hp-IRAK1:K6 poly-Ub oligo-TRAF6 K63-polyubiquitin TRAF6 auto-ubiquitinates with Lys63-linked polyubiquitin chains Authored: Ray, KP, 2010-05-17 EC Number: 6.3.2.19 Edited: Jupe, S, 2010-05-17 Pubmed17135271 Reactome Database ID Release 43446877 Reactome, http://www.reactome.org ReactomeREACT_22430 Reviewed: Pinteaux, E, 2010-05-17 TRAF6 possesses ubiquitin ligase activity and undergoes K-63-linked auto-ubiquitination after its oligomerization. In the first step, ubiquitin is activated by an E1 ubiquitin activating enzyme. The activated ubiquitin is transferred to a E2 conjugating enzyme (a heterodimer of proteins Ubc13 and Uev1A) forming the E2-Ub thioester. Finally, in the presence of ubiquitin-protein ligase E3 (TRAF6, a RING-domain E3), ubiquitin is attached to the target protein (TRAF6 on residue Lysine 124) through an isopeptide bond between the C-terminus of ubiquitin and the epsilon-amino group of a lysine residue in the target protein. In contrast to K-48-linked ubiquitination that leads to the proteosomal degradation of the target protein, K-63-linked polyubiquitin chains act as a scaffold to assemble protein kinase complexes and mediate their activation through proteosome-independent mechanisms. This K63 polyubiquitinated TRAF6 activates the TAK1 kinase complex. has a Stoichiometric coefficient of 3 TRIKA1 hp-IRAK1:oligo-TRAF6