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Conserved domains on  [gi|325495579|gb|ADZ17395|]
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G protein-coupled receptor 62 [Homo sapiens]

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 ...
16-301 5.03e-68

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 cd15220:

Pssm-ID: 475119 [Multi-domain]  Cd Length: 264  Bit Score: 215.01  E-value: 5.03e-68
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  16 LGLILAAVVEVGALLGNGALLVVVLRTPGLRDALYLAHLCVVDLLAAASIMPLGLLAAPPPGLGrVRLGPAPCRAARFLS 95
Cdd:cd15220    1 VGLFCMVLLDLTALVGNTAVMVVIAKTPHLRKFAFVCHLCVVDLLAALLLMPLGILSSSPFFLG-VVFGEAECRVYIFLS 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  96 AALLPACTLGVAALGLARYRLIVHPLR---PGSRPPPVLVLTAVWAAAGLLGA------LSLLGPPPAPPPAPARCSVLA 166
Cdd:cd15220   80 VCLVSASILTISAISVERYYYIVHPMRyevKMTIGLVAAVLVGVWVKALLLGLlpvlgwPSYGGPAPIAARHCSLHWSHS 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579 167 GGLGPFRPLWALLAFALPALLLLGAYGGIFVVarraalrpprpargsrlrsdsldsrlsilpplrprLPGGKAALAPALA 246
Cdd:cd15220  160 GHRGVFVVLFALVCFLLPLLLILVVYCGVFKV-----------------------------------FGGGKAALTLAAI 204
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579 247 VGQFAACWLPYGC-----ACLAPAARAAEAEAAVTWVAYSAFAAHPFLYGLLQRPVRLAL 301
Cdd:cd15220  205 VGQFLCCWLPYFAfhlysALAASPVSGGEAEEVVTWLAYSCFAVNPFFYGLLNRQIREEL 264
 
Name Accession Description Interval E-value
7tmA_GPR61_GPR62-like cd15220
G protein-coupled receptors 61 and 62, member of the class A family of seven-transmembrane G ...
16-301 5.03e-68

G protein-coupled receptors 61 and 62, member of the class A family of seven-transmembrane G protein-coupled receptors; This subgroup includes the orphan receptors GPR61 and GPR62, which are both constitutively active and predominantly expressed in the brain. While GPR61 couples to G(s) subtype of G proteins, the signaling pathway and function of GPR 62 are unknown. GPR61-deficient mice displayed significant hyperphagia and heavier body weight compared to wild-type mice, suggesting that GPR61 is involved in the regulation of food intake and body weight. GPR61 transcript expression was found in the caudate, putamen, and thalamus of human brain, whereas GPR62 transcript expression was found in the basal forebrain, frontal cortex, caudate, putamen, thalamus, and hippocampus. Both receptors share the highest sequence homology with each other and comprise a conserved subgroup within 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, which then activate the heterotrimeric G proteins. Members of this subgroup contain [A/E]RY motif, a variant of the highly conserved Asp-Arg-Tyr (DRY) motif found in the third transmembrane helix (TM3) of the class A GPCRs and important for efficient G protein-coupled signal transduction.


Pssm-ID: 410633 [Multi-domain]  Cd Length: 264  Bit Score: 215.01  E-value: 5.03e-68
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  16 LGLILAAVVEVGALLGNGALLVVVLRTPGLRDALYLAHLCVVDLLAAASIMPLGLLAAPPPGLGrVRLGPAPCRAARFLS 95
Cdd:cd15220    1 VGLFCMVLLDLTALVGNTAVMVVIAKTPHLRKFAFVCHLCVVDLLAALLLMPLGILSSSPFFLG-VVFGEAECRVYIFLS 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  96 AALLPACTLGVAALGLARYRLIVHPLR---PGSRPPPVLVLTAVWAAAGLLGA------LSLLGPPPAPPPAPARCSVLA 166
Cdd:cd15220   80 VCLVSASILTISAISVERYYYIVHPMRyevKMTIGLVAAVLVGVWVKALLLGLlpvlgwPSYGGPAPIAARHCSLHWSHS 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579 167 GGLGPFRPLWALLAFALPALLLLGAYGGIFVVarraalrpprpargsrlrsdsldsrlsilpplrprLPGGKAALAPALA 246
Cdd:cd15220  160 GHRGVFVVLFALVCFLLPLLLILVVYCGVFKV-----------------------------------FGGGKAALTLAAI 204
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579 247 VGQFAACWLPYGC-----ACLAPAARAAEAEAAVTWVAYSAFAAHPFLYGLLQRPVRLAL 301
Cdd:cd15220  205 VGQFLCCWLPYFAfhlysALAASPVSGGEAEEVVTWLAYSCFAVNPFFYGLLNRQIREEL 264
7tm_1 pfam00001
7 transmembrane receptor (rhodopsin family); This family contains, amongst other ...
31-290 1.64e-04

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: 42.67  E-value: 1.64e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579   31 GNGALLVVVLRTPGLRDA--LYLAHLCVVDLLAAASIMPLGLLAAPppGLGRVRLGPAPCRAARFLSAALLPACTLGVAA 108
Cdd:pfam00001   1 GNLLVILVILRNKKLRTPtnIFLLNLAVADLLFSLLTLPFWLVYYL--NHGDWPFGSALCKIVGALFVVNGYASILLLTA 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  109 LGLARYRLIVHPLRPGSRPPP---VLVLTAVWAAAGLLGALSL--LGPPPAPPPAPARCSV-----------------LA 166
Cdd:pfam00001  79 ISIDRYLAIVHPLRYKRRRTPrraKVLILVIWVLALLLSLPPLlfGWTLTVPEGNVTVCFIdfpedlskpvsytllisVL 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  167 GGLGPFrplwallafalpaLLLLGAYGGIFVVARRAALRPPRPARGSRLRsdsldsrlsilpplrprlpggKAALAPALA 246
Cdd:pfam00001 159 GFLLPL-------------LVILVCYTLIIRTLRKSASKQKSSERTQRRR---------------------KALKTLAVV 204
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 325495579  247 VGQFAACWLPYG--------CACLAPAARAAEAEAAVTWVAYSAFAAHPFLY 290
Cdd:pfam00001 205 VVVFILCWLPYHivnlldslALDCELSRLLDKALSVTLWLAYVNSCLNPIIY 256
 
Name Accession Description Interval E-value
7tmA_GPR61_GPR62-like cd15220
G protein-coupled receptors 61 and 62, member of the class A family of seven-transmembrane G ...
16-301 5.03e-68

G protein-coupled receptors 61 and 62, member of the class A family of seven-transmembrane G protein-coupled receptors; This subgroup includes the orphan receptors GPR61 and GPR62, which are both constitutively active and predominantly expressed in the brain. While GPR61 couples to G(s) subtype of G proteins, the signaling pathway and function of GPR 62 are unknown. GPR61-deficient mice displayed significant hyperphagia and heavier body weight compared to wild-type mice, suggesting that GPR61 is involved in the regulation of food intake and body weight. GPR61 transcript expression was found in the caudate, putamen, and thalamus of human brain, whereas GPR62 transcript expression was found in the basal forebrain, frontal cortex, caudate, putamen, thalamus, and hippocampus. Both receptors share the highest sequence homology with each other and comprise a conserved subgroup within 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, which then activate the heterotrimeric G proteins. Members of this subgroup contain [A/E]RY motif, a variant of the highly conserved Asp-Arg-Tyr (DRY) motif found in the third transmembrane helix (TM3) of the class A GPCRs and important for efficient G protein-coupled signal transduction.


