Target Interacting Protein Information

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Target General Information
Target Interacting Proteins
References
Target General Information  Top
Target ID T04361 Target Info
Target Name TGF-beta-activated kinase 1 (MAP3K7)
Synonyms Transforming growth factor-beta-activated kinase 1; TAK1; Mitogen-activated protein kinase kinase kinase 7
Target Type Literature-reported Target
Gene Name MAP3K7
Biochemical Class Kinase
UniProt ID
M3K7_HUMAN 
Target Interacting Proteins  Top
Acyltransferases [+] 1 Acyltransferases +
Interacting Target Name TNF receptor-associated factor 6 (TRAF6) Literature-reported Target Interacting Protein Info
UniProt ID
TRAF6_HUMAN 
Synonyms RNF85; RING-type E3 ubiquitin transferase TRAF6; RING finger protein 85; Interleukin-1 signal transducer; E3 ubiquitin-protein ligase TRAF6
Evidence Score (E-score) 12 Experimental Evidences +
1 Affinity Capture-Western [1]
2 Affinity Capture-Western [2]
3 Affinity Capture-Western [3]
4 Affinity Capture-Western [4]
5 Affinity Capture-Western [5]
6 Affinity Capture-Western [6]
7 Affinity Capture-Western [7]
8 Affinity Capture-Western [8]
9 Affinity Capture-Western [9]
10 Affinity Capture-Western [10]
11 Affinity Capture-Western [11]
12 Yeast two hybrid [12]
Adapter proteins [+] 2 Adapter proteins +
Interacting Protein Name TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 (TAB2) Interacting Protein Interacting Protein Info
UniProt ID
TAB2_HUMAN 
Synonyms CHTD2; MAP3K7IP2; TAB.2
Evidence Score (E-score) 19 Experimental Evidences +
1 Affinity Capture-Luminescence [13]
2 Affinity Capture-MS [14]
3 Affinity Capture-MS [7]
4 Affinity Capture-Western [15]
5 Affinity Capture-Western [2]
6 Affinity Capture-Western [3]
7 Affinity Capture-Western [16]
8 Affinity Capture-Western [17]
9 Affinity Capture-Western [6]
10 Affinity Capture-Western [18]
11 Affinity Capture-Western [19]
12 Affinity Capture-Western [20]
13 Affinity Capture-Western [21]
14 Affinity Capture-Western [22]
15 Affinity Capture-Western [23]
16 Affinity Capture-Western [24]
17 Affinity Capture-Western [25]
18 Yeast two hybrid [1]
19 Yeast two hybrid [26]
Interacting Protein Name TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 (TAB3) Interacting Protein Interacting Protein Info
UniProt ID
TAB3_HUMAN 
Synonyms MAP3K7IP3; NAP1
Evidence Score (E-score) 6 Experimental Evidences +
1 Affinity Capture-MS [14]
2 Affinity Capture-MS [7]
3 Affinity Capture-Western [6]
4 Affinity Capture-Western [19]
5 Affinity Capture-Western [21]
6 Affinity Capture-Western [24]
Kinases [+] 7 Kinases +
Interacting Protein Name Dual specificity mitogen-activated protein kinase kinase 6 (MAP2K6) Interacting Protein Interacting Protein Info
UniProt ID
MP2K6_HUMAN 
Synonyms MAPKK6; MEK6; MKK6; PRKMK6; SAPKK.3; SAPKK3
Evidence Score (E-score) 20 Experimental Evidences +
1 Affinity Capture-Western [27]
2 Biochemical Activity [28]
3 Biochemical Activity [29]
4 Biochemical Activity [30]
5 Biochemical Activity [31]
6 Biochemical Activity [32]
7 Biochemical Activity [33]
8 Biochemical Activity [2]
9 Biochemical Activity [3]
10 Biochemical Activity [34]
11 Biochemical Activity [35]
12 Biochemical Activity [6]
13 Biochemical Activity [36]
14 Biochemical Activity [37]
15 Biochemical Activity [38]
16 Biochemical Activity [39]
17 Biochemical Activity [40]
18 Biochemical Activity [41]
19 Biochemical Activity [42]
20 Biochemical Activity [43]
Interacting Target Name Inhibitor of nuclear factor kappa-B kinase beta (IKKB) Clinical trial Target Interacting Protein Info
UniProt ID
IKKB_HUMAN 
