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Conserved domains on  [gi|11967953|ref|NP_071872|]
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G protein-coupled receptor 88 [Mus musculus]

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 ...
33-347 1.87e-90

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 cd15211:

Pssm-ID: 475119 [Multi-domain]  Cd Length: 283  Bit Score: 273.65  E-value: 1.87e-90
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  33 PVSLLYSGLAIGGTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMPQEAVLGLLPSGsaeppgdwdgGGGSY 112
Cdd:cd15211   1 SLSTVYSFLAVSGTLANVLVIYLVVSFKKLQTTSNAFIVNGCVADLLVCAFWMPQEAVLGSTGTL----------LVLGY 70
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953 113 RLLRGGLLGLGLTVSLLSHCLVALNRYLLITRAPATYQVLYQRRHTVGMLALSWALALGLVLLLPPWAPKPGAE------ 186
Cdd:cd15211  71 RLFREGLLFLGLTVSLLSHSLIALNRYVLITKLPAVYQALYQKRNTEWMIALSWALALGLLLPWLTSFRYPTKSchdsad 150
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953 187 -------PPQVHYPALLAAGALLAQTALLLHCYLGIVRRVRVSVKRVSVLNFhllhqlpgcaaaaaafpaaphapgpgga 259
Cdd:cd15211 151 gsfavvsVLSSRYPALLLAFTVLGQTALVLHCYFGIFRRVQISVKRVSVLNF---------------------------- 202
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953 260 ahpaqpQPLPAALQPRRAQRRLSGLSVLLLCCVFLLATQPLVWVSLASGFSlPVPWGVQAASWLLCCALSALNPLLYTWR 339
Cdd:cd15211 203 ------QIVNNLPYSRPRKDKRLGLYVLLVCCVFLLTTEPLVWVSLAGLFV-PVPVALQTASWLLFCTLFVLNPFLYTWK 275

                ....*...
gi 11967953 340 NEEFRRSV 347
Cdd:cd15211 276 NEEFRRSF 283
 
Name Accession Description Interval E-value
7tmA_GPR88-like cd15211
G protein-coupled receptor 88, member of the class A family of seven-transmembrane G ...
33-347 1.87e-90

G protein-coupled receptor 88, member of the class A family of seven-transmembrane G protein-coupled receptors; GPR88, an orphan G protein-coupled receptor, is predominantly and almost exclusively expressed within medium spiny neurons (MSNs) of the brain's striatum in both human and rodents; thus it is also called Striatum-specific GPCR (STRG). The striatum is known to involve in motor coordination, reward-based decision making, and response learning. GPR88 is shown to co-localize with both dopamine D1 and D2 receptors and displays the highest sequence similarity to receptors for biogenic amines such as dopamine and serotonin. GPR88 knockout mice showed abnormal behaviors observed in schizophrenia, such as disrupted sensorimotor gating, increased stereotypic behavior and locomotor activity in response to treatment with dopaminergic compounds such as apomorphine and amphetamine, respectively, suggesting a role for GPR88 in dopaminergic signaling. Furthermore, the transcriptional profiling studies showed that GPR88 expression is altered in a number of psychiatric disorders such as depression, drug addiction, bipolar and schizophrenia, providing further evidence that GPR88 plays an important role in CNS signaling pathways related to psychiatric disorder. 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: 320339 [Multi-domain]  Cd Length: 283  Bit Score: 273.65  E-value: 1.87e-90
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  33 PVSLLYSGLAIGGTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMPQEAVLGLLPSGsaeppgdwdgGGGSY 112
Cdd:cd15211   1 SLSTVYSFLAVSGTLANVLVIYLVVSFKKLQTTSNAFIVNGCVADLLVCAFWMPQEAVLGSTGTL----------LVLGY 70
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953 113 RLLRGGLLGLGLTVSLLSHCLVALNRYLLITRAPATYQVLYQRRHTVGMLALSWALALGLVLLLPPWAPKPGAE------ 186
Cdd:cd15211  71 RLFREGLLFLGLTVSLLSHSLIALNRYVLITKLPAVYQALYQKRNTEWMIALSWALALGLLLPWLTSFRYPTKSchdsad 150
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953 187 -------PPQVHYPALLAAGALLAQTALLLHCYLGIVRRVRVSVKRVSVLNFhllhqlpgcaaaaaafpaaphapgpgga 259
Cdd:cd15211 151 gsfavvsVLSSRYPALLLAFTVLGQTALVLHCYFGIFRRVQISVKRVSVLNF---------------------------- 202
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953 260 ahpaqpQPLPAALQPRRAQRRLSGLSVLLLCCVFLLATQPLVWVSLASGFSlPVPWGVQAASWLLCCALSALNPLLYTWR 339
Cdd:cd15211 203 ------QIVNNLPYSRPRKDKRLGLYVLLVCCVFLLTTEPLVWVSLAGLFV-PVPVALQTASWLLFCTLFVLNPFLYTWK 275

                ....*...
gi 11967953 340 NEEFRRSV 347
Cdd:cd15211 276 NEEFRRSF 283
7tm_1 pfam00001
7 transmembrane receptor (rhodopsin family); This family contains, amongst other ...
49-166 5.08e-07

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: 50.37  E-value: 5.08e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953    49 NGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMPQEAVLGLLPS----GSAEPPGDWDGGGGSyrllrggllglgL 124
Cdd:pfam00001   2 NLLVILVILRNKKLRTPTNIFLLNLAVADLLFSLLTLPFWLVYYLNHGdwpfGSALCKIVGALFVVN------------G 69
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 11967953   125 TVSLLSHCLVALNRYLLITRaPATYQVLYQRRHTVGMLALSW 166
Cdd:pfam00001  70 YASILLLTAISIDRYLAIVH-PLRYKRRRTPRRAKVLILVIW 110
 
Name Accession Description Interval E-value
7tmA_GPR88-like cd15211
G protein-coupled receptor 88, member of the class A family of seven-transmembrane G ...
33-347 1.87e-90

