Orphan nuclear receptor of retinal photoreceptor cells. Transcriptional factor that is an activator of rod development and repressor of cone development. Binds the promoter region of a number of rod- and cone-specific genes, including rhodopsin, M- and S-opsin and rod-specific phosphodiesterase beta subunit. Enhances rhodopsin expression. Represses M- and S-cone opsin expression. Homodimer. Interacts with PIAS3; the interaction sumoylates NR2E3 and promotes repression of cone-specific gene transcription and activation of rod-specific genes. Component of a rod photoreceptor complex that includes NR2E3, PIAS3, NRL, CRX and/or NR1D1. Binds directly in the complex with CRX, PIAS3 and NR1D1 (By similarity). Interacts (via the DNA-binding domain) with CRX (via its DNA binding domain); the interaction represses S- and M-cone opsin expression. Retina. Rod-specific. Expressed in the outer nuclear lyer of the mature retina. Expression found as early as 18 dpc in developing retina. From P3 to P6, expression increases in developing rods. Expression, thereafter, in the future inner nuclear layer migrating to the final destination of the outer nuclear layer. In the mature retina, exclusively expressed in rods. Di- and tri-sumoylated in developing retina. PIAS3-mediated sumoylation promotes repression of cone-specific gene expression and activation of rod-specific genes. Sumoylation on Lys-178 appears to be the main site. Defects in Nr2e3 are the cause of the retinal degeneration type 7 (Rd7) phenotype characterized by excessive blue cones and loss of rods. Belongs to the nuclear hormone receptor family. NR2 subfamily.