Synonyms Nuclear factor NF-kappa-B inhibitor kinase beta; NFKBIKB; Inhibitory kappa B kinase b; Inhibitor of nuclear factor kappa-B kinase subunit beta; IKK-beta; IKKbeta; IKK-B; IKK-2; IKK2; IkBKB; I-kappa-B-kinase beta; IkappaB kinase beta; I-kappa-B kinase 2; IkappaB kinase 2
Evidence Score (E-score) 11 Experimental Evidences +
1 Affinity Capture-Western [44]
2 Affinity Capture-Western [32]
3 Affinity Capture-Western [45]
4 Affinity Capture-Western [35]
5 Affinity Capture-Western [46]
6 Affinity Capture-Western [47]
7 Affinity Capture-Western [48]
8 Biochemical Activity [29]
9 Biochemical Activity [32]
10 Biochemical Activity [49]
11 Biochemical Activity [50]
Interacting Target Name Inhibitor of nuclear factor kappa-B kinase alpha (IKKA) Literature-reported Target Interacting Protein Info
UniProt ID
IKKA_HUMAN 
Synonyms Transcription factor 16; TCF-16; TCF16; Nuclear factor NF-kappa-B inhibitor kinase alpha; Nuclear factor NFkappaB inhibitor kinase alpha; NFKBIKA; Inhibitory kappa B kinasea; Inhibitor of nuclear factor kappa-B kinase subunit alpha; IKK-alpha; IKK-A; IKK1; IkBKA; I-kappa-B kinase alpha; I-kappa-B kinase 1; IkappaB kinase; I kappa-B kinase alpha; Conserved helix-loop-helix ubiquitous kinase
Evidence Score (E-score) 4 Experimental Evidences +
1 Affinity Capture-Western [51]
2 Affinity Capture-Western [52]
3 Affinity Capture-Western [17]
4 Co-localization [53]
Interacting Target Name MAPK/ERK kinase kinase 3 (MAP3K3) Literature-reported Target Interacting Protein Info
UniProt ID
M3K3_HUMAN 
Synonyms Mitogen-activated protein kinase kinase kinase 3; MEKK3; MEKK 3; MEK kinase 3; MAPKKK3
Evidence Score (E-score) 3 Experimental Evidences +
1 Affinity Capture-Western [5]
2 Affinity Capture-Western [54]
3 Yeast two hybrid [54]
Interacting Target Name Apoptosis signal-regulating kinase 1 (MAP3K5) Clinical trial Target Interacting Protein Info
UniProt ID
M3K5_HUMAN 
Synonyms Mitogen-activated protein kinase kinase kinase 5; MEKK5; MEKK 5; MEK kinase 5; MAPKKK5; MAPK/ERK kinase kinase 5; ASK-1; ASK1
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-Western [4]
2 Yeast two hybrid [4]
Interacting Target Name Receptor-interacting protein 1 (RIPK1) Clinical trial Target Interacting Protein Info
UniProt ID
RIPK1_HUMAN 
Synonyms RIP-1; RIP1; RIP; Receptor-interacting serine/threonine-protein kinase 1; Cell death protein RIP
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-Western [55]
2 Co-fractionation [56]
Interacting Protein Name AMPK subunit alpha-1 (PRKAA1) Interacting Protein Interacting Protein Info
UniProt ID
AAPK1_HUMAN 
Synonyms AMPK; AMPKa1
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-Western [57]
2 Biochemical Activity [18]
Other proteins [+] 3 Other proteins +
Interacting Protein Name TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 (TAB1) Interacting Protein Interacting Protein Info
UniProt ID
TAB1_HUMAN 
Synonyms 3.Tab1; MAP3K7IP1
Evidence Score (E-score) 20 Experimental Evidences +
1 Affinity Capture-MS [14]
2 Affinity Capture-MS [7]
3 Affinity Capture-Western [26]
4 Affinity Capture-Western [30]
5 Affinity Capture-Western [33]
6 Affinity Capture-Western [3]
7 Affinity Capture-Western [16]
8 Affinity Capture-Western [17]
9 Affinity Capture-Western [50]
10 Affinity Capture-Western [36]
11 Affinity Capture-Western [41]
12 Affinity Capture-Western [18]
13 Affinity Capture-Western [19]
14 Affinity Capture-Western [20]
15 Affinity Capture-Western [13]
16 Affinity Capture-Western [58]
17 Affinity Capture-Western [21]
18 Affinity Capture-Western [22]
19 Affinity Capture-Western [23]
20 Affinity Capture-Western [24]
