seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary model represents the seven-transmembrane (7TM) receptors, often referred to as G protein-coupled receptors (GPCRs), which transmit physiological signals from the outside of the cell to the inside via G proteins. GPCRs constitute the largest known superfamily of transmembrane receptors across the three kingdoms of life that respond to a wide variety of extracellular stimuli including peptides, lipids, neurotransmitters, amino acids, hormones, and sensory stimuli such as light, smell and taste. All GPCRs share a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes. However, some 7TM receptors, such as the type 1 microbial rhodopsins, do not activate G proteins. Based on sequence similarity, GPCRs can be divided into six major classes: class A (the rhodopsin-like family), class B (the Methuselah-like, adhesion and secretin-like receptor family), class C (the metabotropic glutamate receptor family), class D (the fungal mating pheromone receptors), class E (the cAMP receptor family), and class F (the frizzled/smoothened receptor family). Nearly 800 human GPCR genes have been identified and are involved essentially in all major physiological processes. Approximately 40% of clinically marketed drugs mediate their effects through modulation of GPCR function for the treatment of a variety of human diseases including bacterial infections.

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gi 7656843    6 VVSFFSLKSDSAPPWMVLAVLWCSMAQTLLLPSFIWSCERYRADVR 51
Cdd:cd14998 256 VVSFSSLKADAAPPWMVLCVLWCSMAQTLLLPSFLWSCERYRADVK 301

orphan G protein-coupled receptors 153 and 162, member of the class A family of seven-transmembrane G protein-coupled receptors; This group contains the G-protein coupled receptor 153 (GPR153), GPR162, and similar proteins. These are orphan GCPRs with unknown endogenous ligand and function. GPR153 and GPR163 are widely expressed in the central nervous system (CNS) and share a common evolutionary ancestor due to a gene duplication event. Although categorized as members of the rhodopsin-like class A GPCRs, both GPR162 and GPR153 contain an HRM-motif instead of the highly conserved Asp-Arg-Tyr (DRY) motif found in the third transmembrane helix (TM3) of class A receptors which is important for efficient G protein-coupled signal transduction. Moreover, the LPxF motif, a variant of NPxxY motif that plays a crucial role during receptor activation, is found at the end of TM7 in both GPR162 and GPR153. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

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                ....*....|....*....|....*....|....*....|....*.
gi 7656843    6 VVSFFSLKSDSAPPWMVLAVLWCSMAQTLLLPSFIWSCERYRADVR 51
Cdd:cd14998 256 VVSFSSLKADAAPPWMVLCVLWCSMAQTLLLPSFLWSCERYRADVK 301

orphan G protein-coupled receptors 153 and 162, member of the class A family of seven-transmembrane G protein-coupled receptors; This group contains the G-protein coupled receptor 153 (GPR153), GPR162, and similar proteins. These are orphan GCPRs with unknown endogenous ligand and function. GPR153 and GPR163 are widely expressed in the central nervous system (CNS) and share a common evolutionary ancestor due to a gene duplication event. Although categorized as members of the rhodopsin-like class A GPCRs, both GPR162 and GPR153 contain an HRM-motif instead of the highly conserved Asp-Arg-Tyr (DRY) motif found in the third transmembrane helix (TM3) of class A receptors which is important for efficient G protein-coupled signal transduction. Moreover, the LPxF motif, a variant of NPxxY motif that plays a crucial role during receptor activation, is found at the end of TM7 in both GPR162 and GPR153. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

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                ....*....|....*....|....*....|....*....|....*.
gi 7656843    6 VVSFFSLKSDSAPPWMVLAVLWCSMAQTLLLPSFIWSCERYRADVR 51
Cdd:cd14998 256 VVSFSSLKADAAPPWMVLCVLWCSMAQTLLLPSFLWSCERYRADVK 301

orphan G protein-coupled receptor 153, member of the class A family of seven-transmembrane G protein-coupled receptors; This subgroup represents the G-protein coupled receptor 153 (GPR153) with unknown endogenous ligand and function. GPR153 shares a common evolutionary origin with GPR162 and is highly expressed in central nervous system (CNS) including the thalamus, cerebellum, and the arcuate nucleus. Although categorized as a member of the rhodopsin-like class A GPCRs, GPR153 contains HRM-motif instead of the highly conserved Asp-Arg-Tyr (DRY) motif found in the third transmembrane helix (TM3) of class A receptors and important for efficient G protein-coupled signal transduction. Moreover, the LPxFL motif, a variant of NPxxY motif that plays a crucial role during receptor activation, is found at the end of TM7 in GPR153. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 7656843    6 VVSFFSLKSDSAPPWMVLAVLWCSMAQTLLLPSFIWSCERYRADVR 51
Cdd:cd15907 256 VVSFASLKADKSYNWMVLCVLWCSVAQSLLLPMFLWACDRYRADIK 301