E3 ubiquitin-protein ligase that is essential for proper development of the forebrain, the eye, and the face. Catalyzes monoubiquitination of serine/threonine-protein phosphatase 2A (PP2A) catalytic subunit PPP2CA/PPP2CB (By similarity). Negatively regulates nitric oxide production by inducing NOS1 and NOS3 translocation to actin cytoskeleton and inhibiting their enzymatic activity (PubMed:11149895, PubMed:15548660, PubMed:16135813). S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine. Interacts with NOS1 and NOS3 (PubMed:11149895, PubMed:15548660). Interacts with PP2A holoenzyme, containing PPP2CA, PPP2CB, PPP2R1A and PPP2R2A subunits (By similarity). Translocates from nucleus to cytoplasm in the G2 phase of the cell cycle (PubMed:16135813). Expressed in heart, brain and lung. Present in endothelial cells (at protein level). The U-box-like region is a truncated U-box domain. It is unknown whether it is functional or not. Belongs to the NOSIP family.