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
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 77025068   1 LVTGWSLAFLAFERYVVICKPFGNFRFSSKHALMVVLATWTIGIGVSIPPFFGWSR 56
Cdd:cd15076  85 LVTGWSLAFLAFERYIVICKPFGNFRFGSKHALGAVVATWIIGIGVSLPPFFGWSR 140

short wave-sensitive 1 opsins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes Short Wave-Sensitive opsin 1 (SWS1), which mediates visual transduction in response to light at short wavelengths (ultraviolet to blue). Vertebrate cone opsins are expressed in cone photoreceptor cells of the retina and involved in mediating photopic vision, which allows color perception. The cone opsins can be classified into four classes according to their peak absorption wavelengths: SWS1 (ultraviolet sensitive), SWS2 (short wave-sensitive), MWS/LWS (medium/long wave-sensitive), and RH2 (medium wave-sensitive, rhodopsin-like opsins). Members of this group belong to the class A of the G protein-coupled receptors and possess seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 77025068   1 LVTGWSLAFLAFERYVVICKPFGNFRFSSKHALMVVLATWTIGIGVSIPPFFGWSR 56
Cdd:cd15076  85 LVTGWSLAFLAFERYIVICKPFGNFRFGSKHALGAVVATWIIGIGVSLPPFFGWSR 140

short wave-sensitive 1 opsins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes Short Wave-Sensitive opsin 1 (SWS1), which mediates visual transduction in response to light at short wavelengths (ultraviolet to blue). Vertebrate cone opsins are expressed in cone photoreceptor cells of the retina and involved in mediating photopic vision, which allows color perception. The cone opsins can be classified into four classes according to their peak absorption wavelengths: SWS1 (ultraviolet sensitive), SWS2 (short wave-sensitive), MWS/LWS (medium/long wave-sensitive), and RH2 (medium wave-sensitive, rhodopsin-like opsins). Members of this group belong to the class A of the G protein-coupled receptors and possess seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 77025068   1 LVTGWSLAFLAFERYVVICKPFGNFRFSSKHALMVVLATWTIGIGVSIPPFFGWSR 56
Cdd:cd15076  85 LVTGWSLAFLAFERYIVICKPFGNFRFGSKHALGAVVATWIIGIGVSLPPFFGWSR 140

medium wave-sensitive opsins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes Medium Wave-Sensitive opsin, which mediates visual transduction in response to light at medium wavelengths (green). Vertebrate cone opsins are expressed in cone photoreceptor cells of the retina and involved in mediating photopic vision, which allows color perception. The cone opsins can be classified into four classes according to their peak absorption wavelengths: SWS1 (ultraviolet sensitive), SWS2 (short wave-sensitive), MWS/LWS (medium/long wave-sensitive), and RH2 (medium wave-sensitive, rhodopsin-like opsins). Members of this group belong to the class A of the G protein-coupled receptors and possess seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 77025068   5 WSLAFLAFERYVVICKPFGNFRFSSKHALMVVLATWTIGIGVSIPPFFGWSR 56
Cdd:cd15080  89 WSLVVLAIERYVVVCKPMSNFRFGENHAIMGVAFTWVMALACAAPPLVGWSR 140

non-visual pinopsins, member of the class A family of seven-transmembrane G protein-coupled receptors; Pinopsins are found in the pineal organ of birds, reptiles and amphibians, but are absent from teleosts and mammals. The vertebrate non-visual opsin family includes pinopsins, parapinopsin, VA (vertebrate ancient) opsins, and parietopsins. These non-visual opsins are expressed in various extra-retinal tissues and/or in non-rod, non-cone retinal cells. They are thought to be involved in light-dependent physiological functions such as photo-entrainment of circadian rhythm, photoperiodicity and body color change. Pinopsins belong the class A of the G protein-coupled receptors and possess seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 77025068   5 WSLAFLAFERYVVICKPFGNFRFSSKHALMVVLATWTIGIGVSIPPFFGWS 55
Cdd:cd15084  99 WSLAILAFERYLVICKPMGDFRFQQRHAVSGCAFTWGWSLLWTSPPLFGWS 149