Pssm-ID: 410633 [Multi-domain]  Cd Length: 264  Bit Score: 215.01  E-value: 5.03e-68
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  16 LGLILAAVVEVGALLGNGALLVVVLRTPGLRDALYLAHLCVVDLLAAASIMPLGLLAAPPPGLGrVRLGPAPCRAARFLS 95
Cdd:cd15220    1 VGLFCMVLLDLTALVGNTAVMVVIAKTPHLRKFAFVCHLCVVDLLAALLLMPLGILSSSPFFLG-VVFGEAECRVYIFLS 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  96 AALLPACTLGVAALGLARYRLIVHPLR---PGSRPPPVLVLTAVWAAAGLLGA------LSLLGPPPAPPPAPARCSVLA 166
Cdd:cd15220   80 VCLVSASILTISAISVERYYYIVHPMRyevKMTIGLVAAVLVGVWVKALLLGLlpvlgwPSYGGPAPIAARHCSLHWSHS 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579 167 GGLGPFRPLWALLAFALPALLLLGAYGGIFVVarraalrpprpargsrlrsdsldsrlsilpplrprLPGGKAALAPALA 246
Cdd:cd15220  160 GHRGVFVVLFALVCFLLPLLLILVVYCGVFKV-----------------------------------FGGGKAALTLAAI 204
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579 247 VGQFAACWLPYGC-----ACLAPAARAAEAEAAVTWVAYSAFAAHPFLYGLLQRPVRLAL 301
Cdd:cd15220  205 VGQFLCCWLPYFAfhlysALAASPVSGGEAEEVVTWLAYSCFAVNPFFYGLLNRQIREEL 264
7tm_classA_rhodopsin-like cd00637
rhodopsin receptor-like class A family of the seven-transmembrane G protein-coupled receptor ...
18-293 5.45e-21

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: 91.20  E-value: 5.45e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  18 LILAAVVEVGALLGNGALLVVVLRTPGLRDA--LYLAHLCVVDLLAAASIMPLGLLAAPppgLGRVRLGPAPCRAARFLS 95
Cdd:cd00637    2 AVLYILIFVVGLVGNLLVILVILRNRRLRTVtnYFILNLAVADLLVGLLVIPFSLVSLL---LGRWWFGDALCKLLGFLQ 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  96 AALLPACTLGVAALGLARYRLIVHPLRPGSRPPP---VLVLTAVW----------------AAAGLLGALSLLGPPPAPP 156
Cdd:cd00637   79 SVSLLASILTLTAISVDRYLAIVHPLRYRRRFTRrraKLLIALIWllslllalppllgwgvYDYGGYCCCCLCWPDLTLS 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579 157 PAPARCSVLAGGLGPFrplwallafalpaLLLLGAYGGIFVVARRAALRPPRPARGSRLRSDSLDSRlsilpplrprlpg 236
Cdd:cd00637  159 KAYTIFLFVLLFLLPL-------------LVIIVCYVRIFRKLRRHRRRIRSSSSNSSRRRRRRRER------------- 212
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 325495579 237 gKAALAPALAVGQFAACWLPYGC------ACLAPAARAAEAEAAVTWVAYSAFAAHPFLYGLL 293
Cdd:cd00637  213 -KVTKTLLIVVVVFLLCWLPYFIlllldvFGPDPSPLPRILYFLALLLAYLNSAINPIIYAFF 274
7tmA_NPYR-like cd15203
neuropeptide Y receptors and related proteins, member of the class A family of ...
18-137 4.20e-07

neuropeptide Y receptors and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; NPY is a 36-amino acid peptide neurotransmitter with a C-terminal tyrosine amide residue that is widely distributed in the brain and the autonomic nervous system of many mammalian species. NPY exerts its functions through five, G-protein coupled receptor subtypes including NPY1R, NPY2R, NPY4R, NPY5R, and NPY6R; however, NPY6R is not functional in humans. NYP receptors are also activated by its two other family members, peptide YY (PYY) and pancreatic polypeptide (PP). They typically couple to Gi or Go proteins, which leads to a decrease in adenylate cyclase activity, thereby decreasing intracellular cAMP levels, and are involved in diverse physiological roles including appetite regulation, circadian rhythm, and anxiety. Also included in this subgroup is prolactin-releasing peptide (PrRP) receptor (previously known as GPR10), which is activated by its endogenous ligand PrRP, a neuropeptide possessing C-terminal Arg-Phe-amide motif. There are two active isoforms of PrRP in mammals: one consists of 20 amino acid residues (PrRP-20) and the other consists of 31 amino acid residues (PrRP-31). PrRP receptor shows significant sequence homology to the NPY receptors, and a micromolar level 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.


Pssm-ID: 320331 [Multi-domain]  Cd Length: 293  Bit Score: 51.07  E-value: 4.20e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  18 LILAAVVEVGALLGNGALLVVVLRTPGLRDA--LYLAHLCVVDLLAAASIMPLGLLAApppgLGRV-RLGPAPCRAARFL 94
Cdd:cd15203    4 ILLYGLIIVLGVVGNLLVIYVVLRNKSMQTVtnIFILNLAVSDLLLCLVSLPFTLIYT----LTKNwPFGSILCKLVPSL 79
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 325495579  95 SAALLPACTLGVAALGLARYRLIVHPLRPG-SRPPPVLVLTAVW 137
Cdd:cd15203   80 QGVSIFVSTLTLTAIAIDRYQLIVYPTRPRmSKRHALLIIALIW 123
7tmA_CCKR-like cd14993
cholecystokinin receptors and related proteins, member of the class A family of ...
18-137 7.58e-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: 50.29  E-value: 7.58e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  18 LILAAVVEVGALLGNGALLVVVLRTPGLRDA--LYLAHLCVVDLLAAASIMPLGLLAApppgLGRV-RLGPAPCRAARFL 94
Cdd:cd14993    4 IVLYVVVFLLALVGNSLVIAVVLRNKHMRTVtnYFLVNLAVADLLVSLFCMPLTLLEN----VYRPwVFGEVLCKAVPYL 79
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 325495579  95 SAALLPACTLGVAALGLARYRLIVHPLRPGSRPP---PVLVLTAVW 137
Cdd:cd14993   80 QGVSVSASVLTLVAISIDRYLAICYPLKARRVSTkrrARIIIVAIW 125
7tmA_CCK_R cd15206
cholecystokinin receptors, member of the class A family of seven-transmembrane G ...
20-122 1.35e-06

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: 49.31  E-value: 1.35e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  20 LAAVVEVGALLGNGALLVVVLRTPGLRDA--LYLAHLCVVDLLAAASIMPLGLLaapPPGLGRVRLGPAPCRAARFLSAA 97
Cdd:cd15206    6 LYSVIFLLAVVGNILVIVTLVQNKRMRTVtnVFLLNLAVSDLLLAVFCMPFTLV---GQLLRNFIFGEVMCKLIPYFQAV 82
                         90       100
                 ....*....|....*....|....*
gi 325495579  98 LLPACTLGVAALGLARYRLIVHPLR 122
Cdd:cd15206   83 SVSVSTFTLVAISLERYFAICHPLK 107
7tmA_GPR83 cd15389
G protein-coupled receptor 83, member of the class A family of seven-transmembrane G ...
18-137 6.00e-06

G protein-coupled receptor 83, member of the class A family of seven-transmembrane G protein-coupled receptors; GPR83, also known as GPR72, is widely expressed in the brain, including hypothalamic nuclei which is involved in regulating energy balance and food intake. The hypothalamic expression of GPR83 is tightly regulated in response to nutrient availability and is decreased in obese mice. A recent study suggests that GPR83 has a critical role in the regulation of systemic energy metabolism via ghrelin-dependent and ghrelin-independent mechanisms. GPR83 shares a significant amino acid sequence identity with the tachykinin receptors, however its endogenous ligand is unknown.


Pssm-ID: 320511 [Multi-domain]  Cd Length: 285  Bit Score: 47.33  E-value: 6.00e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  18 LILA-AVVEVGALLGNGALLVVVLRTPGLRDA--LYLAHLCVVDLLaaasimpLGLLAAPppgLGRVR-------LGPAP 87
Cdd:cd15389    3 LIVAySIIIVISLFGNSLVCHVIFKNKRMHTAtnLFIVNLAVSDIL-------ITLLNTP---FTLVRfvnstwvFGKIM 72
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 325495579  88 CRAARFLSAALLPACTLGVAALGLARYRLIVHPLRPGSRPPP-VLVLTAVW 137
Cdd:cd15389   73 CHLSRFAQYCSVYVSTLTLTAIALDRHRVILHPLKPRITPCQgVVVIAIIW 123
7tmA_NPFFR cd15207
neuropeptide FF receptors, member of the class A family of seven-transmembrane G ...
22-137 6.10e-06

