MAP3K7

Mitogen-activated protein kinase kinase kinase 7
PDB rendering based on 2eva.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2EVA​, 2YIY​, 4GS6​, 4L3P​, 4L52​, 4L53​, 4O91​
Identifiers
Symbols	MAP3K7 ; MEKK7; TAK1; TGF1a
External IDs	OMIM: 602614 MGI: 1346877 HomoloGene: 135715 ChEMBL: 5776 GeneCards: MAP3K7 Gene
EC number	2.7.11.25
Gene ontology Molecular function • magnesium ion binding • protein kinase activity • protein serine/threonine kinase activity • MAP kinase kinase activity • MAP kinase kinase kinase activity • protein binding • ATP binding • scaffold protein binding Cellular component • nucleus • nucleoplasm • Ada2/Gcn5/Ada3 transcription activator complex • cytoplasm • cytosol • plasma membrane • IkappaB kinase complex • endosome membrane • neuronal postsynaptic density Biological process • activation of MAPKK activity • activation of MAPK activity • angiogenesis • neural tube formation • stimulatory C-type lectin receptor signaling pathway • toll-like receptor signaling pathway • positive regulation of T cell cytokine production • MyD88-dependent toll-like receptor signaling pathway • MyD88-independent toll-like receptor signaling pathway • transcription, DNA-templated • apoptotic process • transforming growth factor beta receptor signaling pathway • I-kappaB kinase/NF-kappaB signaling • activation of NF-kappaB-inducing kinase activity • I-kappaB phosphorylation • JNK cascade • positive regulation of interleukin-2 production • toll-like receptor 2 signaling pathway • toll-like receptor 3 signaling pathway • toll-like receptor 4 signaling pathway • toll-like receptor 5 signaling pathway • toll-like receptor 9 signaling pathway • toll-like receptor 10 signaling pathway • TRIF-dependent toll-like receptor signaling pathway • nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway • Fc-epsilon receptor signaling pathway • toll-like receptor TLR1:TLR2 signaling pathway • toll-like receptor TLR6:TLR2 signaling pathway • positive regulation of I-kappaB kinase/NF-kappaB signaling • positive regulation of JUN kinase activity • histone H3 acetylation • innate immune response • T cell receptor signaling pathway • positive regulation of T cell activation • positive regulation of NF-kappaB transcription factor activity • stress-activated MAPK cascade • nucleotide-binding oligomerization domain containing signaling pathway • negative regulation of ripoptosome assembly involved in necroptotic process • regulation of reactive oxygen species metabolic process • negative regulation of apoptotic signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6885	26409
Ensembl	ENSG00000135341	ENSMUSG00000028284
UniProt	O43318	Q62073
RefSeq (mRNA)	NM_003188	NM_009316
RefSeq (protein)	NP_003179	NP_033342
Location (UCSC)	Chr 6: 90.51 – 90.59 Mb	Chr 4: 31.96 – 32.02 Mb
PubMed search

Mitogen-activated protein kinase kinase kinase 7 is an enzyme that in humans is encoded by the MAP3K7 gene.^[1]

Function

The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase mediates the signaling transduction induced by TGF beta and morphogenetic protein (BMP), and controls a variety of cell functions including transcription regulation and apoptosis. In response to IL-1, this protein forms a kinase complex including TRAF6, MAP3K7P1/TAB1 and MAP3K7P2/TAB2; this complex is required for the activation of nuclear factor kappa B. This kinase can also activate MAPK8/JNK, MAP2K4/MKK4, and thus plays a role in the cell response to environmental stresses. Four alternatively spliced transcript variants encoding distinct isoforms have been reported.^[2]

Interactions

MAP3K7 has been shown to interact with:

• ASK1,^[3]
• CHUK,^[4][5]
• MAP2K6,^[4][6][7][8]
• MAP3K7IP1,^{[4][6][9][10]}
• MAP3K7IP2,^[9][11][12]
• MAP3K7IP3,^[7][9]
• Mothers against decapentaplegic homolog 6,^[13][14]
• PPM1B,^[15] and
• TRAF6.^{[3][4][7][11][12][16][17]}

