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

olfactory receptors.

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

Latrotoxin

Family C. Metabotropic neurotransmitter/

Calcium receptors

Metabotropic glutamate receptors

Metabotropic GABA receptors

Calcium receptors

Vomeronasal pheromone receptors

Taste receptors

FIGURE 30-6

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

indicated

( 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

21,

92 (2000).]