Rub1 shares 53% homology with ubiquitin and requires activation via the E2 proteins, including Ula1, Uba3 and Ubc12, in order to conjugate to substrates directed to different proteolytic systems. UBE2D2 catalyzes ubiquitination of IkBa in a phosphorylation and SCFB-TRCP dependent manner. In this particular reaction, E1 first transfers ubiquitin to the E2 component UBE2D2, and UBE2D2 then associates with E3 ligase, which conjugates the poly-ubiquitin chain on a target protein. In this fashion, the chain tags the IkBa for degradation by a proteasome thus lifting the inhibitory effect of IkBa on NFkB and allowing NFkB to enter the nucleus.