Interacting Target Name Tumor necrosis factor (TNF) Successful Target Interacting Protein Info
UniProt ID
TNFA_HUMAN 
Synonyms Tumour necrosis factor alpha; Tumour necrosis factor; Tumor necrosis factor ligand superfamily member 2; Tumor necrosis factor; TNFSF2; TNF-alpha; TNFalpha; TNF-a; TNFA; TNF alpha; Cachectin
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-MS [59]
2 Affinity Capture-Western [60]
Interacting Target Name Pattern recognition receptor NOD2 (NOD2) Clinical trial Target Interacting Protein Info
UniProt ID
NOD2_HUMAN 
Synonyms Nucleotide-binding oligomerization domain-containing protein 2; Nucleotidebinding oligomerization domaincontaining protein 2; Inflammatory bowel disease protein 1; IBD1; Caspase recruitment domain-containing protein 15; Caspase recruitment domaincontaining protein 15; CARD15
Evidence Score (E-score) 2 Experimental Evidences +
1 Affinity Capture-Western [61]
2 Reconstituted Complex [62]
References  Top
REF 1 Interleukin-1 (IL-1) receptor-associated kinase leads to activation of TAK1 by inducing TAB2 translocation in the IL-1 signaling pathway. Mol Cell Biol. 2001 Apr;21(7):2475-84.
REF 2 Poly(I-C)-induced Toll-like receptor 3 (TLR3)-mediated activation of NFkappa B and MAP kinase is through an interleukin-1 receptor-associated kinase (IRAK)-independent pathway employing the signaling components TLR3-TRAF6-TAK1-TAB2-PKR . J Biol Chem. 2003 May 9;278(19):16713-9.
REF 3 Interleukin-1 (IL-1) receptor-associated kinase-dependent IL-1-induced signaling complexes phosphorylate TAK1 and TAB2 at the plasma membrane and activate TAK1 in the cytosol. Mol Cell Biol. 2002 Oct;22(20):7158-67.
REF 4 ASK1 inhibits interleukin-1-induced NF-kappa B activity through disruption of TRAF6-TAK1 interaction. J Biol Chem. 2000 Oct 20;275(42):32747-52.
REF 5 Two mechanistically and temporally distinct NF-kappaB activation pathways in IL-1 signaling. Sci Signal. 2009 Oct 20;2(93):ra66.
REF 6 Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling. EMBO J. 2003 Dec 1;22(23):6277-88.
REF 7 An F-box protein, FBXW5, negatively regulates TAK1 MAP3K in the IL-1beta signaling pathway. Biochem Biophys Res Commun. 2009 Apr 10;381(3):412-7.
REF 8 -TrCP-mediated IRAK1 degradation releases TAK1-TRAF6 from the membrane to the cytosol for TAK1-dependent NF-B activation. Mol Cell Biol. 2012 Oct;32(19):3990-4000.
REF 9 PINK1 stimulates interleukin-1-mediated inflammatory signaling via the positive regulation of TRAF6 and TAK1. Cell Mol Life Sci. 2012 Oct;69(19):3301-15.
REF 10 MyD88 and TNF receptor-associated factor 6 are critical signal transducers in Helicobacter pylori-infected human epithelial cells. J Immunol. 2006 Mar 15;176(6):3796-803.
REF 11 The ubiquitin E3 ligase TRAF6 exacerbates pathological cardiac hypertrophy via TAK1-dependent signalling. Nat Commun. 2016 Jun 1;7:11267.
REF 12 WDR34 is a novel TAK1-associated suppressor of the IL-1R/TLR3/TLR4-induced NF-kappaB activation pathway. Cell Mol Life Sci. 2009 Aug;66(15):2573-84.
REF 13 Transforming growth factor-beta (TGF-beta1) activates TAK1 via TAB1-mediated autophosphorylation, independent of TGF-beta receptor kinase activity in mesangial cells. J Biol Chem. 2009 Aug 14;284(33):22285-96.
REF 14 Mapping a dynamic innate immunity protein interaction network regulating type I interferon production. Immunity. 2011 Sep 23;35(3):426-40.
REF 15 Transforming growth factor beta-activated kinase 1 (TAK1) kinase adaptor, TAK1-binding protein 2, plays dual roles in TAK1 signaling by recruiting both an activator and an inhibitor of TAK1 kinase in tumor necrosis factor signaling pathway. J Biol Chem. 2010 Jan 22;285(4):2333-9.
