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Conserved domains on  [gi|149036820|gb|EDL91438|]
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G protein-coupled receptor 27 [Rattus norvegicus]

Protein Classification

G protein-coupled receptor family protein( domain architecture ID 705710)

G protein-coupled receptor family protein is a seven-transmembrane G protein-coupled receptor (7TM-GPCR) family protein which typically transmits an extracellular signal into the cell by the conformational rearrangement of the 7TM helices and by the subsequent binding and activation of an intracellular heterotrimeric G protein; GPCR ligands include light-sensitive compounds, odors, pheromones, hormones, and neurotransmitters

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
7tm_GPCRs super family cl28897
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
20-351 0e+00

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.


The actual alignment was detected with superfamily member cd15216:

Pssm-ID: 475119 [Multi-domain]  Cd Length: 332  Bit Score: 548.47  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  20 GLRLATLSLLLCVSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLAARRAAAAAGTPPGALGCKLL 99
Cdd:cd15216    1 GLRLATLSLLLCVSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLAARRAAAAAGTPPGALGCKLL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 100 AFLAALFCFHAAFLLLGVGVTRYLAIAHHRFYAERLAGWPCAAMLVCAAWALALAAAFPPVLDGGGADDEDAPCALEQRP 179
Cdd:cd15216   81 AFLAALFCFHAAFLLLGVGVTRYLAIAHHRFYAERLAGWPCAAMLVCAAWALALAAAFPPVLDGGGADDEDAPCALEQRP 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 180 DGAPGALGFLLLLAAVVGATHLVYLRLLFFIHDRRKMRPARLVPAVSHDWTFHGPGATGQAAANWTAGFGRGPTPPALVG 259
Cdd:cd15216  161 DGAPGALGFLLLLAAVVGATHLVYLRLLFFIHDRRKMRPARLVPAVSHDWTFHGPGATGQAAANWTAGFGRGPTPPALVG 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 260 IRPAGPGRGARRLLVLEEFKTEKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRPGAVPQAYLTASVWLTFAQAGINPVV 339
Cdd:cd15216  241 IRPAGPGRGARRLLVLEEFKTEKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRPGAVPQAYLTASVWLTFAQAGINPVV 320
                        330
                 ....*....|..
gi 149036820 340 CFLFNRELRDCF 351
Cdd:cd15216  321 CFLFNRELRDCF 332
 
Name Accession Description Interval E-value
7tmA_SREB1_GPR27 cd15216
super conserved receptor expressed in brain 1 (or GPR27), member of the class A family of ...
20-351 0e+00

super conserved receptor expressed in brain 1 (or GPR27), member of the class A family of seven-transmembrane G protein-coupled receptors; The SREB (super conserved receptor expressed in brain) subfamily consists of at least three members, named SREB1 (GPR27), SREB2 (GPR85), and SREB3 (GPR173). They are very highly conserved G protein-coupled receptors throughout vertebrate evolution, however no endogenous ligands have yet been identified. SREB2 is greatly expressed in brain regions involved in psychiatric disorders and cognition, such as the hippocampal dentate gyrus. Genetic studies in both humans and mice have shown that SREB2 influences brain size and negatively regulates hippocampal adult neurogenesis and neurogenesis-dependent cognitive function, all of which are suggesting a potential link between SREB2 and schizophrenia. All three SREB genes are highly expressed in differentiated hippocampal neural stem cells. Furthermore, 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.


Pssm-ID: 320344 [Multi-domain]  Cd Length: 332  Bit Score: 548.47  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  20 GLRLATLSLLLCVSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLAARRAAAAAGTPPGALGCKLL 99
Cdd:cd15216    1 GLRLATLSLLLCVSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLAARRAAAAAGTPPGALGCKLL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 100 AFLAALFCFHAAFLLLGVGVTRYLAIAHHRFYAERLAGWPCAAMLVCAAWALALAAAFPPVLDGGGADDEDAPCALEQRP 179
Cdd:cd15216   81 AFLAALFCFHAAFLLLGVGVTRYLAIAHHRFYAERLAGWPCAAMLVCAAWALALAAAFPPVLDGGGADDEDAPCALEQRP 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 180 DGAPGALGFLLLLAAVVGATHLVYLRLLFFIHDRRKMRPARLVPAVSHDWTFHGPGATGQAAANWTAGFGRGPTPPALVG 259
Cdd:cd15216  161 DGAPGALGFLLLLAAVVGATHLVYLRLLFFIHDRRKMRPARLVPAVSHDWTFHGPGATGQAAANWTAGFGRGPTPPALVG 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 260 IRPAGPGRGARRLLVLEEFKTEKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRPGAVPQAYLTASVWLTFAQAGINPVV 339
Cdd:cd15216  241 IRPAGPGRGARRLLVLEEFKTEKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRPGAVPQAYLTASVWLTFAQAGINPVV 320
                        330
                 ....*....|..
gi 149036820 340 CFLFNRELRDCF 351
Cdd:cd15216  321 CFLFNRELRDCF 332
7tm_1 pfam00001
7 transmembrane receptor (rhodopsin family); This family contains, amongst other ...
36-146 7.00e-09

7 transmembrane receptor (rhodopsin family); This family contains, amongst other G-protein-coupled receptors (GCPRs), members of the opsin family, which have been considered to be typical members of the rhodopsin superfamily. They share several motifs, mainly the seven transmembrane helices, GCPRs of the rhodopsin superfamily. All opsins bind a chromophore, such as 11-cis-retinal. The function of most opsins other than the photoisomerases is split into two steps: light absorption and G-protein activation. Photoisomerases, on the other hand, are not coupled to G-proteins - they are thought to generate and supply the chromophore that is used by visual opsins.


Pssm-ID: 459624 [Multi-domain]  Cd Length: 256  Bit Score: 56.15  E-value: 7.00e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820   36 GNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLaarRAAAAAGTPPGALGCKLLAFLAALFCFHAAFLLL 115
Cdd:pfam00001   1 GNLLVILVILRNKKLRTPTNIFLLNLAVADLLFSLLTLPFWLV---YYLNHGDWPFGSALCKIVGALFVVNGYASILLLT 77
                          90       100       110
                  ....*....|....*....|....*....|.
gi 149036820  116 GVGVTRYLAIAHHRFYAERLAGWPCAAMLVC 146
Cdd:pfam00001  78 AISIDRYLAIVHPLRYKRRRTPRRAKVLILV 108
 
Name Accession Description Interval E-value
7tmA_SREB1_GPR27 cd15216
super conserved receptor expressed in brain 1 (or GPR27), member of the class A family of ...
20-351 0e+00

super conserved receptor expressed in brain 1 (or GPR27), member of the class A family of seven-transmembrane G protein-coupled receptors; The SREB (super conserved receptor expressed in brain) subfamily consists of at least three members, named SREB1 (GPR27), SREB2 (GPR85), and SREB3 (GPR173). They are very highly conserved G protein-coupled receptors throughout vertebrate evolution, however no endogenous ligands have yet been identified. SREB2 is greatly expressed in brain regions involved in psychiatric disorders and cognition, such as the hippocampal dentate gyrus. Genetic studies in both humans and mice have shown that SREB2 influences brain size and negatively regulates hippocampal adult neurogenesis and neurogenesis-dependent cognitive function, all of which are suggesting a potential link between SREB2 and schizophrenia. All three SREB genes are highly expressed in differentiated hippocampal neural stem cells. Furthermore, 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.


Pssm-ID: 320344 [Multi-domain]  Cd Length: 332  Bit Score: 548.47  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  20 GLRLATLSLLLCVSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLAARRAAAAAGTPPGALGCKLL 99
Cdd:cd15216    1 GLRLATLSLLLCVSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLAARRAAAAAGTPPGALGCKLL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 100 AFLAALFCFHAAFLLLGVGVTRYLAIAHHRFYAERLAGWPCAAMLVCAAWALALAAAFPPVLDGGGADDEDAPCALEQRP 179
Cdd:cd15216   81 AFLAALFCFHAAFLLLGVGVTRYLAIAHHRFYAERLAGWPCAAMLVCAAWALALAAAFPPVLDGGGADDEDAPCALEQRP 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 180 DGAPGALGFLLLLAAVVGATHLVYLRLLFFIHDRRKMRPARLVPAVSHDWTFHGPGATGQAAANWTAGFGRGPTPPALVG 259
Cdd:cd15216  161 DGAPGALGFLLLLAAVVGATHLVYLRLLFFIHDRRKMRPARLVPAVSHDWTFHGPGATGQAAANWTAGFGRGPTPPALVG 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 260 IRPAGPGRGARRLLVLEEFKTEKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRPGAVPQAYLTASVWLTFAQAGINPVV 339
Cdd:cd15216  241 IRPAGPGRGARRLLVLEEFKTEKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRPGAVPQAYLTASVWLTFAQAGINPVV 320
                        330
                 ....*....|..
gi 149036820 340 CFLFNRELRDCF 351
Cdd:cd15216  321 CFLFNRELRDCF 332
7tmA_SREB-like cd15005
super conserved receptor expressed in brain and related proteins, member of the class A family ...
31-351 6.04e-159

super conserved receptor expressed in brain and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; The SREB (super conserved receptor expressed in brain) subfamily consists of at least three members, named SREB1 (GPR27), SREB2 (GPR85), and SREB3 (GPR173). They are very highly conserved G protein-coupled receptors throughout vertebrate evolution, however no endogenous ligands have yet been identified. SREB2 is greatly expressed in brain regions involved in psychiatric disorders and cognition, such as the hippocampal dentate gyrus. Genetic studies in both humans and mice have shown that SREB2 influences brain size and negatively regulates hippocampal adult neurogenesis and neurogenesis-dependent cognitive function, all of which are suggesting a potential link between SREB2 and schizophrenia. All three SREB genes are highly expressed in differentiated hippocampal neural stem cells. Furthermore, 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.


Pssm-ID: 320134 [Multi-domain]  Cd Length: 329  Bit Score: 449.22  E-value: 6.04e-159
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  31 CVSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLAARRAAaaaGTPPGALGCKLLAFLAALFCFHA 110
Cdd:cd15005   12 CVSLAGNLLFSVLIVRDRSLHRAPYYFLLDLCLADGLRSLACFPFVMASVRHGS---GWIYGALSCKVIAFLAVLFCFHS 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 111 AFLLLGVGVTRYLAIAHHRFYAERLAGWPCAAmLVCAAWALALAAAFPPVLDGG--GADDEDAPCALEQRPDGAPGALGF 188
Cdd:cd15005   89 AFTLFCIAVTRYMAIAHHRFYAKRMTFWTCLA-VICMAWTLSVAMAFPPVFDVGtyTFIREEDQCTFEHRSYKANDTLGF 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 189 LLLLAAVVGATHLVYLRLLFFIHDRRKMRPARLVPAVSHDWTFHGPGATGQAAANWTAGFGRGPTPPALVGIRpAGPGRG 268
Cdd:cd15005  168 MLVLAVVIAATHLVYLKLLIFLRHHRKMKPAQLVPAISQNWTFHGPGATGQAAANWTAGFGRGPTPPTLLGIR-QAFHSG 246
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 269 ARRLLVLEEFKTEKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRPGAVPQAYLTASVWLTFAQAGINPVVCFLFNRELR 348
Cdd:cd15005  247 ARRLLVLDEFKMEKRLTRMFYAITLLFLLLWSPYIVACYIRVFVRGYAVPQGFLTAAVWMTFAQAGVNPIVCFFFNRELR 326

                 ...
gi 149036820 349 DCF 351
Cdd:cd15005  327 KCL 329
7tmA_SREB3_GPR173 cd15217
super conserved receptor expressed in brain 3 (or GPR173), member of the class A family of ...
31-351 2.03e-122

super conserved receptor expressed in brain 3 (or GPR173), member of the class A family of seven-transmembrane G protein-coupled receptors; The SREB (super conserved receptor expressed in brain) subfamily consists of at least three members, named SREB1 (GPR27), SREB2 (GPR85), and SREB3 (GPR173). They are very highly conserved G protein-coupled receptors throughout vertebrate evolution, however no endogenous ligands have yet been identified. SREB2 is greatly expressed in brain regions involved in psychiatric disorders and cognition, such as the hippocampal dentate gyrus. Genetic studies in both humans and mice have shown that SREB2 influences brain size and negatively regulates hippocampal adult neurogenesis and neurogenesis-dependent cognitive function, all of which are suggesting a potential link between SREB2 and schizophrenia. All three SREB genes are highly expressed in differentiated hippocampal neural stem cells. Furthermore, 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.


