TAB3

Domain

The RanBP2-type zinc finger (NZF) mediates binding to two consecutive 'Lys-63'-linked ubiquitins.

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).

Isoform 2

May be an oncogenic factor.

Post-translational modifications

Ubiquitinated; following IL1 stimulation or TRAF6 overexpression.

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.

Tissue specificity

Widely expressed. Constitutively overexpressed in certain tumor tissues.

Isoform 1

Major transcript.

Isoform 2

Minor transcript.

Alternative names

• TGF-beta-activated kinase 1 and MAP3K7-binding protein 3
• Mitogen-activated protein kinase kinase kinase 7-interacting protein 3
• NF-kappa-B-activating protein 1
• TAK1-binding protein 3
• TGF-beta-activated kinase 1-binding protein 3
• TAB-3
• MAP3K7IP3
• TAB3

Database links

• entrezGene:257397
• omim:300480
• swissprot:Q8N5C8

Target type

Proteins

Molecular weight

78653Da