G protein-coupled receptor 88, member of the class A family of seven-transmembrane G protein-coupled receptors; GPR88, an orphan G protein-coupled receptor, is predominantly and almost exclusively expressed within medium spiny neurons (MSNs) of the brain's striatum in both human and rodents; thus it is also called Striatum-specific GPCR (STRG). The striatum is known to involve in motor coordination, reward-based decision making, and response learning. GPR88 is shown to co-localize with both dopamine D1 and D2 receptors and displays the highest sequence similarity to receptors for biogenic amines such as dopamine and serotonin. GPR88 knockout mice showed abnormal behaviors observed in schizophrenia, such as disrupted sensorimotor gating, increased stereotypic behavior and locomotor activity in response to treatment with dopaminergic compounds such as apomorphine and amphetamine, respectively, suggesting a role for GPR88 in dopaminergic signaling. Furthermore, the transcriptional profiling studies showed that GPR88 expression is altered in a number of psychiatric disorders such as depression, drug addiction, bipolar and schizophrenia, providing further evidence that GPR88 plays an important role in CNS signaling pathways related to psychiatric disorder. 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: 320339 [Multi-domain]  Cd Length: 283  Bit Score: 273.65  E-value: 1.87e-90
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  33 PVSLLYSGLAIGGTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMPQEAVLGLLPSGsaeppgdwdgGGGSY 112
Cdd:cd15211   1 SLSTVYSFLAVSGTLANVLVIYLVVSFKKLQTTSNAFIVNGCVADLLVCAFWMPQEAVLGSTGTL----------LVLGY 70
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953 113 RLLRGGLLGLGLTVSLLSHCLVALNRYLLITRAPATYQVLYQRRHTVGMLALSWALALGLVLLLPPWAPKPGAE------ 186
Cdd:cd15211  71 RLFREGLLFLGLTVSLLSHSLIALNRYVLITKLPAVYQALYQKRNTEWMIALSWALALGLLLPWLTSFRYPTKSchdsad 150
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953 187 -------PPQVHYPALLAAGALLAQTALLLHCYLGIVRRVRVSVKRVSVLNFhllhqlpgcaaaaaafpaaphapgpgga 259
Cdd:cd15211 151 gsfavvsVLSSRYPALLLAFTVLGQTALVLHCYFGIFRRVQISVKRVSVLNF---------------------------- 202
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953 260 ahpaqpQPLPAALQPRRAQRRLSGLSVLLLCCVFLLATQPLVWVSLASGFSlPVPWGVQAASWLLCCALSALNPLLYTWR 339
Cdd:cd15211 203 ------QIVNNLPYSRPRKDKRLGLYVLLVCCVFLLTTEPLVWVSLAGLFV-PVPVALQTASWLLFCTLFVLNPFLYTWK 275

                ....*...
gi 11967953 340 NEEFRRSV 347
Cdd:cd15211 276 NEEFRRSF 283
7tm_classA_rhodopsin-like cd00637
rhodopsin receptor-like class A family of the seven-transmembrane G protein-coupled receptor ...
35-166 6.80e-16

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: 76.94  E-value: 6.80e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  35 SLLYSGLAIGGTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMPQEAVLGLLPSGSAEPPGDWDGGGGSYrl 114
Cdd:cd00637   2 AVLYILIFVVGLVGNLLVILVILRNRRLRTVTNYFILNLAVADLLVGLLVIPFSLVSLLLGRWWFGDALCKLLGFLQS-- 79
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 11967953 115 lrggllgLGLTVSLLSHCLVALNRYLLITRaPATYQVLYQRRHTVGMLALSW 166
Cdd:cd00637  80 -------VSLLASILTLTAISVDRYLAIVH-PLRYRRRFTRRRAKLLIALIW 123
7tmA_amine_R-like cd14967
amine receptors and similar proteins, member of the class A family of seven-transmembrane G ...
34-166 8.98e-12

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: 64.89  E-value: 8.98e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  34 VSLLYSGLAIGGTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMPQEAVLGLLPsgsaeppgdWDGGGGSYR 113
Cdd:cd14967   2 LAVFLSLIILVTVFGNLLVILAVYRNRRLRTVTNYFIVSLAVADLLVALLVMPFSAVYTLLG---------YWPFGPVLC 72
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
gi 11967953 114 LLRGGLLGLGLTVSLLSHCLVALNRYLLITRaPATYQVLYQRRHTVGMLALSW 166
Cdd:cd14967  73 RFWIALDVLCCTASILNLCAISLDRYLAITR-PLRYRQLMTKKRALIMIAAVW 124
7tmA_GPR84-like cd15210
G protein-coupled receptor 84 and similar proteins, member of the class A family of ...
45-166 4.16e-09

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: 56.89  E-value: 4.16e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  45 GTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMPQEAVLGLLPSGSAEPPGDWDGGGGSYRLLRggllglgl 124
Cdd:cd15210  14 GVPGNLLTVLALLRSKKLRTRTNAFIINLSISDLLFCAFNLPLAASTFLHQAWIHGETLCRVFPLLRYGLVA-------- 85
                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 11967953 125 tVSLLSHCLVALNRYLLITRaPATYQVLYQRRHTVGMLALSW 166
Cdd:cd15210  86 -VSLLTLVLITLNRYILIAH-PSLYPRIYTRRGLALMIAGTW 125
7tmA_NPYR-like cd15203
neuropeptide Y receptors and related proteins, member of the class A family of ...
32-166 9.43e-09

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: 56.07  E-value: 9.43e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  32 IPVSLLYSGLAIGGTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMP--------QEAVLG-----LLPSGS 98
Cdd:cd15203   1 IILILLYGLIIVLGVVGNLLVIYVVLRNKSMQTVTNIFILNLAVSDLLLCLVSLPftliytltKNWPFGsilckLVPSLQ 80
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 11967953  99 AeppgdwdggggsyrllrggllgLGLTVSLLSHCLVALNRYLLI---TRAPatyqvlYQRRHTVGMLALSW 166
Cdd:cd15203  81 G----------------------VSIFVSTLTLTAIAIDRYQLIvypTRPR------MSKRHALLIIALIW 123
7tmA_D1-like_dopamine_R cd15057
D1-like family of dopamine receptors, member of the class A family of seven-transmembrane G ...
32-166 5.12e-08

D1-like family of dopamine receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Dopamine receptors are members of the class A G protein-coupled receptors that are involved in many neurological processes in the central nervous system (CNS). The neurotransmitter dopamine is the primary endogenous agonist for dopamine receptors. Dopamine receptors consist of at least five subtypes: D1, D2, D3, D4, and D5. The D1 and D5 subtypes are members of the D1-like family of dopamine receptors, whereas the D2, D3 and D4 subtypes are members of the D2-like family. The D1-like family receptors are coupled to G proteins of the G(s) family, which activate adenylate cyclase, causing cAMP formation and activation of protein kinase A. In contrast, activation of D2-like family receptors is linked to G proteins of the G(i) family, which inhibit adenylate cyclase. Dopamine receptors are major therapeutic targets for neurological and psychiatric disorders such as drug abuse, depression, schizophrenia, or Parkinson's disease. 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: 320185 [Multi-domain]  Cd Length: 299  Bit Score: 53.97  E-value: 5.12e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  32 IPVSLLYSGLAIGGTLANGMVIYLVSSFRKLQTT-SNAFIVNGCAADLSVCALWMPQEA---VLGLLPSGsaeppgdwdg 107
Cdd:cd15057   1 IITGCILYLLVLLTLLGNALVIAAVLRFRHLRSKvTNYFIVSLAVSDLLVAILVMPWAAvneVAGYWPFG---------- 70
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 11967953 108 gggSYRLLRGGLLGLGLTVSLLSHCLVALNRYLLITRaPATYQVLYQRRHTVGMLALSW 166
Cdd:cd15057  71 ---SFCDVWVSFDIMCSTASILNLCVISVDRYWAISS-PFRYERRMTRRRAFIMIAVAW 125
7tm_1 pfam00001
7 transmembrane receptor (rhodopsin family); This family contains, amongst other ...
49-166 5.08e-07

