From Wikipedia, the free encyclopedia
Jump to: navigation, search
Protein MAP3K7IP1 PDB 2j4o.png
Available structures
PDB Ortholog search: PDBe RCSB
Aliases TAB1, 3'-Tab1, MAP3K7IP1, TGF-beta activated kinase 1/MAP3K7 binding protein 1
External IDs MGI: 1913763 HomoloGene: 4461 GeneCards: TAB1
RNA expression pattern
PBB GE MAP3K7IP1 203901 at fs.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 22: 39.4 – 39.44 Mb Chr 15: 80.13 – 80.16 Mb
PubMed search [1] [2]
View/Edit Human View/Edit Mouse

Mitogen-activated protein kinase kinase kinase 7-interacting protein 1 is an enzyme that in humans is encoded by the MAP3K7IP1 gene.[3][4][5]


The protein encoded by this gene was identified as a regulator of the MAP kinase kinase kinase MAP3K7/TAK1, which is known to mediate various intracellular signaling pathways, such as those induced by TGF beta, interleukin 1, and WNT-1. This protein interacts and thus activates TAK1 kinase. It has been shown that the C-terminal portion of this protein is sufficient for binding and activation of TAK1, while a portion of the N-terminus acts as a dominant-negative inhibitor of TGF beta, suggesting that this protein may function as a mediator between TGF beta receptors and TAK1. This protein can also interact with and activate the mitogen-activated protein kinase 14 (MAPK14/p38alpha), and thus represents an alternative activation pathway, in addition to the MAPKK pathways, which contributes to the biological responses of MAPK14 to various stimuli. Alternatively spliced transcript variants encoding distinct isoforms have been reported.[5]

This protein plays an important role in skin homeostasis,[6][7] wound repair,[8][9] and oncogenesis.[10]


MAP3K7IP1 has been shown to interact with:


  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ Shibuya H, Yamaguchi K, Shirakabe K, Tonegawa A, Gotoh Y, Ueno N, Irie K, Nishida E, Matsumoto K (July 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. 
  4. ^ Sakurai H, Miyoshi H, Toriumi W, Sugita T (May 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. 
  5. ^ a b "Entrez Gene: MAP3K7IP1 mitogen-activated protein kinase kinase kinase 7 interacting protein 1". 
  6. ^ Omori E, Matsumoto K, Sanjo H, Sato S, Akira S, Smart RC, Ninomiya-Tsuji J (July 2006). "TAK1 is a master regulator of epidermal homeostasis involving skin inflammation and apoptosis.". J. Biol. Chem. 281 (28): 19610–19617. doi:10.1074/jbc.M603384200. PMC 1797070Freely accessible. PMID 16675448. 
  7. ^ Sayama K, Hanakawa Y, Nagai H, Shirakata Y, Dai X, Hirakawa S, Tokumaru S, Tohyama M, Yang L, Sato S, Shizuo A, Hashimoto K (August 2006). "Transforming growth factor-beta-activated kinase 1 is essential for differentiation and the prevention of apoptosis in epidermis.". J. Biol. Chem. 281 (31): 22013–22020. doi:10.1074/jbc.M601065200. PMID 16754690. 
  8. ^ Tan SH, Pal M, Tan MJ, Wong MH, Tam FU, Teo JW, Chong HC, Tan CK, Goh YY, Tang MB, Cheung PC, Tan NS (July 2009). "Regulation of cell proliferation and migration by TAK1 via transcriptional control of von Hippel-Lindau tumor suppressor.". J. Biol. Chem. 284 (27): 18047–18058. doi:10.1074/jbc.M109.002691. PMC 2709347Freely accessible. PMID 19419968. 
  9. ^ Lam CR, Tan MJ, Tan SH, Tang MB, Cheung PC, Tan NS (January 2011). "TAK1 regulates SCF expression to modulate PKBα activity that protects keratinocytes from ROS-induced apoptosis.". Cell Death Differ. 18 (7): 1120–9. doi:10.1038/cdd.2010.182. PMID 21233843. 
  10. ^ Omori E, Matsumoto K, Zhu S, Smart RC, Ninomiya-Tsuji J (November 2010). "Ablation of TAK1 upregulates reactive oxygen species and selectively kills tumor cells.". Cancer Res. 70 (21): 8417–8425. doi:10.1158/0008-5472.CAN-10-1227. PMC 2970664Freely accessible. PMID 20959492. 
  11. ^ 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. 5 (4): 649–58. doi:10.1016/s1097-2765(00)80244-0. PMID 10882101. 
  12. ^ Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G (February 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216. 
  13. ^ a b c 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 1223947Freely accessible. PMID 14670075. 
  14. ^ a b 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. 
  15. ^ 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. 
  16. ^ 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. 
  17. ^ Ge B, Gram H, Di Padova F, Huang B, New L, Ulevitch RJ, Luo Y, Han J (February 2002). "MAPKK-independent activation of p38alpha mediated by TAB1-dependent autophosphorylation of p38alpha". Science. 295 (5558): 1291–4. doi:10.1126/science.1067289. PMID 11847341. 
  18. ^ Edlund S, Bu S, Schuster N, Aspenström P, Heuchel R, Heldin NE, ten Dijke P, Heldin CH, Landström M (February 2003). "Transforming growth factor-beta1 (TGF-beta)-induced apoptosis of prostate cancer cells involves Smad7-dependent activation of p38 by TGF-beta-activated kinase 1 and mitogen-activated protein kinase kinase 3". Mol. Biol. Cell. 14 (2): 529–44. doi:10.1091/mbc.02-03-0037. PMC 149990Freely accessible. PMID 12589052. 
  19. ^ 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. 
  20. ^ 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 2603309Freely accessible. PMID 19112497. 
  21. ^ Yamaguchi K, Nagai S, Ninomiya-Tsuji J, Nishita M, Tamai K, Irie K, Ueno N, Nishida E, Shibuya H, Matsumoto K (January 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 1171113Freely accessible. PMID 9878061. 
  22. ^ Sanna MG, da Silva Correia J, Luo Y, Chuang B, Paulson LM, Nguyen B, Deveraux QL, Ulevitch RJ (August 2002). "ILPIP, a novel anti-apoptotic protein that enhances XIAP-mediated activation of JNK1 and protection against apoptosis". J. Biol. Chem. 277 (34): 30454–62. doi:10.1074/jbc.M203312200. PMID 12048196. 
  23. ^ Kurozumi K, Nishita M, Yamaguchi K, Fujita T, Ueno N, Shibuya H (April 1998). "BRAM1, a BMP receptor-associated molecule involved in BMP signalling". Genes Cells. 3 (4): 257–64. doi:10.1046/j.1365-2443.1998.00186.x. PMID 9663660. 

Further reading[edit]