In the nucleus, cellular retinoic acid binding protein 2 (CRABP2), bound to all trans retinoic acid (atRA), directly binds to heterodimeric nuclear retinoic acid receptors (RAR:RXR) to form a complex through which atRA is channeled from the binding protein to RAR (Majumdar et al. 2011). The RAR:RXR heterodimer can be formed between any of three receptor isoforms for each; RARA, RARB, or RARG with RXRA, RXRB, or RXRG (Neiderreither and Dolle 2008). RARA requires sumoylation and phosphorylation for ligand binding and nuclear localisation (Zhu et al. 2009, Santos & Kim 2010).
RAR:RXR bind to their RA response elements (RARE, composed of tandem direct repeats of 5'-AGGTCA-3' spaced by either 2 bp or 5 bp (DR2, DR5) in response to their physiological ligand atRA, and regulate gene expression in various biological processes.