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 154758047  11 KVDRVTIGTLVGVDALMIVTGLIGALSHTPLARYTWWLFSTIAMIVVLYFLATSLRAAAKERGPEVASTFNTLTALVLVL 90
Cdd:cd15244   96 GADRNTIATLIGLDVIMIVTGLVAALTKVPAARIVWWAISTAAFLAVLYFLVVGLTAEASSRSPEVASTFNTLRNLTLVL 175

                         90       100       110
                 ....*....|....*....|....*....|...
gi 154758047  91 WTAYPILWIVGTEGAGVVGLGIETLLFMVLDVT 123
Cdd:cd15244  176 WACYPIVWLIGTEGFGIVGLNIETLLFMVLDLT 208

light-driven outward proton pump bacteriorhodopsin, member of the seven-transmembrane GPCR superfamily; Bacteriorhodopsin (BR) serves as a light-driven retinal-binding outward proton pump, generating an outside positive membrane potential and thus creating an inwardly directed proton motive force (PMF) necessary for ATP synthesis. BR belongs to the microbial rhodopsin family, also known as type I rhodopsins, comprising light-driven inward chloride pump halorhodopsin (HR), light-gated cation channel channelrhodopsin (ChR), light-sensor activating transmembrane transducer protein sensory rhodopsin II (SRII), light-sensor activating soluble transducer protein Anabaena sensory rhodopsin (ASR), and other light-driven proton pumps such as blue-light absorbing and green-light absorbing proteorhodopsins, among others. They have been found in various single-celled microorganisms from all three domains of life, including halophile archaea, gamma-proteobacteria, cyanobacteria, fungi, and green algae. While microbial (type 1) and animal (type 2) rhodopsins have no sequence similarity with each other, they share a common architecture consisting of seven-transmembrane alpha-helices (TM) connected by extracellular loops and intracellular loops. Both types of rhodopsins consist of opsin and a covalently attached retinal (the aldehyde of vitamin A), a photoreactive chromophore, via a protonated Schiff base linkage to an amino group of lysine in the middle of the seventh transmembrane helix (TM7). Upon the absorption of light, microbial rhodopsins undergo light-induced photoisomerization of all-trans retinal into the 13-cis isomer, whereas the photoisomerization of 11-cis retinal to all-trans isomer occurs in the animal rhodopsins. While animal visual rhodopsins are activated by light to catalyze GDP/GTP exchange in the alpha subunit of the retinal G protein transducin (Gt), microbial rhodopsins do not activate G proteins, but instead can function as light-dependent ion pumps, cation channels, and sensors.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154758047  11 KVDRVTIGTLVGVDALMIVTGLIGALSHTPLARYTWWLFSTIAMIVVLYFLATSLRAAAKERGPEVASTFNTLTALVLVL 90
Cdd:cd15244   96 GADRNTIATLIGLDVIMIVTGLVAALTKVPAARIVWWAISTAAFLAVLYFLVVGLTAEASSRSPEVASTFNTLRNLTLVL 175

                         90       100       110
                 ....*....|....*....|....*....|...
gi 154758047  91 WTAYPILWIVGTEGAGVVGLGIETLLFMVLDVT 123
Cdd:cd15244  176 WACYPIVWLIGTEGFGIVGLNIETLLFMVLDLT 208

Bacteriorhodopsin [Energy production and conversion, Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154758047  11 KVDRVTIGTLVGVDALMIVTGLIGALShTPLARYTWWLFSTIAMIVVLYFLATSLRAAAKERGPEVASTFNTLTALVLVL 90
Cdd:COG5524   91 GASRRLLVTLVGADVLMIVTGLAGALS-TGPARWLWGLLSTAAFLVILYLLLGPLRRSAARQGGEVRSLFGKLRNLLVVL 169

                         90       100       110
                 ....*....|....*....|....*....|...
gi 154758047  91 WTAYPILWIVGTEGAGVVGLGIETLLFMVLDVT 123
Cdd:COG5524  170 WLIYPIVWLLGPEGLGLLDVTIETVGYTYLDLL 202

