MAP3K7IP2

TGF-beta activated kinase 1/MAP3K7 binding protein 2
PDB rendering based on 2dae.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2DAE​, 2WWZ​, 2WX0​, 2WX1​
Identifiers
Symbols	TAB2 ; CHTD2; MAP3K7IP2; TAB-2
External IDs	OMIM: 605101 MGI: 1915902 HomoloGene: 9019 GeneCards: TAB2 Gene
Gene ontology Molecular function • protein binding • zinc ion binding • K63-linked polyubiquitin binding Cellular component • cytosol • plasma membrane • endosome membrane Biological process • activation of MAPK activity • stimulatory C-type lectin receptor signaling pathway • toll-like receptor signaling pathway • MyD88-dependent toll-like receptor signaling pathway • MyD88-independent toll-like receptor signaling pathway • I-kappaB kinase/NF-kappaB signaling • JNK cascade • heart development • 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 • innate immune response • positive regulation of protein kinase activity • T cell receptor signaling pathway • positive regulation of NF-kappaB transcription factor activity • stress-activated MAPK cascade • nucleotide-binding oligomerization domain containing signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	23118	68652
Ensembl	ENSG00000055208	ENSMUSG00000015755
UniProt	Q9NYJ8	Q99K90
RefSeq (mRNA)	NM_001292034	NM_138667
RefSeq (protein)	NP_001278963	NP_619608
Location (UCSC)	Chr 6: 149.22 – 149.41 Mb	Chr 10: 7.91 – 7.96 Mb
PubMed search

Mitogen-activated protein kinase kinase kinase 7-interacting protein 2 is an enzyme that in humans is encoded by the MAP3K7IP2 gene.^[1][2][3]

The protein encoded by this gene is an activator of MAP3K7/TAK1, which is required for the IL-1 induced activation of nuclear factor kappaB and MAPK8/JNK. This protein forms a kinase complex with TRAF6, MAP3K7 and TAB1, thus serves as an adaptor linking MAP3K7 and TRAF6. This protein, TAB1, and MAP3K7 also participate in the signal transduction induced by TNFSF11/RANKL through the activation of the receptor activator of NF-kappB (TNFRSF11A/RANK), which may regulate the development and function of osteoclasts.^[3] Mutations in MAP3K7IP2 have been associated with human congenital heart defects.^[4]

Interactions

MAP3K7IP2 has been shown to interact with:

• HDAC3,^[5]
• MAP3K7IP1,^[2][6][7]
• MAP3K7IP3,^[8]
• MAP3K7,^[2][7][9]
• NFKB1,^[5]
• NUMBL,^[10]
• Nuclear receptor co-repressor 1,^[5]
• TRAF2,^[2][11] and
• TRAF6.^{[2][8][9][10][12][13]}

References

1. Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Apr 1999). "Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res 5 (5): 277–86. doi:10.1093/dnares/5.5.277. PMID 9872452.
2. Takaesu G, Kishida S, Hiyama A, Yamaguchi K, Shibuya H, Irie K, Ninomiya-Tsuji J, Matsumoto K (Jul 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.
3. "Entrez Gene: MAP3K7IP2 mitogen-activated protein kinase kinase kinase 7 interacting protein 2".
4. Thienpont B, Zhang L, Postma AV, Breckpot J, Tranchevent LC, Van Loo P, Møllgård K, Tommerup N, Bache I, Tümer Z, van Engelen K, Menten B, Mortier G, Waggoner D, Gewillig M, Moreau Y, Devriendt K, Larsen LA (2010). "Haploinsufficiency of TAB2 causes congenital heart defects in humans.". Am J Hum Genet 86 (6): 839–49. doi:10.1016/j.ajhg.2010.04.011. PMC 3032066. PMID 20493459.
5. Baek SH, Ohgi KA, Rose DW, Koo EH, Glass CK, Rosenfeld MG (Jul 2002). "Exchange of N-CoR corepressor and Tip60 coactivator complexes links gene expression by NF-kappaB and beta-amyloid precursor protein". Cell 110 (1): 55–67. doi:10.1016/S0092-8674(02)00809-7. PMID 12150997.
6. 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 (Feb 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.
7. Cheung PC, Nebreda AR, Cohen P (Feb 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.
8. Ishitani T, Takaesu G, Ninomiya-Tsuji J, Shibuya H, Gaynor RB, Matsumoto K (Dec 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.
9. Takaesu G, Ninomiya-Tsuji J, Kishida S, Li X, Stark GR, Matsumoto K (Apr 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.
10. Ma Q, Zhou L, Shi H, Huo K (Jun 2008). "NUMBL interacts with TAB2 and inhibits TNFalpha and IL-1beta-induced NF-kappaB activation". Cell. Signal. 20 (6): 1044–51. doi:10.1016/j.cellsig.2008.01.015. PMID 18299187.
11. Li S, Wang L, Dorf ME (Jan 2009). "PKC phosphorylation of TRAF2 mediates IKKalpha/beta recruitment and K63-linked polyubiquitination". Mol. Cell 33 (1): 30–42. doi:10.1016/j.molcel.2008.11.023. PMC 2643372. PMID 19150425.
12. 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.
13. Windheim M, Stafford M, Peggie M, Cohen P (Mar 2008). "Interleukin-1 (IL-1) induces the Lys63-linked polyubiquitination of IL-1 receptor-associated kinase 1 to facilitate NEMO binding and the activation of IkappaBalpha kinase". Mol. Cell. Biol. 28 (5): 1783–91. doi:10.1128/MCB.02380-06. PMC 2258775. PMID 18180283.

