1.3E2 (B lymphocyte) ( 17 ) , 293 (epithelial) [IL-1RA (human)] ( 20 , 21 ) , 293 (epithelial) ( 2 , 11 , 17 , 22 ) , 3T3 (fibroblast) ( 3 ) , 70Z/3 ('B lymphocyte, precursor') ( 17 ) , A549 (pulmonary) ( 3 ) , AGS (gastric) ( 8 ) , CNE-2 (squamous) ( 4 ) , colon ( 1 ) , E.coli (bacterial) ( 15 ) , HCT116 (intestinal) ( 1 ) , HeLa (cervical) ( 13 , 16 , 17 , 22 ) , HepG2 (hepatic) ( 14 ) , HT-29 (intestinal) ( 1 ) , Jurkat (T lymphocyte) ( 10 ) , keratinocyte ( 7 ) , macrophage ( 5 ) , MEEC (epithelial) ( 6 ) , MEF (fibroblast) ( 17 ) , mesangial ( 18 ) , NCI-H1299 (pulmonary) ( 3 ) , NCM460 (epithelial) ( 12 ) , NPC (neural crest) ( 4 ) , OVCAR3 (ovarian) ( 19 ) , THP1 (myeloid) ( 5 )

Upstream Regulation
Regulatory protein:	AlphaK3 (human) ( 8 ) , ATM (human) ( 14 ) , Bcl-10 (human) ( 12 ) , CLASP1 (human) ( 14 ) , DUSP14 (human) ( 10 ) , ELF3 (human) ( 3 ) , GPX4 (human) ( 4 ) , HDAC6 (human) ( 1 ) , IKKG (human) ( 17 ) , IRF6 (human) ( 6 ) , P38A (human) ( 22 ) , PPP2CA (mouse) ( 18 ) , RALBP1 (human) ( 14 ) , TAB1 (human) ( 11 , 15 , 22 ) , TAB2 (human) ( 15 , 22 ) , TIFA (human) ( 8 ) , TRAF6 (human) ( 14 ) , UBE2N (human) ( 14 ) , XIAP (human) ( 17 ) , yopJ (bacteria) ( 21 )
Putative in vivo kinases:	TAK1 (human) ( 2 , 4 , 11 , 15 , 18 , 22 )
Kinases, in vitro:	TAK1 (human) ( 21 , 23 )
Putative upstream phosphatases:	PPP2CA (mouse) ( 18 )
Phosphatases, in vitro:	PPP2CA (human) ( 18 , 20 )
Treatments:	(5Z)-7-oxozeaenol ( 2 , 5 ) , ADP-Hep ( 2 ) , adriamycin ( 17 ) , anisomycin ( 16 ) , bacterial infection ( 7 ) , BAPTA-AM ( 14 ) , calyculin_A ( 20 ) , camptothecin ( 17 ) , carrageenan ( 12 ) , ciclosporin ( 20 ) , EGF ( 16 ) , ethanol ( 20 ) , etoposide ( 17 ) , gomisin_A ( 13 ) , gomisin_N ( 13 ) , high_cell_density ( 6 ) , high_glucose ( 3 ) , hypertonic_buffer ( 22 ) , IL-1a ( 20 , 21 ) , IL-1b ( 5 ) , ionizing_radiation ( 14 ) , ionomycin ( 10 ) , low_glucose ( 3 ) , monosodium urate ( 5 ) , NG25 ( 2 ) , okadaic_acid ( 18 , 20 ) , phorbol_ester ( 10 ) , SB203580 ( 13 , 16 , 21 , 22 ) , siRNA ( 4 , 16 , 18 , 22 ) , TAK1_inhibitor ( 9 , 13 ) , Takinib ( 1 ) , tautomycin ( 20 ) , TGF-beta ( 18 ) , TNF ( 8 , 13 , 16 , 17 , 19 , 22 ) , virus infection ( 4 )

Downstream Regulation
Effects of modification on TAK1:	enzymatic activity, induced ( 4 , 5 , 15 , 16 , 17 , 18 , 20 , 22 , 23 ) , intracellular localization ( 11 ) , phosphorylation ( 5 , 22 )
Effects of modification on biological processes:	carcinogenesis, induced ( 4 ) , cell growth, induced ( 4 ) , signaling pathway regulation ( 1 , 4 , 5 , 6 ) , transcription, altered ( 22 )

References
1	Xu G, et al. (2022) HDAC6-dependent deacetylation of TAK1 enhances sIL-6R release to promote macrophage M2 polarization in colon cancer. Cell Death Dis 13, 888 36270986 Curated Info
2	Snelling T, et al. (2022) Coordinated control of the ADP-heptose/ALPK1 signalling network by the E3 ligases TRAF6, TRAF2/c-IAP1 and LUBAC. Biochem J 36098982 Curated Info
3	Ma S, et al. (2022) Translation initiation factor eIF3a regulates glucose metabolism and cell proliferation via promoting small GTPase Rheb synthesis and AMPK activation. J Biol Chem, 102044 35595099 Curated Info
4	Yuan L, et al. (2022) EBV infection-induced GPX4 promotes chemoresistance and tumor progression in nasopharyngeal carcinoma. Cell Death Differ 35105963 Curated Info
5	Singh AK, et al. (2021) Suppression of monosodium urate crystal-induced inflammation by inhibiting TGF-β-activated kinase 1-dependent signaling: role of the ubiquitin proteasome system. Cell Mol Immunol 18, 162-170 31511642 Curated Info
6	Ke CY, Mei HH, Wong FH, Lo LJ (2019) IRF6 and TAK1 coordinately promote the activation of HIPK2 to stimulate apoptosis during palate fusion. Sci Signal 12 31387937 Curated Info
7	Ohshima J, et al. (2019) programs epithelial cells to resist ZEB2 induction by . Proc Natl Acad Sci U S A 116, 8544-8553 30971493 Curated Info
8	Zimmermann S, et al. (2017) ALPK1- and TIFA-Dependent Innate Immune Response Triggered by the Helicobacter pylori Type IV Secretion System. Cell Rep 20, 2384-2395 28877472 Curated Info
9	Huang HL, Chiang CH, Hung WC, Hou MF (2015) Targeting of TGF-β-activated protein kinase 1 inhibits chemokine (C-C motif) receptor 7 expression, tumor growth and metastasis in breast cancer. Oncotarget 6, 995-1007 25557171 Curated Info
10	Yang CY, et al. (2014) Dual-Specificity Phosphatase 14 (DUSP14/MKP6) Negatively Regulates TCR Signaling by Inhibiting TAB1 Activation. J Immunol 192, 1547-57 24403530 Curated Info
11	Pathak S, et al. (2012) O-GlcNAcylation of TAB1 modulates TAK1-mediated cytokine release. EMBO J 31, 1394-404 22307082 Curated Info
12	Bhattacharyya S, et al. (2011) Specific effects of BCL10 Serine mutations on phosphorylations in canonical and noncanonical pathways of NF-{kappa}B activation following carrageenan. Am J Physiol Gastrointest Liver Physiol 301, G475-86 21700900 Curated Info
13	Waiwut P, et al. (2011) Gomisin N enhances TNF-α-induced apoptosis via inhibition of the NF-κB and EGFR survival pathways. Mol Cell Biochem 350, 169-75 21188622 Curated Info
14	Hinz M, et al. (2010) A cytoplasmic ATM-TRAF6-cIAP1 module links nuclear DNA damage signaling to ubiquitin-mediated NF-κB activation. Mol Cell 40, 63-74 20932475 Curated Info
15	Scholz R, et al. (2010) Autoactivation of transforming growth factor beta-activated kinase 1 is a sequential bimolecular process. J Biol Chem 285, 25753-66 20538596 Curated Info
16	Shin MS, et al. (2009) Cross interference with TNF-alpha-induced TAK1 activation via EGFR-mediated p38 phosphorylation of TAK1-binding protein 1. Biochim Biophys Acta 1793, 1156-64 19393267 Curated Info
17	Jin HS, et al. (2009) cIAP1, cIAP2, and XIAP act cooperatively via nonredundant pathways to regulate genotoxic stress-induced nuclear factor-kappaB activation. Cancer Res 69, 1782-91 19223549 Curated Info
18	Kim SI, Kwak JH, Wang L, Choi ME (2008) Protein phosphatase 2A is a negative regulator of transforming growth factor-beta1-induced TAK1 activation in mesangial cells. J Biol Chem 283, 10753-63 18299321 Curated Info
19	Morrison BH, et al. (2007) Effect of inositol hexakisphosphate kinase 2 on transforming growth factor beta-activated kinase 1 and NF-kappaB activation. J Biol Chem 282, 15349-56 17379600 Curated Info
20	Kajino T, et al. (2006) Protein phosphatase 6 down-regulates TAK1 kinase activation in the IL-1 signaling pathway. J Biol Chem 281, 39891-6 17079228 Curated Info
21	Thiefes A, et al. (2006) The Yersinia enterocolitica effector YopP inhibits host cell signalling by inactivating the protein kinase TAK1 in the IL-1 signalling pathway. EMBO Rep 7, 838-44 16845370 Curated Info
22	Singhirunnusorn P, et al. (2005) Critical roles of threonine 187 phosphorylation in cellular stress-induced rapid and transient activation of transforming growth factor-beta-activated kinase 1 (TAK1) in a signaling complex containing TAK1-binding protein TAB1 and TAB2. J Biol Chem 280, 7359-68 15590691 Curated Info
23	Sakurai H, Miyoshi H, Mizukami J, Sugita T (2000) Phosphorylation-dependent activation of TAK1 mitogen-activated protein kinase kinase kinase by TAB1. FEBS Lett 474, 141-5 10838074 Curated Info