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: 50.37  E-value: 5.08e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953    49 NGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMPQEAVLGLLPS----GSAEPPGDWDGGGGSyrllrggllglgL 124
Cdd:pfam00001   2 NLLVILVILRNKKLRTPTNIFLLNLAVADLLFSLLTLPFWLVYYLNHGdwpfGSALCKIVGALFVVN------------G 69
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 11967953   125 TVSLLSHCLVALNRYLLITRaPATYQVLYQRRHTVGMLALSW 166
Cdd:pfam00001  70 YASILLLTAISIDRYLAIVH-PLRYKRRRTPRRAKVLILVIW 110
7tmA_Opsins_type2_animals cd14969
type 2 opsins in animals, member of the class A family of seven-transmembrane G ...
32-166 6.85e-07

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


Pssm-ID: 381741 [Multi-domain]  Cd Length: 284  Bit Score: 50.28  E-value: 6.85e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  32 IPVSLLYSGLAIGGTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMPQEAVlgllpSGSAEPPGDWDGGGGS 111
Cdd:cd14969   1 YVLAVYLSLIGVLGVVLNGLVIIVFLKKKKLRTPLNLFLLNLALADLLMSVVGYPLSFY-----SNLSGRWSFGDPGCVI 75
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 11967953 112 YRLLRGGLLGlgltVSLLSHCLVALNRYLLITRaPATYQVLyQRRHTVGMLALSW 166
Cdd:cd14969  76 YGFAVTFLGL----VSISTLAALAFERYLVIVR-PLKAFRL-SKRRALILIAFIW 124
7tmA_5-HT7 cd15329
serotonin receptor subtype 7, member of the class A family of seven-transmembrane G ...
34-166 2.54e-06

serotonin receptor subtype 7, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT7 receptor, one of 14 mammalian serotonin receptors, is a member of the class A of GPCRs and is activated by the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). 5-HT7 receptor mainly couples to Gs protein, which positively stimulates adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. 5-HT7 receptor is expressed in various human tissues, mainly in the brain, the lower gastrointestinal tract and in vital blood vessels including the coronary artery. 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: 320452 [Multi-domain]  Cd Length: 260  Bit Score: 48.42  E-value: 2.54e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  34 VSLLYSGLAIGGTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMPQEAV---LGLLPSGSaeppgdwdgggg 110
Cdd:cd15329   3 IGIVLLIIILGTVVGNALVIIAVCLVKKLRTPSNYLIVSLAVSDLLVALLVMPLAIIyelSGYWPFGE------------ 70
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 11967953 111 SYRLLRGGLLGLGLTVSLLSHCLVALNRYLLITRaPATYQVLYQRRHTVGMLALSW 166
Cdd:cd15329  71 ILCDVWISFDVLLCTASILNLCAISVDRYLVITR-PLTYAVKRTPKRMALMIAIVW 125
7tmA_Melanopsin-like cd15083
vertebrate melanopsins and related opsins, member of the class A family of seven-transmembrane ...
45-166 2.65e-06

vertebrate melanopsins and related opsins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group represent the Gq-coupled rhodopsin subfamily consists of melanopsins, insect photoreceptors R1-R6, invertebrate Gq opsins as well as their closely related opsins. Melanopsins (also called Opsin-4) are the primary photoreceptor molecules for non-visual functions such as the photo-entrainment of the circadian rhythm and pupillary constriction in mammals. Mammalian melanopsins are expressed only in the inner retina, whereas non-mammalian vertebrate melanopsins are localized in various extra-retinal tissues such as iris, brain, pineal gland, and skin. The outer photoreceptors (R1-R6) are the insect Drosophila equivalent to the vertebrate rods and are responsible for image formation and motion detection. The invertebrate G(q) opsins includes the arthropod and mollusk visual opsins as well as invertebrate melanopsins, which are also found in vertebrates. Arthropods possess color vision by the use of multiple opsins sensitive to different light wavelengths. Members of this subfamily belong to the class A of the G protein-coupled receptors and have seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.


Pssm-ID: 320211 [Multi-domain]  Cd Length: 291  Bit Score: 48.48  E-value: 2.65e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  45 GTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMPQEAVLGLLPSGSaeppgdwdgGGGSYRLLRGGLLGLGL 124
Cdd:cd15083  14 GVVGNGLVIYAFCRFKSLRTPANYLIINLAISDFLMCILNCPLMVISSFSGRWI---------FGKTGCDMYGFSGGLFG 84
                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 11967953 125 TVSLLSHCLVALNRYLLITRaPATYQVLYQRRHTVGMLALSW 166
Cdd:cd15083  85 IMSINTLAAIAVDRYLVITR-PMKASVRISHRRALIVIAVVW 125
7tmA_5-HT1_5_7 cd15064
serotonin receptor subtypes 1, 5 and 7, member of the class A family of seven-transmembrane G ...
32-166 3.00e-06

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: 48.09  E-value: 3.00e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  32 IPVSLLYSGLAIGGTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMPQEAVLGLlpSGSAEPPGDWDGGGGS 111
Cdd:cd15064   1 VLISVLLSLIILATILGNALVIAAILLTRKLHTPANYLIASLAVADLLVAVLVMPLSAVYEL--TGRWILGQVLCDIWIS 78
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 11967953 112 yrllrggLLGLGLTVSLLSHCLVALNRYLLITRaPATYQVLYQRRHTVGMLALSW 166
Cdd:cd15064  79 -------LDVTCCTASILHLCVIALDRYWAITD-AVEYAHKRTPKRAAVMIALVW 125
7tmA_Peropsin cd15073
retinal pigment epithelium-derived rhodopsin homolog, member of the class A family of ...
37-93 8.83e-05

retinal pigment epithelium-derived rhodopsin homolog, member of the class A family of seven-transmembrane G protein-coupled receptors; Peropsin, also known as a retinal pigment epithelium-derived rhodopsin homolog (RRH), is a visual pigment-like protein found exclusively in the apical microvilli of the retinal pigment epithelium. Peropsin belongs to the type 2 opsin family of the class A G-protein coupled receptors. Peropsin presumably plays a physiological role in the retinal pigment epithelium either by detecting light directly or monitoring the levels of retinoids, the primary light absorber in visual perception, or other pigment-related compounds in the eye.