References

1. Kondo M, Osada H, Uchida K, Yanagisawa K, Masuda A, Takagi K, Takahashi T, Takahashi T (February 1998). "Molecular cloning of human TAK1 and its mutational analysis in human lung cancer". Int J Cancer 75 (4): 559–63. doi:10.1002/(SICI)1097-0215(19980209)75:4<559::AID-IJC11>3.0.CO;2-4. PMID 9466656.
2. "Entrez Gene: MAP3K7 mitogen-activated protein kinase kinase kinase 7".
3. Mochida Y, Takeda K, Saitoh M, Nishitoh H, Amagasa T, Ninomiya-Tsuji J, Matsumoto K, Ichijo H (October 2000). "ASK1 inhibits interleukin-1-induced NF-kappa B activity through disruption of TRAF6-TAK1 interaction". J. Biol. Chem. 275 (42): 32747–52. doi:10.1074/jbc.M003042200. PMID 10921914.
4. Ninomiya-Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K (March 1999). "The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway". Nature 398 (6724): 252–6. doi:10.1038/18465. PMID 10094049.
5. Sakurai H, Miyoshi H, Toriumi W, Sugita T (April 1999). "Functional interactions of transforming growth factor beta-activated kinase 1 with IkappaB kinases to stimulate NF-kappaB activation". J. Biol. Chem. 274 (15): 10641–8. doi:10.1074/jbc.274.15.10641. PMID 10187861.
6. Sakurai H, Miyoshi H, Mizukami J, Sugita T (June 2000). "Phosphorylation-dependent activation of TAK1 mitogen-activated protein kinase kinase kinase by TAB1". FEBS Lett. 474 (2-3): 141–5. doi:10.1016/s0014-5793(00)01588-x. PMID 10838074.
7. Ishitani T, Takaesu G, Ninomiya-Tsuji J, Shibuya H, Gaynor RB, Matsumoto K (December 2003). "Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling". EMBO J. 22 (23): 6277–88. doi:10.1093/emboj/cdg605. PMC 291846. PMID 14633987.
8. Wang C, Deng L, Hong M, Akkaraju GR, Inoue J, Chen ZJ (July 2001). "TAK1 is a ubiquitin-dependent kinase of MKK and IKK". Nature 412 (6844): 346–51. doi:10.1038/35085597. PMID 11460167.
9. Cheung PC, Nebreda AR, Cohen P (February 2004). "TAB3, a new binding partner of the protein kinase TAK1". Biochem. J. 378 (Pt 1): 27–34. doi:10.1042/BJ20031794. PMC 1223947. PMID 14670075.
10. Channavajhala PL, Wu L, Cuozzo JW, Hall JP, Liu W, Lin LL, Zhang Y (November 2003). "Identification of a novel human kinase supporter of Ras (hKSR-2) that functions as a negative regulator of Cot (Tpl2) signaling". J. Biol. Chem. 278 (47): 47089–97. doi:10.1074/jbc.M306002200. PMID 12975377.
11. Takaesu G, Kishida S, Hiyama A, Yamaguchi K, Shibuya H, Irie K, Ninomiya-Tsuji J, Matsumoto K (April 2000). "TAB2, a novel adaptor protein, mediates activation of TAK1 MAPKKK by linking TAK1 to TRAF6 in the IL-1 signal transduction pathway". Mol. Cell 5 (4): 649–58. doi:10.1016/s1097-2765(00)80244-0. PMID 10882101.
12. Takaesu G, Ninomiya-Tsuji J, Kishida S, Li X, Stark GR, Matsumoto K (April 2001). "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. 21 (7): 2475–84. doi:10.1128/MCB.21.7.2475-2484.2001. PMC 86880. PMID 11259596.
13. Kimura N, Matsuo R, Shibuya H, Nakashima K, Taga T (June 2000). "BMP2-induced apoptosis is mediated by activation of the TAK1-p38 kinase pathway that is negatively regulated by Smad6". J. Biol. Chem. 275 (23): 17647–52. doi:10.1074/jbc.M908622199. PMID 10748100.
14. Yanagisawa M, Nakashima K, Takeda K, Ochiai W, Takizawa T, Ueno M, Takizawa M, Shibuya H, Taga T (December 2001). "Inhibition of BMP2-induced, TAK1 kinase-mediated neurite outgrowth by Smad6 and Smad7". Genes Cells 6 (12): 1091–9. doi:10.1046/j.1365-2443.2001.00483.x. PMID 11737269.
15. Hanada M, Ninomiya-Tsuji J, Komaki K, Ohnishi M, Katsura K, Kanamaru R, Matsumoto K, Tamura S (February 2001). "Regulation of the TAK1 signaling pathway by protein phosphatase 2C". J. Biol. Chem. 276 (8): 5753–9. doi:10.1074/jbc.M007773200. PMID 11104763.
16. Walsh MC, Kim GK, Maurizio PL, Molnar EE, Choi Y. Unutmaz D, ed. "TRAF6 autoubiquitination-independent activation of the NFkappaB and MAPK pathways in response to IL-1 and RANKL". PLoS ONE 3 (12): e4064. doi:10.1371/journal.pone.0004064. PMC 2603309. PMID 19112497.
17. Sorrentino A, Thakur N, Grimsby S, Marcusson A, von Bulow V, Schuster N, Zhang S, Heldin CH, Landström M (October 2008). "The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner". Nat. Cell Biol. 10 (10): 1199–207. doi:10.1038/ncb1780. PMID 18758450.

