Conserved Protein Domain Family
7tmA_GPR88-like

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cd15211: 7tmA_GPR88-like 
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.
Statistics
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PSSM-Id: 320339
View PSSM: cd15211
Aligned: 4 rows
Threshold Bit Score: 292.139
Threshold Setting Gi: 229464740
Created: 16-Dec-2013
Updated: 26-Jul-2017
Structure
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Aligned Rows:
  next features
Feature 1:putative ligand binding pocket [chemical binding site]
Evidence:
  • Comment:based on the structures of some class A family members with bound ligands (peptides or chemicals), agonists, or antagonists
  • Comment:Small-molecule chemical ligands tend to bind deeper within the receptor core, compared to a peptide ligand neurotensin, which binds towards the extracelllular surface of its receptor.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                               #  ##                    
gi 229464740  33 PVSLLYSGLAIGGTLANGMVIYLVSSFRKlqttSNAFIVNGCAADLSVCALWMPQEAVLGllptgsaeppadwdgaggsY 112
gi 513198607  26 FLSLLYAVLAISGTLSNVVVIYLVFSFKKlqttSNAFIVNGCAADLSVCALWMPQEAVLGllppnss------slrsaeY 99
gi 301609251  21 LVTTVYSLFSVSGTLANVLVIYLVCSFKKlkttSNAFIVNGCVSDLLVCAFWMPQEVILLstgrv----------enhaY 90
gi 125850192  21 SLATVYSFMCVLGTILNLLVIYLVVTFKKlrtaSNAFIVNGCVADLLVCAFWMPHEAVATstgtl----------lvlgY 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1        ###### ##  #                                             # #####                
gi 229464740 113 RLLRGGLLGLGLTVSLLSHCLVALNRYLLITrapatyqalyqrRHTAGMLALSWALALGLVLLLPPWaprpg-------- 184
gi 513198607 100 RLLREGLLGLGLTVSMASHLLVAFNRYVLITklpsvyqalyqrRHTGCMIGLSWALALLLLPLLPGLwttgpapq----- 174
gi 301609251  91 RVFMEGVFFLWMTVSLLSHALIALNRFVMITklptvyhtvyqkRNTEWMIAMAWVLPLAFLLPWLFGqrpreislscpql 170
gi 125850192  91 QAFKEALLFLGITVSLLSHSLIAVNRYVLITktpavyqslyqkRNTEWMIAGSWLLSLGALFPWLTSfryptkschds-- 168
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                    #  ### ### ##                                                       
gi 229464740 185 --------aappRVHYPALLAAAALLAQTALLLHCYLGIVRRvrvsvkrvsvlnfhllhqlpgcaaaaaafpgaqhapgp 256
gi 513198607 175 ----ppprqtdgGSRYPALFLALAVLGQTALLLHCYLGIVRRvrgsakrvsvlnfhl----------------------- 227
gi 301609251 171 rlyvflgqevsvSSTYTAILSAVTVLSQTAIVLHCYFRIFRKvqislkrvsvln-------------------------- 224
gi 125850192 169 -adgsfavvsvlSSRFAAGTLAFTIIGQTLVVVYCYFKIFRRvqisvkrvsiln-------------------------- 221
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                #  ## ##  #      ## ###  #  ##          
gi 229464740 257 ggaahpaqaqplppalhprrAQRRLSGLSVLLLCCVFLLATQPLVWVSLASgfslpvPWGVQAASWLLCCALSALNPLLY 336
gi 513198607 228 -----lhqlpfpaapppprrAQRRLSSVSVLLLCCVFLLGTQPLVWVSLLGfflrpaPPALQAASWLLLCSLSALNPLLY 302
gi 301609251 225 --------fqvvhnlpcscpRKDKRLGLYVLIVCCVFALTTEPFAWTVLYGlfq-plPRTLITGSWLLFCLLFVLNPFIY 295
gi 125850192 222 --------fqivnnlpysypRKDKRLGFYVLAVCFIFILTTEPIFWVLVAGlfv-pvSVAIWTSTWIVFCTIFVSNPFLY 292
                        330
                 ....*....|.
Feature 1                   
gi 229464740 337 TWRNeEFRRSV 347
gi 513198607 303 TWRSeEFRRAA 313
gi 301609251 296 TWKNeEFRRSF 306
gi 125850192 293 TWKNeEFRKSF 303

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