title: The G protein-coupled receptor repertoires of human and mouse.
abstract: Diverse members of the G protein-coupled receptor (GPCR) superfamily participate in a variety of physiological functions and are major targets of pharmaceutical drugs. Here we report that the repertoire of GPCRs for endogenous ligands consists of 367 receptors in humans and 392 in mice. Included here are 26 human and 83 mouse GPCRs not previously identified. A direct comparison of GPCRs in the two species reveals an unexpected level of orthology. The evolutionary preservation of these molecules argues against functional redundancy among highly related receptors. Phylogenetic analyses cluster 60% of GPCRs according to ligand preference, allowing prediction of ligand types for dozens of orphan receptors. Expression profiling of 100 GPCRs demonstrates that most are expressed in multiple tissues and that individual tissues express multiple GPCRs. Over 90% of GPCRs are expressed in the brain. Strikingly, however, the profiles of most GPCRs are unique, yielding thousands of tissue- and cell-specific receptor combinations for the modulation of physiological processes.
authors.affiliation: Primal, Incorporated, 1124 Columbia Street, Seattle, WA 98104, USA. dkv@primalinc.com
authors.forename: Demetrios K
authors.initials: DK
authors.lastname: Vassilatis
authors.forename: John G
authors.initials: JG
authors.lastname: Hohmann
authors.forename: Hongkui
authors.initials: H
authors.lastname: Zeng
authors.forename: Fusheng
authors.initials: F
authors.lastname: Li
authors.forename: Jane E
authors.initials: JE
authors.lastname: Ranchalis
authors.forename: Marty T
authors.initials: MT
authors.lastname: Mortrud
authors.forename: Analisa
authors.initials: A
authors.lastname: Brown
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: Rodriguez
authors.forename: John R
authors.initials: JR
authors.lastname: Weller
authors.forename: Abbie C
authors.initials: AC
authors.lastname: Wright
authors.forename: John E
authors.initials: JE
authors.lastname: Bergmann
authors.forename: George A
authors.initials: GA
authors.lastname: Gaitanaris
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity
chemical_list: D018076:DNA, Complementary; D008024:Ligands; D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins