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Mitogen-activated protein kinase kinase kinase 7
Protein MAP3K7 PDB 2eva.png
PDB rendering based on 2eva.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols MAP3K7 ; MEKK7; TAK1; TGF1a
External IDs OMIM602614 MGI1346877 HomoloGene37743 ChEMBL: 5776 GeneCards: MAP3K7 Gene
EC number
RNA expression pattern
PBB GE MAP3K7 206854 s at tn.png
PBB GE MAP3K7 206853 s at tn.png
PBB GE MAP3K7 211536 x at tn.png
More reference expression data
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:
91.22 – 91.3 Mb
Chr 4:
31.96 – 32.02 Mb
PubMed search [1] [2]

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

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]


MAP3K7 has been shown to interact with Mothers against decapentaplegic homolog 6,[3][4] MAP3K7IP2,[5][6][7] MAP3K7IP1,[5][8][9][10] MAP3K7IP3,[5][11] ASK1,[12] PPM1B,[13] TRAF6,[6][7][9][11][12][14][15] MAP2K6[9][10][11][16] and CHUK.[9][17]


  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. ^ 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. (United States) 275 (23): 17647–52. doi:10.1074/jbc.M908622199. ISSN 0021-9258. PMID 10748100. 
  4. ^ 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 (England) 6 (12): 1091–9. doi:10.1046/j.1365-2443.2001.00483.x. ISSN 1356-9597. PMID 11737269. 
  5. ^ a b c Cheung, Peter C F; Nebreda Angel R, Cohen Philip (February 2004). "TAB3, a new binding partner of the protein kinase TAK1". Biochem. J. (England) 378 (Pt 1): 27–34. doi:10.1042/BJ20031794. PMC 1223947. PMID 14670075. 
  6. ^ a b 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 (United States) 5 (4): 649–58. doi:10.1016/S1097-2765(00)80244-0. ISSN 1097-2765. PMID 10882101. 
  7. ^ a b Takaesu, G; Ninomiya-Tsuji J, Kishida S, Li X, Stark G R, 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. (United States) 21 (7): 2475–84. doi:10.1128/MCB.21.7.2475-2484.2001. ISSN 0270-7306. PMC 86880. PMID 11259596. 
  8. ^ Channavajhala, Padma L; Wu Leeying, Cuozzo John W, Hall J Perry, Liu Wei, Lin Lih-Ling, Zhang Yuhua (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. (United States) 278 (47): 47089–97. doi:10.1074/jbc.M306002200. ISSN 0021-9258. PMID 12975377. 
  9. ^ a b c d 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 (ENGLAND) 398 (6724): 252–6. doi:10.1038/18465. ISSN 0028-0836. PMID 10094049. 
  10. ^ a b 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. (NETHERLANDS) 474 (2–3): 141–5. doi:10.1016/S0014-5793(00)01588-X. ISSN 0014-5793. PMID 10838074. 
  11. ^ a b c Ishitani, Tohru; Takaesu Giichi, Ninomiya-Tsuji Jun, Shibuya Hiroshi, Gaynor Richard B, Matsumoto Kunihiro (December 2003). "Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling". EMBO J. (England) 22 (23): 6277–88. doi:10.1093/emboj/cdg605. ISSN 0261-4189. PMC 291846. PMID 14633987. 
  12. ^ a b 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. (United States) 275 (42): 32747–52. doi:10.1074/jbc.M003042200. ISSN 0021-9258. PMID 10921914. 
  13. ^ 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. (United States) 276 (8): 5753–9. doi:10.1074/jbc.M007773200. ISSN 0021-9258. PMID 11104763. 
  14. ^ Walsh, Matthew C; Kim Gregory K, Maurizio Paul L, Molnar Elizabeth E, Choi Yongwon (2008). "TRAF6 Autoubiquitination-Independent Activation of the NFκB and MAPK Pathways in Response to IL-1 and RANKL". In Unutmaz, Derya. PLoS ONE (United States) 3 (12): e4064. doi:10.1371/journal.pone.0004064. PMC 2603309. PMID 19112497. 
  15. ^ Sorrentino, Alessandro; Thakur Noopur, Grimsby Susanne, Marcusson Anders, von Bulow Verena, Schuster Norbert, Zhang Shouting, Heldin Carl-Henrik, Landström Maréne (October 2008). "The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner". Nat. Cell Biol. (England) 10 (10): 1199–207. doi:10.1038/ncb1780. PMID 18758450. 
  16. ^ Wang, C; Deng L, Hong M, Akkaraju G R, Inoue J, Chen Z J (July 2001). "TAK1 is a ubiquitin-dependent kinase of MKK and IKK". Nature (England) 412 (6844): 346–51. doi:10.1038/35085597. ISSN 0028-0836. PMID 11460167. 
  17. ^ 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. (United States) 274 (15): 10641–8. doi:10.1074/jbc.274.15.10641. ISSN 0021-9258. PMID 10187861. 

Further reading[edit]