Conserved Protein Domain Family
7tmC_mGluR_group2

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cd15284: 7tmC_mGluR_group2 
metabotropic glutamate receptors in group 2, member of the class C family of seven-transmembrane G protein-coupled receptors
The metabotropic glutamate receptors (mGluRs) in group 2 include mGluR 2 and 3. 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
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PSSM-Id: 320411
Aligned: 9 rows
Threshold Bit Score: 475.492
Created: 7-Feb-2014
Updated: 25-Oct-2021
Structure
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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
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                                 #           ##  ##  #  
Q9QYS2       575 AWAIGPVTIACLGFMCTCIVITVFIKHNNtplVKASGRELCYILLFGVSLSYCMTFFFIakpsPVICALRRLGLGTSFAI 654 house mouse
Q14BI2       566 AWAVGPVTIACLGALATLFVLGVFVRHNAtpvVKASGRELCYILLGGVFLCYCMTFIFIakpsTAVCTLRRLGLGTAFSV 645 house mouse
Q4RXB9       539 AWAIGPVTISCLGILCTLSVVGLFFKYNEtpvVKASGRELSYILLLGVLMCYLMTFIYIakpsTAICTLRRLGLGTSFAV 618 spotted green p...
XP_425148    579 VWAIGPVTISCLGFISTLFVFGVFMKNNDtpiVKASGRELCYILLTGVLMCYSMTFIFIakpsTEVCTLRRLGLGTSFAV 658 chicken
XP_002935662 562 AWAVGPVCLSCLGLLSTLFVIGVFVQNNNtpiVKASGRELCYILLCGVLLCYAMTFIFIskpsTSVCTLRRLGLGTSFAI 641 western clawed ...
EMC83258     585 AWAIGPVTIACLGFICTFMVIAVFIKHNNtplVKASGRELCYILLFGVFLSYSMTFFFIakpsPAICTLRRLGLGSSFAV 664 domestic pigeon
Q14832       575 AWAIGPVTIACLGFMCTCMVVTVFIKHNNtplVKASGRELCYILLFGVGLSYCMTFFFIakpsPVICALRRLGLGSSFAI 654 human
AGW27134     577 AWAIGPISIACVGFICTLMVFIVFIRHNDtplVKASGRELCYILLLGVFMSYVMTFIFIakpsPIVCTLRRLGLGTSFAV 656 zebrafish
XP_002935292 421 AWAIGPVTIACLGFVCTCLVGGVFIKNNStplVKASGRELCYILLIGVFMCYCMTFFFIakpsPVICTLRRLGLGTSFVV 500 western clawed ...
Feature 1                                                                                      # 
Q9QYS2       655 CYSALLTKTNCIARIFdgvknga-qrpkfisPSSQVFICLGLILVQIVMVSVWLILETPgtrrytlpekretvilkCNVK 733 house mouse
Q14BI2       646 CYSALLTKTNRIARIFggarega-qrprfisPASQVAICLALISGQLLIVAAWLVVEAPgigketaperrevvtlrCNHR 724 house mouse
Q4RXB9       619 CYSALLTKTNRIARIFsgvkdga-qrprfisPASQVAICGALISCQLLVALIWLMVEGPgvrkevnserrnvvilkCNSR 697 spotted green p...
XP_425148    659 CYSALLTKTNRIARIFsgvkegv-qrprfisPTSQVVICMALISCQLIIVIIWLLVEAPgtgketepdkryivtlkCNNR 737 chicken
XP_002935662 642 CYSALLTKTNRIARIFsgardgv-qrprfisPASQVGICLVLISCQLLVVLIWLLFEPPgtrkdtapdkryivtlkCNSG 720 western clawed ...
EMC83258     665 CYSALLTKTNCIARIFdgvknga-qrpkfisPSSQVFICLSLILVQIVVVSVWLILEAPgtrrytlpekretvilkCNVK 743 domestic pigeon
Q14832       655 CYSALLTKTNCIARIFdgvknga-qrpkfisPSSQVFICLGLILVQIVMVSVWLILEAPgtrrytlaekretvilkCNVK 733 human
AGW27134     657 CYSALLTKTNRIARIFsgvkeggaqrprfisPSSQVFICLSLISVQLLLVSVWLLVEVPgtrrfttpekrqtvilkCNVR 736 zebrafish
XP_002935292 501 CYSALLTKTNRIARIFsgvkdga-qrpkfisPKSQVVICLSLISVQIVVVSVWLMLEFPgtrrytlpekretvilkCNVK 579 western clawed ...
Feature 1           #  ##  #                                 #  ##  #   #         ##  #  #   #   
Q9QYS2       734 DSSMLISLTYDVVLVILCTVYAFKTRKCpenFNEAKFIGFTMYTTCIIWLAFLPIFYvtssdYRVQTTTMCISVSLSGFV 813 house mouse
Q14BI2       725 DASMLGSLAYNVLLIALCTLYAFKTRKCpenFNEAKFIGFTMYTTCIIWLAFLPIFYvtssdYRVQTTTMCVSVSLSGSV 804 house mouse
Q4RXB9       698 DSSMLVSLTYNCVLIILCTVYAFKTRKCpenFNEAKFIGFTMYTTCIIWLAFQPIFYvtasdYRVQTTTMCISVSLSGSV 777 spotted green p...
XP_425148    738 DSNMLISLTYNVLLIVLCTVYAFKTRKCpenFNEAKFIGFTMYTTCIIWLAFLPIFYvtssdYRVQTTTMCISVSLSGTV 817 chicken
XP_002935662 721 DGSMLISLSYNVLLVLLCTLYAFKTRKCpenFNEAKFIGFTMYTTCIIWLAFLPIYYvtssdYRVQTTTLCVSVSLSGSV 800 western clawed ...
EMC83258     744 DSSMLISLTYDVILVVLCTVYAFKTRKCpenFNEAKFIGFTMYTTCIIWLAFLPIFYvtssdYRVQTTTMCISVSLSGFV 823 domestic pigeon
Q14832       734 DSSMLISLTYDVILVILCTVYAFKTRKCpenFNEAKFIGFTMYTTCIIWLAFLPIFYvtssdYRVQTTTMCISVSLSGFV 813 human
AGW27134     737 DSSMLMSLSYDVVLVVLCTVYAFKTRKCpenFNEAKFIGFTMYTTCIIWLAFLPIFYvtssdYRVQTTTMCISVSLSGFV 816 zebrafish
XP_002935292 580 DSSMLISLTYDVVLVILCTVYAFKTRKCpenFNEAKFIGFTMYTTCIIWLAFLPIFYvtssdYRVQTTTMCISVSLSGFV 659 western clawed ...
Feature 1                       
Q9QYS2       814 VLGCLFAPKVHIVLF 828 house mouse
Q14BI2       805 VLGCLFAPKLHIILF 819 house mouse
Q4RXB9       778 VLGCLFAPKVHIILF 792 spotted green pufferfish
XP_425148    818 VLGCLFTPKLHIILF 832 chicken
XP_002935662 801 VLGCLFTPKLHIIIF 815 western clawed frog
EMC83258     824 VLGCLFAPKVHIILF 838 domestic pigeon
Q14832       814 VLGCLFAPKVHIILF 828 human
AGW27134     817 VLGCMFAPKVHIIMF 831 zebrafish
XP_002935292 660 VLGCLFAPKVHIILF 674 western clawed frog

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