TAB3

The product of this gene functions in the NF-kappaB signal transduction pathway. The encoded protein, and the similar and functionally redundant protein MAP3K7IP2/TAB2, forms a ternary complex with the protein kinase MAP3K7/TAK1 and either TRAF2 or TRAF6 in response to stimulation with the pro-inflammatory cytokines TNF or IL-1. Subsequent MAP3K7/TAK1 kinase activity triggers a signaling cascade leading to activation of the NF-kappaB transcription factor. The human genome contains a related pseudogene. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

Full Name

TAB3 Gene(Protein Coding) TGF-Beta Activated Kinase 1 And MAP3K7 Binding Protein 3

Function

Adapter required to activate the JNK and NF-kappa-B signaling pathways through the specific recognition of 'Lys-63'-linked polyubiquitin chains by its RanBP2-type zinc finger (NZF) (PubMed:14633987, PubMed:14766965, PubMed:15327770, PubMed:22158122).
Acts as an adapter linking MAP3K7/TAK1 and TRAF6 to 'Lys-63'-linked polyubiquitin chains (PubMed:14633987, PubMed:14766965, PubMed:15327770, PubMed:22158122).
The RanBP2-type zinc finger (NZF) specifically recognizes Lys-63'-linked polyubiquitin chains unanchored or anchored to the substrate proteins such as RIPK1/RIP1: this acts as a scaffold to organize a large signaling complex to promote autophosphorylation of MAP3K7/TAK1, and subsequent activation of I-kappa-B-kinase (IKK) core complex by MAP3K7/TAK1 (PubMed:15327770, PubMed:22158122).4 Publications
Isoform 2
May be an oncogenic factor.

Biological Process

Biological Process negative regulation of autophagyTAS:ParkinsonsUK-UCL1 Publication
Biological Process positive regulation of I-kappaB kinase/NF-kappaB signalingIDA:UniProtKB2 Publications

Cellular Location

cytosol
endosome membrane
extracellular exosome
plasma membrane

PTM

Ubiquitinated; following IL1 stimulation or TRAF6 overexpression.
Degraded in a lysosome-dependent manner following interactiuon with TRIM38.
Phosphorylated at Ser-506 by MAPKAPK2 and MAPKAPK3 following IL1 treatment.
(Microbial infection) Methylated at Cys-692 by enteropathogenic E.coli protein NleE or S.flexneri protein OspZ: methylation disrupts zinc-binding and ability to bind 'Lys-63'-linked ubiquitin, leading to NF-kappa-B inactivation.