light-driven outward proton pump bacteriorhodopsin, member of the seven-transmembrane GPCR superfamily; Bacteriorhodopsin (BR) serves as a light-driven retinal-binding outward proton pump, generating an outside positive membrane potential and thus creating an inwardly directed proton motive force (PMF) necessary for ATP synthesis. BR belongs to the microbial rhodopsin family, also known as type I rhodopsins, comprising light-driven inward chloride pump halorhodopsin (HR), light-gated cation channel channelrhodopsin (ChR), light-sensor activating transmembrane transducer protein sensory rhodopsin II (SRII), light-sensor activating soluble transducer protein Anabaena sensory rhodopsin (ASR), and other light-driven proton pumps such as blue-light absorbing and green-light absorbing proteorhodopsins, among others. They have been found in various single-celled microorganisms from all three domains of life, including halophile archaea, gamma-proteobacteria, cyanobacteria, fungi, and green algae. While microbial (type 1) and animal (type 2) rhodopsins have no sequence similarity with each other, they share a common architecture consisting of seven-transmembrane alpha-helices (TM) connected by extracellular loops and intracellular loops. Both types of rhodopsins consist of opsin and a covalently attached retinal (the aldehyde of vitamin A), a photoreactive chromophore, via a protonated Schiff base linkage to an amino group of lysine in the middle of the seventh transmembrane helix (TM7). Upon the absorption of light, microbial rhodopsins undergo light-induced photoisomerization of all-trans retinal into the 13-cis isomer, whereas the photoisomerization of 11-cis retinal to all-trans isomer occurs in the animal rhodopsins. While animal visual rhodopsins are activated by light to catalyze GDP/GTP exchange in the alpha subunit of the retinal G protein transducin (Gt), microbial rhodopsins do not activate G proteins, but instead can function as light-dependent ion pumps, cation channels, and sensors.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154758047  11 KVDRVTIGTLVGVDALMIVTGLIGALSHTPLARYTWWLFSTIAMIVVLYFLATSLRAAAKERGPEVASTFNTLTALVLVL 90
Cdd:cd15244   96 GADRNTIATLIGLDVIMIVTGLVAALTKVPAARIVWWAISTAAFLAVLYFLVVGLTAEASSRSPEVASTFNTLRNLTLVL 175

                         90       100       110
                 ....*....|....*....|....*....|...
gi 154758047  91 WTAYPILWIVGTEGAGVVGLGIETLLFMVLDVT 123
Cdd:cd15244  176 WACYPIVWLIGTEGFGIVGLNIETLLFMVLDLT 208

Bacteriorhodopsin-like protein; The bacterial opsins are retinal-binding proteins that provide light- dependent ion transport and sensory functions to a family of halophilic bacteria. They are integral membrane proteins believed to contain seven transmembrane (TM) domains, the last of which contains the attachment point for retinal (a conserved lysine). This family also includes distantly related proteins that do not contain the retinal binding lysine and so cannot function as opsins. Some fungal examples are: Swiss:O74870, Swiss:P25619, Swiss:P38079, Swiss:Q12117.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154758047   11 KVDRVTIGTLVGVDALMIVTGLIGALSHTPLARYTWWLFSTIAMIVVLYFLATSLRAAAKERGPEVA-STFNTLTALVLV 89
Cdd:pfam01036  95 KADRRTIGWLITADILMIVTGYLGALTSTGLVRYLWFAIGTAFFLYVLYVLFKPFAEAAKTRPSGLArSLYTTLRNLFVV 174

                          90       100       110
                  ....*....|....*....|....*....|....
gi 154758047   90 LWTAYPILWIVGTEGAGVVGLGIETLLFMVLDVT 123
Cdd:pfam01036 175 SWLLYPIVWLLGPEGAGVLDVTVRTALYVVLDFV 208

Bacteriorhodopsin-like protein; The bacterial opsins are retinal-binding proteins that provide light- dependent ion transport and sensory functions to a family of halophilic bacteria.. They are integral membrane proteins believed to contain seven transmembrane (TM) domains, the last of which contains the attachment point for retinal (a conserved lysine).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154758047    12 VDRVTIGTLVGVDALMIVTGLIGALSHTPlARYTWWLFSTIAMIVVLYFLATSLRAAAKERGPEVASTFNTLTALVLVLW 91
Cdd:smart01021  97 VSRATIAFLIAADVVMIVTGLAAALTTST-YKWGWFTISTAAFLVLLYVLLVPLRRSAKARGSEVRRLFLTLRNLTVVLW 175

                           90       100       110
                   ....*....|....*....|....*....|.
gi 154758047    92 TAYPILWIVGtEGAGVVGLGIETLLFMVLDV 122
Cdd:smart01021 176 LLYPIVWGLG-EGGNLIQVDSEAIFYGILDV 205

