Reactome: A Curated Pathway Database

Auto-ubiquitination of TRAF6

Stable Identifier
Homo sapiens
Locations in the PathwayBrowser

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.

Literature References
Participant Of
This entity is regulated by:
Title Physical Entity Activity
ubiquitin-protein transferase activity of TRAF6 trimer bound to CBM complex [plasma membrane] TRAF6 trimer bound to CBM complex [plasma membrane] ubiquitin-protein transferase activity (0004842)
Orthologous Events