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 (PubMed:25546391). Negatively regulates nitric oxide production by inducing NOS1 and NOS3 translocation to actin cytoskeleton and inhibiting their enzymatic activity (By similarity). 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. Protein modification; protein ubiquitination. Interacts with NOS1 and NOS3 (By similarity). Interacts with PP2A holoenzyme, containing PPP2CA, PPP2CB, PPP2R1A and PPP2R2A subunits (PubMed:25546391). Translocates from nucleus to cytoplasm in the G2 phase of the cell cycle. The U-box-like region is a truncated U-box domain. It is unknown whether it is functional or not. Although mutant embryos are present at the expected Mendelian rate at 18.5 dpc, they die shortly after birth with signs of respiratory distress and cyanosis, likely due to craniofacial malformations. Malformations in knockout mice range from ocular hypotelorism, narrow snout, laterally cleft lip, and cleft secondary palate to cyclopia and presence of proboscis or a single head-like protrusion devoid of facial features. In addition, the weight of knockout embryos is significantly reduced. In knockout animals, PP2A activity is increased in palatal and facial tissues as compared to wild-type, but not in lungs, which do not seem to be affected by the mutation. Belongs to the NOSIP family.