Family A. Rhodopsin/f}2 adrenergic receptor-like
Biogenic amine receptors (adrenergic, serotonin,
dopamine, muscarinic, histamine)
CCK, endothelin, tachykinin, neuropeptide Y, TRH, neurotensin,
bombesin, and growth hormone secretagogues receptors
plus vertebrate opsins
Invertebrate opsins and bradykinn receptors
Adenosine, cannabinoid, melanocortin, and
Chemokine, fMLP, CSA, GnRH, eicosanoid, leukotriene,
FSH, LH, TSH, fMLP, galanin, nucleotide, opioid, oxytocin,
vasopressin, somatostatin, and protease-activated
receptors plus others.
Melatonin receptors and other non-dassified
Family B. Glucagon/VIP/Calcitonin receptor-like
Calcitonin, CGRP and CRF receptors
PTH and PTHrP receptors
Glucagon, glucagon-like peptide, GIP, GHRH, PACAP, VIP,
and secretin receptors
Family C. Metabotropic neurotransmitter/
Metabotropic glutamate receptors
Metabotropic GABA receptors
Vomeronasal pheromone receptors
G-protein-coupled seven-transmembrane receptors (GPCR). These can be divided into three major subfamilies (1). A
snake diagram for a prototypic member of each subfamily is shown. Family A receptor
( u p p e r p a n e l )
can be subdivided
phylogenetically into six subgroups as indicated. Family A receptors are characterized by a series of highly conserved
key residues (
b l a c k l e t t e r i n w h i t e c i r c l e s ) .
In most family A receptors a disulfide bridge connects the second (ECL2)
and third extracellular loops (ECL3)
( w h i t e l e t t e r s i n b l a c k c i r c l e s ) .
In addition, a majority of the receptors have a
palmitoylated cysteine in the carboxy terminal tail causing formation of a putative fourth intracellular loop.
Family B receptors
( m i d d l e p a n e l )
are characterized by a long amino terminus containing several cysteines that form
a network of disulfide bridges. The B receptors contain, like the A receptors, a disulfide bridge connecting ECL2 and
ECL3. However, the palmitoylation site is missing. Moreover, the conserved prolines are different from the conserved
prolines in the A receptors and the DRY motif at the bottom of TM 3 is absent.
Family C receptors
( l o w e r p a n e l )
are characterized by a very long amino terminus (~600 amino acids). The amino
terminal domain contains the ligand binding site. Except for two cysteines that form a putative disulfide bridge, the C
receptors do not have any of the key features characterizing A and B receptors. Some highly conserved residues are
( b l a c k l e t t e r i n w h i t e c i r c l e s ) .
A unique characteristic of the C receptors is a very short and highly conserved
third intracellular loop. [Reproduced with permission from U. Gether,
E n d o c r i n e R e v i e w s