Pssm-ID: 320345 [Multi-domain]  Cd Length: 329  Bit Score: 356.57  E-value: 2.03e-122
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  31 CVSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLAARRAAAAAGTppgALGCKLLAFLAALFCFHA 110
Cdd:cd15217   12 CVSLAGNLIVSLLVLKDRALHKAPYYFLLDLCLADTIRSAVCFPFVLVSIRNGSAWTYS---VLSCKIVAFMAVLFCFHA 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 111 AFLLLGVGVTRYLAIAHHRFYAERLAGWPCAAmLVCAAWALALAAAFPPVLDGGGAD--DEDAPCALEQRPDGAPGALGF 188
Cdd:cd15217   89 AFMLFCISVTRYMAIAHHRFYSKRMTFWTCIA-VICMVWTLSVAMAFPPVFDVGTYKfiREEDQCIFEHRYFKANDTLGF 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 189 LLLLAAVVGATHLVYLRLLFFIHDRRKMRPARLVPAVSHDWTFHGPGATGQAAANWTAGFGRGPTPPALVGIRPAGPGRG 268
Cdd:cd15217  168 MLMLAVLIVATHIVYGKLLLFEYRHRKMKPVQMVPAISQNWTFHGPGATGQAAANWIAGFGRGPMPPTLLGIRQNAHTAN 247
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 269 aRRLLVLEEFKTEKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRPGAVPQAYLTASVWLTFAQAGINPVVCFLFNRELR 348
Cdd:cd15217  248 -RRLLGMEEFKAEKRLGRMFYVITLSFLVLWSPYIVACYWRVFVKACSIPHRYLSTAVWMSFAQAGVNPIVCFLLNKDLK 326

                 ...
gi 149036820 349 DCF 351
Cdd:cd15217  327 KCL 329
7tmA_SREB2_GPR85 cd15218
super conserved receptor expressed in brain 2 (or GPR85), member of the class A family of ...
32-351 1.08e-108

super conserved receptor expressed in brain 2 (or GPR85), member of the class A family of seven-transmembrane G protein-coupled receptors; The SREB (super conserved receptor expressed in brain) subfamily consists of at least three members, named SREB1 (GPR27), SREB2 (GPR85), and SREB3 (GPR173). They are very highly conserved G protein-coupled receptors throughout vertebrate evolution, however no endogenous ligands have yet been identified. SREB2 is greatly expressed in brain regions involved in psychiatric disorders and cognition, such as the hippocampal dentate gyrus. Genetic studies in both humans and mice have shown that SREB2 influences brain size and negatively regulates hippocampal adult neurogenesis and neurogenesis-dependent cognitive function, all of which are suggesting a potential link between SREB2 and schizophrenia. All three SREB genes are highly expressed in differentiated hippocampal neural stem cells. Furthermore, 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.


Pssm-ID: 320346 [Multi-domain]  Cd Length: 330  Bit Score: 321.60  E-value: 1.08e-108
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  32 VSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMlaaRRAAAAAGTPPGALGCKLLAFLAALFCFHAA 111
Cdd:cd15218   13 VSVVGNLLISILLVKDKTLHRAPYYFLLDLCCSDILRSAICFPFVF---TSVKNGSTWTYGTLTCKVIAFLGVLSCFHTA 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 112 FLLLGVGVTRYLAIAHHRFYAERLAGWPCAAmLVCAAWALALAAAFPPVLDGGGAD--DEDAPCALEQRPDGAPGALGFL 189
Cdd:cd15218   90 FMLFCISVTRYLAIAHHRFYTKRLTFWTCLA-VICMVWTLSVAMAFPPVLDVGTYSfiREEDQCTFQHRSFRANDSLGFM 168
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 190 LLLAAVVGATHLVYLRLLFFIHDRRKMRPARLVPAVSHDWTFHGPGATGQAAANWTAGFGRGPTPPALVGIRPAGPGRGA 269
Cdd:cd15218  169 LLLALILLATQLVYLKLIFFVHDRRKMKPVQFVAAVSQNWTFHGPGASGQAAANWLAGFGRGPTPPTLLGIRQNANTTGR 248
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 270 RRLLVLEEFKTEKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRPGAVPQAYLTASVWLTFAQAGINPVVCFLFNRELRD 349
Cdd:cd15218  249 RRLLVLDEFKMEKRISRMFYIMTFLFLTLWGPYLVACYWRVFARGPVVPGGFLTAAVWMSFAQAGINPFVCIFSNRELRR 328

                 ..
gi 149036820 350 CF 351
Cdd:cd15218  329 CF 330
7tm_classA_rhodopsin-like cd00637
rhodopsin receptor-like class A family of the seven-transmembrane G protein-coupled receptor ...
31-344 5.71e-19

rhodopsin receptor-like class A family of the seven-transmembrane G protein-coupled receptor superfamily; Class A rhodopsin-like receptors constitute about 90% of all GPCRs. The class A GPCRs include 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. Based on sequence similarity, GPCRs can be divided into six major classes: class A (rhodopsin-like family), class B (Methuselah-like, adhesion and secretin-like receptor family), class C (metabotropic glutamate receptor family), class D (fungal mating pheromone receptors), class E (cAMP receptor family), and class F (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.


Pssm-ID: 410626 [Multi-domain]  Cd Length: 275  Bit Score: 85.80  E-value: 5.71e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  31 CVSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLAARRAAAaagtPPGALGCKLLAFLAALFCFHA 110
Cdd:cd00637   10 VVGLVGNLLVILVILRNRRLRTVTNYFILNLAVADLLVGLLVIPFSLVSLLLGRW----WFGDALCKLLGFLQSVSLLAS 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 111 AFLLLGVGVTRYLAIAHHRFYAERLAGWPCAAMLVCaAWALALAAAFPPVLDGGGADDEDAPCALEQRPDGAPGALGFLL 190
Cdd:cd00637   86 ILTLTAISVDRYLAIVHPLRYRRRFTRRRAKLLIAL-IWLLSLLLALPPLLGWGVYDYGGYCCCCLCWPDLTLSKAYTIF 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 191 LLAAVVG--ATHLVYLRLLFFIHDRRKMRPARLVPAVSHdwtfhgpgatgqaaanwtagfgrgptppalvgirpagpgRG 268
Cdd:cd00637  165 LFVLLFLlpLLVIIVCYVRIFRKLRRHRRRIRSSSSNSS---------------------------------------RR 205
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 149036820 269 ARRllvleefKTEKRLCKMFYAITLLFLLLWGPYVVASYLRVLVR-PGAVPQAYLTASVWLTFAQAGINPVVCFLFN 344
Cdd:cd00637  206 RRR-------RRERKVTKTLLIVVVVFLLCWLPYFILLLLDVFGPdPSPLPRILYFLALLLAYLNSAINPIIYAFFN 275
7tmA_Opsins_type2_animals cd14969
type 2 opsins in animals, member of the class A family of seven-transmembrane G ...
32-351 2.09e-10

type 2 opsins in animals, member of the class A family of seven-transmembrane G protein-coupled receptors; This rhodopsin family represents the type 2 opsins found in vertebrates and invertebrates except sponge. Type 2 opsins primarily function as G protein coupled receptors and are responsible for vision as well as for circadian rhythm and pigment regulation. On the contrary, type 1 opsins such as bacteriorhodopsin and proteorhodopsin are found in both prokaryotic and eukaryotic microbes, functioning as light-gated ion channels, proton pumps, sensory receptors and in other unknown functions. Although these two opsin types share seven-transmembrane domain topology and a conserved lysine reside in the seventh helix, type 1 opsins do not activate G-proteins and are not evolutionarily related to type 2. Type 2 opsins can be classified into six distinct subfamilies including the vertebrate opsins/encephalopsins, the G(o) opsins, the G(s) opsins, the invertebrate G(q) opsins, the photoisomerases, and the neuropsins.


Pssm-ID: 381741 [Multi-domain]  Cd Length: 284  Bit Score: 61.07  E-value: 2.09e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  32 VSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLAARRAAAAAGTPpgalGCKLLAFLAALFCFHAA 111
Cdd:cd14969   13 LGVVLNGLVIIVFLKKKKLRTPLNLFLLNLALADLLMSVVGYPLSFYSNLSGRWSFGDP----GCVIYGFAVTFLGLVSI 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 112 FLLLGVGVTRYLAIAhHRFYAERLAGWpCAAMLVCAAWALALAAAFPP-------VLDGGGADdedapCALEQRPDGApg 184
Cdd:cd14969   89 STLAALAFERYLVIV-RPLKAFRLSKR-RALILIAFIWLYGLFWALPPlfgwssyVPEGGGTS-----CSVDWYSKDP-- 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 185 algfllllaavVGATHLVYLRLLFFIhdrrkmrparlVPAVSHDWTFhgpgatgqaaaNWTAGFGRGPTPPALVGIRPAG 264
Cdd:cd14969  160 -----------NSLSYIVSLFVFCFF-----------LPLAIIIFCY-----------YKIYRTLRKMSKRAARRKNSAI 206
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 265 PGRGarrllvleeFKTEKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRPGAVPQAYLTASVWltFAQAGI--NPVVCFL 342
Cdd:cd14969  207 TKRT---------KKAEKKVAKMVLVMIVAFLIAWTPYAVVSLYVSFGGESTIPPLLATIPAL--FAKSSTiyNPIIYVF 275

                 ....*....
gi 149036820 343 FNRELRDCF 351
Cdd:cd14969  276 MNKQFRRAL 284
7tm_1 pfam00001
7 transmembrane receptor (rhodopsin family); This family contains, amongst other ...
36-146 7.00e-09

7 transmembrane receptor (rhodopsin family); This family contains, amongst other G-protein-coupled receptors (GCPRs), members of the opsin family, which have been considered to be typical members of the rhodopsin superfamily. They share several motifs, mainly the seven transmembrane helices, GCPRs of the rhodopsin superfamily. All opsins bind a chromophore, such as 11-cis-retinal. The function of most opsins other than the photoisomerases is split into two steps: light absorption and G-protein activation. Photoisomerases, on the other hand, are not coupled to G-proteins - they are thought to generate and supply the chromophore that is used by visual opsins.