long wave-sensitive opsins, member of the class A family of seven-transmembrane G protein-coupled receptors; Long Wave-Sensitive opsin is also called red-sensitive opsin or red cone photoreceptor pigment, which mediates visual transduction in response to light at long wavelengths. Vertebrate cone opsins are expressed in cone photoreceptor cells of the retina and involved in mediating photopic vision, which allows color perception. The cone opsins can be classified into four classes according to their peak absorption wavelengths: SWS1 (ultraviolet sensitive), SWS2 (short wave-sensitive), MWS/LWS (medium/long wave-sensitive), and RH2 (medium wave-sensitive, rhodopsin-like opsins). Members of this group belong to the class A of the G protein-coupled receptors and possess seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 77025068   5 WSLAFLAFERYVVICKPFGNFRFSSKHALMVVLATWTIGIGVSIPPFFGWSR 56
Cdd:cd15081 101 WSLTIISWERWVVVCKPFGNIKFDGKLAIVGIIFSWVWSAVWCAPPIFGWSR 152

non-visual parapinopsin, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes the non-visual pineal pigment, parapinopsin, which is a member of the class A of the seven transmembrane G protein-coupled receptors. Parapinopsin serves as a UV-sensitive pigment for the wavelength discrimination in the pineal-related organs of lower vertebrates such as reptiles, amphibians, and fish. Although parapinopsin is phylogenetically related to vertebrate visual pigments such as rhodopsin, which releases its retinal chromophore and bleaches, the parapinopsin photoproduct is stable and does not bleach. The vertebrate non-visual opsin family includes pinopsins, parapinopsin, VA (vertebrate ancient) opsins, and parietopsins. These non-visual opsins are expressed in various extra-retinal tissues and/or in non-rod, non-cone retinal cells.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 77025068   6 SLAFLAFERYVVICKPFGNFRFSSKHALMVVLATWTIGIGVSIPPFFGWSR 56
Cdd:cd15075  90 TVAVIAVDRLFVVCKPLGTLTFQTRHALAGIASSWLWSLIWNTPPLFGWGS 140

invertebrate Gq opsins, member of the class A family of seven-transmembrane G protein-coupled receptors; The invertebrate Gq-coupled opsin subfamily includes the arthropod and mollusc visual opsins. Like the vertebrate visual opsins, arthropods possess color vision by the use of multiple opsins sensitive to different light wavelengths. The invertebrate Gq opsins are closely related to the vertebrate melanopsins, the primary photoreceptor molecules for non-visual responses to light, and the R1-R6 photoreceptors, which are the fly equivalent to the vertebrate rods. The Gq opsins belong the class A of the G protein-coupled receptors and possess seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 77025068   6 SLAFLAFERYVVICKPFGNFR-FSSKHALMVVLATWTIGIGVSIPPFFGWSR 56
Cdd:cd15337  91 TLAAISIDRYLVIAKPLEAMKkMTFKRAFIMIIIIWLWSLLWSIPPFFGWGR 142

neuropsin (Opsin-5), member of the class A family of seven-transmembrane G protein-coupled receptors; Neuropsin, also known as Opsin-5, is a photoreceptor protein expressed in the retina, brain, testes, and spinal cord. Neuropsin belongs to the type 2 opsin family of the class A G-protein coupled receptors. Mammalian neuropsin activates Gi protein-mediated photo-transduction pathway in a UV-dependent manner, whereas, in non-mammalian vertebrates, neuropsin is involved in regulating the photoperiodic control of seasonal reproduction in birds such as quail. As with other opsins, it may also act as a retinal photoisomerase.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 77025068   1 LVTGWSLAFLAFERYVVICKPFGNFRFSSKHALMVVLATWTIGIGVSIPPFFGWSR 56
Cdd:cd15074  85 CCSINTLTAISIYRYLKICHPPYGPKLSRRHVCIVIVAIWLYALFWAVAPLVGWGS 140

vertebrate melanopsins (Opsin-4), member of the class A family of seven-transmembrane G protein-coupled receptors; Melanopsin (also called Opsin-4) is the G protein-coupled photopigment that mediates non-visual responses to light. In mammals, these photoresponses include the photo-entrainment of circadian rhythm, pupillary constriction, and acute nocturnal melatonin suppression. Mammalian melanopsins are expressed only in the inner retina, whereas non-mammalian vertebrate melanopsins are localized in various extra-retinal tissues such as iris, brain, pineal gland, and skin. Melanopsins belong the class A of the G protein-coupled receptors and possess seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 77025068   6 SLAFLAFERYVVICKPFGNFRFSSKH-ALMVVLATWTIGIGVSIPPFFGWS 55
Cdd:cd15336  90 TLLAISLDRYLVITKPLASIRWVSKKrAMIIILLVWLYSLAWSLPPLFGWS 140