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: 47.23  E-value: 6.10e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  22 AVVEVGALLGNGALLVVVLRTPGLRDA--LYLAHLCVVDLLAAASIMPLGLLAAPppgLGRVRLGPAPCRAARFLSAALL 99
Cdd:cd15207    8 SLIFLLCVVGNVLVCLVVAKNPRMRTVtnYFILNLAVSDLLVGVFCMPFTLVDNI---LTGWPFGDVMCKLSPLVQGVSV 84
                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 325495579 100 PACTLGVAALGLARYRLIVHPLRPG-SRPPPVLVLTAVW 137
Cdd:cd15207   85 AASVFTLVAIAVDRYRAVVHPTEPKlTNRQAFVIIVAIW 123
7tmA_TACR-like cd15202
tachykinin receptors and related receptors, member of the class A family of ...
19-137 7.84e-06

tachykinin receptors and related receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes the neurokinin/tachykinin receptors and its closely related receptors such as orphan GPR83 and leucokinin-like peptide receptor. 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: 320330 [Multi-domain]  Cd Length: 288  Bit Score: 47.12  E-value: 7.84e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  19 ILAAVVEVGALLGNGALLVVVLRTPGLRDA--LYLAHLCVVDLLAAASIMPLGLLAAPppgLGRVRLGPAPCRAARFLSA 96
Cdd:cd15202    5 VAYSFIIVFSLFGNVLVCWIIFKNQRMRTVtnYFIVNLAVADIMITLFNTPFTFVRAV---NNTWIFGLFMCHFSNFAQY 81
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 325495579  97 ALLPACTLGVAALGLARYRLIVHPLRPG-SRPPPVLVLTAVW 137
Cdd:cd15202   82 CSVHVSAYTLTAIAVDRYQAIMHPLKPRiSKTKAKFIIAVIW 123
7tmA_PR4-like cd15392
neuropeptide Y receptor-like found in insect and related proteins, member of the class A ...
22-137 9.62e-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: 46.58  E-value: 9.62e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  22 AVVEVGALLGNGALLVVVLRTPGLRDA--LYLAHLCVVDLLAAASIMPLGLLAAPPpgLGRVRLGPAPCRAARFLSA--A 97
Cdd:cd15392    8 STIFVLAVGGNGLVCYIVVSYPRMRTVtnYFIVNLALSDILMAVFCVPFSFIALLI--LQYWPFGEFMCPVVNYLQAvsV 85
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 325495579  98 LLPACTLgvAALGLARYRLIVHPLRPG-SRPPPVLVLTAVW 137
Cdd:cd15392   86 FVSAFTL--VAISIDRYVAIMWPLRPRmTKRQALLLIAVIW 124
7tmA_ETH-R cd14997
ecdysis-triggering hormone receptors, member of the class A family of seven-transmembrane G ...
22-125 1.11e-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: 46.51  E-value: 1.11e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  22 AVVEVGALLGNGALLVVVLRTPGLRDA--LYLAHLCVVDLLAAASIMPLGLLA--APPPGLgrvrLGPAPCRAARFLSAA 97
Cdd:cd14997    8 GVIFVVGVLGNVLVGIVVWKNKDMRTPtnIFLVNLSVADLLVLLVCMPVALVEtwAREPWL----LGEFMCKLVPFVELT 83
                         90       100
                 ....*....|....*....|....*...
gi 325495579  98 LLPACTLGVAALGLARYRLIVHPLRPGS 125
Cdd:cd14997   84 VAHASVLTILAISFERYYAICHPLQAKY 111
7tmA_Vasopressin-like cd14986
vasopressin receptors and its related G protein-coupled receptors, member of the class A ...
18-137 1.80e-05

vasopressin receptors and its related G protein-coupled receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Members of this group form a subfamily within the class A G-protein coupled receptors (GPCRs), which includes the vasopressin and oxytocin receptors, the gonadotropin-releasing hormone receptors (GnRHRs), the neuropeptide S receptor (NPSR), and orphan GPR150. These receptors share significant sequence homology with each other, suggesting that they have a common evolutionary origin. Vasopressin, also known as arginine vasopressin or anti-diuretic hormone, is a neuropeptide synthesized in the hypothalamus. The actions of vasopressin are mediated by the interaction of this hormone with three tissue-specific subtypes: V1AR, V1BR, and V2R. Although vasopressin differs from oxytocin by only two amino acids, they have divergent physiological functions. Vasopressin is involved in regulating osmotic and cardiovascular homeostasis, whereas oxytocin plays an important role in the uterus during childbirth and in lactation. 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. Neuropeptide S (NPS) promotes arousal and anxiolytic-like effects by activating its cognate receptor NPSR. NPSR has also been associated with asthma and allergy. GPR150 is an orphan receptor closely related to the oxytocin and vasopressin receptors.


Pssm-ID: 320117 [Multi-domain]  Cd Length: 295  Bit Score: 45.83  E-value: 1.80e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  18 LILAAVVEVGALLGNGALLVVVLRTPG--LRDALYLAHLCVVDLLAA-ASIMPLGLLAApppgLGRVRLGPAPCRAARFL 94
Cdd:cd14986    4 VAVLGVLFVFTLVGNGLVILVLRRKRKkrSRVNIFILNLAIADLVVAfFTVLTQIIWEA----TGEWVAGDVLCRIVKYL 79
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 325495579  95 SAALLPACTLGVAALGLARYRLIVHPLRPGSRPPPVLVLTAV-W 137
Cdd:cd14986   80 QVVGLFASTYILVSMSLDRYQAIVKPMSSLKPRKRARLMIVVaW 123
7tmA_Mel1C cd15401
melatonin receptor subtype 1C, member of the class A family of seven-transmembrane G ...
18-122 2.85e-05

melatonin receptor subtype 1C, 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: 320523 [Multi-domain]  Cd Length: 279  Bit Score: 45.29  E-value: 2.85e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  18 LILAAVVEVgalLGNGALLVVVLRTPGLRDA--LYLAHLCVVDLLAAASIMPLGLLAAPPPGLgrvRLGPAPCRAARFLS 95
Cdd:cd15401    7 LIFTIVVDV---LGNLLVILSVLRNKKLRNAgnIFVVSLSVADLVVAVYPYPLILLAIFHNGW---TLGNIHCQISGFLM 80
                         90       100
                 ....*....|....*....|....*..
gi 325495579  96 AALLPACTLGVAALGLARYRLIVHPLR 122
Cdd:cd15401   81 GLSVIGSVFNITAIAINRYCYICHSLR 107
7tmA_NTSR-like cd14979
neurotensin receptors and related G protein-coupled receptors, member of the class A family of ...
16-137 4.91e-05

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: 44.65  E-value: 4.91e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  16 LGLILAAVVEVGaLLGNGALLVVVLRTPGLRDA--LYLAHLCVVDLLAAASIMPLGLLAA----PPPglgrvrLGPAPCR 89
Cdd:cd14979    3 VTAIYVAIFVVG-IVGNLLTCIVIARHKSLRTTtnYYLFSLAVSDLLILLVGLPVELYNFwwqyPWA------FGDGGCK 75
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 325495579  90 AARFLSAALLPACTLGVAALGLARYRLIVHPLRPGSRPPP---VLVLTAVW 137
Cdd:cd14979   76 LYYFLFEACTYATVLTIVALSVERYVAICHPLKAKTLVTKrrvKRFILAIW 126
7tmA_GPR135 cd15212
G protein-coupled receptor 135, member of the class A family of seven-transmembrane G ...
30-137 7.46e-05

G protein-coupled receptor 135, member of the class A family of seven-transmembrane G protein-coupled receptors; GPR135, also known as the somatostatin- and angiotensin-like peptide receptor (SALPR), is found in various tissues including eye, brain, cervix, stomach, and testis. Pharmacological studies have shown that relaxin-3 (R3) is a high-affinity endogenous ligand for GPR135. R3 has recently been identified as a new member of the insulin/relaxin family of peptide hormones and is exclusively expressed in the brain neurons. In addition to GPR135, R3 also acts as an agonist for GPR142, a pseudogene in the rat, and can activate LGR7 (leucine repeat-containing G-protein receptor-7), which is the main receptor for relaxin-1 (R1) and relaxin-2 (R2). While R1 and R2 are hormones primarily associated with reproduction and pregnancy, R3 is involved in neuroendocrine and sensory processing. 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: 320340 [Multi-domain]  Cd Length: 285  Bit Score: 43.99  E-value: 7.46e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  30 LGNGALLVVVLRTPGLRDAL--YLAHLCVVDLLAAASIMPLGL--LAAPPPGLgrvrLGPAPCRAARFLSAALLPACTLG 105
Cdd:cd15212   16 LGNCAVIGVIVKHRQLRTVTnaFILSLSLSDLLTALLCLPFAFltLFSRPGWL----FGDRLCLANGFFNACFGIVSTLT 91
                         90       100       110
                 ....*....|....*....|....*....|...
gi 325495579 106 VAALGLARYRLIVHPLRPG-SRPPPVLVLTAVW 137
Cdd:cd15212   92 MTLISFDRYYAIVRQPQGKiGRRRALQLLAAAW 124
7tmA_CCK-BR cd15979
cholecystokinin receptor type B, member of the class A family of seven-transmembrane G ...
15-137 1.16e-04

cholecystokinin receptor type B, 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: 320645 [Multi-domain]  Cd Length: 275  Bit Score: 43.26  E-value: 1.16e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  15 SLGLILAAVVEVGALLGNGALLVVVLRTPGLRDAL--YLAHLCVVDLLAAASIMPLGLLaapPPGLGRVRLGPAPCRAAR 92
Cdd:cd15979    1 TVRILLYSVIFLLSVFGNMLIIVVLGLNKRLRTVTnsFLLSLALSDLMLAVFCMPFTLI---PNLMGTFIFGEVICKAVA 77
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 325495579  93 FLSAALLPACTLGVAALGLARYRLIVHPLRP---GSRPPPVLVLTAVW 137
Cdd:cd15979   78 YLMGVSVSVSTFSLVAIAIERYSAICNPLQSrvwQTRSHAYRVIAATW 125
7tmA_GPR26_GPR78-like cd15219
G protein-coupled receptors 26 and 78, member of the class A family of seven-transmembrane G ...
19-126 1.22e-04