Pssm-ID: 459624 [Multi-domain]  Cd Length: 256  Bit Score: 56.15  E-value: 7.00e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820   36 GNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLaarRAAAAAGTPPGALGCKLLAFLAALFCFHAAFLLL 115
Cdd:pfam00001   1 GNLLVILVILRNKKLRTPTNIFLLNLAVADLLFSLLTLPFWLV---YYLNHGDWPFGSALCKIVGALFVVNGYASILLLT 77
                          90       100       110
                  ....*....|....*....|....*....|.
gi 149036820  116 GVGVTRYLAIAHHRFYAERLAGWPCAAMLVC 146
Cdd:pfam00001  78 AISIDRYLAIVHPLRYKRRRTPRRAKVLILV 108
7tmA_amine_R-like cd14967
amine receptors and similar proteins, member of the class A family of seven-transmembrane G ...
31-351 8.65e-09

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.


Pssm-ID: 320098 [Multi-domain]  Cd Length: 259  Bit Score: 55.65  E-value: 8.65e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  31 CVSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLaarrAAAAAGTPPGALGCKLLAFLAALFCFHA 110
Cdd:cd14967   11 LVTVFGNLLVILAVYRNRRLRTVTNYFIVSLAVADLLVALLVMPFSAV----YTLLGYWPFGPVLCRFWIALDVLCCTAS 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 111 AFLLLGVGVTRYLAIAHHRFYAER----------LAGWPCAAMLvcaawalalaaAFPPVLdGGGADDEDAPCALEQRPd 180
Cdd:cd14967   87 ILNLCAISLDRYLAITRPLRYRQLmtkkralimiAAVWVYSLLI-----------SLPPLV-GWRDETQPSVVDCECEF- 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 181 gapgalgfllllaaVVGATHLVYLRLLFFIhdrrkmrparlVPAVSHDWTFhgpgatgqaaanwtagfgrgptppalvgi 260
Cdd:cd14967  154 --------------TPNKIYVLVSSVISFF-----------IPLLIMIVLY----------------------------- 179
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 261 rpagpgrgARRLLVLeefKTEKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRPGAVPQAYLTASVWLTFAQAGINPVVC 340
Cdd:cd14967  180 --------ARIFRVA---RRELKAAKTLAIIVGAFLLCWLPFFIIYLVSAFCPPDCVPPILYAVFFWLGYLNSALNPIIY 248
                        330
                 ....*....|.
gi 149036820 341 FLFNRELRDCF 351
Cdd:cd14967  249 ALFNRDFRRAF 259
7tmA_CCKR-like cd14993
cholecystokinin receptors and related proteins, member of the class A family of ...
31-127 4.64e-07

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.


Pssm-ID: 320124 [Multi-domain]  Cd Length: 296  Bit Score: 50.68  E-value: 4.64e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  31 CVSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLAARRAAAAAgtppGALGCKLLAFLAALFCFHA 110
Cdd:cd14993   12 LLALVGNSLVIAVVLRNKHMRTVTNYFLVNLAVADLLVSLFCMPLTLLENVYRPWVF----GEVLCKAVPYLQGVSVSAS 87
                         90
                 ....*....|....*..
gi 149036820 111 AFLLLGVGVTRYLAIAH 127
Cdd:cd14993   88 VLTLVAISIDRYLAICY 104
7tmA_5-HT2B cd15306
serotonin receptor subtype 2B, member of the class A family of seven-transmembrane G ...
271-357 8.75e-07

serotonin receptor subtype 2B, 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.


Pssm-ID: 341347 [Multi-domain]  Cd Length: 277  Bit Score: 49.83  E-value: 8.75e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 271 RLLVLEEFKTEKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRP--GAVPQAYLTASVWLTFAQAGINPVVCFLFNRELR 348
Cdd:cd15306  188 HALRKQTITNEQRASKVLGIVFFLFLLMWCPFFITNITSVLCDScnQTTLQMLMEIFVWIGYVSSGVNPLVYTLFNKTFR 267

                 ....*....
gi 149036820 349 DCFRAQFPC 357
Cdd:cd15306  268 DAFGRYITC 276
7tmA_5-HT2C cd15305
serotonin receptor subtype 2C, member of the class A family of seven-transmembrane G ...
276-357 1.90e-06

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.


Pssm-ID: 341346 [Multi-domain]  Cd Length: 275  Bit Score: 48.75  E-value: 1.90e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 276 EEFKTEKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRPGA---VPQAYLTASVWLTFAQAGINPVVCFLFNRELRDCFR 352
Cdd:cd15305  191 QAINNERRASKVLGIVFFLFLIMWCPFFITNILSVLCKEACdqkLMEELLNVFVWVGYVSSGINPLVYTLFNKTYRRAFS 270

                 ....*
gi 149036820 353 AQFPC 357
Cdd:cd15305  271 NYIRC 275
7tmA_PR4-like cd15392
neuropeptide Y receptor-like found in insect and related proteins, member of the class A ...
32-127 3.55e-06

neuropeptide Y receptor-like found in insect and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subgroup includes a novel G protein-coupled receptor (also known as PR4 receptor) from Drosophila melanogaster, which can be activated by the members of the neuropeptide Y (NPY) family, including NPY, peptide YY (PYY) and pancreatic polypeptide (PP), when expressed in Xenopus oocytes. These homologous peptides of 36-amino acids in length contain a hairpin-like structural motif, which referred to as the pancreatic polypeptide fold, and function as gastrointestinal hormones and neurotransmitters. The PR4 receptor also shares strong sequence homology to the mammalian tachykinin receptors (NK1R, NK2R, and NK3R), whose endogenous ligands are substance P (SP), neurokinin A (NKA), and neurokinin B (NKB), respectively. The tachykinins function as excitatory transmitters on neurons and cells in the gastrointestinal tract.


Pssm-ID: 320514 [Multi-domain]  Cd Length: 287  Bit Score: 48.13  E-value: 3.55e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  32 VSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLP----AVMLAARRaaaaagtPPGALGCKLLAFLAALFC 107
Cdd:cd15392   13 LAVGGNGLVCYIVVSYPRMRTVTNYFIVNLALSDILMAVFCVPfsfiALLILQYW-------PFGEFMCPVVNYLQAVSV 85
                         90       100
                 ....*....|....*....|
gi 149036820 108 FHAAFLLLGVGVTRYLAIAH 127
Cdd:cd15392   86 FVSAFTLVAISIDRYVAIMW 105
7tmA_OXR cd15208
orexin receptors, member of the class A family of seven-transmembrane G protein-coupled ...
32-127 1.04e-05

orexin receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; 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. Thus, activation of OX1R or OX2R will activate phospholipase activity and the phosphatidylinositol and calcium signaling pathways. Additionally, OX2R activation can also lead to inhibition of adenylate cyclase.


Pssm-ID: 320336 [Multi-domain]  Cd Length: 303  Bit Score: 46.61  E-value: 1.04e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  32 VSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLAARRAAAAAGTppgaLGCKLLAFLAALFCFHAA 111
Cdd:cd15208   13 VGLVGNVLVCFAVWRNHHMRTVTNYFIVNLSLADFLVIIICLPATLLVDVTETWFFGQ----VLCKIIPYLQTVSVSVSV 88
                         90
                 ....*....|....*.
gi 149036820 112 FLLLGVGVTRYLAIAH 127
Cdd:cd15208   89 LTLSCIALDRWYAICH 104
7tmA_Beta3_AR cd15959
beta-3 adrenergic receptors (adrenoceptors), member of the class A family of ...
32-339 1.34e-05

beta-3 adrenergic receptors (adrenoceptors), member of the class A family of seven-transmembrane G protein-coupled receptors; The beta-3 adrenergic receptor (beta-3 adrenoceptor), also known as beta-3 AR, is activated by adrenaline and plays important roles in regulating cardiac function and heart rate. The human heart contains three subtypes of the beta AR: beta-1 AR, beta-2 AR, and beta-3 AR. Beta-1 AR and beta-2 AR, which expressed at about a ratio of 70:30, are the major subtypes involved in modulating cardiac contractility and heart rate by positively stimulating the G(s) protein-adenylate cyclase-cAMP-PKA signaling pathway. In contrast, beta-3 AR produces negative inotropic effects by activating inhibitory G(i) proteins. The aberrant expression of betrayers can lead to cardiac dysfunction such as arrhythmias or heart failure.


Pssm-ID: 320625 [Multi-domain]  Cd Length: 302  Bit Score: 46.44  E-value: 1.34e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  32 VSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAvmlaARRAAAAAGTPPGALGCKLLAFLAALFCFHAA 111
Cdd:cd15959   13 VIVGGNLLVIVAIAKTPRLQTMTNVFVTSLACADLVMGLLVVPP----GATILLTGHWPLGTTVCELWTSVDVLCVTASI 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 112 FLLLGVGVTRYLAIAHHRFYaERLAGWPCAAMLVCAAWALALAAAFPPVLDG---GGADDEDAPCAleqrpDGAPGALGF 188
Cdd:cd15959   89 ETLCAIAVDRYLAITNPLRY-EALVTKRRARTAVCLVWAISAAISFLPIMNQwwrDGADEEAQRCY-----DNPRCCDFV 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 189 LLLLAAVVGATHLVYLRLL--FFIHDRRKMRPARLVPAVSHDwtfhgpgatgqaaanwtagFGR-GPTPPALVGIRPAGp 265
Cdd:cd15959  163 TNMPYAIVSSTVSFYVPLLvmIFVYVRVFVVATRQVRLIRKD-------------------KVRfPPEESPPAESRPAC- 222
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 149036820 266 GRGARRLLVLEEFKTEKRLCkmfyAITLLFLLLWGPYVVASYLRVLVRPGAVPQAYLTASvWLTFAQAGINPVV 339
Cdd:cd15959  223 GRRPSRLLAIKEHKALKTLG----IIMGTFTLCWLPFFVANIIKVFCRSLVPDPAFLFLN-WLGYANSAFNPII 291
7tmA_EDG-like cd14972
endothelial differentiation gene family, member of the class A family of seven-transmembrane G ...
31-145 1.82e-05

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.


Pssm-ID: 341317 [Multi-domain]  Cd Length: 275  Bit Score: 45.75  E-value: 1.82e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  31 CVSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLAARRAAAAagTPPGALGCKLLAFLAALfcfHA 110
Cdd:cd14972   10 VFIVVENSLVLAAIIKNRRLHKPMYILIANLAAADLLAGIAFVFTFLSVLLVSLTP--SPATWLLRKGSLVLSLL---AS 84
                         90       100       110
                 ....*....|....*....|....*....|....*
gi 149036820 111 AFLLLGVGVTRYLAIAHHRFYAERLAGWPCAAMLV 145
Cdd:cd14972   85 AYSLLAIAVDRYISIVHGLTYVNNVTNKRVKVLIA 119
7tmA_5-HT2A cd15304
serotonin receptor subtype 2A, member of the class A family of seven-transmembrane G ...
276-351 2.16e-05

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.


