The G protein-coupled receptor repertoires of human and mouse

Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4903-8. doi: 10.1073/pnas.0230374100. Epub 2003 Apr 4.

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Brain / metabolism
  • DNA, Complementary / genetics
  • GTP-Binding Proteins / genetics*
  • GTP-Binding Proteins / metabolism*
  • Gene Expression
  • Humans
  • In Situ Hybridization
  • Ligands
  • Mice
  • Molecular Sequence Data
  • Phylogeny
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Species Specificity

Substances

  • DNA, Complementary
  • Ligands
  • Receptors, Cell Surface
  • GTP-Binding Proteins

Associated data

  • GENBANK/AY255527
  • GENBANK/AY255528
  • GENBANK/AY255529
  • GENBANK/AY255530
  • GENBANK/AY255531
  • GENBANK/AY255532
  • GENBANK/AY255533
  • GENBANK/AY255534
  • GENBANK/AY255535
  • GENBANK/AY255536
  • GENBANK/AY255537
  • GENBANK/AY255538
  • GENBANK/AY255539
  • GENBANK/AY255540
  • GENBANK/AY255541
  • GENBANK/AY255542
  • GENBANK/AY255543
  • GENBANK/AY255544
  • GENBANK/AY255545
  • GENBANK/AY255546
  • GENBANK/AY255547
  • GENBANK/AY255548
  • GENBANK/AY255549
  • GENBANK/AY255550
  • GENBANK/AY255551
  • GENBANK/AY255552
  • GENBANK/AY255553
  • GENBANK/AY255554
  • GENBANK/AY255555
  • GENBANK/AY255556
  • GENBANK/AY255557
  • GENBANK/AY255558
  • GENBANK/AY255559
  • GENBANK/AY255560
  • GENBANK/AY255561
  • GENBANK/AY255562
  • GENBANK/AY255563
  • GENBANK/AY255564
  • GENBANK/AY255565
  • GENBANK/AY255566
  • GENBANK/AY255567
  • GENBANK/AY255568
  • GENBANK/AY255569
  • GENBANK/AY255570
  • GENBANK/AY255571
  • GENBANK/AY255572
  • GENBANK/AY255573
  • GENBANK/AY255574
  • GENBANK/AY255575
  • GENBANK/AY255576
  • GENBANK/AY255577
  • GENBANK/AY255578
  • GENBANK/AY255579
  • GENBANK/AY255580
  • GENBANK/AY255581
  • GENBANK/AY255582
  • GENBANK/AY255583
  • GENBANK/AY255584
  • GENBANK/AY255585
  • GENBANK/AY255586
  • GENBANK/AY255587
  • GENBANK/AY255588
  • GENBANK/AY255589
  • GENBANK/AY255590
  • GENBANK/AY255591
  • GENBANK/AY255592
  • GENBANK/AY255593
  • GENBANK/AY255594
  • GENBANK/AY255595
  • GENBANK/AY255596
  • GENBANK/AY255597
  • GENBANK/AY255598
  • GENBANK/AY255599
  • GENBANK/AY255600
  • GENBANK/AY255601
  • GENBANK/AY255602
  • GENBANK/AY255603
  • GENBANK/AY255604
  • GENBANK/AY255605
  • GENBANK/AY255606
  • GENBANK/AY255607
  • GENBANK/AY255608
  • GENBANK/AY255609
  • GENBANK/AY255610
  • GENBANK/AY255611
  • GENBANK/AY255612
  • GENBANK/AY255613
  • GENBANK/AY255614
  • GENBANK/AY255615
  • GENBANK/AY255616
  • GENBANK/AY255617
  • GENBANK/AY255618
  • GENBANK/AY255619
  • GENBANK/AY255620
  • GENBANK/AY255621
  • GENBANK/AY255622
  • GENBANK/AY255623