REF 16 Reciprocal inhibition between the transforming growth factor--activated kinase 1 (TAK1) and apoptosis signal-regulating kinase 1 (ASK1) mitogen-activated protein kinase kinase kinases and its suppression by TAK1-binding protein 2 (TAB2), an adapter protein for TAK1. J Biol Chem. 2012 Jan 27;287(5):3381-91.
REF 17 Constitutive association of TGF-beta-activated kinase 1 with the IkappaB kinase complex in the nucleus and cytoplasm of human neutrophils and its impact on downstream processes. J Immunol. 2010 Apr 1;184(7):3897-906.
REF 18 Autoactivation of transforming growth factor beta-activated kinase 1 is a sequential bimolecular process. J Biol Chem. 2010 Aug 13;285(33):25753-66.
REF 19 TAB3, a new binding partner of the protein kinase TAK1. Biochem J. 2004 Feb 15;378(Pt 1):27-34.
REF 20 HSP90 is required for TAK1 stability but not for its activation in the pro-inflammatory signaling pathway. FEBS Lett. 2008 Dec 10;582(29):4023-31.
REF 21 HIV-1 Vpr stimulates NF-B and AP-1 signaling by activating TAK1. Retrovirology. 2014 Jun 9;11:45.
REF 22 Phosphoinositide-dependent kinase-1 inhibits TRAF6 ubiquitination by interrupting the formation of TAK1-TAB2 complex in TLR4 signaling. Cell Signal. 2015 Dec;27(12):2524-33.
REF 23 Cereblon negatively regulates TLR4 signaling through the attenuation of ubiquitination of TRAF6. Cell Death Dis. 2016 Jul 28;7(7):e2313.
REF 24 Interleukin-1 and TRAF6-dependent activation of TAK1 in the absence of TAB2 and TAB3. Biochem J. 2017 Jun 26;474(13):2235-2248.
REF 25 Salt-inducible kinases 1 and 3 negatively regulate Toll-like receptor 4-mediated signal. Mol Endocrinol. 2013 Nov;27(11):1958-68.
REF 26 TAB1: an activator of the TAK1 MAPKKK in TGF-beta signal transduction. Science. 1996 May 24;272(5265):1179-82.
REF 27 The scaffold protein RACK1 mediates the RANKL-dependent activation of p38 MAPK in osteoclast precursors. Sci Signal. 2015 Jun 2;8(379):ra54.
REF 28 TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature. 2001 Jul 19;412(6844):346-51.
REF 29 ATM- and NEMO-dependent ELKS ubiquitination coordinates TAK1-mediated IKK activation in response to genotoxic stress. Mol Cell. 2010 Oct 8;40(1):75-86.
REF 30 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. 2005 Feb 25;280(8):7359-68.
REF 31 Smad7 binds to the adaptors TAB2 and TAB3 to block recruitment of the kinase TAK1 to the adaptor TRAF2. Nat Immunol. 2007 May;8(5):504-13.
REF 32 Phosphorylation and ubiquitination of the IkappaB kinase complex by two distinct signaling pathways. EMBO J. 2007 Apr 4;26(7):1794-805.
REF 33 A resorcylic acid lactone, 5Z-7-oxozeaenol, prevents inflammation by inhibiting the catalytic activity of TAK1 MAPK kinase kinase. J Biol Chem. 2003 May 16;278(20):18485-90.
REF 34 The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway. Nature. 1999 Mar 18;398(6724):252-6.
REF 35 Retroviral oncoprotein Tax deregulates NF-kappaB by activating Tak1 and mediating the physical association of Tak1-IKK. EMBO Rep. 2007 May;8(5):510-5.
REF 36 Phosphorylation-dependent activation of TAK1 mitogen-activated protein kinase kinase kinase by TAB1. FEBS Lett. 2000 Jun 2;474(2-3):141-5.
REF 37 Direct activation of protein kinases by unanchored polyubiquitin chains. Nature. 2009 Sep 3;461(7260):114-9.
REF 38 STAT3 regulates Nemo-like kinase by mediating its interaction with IL-6-stimulated TGFbeta-activated kinase 1 for STAT3 Ser-727 phosphorylation. Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4524-9.
REF 39 Osmotic stress activates the TAK1-JNK pathway while blocking TAK1-mediated NF-kappaB activation: TAO2 regulates TAK1 pathways. J Biol Chem. 2006 Sep 29;281(39):28802-10.