Pssm-ID: 341345 [Multi-domain]  Cd Length: 267  Bit Score: 45.69  E-value: 2.16e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 149036820 276 EEFKTEKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRPGAVPQ---AYLTASVWLTFAQAGINPVVCFLFNRELRDCF 351
Cdd:cd15304  189 QSISNEQKASKVLGIVFFLFVVMWCPFFITNVMAVICKESCNEVvigGLLNVFVWIGYLSSAVNPLVYTLFNKTYRSAF 267
7tmA_5-HT2 cd15052
serotonin receptor subtype 2, member of the class A family of seven-transmembrane G ...
280-351 2.38e-05

serotonin receptor subtype 2, 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.


Pssm-ID: 320180 [Multi-domain]  Cd Length: 262  Bit Score: 45.38  E-value: 2.38e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 149036820 280 TEKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRPG--AVPQAYLTASVWLTFAQAGINPVVCFLFNRELRDCF 351
Cdd:cd15052  189 NEQKASKVLGIVFAVFVICWCPFFITNILTGLCEECncRISPWLLSVFVWLGYVSSTINPIIYTIFNKTFRRAF 262
7tmA_PrRP_R cd15394
prolactin-releasing peptide receptor, member of the class A family of seven-transmembrane G ...
32-146 2.58e-05

prolactin-releasing peptide receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; Prolactin-releasing peptide (PrRP) receptor (previously known as GPR10) is expressed in the central nervous system with the highest levels located in the anterior pituitary and is activated by its endogenous ligand PrRP, a neuropeptide possessing a C-terminal Arg-Phe-amide motif. There are two active isoforms of PrRP in mammals: one consists of 20 amino acids (PrRP-20) and the other consists of 31 amino acids (PrRP-31), where PrRP-20 is a C-terminal fragment of PrRP-31. Binding of PrRP to the receptor coupled to G(i/o) proteins activates the extracellular signal-related kinase (ERK) and it can also couple to G(q) protein leading to an increase in intracellular calcium and activation of c-Jun N-terminal protein kinase (JNK). The PrRP receptor shares significant sequence homology with the neuropeptide Y (NPY) receptor, and micromolar levels of NPY can bind and completely inhibit the PrRP-evoked intracellular calcium response in PrRP receptor-expressing cells, suggesting that the PrRP receptor shares a common ancestor with the NPY receptors. PrRP has been shown to reduce food intake and body weight and modify body temperature when administered in rats. It also has been shown to decrease circulating growth hormone levels by activating somatostatin-secreting neurons in the hypothalamic periventricular nucleus.


Pssm-ID: 320516 [Multi-domain]  Cd Length: 286  Bit Score: 45.50  E-value: 2.58e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  32 VSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPavmLAARRAAAAAGTPPGALGCKLLAFLAALFCFHAA 111
Cdd:cd15394   13 VGVVGNYLLIYVICRTKKMHNVTNFLIGNLAFSDMLMCATCVP---LTLAYAFEPRGWVFGRFMCYFVFLMQPVTVYVSV 89
                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 149036820 112 FLLLGVGVTRYLAIAH--HRfyaeRLAGWPCAAMLVC 146
Cdd:cd15394   90 FTLTAIAVDRYYVTVYplRR----RISRRTCAYIVAA 122
7tmA_mAChR_M1 cd17790
muscarinic acetylcholine receptor subtype M1, member of the class A family of ...
274-351 3.23e-05

muscarinic acetylcholine receptor subtype M1, member of the class A family of seven-transmembrane G protein-coupled receptors; Muscarinic acetylcholine receptors (mAChRs) regulate the activity of many fundamental central and peripheral functions. The mAChR family consists of 5 subtypes M1-M5, which can be further divided into two major groups according to their G-protein coupling preference. The M1, M3 and M5 receptors selectively interact with G proteins of the G(q/11) family, whereas the M2 and M4 receptors preferentially link to the G(i/o) types of G proteins. Activation of mAChRs by agonist (acetylcholine) leads to a variety of biochemical and electrophysiological responses. M1 is the dominant mAChR subtype involved in learning and memory. It is linked to synaptic plasticity, neuronal excitability, and neuronal differentiation during early development. 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.


Pssm-ID: 341356 [Multi-domain]  Cd Length: 262  Bit Score: 44.96  E-value: 3.23e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 274 VLEEFKTEKRLCKMFYAITLLFLLLWGPYVVAsylrVLVR---PGAVPQAYLTASVWLTFAQAGINPVVCFLFNRELRDC 350
Cdd:cd17790  186 IYRETIKEKKAARTLSAILLAFILTWTPYNIM----VLVStfcKDCVPKTLWELGYWLCYVNSTVNPMCYALCNKSFRDT 261

                 .
gi 149036820 351 F 351
Cdd:cd17790  262 F 262
7tmA_mAChR_M3 cd15299
muscarinic acetylcholine receptor subtype M3, member of the class A family of ...
274-357 4.05e-05

muscarinic acetylcholine receptor subtype M3, member of the class A family of seven-transmembrane G protein-coupled receptors; Muscarinic acetylcholine receptors (mAChRs) regulate the activity of many fundamental central and peripheral functions. The mAChR family consists of 5 subtypes M1-M5, which can be further divided into two major groups according to their G-protein coupling preference. The M1, M3 and M5 receptors selectively interact with G proteins of the G(q/11) family, whereas the M2 and M4 receptors preferentially link to the G(i/o) types of G proteins. The M3 receptor is mainly located in smooth muscle, exocrine glands and vascular endothelium. It induces vomiting in the central nervous system and is a critical regulator of glucose homeostasis by modulating insulin secretion. Generally, M3 receptor causes contraction of smooth muscle resulting in vasoconstriction and increased glandular secretion. 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.


Pssm-ID: 320426 [Multi-domain]  Cd Length: 274  Bit Score: 44.94  E-value: 4.05e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 274 VLEEFKTEKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRPgAVPQAYLTASVWLTFAQAGINPVVCFLFNRELRDCFRA 353
Cdd:cd15299  189 IYKETIKEKKAAQTLSAILLAFIITWTPYNIMVLVNTFCDS-CIPKTYWNLGYWLCYINSTVNPVCYALCNKTFRTTFKM 267

                 ....
gi 149036820 354 QFPC 357
Cdd:cd15299  268 LLLC 271
7tmA_TACR_family cd14992
tachykinin receptor and closely related proteins, member of the class A family of ...
32-127 5.17e-05

tachykinin receptor and closely related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subfamily includes G-protein coupled receptors for a variety of neuropeptides of the tachykinin (TK) family as well as closely related receptors. The tachykinins are widely distributed throughout the mammalian central and peripheral nervous systems and act as excitatory transmitters on neurons and cells in the gastrointestinal tract. The TKs are characterized by a common five-amino acid C-terminal sequence, Phe-X-Gly-Leu-Met-NH2, where X is a hydrophobic residue. The three major mammalian tachykinins are substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). The physiological actions of tachykinins are mediated through three types of receptors: neurokinin receptor type 1 (NK1R), NK2R, and NK3R. SP is a high-affinity endogenous ligand for NK1R, which interacts with the Gq protein and activates phospholipase C, leading to elevation of intracellular calcium. NK2R is a high-affinity receptor for NKA, the tachykinin neuropeptide substance K. SP and NKA are found in the enteric nervous system and mediate in the regulation of gastrointestinal motility, secretion, vascular permeability, and pain perception. NK3R is activated by its high-affinity ligand, NKB, which is primarily involved in the central nervous system and plays a critical role in the regulation of gonadotropin hormone release and the onset of puberty.


Pssm-ID: 320123 [Multi-domain]  Cd Length: 291  Bit Score: 44.73  E-value: 5.17e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  32 VSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLAARRAAAaagtPPGALGCKLLAFLAALFCFHAA 111
Cdd:cd14992   13 VSVVGNFIVIAALARHKNLRGATNYFIASLAISDLLMALFCTPFNFTYVVSLSW----EYGHFLCKIVNYLRTVSVYASS 88
                         90
                 ....*....|....*.
gi 149036820 112 FLLLGVGVTRYLAIAH 127
Cdd:cd14992   89 LTLTAIAFDRYFAIIH 104
7tmA_D3_dopamine_R cd15310
D3 subtype of the D2-like family of dopamine receptors, member of the class A family of ...
281-351 8.22e-05

D3 subtype of the D2-like family of dopamine receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Dopamine receptors are members of the class A G protein-coupled receptors that are involved in many neurological processes in the central nervous system (CNS). The neurotransmitter dopamine is the primary endogenous agonist for dopamine receptors. Dopamine receptors consist of at least five subtypes: D1, D2, D3, D4, and D5. The D1 and D5 subtypes are members of the D1-like family of dopamine receptors, whereas the D2, D3 and D4 subtypes are members of the D2-like family. Activation of D2-like family receptors is linked to G proteins of the G(i) family. This leads to a decrease in adenylate cyclase activity, thereby decreasing cAMP levels. Dopamine receptors are major therapeutic targets for neurological and psychiatric disorders such as drug abuse, depression, schizophrenia, or Parkinson's disease.


Pssm-ID: 320436 [Multi-domain]  Cd Length: 259  Bit Score: 43.80  E-value: 8.22e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 149036820 281 EKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRPGAVPQAYLTASVWLTFAQAGINPVVCFLFNRELRDCF 351
Cdd:cd15310  189 EKKATQMLAIVLGAFIVCWLPFFLTHILNTHCQACHVPPELYSATTWLGYVNSALNPVIYTTFNIEFRRAF 259
7tmA_ETH-R cd14997
ecdysis-triggering hormone receptors, member of the class A family of seven-transmembrane G ...
32-127 9.45e-05

ecdysis-triggering hormone receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; This subgroup represents the ecdysis-triggering hormone receptors found in insects, which are members of the class A family of seven-transmembrane G-protein coupled receptors. Ecdysis-triggering hormones are vital regulatory signals that govern the stereotypic physiological sequence leading to cuticle shedding in insects. Thus, the ETH signaling system has been a target for the design of more sophisticated insect-selective pest control strategies. Two subtypes of ecdysis-triggering hormone receptor were identified in Drosophila melanogaster. Blood-borne ecdysis-triggering hormone (ETH) activates the behavioral sequence through direct actions on the central nervous system. In insects, ecdysis is thought to be controlled by the interaction between peptide hormones; in particular between ecdysis-triggering hormone (ETH) from the periphery and eclosion hormone (EH) and crustacean cardioactive peptide (CCAP) from the central nervous system. 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.


Pssm-ID: 320128 [Multi-domain]  Cd Length: 294  Bit Score: 43.82  E-value: 9.45e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  32 VSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLAARRAAaaagtpPGALG---CKLLAFLAALFCF 108
Cdd:cd14997   13 VGVLGNVLVGIVVWKNKDMRTPTNIFLVNLSVADLLVLLVCMPVALVETWARE------PWLLGefmCKLVPFVELTVAH 86
                         90
                 ....*....|....*....
gi 149036820 109 HAAFLLLGVGVTRYLAIAH 127
Cdd:cd14997   87 ASVLTILAISFERYYAICH 105
7tmA_D2-like_dopamine_R cd15053
D2-like dopamine receptors, member of the class A family of seven-transmembrane G ...
32-132 2.25e-04

D2-like dopamine receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Dopamine receptors are members of the class A G protein-coupled receptors that are involved in many neurological processes in the central nervous system (CNS). The neurotransmitter dopamine is the primary endogenous agonist for dopamine receptors. Dopamine receptors consist of at least five subtypes: D1, D2, D3, D4, and D5. The D1 and D5 subtypes are members of the D1-like family of dopamine receptors, whereas the D2, D3 and D4 subtypes are members of the D2-like family. The D1-like family receptors are coupled to G proteins of the G(s) family, which activate adenylate cyclase, causing cAMP formation and activation of protein kinase A. In contrast, activation of D2-like family receptors is linked to G proteins of the G(i) family, which inhibit adenylate cyclase. Dopamine receptors are major therapeutic targets for neurological and psychiatric disorders such as drug abuse, depression, schizophrenia, or Parkinson's disease.


