RWD domain-containing protein 3 (RWDD3)

Enhancer of SUMO conjugation.

Via its interaction with UBE2I/UBC9, raises SUMO conjugation to proteins by promoting the binding of E1 and E2 enzymes, thioester linkage between SUMO and UBE2I/UBC9 and transfer of SUMO to specific target proteins including HIF1A, PIAS, NFKBIA, NR3C1 and TOP1.

Isoform 1 and isoform 2 positively regulate the NF-kappa-B signaling pathway by enhancing the sumoylation of NF-kappa-B inhibitor alpha (NFKBIA), promoting its stabilization which consequently leads to an increased inhibition of NF-kappa-B transcriptional activity. Isoform 1 and isoform 2 negatively modulate the hypoxia-inducible factor-1 alpha (HIF1A) signaling pathway by increasing the sumoylation of HIF1A, boosting its own insertion, transcriptional activity and the expression of its target gene VEGFA during hypoxia.