Disease relevance of MAP3K7IP2

• Contribution of single nucleotide polymorphisms within FCRL3 and MAP3K7IP2 to the pathogenesis of Graves' disease [1].

High impact information on MAP3K7IP2

• This is based on an evolutionarily conserved receptor N-terminal L/HX7LL motif, selectively present in sex steroid receptors, that causes recruitment of TAB2 as a component of an N-CoR corepressor complex [2].
• The fragment forms a complex with the adaptor TAB2 and the corepressor N-CoR and transits to the nucleus, where it represses transcription of genes that promote the formation of astrocytes [3].
• TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains [4].
• However, IL-1-induced activation of NF-kappaB is not impaired in TAB2-deficient embryonic fibroblasts [5].
• Here, we show that endogenous and overexpressed TAB2, TRAF6 and TAK1 co-immunoprecipitated with Edaradd in 293 cells [6].

Biological context of MAP3K7IP2

• TAB2 (MAP3K7IP2 [mitogen-activating protein kinase kinase kinase 7 interacting protein 2]) is a potential candidate gene for type 1 diabetes because it is located on chromosome 6q25 and is involved in nuclear factor (NF)-kappaB regulation [7].
• These results indicate critical roles of Thr-187 phosphorylation in the stress-induced rapid and transient activation of TAK1 in a signaling complex containing TAB1 and TAB2 [8].
• Here we present evidence that TAB2 and TAB3 are receptors that bind preferentially to lysine 63-linked polyubiquitin chains through a highly conserved zinc finger (ZnF) domain [4].
• However, both TAB2 and SUMO are involved in NF-kappaB activation and may thus be involved in type 1 diabetes through apoptosis in pancreatic beta-cells [7].
• A cDNA clone (TAB2) encoding a nucleoside diphosphate (NDP) kinase has been isolated from a tomato (Lycopersicon esculentum Mill. cv. Ailsa Craig) cDNA library [9].

Anatomical context of MAP3K7IP2

• TAB2 is recruited to this complex following translocation from the membrane to the cytosol upon IL-1 stimulation [10].
• These results suggest that the formation of the TRAF6-TAB2-TAK1 complex is involved in the RANK signaling pathway and may regulate the development and function of osteoclasts [11].

Associations of MAP3K7IP2 with chemical compounds

• Our results indicate that TAB3 is phosphorylated via the SAPK2a/p38alpha pathway, whereas TAB2 is phosphorylated at two or more sites by both an SAPK2a/p38alpha-dependent and an SB 203580-independent kinase [12].
• (2006) discover that proinflammatory signals switch repressed steroid hormone receptors into transcriptional activators by targeting TAB2, an adaptor protein that tethers corepressors [13].

Regulatory relationships of MAP3K7IP2

• SUMO4 and MAP3K7IP2 SNP did not significantly influence predisposition to and features of RA, in contrast to previous genetic and functional evidence that suggested their involvement [14].

Other interactions of MAP3K7IP2

• To gain further insight into the mechanism of IKK activation by Edar and Edaradd, we performed a yeast two-hybrid screen and isolated TAB2 (TAK1-binding protein 2) as a binding partner of Edaradd [6].
• In IRAK-deficient cells, TAB2 translocation and its association with TRAF6 are abolished [10].
• Meta-analysis of published studies and the present data confirmed a highly significant association in Asian populations (summary OR 1.29, P = 7.0 x 10(-6)) but indicated heterogeneity in the genetic effect of the SUMO4/MAP3K7IP2 locus on type 1 diabetes among diverse ethnic groups [15].
• These data indicate that the MAP3K7IP2/SUMO4 locus in the IDDM5 interval is associated with type 1 diabetes in Asian populations [15].
• SUMO4 and MAP3K7IP2 single nucleotide polymorphisms and susceptibility to rheumatoid arthritis [14].

Analytical, diagnostic and therapeutic context of MAP3K7IP2

• Southern blot analysis indicates that TAB2 is a member of a small gene family [9].
• The data presented demonstrates the Tab2 tag-anti-Tab2 antibody combination is a reliable tool enabling specific Western blot detection, FACS analysis, and immunoprecipitation as well as non-denaturing protein affinity purification [16].

References