The G protein-coupled receptor repertoires of human and mouse.
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.
Vassilatis
Demetrios K
DK
Primal, Incorporated, 1124 Columbia Street, Seattle, WA 98104, USA. dkv@primalinc.com
Hohmann
John G
JG
Zeng
Hongkui
H
Li
Fusheng
F
Ranchalis
Jane E
JE
Mortrud
Marty T
MT
Brown
Analisa
A
Rodriguez
Stephanie S
SS
Weller
John R
JR
Wright
Abbie C
AC
Bergmann
John E
JE
Gaitanaris
George A
GA
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
D018076:DNA, Complementary; D008024:Ligands; D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins