4OR2


Conserved Protein Domain Family
7tmC_mGluRs

?
cd15045: 7tmC_mGluRs 
Click on image for an interactive view with Cn3D
metabotropic glutamate receptors, member of the class C family of seven-transmembrane G protein-coupled receptors
The metabotropic glutamate receptors (mGluRs) 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 I 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 (Gi/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: 320173
Aligned: 23 rows
Threshold Bit Score: 317.265
Created: 10-Dec-2013
Updated: 17-Oct-2022
Structure
?
Program:
Drawing:
Aligned Rows:
  next features
Conserved site includes 21 residues -Click on image for an interactive view with Cn3D
Feature 1:allosteric modulator binding site [chemical binding site]
Evidence:
  • Structure:4OR2: Human mGluR1 receptor binds a negative allosteric modulator FITM, contacts at 4A
    View structure with Cn3D

Sequence Alignment
?
Format: Row Display: Color Bits: Type Selection:
Feature 1                                                                 #           ##  ##  #  
4OR2_A       120 IESIIAIAFSCLGILVTLFVTLIFVLYRDtpvVKSSSRELCYIILAGIFLGYVCPFTLIakptTTSCYLQRLLVGLSSAM 199 
Q9QYS2       575 AWAIGPVTIACLGFMCTCIVITVFIKHNNtplVKASGRELCYILLFGVSLSYCMTFFFIakpsPVICALRRLGLGTSFAI 654  house mouse
EKC28581     293 PYVILIFVLSSVGIVLCSIVSVVFVFKRStpiVKATGFETSLVLLVGILLSYISPFILVsepsTASCAFFRIFLGLSYTM 372  Pacific oyster
ELU18505     594 PWAISVLAMASVGILLTIVVLCIFVTYLDtpvIKASGRELSLVLMAGILLSYGTVFAVVappsVPICSISHLLLGLSYTV 673  Capitella sp. ...
EFX68215     512 PWAAGSMAFALFGILLTLAVAFIFWRHRQtpvIKASGRELSAILLLATLCSFAMTFLIAsrptGFKCGVTRFSLGLTHTV 591  common water flea
KDR13891     530 PWAIAAMAVASLGILVTVFVFIIFWTYSDtpvVKASGRELSYLLLVGILASFCVTFVIVahptSFTCGLTRFFLGFCYTL 609  Zootermopsis n...
XP_002731157 555 SWGIGVLCFATAGVIVTSLVIVVFIKNNDtpiVKASGRELTYVLLVGIFLSYVISFVVVakpsVATCAATKFGIGFCFTL 634  Saccoglossus k...
XP_003739342 595 PWAIGSISFASIGMLVVIYISLVFRRFSDtpiIKASGRELSYLLLFGIFLSFSLTFVIVakptAVTCGLTRFFLGFCYTT 674  western predat...
XP_008217254 572 PWAVSAMAVATCGILLTIFVLCVFWLYSEtpiIKASGRELSCLLLLGTLASFLMTFAIIarpnTQTCAITRFGIGLCYTL 651  jewel wasp
XP_003700472 594 PWAVVATVNVFPGIAFTSFVCSVFWKYRDtpmIKASGRELSFLLLLGTFGCFSMTFAVVakpsVHSCAVVRFGIGFCYTI 673  alfalfa leafcu...
Feature 1                                                                                        
4OR2_A       200 CYSALVTKTNRIarilagskkkic-------trkprfmsawaQVIIASILISVQLTLVVTLIIMEPpmpilsyp----si 268 
Q9QYS2       655 CYSALLTKTNCIarifdgvknga---------qrpkfispssQVFICLGLILVQIVMVSVWLILETpgtrrytlp--ekr 723  house mouse
EKC28581     373 AYSSILSKLMVYnrafdlqssiknktiqgqpllhrnictmktALVMTLTLSALHLFAIVFWIIGDTpvtvvsysitresa 452  Pacific oyster
ELU18505     674 IYASILTKTSRIarifadhrgtp---------nktrftspgsQIVIVGVLVFGECVILAIWMAASPpkvihtypt---rg 741  Capitella sp. ...