Pssm-ID: 320201 [Multi-domain]  Cd Length: 280  Bit Score: 43.96  E-value: 8.83e-05
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 11967953  37 LYSGLA-IGGTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMPQEAVLGL 93
Cdd:cd15073   5 AYLIVAgIISTISNGIVLVTFVKFRELRTPTNALIINLAVTDLGVSIIGYPFSAASDL 62
7tmA_GPRnna14-like cd15001
GPRnna14 and related proteins, member of the class A family of seven-transmembrane G ...
33-86 1.03e-04

GPRnna14 and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes the orphan G-protein coupled receptor GPRnna14 found in body louse (Pediculus humanus humanus) as well as its closely related proteins of unknown function. These receptors are members of the class A rhodopsin-like G-protein coupled receptors. As an obligatory parasite of humans, the body louse is an important vector for human diseases, including epidemic typhus, relapsing fever, and trench fever. GPRnna14 shares significant sequence similarity with the members of the neurotensin receptor family. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.


Pssm-ID: 320132 [Multi-domain]  Cd Length: 266  Bit Score: 43.42  E-value: 1.03e-04
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 11967953  33 PVSLLYSGLAIGGTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMP 86
Cdd:cd15001   1 PVIIVYVITFVLGLIGNSLVIFVVARFRRMRSVTNVFLASLATADLLLLVFCVP 54
7tmA_Beta_AR cd15058
beta adrenergic receptors (adrenoceptors), member of the class A family of seven-transmembrane ...
33-156 1.04e-04

beta adrenergic receptors (adrenoceptors), member of the class A family of seven-transmembrane G protein-coupled receptors; The beta adrenergic receptor (beta adrenoceptor), also known as beta AR, is activated by hormone adrenaline (epinephrine) and plays important roles in regulating cardiac function and heart rate, as well as pulmonary physiology. The human heart contains three subtypes of the beta AR: beta-1 AR, beta-2 AR, and beta-3 AR. Beta-1 AR and beta-2 AR, which expressed at about a ratio of 70:30, are the major subtypes involved in modulating cardiac contractility and heart rate by positively stimulating the G(s) protein-adenylate cyclase-cAMP-PKA signaling pathway. In contrast, beta-3 AR produces negative inotropic effects by activating inhibitory G(i) proteins. The aberrant expression of beta-ARs can lead to cardiac dysfunction such as arrhythmias or heart failure. 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: 320186 [Multi-domain]  Cd Length: 305  Bit Score: 43.59  E-value: 1.04e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  33 PVSLLYSGLAIGGTLA-NGMVIYLVSSFRKLQTTSNAFIVNGCAADLsvcalwmpqeaVLGLL--PSGSAEPPGDWDGGG 109
Cdd:cd15058   1 PGLLLLLALIILAIVVgNLLVIIAIARTSRLQTMTNIFITSLACADL-----------VMGLLvvPLGATIVVTGKWQLG 69
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 11967953 110 GSYRLLRGGLLGLGLTVSLLSHCLVALNRYLLITRaPATYQVLYQRR 156
Cdd:cd15058  70 NFWCELWTSVDVLCVTASIETLCVIAVDRYIAITR-PLRYQVLLTKR 115
7tmA_tyramine_R-like cd15061
tyramine receptors and similar proteins, member of the class A family of seven-transmembrane G ...
40-166 1.75e-04

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: 42.73  E-value: 1.75e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  40 GLAIGGtlaNGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMPQEAVLGLLpsGSAEPPGDWDGGGGSyrllrggL 119
Cdd:cd15061  11 IFTIFG---NLLVILAVATTRRLRTITNCYIVSLATADLLVGVLVLPLAIIRQLL--GYWPLGSHLCDFWIS-------L 78
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 11967953 120 LGLGLTVSLLSHCLVALNRYLLITRaPATYQVLYQRRHTVGMLALSW 166
Cdd:cd15061  79 DVLLCTASILNLCCISLDRYFAITY-PLKYRTKRSRRLAITMILAVW 124
7tmA_Histamine_H3R_H4R cd15048
histamine receptor subtypes H3R and H4R, member of the class A family of seven-transmembrane G ...
32-166 2.65e-04

histamine receptor subtypes H3R and H4R, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes histamine subtypes H3R and H4R, members of the histamine receptor family, which belong to the class A of GPCRs. Histamine plays a key role as chemical mediator and neurotransmitter in various physiological and pathophysiological processes in the central and peripheral nervous system. Histamine exerts its functions by binding to four different G protein-coupled receptors (H1-H4). The H3 and H4 receptors couple to the G(i)-proteins, which leading to the inhibition of cAMP formation. The H3R receptor functions as a presynaptic autoreceptors controlling histamine release and synthesis. The H4R plays an important role in histamine-mediated chemotaxis in mast cells and eosinophils. 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: 320176 [Multi-domain]  Cd Length: 296  Bit Score: 42.29  E-value: 2.65e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  32 IPVSLLYSGLAIGGTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMPQEAVLGLLPSGSAEPPGDWDGGGGS 111
Cdd:cd15048   1 IVLAVLISVLILVTVIGNLLVILAFIKDKKLRTVSNFFLLNLAVADFLVGLVSMPFYIPYTLTGKWPFGKVFCKAWLVVD 80
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 11967953 112 YRLLrggllglglTVSLLSHCLVALNRYLLITRAPaTYQVLYQRRHTVGMLALSW 166
Cdd:cd15048  81 YTLC---------TASALTIVLISLDRYLSVTKAV-KYRAKQTKRRTVLLMALVW 125
7tmA_NPY2R cd15399
neuropeptide Y receptor type 2, member of the class A family of seven-transmembrane G ...
36-94 2.78e-04

neuropeptide Y receptor type 2, 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 G(i) or G(o) 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. When NPY signals through NPY2R in concert with NPY5R, it induces angiogenesis and consequently plays an important role in revascularization and wound healing. On the other hand, when NPY acts through NPY1R and NPYR5, it acts as a vascular mitogen, leading to restenosis and atherosclerosis.


Pssm-ID: 320521 [Multi-domain]  Cd Length: 285  Bit Score: 42.50  E-value: 2.78e-04
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 11967953  36 LLYSGLAIGGTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMPQEAVLGLL 94
Cdd:cd15399   5 LAYCSIILLGVVGNSLVIYVVIKFKNMRTVTNFFIANLAVADLMVNTLCLPFTLVYTLL 63
7tmA_D2-like_dopamine_R cd15053
D2-like dopamine receptors, member of the class A family of seven-transmembrane G ...
36-86 3.15e-04