Pssm-ID: 320181 [Multi-domain]  Cd Length: 263  Bit Score: 42.33  E-value: 2.25e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  32 VSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLP-AVMLAARRAAAAAGTppgaLGCKLLAFLAALFCFHA 110
Cdd:cd15053   13 LTVFGNVLVIMSVFRERSLQTATNYFIVSLAVADLLVAILVMPfAVYVEVNGGKWYLGP----ILCDIYIAMDVMCSTAS 88
                         90       100
                 ....*....|....*....|..
gi 149036820 111 AFLLLGVGVTRYLAIAHHRFYA 132
Cdd:cd15053   89 IFNLCAISIDRYIAVTQPIKYA 110
7tmA_5-HT2A cd15304
serotonin receptor subtype 2A, member of the class A family of seven-transmembrane G ...
32-130 2.61e-04

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.


Pssm-ID: 341345 [Multi-domain]  Cd Length: 267  Bit Score: 42.23  E-value: 2.61e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  32 VSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLaarRAAAAAGTPPGALGCKLLAFLAALFCFHAA 111
Cdd:cd15304   13 LTIAGNILVIMAVSLEKKLQNATNYFLMSLAIADMLLGFLVMPVSML---TILYGYRWPLPSKLCAVWIYLDVLFSTASI 89
                         90       100
                 ....*....|....*....|...
gi 149036820 112 FLLLGVGVTRYLAIA----HHRF 130
Cdd:cd15304   90 MHLCAISLDRYIAIRnpihHSRF 112
7tmA_Opsin5_neuropsin cd15074
neuropsin (Opsin-5), member of the class A family of seven-transmembrane G protein-coupled ...
279-350 3.57e-04

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.


Pssm-ID: 320202 [Multi-domain]  Cd Length: 284  Bit Score: 41.88  E-value: 3.57e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 149036820 279 KTEKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRPGAVP-QAYLTASVwltFAQAG--INPVVCFLFNRELRDC 350
Cdd:cd15074  212 KIERKVTKVAVLICAGFLIAWTPYAVVSMWSAFGSPDSVPiLASILPAL---FAKSScmYNPIIYLLFSSKFRQD 283
7tmA_GPRnna14-like cd15001
GPRnna14 and related proteins, member of the class A family of seven-transmembrane G ...
32-127 4.08e-04

GPRnna14 and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes the orphan G-protein coupled receptor GPRnna14 found in body louse (Pediculus humanus humanus) as well as its closely related proteins of unknown function. These receptors are members of the class A rhodopsin-like G-protein coupled receptors. As an obligatory parasite of humans, the body louse is an important vector for human diseases, including epidemic typhus, relapsing fever, and trench fever. GPRnna14 shares significant sequence similarity with the members of the neurotensin receptor family. 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.


Pssm-ID: 320132 [Multi-domain]  Cd Length: 266  Bit Score: 41.49  E-value: 4.08e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  32 VSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPaVMLAARRAAAAAGtppGALGCKLLAFLAALFCFHAA 111
Cdd:cd15001   12 LGLIGNSLVIFVVARFRRMRSVTNVFLASLATADLLLLVFCVP-LKTAEYFSPTWSL---GAFLCKAVAYLQLLSFICSV 87
                         90
                 ....*....|....*.
gi 149036820 112 FLLLGVGVTRYLAIAH 127
Cdd:cd15001   88 LTLTAISIERYYVILH 103
7tmA_NPFFR cd15207
neuropeptide FF receptors, member of the class A family of seven-transmembrane G ...
33-127 5.33e-04

neuropeptide FF receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Neuropeptide FF (NPFF) is a mammalian octapeptide that belongs to a family of neuropeptides containing an RF-amide motif at their C-terminus that have 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 these peptides 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. NPFF has been shown to inhibit adenylate cyclase via the Gi protein coupled to NPFF1-R.


Pssm-ID: 320335 [Multi-domain]  Cd Length: 291  Bit Score: 41.45  E-value: 5.33e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  33 SLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLaarrAAAAAGTPPGALGCKLLAFLAALFCFHAAF 112
Cdd:cd15207   14 CVVGNVLVCLVVAKNPRMRTVTNYFILNLAVSDLLVGVFCMPFTLV----DNILTGWPFGDVMCKLSPLVQGVSVAASVF 89
                         90
                 ....*....|....*
gi 149036820 113 LLLGVGVTRYLAIAH 127
Cdd:cd15207   90 TLVAIAVDRYRAVVH 104
7tmA_Melanopsin cd15336
vertebrate melanopsins (Opsin-4), member of the class A family of seven-transmembrane G ...
31-125 5.43e-04

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.


Pssm-ID: 320458 [Multi-domain]  Cd Length: 290  Bit Score: 41.24  E-value: 5.43e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  31 CVSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLAARRAAAAAGTppgaLGCKLLAFLAALFCFHA 110
Cdd:cd15336   12 ITGMLGNALVIYAFCRSKKLRTPANYFIINLAVSDFLMSLTQSPIFFVNSLHKRWIFGE----KGCELYAFCGALFGITS 87
                         90
                 ....*....|....*
gi 149036820 111 AFLLLGVGVTRYLAI 125
Cdd:cd15336   88 MITLLAISLDRYLVI 102
7tmA_NPFFR cd15207
neuropeptide FF receptors, member of the class A family of seven-transmembrane G ...
279-351 5.47e-04

neuropeptide FF receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Neuropeptide FF (NPFF) is a mammalian octapeptide that belongs to a family of neuropeptides containing an RF-amide motif at their C-terminus that have 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 these peptides 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. NPFF has been shown to inhibit adenylate cyclase via the Gi protein coupled to NPFF1-R.


Pssm-ID: 320335 [Multi-domain]  Cd Length: 291  Bit Score: 41.45  E-value: 5.47e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 149036820 279 KTEKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRPGAVPQAYLTASV-----WLTFAQAGINPVVCFLFNRELRDCF 351
Cdd:cd15207  214 KKKVRVIKMLIVVVVLFALSWLPLHTVTMLDDFGNLSPNQREVLYVYIypiahWLAYFNSCVNPIVYGYFNRNFRKGF 291
7tmA_D4_dopamine_R cd15308
D4 dopamine receptor of the D2-like family, member of the class A family of ...
281-351 5.99e-04

D4 dopamine receptor of the D2-like family, member of the class A family of seven-transmembrane G protein-coupled receptors; Dopamine receptors are members of the class A G protein-coupled receptors that are involved in many neurological processes in the central nervous system (CNS). The neurotransmitter dopamine is the primary endogenous agonist for dopamine receptors. Dopamine receptors consist of at least five subtypes: D1, D2, D3, D4, and D5. The D1 and D5 subtypes are members of the D1-like family of dopamine receptors, whereas the D2, D3 and D4 subtypes are members of the D2-like family. Activation of D2-like family receptors is linked to G proteins of the G(i) family. This leads to a decrease in adenylate cyclase activity, thereby decreasing cAMP levels. Dopamine receptors are major therapeutic targets for neurological and psychiatric disorders such as drug abuse, depression, schizophrenia, or Parkinson's disease.


Pssm-ID: 320434 [Multi-domain]  Cd Length: 258  Bit Score: 40.97  E-value: 5.99e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 149036820 281 EKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRPGAVPQAYLTASVWLTFAQAGINPVVCFLFNRELRDCF 351
Cdd:cd15308  188 ERKAMRVLPVVVGAFLFCWTPFFVVHITRALCESCSIPPQLISIVTWLGYVNSALNPVIYTVFNAEFRNVF 258
7tmA_Adenosine_R cd14968
adenosine receptor subfamily, member of the class A family of seven-transmembrane G ...
32-125 6.27e-04

adenosine receptor subfamily, member of the class A family of seven-transmembrane G protein-coupled receptors; The adenosine receptors (or P1 receptors), a family of G protein-coupled purinergic receptors, bind adenosine as their endogenous ligand. There are four types of adenosine receptors in human, designated as A1, A2A, A2B, and A3. Each type is encoded by a different gene and has distinct functions with some overlap. For example, both A1 and A2A receptors are involved in regulating myocardial oxygen consumption and coronary blood flow in the heart, while the A2A receptor also has a broad spectrum of anti-inflammatory effects in the body. These two receptors also expressed in the brain, where they have important roles in the release of other neurotransmitters such as dopamine and glutamate, while the A2B and A3 receptors found primarily in the periphery and play important roles in inflammation and immune responses. The A1 and A3 receptors preferentially interact with G proteins of the G(i/o) family, thereby lowering the intracellular cAMP levels, whereas the A2A and A2B receptors interact with G proteins of the G(s) family, activating adenylate cyclase to elevate cAMP levels.


Pssm-ID: 341316 [Multi-domain]  Cd Length: 285  Bit Score: 41.09  E-value: 6.27e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  32 VSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLaarraaAAAGTPPGALGCKLLAFLAALFCFHAA 111
Cdd:cd14968   13 LSVLGNVLVIWAVKLNRALRTVTNYFIVSLAVADILVGALAIPLAIL------ISLGLPTNFHGCLFMACLVLVLTQSSI 86
                         90
                 ....*....|....
gi 149036820 112 FLLLGVGVTRYLAI 125
Cdd:cd14968   87 FSLLAIAIDRYLAI 100
7tmA_GPR161 cd15214
orphan G protein-coupled receptor 161, member of the class A family of seven-transmembrane G ...
285-348 7.41e-04

orphan G protein-coupled receptor 161, member of the class A family of seven-transmembrane G protein-coupled receptors; GPR161, an orphan GPCR, is a negative regulator of Sonic hedgehog (Shh) signaling, which promotes the processing of zinc finger protein GLI3 into its transcriptional repressor form (GLI3R) during neural tube development. In the absence of Shh, this proteolytic processing is normally mediated by cAMP-dependent protein kinase A (PKA). GPR161 is recruited to primary cilia by a mechanism depends on TULP3 (tubby-related protein 3) and the intraflagellar complex A (IFT-A). Moreover, Gpr161 knockout mice show phenotypes observed in Tulp3/IFT-A mutants, and cause increased Shh signaling in the neural tube. Taken together, GPR161 negatively regulates the PKA-dependent GLI3 processing in the absence of Shh signal by coupling to G(s) protein, which causes activation of adenylate cyclase, elevated cAMP levels, and activation of PKA. Conversely, in the presence of Shh, GPR161 is removed from the cilia by internalization into the endosomal recycling compartment, leading to downregulation of its activity and thereby allowing Shh signaling to proceed. In addition, GPR161 is over-expressed in triple-negative breast cancer (lacking estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) expression) and correlates with poor prognosis. Mutations of GPR161 have also been implicated as a novel cause for pituitary stalk interruption syndrome (PSIS), a rare congenital disease of the pituitary gland. GPR161 is a member of the class A family of GPCRs, which contains receptors for hormones, neurotransmitters, sensory stimuli, 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.