REF 40 Protein phosphatase 6 down-regulates TAK1 kinase activation in the IL-1 signaling pathway. J Biol Chem. 2006 Dec 29;281(52):39891-6.
REF 41 TAK1 mitogen-activated protein kinase kinase kinase is activated by autophosphorylation within its activation loop. J Biol Chem. 2000 Mar 10;275(10):7359-64.
REF 42 Helicobacter pylori activates NF-B by inducing Ubc13-mediated ubiquitination of lysine 158 of TAK1. J Cell Biochem. 2013 Oct;114(10):2284-92.
REF 43 USP18 inhibits NF-B and NFAT activation during Th17 differentiation by deubiquitinating the TAK1-TAB1 complex. J Exp Med. 2013 Jul 29;210(8):1575-90.
REF 44 Altered TAB1:I kappaB kinase interaction promotes transforming growth factor beta-mediated nuclear factor-kappaB activation during breast cancer progression. Cancer Res. 2008 Mar 1;68(5):1462-70.
REF 45 USP4 targets TAK1 to downregulate TNF-induced NF-B activation. Cell Death Differ. 2011 Oct;18(10):1547-60.
REF 46 LATS2 inhibits the activity of NF- B signaling by disrupting the interaction between TAK1 and IKK. Tumour Biol. 2015 Sep;36(10):7873-9.
REF 47 IFIT5 positively regulates NF-B signaling through synergizing the recruitment of IB kinase (IKK) to TGF--activated kinase 1 (TAK1). Cell Signal. 2015 Dec;27(12):2343-54.
REF 48 pVHL mediates K63-linked ubiquitination of IKK, leading to IKK inactivation. Cancer Lett. 2016 Dec 1;383(1):1-8.
REF 49 USP10 inhibits genotoxic NF-B activation by MCPIP1-facilitated deubiquitination of NEMO. EMBO J. 2013 Dec 11;32(24):3206-19.
REF 50 TAB4 stimulates TAK1-TAB1 phosphorylation and binds polyubiquitin to direct signaling to NF-kappaB. J Biol Chem. 2008 Jul 11;283(28):19245-54.
REF 51 Functional interactions of transforming growth factor beta-activated kinase 1 with IkappaB kinases to stimulate NF-kappaB activation. J Biol Chem. 1999 Apr 9;274(15):10641-8.
REF 52 Molecular determinants of NF-kappaB-inducing kinase action. Mol Cell Biol. 1998 Oct;18(10):5899-907.
REF 53 Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network. J Proteome Res. 2014 Dec 5;13(12):5339-46.
REF 54 TAK1 is recruited to the tumor necrosis factor-alpha (TNF-alpha) receptor 1 complex in a receptor-interacting protein (RIP)-dependent manner and cooperates with MEKK3 leading to NF-kappaB activation. J Biol Chem. 2005 Dec 30;280(52):43056-63.
REF 55 Ubiquitination of RIP is required for tumor necrosis factor alpha-induced NF-kappaB activation. J Biol Chem. 2006 May 12;281(19):13636-43.
REF 56 A cytosolic ATM/NEMO/RIP1 complex recruits TAK1 to mediate the NF-kappaB and p38 mitogen-activated protein kinase (MAPK)/MAPK-activated protein 2 responses to DNA damage. Mol Cell Biol. 2011 Jul;31(14):2774-86.
REF 57 AICAR induces cyclooxygenase-2 expression through AMP-activated protein kinase-transforming growth factor-beta-activated kinase 1-p38 mitogen-activated protein kinase signaling pathway. Biochem Pharmacol. 2010 Oct 15;80(8):1210-20.
REF 58 TAB1beta (transforming growth factor-beta-activated protein kinase 1-binding protein 1beta ), a novel splicing variant of TAB1 that interacts with p38alpha but not TAK1. J Biol Chem. 2003 Jan 24;278(4):2286-93.
REF 59 SPATA2 links CYLD to the TNF- receptor signaling complex and modulates the receptor signaling outcomes. EMBO J. 2016 Sep 1;35(17):1868-84.
REF 60 Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO. Mol Cell. 2006 Apr 21;22(2):245-57.
REF 61 TAK1 is a central mediator of NOD2 signaling in epidermal cells. J Biol Chem. 2008 Jan 4;283(1):137-44.
REF 62 Reciprocal cross-talk between Nod2 and TAK1 signaling pathways. J Biol Chem. 2004 Jun 11;279(24):25876-82.

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