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


Pssm-ID: 320181 [Multi-domain]  Cd Length: 263  Bit Score: 41.95  E-value: 3.15e-04
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 11967953  36 LLYSGLAIGGtlaNGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMP 86
Cdd:cd15053   8 LLLPLLTVFG---NVLVIMSVFRERSLQTATNYFIVSLAVADLLVAILVMP 55
7tmA_5-HT6 cd15054
serotonin receptor subtype 6, member of the class A family of seven-transmembrane G ...
46-143 5.28e-04

serotonin receptor subtype 6, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT6 receptors are a subfamily of serotonin receptors that bind the neurotransmitter serotonin (5HT; 5-hydroxytryptamine) in the mammalian central nervous system (CNS). 5-HT6 receptors are selectively linked to G proteins of the G(s) family, which positively stimulate adenylate cyclase, causing cAMP formation and activation of protein kinase A. The 5-HT6 receptors mediates excitatory neurotransmission and are involved in learning and memory; thus they are promising targets for the treatment of cognitive impairment. 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: 320182 [Multi-domain]  Cd Length: 267  Bit Score: 41.33  E-value: 5.28e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  46 TLANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMPQEAVLGLLpsgsaeppgDWDGGGGSYRLLRGGLLGLGLT 125
Cdd:cd15054  15 VAGNSLLILLIFTQRSLRNTSNYFLVSLFMSDLMVGLVVMPPAMLNALY---------GRWVLARDFCPIWYAFDVMCCS 85
                        90
                ....*....|....*...
gi 11967953 126 VSLLSHCLVALNRYLLIT 143
Cdd:cd15054  86 ASILNLCVISLDRYLLII 103
7tmA_Melanopsin cd15336
vertebrate melanopsins (Opsin-4), member of the class A family of seven-transmembrane G ...
41-166 5.89e-04

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


Pssm-ID: 320458 [Multi-domain]  Cd Length: 290  Bit Score: 41.24  E-value: 5.89e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  41 LAIG--GTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMP--------QEAVLGLLPSgsaeppgdwdgggg 110
Cdd:cd15336   8 LIIGitGMLGNALVIYAFCRSKKLRTPANYFIINLAVSDFLMSLTQSPiffvnslhKRWIFGEKGC-------------- 73
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 11967953 111 syrLLRGGLLGLGLTVSLLSHCLVALNRYLLITRAPATYQVLYQRRhTVGMLALSW 166
Cdd:cd15336  74 ---ELYAFCGALFGITSMITLLAISLDRYLVITKPLASIRWVSKKR-AMIIILLVW 125
7tmA_Opsin_Gq_invertebrates cd15337
invertebrate Gq opsins, member of the class A family of seven-transmembrane G protein-coupled ...
43-82 7.55e-04

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


Pssm-ID: 320459 [Multi-domain]  Cd Length: 292  Bit Score: 41.15  E-value: 7.55e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 11967953  43 IGGTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCA 82
Cdd:cd15337  12 ILGVIGNLLVIYLFSKTKSLRTPSNMFIINLAISDFGFSA 51
7tmA_leucokinin-like cd15393
leucokinin-like peptide receptor from tick and related proteins, member of the class A family ...
35-78 8.61e-04

leucokinin-like peptide receptor from tick and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subgroup includes a leucokinin-like peptide receptor from the Southern cattle tick, Boophilus microplus, a pest of cattle world-wide. Leucokinins are invertebrate neuropeptides that exhibit myotropic and diuretic activity. This receptor is the first neuropeptide receptor known from the Acari and the second known in the subfamily of leucokinin-like peptide G-protein-coupled receptors. The other known leucokinin-like peptide receptor is a lymnokinin receptor from the mollusc Lymnaea stagnalis.


Pssm-ID: 320515 [Multi-domain]  Cd Length: 288  Bit Score: 40.85  E-value: 8.61e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 11967953  35 SLLYSGLAIGGTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADL 78
Cdd:cd15393   4 SILYGIISLVAVVGNFLVIWVVAKNRRMRTVTNIFIANLAVADI 47
7tmA_Dop1R2-like cd15067
dopamine 1-like receptor 2 from Drosophila melanogaster and similar proteins, member of the ...
37-166 9.09e-04

dopamine 1-like receptor 2 from Drosophila melanogaster and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; G protein-coupled dopamine 1-like receptor 2 is expressed in Drosophila heads and it shows significant sequence similarity with vertebrate and invertebrate dopamine receptors. Although the Drosophila Dop1R2 receptor does not cluster into the D1-like structural group, it does show pharmacological properties similar to D1-like receptors. As shown in vertebrate D1-like receptors, agonist stimulation of Dop1R2 activates adenylyl cyclase to increase cAMP levels and also generates a calcium signal through stimulation of phospholipase C.


Pssm-ID: 320195 [Multi-domain]  Cd Length: 262  Bit Score: 40.42  E-value: 9.09e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  37 LYSGLAIGGtlaNGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMPQEAVLgllpsgsaEPPGDWDGGGGSYRLLR 116
Cdd:cd15067   8 LFCLVTVAG---NLLVILAVLRERYLRTVTNYFIVSLAVADLLVGSIVMPFSILH--------EMTGGYWLFGRDWCDVW 76
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 11967953 117 GGLLGLGLTVSLLSHCLVALNRYLLITRaPATYQVLYQRRHTVGMLALSW 166
Cdd:cd15067  77 HSFDVLASTASILNLCVISLDRYWAITD-PISYPSRMTKRRALIMIALVW 125
7tmA_Histamine_H2R cd15051
histamine subtype H2 receptor, member of the class A family of seven-transmembrane G ...
47-166 1.27e-03

histamine subtype H2 receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes histamine receptor subtype H2R, a member of histamine receptor family, which belongs to the class A of GPCRs. Histamine plays a key role as chemical mediator and neurotransmitter in various physiological and pathophysiological processes in the central and peripheral nervous system. Histamine exerts its functions by binding to four different G protein-coupled receptors (H1-H4). The H2R subtype selectively interacts with the G(s)-type G protein that activates adenylate cyclase, leading to increased cAMP production and activation of Protein Kinase A. H2R is found in various tissues such as the brain, stomach, and heart. Its most prominent role is in histamine-induced gastric acid secretion. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.


Pssm-ID: 320179 [Multi-domain]  Cd Length: 287  Bit Score: 40.39  E-value: 1.27e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  47 LANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMPQEAVLGLLPSGSaeppgdwdgGGGSYRLLRGGLLGLGLTV 126
Cdd:cd15051  16 IGNVLVCLAVAVNRRLRNLTNYFIVSLAVTDLLLGLLVLPFSAIYELRGEWP---------LGPVFCNIYISLDVMLCTA 86
                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 11967953 127 SLLSHCLVALNRYLLITrAPATYQVLYQRRHTVGMLALSW 166
Cdd:cd15051  87 SILNLFAISLDRYLAIT-APLRYPSRVTPRRVAIALAAIW 125
7tmA_Beta1_AR cd15958
beta-1 adrenergic receptors (adrenoceptors), member of the class A family of ...
34-166 1.91e-03