Further reading

• Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T (2003). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones". DNA Res. 9 (3): 99–106. doi:10.1093/dnares/9.3.99. PMID 12168954.
• 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.
• Takaesu G, Ninomiya-Tsuji J, Kishida S, Li X, Stark GR, Matsumoto K (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.
• 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.
• Mizukami J, Takaesu G, Akatsuka H, Sakurai H, Ninomiya-Tsuji J, Matsumoto K, Sakurai N (2002). "Receptor activator of NF-kappaB ligand (RANKL) activates TAK1 mitogen-activated protein kinase kinase kinase through a signaling complex containing RANK, TAB2, and TRAF6". Mol. Cell. Biol. 22 (4): 992–1000. doi:10.1128/MCB.22.4.992-1000.2002. PMC 134634. PMID 11809792.
• Sanna MG, da Silva Correia J, Luo Y, Chuang B, Paulson LM, Nguyen B, Deveraux QL, Ulevitch RJ (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.
• Baek SH, Ohgi KA, Rose DW, Koo EH, Glass CK, Rosenfeld MG (2002). "Exchange of N-CoR corepressor and Tip60 coactivator complexes links gene expression by NF-kappaB and beta-amyloid precursor protein". Cell 110 (1): 55–67. doi:10.1016/S0092-8674(02)00809-7. PMID 12150997.
• Jiang Z, Ninomiya-Tsuji J, Qian Y, Matsumoto K, Li X (2002). "Interleukin-1 (IL-1) receptor-associated kinase-dependent IL-1-induced signaling complexes phosphorylate TAK1 and TAB2 at the plasma membrane and activate TAK1 in the cytosol". Mol. Cell. Biol. 22 (20): 7158–67. doi:10.1128/MCB.22.20.7158-7167.2002. PMC 139807. PMID 12242293.
• Jiang Z, Zamanian-Daryoush M, Nie H, Silva AM, Williams BR, Li X (2003). "Poly(I-C)-induced Toll-like receptor 3 (TLR3)-mediated activation of NFkappa B and MAP kinase is through an interleukin-1 receptor-associated kinase (IRAK)-independent pathway employing the signaling components TLR3-TRAF6-TAK1-TAB2-PKR". J. Biol. Chem. 278 (19): 16713–9. doi:10.1074/jbc.M300562200. PMID 12609980.
• Matsuda A, Suzuki Y, Honda G, Muramatsu S, Matsuzaki O, Nagano Y, Doi T, Shimotohno K, Harada T, Nishida E, Hayashi H, Sugano S (2003). "Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways". Oncogene 22 (21): 3307–18. doi:10.1038/sj.onc.1206406. PMID 12761501.
• Ishitani T, Takaesu G, Ninomiya-Tsuji J, Shibuya H, Gaynor RB, Matsumoto K (2004). "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.
• 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.
• 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 (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.
• Owerbach D, Piña L, Gabbay KH (2004). "A 212-kb region on chromosome 6q25 containing the TAB2 gene is associated with susceptibility to type 1 diabetes". Diabetes 53 (7): 1890–3. doi:10.2337/diabetes.53.7.1890. PMID 15220215.
• Kanayama A, Seth RB, Sun L, Ea CK, Hong M, Shaito A, Chiu YH, Deng L, Chen ZJ (2004). "TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains". Mol. Cell 15 (4): 535–48. doi:10.1016/j.molcel.2004.08.008. PMID 15327770.