Urocortin III
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Urocortin III, a 38–41 amino acid peptide, is a member of the CRF (corticotropin-releasing factor), also known as CRH (corticotropin-releasing hormone)[1] family of peptides, with a long evolutionary lineage.[2][3]
Separate chromosomes harbouring two exons each are home to the genes encoding UCN, UCN2, and UCN3.[4] A gene on human chromosome 10p15 at location 5.40 Mb encodes the urocortin, UCN III, which has been discovered more recently. A 161 amino acid precursor is produced when the UCN III gene is translated.[5] Mature UCN III with 38 or 41 amino acids would be produced by proteolytic cleavage between arginine- or threonine-lysine residues. Human plasma contains both the 38 and 41 amino acid forms of UCN III, although the 38 amino acid form is more prevalent, according to findings from high-performance liquid chromatography.[2]
Each urocortin peptide has a distinct expression location and function, yet they all share conserved structural similarity.[4] Urocortins' structures, as determined by nuclear magnetic resonance, exhibit alpha-helical secondary structures, which support biological activity and binding selectivity.[6]
Multiple urocortin genes are present in vertebrate lineages as a result of the two waves of vertebrate whole-genome duplication.[7] Two ligands, the CRF/UCN1 and UCN2/UCN3 paralogs, and two receptors, CRFR1 and CRFR2, were produced by a first genome duplication in early vertebrates.[8][9] The CRF system observed in modern vertebrates, which has four ligands and two receptors, was then created by a second genome duplication that split the gene between UCN2 and UCN3 and between CRF and UCN1.[10] Two peptide genes were hypothesized to have been present in a vertebrate progenitor that gave rise to the different lineages that contained urocortin (UCN I), CRH1, and CRH2 in one group and urocortin II (UCN II) and urocortin III (UCN III ) in the other.[7]
In many vertebrates, there are five members of the corticotropin-releasing hormone and urocortin family of peptides: CRH (crha/crhb in teleosts), CRH2, UCN/UTS1, UCN II, and UCN III.[11] The two receptors, CRFR1 and CRFR2, and the four ligands, CRF, Urocortin1 (UCN1), UCN2, and UCN3, make up the mammalian CRF system.[12] Genes for mentioned proteins can perform a multitude of tasks in a wide range of animals due to differences in their expression patterns and receptor affinities.[11]
Urocortin affinity to receptors
Compared to UCN II or UCN III, UCN I has a greater binding affinity for the CRHR1 receptor.[6] Urocortin III is extremely selective for the CRF2 receptor, in contrast to Urocortin I and comparable to Urocortin II.[5] Of the two closely related CRF receptors (CRFR1 and CRFR2) that are members of the class B family of G protein-coupled receptors, each peptide activates at least one of them.[13] CRFR2 can be effectively activated by UCN II and UCN III.[2][14] By attaching itself to CRHR2 with a strong affinity, this peptide (UCNIII) helps regulate a number of bodily processes.[15] All things considered, UCNs have approximately ten times more affinity for CRHR2 than CRH.[16]