relaxin family peptide receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes relaxin/insulin-like family peptide receptor 1 (RXFP1 or LGR7) and 2 (RXFP2 or LGR8), which contain a very large extracellular N-terminal domain with numerous leucine-rich repeats responsible for hormone recognition and binding. Relaxin is a member of the insulin superfamily that has diverse actions in both reproductive and non-reproductive tissues. The relaxin-like peptide family includes relaxin-1, relaxin-2, and the insulin-like (INSL) peptides such as INSL3, INSL4, INSL5 and INSL6. The relaxin family peptides share high structural but low sequence similarity, and exert their physiological functions by activating a group of four GPCRs, RXFP1-4. Relaxin and INSL3 are the endogenous ligands for RXFP1 and RXFP2, respectively. Upon receptor binding, relaxin activates a variety of signaling pathways to produce second messengers such as cAMP.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 77025068   7 LAFLAFERYVVICKPFGNFRFSSKHALMVVLATWTIGIGVSIPPFFGW 54
Cdd:cd15137  98 LTLITLDRFICIVFPFSGRRLGLRRAIIVLACIWLIGLLLAVLPLLPW 145

cholecystokinin receptors and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group represents four G-protein coupled receptors that are members of the RFamide receptor family, including cholecystokinin receptors (CCK-AR and CCK-BR), orexin receptors (OXR), neuropeptide FF receptors (NPFFR), and pyroglutamylated RFamide peptide receptor (QRFPR). These RFamide receptors are activated by their endogenous peptide ligands that share a common C-terminal arginine (R) and an amidated phenylanine (F) motif. CCK-AR (type A, alimentary; also known as CCK1R) is found abundantly on pancreatic acinar cells and binds only sulfated CCK-peptides with very high affinity, whereas CCK-BR (type B, brain; also known as CCK2R), the predominant form in the brain and stomach, binds CCK or gastrin and discriminates poorly between sulfated and non-sulfated peptides. CCK is implicated in regulation of digestion, appetite control, and body weight, and is involved in neurogenesis via CCK-AR. There is some evidence to support that CCK and gastrin, via their receptors, are involved in promoting cancer development and progression, acting as growth and invasion factors. Orexins (OXs; also referred to as hypocretins) are neuropeptide hormones that regulate the sleep-wake cycle and potently influence homeostatic systems regulating appetite and feeding behavior or modulating emotional responses such as anxiety or panic. OXs are synthesized as prepro-orexin (PPO) in the hypothalamus and then proteolytically cleaved into two forms of isoforms: orexin-A (OX-A) and orexin-B (OX-B). OXA is a 33 amino-acid peptide with N-terminal pyroglutamyl residue and two intramolecular disulfide bonds, whereas OXB is a 28 amino-acid linear peptide with no disulfide bonds. OX-A binds orexin receptor 1 (OX1R) with high-affinity, but also binds with somewhat low-affinity to OX2R, and signals primarily to Gq coupling, whereas OX-B shows a strong preference for the orexin receptor 2 (OX2R) and signals through Gq or Gi/o coupling. The 26RFa, also known as QRFP (Pyroglutamylated RFamide peptide), is a 26-amino acid residue peptide that exerts similar orexigenic activity including the regulation of feeding behavior in mammals. It is the ligand for G-protein coupled receptor 103 (GPR103), which is predominantly expressed in paraventricular (PVN) and ventromedial (VMH) nuclei of the hypothalamus. GPR103 shares significant protein sequence homology with orexin receptors (OX1R and OX2R), which have recently shown to produce a neuroprotective effect in Alzheimer's disease by forming a functional heterodimer with GPR103. Neuropeptide FF (NPFF) is a mammalian octapeptide that has been implicated in a wide range of physiological functions in the brain including pain sensitivity, insulin release, food intake, memory, blood pressure, and opioid-induced tolerance and hyperalgesia. The effects of NPFF are mediated through neuropeptide FF1 and FF2 receptors (NPFF1-R and NPFF2-R) which are predominantly expressed in the brain. NPFF induces pro-nociceptive effects, mainly through the NPFF1-R, and anti-nociceptive effects, mainly through the NPFF2-R.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 77025068   5 WSLAFLAFERYVVICKPFGNFRFSSK-HALMVVLATWTIGIGVSIP 49
Cdd:cd14993  89 LTLVAISIDRYLAICYPLKARRVSTKrRARIIIVAIWVIAIIIMLP 134

