The CRFR (Corticotropin-releasing Factor Receptor, CRHR) belongs to the G-coupled receptor superfamily. Two receptor subtypes, CRF1 receptor and CRF2 receptor, and several splice variants for both receptor subtypes have been discovered. CRF itself has a greater affinity for CRF1 receptors while urocortin 1 (Ucn 1) binds with high affinity to both receptors and Ucn 2 and Ucn 3 both preferentially bind to CRF2 receptors.
Two CRF receptor subtypes are encoded by distinct genes which exhibit diverse alternative pre-mRNA splicing patterns resulting in multiple variants derived from partial or total exon deletions or insertions. With regard to the nine human CRF1 variants, CRF1a-i, described, CRF1a being the main wild type functional receptor while the other isoforms may modulate CRF signaling. For the CRF2, three functionally active splice variants, CRF2a-c, have been described in humans.