Further reading

• DuBridge RB, Tang P, Hsia HC, Leong PM, Miller JH, Calos MP (1987). "Analysis of mutation in human cells by using an Epstein-Barr virus shuttle system". Mol. Cell. Biol. 7 (1): 379–87. doi:10.1128/mcb.7.1.379. PMC 365079. PMID 3031469.
• Hirose T, Fujimoto W, Tamaai T, Kim KH, Matsuura H, Jetten AM (1995). "TAK1: molecular cloning and characterization of a new member of the nuclear receptor superfamily". Mol. Endocrinol. 8 (12): 1667–80. doi:10.1210/me.8.12.1667. PMID 7708055.
• Yamaguchi K, Shirakabe K, Shibuya H, Irie K, Oishi I, Ueno N, Taniguchi T, Nishida E, Matsumoto K (1996). "Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction". Science 270 (5244): 2008–11. doi:10.1126/science.270.5244.2008. PMID 8533096.
• Shibuya H, Yamaguchi K, Shirakabe K, Tonegawa A, Gotoh Y, Ueno N, Irie K, Nishida E, Matsumoto K (1996). "TAB1: an activator of the TAK1 MAPKKK in TGF-beta signal transduction". Science 272 (5265): 1179–82. doi:10.1126/science.272.5265.1179. PMID 8638164.
• Wang W, Zhou G, Hu MC, Yao Z, Tan TH (1997). "Activation of the hematopoietic progenitor kinase-1 (HPK1)-dependent, stress-activated c-Jun N-terminal kinase (JNK) pathway by transforming growth factor beta (TGF-beta)-activated kinase (TAK1), a kinase mediator of TGF beta signal transduction". J. Biol. Chem. 272 (36): 22771–5. doi:10.1074/jbc.272.36.22771. PMID 9278437.
• Liu X, Sun Y, Constantinescu SN, Karam E, Weinberg RA, Lodish HF (1997). "Transforming growth factor β-induced phosphorylation of Smad3 is required for growth inhibition and transcriptional induction in epithelial cells". Proc. Natl. Acad. Sci. U.S.A. 94 (20): 10669–74. doi:10.1073/pnas.94.20.10669. PMC 23442. PMID 9380693.
• Sakurai H, Shigemori N, Hasegawa K, Sugita T (1998). "TGF-beta-activated kinase 1 stimulates NF-kappa B activation by an NF-kappa B-inducing kinase-independent mechanism". Biochem. Biophys. Res. Commun. 243 (2): 545–9. doi:10.1006/bbrc.1998.8124. PMID 9480845.
• Yan ZH, Karam WG, Staudinger JL, Medvedev A, Ghanayem BI, Jetten AM (1998). "Regulation of peroxisome proliferator-activated receptor alpha-induced transactivation by the nuclear orphan receptor TAK1/TR4". J. Biol. Chem. 273 (18): 10948–57. doi:10.1074/jbc.273.18.10948. PMID 9556573.
• Lee FS, Peters RT, Dang LC, Maniatis T (1998). "MEKK1 activates both IκB kinase α and IκB kinase β". Proc. Natl. Acad. Sci. U.S.A. 95 (16): 9319–24. doi:10.1073/pnas.95.16.9319. PMC 21336. PMID 9689078.