EFX68215     592 AFAAIAVKTNRVarifgtkktgsts----ltcprakyisprsQLAITGALTLIEVFVNASWLIYQPprtthifpd---ry 664  common water flea
KDR13891     610 CYAAIVTKTNRIarifsnrpisp---------hktrytspksQLVITALLTSVEVVINVSWLMYEPpsvthsfpt---re 677  Zootermopsis n...
XP_002731157 635 CYAAMLTKTNRIarifdrakssv---------kntkyisptsQLVICTCIMCVEFVVLGAWFAFQPprttyhhpv---re 702  Saccoglossus k...
XP_003739342 675 CYAAIVTKTSRIarifahgtkgr--------shkirytsprsQLLITALLVSVEVIVNVLWLMYDPpdatniypt---re 743  western predat...
XP_008217254 652 CYSALVTKTNRIhrifnnatnsp---------hkprytsprsQLIITGIITFIEVLINGAWLLKAPpsatyafpt---rd 719  jewel wasp
XP_003700472 674 CYAALATKINRIhrifndparsp---------rkrrytsprsQLAIASILSMIEVAFDASWLLKEPpavthsyps---rd 741  alfalfa leafcu...
Feature 1                #    #  ##  #                                 #  ##  #   #         ##  #
4OR2_A       269 kevyliCNTSNLGVVAPLGYNGLLIMSCTYYAFKTRNVpanFNEAKYIAFTMYTTCIIWLAFVPIYFg----SNYKIITT 344 
Q9QYS2       724 etvilkCNVKDSSMLISLTYDVVLVILCTVYAFKTRKCpenFNEAKFIGFTMYTTCIIWLAFLPIFYvtssdYRVQTTTM 803  house mouse
EKC28581     453 ignrscIDLRNFSYFVSLGWSFLLMIACLVFALKTRKLpdgMNDSHEIMYCSFTSFILWITFIPLYAfs-dnKVVKVMSL 531  Pacific oyster
ELU18505     742 qnvlacDNAEGAHSLIPLIYPFLLLLLCAVYVFKTRKTpdgFNETRLIAFTSYTTVVIWLAFTPLYAiv-tdSHVRGFIL 820  Capitella sp. ...
EFX68215     665 krvlicEGMDHYTYLVGLVYPLILIGCCTVYAFQTRKCpggFNEARYIGFTTYTTCVLWMAFIPLFLta-ptTTLRIVTL 743  common water flea
KDR13891     678 srmlicEGLDGYSYMVGLLYPFVLIGLCTAYAVKTRKCpggFNETRHIAFTNYTAIIIWLAFVPLYLas-nsNSIRVVTL 756  Zootermopsis n...
XP_002731157 703 kneltcSGATDATYLIGLMYPFFLMVFCTVYAFKTRNCpegFNEAKYIGFSMYTTCVIWLSFVPIYFvssrnVALRVTTL 782  Saccoglossus k...
XP_003739342 744 esvlicARSDDHKYLIGLVYPFILMCFCTVYAFKTRKCpdgFNEARYLTFTNYTTCVVWLAFLPLFVls-tnNAIRAVTL 822  western predat...
XP_008217254 720 trlricQGFDDRSYTIGLIYPFILIVVCTVYAVKTRKCpegFNETRYIAFTNYTTMILWLAFVPLYLas-tsNAIRVVTL 798  jewel wasp
XP_003700472 742 anvrvcKGSEDGSYVIGLLYPFVLTVASTVYAIKTRKCpegFNETRRIAFANYATIILWLAFVPLYLas-ssNEVKVITL 820  alfalfa leafcu...
Feature 1          #   #                  
4OR2_A       345 CFAVSLSVTVALGCMFTPKMYIIIA 369 
Q9QYS2       804 CISVSLSGFVVLGCLFAPKVHIVLF 828  house mouse
EKC28581     532 SIALVVHGTLCLLCLFVTKIYIVVF 556  Pacific oyster
ELU18505     821 AVALCLTAFLCLACLFIPKVYICLL 845  Capitella sp. I Grassle & Grassle, 1976
EFX68215     744 AMSMSISGIVQLACLFAPKVYIVLC 768  common water flea
KDR13891     757 AISLSLSGLVQLACLFFPKLYIVLF 781  Zootermopsis nevadensis
XP_002731157 783 SVSVGLCATVILCCIFAPKLYIILI 807  Saccoglossus kowalevskii
XP_003739342 823 SFLLNLSGTVQIFCLFVPKVYIALF 847  western predatory mite
XP_008217254 799 ALSLSLSALVQLACLFFPKVYIVLM 823  jewel wasp
XP_003700472 821 ALSLSLNGLVQLLCLFLPKVYVVLI 845  alfalfa leafcutting bee

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