TAB1

Mitogen-activated protein kinase kinase kinase 7-interacting protein 1 is an enzyme that in humans is encoded by the TAB1 gene.^[5][6][7]

TAB1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2J4O, 2POM, 2POP, 2YDS, 2YIY, 4AY5, 4AY6, 4GS6, 4KA3, 4L3P, 4L53, 4O91, 5DIY, 5JGA, 5JGD
Identifiers
Aliases	TAB1, 3'-Tab1, MAP3K7IP1, TGF-beta activated kinase 1/MAP3K7 binding protein 1, TGF-beta activated kinase 1 (MAP3K7) binding protein 1
External IDs	OMIM: 602615 MGI: 1913763 HomoloGene: 4461 GeneCards: TAB1
Gene location (Human) Chr. Chromosome 22 (human)^[1] Band 22q13.1 Start 39,399,778 bp^[1] End 39,437,060 bp^[1]
Gene location (Mouse) Chr. Chromosome 15 (mouse)^[2] Band 15|15 E1 Start 80,017,328 bp^[2] End 80,045,908 bp^[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in parotid gland sural nerve subthalamic nucleus right ventricle nucleus accumbens external globus pallidus ganglionic eminence pons amygdala prefrontal cortex Top expressed in internal carotid artery external carotid artery saccule lip Paneth cell neural tube conjunctival fornix renal corpuscle urethra female urethra More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein serine/threonine phosphatase activity protein binding catalytic activity kinase activator activity enzyme activator activity protein-containing complex binding mitogen-activated protein kinase p38 binding protein kinase activator activity Cellular component endosome membrane cytosol nuclear speck protein-containing complex nucleus Biological process cardiac septum development lung development protein dephosphorylation heart morphogenesis stimulatory C-type lectin receptor signaling pathway in utero embryonic development MyD88-dependent toll-like receptor signaling pathway coronary vasculature development Fc-epsilon receptor signaling pathway JNK cascade aorta development positive regulation of NF-kappaB transcription factor activity I-kappaB kinase/NF-kappaB signaling transforming growth factor beta receptor signaling pathway nucleotide-binding oligomerization domain containing signaling pathway positive regulation of MAP kinase activity protein deubiquitination interleukin-1-mediated signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 10454 66513 Ensembl ENSG00000100324 ENSMUSG00000022414 UniProt Q15750 Q8CF89 RefSeq (mRNA) NM_153497 NM_006116 NM_025609 RefSeq (protein) NP_006107 NP_705717 NP_079885 Location (UCSC) Chr 22: 39.4 – 39.44 Mb Chr 15: 80.02 – 80.05 Mb PubMed search ^[3] ^[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

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.^[7] TAB1 contains multiple amino acid sites that are phosphorylated and ubiquitinated.^[8]

This protein plays an important role in skin homeostasis,^[9][10] wound repair,^[11][12] and oncogenesis.^[13]

Interactions

TAB1 has been shown to interact with:

• MAP3K7IP2,^[14][15][16]
• MAP3K7IP3,^[16]
• MAP3K7,^{[16][17][18][19]}
• MAP3K1,^[20]
• MAPK14,^[21]
• Mothers against decapentaplegic homolog 7,^[22][23]
• TRAF6,^[14][17][24]
• XIAP,^[25][26] and
• ZMYND11.^[27]

References

1. GRCh38: Ensembl release 89: ENSG00000100324 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000022414 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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. Bibcode:1996Sci...272.1179S. doi:10.1126/science.272.5265.1179. PMID 8638164. S2CID 84807994.
6. 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.
7. "Entrez Gene: MAP3K7IP1 mitogen-activated protein kinase kinase kinase 7 interacting protein 1".
8. "TAB1 (human)". www.phosphosite.org. Retrieved 2020-10-31.
9. 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 1797070. PMID 16675448.
10. 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.
11. 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 2709347. PMID 19419968.
12. 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. PMC 3131962. PMID 21233843.
13. 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 2970664. PMID 20959492.
14. 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.
15. 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. S2CID 11683986.
16. 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.
17. 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. Bibcode:1999Natur.398..252N. doi:10.1038/18465. PMID 10094049. S2CID 4421236.
18. 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.
19. 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. S2CID 30831863.
20. Charlaftis N, Suddason T, Wu X, Anwar S, Karin M, Gallagher E (November 2014). "The MEKK1 PHD ubiquitinates TAB1 to activate MAPKs in response to cytokines". The EMBO Journal. 33 (21): 2581–96. doi:10.15252/embj.201488351. PMC 4282369. PMID 25260751.
21. 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. Bibcode:2002Sci...295.1291G. doi:10.1126/science.1067289. PMID 11847341. S2CID 93896233.
22. 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 149990. PMID 12589052.
23. 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.
24. Walsh MC, Kim GK, Maurizio PL, Molnar EE, Choi Y (2008). 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. Bibcode:2008PLoSO...3.4064W. doi:10.1371/journal.pone.0004064. PMC 2603309. PMID 19112497.
25. 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 1171113. PMID 9878061.
26. 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.
27. 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. S2CID 29818690.