G protein-coupled receptors 26 and 78, member of the class A family of seven-transmembrane G protein-coupled receptors; Orphan G-protein coupled receptor 26 (GPR26) and GPR78 are constitutively active and coupled to increased cAMP formation. They are closely related based on sequence homology and comprise a conserved subgroup within the class A G-protein coupled receptor (GPCR) superfamily. Both receptors are widely expressed in selected tissues of the brain but their endogenous ligands are unknown. GPR26 knockout mice showed increased levels of anxiety- and depression-like behaviors, whereas GPR78 has been implicated in susceptibility to bipolar affective disorder and schizophrenia. 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: 320347 [Multi-domain]  Cd Length: 264  Bit Score: 43.22  E-value: 1.22e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  19 ILAAVVEVGALLGNGALLVVVLRTPGLRD---ALYLAHLCVVDLLAAASIMP---LGLLAAPPPGlgrvrlGPAPCRAAR 92
Cdd:cd15219    4 VLLVVVLVVSLLSNLLVLLCFLYSAELRKqvpGIFLLNLSFCNLLLTVLNMPftlLGVVRNRQPF------GDGFCQAVG 77
                         90       100       110
                 ....*....|....*....|....*....|....
gi 325495579  93 FLSAALLPACTLGVAALGLARYRLIVHPLRPGSR 126
Cdd:cd15219   78 FLETFLTSNAMLSMAALSIDRWIAVVFPLSYTSK 111
7tmA_QRFPR cd15205
pyroglutamylated RFamide peptide receptor, member of the class A family of seven-transmembrane ...
18-122 1.23e-04

pyroglutamylated RFamide peptide receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; 26RFa, also known as QRFP (Pyroglutamylated RFamide peptide), is a 26-amino acid residue peptide that belongs to a family of neuropeptides containing an Arg-Phe-NH2 (RFamide) motif at its C-terminus. 26Rfa/QRFP 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.


Pssm-ID: 320333 [Multi-domain]  Cd Length: 298  Bit Score: 43.23  E-value: 1.23e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  18 LILAAVVEVGALLGNGALLVVVLRTPGLRDA--LYLAHLCVVDLLAAASIMPLGLLAAPppgLGRVRLGPAPCRAARFLS 95
Cdd:cd15205    4 VITYVLIFVLALFGNSLVIYVVTRKRAMRTAtnIFICSLALSDLLITFFCIPFTLLQNI---SSNWLGGAFMCKMVPFVQ 80
                         90       100
                 ....*....|....*....|....*..
gi 325495579  96 AALLPACTLGVAALGLARYRLIVHPLR 122
Cdd:cd15205   81 STAVVTSILTMTCIAVERHQGIVHPLK 107
7tm_1 pfam00001
7 transmembrane receptor (rhodopsin family); This family contains, amongst other ...
31-290 1.64e-04

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: 42.67  E-value: 1.64e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579   31 GNGALLVVVLRTPGLRDA--LYLAHLCVVDLLAAASIMPLGLLAAPppGLGRVRLGPAPCRAARFLSAALLPACTLGVAA 108
Cdd:pfam00001   1 GNLLVILVILRNKKLRTPtnIFLLNLAVADLLFSLLTLPFWLVYYL--NHGDWPFGSALCKIVGALFVVNGYASILLLTA 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  109 LGLARYRLIVHPLRPGSRPPP---VLVLTAVWAAAGLLGALSL--LGPPPAPPPAPARCSV-----------------LA 166
Cdd:pfam00001  79 ISIDRYLAIVHPLRYKRRRTPrraKVLILVIWVLALLLSLPPLlfGWTLTVPEGNVTVCFIdfpedlskpvsytllisVL 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  167 GGLGPFrplwallafalpaLLLLGAYGGIFVVARRAALRPPRPARGSRLRsdsldsrlsilpplrprlpggKAALAPALA 246
Cdd:pfam00001 159 GFLLPL-------------LVILVCYTLIIRTLRKSASKQKSSERTQRRR---------------------KALKTLAVV 204
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 325495579  247 VGQFAACWLPYG--------CACLAPAARAAEAEAAVTWVAYSAFAAHPFLY 290
Cdd:pfam00001 205 VVVFILCWLPYHivnlldslALDCELSRLLDKALSVTLWLAYVNSCLNPIIY 256
7tmA_amine_R-like cd14967
amine receptors and similar proteins, member of the class A family of seven-transmembrane G ...
16-301 1.65e-04

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: 42.94  E-value: 1.65e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  16 LGLILAAVVeVGALLGNGALLVVVLRTPGLRDA--LYLAHLCVVDLLAAASIMPLGLLAAPppgLGRVRLGPAPCRAARF 93
Cdd:cd14967    2 LAVFLSLII-LVTVFGNLLVILAVYRNRRLRTVtnYFIVSLAVADLLVALLVMPFSAVYTL---LGYWPFGPVLCRFWIA 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  94 LSAALLPACTLGVAALGLARYRLIVHPLRPGSRPPP---VLVLTAVWAAAGLlgalsllgpppapppaparCSVLAGGLG 170
Cdd:cd14967   78 LDVLCCTASILNLCAISLDRYLAITRPLRYRQLMTKkraLIMIAAVWVYSLL-------------------ISLPPLVGW 138
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579 171 PFRPLWALLAFALPALLLLG-------------------AYGGIFVVARRAAlrpprpargsrlrsdsldsrlsilpplr 231
Cdd:cd14967  139 RDETQPSVVDCECEFTPNKIyvlvssvisffipllimivLYARIFRVARREL---------------------------- 190
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 325495579 232 prlpggKAALAPALAVGQFAACWLPYGC-----ACLAPAARAAEAEAAVTWVAYSAFAAHPFLYGLLQRPVRLAL 301
Cdd:cd14967  191 ------KAAKTLAIIVGAFLLCWLPFFIiylvsAFCPPDCVPPILYAVFFWLGYLNSALNPIIYALFNRDFRRAF 259
7tmA_CCK-AR cd15978
cholecystokinin receptor type A, member of the class A family of seven-transmembrane G ...
18-137 3.18e-04

cholecystokinin receptor type A, 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: 320644 [Multi-domain]  Cd Length: 278  Bit Score: 42.16  E-value: 3.18e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  18 LILAAVVEVGALLGNGALLVVVLRTPGLRDA--LYLAHLCVVDLLAAASIMPLGLLaapPPGLGRVRLGPAPCRAARFLS 95
Cdd:cd15978    4 ILLYSLIFLLSVLGNSLIIAVLIRNKRMRTVtnIFLLSLAVSDLMLCLFCMPFTLI---PNLLKDFIFGSAVCKTATYFM 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 325495579  96 AALLPACTLGVAALGLARYRLIVHPLRP---GSRPPPVLVLTAVW 137
Cdd:cd15978   81 GISVSVSTFNLVAISLERYSAICKPLKSrvwQTKSHALKVIAATW 125
7tmA_Angiotensin_R-like cd14985
angiotesin receptor family and its related G protein-coupled receptors, member of the class A ...
29-137 3.76e-04

