Ubiquitin-conjugating enzyme 13 (Ubc13) was initially discovered in S. cerevisiae as a DNA-damage inducible protein involved in the error-free DNA postreplication repair pathway. It has recently been shown to be an important component of the Toll-like receptor and IL-1R signaling pathway. Signals from these pathways are relayed by a number of downstream molecules such as MyD88 and tumor necrosis factor receptor associated factor (TRAF6), ultimately activating various kinases and transcription factors. Ubc13 is part of a dimeric ubiquitin-conjugating enzyme complex also containing UEV1A (ubiquitin-conjugating enzyme E2 variant 1) that together with TRAF6 activates TAK1, a member of the mitogen-activated protein kinase kinase kinase family. The Ubc13-UEV1A complex also mediates the Lys-63 ubiquitination of TRAF-6, and this ubiquitination is essential for TAK1 activation.