E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as IKBKG, AKT1 and AKT2. Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation. Leads to the activation of NF-kappa-B and JUN. May be essential for the formation of functional osteoclasts. Seems to also play a role in dendritic cells (DCs) maturation and/or activation. Represses c-Myb-mediated transactivation, in B lymphocytes. Adapter protein that seems to play a role in signal transduction initiated via TNF receptor, IL-1 receptor and IL-17 receptor.

Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Protein modification; protein ubiquitination.

Belongs to the TNF receptor-associated factor family. A subfamily.
Contains 1 MATH domain.
Contains 1 RING-type zinc finger.
Contains 2 TRAF-type zinc fingers.

The coiled coil domain mediates homo- and hetero-oligomerization.
The MATH/TRAF domain binds to receptor cytoplasmic domains.

Sumoylated on Lys-124, Lys-142 and Lys-453 by SUMO1.
Polyubiquitinated on Lys-124; after cell stimulation with IL-1-beta or TGF-beta. This ligand-induced cell stimulation leads to dimerization/oligomerization of TRAF6 molecules, followed by auto-ubiquitination which involves UBE2N and UBE2V1 and leads to TRAF6 activation. This 'Lys-63' site-specific poly-ubiquitination appears to be associated with the activation of signaling molecules. Endogenous autoubiquitination occurs only for the cytoplasmic form.

Cytoplasm. Cytoplasm > cell cortex. Nucleus. Found in the nuclei of some agressive B-cell lymphoma cell lines as well as in the nuclei of both resting and activated T-and B-lymphocytes. Found in punctate nuclear body protein complexes. Ubiquitination may occur in the cytoplasm and sumoylation in the nucleus.