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


Pssm-ID: 341320 [Multi-domain]  Cd Length: 284  Bit Score: 41.98  E-value: 3.76e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  29 LLGNGALLVVVLRTPGLRDA--LYLAHLCVVDLLAAASimpLGLLAAPPPGLGRVRLGPAPCRAARFLSAALLPACTLGV 106
Cdd:cd14985   15 LLGNLFVVWVFLFPRGPKRVadIFIANLAAADLVFVLT---LPLWATYTANQYDWPFGAFLCKVSSYVISVNMFASIFLL 91
                         90       100       110
                 ....*....|....*....|....*....|....
gi 325495579 107 AALGLARYRLIVHPL--RPGSRPPPVLVLTA-VW 137
Cdd:cd14985   92 TCMSVDRYLAIVHPVasRRLRRRRQARVTCAlIW 125
7tmA_PrRP_R cd15394
prolactin-releasing peptide receptor, member of the class A family of seven-transmembrane G ...
21-137 4.03e-04

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: 41.65  E-value: 4.03e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  21 AAVVEVGaLLGNGALLVVVLRTPGLRDA--LYLAHLCVVDLLAAASIMPLGLLAAPPPGlGRVrLGPAPCRAARFLSAAL 98
Cdd:cd15394    8 SLVVLVG-VVGNYLLIYVICRTKKMHNVtnFLIGNLAFSDMLMCATCVPLTLAYAFEPR-GWV-FGRFMCYFVFLMQPVT 84
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 325495579  99 LPACTLGVAALGLARYRLIVHPLRP-GSRPPPVLVLTAVW 137
Cdd:cd15394   85 VYVSVFTLTAIAVDRYYVTVYPLRRrISRRTCAYIVAAIW 124
7tmA_TRH-R cd14995
thyrotropin-releasing hormone receptor, member of the class A family of seven-transmembrane G ...
12-122 5.64e-04

thyrotropin-releasing hormone receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; TRH-R is a member of the class A rhodopsin-like G protein-coupled receptors, which binds the tripeptide thyrotropin releasing hormone. The TRH-R activates phosphoinositide metabolism through a pertussis-toxin-insensitive G-protein, the G(q)/G(11) class. TRH stimulates the synthesis and release of thyroid-stimulating hormone in the anterior pituitary. TRH is produced in many other tissues, especially within the nervous system, where it appears to act as a neurotransmitter/neuromodulator. It also stimulates the synthesis and release of prolactin. In the CNS, TRH stimulates a number of behavioral and pharmacological actions, including increased turnover of catecholamines in the nucleus accumbens. There are two thyrotropin-releasing hormone receptors in some mammals, thyrotropin-releasing hormone receptor 1 (TRH1) which has been found in a number of species including rat, mouse, and human and thyrotropin-releasing hormone receptor 2 (TRH2) which has, only been found in rodents. These TRH receptors are found in high levels in the anterior pituitary, and are also found in the retina and in certain areas of the brain.


Pssm-ID: 320126 [Multi-domain]  Cd Length: 269  Bit Score: 41.22  E-value: 5.64e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  12 VAGSLGLILAAVvevgALLGNGALLVVVLRTPGLRDAL--YLAHLCVVDLLA-AASIMP--LGLLAAPPPGLgrvrLGPA 86
Cdd:cd14995    2 VATFLVLLICGV----GIVGNIMVVLVVLRTRHMRTPTncYLVSLAVADLMVlVAAGLPneIESLLGPDSWI----YGYA 73
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 325495579  87 PCRAARFLSAALLPACTLGVAALGLARYRLIVHPLR 122
Cdd:cd14995   74 GCLLITYLQYLGINASSLSITAFTIERYIAICHPMK 109
7tmA_P2Y11 cd15376
P2Y purinoceptor 11, member of the class A family of seven-transmembrane G protein-coupled ...
28-137 5.64e-04

P2Y purinoceptor 11, member of the class A family of seven-transmembrane G protein-coupled receptors; P2Y11 belongs to the P2Y receptor family of purinergic G-protein coupled receptors. The activation of P2Y11 is a major pathway of macrophage activation that leads to the release of cytokines. The P2Y receptor family is composed of eight subtypes, which are activated by naturally occurring extracellular nucleotides such as ATP, ADP, UTP, UDP, and UDP-glucose. These eight receptors are ubiquitous in human tissues and can be further classified into two subfamilies based on sequence homology and second messenger coupling: a subfamily of five P2Y1-like receptors (P2Y1, P2Y2, P2Y4, P2Y6, and P2Y11Rs) that are coupled to G(q) protein to activate phospholipase C (PLC) and a second subfamily of three P2Y12-like receptors (P2Y12, P2YR13, and P2Y14Rs) that are coupled to G(i) protein to inhibit adenylate cyclase. Several cloned subtypes, such as P2Y3, P2Y5, and P2Y7-10, are not functional mammalian nucleotide receptors. The native agonists for P2Y receptors are: ATP (P2Y2, P2Y12), ADP (P2Y1, P2Y12, and P2Y13), UTP (P2Y2, P2Y4), UDP (P2Y6, P2Y14), and UDP-glucose (P2Y14).


Pssm-ID: 320498 [Multi-domain]  Cd Length: 284  Bit Score: 41.22  E-value: 5.64e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  28 ALLGNGA---LLVVVLRTPGLRDALYLAHLCVVDLLAAASIMPLGLLAAPPPGLgrvRLGPAPCRAARFLSAALLPACTL 104
Cdd:cd15376   14 AVLGNGLalwLFVTRERRPWHTGVVFSFNLAVSDLLYALSLPLLAAYYYPPKNW---RFGEAACKLERFLFTCNLYGSIF 90
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 325495579 105 GVAALGLARYRLIVHPLRPGSRPPPV---LVLTAVW 137
Cdd:cd15376   91 FITCISLNRYLGIVHPFFTRSHVRPKhakLVSLAVW 126
7tmA_NPFFR2 cd15980
neuropeptide FF receptor 2, member of the class A family of seven-transmembrane G ...
29-137 6.72e-04

neuropeptide FF receptor 2, 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: 320646 [Multi-domain]  Cd Length: 299  Bit Score: 41.03  E-value: 6.72e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  29 LLGNGALLVVVLRTPGLRDA--LYLAHLCVVDLLAAASIMPLGLLAAPPPGLgrvRLGPAPCRAARFLSAALLPACTLGV 106
Cdd:cd15980   15 MMGNGVVCFIVLRSKHMRTVtnLFILNLAISDLLVGIFCMPTTLLDNIIAGW---PFGSTVCKMSGMVQGISVSASVFTL 91
                         90       100       110
                 ....*....|....*....|....*....|..
gi 325495579 107 AALGLARYRLIVHPLRPG-SRPPPVLVLTAVW 137
Cdd:cd15980   92 VAIAVDRFRCIVYPFKQKlTISTAVVIIVIIW 123
7tmA_NTSR1 cd15355
neurotensin receptor subtype 1, member of the class A family of seven-transmembrane G ...
18-137 7.12e-04

neurotensin receptor subtype 1, member of the class A family of seven-transmembrane G protein-coupled receptors; Neurotensin (NTS) is a 13 amino-acid neuropeptide that functions as both a neurotransmitter and a hormone in the nervous system and peripheral tissues, respectively. NTS exerts various biological activities through activation of the G protein-coupled neurotensin receptors, NTSR1 and NTSR2. In the brain, NTS is involved in the modulation of dopamine neurotransmission, opioid-independent analgesia, hypothermia, and the inhibition of food intake, while in the periphery NTS promotes the growth of various normal and cancer cells and acts as a paracrine and endocrine modulator of the digestive tract. The third neurotensin receptor, NTSR3 or also called sortilin, is not a G protein-coupled receptor.


Pssm-ID: 320477 [Multi-domain]  Cd Length: 310  Bit Score: 40.99  E-value: 7.12e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  18 LILAAVVEVGaLLGNGALLVVVLRTPGLRDA-----LYLAHLCVVDLLAAASIMPLGL-----LAAPppglgrVRLGPAP 87
Cdd:cd15355    5 AIYLALFVVG-TVGNSITLYTLARKKSLQHLqstvhYHLASLALSDLLILLLAMPVELynfiwVHHP------WAFGDAA 77
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 325495579  88 CRAARFLSAALLPACTLGVAALGLARYRLIVHPLRPG---SRPPPVLVLTAVW 137
Cdd:cd15355   78 CRGYYFLRDACTYATALNVASLSVERYLAICHPFKAKslmSRSRTKKFISAIW 130
7tmA_Vasopressin_Oxytocin cd15196
vasopressin and oxytocin receptors, member of the class A family of seven-transmembrane G ...
22-122 1.01e-03

vasopressin and oxytocin receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Vasopressin (also known as arginine vasopressin or anti-diuretic hormone) and oxytocin are synthesized in the hypothalamus and are released from the posterior pituitary gland. The actions of vasopressin are mediated by the interaction of this hormone with three receptor subtypes: V1aR, V1bR, and V2R. These subtypes are differ in localization, function, and signaling pathways. Activation of V1aR and V1bR stimulate phospholipase C, while activation of V2R stimulates adenylate cyclase. Although vasopressin and oxytocin differ only by two amino acids and stimulate the same cAMP/PKA pathway, they have divergent physiological functions. Vasopressin is involved in regulating blood pressure and the balance of water and sodium ions, whereas oxytocin plays an important role in the uterus during childbirth and in lactation.


