RWD domain-containing protein 3 (RWDD3)

RWD domain-containing protein 3 (RWDD3) is a mammalian regulatory protein defined by its RWD domain, a conserved sequence motif of approximately 110 amino acids involved in protein-protein binding[1][5]. RWDD3, also known as RSUME, functions primarily as an enhancer of SUMO conjugation by facilitating interactions between E1 (SAE2), E2 (UBE2I/UBC9), and target substrates, thereby increasing the sumoylation of specific proteins including HIF1A (a key factor in hypoxia response), NF-kappaB inhibitor alpha (NFKBIA, critical for inflammatory signaling), and glucocorticoid receptor NR3C1[2][3]. This regulatory activity impacts multiple cell signaling pathways, such as negative regulation of NF-kappaB activity, positive regulation of HIF1A, and modulation of glucocorticoid signaling. RWDD3 localizes to both the cytoplasm and nucleus, where it enables SUMOylation-dependent gene regulation and protein stabilization[2][4]. It is not an enzyme, receptor, or canonical drug target, but is of interest for therapeutic intervention via its indirect regulatory roles in inflammation, hypoxia/cancer, and possibly other diseases[3][2]. RWDD3 does not have a role in ubiquitination; its function is specific to SUMO modification machinery[2][3].

Other names

RSUMERWD domain-containing sumoylation enhancerDKFZP566K023RWD domain containing 3