Conserved Protein Domain Family
7tmC_mGluR_group3

?
cd15286: 7tmC_mGluR_group3 
metabotropic glutamate receptors in group 3, member of the class C family of seven-transmembrane G protein-coupled receptors
The metabotropic glutamate receptors (mGluRs) in group 3 include mGluRs 4, 6, 7, and 8. They are homodimeric class C G-protein coupled receptors which are activated by glutamate, the major excitatory neurotransmitter of the CNS. mGluRs are involved in regulating neuronal excitability and synaptic transmission via intracellular activation of second messenger signaling pathways. While the ionotropic glutamate receptor subtypes (AMPA, NMDA, and kainite) mediate fast excitatory postsynaptic transmission, mGluRs are known to mediate slower excitatory postsynaptic responses and to be involved in synaptic plasticity in the mammalian brain. In addition to seven-transmembrane helices, the class C GPCRs are characterized by a large N-terminal extracellular Venus flytrap-like domain, which is composed of two adjacent lobes separated by a cleft which binds an endogenous ligand. Moreover, they exist as either homo- or heterodimers, which are essential for their function. For instance, mGluRs form homodimers via interactions between the N-terminal Venus flytrap domains and the intermolecular disulphide bonds between cysteine residues located in the cysteine-rich domain (CRD). At least eight different subtypes of metabotropic receptors (mGluR1-8) have been identified and further classified into three groups based on their sequence homology, pharmacological properties, and signaling pathways. Group 1 (mGluR1 and mGluR5) receptors are predominantly located postsynaptically on neurons and are involved in long-term synaptic plasticity in the brain, including long-term potentiation (LTP) in the hippocampus and long-term depression (LTD) in the cerebellum. They are coupled to G(q/11) proteins, thereby activating phospholipase C to generate inositol-1,4,5-triphosphate (IP3) and diacyglycerol (DAG), which in turn lead to Ca2+ release and protein kinase C activation, respectively. Group 1 mGluR expression is shown to be strongly upregulated in animal models of epilepsy, brain injury, inflammatory, and neuropathic pain, as well as in patients with amyotrophic lateral sclerosis or multiple sclerosis. Group 2 (mGluR2 and mGluR3) and 3 (mGluR4, mGluR6, mGluR7, and mGluR8) receptors are predominantly localized presynaptically in the active region of neurotransmitter release. They are coupled to G(i/o) proteins, which leads to inhibition of adenylate cyclase activity and cAMP formation, and consequently to a decrease in protein kinase A (PKA) activity. Ultimately, activation of these receptors leads to inhibition of neurotransmitter release such as glutamate and GABA via inhibition of Ca2+ channels and activation of K+ channels. Furthermore, while activation of Group 1 mGluRs increases NMDA (N-methyl-D-aspartate) receptor activity and risk of neurotoxicity, Group 2 and 3 mGluRs decrease NMDA receptor activity and prevent neurotoxicity.
Statistics
?
PSSM-Id: 320413
View PSSM: cd15286
Aligned: 8 rows
Threshold Bit Score: 469.669
Threshold Setting Gi: 557317788
Created: 7-Feb-2014
Updated: 26-Jul-2017
Structure
?
Aligned Rows:
  next features
Feature 1:putative allosteric modulator binding site [chemical binding site]
Evidence:
  • Comment:based on the binding of human mGluR1 receptor to a negative allosteric modulator FITM (contacts at 4A)