Anabaena sensory rhodopsin and similar proteins, member of the seven-transmembrane GPCR superfamily; This subgroup includes eubacterial sensory rhodopsin from the freshwater cyanobacterium Anabaena and its closely related proteins. Unlike other sensory rhodopsins (SRI and SRII), the Anabaena sensory rhodopsin (ASR) activates a soluble transducer protein (ASRT), which may leading to transcriptional control of several genes. Although ASRT was shown to interact with DNA in vitro, the exact mechanism of photosensory transduction is not clearly understood. Moreover, the regulation of CRP (cAMP receptor protein) expression by ASR has been reported demonstrating a direct interaction of the C-terminal region of ASR with DNA, suggesting that ASR itself may also work as a transcription factor. ASR belongs to the microbial rhodopsin family, also known as type I rhodopsins, comprising the light-driven inward chloride pump halorhodopsin (HR), the outward proton pump bacteriorhodopsin (BR), the light-gated cation channel channelrhodopsin (ChR), the light-sensor activating transmembrane transducer protein sensory rhodopsin II (SRII), and the other light-driven proton pumps such as blue-light absorbing and green-light absorbing proteorhodopsins, among others. Microbial rhodopsins have been found in various single-celled microorganisms from all three domains of life, including halophile archaea, gamma-proteobacteria, cyanobacteria, fungi, and green algae. While microbial (type 1) and animal (type 2) rhodopsins have no sequence similarity with each other, they share a common architecture consisting of seven-transmembrane alpha-helices (TM) connected by extracellular loops and intracellular loops. Both types of rhodopsins consist of opsin and a covalently attached retinal (the aldehyde of vitamin A), a photoreactive chromophore, via a protonated Schiff base linkage to an amino group of lysine in the middle of the seventh transmembrane helix (TM7). Upon the absorption of light, microbial rhodopsins undergo light-induced photoisomerization of all-trans retinal into the 13-cis isomer, whereas the photoisomerization of 11-cis retinal to all-trans isomer occurs in the animal rhodopsins. While animal visual rhodopsins are activated by light to catalyze GDP/GTP exchange in the alpha subunit of the retinal G protein transducin (Gt), microbial rhodopsins do not activate G proteins, but instead can function as light-dependent ion pumps, cation channels, and sensors.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154758047  16 TIGTLVGVDALMIVT-GLIGALSHTPLARYTWWLFSTIAMIVVLYFLATSLRAAAKERGPEVASTFNTLTALVLVLWTAY 94
Cdd:cd15240  100 TVIGFLMSDQIMIVTaLLFGLSSERAWVKWTWYACSCGAFLGVLYGIWVPLREETRTERSDLANAYRKNVAFLTVVWIIY 179

                         90       100
                 ....*....|....*....|....*....
gi 154758047  95 PILWIVGTEGAGVVGLGIETLLFMVLDVT 123
Cdd:cd15240  180 PIVLIVGPDGLGWISPTLDTALFAVLDFF 208

light-driven inward chloride pump halorhodopsin, member of the seven-transmembrane GPCR superfamily; Halorhodopsin (HR) acts as a light-driven inward-directed chloride pump. When activated by yellow light, HR pumps chloride ions into the cell cytoplasm, generating a negative-inside membrane potential which drives proton uptake. The resulting electrochemical ion gradient provides an energy source to the cell and contributes to pH homeostasis. HR is found in phylogenetically ancient archaea, known as halobacteria which live in high salty environments. HR belongs to the microbial rhodopsin family, also known as type I rhodopsins, comprising light-driven retinal-binding outward pump bacteriorhodopsin (BR), light-gated cation channel channelrhodopsin (ChR), light-sensor activating transmembrane transducer protein sensory rhodopsin II (SRII), light-sensor activating soluble transducer protein Anabaena sensory rhodopsin (ASR), and other light-driven proton pumps such as blue-light absorbing and green-light absorbing proteorhodopsins, among others. They have been found in various single-celled microorganisms from all three domains of life, including halophile archaea, gamma-proteobacteria, cyanobacteria, fungi, and green algae. While microbial (type 1) and animal (type 2) rhodopsins have no sequence similarity with each other, they share a common architecture consisting of seven-transmembrane alpha-helices (TM) connected by extracellular loops and intracellular loops. Both types of rhodopsins consist of opsin and a covalently attached retinal (the aldehyde of vitamin A), a photoreactive chromophore, via a protonated Schiff base linkage to an amino group of lysine in the middle of the seventh transmembrane helix (TM7). Upon the absorption of light, microbial rhodopsins undergo light-induced photoisomerization of all-trans retinal into the 13-cis isomer, whereas the photoisomerization of 11-cis retinal to all-trans isomer occurs in the animal rhodopsins. While animal visual rhodopsins are activated by light to catalyze GDP/GTP exchange in the alpha subunit of the retinal G protein transducin (Gt), microbial rhodopsins do not activate G proteins, but instead can function as light-dependent ion pumps, cation channels, and sensors.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154758047  12 VDRVTIGTLVGVDALMIVTGLIGALSHTPLA-RYTWWLFSTIAMIVVLYFLATSLRAAAKERGpeVASTFNTLTALVLVL 90
Cdd:cd15243  103 SNTTKLFTAIAADIGMCVTGLAAALTTSSHLmRWVWYAISCAFFVVVLYVLLVEWAADADAAG--TADIFSTLKVLTVVL 180

