Conserved Protein Domain Family
7tmC_GABA-B-R2

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cd15294: 7tmC_GABA-B-R2 
gamma-aminobutyric acid type B receptor subunit 2, member of the class C family of seven-transmembrane G protein-coupled receptors
The type B receptor for gamma-aminobutyric acid, GABA-B, is activated by its endogenous ligand GABA, the principal inhibitory neurotransmitter. The functional GABA-B receptor is an obligatory heterodimer composed of two related subunits, GABA-B1, which is primarily involved in GABA ligand binding, and GABA-B2, which is responsible for both G-protein coupling and trafficking of the heterodimer to the plasma membrane. Activation of GABA-B couples to G(i/o)-type G proteins, which in turn modulate three major downstream effectors: adenylate cyclase, voltage-sensitive Ca2+ channels, and inwardly-rectifying K+ channels. Consequently, GABA-B receptor produces slow and sustained inhibitory responses by decreased neurotransmitter release via inhibition of Ca2+ channels and by postsynaptic hyperpolarization via the activation of K+ channels through the G-protein beta-gamma dimer. The GABA-B is expressed in both pre- and postsynaptic sites of glutamatergic and GABAergic neurons in the brain where it regulates synaptic activity. Thus, the GABA-B receptor agonist, baclofen, is used to treat muscle tightness and cramping caused by spasticity in multiple sclerosis patients. Moreover, GABA-B antagonists improves cognitive performance in mammals, while GABA-B agonists suppress cognitive behavior. In most of the class C family members, the extracellular Venus-flytrap domain in the N-terminus is connected to the seven-transmembrane (7TM) via a cysteine-rich domain (CRD). However, in the GABA-B receptor, the CRD is absent in both subunits and the Venus-flytrap ligand-binding domain is directly connected to the 7TM via a 10-15 amino acids linker, suggesting that GABA-B receptor may utilize a different activation mechanism.
Statistics
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PSSM-Id: 320421
View PSSM: cd15294
Aligned: 9 rows
Threshold Bit Score: 460.356
Threshold Setting Gi: 316977917
Created: 10-Feb-2014
Updated: 26-Jul-2017
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:
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                  #                  ##  
gi 62739378   479 PLYSILSTITIIGMIMASTFLFFNIKNRNqkmIKMSSPYMNNLIILGGMLSYASIFLFGLDGSFvsantFETLCTVRTWI 558
gi 82254866   391 PLYSILSTITILGMFMAGAFLFFNIKNRNhrlIKMSSPYMNNLIILGGMLSYASIFLFGLDGGFvsdkeFETLCTVRTWI 470
gi 483523637   48 PLYSILSALTILGMIMASAFLFFNIKNRNqklIKMSSPYMNNLIILGGMLSYASIFLFGLDGSFvsektFETLCTVRTWI 127
gi 158705934  479 PLYSILSALTILGMIMASAFLFFNIKNRNqklIKMSSPYMNNLIILGGMLSYASIFLFGLDGSFvsektFETLCTVRTWI 558
gi 321470990  499 PVFVTLTIVAALGIVLASSFLAINIRFRNqryIKMSSPYLNNTIIIGCLLTYTSVILLGLDSHLtsesaLPVICTARIWT 578
gi 443683718  361 TIYVVMCSFSGLGIIIALTFLAINIRFRRhryIKMSSPNMNNLIIMGCVFAYTSVFLLGADGGLvpphhYAILCSGRTWI 440
gi 74864600   446 TIYIVSASASVIGVIIATVFLAFNIKYRNqryIKMSSPHLNNLIIVGCMMTYLSIIFLGLDTTLssvaaFPYICTARAWI 525