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


Pssm-ID: 320624 [Multi-domain]  Cd Length: 298  Bit Score: 39.88  E-value: 1.91e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  34 VSLLYSGLAIGGTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMPQEAVL---GLLPSGSAeppgdwdgggg 110
Cdd:cd15958   3 MSLLMALIVLLIVAGNVLVIVAIGRTQRLQTLTNLFITSLACADLVMGLLVVPFGATLvvrGRWLYGSF----------- 71
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 11967953 111 sYRLLRGGLLGLGLTVSLLSHCLVALNRYLLITrAPATYQVLYQRRHTVGMLALSW 166
Cdd:cd15958  72 -FCELWTSVDVLCVTASIETLCVIAIDRYLAIT-SPFRYQSLLTRARAKGIVCTVW 125
7tmA_alpha1D_AR cd15327
alpha-1 adrenergic receptors subtype D, member of the class A family of seven-transmembrane G ...
47-166 2.07e-03

alpha-1 adrenergic receptors subtype D, member of the class A family of seven-transmembrane G protein-coupled receptors; The alpha-1 adrenergic receptors (or adrenoceptors) are a subfamily of the class A rhodopsin-like GPCRs that share a common architecture of seven transmembrane helices. This subfamily consists of three highly homologous receptor subtypes that primarily mediate smooth muscle contraction: alpha-1A, alpha-1B, and alpha-1D. Activation of alpha-1 receptors by catecholamines such as norepinephrine and epinephrine couples to the G(q) protein, which then activates the phospholipase C pathway, leading to an increase in IP3 and calcium. Consequently, the elevation of intracellular calcium concentration leads to vasoconstriction in smooth muscle of blood vessels. In addition, activation of alpha-1 receptors by phenylpropanolamine (PPA) produces anorexia and may induce appetite suppression in rats.


Pssm-ID: 320450 [Multi-domain]  Cd Length: 261  Bit Score: 39.51  E-value: 2.07e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  47 LANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMPQEA---VLGLLPSGSAeppgdwdggggsYRLLRGGLLGLG 123
Cdd:cd15327  16 VGNILVILSVACNRHLQTVTNYFIVNLAIADLLLSTTVLPFSAtleVLGFWAFGRV------------FCDIWAAVDVLC 83
                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 11967953 124 LTVSLLSHCLVALNRYLLItRAPATYQVLYQRRHTVGMLALSW 166
Cdd:cd15327  84 CTASILSLCVISVDRYVGV-KHSLKYPTIMTERKAGVILVLLW 125
7tmA_Histamine_H1R cd15050
histamine subtype H1 receptor, member of the class A family of seven-transmembrane G ...
32-86 2.08e-03

histamine subtype H1 receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes histamine receptor subtype H1R, a member of histamine receptor family, which belongs to the class A of GPCRs. Histamine plays a key role as chemical mediator and neurotransmitter in various physiological and pathophysiological processes in the central and peripheral nervous system. Histamine exerts its functions by binding to four different G protein-coupled receptors (H1-H4). H1R selectively interacts with the G(q)-type G protein that activates phospholipase C and the phosphatidylinositol pathway. Antihistamines, a widely used anti-allergy medication, act on the H1 subtype and produce drowsiness as a side effect. 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: 320178 [Multi-domain]  Cd Length: 263  Bit Score: 39.33  E-value: 2.08e-03
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 11967953  32 IPVSLLYSGLAIGGTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMP 86
Cdd:cd15050   1 APLGIALSTISLITVILNLLVLYAVRTERKLHTVGNLYIVSLSVADLIVGAVVMP 55
7tmA_D3_dopamine_R cd15310
D3 subtype of the D2-like family of dopamine receptors, member of the class A family of ...
35-166 2.16e-03

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


Pssm-ID: 320436 [Multi-domain]  Cd Length: 259  Bit Score: 39.57  E-value: 2.16e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  35 SLLYSGLAIGGTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMPQEAVLgllpsgsaEPPGDWDGGGGSYRL 114
Cdd:cd15310   4 ALSYCALILAIVFGNVLVCMAVLRERALQTTTNYLVVSLAVADLLVATLVMPWVVYL--------EVTGGVWNFSRICCD 75
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 11967953 115 LRGGLLGLGLTVSLLSHCLVALNRYLLITRaPATYQVLY---QRRHTVGMLALSW 166
Cdd:cd15310  76 VFVTLDVMMCTASILNLCAISIDRYTAVVM-PVHYQHGTgqsSCRRVSLMITAVW 129
7tmA_photoreceptors_insect cd15079
insect photoreceptors R1-R6 and similar proteins, member of the class A family of ...
36-85 2.73e-03

insect photoreceptors R1-R6 and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes the insect photoreceptors and their closely related proteins. The Drosophila eye is composed of about 800 unit eyes called ommatidia, each of which contains eight photoreceptor cells (R1-R8). The six outer photoreceptors (R1-R6) function like the vertebrate rods and are responsible for motion detection in dim light and image formation. The R1-R6 photoreceptors express a blue-absorbing pigment, Rhodopsin 1(Rh1). The inner photoreceptors (R7 and R8) are considered the equivalent of the color-sensitive vertebrate cone cells, which express a range of different pigments. The R7 photoreceptors express one of two different UV absorbing pigments, either Rh3 or Rh4. Likewise, the R8 photoreceptors express either the blue absorbing pigment Rh5 or green absorbing pigment Rh6. These photoreceptors belong the class A of the G protein-coupled receptors and possess seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.


Pssm-ID: 320207 [Multi-domain]  Cd Length: 292  Bit Score: 39.10  E-value: 2.73e-03
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 11967953  36 LLYSGLAIGGTLANGMVIYLVSSFRKLQTTSNAFIVNgcaadLSVCALWM 85
Cdd:cd15079   5 FIYIFLGIVSLLGNGLVIYIFSTTKSLRTPSNMLVVN-----LAISDFLM 49
7tmA_KiSS1R cd15095
KiSS1-derived peptide (kisspeptin) receptor, member of the class A family of ...
34-96 2.97e-03

KiSS1-derived peptide (kisspeptin) receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; The G protein-coupled KiSS1-derived peptide receptor (GPR54 or kisspeptin receptor) binds the peptide hormone kisspeptin (previously known as metastin), which encoded by the metastasis suppressor gene (KISS1) expressed in various endocrine and reproductive tissues. The KiSS1 receptor is coupled to G proteins of the G(q/11) family, which lead to activation of phospholipase C and increase of intracellular calcium. This signaling cascade plays an important role in reproduction by regulating the secretion of gonadotropin-releasing hormone.


Pssm-ID: 320223 [Multi-domain]  Cd Length: 288  Bit Score: 39.19  E-value: 2.97e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 11967953  34 VSLLYSGLAIGGTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMPQEAVLGLLPS 96
Cdd:cd15095   3 VPLIFAIIFLVGLAGNSLVIYVVSRHREMRTVTNYYIVNLAVTDLAFLVCCVPFTAALYATPS 65
7tmA_ETH-R cd14997
ecdysis-triggering hormone receptors, member of the class A family of seven-transmembrane G ...
34-86 3.01e-03

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: 39.20  E-value: 3.01e-03
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 11967953  34 VSLLYSGLAIGGTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMP 86
Cdd:cd14997   3 VSVVYGVIFVVGVLGNVLVGIVVWKNKDMRTPTNIFLVNLSVADLLVLLVCMP 55
7tmA_AstC_insect cd15094
somatostatin-like receptor for allatostatin C, member of the class A family of ...
36-78 3.85e-03

somatostatin-like receptor for allatostatin C, member of the class A family of seven-transmembrane G protein-coupled receptors; G protein-coupled somatostatin receptors (SSTRs) are composed of five distinct subtypes (SSTR1-5) that display strong sequence similarity with opioid receptors. All five receptor subtypes bind the natural 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. In Drosophila melanogaster and other insects, a 15-amino-acid peptide named allatostatin C(AstC) binds the somatostatin-like receptors. Two AstC receptors have been identified in Drosophila with strong sequence homology to human somatostatin and opioid receptors.