Sequence Alignment
?
Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                 #           ##  ##  #  
gi 12644040  582 PWAVVPVFVAILGIIATTFVIVTFVRYNDtpiVRASGRELSYVLLTGIFLCYSITFLMIaapdTIICSFRRVFLGLGMCF 661
gi 547904    589 PWAVIPVFLAMLGIIATIFVMATFIRYNDtpiVRASGRELSYVLLTGIFLCYIITFLMIakpdVAVCSFRRVFLGLGMCI 668
gi 239938639 584 PWAAPPLLLAVLGIVATTTVVATFVRYNNtpiVRASGRELSYVLLTGIFLIYAITFLMVaepgAAVCAARRLFLGLGTTL 663
gi 545273585 585 PWAVIPVLIAILGIIATLFVVVTFIRYNDtpiVKASGRELSYVLLTGIFLCYATTFLMIstpdVGICSLRRIFLGLGMSI 664
gi 82263813  604 AWALLPVFLSVLGLVATSFVAVTFLRYRHtplVRASGRELSFLLLCGIFLCYLATFPMLaapgVLVCSLRRVLLGLGLSC 683
gi 529430328 561 PWAAVPLALATLGLMATGFILVTFIKHHEtpiVKASGRELSYVLLAGIALVYAITFIMVaepgVGVCTLRRLFLGLGMTL 640
gi 543381155 587 PCAAVPLALATLGLMATAFVLATFVRHHEtpiVKASGRELSYVLLAGIALVYAITFLMVaepgVGVCALRRLFLGAGMSL 666
gi 557317788 566 PWAAVPVALAVVGMGATLFVLVTFVRHNDtpvVRASGRELSYLLLAGILLVYLATFLLVaepqASVCAGRRLLLGQGLAV 645
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
gi 12644040  662 SYAALLTKTNRIHRIFEQGKksvtapkfispasQLVITFSLISVQLLGVFVWFVVDPphiiidygeqrtlDPEKARGVLK 741
gi 547904    669 SYAALLTKTNRIYRIFEQGKksvtaprlisptsQLAITSSLISVQLLGVFIWFGVDPpniiidydehktmNPEQARGVLK 748
gi 239938639 664 SYSALLTKTNRIYRIFEQGKrsvtpppfisptsQLVITFSLTSLQVVGMIAWLGARPphsvidyeeqrtvDPEQARGVLK 743
gi 545273585 665 SYAALLTKTNRIYRILEQGKmtvsaprfispasQLIITFSLISVQLLGVCIWFAVDPsqalidyedqrtiDPEMARGVLK 744
gi 82263813  684 SYAALLTKTNRIHRIFQQGRkavlaprcispasQLLVAFSLISVQLLGILVWFAADPphsfvdygerrtpDPEQARGVLR 763
gi 529430328 641 TYAALLTKTNRIYRIFEQGKrsvtpprfitptpQLLITFPLSGLQLVAVAAWLLVRPphalidydmgrtpDPEDARGVLR 720
gi 543381155 667 TYAALLTKTNRIYRIFEQGKrsvtpprfisptsQLVITFTLSGLQLVAAATWLLLRPphalidyemgrtpDPEAARGVLR 746
gi 557317788 646 TYAALLTKTNRIYRIFEQGKksvtpprfisprsQLVIAGGLSLVQAAGALAWVAASPphavvdfargrhgDPREARAVLR 725
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1          #    #  ##  #                                 #  ##  #   #                    
gi 12644040  742 CDISDLSLICSLGYSILLMVTCTVYAIKTRGVPEtFNEAKPIGFTMYTTCIIWLAFIPIFFGTAQsa------------- 808
gi 547904    749 CDITDLQIICSLGYSILLMVTCTVYAIKTRGVPEnFNEAKPIGFTMYTTCIVWLAFIPIFFGTAQsa------------- 815
gi 239938639 744 CDMSDLSLIGCLGYSLLLMVTCTVYAIKARGVPEtFNEAKPIGFTMYTTCIIWLAFVPIFFGTAQsa------------- 810
gi 545273585 745 CDISDLSLICLLGYSMLLMVTCTVYAIKTRGVPEtFNEAKPIGFTMYTTCIIWLAFIPIFFGTSQst------------- 811
gi 82263813  764 CDISDLALICSLGYSILLMVTCTVYAIKTRGVPEtFNEAKPIGFTMYTTCIIWLAFIPIFFGTAQsaervsgsslltvlr 843
gi 529430328 721 CDMAEGGTLACLAYALLLMLTCTVYAVKARGVPEtFNEAKPIGFAMYTTCVVWLAFGPIFFGAAQsa------------- 787
gi 543381155 747 CDMAEGATLACLAYALLLMLTCTVYAVKARGVPEtFNEAKPIGFAMYTTCVVWLAFGPIFFGAAQsa------------- 813
gi 557317788 726 CDMSDLSILGCLAYGLGLMATGTIYAVKARGVPEaFNEAKPVGFAMYTTCVVWLAFVPIFFGTAQae------------- 792
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
Feature 1                                ##  #  #   #                           
gi 12644040  809 -------------------ekMYIQTTTLTVSMSLSASVSLGMLYMPKVYIIIFHPEQNvQKR 852
gi 547904    816 -------------------ekLYIQTTTLTISMNLSASVALGMLYMPKVYIIIFHPELNvQKR 859
gi 239938639 811 -------------------ekIYIQTTTLTVSLSLSASVSLGMLYVPKTYVILFHPEQNvQKR 854
gi 545273585 812 -------------------ekMYIQTTTLTISVSLSASVSLGMLYMPKVYVVLFHPEQNvAKR 855
gi 82263813  844 tasclspgltlalansapslqLHIQTAMLTVSLSLSASVSLGMLFVPKVYIIIFHPEQNvGKP 906
gi 529430328 788 -------------------erVHMQTATLTVSMSLSASVPLGLLYAPKVYVILLHPERN-QPR 830
gi 543381155 814 -------------------erVHVQTATLTVSMSLSASVPLGLLYAPKVYVILLHPERN-QPK 856
gi 557317788 793 -------------------ekLYVQTATLTVSLSLSASVPLGLLFLPKVHVVLLRPELN-VAK 835

| Disclaimer | Privacy statement | Accessibility |
NCBI Home NCBI Search NCBI SiteMap