stabilize the core clock mechanism, helping to buffer it against changes in the environment. Mechanism Specific association with ROR elements (RORE) in regulatory regions is necessary for RORα's function as a transcriptional activator. RORα achieves this by specific binding to a consensus core motif in RORE, RGGTCA. This interaction is possible through the association of RORα's first zinc finger with the core motif in the major groove, the P-box, and the association of its C-terminal extension with the AT-rich region in the 5’ region of RORE. Homology RORα, RORβ, and RORγ are all transcriptional activators recognizing ROR-response elements. ROR-alpha is expressed in a variety of cell types and is involved in regulating several aspects of development, inflammatory responses, and lymphocyte development. The RORα isoforms (RORα1 through RORα3) arise via alternative RNA processing, with RORα2 and RORα3 sharing an amino-terminal region different from RORα1. In contrast to RORα, RORβ is expressed in Central Nervous System (CNS) tissues involved in processing sensory information and in generating circadian rhythms while RORγ is critical in lymph node organogenesis and thymopoeisis. The DNA-binding domains of the DHR3 orphan receptor in Drosophila shows especially close homology within amino and carboxy regions adjacent to the second zinc finger region in RORα, suggesting that this group of residues is important for the proteins' functionalities. PDP1 and VRI in Drosophila regulate circadian rhythm's by competing for the same binding site, the VP box, similarly to how ROR and REV-ERB competitively bind to RRE. PDP1 and VRI constitute a feedback loop and are functional homologs of ROR and REV-ERB in mammals. Direct orthologs of this gene have been identified in mice and humans. Human cytochrome c pseudogene HC2 and RORα share overlapping genomic organization with the HC2 pseudogene located within the RORα2 transcription unit. The nucleotide and deduced amino acid sequences of cytochrome c-processed pseudogene are on the sense strand while those of the RORα2 amino-terminal exon are on the antisense strand. Interactions DNA: RORα binds to the P-box of the RORE. Co-activators: SRC-1, CBP, p300, TRIP-l, TRIP-230, transcription intermediary protein-1 (TIF-1), peroxisome proliferator-binding protein (PBP), and GRIP-1 physically interact with RORα. LXXLL motif: ROR interacts with SRC-1, GRIP-l, CBP, and p300 via the LXXLL (L=Leucine, X=any amino acid) motifs on these proteins. Ubiquitination: RORα is targeted for the proteasome by ubiquitination. A co-repressor, Hairless, stabilizes RORα by protecting it from this process, which also represses RORα. Sumoylation: UBE21/UBC9: Ubiquitin-conjugating