modified RING finger, H2 subclass (C3H2C2D-type), found in RING-box protein 1 (RBX1) and similar proteins
RBX1, also known as Hrt1, protein ZYP, RING finger protein 75 (RNF75), or regulator of cullins 1 (ROC1), is an E3 ubiquitin-protein ligase necessary for ubiquitin ligation activity of the multimeric cullin (Cul)-RING E3 ligases (CRLs). RBX1-containing CRLs are involved in NEDD8 pathway and RBX1 specifically regulate NEDD8ylation of Cul1-4. It can also bind and activate HIV-1 Vif-Cullin5 E3 ligase complex in vitro. Moreover, RBX1 is an essential element of Skp1/Cullins/F-box (SCF) E3-ubiquitin ligase complex that targets diverse proteins for proteasome-mediated degradation. It is a direct functional target of miR-194 and plays an important role in proliferation and migration of gastric cancer (GC) cells. RBX1 is also an essential component of KEAP1/CUL3/RBX1 E3-ubiquitin ligase complex that functions as a regulator of NFE2-related factor 2 (NRF2) and plays a key role in NRF2 pathway deregulation in multiple tumor types, including ovarian carcinomas (OVCA) and papillary thyroid carcinoma (PTC). Furthermore, RBX1 associates with DDB1, Cul4A, and Fbxw5 to form the Fbxw5-DDB1-Cul4A-Rbx1 complex that may function as a dual SUMO/ubiquitin ligase suppressing c-Myb activity through sumoylation or ubiquitination. RBX1 contains a C-terminal modified RING-H2 finger that is C3H2C2D-type, rather than the canonical C3H2C3-type. The modified RING-H2 finger is essential for its ligase activity.