| Post Translational Modifications | Phosphorylated at all three sites Ser-423, Thr-431 and Ser-438 by MAPK14 when cells were exposed to cellular stresses, or stimulated with TNF-alpha, IL1 or LPS. These phosphorylations inhibit TAK1 activation by a feedback control mechanism. Dephosphorylated by DUSP14 at Ser-438, leading to TAB1-MAP3K7/TAK1 complex inactivation in T-cells. Ubiquitinated by MAP3K1 with 'Lys-63'-linked polyubiquitin.leading to activation of TAK1 and of JNK and p38 MAP kinases following EGF and TGF-beta stimulation. Ubiquitinated by ITCH with 'Lys-48'-linked polyubiquitin.leading to proteasomal degradation. Ubiquitinated by RNF114 during maternal-to-zygotic transition.leading to degradation. (Microbial infection) Deubiquitinated by Y.enterocolitica YopP. O-GlcNAcylated at Ser-395 by OGT is required for full MAP3K7/TAK1 activation upon stimulation with IL-1 or osmotic stress. Deglycosylated at Ser-395 by OGA. |
| Function | Key adapter protein that plays an essential role in JNK and NF-kappa-B activation and proinflammatory cytokines production in response to stimulation with TLRs and cytokines. Mechanistically, associates with the catalytic domain of MAP3K7/TAK1 to trigger MAP3K7/TAK1 autophosphorylation leading to its full activation. Similarly, associates with MAPK14 and triggers its autophosphorylation and subsequent activation. In turn, MAPK14 phosphorylates TAB1 and inhibits MAP3K7/TAK1 activation in a feedback control mechanism. Plays also a role in recruiting MAPK14 to the TAK1 complex for the phosphorylation of the TAB2 and TAB3 regulatory subunits. |
| Protein Name | Tgf-Beta-Activated Kinase 1 And Map3k7-Binding Protein 1Mitogen-Activated Protein Kinase Kinase Kinase 7-Interacting Protein 1Tgf-Beta-Activated Kinase 1-Binding Protein 1Tak1-Binding Protein 1 |
| Database Links | Reactome: R-HSA-168638Reactome: R-HSA-2871837Reactome: R-HSA-445989Reactome: R-HSA-450302Reactome: R-HSA-450321Reactome: R-HSA-5357956Reactome: R-HSA-5607764Reactome: R-HSA-5689880Reactome: R-HSA-9014325Reactome: R-HSA-9020702Reactome: R-HSA-937042Reactome: R-HSA-937072Reactome: R-HSA-9645460Reactome: R-HSA-9705671Reactome: R-HSA-975163 |
| Cellular Localisation | CytoplasmCytosolEndoplasmic Reticulum MembranePeripheral Membrane ProteinCytoplasmic SideRecruited To The Endoplasmic Reticulum Following Interaction With Sting1 |
| Alternative Protein Names | Tgf-Beta-Activated Kinase 1 And Map3k7-Binding Protein 1 proteinMitogen-Activated Protein Kinase Kinase Kinase 7-Interacting Protein 1 proteinTgf-Beta-Activated Kinase 1-Binding Protein 1 proteinTak1-Binding Protein 1 proteinTAB1 proteinMAP3K7IP1 protein |
Information sourced from Uniprot.org