Pssm-ID: 320324 [Multi-domain]  Cd Length: 264  Bit Score: 40.30  E-value: 1.01e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  22 AVVEVGALLGNGALLVVVL--RTPGLRDALYLAHLCVVDLLAAA-SIMPLGLLAAPppglGRVRLGPAPCRAARFLSAAL 98
Cdd:cd15196    8 ATILVLALFGNSCVLLVLYrrRRKLSRMHLFILHLSVADLLVALfNVLPQLIWDIT----YRFYGGDLLCRLVKYLQVVG 83
                         90       100
                 ....*....|....*....|....
gi 325495579  99 LPACTLGVAALGLARYRLIVHPLR 122
Cdd:cd15196   84 MYASSYVLVATAIDRYIAICHPLS 107
7tmA_GHSR-like cd15928
growth hormone secretagogue receptor, motilin receptor, and related proteins, member of the ...
29-122 1.14e-03

growth hormone secretagogue receptor, motilin receptor, and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subfamily includes growth hormone secretagogue receptor (GHSR or ghrelin receptor), motilin receptor (also called GPR38), and related proteins. Both GHSR and GPR38 bind peptide hormones. Ghrelin, the endogenous ligand for GHSR, is an acylated 28-amino acid peptide hormone produced by ghrelin cells in the gastrointestinal tract. Ghrelin is also called the hunger hormone and is involved in the regulation of growth hormone release, appetite and feeding, gut motility, lipid and glucose metabolism, and energy balance. Motilin, the ligand for GPR38, is a 22 amino acid peptide hormone expressed throughout the gastrointestinal tract and stimulates contraction of gut smooth muscle. It is involved in the regulation of digestive tract motility.


Pssm-ID: 320594 [Multi-domain]  Cd Length: 288  Bit Score: 40.17  E-value: 1.14e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  29 LLGNGALLVVVLRTPGLRDA--LYLAHLCVVDLLAAAsIMPLGL--LAAPPPGlgrvRLGPAPCRAARFLSAALLPACTL 104
Cdd:cd15928   15 ASGNLLTVLVIGRSRDMRTTtnLYLSSLAVSDLLIFL-VLPLDLyrLWRYRPW----RFGDLLCRLMYFFSETCTYASIL 89
                         90
                 ....*....|....*...
gi 325495579 105 GVAALGLARYRLIVHPLR 122
Cdd:cd15928   90 HITALSVERYLAICHPLR 107
7tmA_NMU-R1 cd15358
neuromedin U receptor subtype 1, member of the class A family of seven-transmembrane G ...
26-137 1.22e-03

neuromedin U receptor subtype 1, member of the class A family of seven-transmembrane G protein-coupled receptors; Neuromedin U (NMU) is a highly conserved neuropeptide with a common C-terminal heptapeptide sequence (FLFRPRN-amide) found at the highest levels in the gastrointestinal tract and pituitary gland of mammals. Disruption or replacement of residues in the conserved heptapeptide region can result in the reduced ability of NMU to stimulate smooth-muscle contraction. Two G-protein coupled receptor subtypes, NMU-R1 and NMU-R2, with a distinct expression pattern, have been identified to bind NMU. NMU-R1 is expressed primarily in the peripheral nervous system, while NMU-R2 is mainly found in the central nervous system. Neuromedin S, a 36 amino-acid neuropeptide that shares a conserved C-terminal heptapeptide sequence with NMU, is a highly potent and selective NMU-R2 agonist. Pharmacological studies have shown that both NMU and NMS inhibit food intake and reduce body weight, and that NMU increases energy expenditure.


Pssm-ID: 320480 [Multi-domain]  Cd Length: 305  Bit Score: 40.14  E-value: 1.22e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  26 VGALlGNGALLVVVLRTPGLRDA--LYLAHLCVVDLLAAASIMPLGL--LAAPPPGLgrvrLGPAPCRAARFLSAALLPA 101
Cdd:cd15358   13 VGAV-GNGLTCIVILRHKVMRTPtnYYLFSLAVSDLLVLLLGMPLELyeMWSNYPFL----LGAGGCYFKTLLFETVCFA 87
                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 325495579 102 CTLGVAALGLARYRLIVHPLRPGS---RPPPVLVLTAVW 137
Cdd:cd15358   88 SILNVTALSVERYIAVVHPLKAKYvvtRTHAKRVIGAVW 126
7tmA_NMU-R cd15133
neuromedin U receptors, member of the class A family of seven-transmembrane G protein-coupled ...
23-137 1.33e-03

neuromedin U receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Neuromedin U (NMU) is a highly conserved neuropeptide with a common C-terminal heptapeptide sequence (FLFRPRN-amide) found at the highest levels in the gastrointestinal tract and pituitary gland of mammals. Disruption or replacement of residues in the conserved heptapeptide region can result in the reduced ability of NMU to stimulate smooth-muscle contraction. Two G-protein coupled receptor subtypes, NMU-R1 and NMU-R2, with a distinct expression pattern, have been identified to bind NMU. NMU-R1 is expressed primarily in the peripheral nervous system, while NMU-R2 is mainly found in the central nervous system. Neuromedin S, a 36 amino-acid neuropeptide that shares a conserved C-terminal heptapeptide sequence with NMU, is a highly potent and selective NMU-R2 agonist. Pharmacological studies have shown that both NMU and NMS inhibit food intake and reduce body weight, and that NMU increases energy expenditure.


Pssm-ID: 320261 [Multi-domain]  Cd Length: 298  Bit Score: 40.21  E-value: 1.33e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  23 VVEVGALLGNGALLVVVLRTPGLRDA--LYLAHLCVVDLLAAASIMPLGL--LAAPPPGLgrvrLGPAPCRAARFLSAAL 98
Cdd:cd15133    9 LIFVVGVVGNVLTCLVIARHKAMRTPtnYYLFSLAVSDLLVLLLGMPLELyeLWQNYPFL----LGSGGCYFKTFLFETV 84
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 325495579  99 LPACTLGVAALGLARYRLIVHPLRPGS---RPPPVLVLTAVW 137
Cdd:cd15133   85 CLASILNVTALSVERYIAVVHPLAARTcstRPRVTRVLGCVW 126
7tmA_TACR_family cd14992
tachykinin receptor and closely related proteins, member of the class A family of ...
23-137 1.57e-03

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: 40.11  E-value: 1.57e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  23 VVEVGALLGNGALLVVVLRTPGLRDA--LYLAHLCVVDLLAAASIMPLGLlaapppGLGRVRLGPAP---CRAARFLSAA 97
Cdd:cd14992    9 VIILVSVVGNFIVIAALARHKNLRGAtnYFIASLAISDLLMALFCTPFNF------TYVVSLSWEYGhflCKIVNYLRTV 82
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 325495579  98 LLPACTLGVAALGLARYRLIVHPLRPGSR---PPPVLVLTAVW 137
Cdd:cd14992   83 SVYASSLTLTAIAFDRYFAIIHPLKPRHRqsyTTTVIIIITIW 125
7tmA_tyramine_R-like cd15061
tyramine receptors and similar proteins, member of the class A family of seven-transmembrane G ...
19-137 1.75e-03

tyramine receptors and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes tyramine-specific receptors and similar proteins found in insects and other invertebrates. These tyramine receptors form a distinct receptor family that is phylogenetically different from the other tyramine/octopamine receptors which also found in invertebrates. Both octopamine and tyramine mediate their actions via G protein-coupled receptors (GPCRs) and are the invertebrate equivalent of vertebrate adrenergic neurotransmitters. In Drosophila, octopamine is involved in ovulation by mediating an egg release from the ovary, while a physiological role for tyramine in this process is not fully understood. 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: 320189 [Multi-domain]  Cd Length: 256  Bit Score: 39.65  E-value: 1.75e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  19 ILAAVVEVGALLGNGALLVVVLRTPGLRDA--LYLAHLCVVDLLAAASIMPLGLLAApppGLGRVRLGPAPCRAARFLSA 96
Cdd:cd15061    4 SFLILAIIFTIFGNLLVILAVATTRRLRTItnCYIVSLATADLLVGVLVLPLAIIRQ---LLGYWPLGSHLCDFWISLDV 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 325495579  97 ALLPACTLGVAALGLARYRLIVHPL---RPGSRPPPVLVLTAVW 137
Cdd:cd15061   81 LLCTASILNLCCISLDRYFAITYPLkyrTKRSRRLAITMILAVW 124
7tmA_ET_R-like cd14977
endothelin receptors and related proteins, member of the class A family of seven-transmembrane ...
19-122 1.81e-03

endothelin receptors and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subfamily of G-protein coupled receptors includes endothelin receptors, bombesin receptor subtype 3 (BRS-3), gastrin-releasing peptide receptor (GRPR), neuromedin B receptor (NMB-R), endothelin B receptor-like 2 (ETBR-LP-2), and GRP37. The endothelin receptors and related proteins are members of the seven transmembrane rhodopsin-like G-protein coupled receptor family (class A GPCRs) which activate multiple effectors via different types of G protein.