Pssm-ID: 320222 [Multi-domain]  Cd Length: 282  Bit Score: 38.61  E-value: 3.85e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 11967953  36 LLYSGLAIGGTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADL 78
Cdd:cd15094   5 VLYGLICIVGLVGNGLVIYVVLRYAKMKTVTNLYILNLAVADE 47
7tmA_D1A_dopamine_R cd15320
D1A (or D1) subtype dopamine receptor, member of the class A family of seven-transmembrane G ...
31-166 3.95e-03

D1A (or D1) subtype dopamine receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; Dopamine receptors are members of the class A G protein-coupled receptors that are involved in many neurological processes in the central nervous system (CNS). The neurotransmitter dopamine is the primary endogenous agonist for dopamine receptors. Dopamine receptors consist of at least five subtypes: D1, D2, D3, D4, and D5. The D1 and D5 subtypes are members of the D1-like family of dopamine receptors, whereas the D2, D3 and D4 subtypes are members of the D2-like family. The D1-like family receptors are coupled to G proteins of the G(s) family, which activate adenylate cyclase, causing cAMP formation and activation of protein kinase A. Dopamine receptors are major therapeutic targets for neurological and psychiatric disorders such as drug abuse, depression, schizophrenia, or Parkinson's disease.


Pssm-ID: 320443 [Multi-domain]  Cd Length: 319  Bit Score: 38.83  E-value: 3.95e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  31 RIPVSLLYSGLAIGGTLANGMVIYLVSSFRKLQT-TSNAFIVNGCAADLSVCALWMPQEAV---LGLLPSGsaeppgdwd 106
Cdd:cd15320   1 RVLTGCFLSVLILSTLLGNTLVCAAVIRFRHLRSkVTNFFVISLAVSDLLVAVLVMPWKAVaeiAGFWPFG--------- 71
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953 107 ggggSYRLLRGGLLGLGLTVSLLSHCLVALNRYLLITrAPATYQVLYQRRHTVGMLALSW 166
Cdd:cd15320  72 ----SFCNIWVAFDIMCSTASILNLCVISVDRYWAIS-SPFRYERKMTPKVAFIMISVAW 126
7tmA_Octopamine_R cd15063
octopamine receptors in invertebrates, member of the class A family of seven-transmembrane G ...
47-166 4.00e-03

octopamine receptors in invertebrates, member of the class A family of seven-transmembrane G protein-coupled receptors; G-protein coupled receptor for octopamine (OA), which functions as a neurotransmitter, neurohormone, and neuromodulator in invertebrate nervous system. Octopamine (also known as beta, 4-dihydroxyphenethylamine) is an endogenous trace amine that is highly similar to norepinephrine, but lacks a hydroxyl group, and has effects on the adrenergic and dopaminergic nervous systems. Based on the pharmacological and signaling profiles, the octopamine receptors can be classified into at least two groups: OA1 receptors elevate intracellular calcium levels in muscle, whereas OA2 receptors activate adenylate cyclase and increase cAMP production.


Pssm-ID: 320191 [Multi-domain]  Cd Length: 266  Bit Score: 38.63  E-value: 4.00e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  47 LANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMPQEAVLGLLPsgsaeppgdWDGGGGSYRLLRGGLLGLGLTV 126
Cdd:cd15063  16 LGNLLVIAAVLCSRKLRTVTNLFIVSLACADLLVGTLVLPFSAVNEVLD---------VWIFGHTWCQIWLAVDVWMCTA 86
                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 11967953 127 SLLSHCLVALNRYLLITRaPATYQVLYQRRHTVGMLALSW 166
Cdd:cd15063  87 SILNLCAISLDRYLAITR-PIRYPSLMSTKRAKCLIAGVW 125
7tmA_5-HT1B_1D cd15333
serotonin receptor subtypes 1B and 1D, member of the class A family of seven-transmembrane G ...
29-166 4.20e-03

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


Pssm-ID: 320455 [Multi-domain]  Cd Length: 265  Bit Score: 38.62  E-value: 4.20e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  29 GRRIPVSLLYSGLAIGGTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMPQEAVLGLlpSGSAEPPGDWDGG 108
Cdd:cd15333   2 GLKISLAVLLALITLATTLSNAFVIATIYLTRKLHTPANYLIASLAVTDLLVSILVMPISIVYTV--TGTWTLGQVVCDI 79
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 11967953 109 GGSyrllrggLLGLGLTVSLLSHCLVALNRYLLITRApATYQVLYQRRHTVGMLALSW 166
Cdd:cd15333  80 WLS-------SDITCCTASILHLCVIALDRYWAITDA-VEYSKKRTPKRAAVMIALVW 129
7tmA_CCKR-like cd14993
cholecystokinin receptors and related proteins, member of the class A family of ...
35-86 4.85e-03

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: 38.35  E-value: 4.85e-03
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 11967953  35 SLLYSGLAIGGTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMP 86
Cdd:cd14993   4 IVLYVVVFLLALVGNSLVIAVVLRNKHMRTVTNYFLVNLAVADLLVSLFCMP 55
7tmA_5-HT4 cd15056
serotonin receptor subtype 4, member of the class A family of seven-transmembrane G ...
47-166 4.94e-03

serotonin receptor subtype 4, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT4 subtype is a member of the serotonin receptor family that belongs to the class A G protein-coupled receptors, and binds the neurotransmitter serotonin (5HT; 5-hydroxytryptamine) in the mammalian central nervous system (CNS). 5-HT4 receptors are selectively linked to G proteins of the G(s) family, which positively stimulate adenylate cyclase, causing cAMP formation and activation of protein kinase A. 5-HT4 receptor-specific agonists have been shown to enhance learning and memory in animal studies. Moreover, hippocampal 5-HT4 receptor expression has been reported to be inversely correlated with memory performance in humans. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.


