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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29611544   1 ATSCYERMFYGHVLKRFRQPNFARTMCIYIWGVVLVIIIPVTLYYSVVEATEEGQSQCYNRQMELGARPSQIAGLIGTTF 80
Cdd:cd14996 115 KQSCYEKIFYGHFLKRFRQPKFARYLCIYIWGVVLCIIIPVVVYYSVREADEDGESLCYNRQVELGAKGSQIAGLIATTF 194

                        90       100
                ....*....|....*....|....
gi 29611544  81 IGFSFLVVVTSYYSLVSHLRRVRT 104
Cdd:cd14996 195 FFLFFLVVLLSYYSFVNHLRRIQK 218

orphan G protein-coupled receptor 82, member of the class A family of seven-transmembrane G protein-coupled receptors; This subgroup represents the G-protein coupled receptor 82 of unknown function. GPR82 is a member of the rhodopsin-like, class A GPCRs, which is a widespread protein family that includes the light-sensitive rhodopsin as well as receptors for biogenic amines, lipids, nucleotides, odorants, peptide hormones, and a variety of other ligands. 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        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29611544   1 ATSCYERMFYGHVLKRFRQPNFARTMCIYIWGVVLVIIIPVTLYYSVVEATEEGQSQCYNRQMELGARPSQIAGLIGTTF 80
Cdd:cd14996 115 KQSCYEKIFYGHFLKRFRQPKFARYLCIYIWGVVLCIIIPVVVYYSVREADEDGESLCYNRQVELGAKGSQIAGLIATTF 194

                        90       100
                ....*....|....*....|....
gi 29611544  81 IGFSFLVVVTSYYSLVSHLRRVRT 104
Cdd:cd14996 195 FFLFFLVVLLSYYSFVNHLRRIQK 218

orphan G protein-coupled receptor 82, member of the class A family of seven-transmembrane G protein-coupled receptors; This subgroup represents the G-protein coupled receptor 82 of unknown function. GPR82 is a member of the rhodopsin-like, class A GPCRs, which is a widespread protein family that includes the light-sensitive rhodopsin as well as receptors for biogenic amines, lipids, nucleotides, odorants, peptide hormones, and a variety of other ligands. 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        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29611544   1 ATSCYERMFYGHVLKRFRQPNFARTMCIYIWGVVLVIIIPVTLYYSVVEATEEGQSQCYNRQMELGARPSQIAGLIGTTF 80
Cdd:cd14996 115 KQSCYEKIFYGHFLKRFRQPKFARYLCIYIWGVVLCIIIPVVVYYSVREADEDGESLCYNRQVELGAKGSQIAGLIATTF 194

                        90       100
                ....*....|....*....|....
gi 29611544  81 IGFSFLVVVTSYYSLVSHLRRVRT 104
Cdd:cd14996 195 FFLFFLVVLLSYYSFVNHLRRIQK 218

opioid receptors and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes opioid receptors, somatostatin receptors, melanin-concentrating hormone receptors (MCHRs), and neuropeptides B/W receptors. Together they constitute the opioid receptor-like family, members of the class A G-protein coupled receptors. Opioid receptors are coupled to inhibitory G proteins of the G(i/o) family and are involved in regulating a variety of physiological functions such as pain, addiction, mood, stress, epileptic seizure, and obesity, among many others. G protein-coupled somatostatin receptors (SSTRs), which display strong sequence similarity with opioid receptors, binds somatostatin (somatotropin release inhibiting factor), a polypeptide hormone that regulates a wide variety of physiological functions such as neurotransmission, cell proliferation, contractility of smooth muscle cells, and endocrine signaling as well as inhibition of the release of many secondary hormones. MCHR binds melanin concentrating hormone and is presumably involved in the neuronal regulation of food intake. Despite strong homology with somatostatin receptors, MCHR does not appear to bind somatostatin. Neuropeptides B/W receptors are primarily expressed in the CNS and stimulate the cortisol secretion by activating the adenylate cyclase- and the phospholipase C-dependent signaling pathways.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29611544  16 RFRQPNFARTMCIYIWGVVLVIIIPVTLYYSVVEAtEEGQSQCynrQMELGARPSQIAGL--IGTTFIGFS--FLVVVTS 91
Cdd:cd14970 109 RFRTPRKAKLVSLCVWALSLVLGLPVIIFARTLQE-EGGTISC---NLQWPDPPDYWGRVftIYTFVLGFAvpLLVITVC 184

                        90
                ....*....|..
gi 29611544  92 YYSLVSHLRRVR 103
Cdd:cd14970 185 YSLIIRRLRSSR 196

angiotesin receptor family and its related G protein-coupled receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes the angiotensin receptors, the bradykinin receptors, apelin receptor as well as putative G-protein coupled receptors (GPR15 and GPR25). Angiotensin II (Ang II), the main effector in the renin-angiotensin system, plays a crucial role in the regulation of cardiovascular homeostasis through its type 1 (AT1) and type 2 (AT2) receptors. Ang II contributes to cardiovascular diseases such as hypertension and atherosclerosis via AT1R activation. Ang II increases blood pressure through Gq-mediated activation of phospholipase C, resulting in phosphoinositide (PI) hydrolysis and increased intracellular calcium levels. Through the AT2 receptor, Ang II counteracts the vasoconstrictor action of AT1R and thereby induces vasodilation, sodium excretion, and reduction of blood pressure. Bradykinins (BK) are pro-inflammatory peptides that mediate various vascular and pain responses to tissue injury through its B1 and B2 receptors. Apelin (APJ) receptor binds the endogenous peptide ligands, apelin and Toddler/Elabela. APJ is an adipocyte-derived hormone that is ubiquitously expressed throughout the human body, and Toddler/Elabela is a short secretory peptide that is required for normal cardiac development in zebrafish. Activation of APJ receptor plays key roles in diverse physiological processes including vasoconstriction and vasodilation, cardiac muscle contractility, angiogenesis, and regulation of water balance and food intake. Orphan receptors, GPR15 and GPR25, share strong sequence homology to the angiotensin II type AT1 and AT2 receptors.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29611544  15 KRFRQPNFARTMCIYIWGVVLVIIIPVTLYYSVVEATEEGQSQCYnrqMELGARPSQIAGLIGTTFIGF--SFLVVVTSY 92
Cdd:cd14985 109 RRLRRRRQARVTCALIWVVACLLSLPTFLLRSLQAIENLNKTACI---MLYPHEAWHFGLSLELNILGFvlPLLIILTCY 185

                ....*....
gi 29611544  93 YSLVSHLRR 101
Cdd:cd14985 186 FHIARSLRK 194