amine receptors and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; Amine receptors of the class A family of GPCRs include adrenoceptors, 5-HT (serotonin) receptors, muscarinic cholinergic receptors, dopamine receptors, histamine receptors, and trace amine receptors. The receptors of amine subfamily are major therapeutic targets for the treatment of neurological disorders and psychiatric diseases. 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
                ....*....|....*....|....*....|....*....|....*....|..
gi 77025068   5 WSLAFLAFERYVVICKPFG-NFRFSSKHALMVVLATWTIGIGVSIPPFFGWS 55
Cdd:cd14967  88 LNLCAISLDRYLAITRPLRyRQLMTKKRALIMIAAVWVYSLLISLPPLVGWR 139

serotonin receptor subtype 2C, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT2 receptors are a subfamily of serotonin receptors that bind the neurotransmitter serotonin (5HT; 5-hydroxytryptamine) in the central nervous system (CNS). The 5-HT2 subfamily is composed of three subtypes that mediate excitatory neurotransmission: 5-HT2A, 5-HT2B, and 5-HT2C. They are selectively linked to G proteins of the G(q/11) family and activate phospholipase C, which leads to activation of protein kinase C and calcium release. In the CNS, serotonin is involved in the regulation of appetite, mood, sleep, cognition, learning and memory, as well as implicated in diseases such as migraine, schizophrenia, and depression. Indeed, 5-HT2 receptors are attractive targets for a variety of psychoactive drugs, ranging from atypical antipsychotic drugs, antidepressants, and anxiolytics, which have an antagonistic action on 5-HT2 receptors, to hallucinogens, which act as agonists at postsynaptic 5-HT2 receptors. 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 77025068   7 LAFLAFERYVVICKPFGNFRFSSK-HALMVVLATWTIGIGVSIP 49
Cdd:cd15305  92 LCAISLDRYVAIRNPIEHSRFNSRtKAMMKIAAVWTISIGISMP 135

serotonin receptor subtype 2A, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT2 receptors are a subfamily of serotonin receptors that bind the neurotransmitter serotonin (5HT; 5-hydroxytryptamine) in the central nervous system (CNS). The 5-HT2 subfamily is composed of three subtypes that mediate excitatory neurotransmission: 5-HT2A, 5-HT2B, and 5-HT2C. They are selectively linked to G proteins of the G(q/11) family and activate phospholipase C, which leads to activation of protein kinase C and calcium release. In the CNS, serotonin is involved in the regulation of appetite, mood, sleep, cognition, learning and memory, as well as implicated in diseases such as migraine, schizophrenia, and depression. Indeed, 5-HT2 receptors are attractive targets for a variety of psychoactive drugs, ranging from atypical antipsychotic drugs, antidepressants, and anxiolytics, which have an antagonistic action on 5-HT2 receptors, to hallucinogens, which act as agonists at postsynaptic 5-HT2 receptors. 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 77025068   7 LAFLAFERYVVICKPFGNFRFSSK-HALMVVLATWTIGIGVSIP-PFFG 53
Cdd:cd15304  92 LCAISLDRYIAIRNPIHHSRFNSRtKAFLKIIAVWTISVGISMPiPVFG 140

serotonin receptor subtype 1A from vertebrates, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT1 receptors, one of 14 mammalian 5-HT receptors, is a member of the class A of GPCRs and is activated by the endogenous neurotransmitter and peripheral signal mediator serotonin (5-hydroxytryptamine, 5-HT). The 5-HT1 receptors mediate inhibitory neurotransmission by coupling to G proteins of the G(i/o) family, which lead to a decrease in adenylate cyclase activity, thereby decreasing intracellular cAMP levels and calcium influx. The 5-HT1 receptor subfamily includes 5 subtypes: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F. There is no 5-HT1C receptor subtype, as it has been reclassified as the 5-HT2C receptor. In the CNS, serotonin is involved in the regulation of appetite, mood, sleep, cognition, learning and memory, as well as implicated in neurologic disorders such as migraine, schizophrenia, and depression.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 77025068   7 LAFLAFERYVVICKP--FGNFRFSSKHALMVVLaTWTIGIGVSIPPFFGW 54
Cdd:cd15330  91 LCAIALDRYWAITDPidYVNKRTPRRAAVLISL-TWLIGFSISIPPMLGW 139