• Yamaguchi K, Nagai S, Ninomiya-Tsuji J, Nishita M, Tamai K, Irie K, Ueno N, Nishida E, Shibuya H, Matsumoto K (1999). "XIAP, a cellular member of the inhibitor of apoptosis protein family, links the receptors to TAB1-TAK1 in the BMP signaling pathway". EMBO J. 18 (1): 179–87. doi:10.1093/emboj/18.1.179. PMC 1171113. PMID 9878061.
• Lallena MJ, Diaz-Meco MT, Bren G, Payá CV, Moscat J (1999). "Activation of IκB Kinase β by Protein Kinase C Isoforms". Mol. Cell. Biol. 19 (3): 2180–8. PMC 84010. PMID 10022904.
• Ninomiya-Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K (1999). "The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway". Nature 398 (6724): 252–6. doi:10.1038/18465. PMID 10094049.
• Sakurai H, Miyoshi H, Toriumi W, Sugita T (1999). "Functional interactions of transforming growth factor beta-activated kinase 1 with IkappaB kinases to stimulate NF-kappaB activation". J. Biol. Chem. 274 (15): 10641–8. doi:10.1074/jbc.274.15.10641. PMID 10187861.
• Delhase M, Hayakawa M, Chen Y, Karin M (1999). "Positive and negative regulation of IkappaB kinase activity through IKKbeta subunit phosphorylation". Science 284 (5412): 309–13. doi:10.1126/science.284.5412.309. PMID 10195894.
• Zhou G, Lee SC, Yao Z, Tan TH (1999). "Hematopoietic progenitor kinase 1 is a component of transforming growth factor beta-induced c-Jun N-terminal kinase signaling cascade". J. Biol. Chem. 274 (19): 13133–8. doi:10.1074/jbc.274.19.13133. PMID 10224067.
• Kimura N, Matsuo R, Shibuya H, Nakashima K, Taga T (2000). "BMP2-induced apoptosis is mediated by activation of the TAK1-p38 kinase pathway that is negatively regulated by Smad6". J. Biol. Chem. 275 (23): 17647–52. doi:10.1074/jbc.M908622199. PMID 10748100.
• Yamamoto Y, Yin MJ, Gaynor RB (2000). "IκB Kinase α (IKKα) Regulation of IKKβ Kinase Activity". Mol. Cell. Biol. 20 (10): 3655–66. doi:10.1128/MCB.20.10.3655-3666.2000. PMC 85658. PMID 10779355.
• Hofer-Warbinek R, Schmid JA, Stehlik C, Binder BR, Lipp J, de Martin R (2000). "Activation of NF-kappa B by XIAP, the X chromosome-linked inhibitor of apoptosis, in endothelial cells involves TAK1". J. Biol. Chem. 275 (29): 22064–8. doi:10.1074/jbc.M910346199. PMID 10807933.
• 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 (2–3): 141–5. doi:10.1016/S0014-5793(00)01588-X. PMID 10838074.