Pssm-ID: 320108 [Multi-domain]  Cd Length: 292  Bit Score: 39.71  E-value: 1.81e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  19 ILAAVVEVGALLGNGALLVVVLRTPGLRDAL--YLAHLCVVDLLAAASIMPLGLLAAPPPGLGrvrLGPAPCRAARFLSA 96
Cdd:cd14977    5 SLSLVIFAVGIIGNLMVLCIVCTNYYMRSVPniLIASLALGDLLLLLLCVPLNAYNLLTKDWL---FGDVMCKLVPFIQV 81
                         90       100
                 ....*....|....*....|....*.
gi 325495579  97 ALLPACTLGVAALGLARYRLIVHPLR 122
Cdd:cd14977   82 TSLGVTVFSLCALSIDRYRAAVNSMP 107
7tmA_GPR84-like cd15210
G protein-coupled receptor 84 and similar proteins, member of the class A family of ...
12-137 1.87e-03

G protein-coupled receptor 84 and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; GPR84, also known as the inflammation-related G-Protein coupled receptor EX33, is a receptor for medium-chain free fatty acid (FFA) with carbon chain lengths of C9 to C14. Among these medium-chain FFAs, capric acid (C10:0), undecanoic acid (C11:0), and lauric acid (C12:0) are the most potent endogenous agonists of GPR84, whereas short-chain and long-chain saturated and unsaturated FFAs do not activate this receptor. GPR84 contains a [G/N]RY-motif instead of the highly conserved Asp-Arg-Tyr (DRY) motif found in the third transmembrane helix (TM3) of the rhodopsin-like class A receptors and 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, which then activate the heterotrimeric G proteins. In the case of GPR84, activation of the receptor couples to a pertussis toxin sensitive G(i/o)-protein pathway. GPR84 knockout mice showed increased Th2 cytokine production including IL-4, IL-5, and IL-13 compared to wild-type mice. It has been also shown that activation of GPR84 augments lipopolysaccharide-stimulated IL-8 production in polymorphonuclear leukocytes and TNF-alpha production in macrophages, suggesting that GPR84 may function as a proinflammatory receptor.


Pssm-ID: 320338 [Multi-domain]  Cd Length: 254  Bit Score: 39.56  E-value: 1.87e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  12 VAGSLGLILAAVVEVGALLgngaLLVVVLRTPGLRD--ALYLAHLCVVDLLAAASIMPLgllAAPPPGLGRVRLGPAPCR 89
Cdd:cd15210    2 FAAVWGIVFMVVGVPGNLL----TVLALLRSKKLRTrtNAFIINLSISDLLFCAFNLPL---AASTFLHQAWIHGETLCR 74
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 325495579  90 AARFLSAALLPACTLGVAALGLARYRLIVHPLRPG---SRPPPVLVLTAVW 137
Cdd:cd15210   75 VFPLLRYGLVAVSLLTLVLITLNRYILIAHPSLYPriyTRRGLALMIAGTW 125
7tmA_Galanin_R-like cd14971
galanin receptor and related proteins, member of the class A family of seven-transmembrane G ...
18-136 3.06e-03

galanin receptor and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subfamily includes G-protein coupled galanin receptors, kisspeptin receptor and allatostatin-A receptor (AstA-R) in insects. These receptors, which are members of the class A of seven transmembrane GPCRs, share a high degree of sequence homology among themselves. The galanin receptors bind galanin, a neuropeptide that is widely expressed in the brain, peripheral tissues, and endocrine glands. Galanin is implicated in numerous neurological and psychiatric diseases including Alzheimer's disease, eating disorders, and epilepsy, among many others. KiSS1-derived peptide receptor (also known as GPR54 or kisspeptin receptor) binds the peptide hormone kisspeptin (metastin), which encoded by the metastasis suppressor gene (KISS1) expressed in various endocrine and reproductive tissues. AstA-R is a G-protein coupled receptor that binds allatostatin A. Three distinct types of allatostatin have been identified in the insects and crustaceans: AstA, AstB, and AstC. They both inhibit the biosynthesis of juvenile hormone and exert an inhibitory influence on food intake. Therefore, allatostatins are considered as potential targets for insect control.


Pssm-ID: 320102 [Multi-domain]  Cd Length: 281  Bit Score: 38.99  E-value: 3.06e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  18 LILAAVVEVGaLLGNGALLVVVLRTPGLRDA--LYLAHLCVVDLLAAASIMPLGLLAAPPPGLgrvRLGPAPCRAARFLS 95
Cdd:cd14971    5 LFFALIFLLG-LVGNSLVILVVARNKPMRSTtnLFILNLAVADLTFLLFCVPFTATIYPLPGW---VFGDFMCKFVHYFQ 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 325495579  96 AALLPACTLGVAALGLARYRLIVHPLRPGSRPPPVLVLTAV 136
Cdd:cd14971   81 QVSMHASIFTLVAMSLDRFLAVVYPLRSLHIRTPRNALAAS 121
7tmA_OR2A-like cd15420
olfactory receptor subfamily 2A and related proteins, member of the class A family of ...
20-122 3.54e-03

olfactory receptor subfamily 2A and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes human olfactory receptor subfamily 2A 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: 320542 [Multi-domain]  Cd Length: 277  Bit Score: 38.85  E-value: 3.54e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  20 LAAVVEVGALLGNGALLVVVLRTPGLRDALY--LAHLCVVDLLAAASIMP--LGLLAAPppglgRVRLGPAPCRAARFLS 95
Cdd:cd15420    6 LFSLLYIFTLLGNGLILGLIWLDSRLHTPMYffLSHLAVVDICYASSTVPhmLGNLLKQ-----RKTISFAGCGTQMYLF 80
                         90       100
                 ....*....|....*....|....*...
gi 325495579  96 AAL-LPACTLgVAALGLARYRLIVHPLR 122
Cdd:cd15420   81 LALaHTECVL-LAVMSYDRYVAICHPLR 107
7tmA_5-HT1_5_7 cd15064
serotonin receptor subtypes 1, 5 and 7, member of the class A family of seven-transmembrane G ...
19-121 3.88e-03

serotonin receptor subtypes 1, 5 and 7, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes serotonin receptor subtypes 1, 5, and 7 that are activated by the neurotransmitter serotonin. The 5-HT1 and 5-HT5 receptors mediate inhibitory neurotransmission by coupling to G proteins of the G(i/o) family. The 5-HT1 receptor subfamily includes 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F. There is no 5-HT1C receptor subtype, as it has been reclassified as 5-HT2C receptor. The 5-HT5A and 5-HT5B receptors have been cloned from rat and mouse, but only the 5-HT5A isoform has been identified in human because of the presence of premature stop codons in the human 5-HT5B gene, which prevents a functional receptor from being expressed. The 5-HT7 receptor is coupled to Gs, which positively stimulates adenylate cyclase activity, leading to increased intracellular cAMP formation and calcium influx. In the CNS, serotonin is involved in the regulation of appetite, mood, sleep, cognition, learning and memory, as well as implicated in neurologic disorders such as migraine, schizophrenia, and depression.


