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TGF-beta activated kinase 1/MAP3K7 binding protein 1
Protein MAP3K7IP1 PDB 2j4o.png
PDB rendering based on 2j4o.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols TAB1 ; 3'-Tab1; MAP3K7IP1
External IDs OMIM602615 MGI1913763 HomoloGene4461 ChEMBL: 5605 GeneCards: TAB1 Gene
RNA expression pattern
PBB GE MAP3K7IP1 203901 at tn.png
More reference expression data
Species Human Mouse
Entrez 10454 66513
Ensembl ENSG00000100324 ENSMUSG00000022414
UniProt Q15750 Q8CF89
RefSeq (mRNA) NM_006116 NM_025609
RefSeq (protein) NP_006107 NP_079885
Location (UCSC) Chr 22:
39.8 – 39.83 Mb
Chr 15:
80.13 – 80.16 Mb
PubMed search [1] [2]

Mitogen-activated protein kinase kinase kinase 7-interacting protein 1 is an enzyme that in humans is encoded by the MAP3K7IP1 gene.[1][2][3]

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.[3]

This protein plays an important role in skin homeostasis,[4][5] wound repair,[6][7] and oncogenesis.[8]


MAP3K7IP1 has been shown to interact with ZMYND11,[9] MAPK14,[10] Mothers against decapentaplegic homolog 7,[11][12] TRAF6,[13][14][15] MAP3K7IP2,[13][16][17] XIAP,[18][19] MAP3K7[14][17][20][21] and MAP3K7IP3.[17]


  1. ^ 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. 
  2. ^ 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. 
  3. ^ a b "Entrez Gene: MAP3K7IP1 mitogen-activated protein kinase kinase kinase 7 interacting protein 1". 
  4. ^ Omori E, et al. (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 1797070. PMID 16675448. 
  5. ^ Sayama K, et al. (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. 
  6. ^ Tan SH, et al., (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 2709347. PMID 19419968. 
  7. ^ Lam CR, et al., (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. 
  8. ^ Omori E, et al. (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 2970664. PMID 20959492. 
  9. ^ 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 (ENGLAND) 3 (4): 257–64. doi:10.1046/j.1365-2443.1998.00186.x. ISSN 1356-9597. PMID 9663660. 
  10. ^ Ge, Baoxue; Gram Hermann; Di Padova Franco; Huang Betty; New Liguo; Ulevitch Richard J; Luo Ying; Han Jiahuai (February 2002). "MAPKK-independent activation of p38alpha mediated by TAB1-dependent autophosphorylation of p38alpha". Science (United States) 295 (5558): 1291–4. doi:10.1126/science.1067289. PMID 11847341. 
  11. ^ Edlund, Sofia; Bu Shizhong; Schuster Norbert; Aspenström Pontus; Heuchel Rainer; Heldin Nils-Erik; ten Dijke Peter; Heldin Carl-Henrik; Landström Maréne (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 (United States) 14 (2): 529–44. doi:10.1091/mbc.02-03-0037. ISSN 1059-1524. PMC 149990. PMID 12589052. 
  12. ^ 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. 
  13. ^ 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. 
  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 (ENGLAND) 398 (6724): 252–6. doi:10.1038/18465. ISSN 0028-0836. PMID 10094049. 
  15. ^ Walsh, Matthew C; Kim Gregory K; Maurizio Paul L; Molnar Elizabeth E; Choi Yongwon (2008). Unutmaz, Derya, ed. "TRAF6 autoubiquitination-independent activation of the NFkappaB and MAPK pathways in response to IL-1 and RANKL". PLoS ONE (United States) 3 (12): e4064. doi:10.1371/journal.pone.0004064. PMC 2603309. PMID 19112497. 
  16. ^ Bouwmeester, Tewis; Bauch Angela, Ruffner Heinz, Angrand Pierre-Olivier, Bergamini Giovanna, Croughton Karen, Cruciat Cristina, Eberhard Dirk, Gagneur Julien, Ghidelli Sonja, Hopf Carsten, Huhse Bettina, Mangano Raffaella, Michon Anne-Marie, Schirle Markus, Schlegl Judith, Schwab Markus, Stein Martin A, Bauer Andreas, Casari Georg, Drewes Gerard, Gavin Anne-Claude, Jackson David B, Joberty Gerard, Neubauer Gitte, Rick Jens, Kuster Bernhard, Superti-Furga Giulio (February 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. (England) 6 (2): 97–105. doi:10.1038/ncb1086. ISSN 1465-7392. PMID 14743216. 
  17. ^ 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. 
  18. ^ 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. (ENGLAND) 18 (1): 179–87. doi:10.1093/emboj/18.1.179. ISSN 0261-4189. PMC 1171113. PMID 9878061. 
  19. ^ Sanna, M Germana; da Silva Correia Jean; Luo Ying; Chuang Betty; Paulson Lorien M; Nguyen Binh; Deveraux Quinn L; Ulevitch Richard J (August 2002). "ILPIP, a novel anti-apoptotic protein that enhances XIAP-mediated activation of JNK1 and protection against apoptosis". J. Biol. Chem. (United States) 277 (34): 30454–62. doi:10.1074/jbc.M203312200. ISSN 0021-9258. PMID 12048196. 
  20. ^ 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. 
  21. ^ 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. 

Further reading[edit]