endothelial differentiation gene family, member of the class A family of seven-transmembrane G protein-coupled receptors; This group represents the endothelial differentiation gene (Edg) family of G-protein coupled receptors, melanocortin/ACTH receptors, and cannabinoid receptors as well as their closely related receptors. The Edg GPCRs bind blood borne lysophospholipids including sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA), which are involved in the regulation of cell proliferation, survival, migration, invasion, endothelial cell shape change and cytoskeletal remodeling. The Edg receptors are classified into two subfamilies: the lysophosphatidic acid subfamily that includes LPA1 (Edg2), LPA2 (Edg4), and LPA3 (Edg7); and the S1P subfamily that includes S1P1 (Edg1), S1P2 (Edg5), S1P3 (Edg3), S1P4 (Edg6), and S1P5 (Edg8). Melanocortin receptors bind a group of pituitary peptide hormones known as melanocortins, which include adrenocorticotropic hormone (ACTH) and the different isoforms of melanocyte-stimulating hormones. Two types of cannabinoid receptors, CB1 and CB2, are activated by naturally occurring endocannabinoids, cannabis plant-derived cannabinoids such as tetrahydrocannabinol, or synthetic cannabinoids. The CB receptors are involved in the various physiological processes such as appetite, mood, memory, and pain sensation. CB1 receptor is expressed predominantly in central and peripheral neurons, while CB2 receptor is found mainly in the immune system.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 77025068   6 SLAFLAFERYVVICKP-FGNFRFSSKHALMVVLATWTIGIGVSIPPFFGW 54
Cdd:cd14972  87 SLLAIAVDRYISIVHGlTYVNNVTNKRVKVLIALVWVWSVLLALLPVLGW 136

teleost multiple tissue (tmt) opsin, member of the class A family of seven-transmembrane G protein-coupled receptors; Teleost multiple tissue (tmt) opsins are homologs of encephalopsin. Mouse encephalopsin (or panopsin) is highly expressed in the brain and testes, whereas the teleost homologs are localized to multiple tissues. The exact functions of the encephalopsins and tmt-opsins are unknown. The vertebrate non-visual opsin family includes pinopsins, parapinopsin, VA (vertebrate ancient) opsins, and parietopsins. These non-visual opsins are expressed in various extra-retinal tissues and/or in non-rod, non-cone retinal cells. They are thought to be involved in light-dependent physiological functions such as photo-entrainment of circadian rhythm, photoperiodicity and body color change. Tmt opsins belong to the class A of the G protein-coupled receptors and show strong homology to the vertebrate visual opsins.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 77025068   6 SLAFLAFERYVVICKPFGNFRFSSKHALMVVLATWTIGIGVSIPPFFGWSR 56
Cdd:cd15086  90 SLAVLSYERYCTLLRPTEADVSDYRKAWLGVGGSWLYSLLWTLPPLLGWSS 140

G protein-coupled receptor 39, member of the class A family of seven-transmembrane G protein-coupled receptors; GPR39 is an orphan G protein-coupled receptor that belongs to the growth hormone secretagogue and neurotensin receptor subfamily. GPR39 is expressed in peripheral tissues such as pancreas, gut, gastrointestinal tract, liver, kidney as well as certain regions of the brain. The divalent metal ion Zn(2+) has been shown to be a ligand capable of activating GPR39. Thus, it has been suggested that GPR39 function as a G(q)-coupled Zn(2+)-sensing receptor which involved in the regulation of endocrine pancreatic function, body weight, gastrointestinal mobility, and cell death.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 77025068   7 LAFLAFERYVVICKPFGNFRFSSKHALMVVLATWTIGIGVSIPPFF 52
Cdd:cd15135  96 VATLSFERYIAICHPFKYKALSGSRVRLLICFVWLTSALVALPLLF 141

adenosine receptor subtype 2AB, member of the class A family of seven-transmembrane G protein-coupled receptors; The A2B receptor, a member of the adenosine receptor family of G protein-coupled receptors, binds adenosine as its endogenous ligand and is involved in regulating myocardial oxygen consumption and coronary blood flow. High-affinity A2A and low-affinity A2B receptors are preferentially coupled to G proteins of the stimulatory (Gs) family, which lead to activation of adenylate cyclase and thereby increasing the intracellular cAMP levels. The A2A receptor activation protects against tissue injury and acts as anti-inflammatory agent. In human skin endothelial cells, activation of A2B receptor, but not the A2A receptor, promotes angiogenesis. Alternatively, activated A2A receptor, but not the A2B receptor, promotes angiogenesis in human umbilical vein and lung microvascular endothelial cells. The A2A receptor alters cardiac contractility indirectly by modulating the anti-adrenergic effect of A1 receptor, while the A2B receptor exerts direct effects on cardiac contractile function, but does not modulate beta-adrenergic or A1 anti-adrenergic effects.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 77025068   5 WSLAFLAFERYVVICKPFG-NFRFSSKHALMVVLATWTIGIGVSIPPFFGWSR 56
Cdd:cd15069  87 FSLLAVAVDRYLAIKVPLRyKSLVTGKRARGVIAVLWVLAFGIGLTPFLGWNK 139