Pssm-ID: 320184 [Multi-domain]  Cd Length: 294  Bit Score: 38.62  E-value: 4.94e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  47 LANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMP---QEAVLGLLPSGSaeppgdwdggggSYRLLRGGLLGLG 123
Cdd:cd15056  16 LGNLLVIVAVCTDRQLRKKTNYFVVSLAVADLLVAVLVMPfgaIELVNNRWIYGE------------TFCLVRTSLDVLL 83
                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 11967953 124 LTVSLLSHCLVALNRYLLITRAPATYQVLYQRRHTvgMLALSW 166
Cdd:cd15056  84 TTASIMHLCCIALDRYYAICCQPLVYKMTPLRVAV--MLGGCW 124
7tmA_alpha1_AR cd15062
alpha-1 adrenergic receptors, member of the class A family of seven-transmembrane G ...
32-164 5.08e-03

alpha-1 adrenergic receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; The alpha-1 adrenergic receptors (or adrenoceptors) are a subfamily of the class A rhodopsin-like GPCRs that share a common architecture of seven transmembrane helices. This subfamily consists of three highly homologous receptor subtypes that primarily mediate smooth muscle contraction: alpha-1A, alpha-1B, and alpha-1D. Activation of alpha-1 receptors by catecholamines such as norepinephrine and epinephrine couples to the G(q) protein, which then activates the phospholipase C pathway, leading to an increase in IP3 and calcium. Consequently, the elevation of intracellular calcium concentration leads to vasoconstriction in smooth muscle of blood vessels. In addition, activation of alpha-1 receptors by phenylpropanolamine (PPA) produces anorexia and may induce appetite suppression in rats.


Pssm-ID: 320190 [Multi-domain]  Cd Length: 261  Bit Score: 38.24  E-value: 5.08e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  32 IPVSLLYSGLAIGGTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMPQEA---VLGLLPSGSAeppgdwdgg 108
Cdd:cd15062   1 IVVGVALGAFILFAIGGNLLVILSVACNRHLRTPTHYFIVNLAVADLLLSFTVLPFSAtleVLGYWAFGRI--------- 71
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 11967953 109 ggsYRLLRGGLLGLGLTVSLLSHCLVALNRYLLITRAPATYQVLYQRRHTVGMLAL 164
Cdd:cd15062  72 ---FCDVWAAVDVLCCTASIMSLCVISVDRYIGVRYPLNYPTIVTARRATVALLIV 124
7tmA_alpha1A_AR cd15325
alpha-1 adrenergic receptors subtype A, member of the class A family of seven-transmembrane G ...
32-166 5.79e-03

alpha-1 adrenergic receptors subtype A, member of the class A family of seven-transmembrane G protein-coupled receptors; The alpha-1 adrenergic receptors (or adrenoceptors) are a subfamily of the class A rhodopsin-like GPCRs that share a common architecture of seven transmembrane helices. This subfamily consists of three highly homologous receptor subtypes that primarily mediate smooth muscle contraction: alpha-1A, alpha-1B, and alpha-1D. Activation of alpha-1 receptors by catecholamines such as norepinephrine and epinephrine couples to the G(q) protein, which then activates the phospholipase C pathway, leading to an increase in IP3 and calcium. Consequently, the elevation of intracellular calcium concentration leads to vasoconstriction in smooth muscle of blood vessels. In addition, activation of alpha-1 receptors by phenylpropanolamine (PPA) produces anorexia and may induce appetite suppression in rats.


Pssm-ID: 320448 [Multi-domain]  Cd Length: 261  Bit Score: 37.95  E-value: 5.79e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  32 IPVSLLYSGLAIGGTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADLSVCALWMPQEAVLGLLpsgsaeppgDWDGGGGS 111
Cdd:cd15325   1 IVLGVILGGFILFGVLGNILVILSVACHRHLQTVTHYFIVNLAVADLLLTSTVLPFSAIFEIL---------GYWAFGRV 71
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 11967953 112 YRLLRGGLLGLGLTVSLLSHCLVALNRYLLITRaPATYQVLYQRRHTVGMLALSW 166
Cdd:cd15325  72 FCNIWAAVDVLCCTASIMSLCIISIDRYIGVSY-PLRYPSIMTERRGLLALLCVW 125
7tmA_Beta2_AR cd15957
beta-2 adrenergic receptors (adrenoceptors), member of the class A family of ...
49-166 6.16e-03

beta-2 adrenergic receptors (adrenoceptors), member of the class A family of seven-transmembrane G protein-coupled receptors; Beta-2 AR is activated by adrenaline that plays important roles in cardiac function and pulmonary physiology. While beta-1 AR and beta-2 AR are the major subtypes involved in modulating cardiac contractility and heart rate by positively stimulating the G(s) protein-adenylate cyclase-cAMP-PKA signaling pathway, beta-2 AR can couple to both G(s) and G(i) proteins in the heart. Moreover, beta-2 AR activation leads to smooth muscle relaxation and bronchodilation in the lung. The beta adrenergic receptors are a subfamily of the class A rhodopsin-like G protein-coupled receptors.


Pssm-ID: 341355 [Multi-domain]  Cd Length: 301  Bit Score: 38.31  E-value: 6.16e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 11967953  49 NGMVIYLVSSFRKLQTTSNAFIVNGCAADLsvcalwmpqeaVLGLL--PSGSAEPPGDWDGGGGSYRLLRGGLLGLGLTV 126
Cdd:cd15957  18 NVLVITAIAKFERLQTVTNYFITSLACADL-----------VMGLAvvPFGAAHILLKTWTFGNFWCEFWTSIDVLCVTA 86
                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 11967953 127 SLLSHCLVALNRYLLITrAPATYQVLYQRRHTVGMLALSW 166
Cdd:cd15957  87 SIETLCVIAVDRYFAIT-SPFKYQSLLTKNKARVIILMVW 125
7tmA_NOFQ_opioid_R cd15092
nociceptin/orphanin FQ peptide receptor, member of the class A family of seven-transmembrane G ...
32-99 6.97e-03

nociceptin/orphanin FQ peptide receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; The nociceptin (NOP) receptor binds nociceptin or orphanin FQ, a 17 amino acid endogenous neuropeptide. The NOP receptor is involved in the modulation of various brain activities including instinctive and emotional behaviors. The opioid receptor family is composed of four major subtypes: mu (MOP), delta (DOP), kappa (KOP) opioid receptors, and the nociceptin/orphanin FQ peptide receptor (NOP). They are distributed widely in the central nervous system and respond to classic alkaloid opiates, such as morphine and heroin, as well as to endogenous peptide ligands, which include dynorphins, enkephalins, endorphins, endomorphins, and nociceptin. Opioid receptors are coupled to inhibitory G proteins of the G(i/o) family and involved in regulating a variety of physiological functions such as pain, addiction, mood, stress, epileptic seizure, and obesity, among many others.


Pssm-ID: 320220 [Multi-domain]  Cd Length: 279  Bit Score: 37.92  E-value: 6.97e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 11967953  32 IPVSLLYSGLAIGGTLANGMVIYLVSSFRKLQTTSNAFIVNGCAADlSVCALWMP---QEAVLGLLPSGSA 99
Cdd:cd15092   1 VTIVVVYLIVCVVGLVGNCLVMYVILRHTKMKTATNIYIFNLALAD-TLVLLTLPfqgTDIFLGFWPFGNA 70
 
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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