TAB1

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 (PubMed:22307082, PubMed:24403530). Mechanistically, associates with the catalytic domain of MAP3K7/TAK1 to trigger MAP3K7/TAK1 autophosphorylation leading to its full activation (PubMed:10838074, PubMed:25260751, PubMed:37832545). Similarly, associates with MAPK14 and triggers its autophosphorylation and subsequent activation (PubMed:11847341, PubMed:29229647). In turn, MAPK14 phosphorylates TAB1 and inhibits MAP3K7/TAK1 activation in a feedback control mechanism (PubMed:14592977). Plays also a role in recruiting MAPK14 to the TAK1 complex for the phosphorylation of the TAB2 and TAB3 regulatory subunits (PubMed:18021073).

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 (PubMed:14592977). These phosphorylations inhibit TAK1 activation by a feedback control mechanism (PubMed:14592977). Dephosphorylated by DUSP14 at Ser-438, leading to TAB1-MAP3K7/TAK1 complex inactivation in T-cells (PubMed:24403530).

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 (PubMed:25260751). Ubiquitinated by ITCH with 'Lys-48'-linked polyubiquitin; leading to proteasomal degradation (PubMed:25714464). Ubiquitinated by RNF114 during maternal-to-zygotic transition; leading to degradation (By similarity).

(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 (PubMed:22307082). Deglycosylated at Ser-395 by OGA (PubMed:28939839).

Tissue Specificity

Ubiquitous.

Cellular localization

• Cytoplasm
• Cytosol
• Endoplasmic reticulum membrane
• Peripheral membrane protein
• Cytoplasmic side
• Recruited to the endoplasmic reticulum following interaction with STING1.

Alternative names

MAP3K7IP1, TAB1, TGF-beta-activated kinase 1 and MAP3K7-binding protein 1, Mitogen-activated protein kinase kinase kinase 7-interacting protein 1, TGF-beta-activated kinase 1-binding protein 1, TAK1-binding protein 1

Database links

swissprot:Q15750 omim:602614 entrezGene:6885 swissprot:O43318 omim:602615 entrezGene:10454