Pssm-ID: 320342 [Multi-domain]  Cd Length: 261  Bit Score: 40.69  E-value: 7.41e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 149036820 285 CKMFYAITLL---FLLLWGPYVVASYLRVLVRPGAVPQAYLTASVWLTFAQAGINPVVCFLFNRELR 348
Cdd:cd15214  192 CKAFITILVVlgaFVTTWGPYMVVISTEALWGKNSVSPQLETLATWLSFTSAVCHPLIYGLWNKTVR 258
7tmA_TAAR5-like cd15317
trace amine-associated receptor 5 and similar receptors, member of the class A family of ...
32-127 7.99e-04

trace amine-associated receptor 5 and similar receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Included in this group are mammalian TAAR5, TAAR6, TAAR8, TAAR9, and similar proteins. They are among the 15 identified trace amine-associated receptors (TAARs), a distinct subfamily within the class A G protein-coupled receptors. Trace amines are endogenous amines of unknown function that have strong structural and metabolic similarity to classical monoamine neurotransmitters (serotonin, noradrenaline, adrenaline, dopamine, and histamine), which play critical roles in human and animal physiological activities such as cognition, consciousness, mood, motivation, perception, and autonomic responses. However, trace amines are found in the mammalian brain at very low concentrations compared to classical monoamines. Trace amines, including p-tyramine, beta-phenylethylamine, and tryptamine, are also thought to act as chemical messengers to exert their biological effects in vertebrates. 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.


Pssm-ID: 320440 [Multi-domain]  Cd Length: 290  Bit Score: 40.89  E-value: 7.99e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  32 VSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLAARRAAAAAGTppgaLGCKLLAFLAALFCFHAA 111
Cdd:cd15317   13 ITVSGNLVVIISISHFKQLHSPTNMLVLSLATADFLLGLCVMPFSMIRTVETCWYFGD----LFCKFHTGLDLLLCTTSI 88
                         90
                 ....*....|....*.
gi 149036820 112 FLLLGVGVTRYLAIAH 127
Cdd:cd15317   89 FHLCFIAIDRYYAVCD 104
7tmA_NTSR-like cd14979
neurotensin receptors and related G protein-coupled receptors, member of the class A family of ...
32-127 8.86e-04

neurotensin receptors and related G protein-coupled receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; This subfamily includes the neurotensin receptors and related G-protein coupled receptors, including neuromedin U receptors, growth hormone secretagogue receptor, motilin receptor, the putative GPR39 and the capa receptors from insects. These receptors all bind peptide hormones with diverse physiological effects. 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.


Pssm-ID: 320110 [Multi-domain]  Cd Length: 300  Bit Score: 40.80  E-value: 8.86e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  32 VSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLAARRAAAAagtPPGALGCKLLAFLAALFCFHAA 111
Cdd:cd14979   13 VGIVGNLLTCIVIARHKSLRTTTNYYLFSLAVSDLLILLVGLPVELYNFWWQYPW---AFGDGGCKLYYFLFEACTYATV 89
                         90
                 ....*....|....*.
gi 149036820 112 FLLLGVGVTRYLAIAH 127
Cdd:cd14979   90 LTIVALSVERYVAICH 105
7tmA_TAAR5 cd15318
trace amine-associated receptor 5, member of the class A family of seven-transmembrane G ...
32-138 1.02e-03

trace amine-associated receptor 5, member of the class A family of seven-transmembrane G protein-coupled receptors; The trace amine-associated receptor 5 is one of the 15 identified amine-activated G protein-coupled receptors (TAARs), a distinct subfamily within the class A G protein-coupled receptors. Trace amines are endogenous amines of unknown function that have strong structural and metabolic similarity to classical monoamine neurotransmitters (serotonin, noradrenaline, adrenaline, dopamine, and histamine), which play critical roles in human and animal physiological activities such as cognition, consciousness, mood, motivation, perception, and autonomic responses. However, trace amines are found in the mammalian brain at very low concentrations compared to classical monoamines. Trace amines, including p-tyramine, beta-phenylethylamine, and tryptamine, are also thought to act as chemical messengers to exert their biological effects in vertebrates. 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.


Pssm-ID: 320441 [Multi-domain]  Cd Length: 282  Bit Score: 40.61  E-value: 1.02e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  32 VSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLAARRAAAAAGTppgaLGCKLLAFLAALFCFHAA 111
Cdd:cd15318   13 IIVLGNLFVVVTVSHFKALHTPTNFLLLSLALADMLLGLTVLPFSTIRSVESCWYFGD----SFCRLHTCLDTLFCLTSI 88
                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 149036820 112 FLLLGVGVTRYLAIAHHRFYAER----------LAGW 138
Cdd:cd15318   89 FHLCFISIDRHCAICDPLLYPSKftirvacifiAAGW 125
7tmA_PSP24-like cd15213
G protein-coupled receptor PSP24 and similar proteins, member of the class A family of ...
32-129 1.71e-03

G protein-coupled receptor PSP24 and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes two human orphan receptors, GPR45 and GPR65, and their closely related proteins found in vertebrates and invertebrates. GPR45 and GPR 65 are also called PSP24-alpha (or PSP24-1) and PSP24-beta (or PSP24-2) in other vertebrates, respectively. These receptors exhibit the highest sequence homology to each other. PSP24 was originally identified as a novel, high-affinity lysophosphatidic acid (LPA) receptor in Xenopus laevis oocytes; however, PSP24 receptors (GPR45 and GPR63) have not been shown to be activated by LPA. Instead, sphingosine 1-phosphate and dioleoylphosphatidic acid have been shown to act as low affinity agonists for GPR63. PSP24 receptors are highly expressed in neuronal cells of cerebellum and their expression level remains constant from the early embryonic stages to adulthood, suggesting the important role of PSP24s in brain neuronal functions. Members of this subgroup contain the highly conserved Asp-Arg-Tyr/Phe (DRY/F) motif found in the third transmembrane helix (TM3) of the rhodopsin-like class A receptors which is important for efficient G protein-coupled signal transduction. 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.


Pssm-ID: 320341 [Multi-domain]  Cd Length: 262  Bit Score: 39.66  E-value: 1.71e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  32 VSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLAARRAAAAAGTPPgalgCKLLAFLAALFCFHAA 111
Cdd:cd15213   13 VGFLGNSIVCLIVYQKPAMRSAINLLLANLAFSDIMLSLVCMPFAAVTIITGRWIFGDIF----CRISAMLYWFFVLEGV 88
                         90
                 ....*....|....*...
gi 149036820 112 FLLLGVGVTRYLAIAHHR 129
Cdd:cd15213   89 AILLIISVDRYLIIVQRQ 106
7tmA_5-HT2_insect-like cd15307
serotonin receptor subtype 2 from insects, member of the class A family of seven-transmembrane ...
279-357 1.85e-03

serotonin receptor subtype 2 from insects, 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.


Pssm-ID: 320433 [Multi-domain]  Cd Length: 279  Bit Score: 39.55  E-value: 1.85e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 279 KTEKRLCKMFYAITLLFLLLWGPYVVASylrVLVRPGAVPQAYLTASV-----WLTFAQAGINPVVCFLFNRELRDCFRA 353
Cdd:cd15307  198 RLEQKATKVLGVVFFTFVILWSPFFVLN---LLPTVCAECEERISHWVfdvvtWLGYASSMVNPIFYTIFNKVFRQAFKK 274

                 ....
gi 149036820 354 QFPC 357
Cdd:cd15307  275 VLLC 278
7tmA_GnRHR_invertebrate cd15384
invertebrate gonadotropin-releasing hormone receptors, member of the class A family of ...
32-126 2.39e-03

invertebrate gonadotropin-releasing hormone receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; GnRHR, also known as luteinizing hormone releasing hormone receptor (LHRHR), plays an central role in vertebrate reproductive function; its activation by binding to GnRH leads to the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. GnRHR is expressed predominantly in the gonadotrope membrane of the anterior pituitary as well as found in numerous extrapituitary tissues including lymphocytes, breast, ovary, prostate, and cancer cell lines. There are at least two types of GnRH receptors, GnRHR1 and GnRHR2, which couple primarily to G proteins of the Gq/11 family. GnRHR is closely related to the adipokinetic hormone receptor (AKH), which binds to a lipid-mobilizing hormone that is involved in control of insect metabolism. They share a common ancestor and are members of the class A of the seven-transmembrane, G-protein coupled receptor (GPCR) superfamily.


Pssm-ID: 320506 [Multi-domain]  Cd Length: 293  Bit Score: 39.34  E-value: 2.39e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  32 VSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLAARRAAAAAGTppgaLGCKLLAFLAALFCFHAA 111
Cdd:cd15384   13 ISFIGNLLTIIQIYRLRRSRRTIYSLLLHLAIADLLVTFFCIPSEAIWAYTVAWLAGN----TMCKLVKYLQVFGLYLST 88
                         90
                 ....*....|....*
gi 149036820 112 FLLLGVGVTRYLAIA 126
Cdd:cd15384   89 YITVLISLDRCVAIL 103
7tmA_OR52B-like cd15221
olfactory receptor subfamily 52B and related proteins, member of the class A family of ...
32-127 2.66e-03

olfactory receptor subfamily 52B and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes human olfactory receptor (OR) subfamilies 52B, 52D, 52H and related proteins in other mammals, sauropsids, and amphibians. Olfactory receptors (ORs) play a central role in olfaction, the sense of smell. ORs belong to the class A rhodopsin-like family of G protein-coupled receptors and constitute the largest multigene family in mammals of approximately 1,000 genes. More than 60% of human ORs are non-functional pseudogenes compared to only about 20% in mouse. Each OR can recognize structurally similar odorants, and a single odorant can be detected by several ORs. Binding of an odorant to the olfactory receptor induces a conformational change that leads to the activation of the olfactory-specific G protein (Golf). The G protein (Golf and/or Gs) in turn stimulates adenylate cyclase to make cAMP. The cAMP opens cyclic nucleotide-gated ion channels, which allow the influx of calcium and sodium ions, resulting in depolarization of the olfactory receptor neuron and triggering an action potential which transmits this information to the brain. A consensus nomenclature system based on evolutionary divergence is used here to classify the olfactory receptor family. The nomenclature begins with the root name OR, followed by an integer representing a family, a letter denoting a subfamily, and an integer representing the individual gene within the subfamily.