Further reading

• Kurozumi K, Nishita M, Yamaguchi K, Fujita T, Ueno N, Shibuya H (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. S2CID 29818690.
• 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.
• 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. Bibcode:1999Natur.398..252N. doi:10.1038/18465. PMID 10094049. S2CID 4421236.
• Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP (1999). "The DNA sequence of human chromosome 22". Nature. 402 (6761): 489–95. Bibcode:1999Natur.402..489D. doi:10.1038/990031. PMID 10591208.
• Kishimoto K, Matsumoto K, Ninomiya-Tsuji J (2000). "TAK1 mitogen-activated protein kinase kinase kinase is activated by autophosphorylation within its activation loop". J. Biol. Chem. 275 (10): 7359–64. doi:10.1074/jbc.275.10.7359. PMID 10702308.
• 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. S2CID 30831863.
• Ono K, Ohtomo T, Sato S, Sugamata Y, Suzuki M, Hisamoto N, Ninomiya-Tsuji J, Tsuchiya M, Matsumoto K (2001). "An evolutionarily conserved motif in the TAB1 C-terminal region is necessary for interaction with and activation of TAK1 MAPKKK". J. Biol. Chem. 276 (26): 24396–400. doi:10.1074/jbc.M102631200. PMID 11323434.
• Qian Y, Commane M, Ninomiya-Tsuji J, Matsumoto K, Li X (2001). "IRAK-mediated translocation of TRAF6 and TAB2 in the interleukin-1-induced activation of NFkappa B." J. Biol. Chem. 276 (45): 41661–7. doi:10.1074/jbc.M102262200. PMID 11518704.
• Yanagisawa M, Nakashima K, Takeda K, Ochiai W, Takizawa T, Ueno M, Takizawa M, Shibuya H, Taga T (2002). "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.
• Ge B, Gram H, Di Padova F, Huang B, New L, Ulevitch RJ, Luo Y, Han J (2002). "MAPKK-independent activation of p38alpha mediated by TAB1-dependent autophosphorylation of p38alpha". Science. 295 (5558): 1291–4. Bibcode:2002Sci...295.1291G. doi:10.1126/science.1067289. PMID 11847341. S2CID 93896233.
• Sakurai H, Nishi A, Sato N, Mizukami J, Miyoshi H, Sugita T (2002). "TAK1-TAB1 fusion protein: a novel constitutively active mitogen-activated protein kinase kinase kinase that stimulates AP-1 and NF-kappaB signaling pathways". Biochem. Biophys. Res. Commun. 297 (5): 1277–81. doi:10.1016/S0006-291X(02)02379-3. PMID 12372426.
• Ge B, Xiong X, Jing Q, Mosley JL, Filose A, Bian D, Huang S, Han J (2003). "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. 278 (4): 2286–93. doi:10.1074/jbc.M210918200. PMID 12429732.
• Ishitani T, Kishida S, Hyodo-Miura J, Ueno N, Yasuda J, Waterman M, Shibuya H, Moon RT, Ninomiya-Tsuji J, Matsumoto K (2003). "The TAK1-NLK mitogen-activated protein kinase cascade functions in the Wnt-5a/Ca(2+) pathway to antagonize Wnt/beta-catenin signaling". Mol. Cell. Biol. 23 (1): 131–9. doi:10.1128/MCB.23.1.131-139.2003. PMC 140665. PMID 12482967.
• Suzawa M, Takada I, Yanagisawa J, Ohtake F, Ogawa S, Yamauchi T, Kadowaki T, Takeuchi Y, Shibuya H, Gotoh Y, Matsumoto K, Kato S (2003). "Cytokines suppress adipogenesis and PPAR-gamma function through the TAK1/TAB1/NIK cascade". Nat. Cell Biol. 5 (3): 224–30. doi:10.1038/ncb942. PMID 12598905. S2CID 114603.
• Tanno M, Bassi R, Gorog DA, Saurin AT, Jiang J, Heads RJ, Martin JL, Davis RJ, Flavell RA, Marber MS (2003). "Diverse mechanisms of myocardial p38 mitogen-activated protein kinase activation: evidence for MKK-independent activation by a TAB1-associated mechanism contributing to injury during myocardial ischemia". Circ. Res. 93 (3): 254–61. doi:10.1161/01.RES.0000083490.43943.85. PMID 12829618.
• Channavajhala PL, Wu L, Cuozzo JW, Hall JP, Liu W, Lin LL, Zhang Y (2004). "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.
• Cheung PC, Nebreda AR, Cohen P (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.