                         90       100       110
                 ....*....|....*....|....*....|..
gi 154758047  91 WTAYPILWIVGTEGAGVVGLGIETLLFMVLDV 122
Cdd:cd15243  181 WLGYPIVWALGVEGLALLSVGATSWAYSGLDI 212

green- and blue-light absorbing proteorhodopsins, member of the seven-transmembrane GPCR superfamily; This subgroup represents blue-light absorbing and green-light absorbing proteorhodopsins (PRs), which act as a light-driven proton pump that plays a major role in supplying light energy for phototropic marine microorganisms, by a mechanism similar to that of bacteriorhodopsin. PRs are found in most marine bacteria in surface waters, as well as in archaea and eukaryotes. They belong to the microbial rhodopsin family, also known as type 1 rhodopsins, comprising the light-driven inward chloride pump halorhodopsin (HR), the light-gated cation channel channelrhodopsin (ChR), the light-sensor activating transmembrane transducer protein sensory rhodopsin II (SRII), the light-sensor activating soluble transducer protein Anabaena sensory rhodopsin (ASR), and the other light-driven proton pumps such as bacteriorhodopsin (BR). They have been found in various single-celled microorganisms from all three domains of life, including halophile archaea, gamma-proteobacteria, cyanobacteria, fungi, and green algae. While microbial (type 1) and animal (type 2) rhodopsins have no sequence similarity with each other, they share a common architecture consisting of seven-transmembrane alpha-helices (TM) connected by extracellular loops and intracellular loops. Both types of rhodopsins consist of opsin and a covalently attached retinal (the aldehyde of vitamin A), a photoreactive chromophore, via a protonated Schiff base linkage to an amino group of lysine in the middle of the seventh transmembrane helix (TM7). Upon the absorption of light, microbial rhodopsins undergo light-induced photoisomerization of all-trans retinal into the 13-cis isomer, whereas the photoisomerization of 11-cis retinal to all-trans isomer occurs in the animal rhodopsins. While animal visual rhodopsins are activated by light to catalyze GDP/GTP exchange in the alpha subunit of the retinal G protein transducin (Gt), microbial rhodopsins do not activate G proteins, but instead can function as light-dependent ion pumps, cation channels, and sensors.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154758047  20 LVGVDALMIVTGLIGALSHTPLARYTWWLFSTIAMIVVLYFLATSLRAAAKERGPEVASTFNTLTALVLVLWTAYPILWI 99
Cdd:cd15242  112 LGGASALMIVLGYPGEIGADLGTRWLWGVLSMIPFLYIIYELFVGLAKAIARQPAAVRGAVNTLRWIVLVGWAIYPIGYM 191

                         90
                 ....*....|
gi 154758047 100 VGTEGAGVVG 109
Cdd:cd15242  192 AGYLGLTGGG 201

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 154758047  11 KVDRVTIGTLVGVDALMIVTGLIGALS------------HTPLARYTWWLFSTIAMIVVLYFLATSLRAAAKE------- 71
Cdd:cd14964  113 GKTRVIILGCWGVSLLLSIPPLVGKGAipryntltgscyLICTTIYLTWGFLLVSFLLPLVAFLVIFSRIVLRlrrrvra 192

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 154758047  72 ----------RGPEVASTFNTLTALVLVLWTAYPILWIVGTEGAGVVGLGIETLLFMVLDVT 123
Cdd:cd14964  193 irsaaslntdKNLKATKSLLILVITFLLCWLPFSIVFILHALVAAGQGLNLLSILANLLAVL 254