Pssm-ID: 320349  Cd Length: 275  Bit Score: 39.20  E-value: 2.66e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  32 VSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAvMLAARRaaaaagtppgaLGCKLLAF---LAALFCF 108
Cdd:cd15221   13 VALLGNSLLLFVIVTERSLHEPMYLFLSMLAVTDLLLSTTTVPK-MLAIFW-----------FGAGEISFdgcLTQMFFV 80
                         90       100
                 ....*....|....*....|....
gi 149036820 109 HAAFL-----LLGVGVTRYLAIAH 127
Cdd:cd15221   81 HFVFVtesaiLLAMAFDRYVAICY 104
7tmA_Bradykinin_R cd15189
bradykinin receptors, member of the class A family of seven-transmembrane G protein-coupled ...
277-339 2.72e-03

bradykinin receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; The bradykinin receptor family is a group of the seven transmembrane G-protein coupled receptors, whose endogenous ligand is the pro-inflammatory nonapeptide bradykinin that mediates various vascular and pain responses. Two major bradykinin receptor subtypes, B1 and B2, have been identified based on their pharmacological properties. The B1 receptor is rapidly induced by tissue injury and inflammation, whereas the B2 receptor is ubiquitously expressed on many tissue types. Both receptors contain three consensus sites for N-linked glycosylation in extracellular domains and couple to G(q) protein to activate phospholipase C, leading to phosphoinositide hydrolysis and intracellular calcium mobilization. They can also interact with G(i) protein to inhibit adenylate cyclase and activate the MAPK (mitogen-activated protein kinase) pathways.


Pssm-ID: 320317 [Multi-domain]  Cd Length: 284  Bit Score: 39.37  E-value: 2.72e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 149036820 277 EFKTEKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRPGAVPQAY--------LTASVWLTFAQAGINPVV 339
Cdd:cd15189  202 EDRNDSKATALVLAVTLLFLVCWGPYHFFTFLDFLFDVGVLDECFwehfidigLQLAVFLAFSNSCLNPVL 272
7tmA_NKR_NK3R cd16003
neuromedin-K receptor, member of the class A family of seven-transmembrane G protein-coupled ...
276-351 3.15e-03

neuromedin-K receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; The neuromedin-K receptor (NKR), also known as tachykinin receptor 3 (TACR3) or neurokinin B receptor or NK3R, is a G-protein coupled receptor that specifically binds to neurokinin B. The tachykinins (TKs) act as excitatory transmitters on neurons and cells in the gastrointestinal tract. The TKs are characterized by a common five-amino acid C-terminal sequence, Phe-X-Gly-Leu-Met-NH2, where X is a hydrophobic residue. The three major mammalian tachykinins are substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). The physiological actions of tachykinins are mediated through three types of receptors: neurokinin receptor type 1 (NK1R), NK2R, and NK3R. NK3R is activated by its high-affinity ligand, NKB, which is primarily involved in the central nervous system and plays a critical role in the regulation of gonadotropin hormone release and the onset of puberty.


Pssm-ID: 320669 [Multi-domain]  Cd Length: 282  Bit Score: 39.14  E-value: 3.15e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 276 EEFKTEKRLCKMFYAITLLFLLLWGPY----VVASYLRVLVRPGAVPQAYLtASVWLTFAQAGINPVVCFLFNRELRDCF 351
Cdd:cd16003  204 EQLRAKRKVVKMMIIVVLTFAICWLPYhiyfIVTGLYQQLNRWKYIQQVYL-ASFWLAMSSTMYNPIIYCCLNKRFRAGF 282
7tmA_mAChR cd15049
muscarinic acetylcholine receptor subfamily, member of the class A family of ...
281-351 3.47e-03

muscarinic acetylcholine receptor subfamily, member of the class A family of seven-transmembrane G protein-coupled receptors; Muscarinic acetylcholine receptors (mAChRs) regulate the activity of many fundamental central and peripheral functions. The mAChR family consists of 5 subtypes M1-M5, which can be further divided into two major groups according to their G-protein coupling preference. The M1, M3 and M5 receptors selectively interact with G proteins of the G(q/11) family, whereas the M2 and M4 receptors preferentially link to the G(i/o) types of G proteins. Activation of mAChRs by agonist (acetylcholine) leads to a variety of biochemical and electrophysiological responses. In general, the exact nature of these responses and the subsequent physiological effects mainly depend on the molecular and pharmacological identity of the activated receptor subtype(s). 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.


Pssm-ID: 341322 [Multi-domain]  Cd Length: 262  Bit Score: 38.84  E-value: 3.47e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 149036820 281 EKRLCKMFYAITLLFLLLWGPYVVAsylrVLVR---PGAVPQAYLTASVWLTFAQAGINPVVCFLFNRELRDCF 351
Cdd:cd15049  193 ERKAARTLSAILLAFIITWTPYNIL----VLVStfcAKCIPDTLWSFGYWLCYINSTINPFCYALCNKTFRKTF 262
7tmA_OR5C1-like cd15945
olfactory receptor subfamily 5C1 and related proteins, member of the class A family of ...
32-145 3.59e-03

olfactory receptor subfamily 5C1 and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes human olfactory receptor subfamily 5C1 and related proteins in other mammals and sauropsids. Olfactory receptors (ORs) play a central role in olfaction, the sense of smell. ORs belong to the class A rhodopsin-like family of G protein-coupled receptors and constitute the largest multigene family in mammals of approximately 1,000 genes. More than 60% of human ORs are non-functional pseudogenes compared to only about 20% in mouse. Each OR can recognize structurally similar odorants, and a single odorant can be detected by several ORs. Binding of an odorant to the olfactory receptor induces a conformational change that leads to the activation of the olfactory-specific G protein (Golf). The G protein (Golf and/or Gs) in turn stimulates adenylate cyclase to make cAMP. The cAMP opens cyclic nucleotide-gated ion channels, which allow the influx of calcium and sodium ions, resulting in depolarization of the olfactory receptor neuron and triggering an action potential which transmits this information to the brain. A consensus nomenclature system based on evolutionary divergence is used here to classify the olfactory receptor family. The nomenclature begins with the root name OR, followed by an integer representing a family, a letter denoting a subfamily, and an integer representing the individual gene within the subfamily.


Pssm-ID: 320611  Cd Length: 292  Bit Score: 38.96  E-value: 3.59e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  32 VSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAvMLAARRAAAAAGTPPgalGCKLLAFLAALFCFHAA 111
Cdd:cd15945   26 LTLVGNVGMIILIRMDSQLHTPMYYFLSNLSFLDLCYSTAIGPK-MLVDLLAKRKSIPFY---GCALQMFFFAAFADAEC 101
                         90       100       110
                 ....*....|....*....|....*....|....
gi 149036820 112 FLLLGVGVTRYLAIAHHRFYAERLAGWPCAAMLV 145
Cdd:cd15945  102 LLLAVMAYDRYVAICNPLLYTTAMSRRVCYLLLV 135
7tmA_5-HT4 cd15056
serotonin receptor subtype 4, member of the class A family of seven-transmembrane G ...
276-351 4.02e-03

serotonin receptor subtype 4, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT4 subtype is a member of the serotonin receptor family that belongs to the class A G protein-coupled receptors, and binds the neurotransmitter serotonin (5HT; 5-hydroxytryptamine) in the mammalian central nervous system (CNS). 5-HT4 receptors are selectively linked to G proteins of the G(s) family, which positively stimulate adenylate cyclase, causing cAMP formation and activation of protein kinase A. 5-HT4 receptor-specific agonists have been shown to enhance learning and memory in animal studies. Moreover, hippocampal 5-HT4 receptor expression has been reported to be inversely correlated with memory performance in humans. 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.


Pssm-ID: 320184 [Multi-domain]  Cd Length: 294  Bit Score: 38.62  E-value: 4.02e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 149036820 276 EEFKTEKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRPgAVPQAYLTASVWLTFAQAGINPVVCFLFNRELRDCF 351
Cdd:cd15056  220 SRMRTETKAAKTLGIIMGCFCVCWAPFFVTNIVDPFIGY-RVPYLLWTAFLWLGYINSGLNPFLYAFFNKSFRRAF 294
7tmA_Mel1B cd15400
melatonin receptor subtype 1B, member of the class A family of seven-transmembrane G ...
32-138 4.08e-03

melatonin receptor subtype 1B, member of the class A family of seven-transmembrane G protein-coupled receptors; Melatonin (N-acetyl-5-methoxytryptamine) is a naturally occurring sleep-promoting chemical found in vertebrates, invertebrates, bacteria, fungi, and plants. In mammals, melatonin is secreted by the pineal gland and is involved in regulation of circadian rhythms. Its production peaks during the nighttime, and is suppressed by light. Melatonin is shown to be synthesized in other organs and cells of many vertebrates, including the Harderian gland, leukocytes, skin, and the gastrointestinal (GI) tract, which contains several hundred times more melatonin than the pineal gland and is involved in the regulation of GI motility, inflammation, and sensation. Melatonin exerts its pleiotropic physiological effects through specific membrane receptors, named MT1A, MT1B, and MT1C, which belong to the class A rhodopsin-like G-protein coupled receptor family. MT1A and MT1B subtypes are present in mammals, whereas MT1C subtype has been found in amphibians and birds. The melatonin receptors couple to G proteins of the G(i/o) class, leading to the inhibition of adenylate cyclase.


Pssm-ID: 320522 [Multi-domain]  Cd Length: 279  Bit Score: 38.68  E-value: 4.08e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  32 VSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLaarrAAAAAGTPPGALGCKLLAFLAALFCFHAA 111
Cdd:cd15400   13 VDILGNLLVIISVFRNRKLRNSGNVFVVSLALADLVVALYPYPLVLV----AIFHNGWALGEMHCKVSGFVMGLSVIGSI 88
                         90       100
                 ....*....|....*....|....*..
gi 149036820 112 FLLLGVGVTRYLAIAHHRFYAERLAGW 138
Cdd:cd15400   89 FNITGIAINRYCYICHSFAYDKLYSRW 115
7tmA_Encephalopsin cd15078
encephalopsins (opsin-3), member of the class A family of seven-transmembrane G ...
274-350 4.26e-03

encephalopsins (opsin-3), member of the class A family of seven-transmembrane G protein-coupled receptors; Encephalopsin, also called Opsin-3 or Panopsin, is a mammalian extra-retinal opsin that is highly localized in the brain. It is thought to play a role in encephalic photoreception. Encephalopsin belongs to the class A of the G protein-coupled receptors and shows strong homology to the vertebrate visual opsins.


Pssm-ID: 320206 [Multi-domain]  Cd Length: 279  Bit Score: 38.66  E-value: 4.26e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 149036820 274 VLEEFKTEKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRPGAVPQAYLTASVWLTFAQAGINPVVCFLFNRELRDC 350
Cdd:cd15078  202 VIKILKYEKKVAKMCLLMISTFLICWMPYAVVSLLVTSGYSKLVTPTIAIIPSLFAKSSTAYNPVIYIFMIRKFRQC 278
7tmA_alpha2C_AR cd15323
alpha-2 adrenergic receptors subtype C, member of the class A family of seven-transmembrane G ...
281-351 5.13e-03

alpha-2 adrenergic receptors subtype C, member of the class A family of seven-transmembrane G protein-coupled receptors; The alpha-2 adrenergic receptors (or adrenoceptors) are a subfamily of the class A rhodopsin-like GPCRs that share a common architecture of seven transmembrane helices. This subfamily consists of three highly homologous receptor subtypes that have a key role in neurotransmitter release: alpha-2A, alpha-2B, and alpha-2C. In addition, a fourth subtype, alpha-2D is present in ray-finned fishes and amphibians, but is not found in humans. The alpha-2 receptors are found in both central and peripheral nervous system and serve to produce inhibitory functions through the G(i) proteins. Thus, the alpha-2 receptors inhibit adenylate cyclase, which decreases cAMP production and thereby decreases calcium influx during the action potential. Consequently, lowered levels of calcium will lead to a decrease in neurotransmitter release by negative feedback.