Pssm-ID: 320192 [Multi-domain]  Cd Length: 258  Bit Score: 38.46  E-value: 3.88e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  19 ILAAVVEVGALLGNGALLVVVLRTPGLRD-ALYL-AHLCVVDLLAAASIMPLGLLAAPppgLGRVRLGPAPCRAarFLSA 96
Cdd:cd15064    5 VLLSLIILATILGNALVIAAILLTRKLHTpANYLiASLAVADLLVAVLVMPLSAVYEL---TGRWILGQVLCDI--WISL 79
                         90       100
                 ....*....|....*....|....*...
gi 325495579  97 ALLpACT---LGVAALGLARYRLIVHPL 121
Cdd:cd15064   80 DVT-CCTasiLHLCVIALDRYWAITDAV 106
7tmA_PSP24-like cd15213
G protein-coupled receptor PSP24 and similar proteins, member of the class A family of ...
15-119 4.21e-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: 38.50  E-value: 4.21e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  15 SLGLILAAVVEVGaLLGNGALLVVVLRTPGLRDA--LYLAHLCVVDLLAAASIMPLGLLAAPppgLGRVRLGPAPCRAAR 92
Cdd:cd15213    2 TLAILMILMIFVG-FLGNSIVCLIVYQKPAMRSAinLLLANLAFSDIMLSLVCMPFAAVTII---TGRWIFGDIFCRISA 77
                         90       100
                 ....*....|....*....|....*..
gi 325495579  93 FLSAALLPACTLGVAALGLARYRLIVH 119
Cdd:cd15213   78 MLYWFFVLEGVAILLIISVDRYLIIVQ 104
7tmA_Mel1 cd15209
melatonin receptor 1, member of the class A family of seven-transmembrane G protein-coupled ...
18-122 4.70e-03

melatonin receptor 1, 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: 320337 [Multi-domain]  Cd Length: 279  Bit Score: 38.22  E-value: 4.70e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  18 LILAAVVEVgalLGNGALLVVVLRTPGLRDA--LYLAHLCVVDLLAAASIMPLGLLAAPPPGLGrvrLGPAPCRAARFLS 95
Cdd:cd15209    7 LIVTIVVDV---LGNLLVILSVLRNKKLRNAgnIFVVSLSVADLVVAIYPYPLILHAIFHNGWT---LGQLHCQASGFIM 80
                         90       100
                 ....*....|....*....|....*..
gi 325495579  96 AALLPACTLGVAALGLARYRLIVHPLR 122
Cdd:cd15209   81 GLSVIGSIFNITAIAINRYCYICHSLQ 107
7tm_GPCRs cd14964
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
18-136 5.93e-03

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.


Pssm-ID: 410628 [Multi-domain]  Cd Length: 267  Bit Score: 38.18  E-value: 5.93e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  18 LILAAVVEVGALLGNGALLVVVLRTPGLRD--ALYLAHLCVVDLLAAASImplgLLAAPPPGLGRVRLGP-APCRAARFL 94
Cdd:cd14964    2 TIILSLLTCLGLLGNLLVLLSLVRLRKRPRstRLLLASLAACDLLASLVV----LVLFFLLGLTEASSRPqALCYLIYLL 77
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 325495579  95 SAALLPACTLGVAALGLARYRLIVHPLRPGSRPPPVLVLTAV 136
Cdd:cd14964   78 WYGANLASIWTTLVLTYHRYFALCGPLKYTRLSSPGKTRVII 119
7tmA_NPSR cd15197
neuropeptide S receptor, member of the class A family of seven-transmembrane G protein-coupled ...
17-135 6.56e-03

neuropeptide S receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; Neuropeptide S (NPS) promotes arousal and anxiolytic-like effects by activating its cognate receptor NPSR. NPSR is widely expressed in the brain, and its activation induces an elevation of intracellular calcium and cAMP concentrations, presumably by coupling to G(s) and G(q) proteins. Mutations in NPSR have been associated with an increased susceptibility to asthma. NPSR was originally identified as an orphan receptor GPR154 and is also known as G protein receptor for asthma susceptibility (GPRA) or vasopressin receptor-related receptor 1 (VRR1).


Pssm-ID: 320325 [Multi-domain]  Cd Length: 294  Bit Score: 38.17  E-value: 6.56e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  17 GLILAAVVEVGALLGNGALLVVVLRTP--GLRDALYLAHLCVVDLLAA-ASIMPLGLLAAPppglGRVRLGPAPCRAARF 93
Cdd:cd15197    3 QLATLWVLFVFIVVGNSSVLFALWMRKakKSRMNFFITQLAIADLCVGlINVLTDIIWRIT----VEWRAGDFACKVIRY 78
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 325495579  94 LSAALLPACTLGVAALGLARYRLIVHPLR--PGSRPPPVLVLTA 135
Cdd:cd15197   79 LQVVVTYASTYVLVALSIDRYDAICHPMNfsQSGRQARVLICVA 122
7tmA_Bombesin_R-like cd15927
bombesin receptor subfamily, member of the class A family of seven-transmembrane G ...
19-136 7.06e-03

bombesin receptor subfamily, member of the class A family of seven-transmembrane G protein-coupled receptors; This bombesin subfamily of G-protein coupled receptors consists of neuromedin B receptor (NMBR), gastrin-releasing peptide receptor (GRPR), and bombesin receptor subtype 3 (BRS-3). Bombesin is a tetradecapeptide, originally isolated from frog skin. Mammalian bombesin-related peptides are widely distributed in the gastrointestinal and central nervous systems. The bombesin family receptors couple mainly to the G proteins of G(q/11) family. NMBR functions as the receptor for the neuropeptide neuromedin B, a potent mitogen and growth factor for normal and cancerous lung and for gastrointestinal epithelial tissues. Gastrin-releasing peptide is an endogenous ligand for GRPR and shares high sequence homology with NMB in the C-terminal region. Both NMB and GRP possess bombesin-like biochemical properties. BRS-3 is classified as an orphan receptor and suggested to play a role in sperm cell division and maturation. BRS-3 interacts with known naturally-occurring bombesin-related peptides with low affinity; however, no endogenous high-affinity ligand to the receptor has been identified. The bombesin receptor family belongs to the seven transmembrane rhodopsin-like G-protein coupled receptors (class A GPCRs), which perceive extracellular signals and transduce them to guanine nucleotide-binding (G) proteins.


Pssm-ID: 320593 [Multi-domain]  Cd Length: 294  Bit Score: 38.02  E-value: 7.06e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  19 ILAAVVEVGALLGNGALLVVVLRTPGLRDA--LYLAHLCVVDLLaaasimplgLLAAPPPGLGRVRL------GPAPCRA 90
Cdd:cd15927    5 ILFALIFLVGVLGNGTLILIFLRNKSMRNVpnIFILSLALGDLL---------LLLTCVPFTSTIYTldswpfGEFLCKL 75
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 325495579  91 ARFLSAAllpacTLGVA-----ALGLARYRLIVHPLR-PGSRPPPVLVLTAV 136
Cdd:cd15927   76 SEFLKDT-----SIGVSvftltALSADRYFAIVNPMRkHRSQATRRTLVTAA 122
7tmA_OR52I-like cd15950
olfactory receptor subfamily 52I and related proteins, member of the class A family of ...
28-122 7.68e-03

olfactory receptor subfamily 52I and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes human olfactory receptor subfamily 52I 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: 320616  Cd Length: 275  Bit Score: 37.78  E-value: 7.68e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  28 ALLGNGALLVVVLRTPGLRDALY--LAHLCVVDLLAAASIMP--LGLLAapppgLGRVRLGPAPCRAARFLSAALLPACT 103
Cdd:cd15950   14 ALLGNGTILLVIKLDPSLHEPMYyfLCMLAVIDLVMSTSIVPkmLSIFW-----LGSAEISFEACFTQMFFVHSFTAVES 88
                         90
                 ....*....|....*....
gi 325495579 104 LGVAALGLARYRLIVHPLR 122
Cdd:cd15950   89 GVLLAMAFDRYVAICHPLR 107
7tmA_Opioid_R-like cd14970
opioid receptors and related proteins, member of the class A family of seven-transmembrane G ...
19-137 8.37e-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: 37.66  E-value: 8.37e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 325495579  19 ILAAVVEVGALLGNGALLVVVLRTPGLRDA--LYLAHLCVVDLLaAASIMPlgLLAApPPGLGRVRLGPAPCRAARFLSA 96
Cdd:cd14970    5 AVYSVVCVVGLTGNSLVIYVILRYSKMKTVtnIYILNLAVADEL-FLLGLP--FLAT-SYLLGYWPFGEVMCKIVLSVDA 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 325495579  97 ALLPACTLGVAALGLARYRLIVHPLR-PGSRPPPV--LVLTAVW 137
Cdd:cd14970   81 YNMFTSIFCLTVMSVDRYLAVVHPVKsLRFRTPRKakLVSLCVW 124
 
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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