super conserved receptor expressed in brain and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors
The SREB (super conserved receptor expressed in brain) subfamily consists of at least three members, named SREB1 (GPR27), SREB2 (GPR85), and SREB3 (GPR173). They are very highly conserved G protein-coupled receptors throughout vertebrate evolution, however no endogenous ligands have yet been identified. SREB2 is greatly expressed in brain regions involved in psychiatric disorders and cognition, such as the hippocampal dentate gyrus. Genetic studies in both humans and mice have shown that SREB2 influences brain size and negatively regulates hippocampal adult neurogenesis and neurogenesis-dependent cognitive function, all of which are suggesting a potential link between SREB2 and schizophrenia. All three SREB genes are highly expressed in differentiated hippocampal neural stem cells. Furthermore, all GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.
Comment:based on the structures of some class A family members with bound ligands (peptides or chemicals), agonists, or antagonists
Comment:Small-molecule chemical ligands tend to bind deeper within the receptor core, compared to a peptide ligand neurotensin, which binds towards the extracellular surface of its receptor.
Jiyao W et al.(2023). "The conserved domain database in 2023.",