Pssm-ID: 320446 [Multi-domain]  Cd Length: 261  Bit Score: 38.38  E-value: 5.13e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 149036820 281 EKRLCKMFYAITLLFLLLWGPYVVASYLRVLVR-PGAVPQAYLTASVWLTFAQAGINPVVCFLFNRELRDCF 351
Cdd:cd15323  190 EKRFTFVLAVVMGVFVVCWFPFFFSYSLYGICReACEVPEPLFKFFFWIGYCNSSLNPVIYTIFNQDFRRSF 261
7tmA_D2_dopamine_R cd15309
D2 subtype of the D2-like family of dopamine receptors, member of the class A family of ...
278-351 5.44e-03

D2 subtype of the D2-like family of dopamine receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Dopamine receptors are members of the class A G protein-coupled receptors that are involved in many neurological processes in the central nervous system (CNS). The neurotransmitter dopamine is the primary endogenous agonist for dopamine receptors. Dopamine receptors consist of at least five subtypes: D1, D2, D3, D4, and D5. The D1 and D5 subtypes are members of the D1-like family of dopamine receptors, whereas the D2, D3 and D4 subtypes are members of the D2-like family. Activation of D2-like family receptors is linked to G proteins of the G(i) family. This leads to a decrease in adenylate cyclase activity, thereby decreasing cAMP levels. Dopamine receptors are major therapeutic targets for neurological and psychiatric disorders such as drug abuse, depression, schizophrenia, or Parkinson's disease.


Pssm-ID: 320435 [Multi-domain]  Cd Length: 254  Bit Score: 38.09  E-value: 5.44e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 149036820 278 FKTEKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRPGaVPQAYLTASVWLTFAQAGINPVVCFLFNRELRDCF 351
Cdd:cd15309  182 LQKEKKATQMLAIVLGVFIICWLPFFITHILNMHCDCN-IPPALYSAFTWLGYVNSAVNPIIYTTFNIEFRKAF 254
7tmA_GPR101 cd15215
orphan G protein-coupled receptor 101, member of the class A family of seven-transmembrane G ...
31-135 6.20e-03

orphan G protein-coupled receptor 101, member of the class A family of seven-transmembrane G protein-coupled receptors; Gpr101, an orphan GPCR, is predominantly expressed in the brain within discrete nuclei and is predicted to couple to the stimulatory G(s) protein, a potent activator of adenylate cyclase. GPR101 has been implicated in mediating the actions of GnRH-(1-5), a pentapeptide formed by metallopeptidase cleavage of the decapeptide gonadotropin-releasing hormone (GnRH), which plays a critical role in the regulation of the hypothalamic-pituitary-gonadal axis. GnRH-(1-5) acts on GPR101 to stimulate epidermal growth factor (EFG) release and EFG-receptor (EGFR) phosphorylation, leading to enhanced cell migration and invasion in the Ishikawa endometrial cancer cell line. Furthermore, these effects of GnRH-(1-5) are also dependent on enzymatic activation of matrix metallopeptidase-9 (MMP-9). GPR101 is a member of the class A family of GPCRs, which includes receptors for hormones, neurotransmitters, sensory stimuli, 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.


Pssm-ID: 320343 [Multi-domain]  Cd Length: 261  Bit Score: 37.90  E-value: 6.20e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  31 CVSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLAARRAAAaagtPPGALGCKLLAFLAALFCFHA 110
Cdd:cd15215   11 CASLFGNIVLLLVFQRKPQLLQVANRFIFNLLVADLLQTVLVMPWVIATSVPLFW----PLDSHLCTALVVLMHLFAFAG 86
                         90       100
                 ....*....|....*....|....*
gi 149036820 111 AFLLLGVGVTRYLAIAHHRFYAERL 135
Cdd:cd15215   87 VNTIVVVSVDRYLAIIHPLSYPTKM 111
7tmA_mAChR_M4 cd15298
muscarinic acetylcholine receptor subtype M4, member of the class A family of ...
281-351 6.48e-03

muscarinic acetylcholine receptor subtype M4, member of the class A family of seven-transmembrane G protein-coupled receptors; Muscarinic acetylcholine receptors (mAChRs) regulate the activity of many fundamental central and peripheral functions. The mAChR family consists of 5 subtypes M1-M5, which can be further divided into two major groups according to their G-protein coupling preference. The M1, M3 and M5 receptors selectively interact with G proteins of the G(q/11) family, whereas the M2 and M4 receptors preferentially link to G(i/o) types of G proteins. The M4 receptor is mainly found in the CNS and function as an inhibitory autoreceptor regulating acetycholine release. 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.


Pssm-ID: 341344 [Multi-domain]  Cd Length: 262  Bit Score: 38.08  E-value: 6.48e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 149036820 281 EKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRpGAVPQAYLTASVWLTFAQAGINPVVCFLFNRELRDCF 351
Cdd:cd15298  193 ERKVTRTIFAILLAFILTWTPYNVMVLVNTFCQ-SCIPDTVWSIGYWLCYVNSTINPACYALCNATFKKTF 262
7tmA_mAChR_M2 cd15297
muscarinic acetylcholine receptor subtype M2, member of the class A family of ...
281-351 6.60e-03

muscarinic acetylcholine receptor subtype M2, member of the class A family of seven-transmembrane G protein-coupled receptors; Muscarinic acetylcholine receptors (mAChRs) regulate the activity of many fundamental central and peripheral functions. The mAChR family consists of 5 subtypes M1-M5, which can be further divided into two major groups according to their G-protein coupling preference. The M1, M3 and M5 receptors selectively interact with G proteins of the G(q/11) family, whereas the M2 and M4 receptors preferentially link to the G(i/o) types of G proteins. Activation of M2 receptor causes a decrease in cAMP production, generally leading to inhibitory-type effects. This causes an outward current of potassium in the heart, resulting in a decreased heart rate. 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.


Pssm-ID: 320424 [Multi-domain]  Cd Length: 262  Bit Score: 38.02  E-value: 6.60e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 149036820 281 EKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRPgAVPQAYLTASVWLTFAQAGINPVVCFLFNRELRDCF 351
Cdd:cd15297  193 EKKVTRTILAILLAFIITWTPYNVMVLINTFCAS-CIPNTVWTIGYWLCYINSTINPACYALCNATFKKTF 262
7tmA_CCK_R cd15206
cholecystokinin receptors, member of the class A family of seven-transmembrane G ...
272-351 7.06e-03

cholecystokinin receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Cholecystokinin receptors (CCK-AR and CCK-BR) are a group of G-protein coupled receptors which bind the peptide hormones cholecystokinin (CCK) or gastrin. CCK, which facilitates digestion in the small intestine, and gastrin, a major regulator of gastric acid secretion, are highly similar peptides. Like gastrin, CCK is a naturally-occurring linear peptide that is synthesized as a preprohormone, then proteolytically cleaved to form a family of peptides with the common C-terminal sequence (Gly-Trp-Met-Asp-Phe-NH2), which is required for full biological activity. 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.


Pssm-ID: 320334 [Multi-domain]  Cd Length: 269  Bit Score: 37.76  E-value: 7.06e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 272 LLVLEEFKTEKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRPGAvpQAYLTASV-----WLTFAQAGINPVV-CFLfNR 345
Cdd:cd15206  187 LISWTLLEAKKRVIRMLFVIVVEFFICWTPLYVINTWKAFDPPSA--ARYVSSTTisliqLLAYISSCVNPITyCFM-NK 263

                 ....*.
gi 149036820 346 ELRDCF 351
Cdd:cd15206  264 RFRQAF 269
7tmA_Mel1A cd15402
melatonin receptor subtype 1A, member of the class A family of seven-transmembrane G ...
32-131 7.36e-03

melatonin receptor subtype 1A, member of the class A family of seven-transmembrane G protein-coupled receptors; Melatonin (N-acetyl-5-methoxytryptamine) is a naturally occurring sleep-promoting chemical found in vertebrates, invertebrates, bacteria, fungi, and plants. In mammals, melatonin is secreted by the pineal gland and is involved in regulation of circadian rhythms. Its production peaks during the nighttime, and is suppressed by light. Melatonin is shown to be synthesized in other organs and cells of many vertebrates, including the Harderian gland, leukocytes, skin, and the gastrointestinal (GI) tract, which contains several hundred times more melatonin than the pineal gland and is involved in the regulation of GI motility, inflammation, and sensation. Melatonin exerts its pleiotropic physiological effects through specific membrane receptors, named MT1A, MT1B, and MT1C, which belong to the class A rhodopsin-like G-protein coupled receptor family. MT1A and MT1B subtypes are present in mammals, whereas MT1C subtype has been found in amphibians and birds. The melatonin receptors couple to G proteins of the G(i/o) class, leading to the inhibition of adenylate cyclase.


Pssm-ID: 320524 [Multi-domain]  Cd Length: 279  Bit Score: 37.96  E-value: 7.36e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  32 VSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLRALACLPAVMLAARRAaaaaGTPPGALGCKLLAFLAALFCFHAA 111
Cdd:cd15402   13 VDILGNLLVILSVYRNKKLRNAGNIFVVSLAVADLVVAIYPYPLVLTSIFHN----GWNLGYLHCQISGFLMGLSVIGSI 88
                         90       100
                 ....*....|....*....|
gi 149036820 112 FLLLGVGVTRYLAIAHHRFY 131
Cdd:cd15402   89 FNITGIAINRYCYICHSLKY 108
7tmA_Parietopsin cd15085
non-visual parietopsins, member of the class A family of seven-transmembrane G protein-coupled ...
281-350 7.51e-03

non-visual parietopsins, member of the class A family of seven-transmembrane G protein-coupled receptors; Parietopsin is a non-visual green light-sensitive opsin that was initially identified in the parietal eye of lizards. 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. Parietopsin belongs to the class A of the G protein-coupled receptors and shows strong homology to the vertebrate visual opsins.


Pssm-ID: 320213 [Multi-domain]  Cd Length: 280  Bit Score: 37.91  E-value: 7.51e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820 281 EKRLCKMFYAITLLFLLLWGPYVVASYLRVLVRPGAVPQAYLTASVWLTFAQAGINPVVCFLFNRELRDC 350
Cdd:cd15085  210 EERAVIMVLAMVIAFLICWLPYTVFALIVVVNPELSISPLAATMPTYFAKTSPVYNPIIYIFLNKQFRES 279
7tmA_Opioid_R-like cd14970
opioid receptors and related proteins, member of the class A family of seven-transmembrane G ...
32-127 9.74e-03

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.


Pssm-ID: 320101 [Multi-domain]  Cd Length: 282  Bit Score: 37.27  E-value: 9.74e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149036820  32 VSLAGNVLFALLIVRERSLHRAPYYLLLDLCLADGLrALACLPavmlAARRAAAAAGTPPGALGCKLLAFLAALFCFHAA 111
Cdd:cd14970   13 VGLTGNSLVIYVILRYSKMKTVTNIYILNLAVADEL-FLLGLP----FLATSYLLGYWPFGEVMCKIVLSVDAYNMFTSI 87
                         90
                 ....*....|....*.
gi 149036820 112 FLLLGVGVTRYLAIAH 127
Cdd:cd14970   88 FCLTVMSVDRYLAVVH 103
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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