{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Xu B"],"funding":["Tongji University","National Natural Science Foundation of China","National Key Research and Development Program of China"],"pagination":["630-640"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10928900"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7(3)"],"pubmed_abstract":["Melanocortin-4 receptor (MC4R) functions as a crucial neuroendocrine G protein-coupled receptor (GPCR) in the central nervous system of mammals, displaying agonist-independent constitutive activity that is mainly determined by its N-terminal domain. We previously reported that zebrafish MC4R exhibited a much higher basal cAMP level in comparison to mammalian MC4Rs. However, the functional evolution of constitutive activities in chordate MC4Rs remains to be elucidated. Here we cloned and compared the constitutive activities of MC4Rs from nine vertebrate species and showed that the additive action of the N-terminus with the extracellular region or transmembrane domain exhibited a combined pharmacological effect on the MC4R constitutive activity. In addition, we demonstrated that four residue"],"journal":["ACS pharmacology & translational science"],"pubmed_title":["Evolutionary Identification of the Requirement of the Second Intracellular Loop for the Constitutive Activity of Melanocortin-4 Receptors."],"pmcid":["PMC10928900"],"funding_grant_id":["32271165","2022-2-ZD-02","2019YFA0111400"],"pubmed_authors":["Yao J","Li J","Liu L","Fu Y","Ma Z","Yan X","Li L","Zhu M","Li Y","Lyu J","Xu B","Zhang C","Song W"],"additional_accession":[]},"is_claimable":false,"name":"Evolutionary Identification of the Requirement of the Second Intracellular Loop for the Constitutive Activity of Melanocortin-4 Receptors.","description":"Melanocortin-4 receptor (MC4R) functions as a crucial neuroendocrine G protein-coupled receptor (GPCR) in the central nervous system of mammals, displaying agonist-independent constitutive activity that is mainly determined by its N-terminal domain. We previously reported that zebrafish MC4R exhibited a much higher basal cAMP level in comparison to mammalian MC4Rs. However, the functional evolution of constitutive activities in chordate MC4Rs remains to be elucidated. Here we cloned and compared the constitutive activities of MC4Rs from nine vertebrate species and showed that the additive action of the N-terminus with the extracellular region or transmembrane domain exhibited a combined pharmacological effect on the MC4R constitutive activity. In addition, we demonstrated that four residue","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-06-02T04:10:33.093Z","creation":"2025-04-19T21:16:05.021Z"},"accession":"S-EPMC10928900","cross_references":{"pubmed":["38481681"],"doi":["10.1021/acsptsci.3c00169"]}}