gi 316977917  493 SVFYIMCSLVAICIMLAIALLTVNIYFRNhkfIKMSSPNVNNLIILGSIMTYCSVILLGIDTNMvseldYSRMCTAKVWI 572
gi 392898845  439 ILFLAMSLLALIGIFLALIFLLINFRYRNhrfIKMSSPNLNNIIIAGSICTFASVIMLGLDTRIvspdvFVWLCYTKTWT 518
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1         ##  #                                                                           
gi 62739378   559 LTVGYTTAFGAMFAKTWRVHAIFKNvkmkkkiiKDQKLLIIVGGMLLIDLCILICWQIVDPLKRTVEeyn---------- 628
gi 82254866   471 LIVGYTTAFGAMFAKTWRVHAIFKNvkmkkkiiKDQKLLIIVGGMLLIDLCILICWQIVDPLKRTVEeysleivgaffep 550
gi 483523637  128 LTVGYTTAFGAMFAKTWRVHAIFKNvkmkkkiiKDQKLLVIVGGMLLIDLCILICWQVVDPLRRTVEkyn---------- 197
gi 158705934  559 LTVGYTTAFGAMFAKTWRVHAIFKNvkmkkkiiKDQKLLVIVGGMLLIDLCILICWQAVDPLRRTVErys---------- 628
gi 321470990  579 LMAGFTLAFGSMFSKTWRVHSIFTDvklnkkaiKDYQLFMVVGVLLTIDIAILTTWQVIDPFYRETKlle---------- 648
gi 443683718  441 MCVGFTLSFGAMFSKTWRVHAIFTNiklnkkviKDYKLFLLVAFLLFIDIVILSAWQIFDPPERETKnlr---------- 510
gi 74864600   526 LMAGFSLSFGAMFSKTWRVHSIFTDlklnkkviKDYQLFMVVGVLLAIDIAIITTWQIADPFYRETKqle---------- 595
gi 316977917  573 LCFGFTLAFGSMFAKTWRVHSIFNDihlhkkaiKDYKLFLIVGVLLLIDVLILSTWLIIDPMQMAVKqlp---------- 642
gi 392898845  519 LCIGFTLSFGAMFSKTWRVHSIFTNirmdrkaiKDSKLFIILGILLFIDICVLVTWAFVSPFSYTVTel----------- 587
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                   #    #  ##  #                                  #  ##  
gi 62739378   629 ----lepDPAGRDVAIRPFLEHCENTHMTIWLGIVYAYKGLLMLFGCFLAWETRNVsipaLNDSKYIGMSVYNVGIMCII 704
gi 82254866   551 lsskrgaDPQGRDIAIRPFLEHCENTHMTIWLGIVYAYKGLLMLFGCFLAWETRNVsipaLNDSKYIGMSVYNVGIMCII 630
gi 483523637  198 ----mepDPAGRDISIRPILEHCENTHMTIWLGIVYAYKGLLMLFGCFLAWETRNVsipaLNDSKYIGMSVYNVGIMCII 273
gi 158705934  629 ----mepDPAGRDISIRPLLEHCENTHMTIWLGIVYAYKGLLMLFGCFLAWETRNVsipaLNDSKYIGMSVYNVGIMCII 704
gi 321470990  649 ----pypHPSQDNAEIRPENEYCQSNHMTIFVSSIYAYKGLLMAFGCFLAWETRNVnipaLNDSKYIGMSVYNVVIMCVI 724
gi 443683718  511 ----ariDPREMDVEILPVMEFCISRHMTIWLISIYVYKGLLLVFGCFLAWETRQVsiaaLNDSKYIGMSVYNVVIMCVS 586
gi 74864600   596 ----plhHENIDDVLVIPENEYCQSEHMTIFVSIIYAYKGLLLVFGAFLAWETRHVsipaLNDSKHIGFSVYNVFITCLA 671
gi 316977917  643 -----teKDERSNMLIKPTIEYCKTDYTVVFQALLYGYKGIFLVLGCFLAWETRNVnvpaLNDSKYIGMSVYNVVLVCGV 717
gi 392898845  588 ------pHIPEDNIVIIPEVEKCNSSHSGVFQAVLYAVKGVLMILGCFLAWETRHVnvpaLNDSKYIGTSVYCCVVMSVL 661
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
Feature 1         #   #         ##  #  #   #                  
gi 62739378   705 GAAVSFltRDQPNVQFCIVALVIIFCSTITLCLVFVPKLITLRT 748
gi 82254866   631 GAAVSFltRDQPNVQFCIVALVIIFCSTITLCLVFVPKFITMRT 674
gi 483523637  274 GAAVSFltRDQPNVQFCIVALVIIFCSTITLCLVFVPKLITLRT 317
gi 158705934  705 GAAVSFltRDQPNVQFCIVALVIIFCSTITLCLVFVPKLITLRT 748
gi 321470990  725 GGAVSFilEDEQDVSYVIISIFIVFCTTGTLCLVFVPKLIELRR 768
gi 443683718  587 GVPVTFiiKDRPDAAYLIIALFITFSTTITLCLVFMPKIVQLKR 630
gi 74864600   672 GAAISLvlSDRKDLVFVLLSFFIIFCTTATLCLVFVPKLVELKR 715
gi 316977917  718 GVAISFilQDQINECYIIISMFIIFCTTVTLALVFVPKIVELMQ 761
gi 392898845  662 GLSTSVilQERVNEMFSLASFFVIFSTTLTLCLVFVPKVIELAR 705

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