Conserved Protein Domain Family
7tmC_GABA-B-R1

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cd15291: 7tmC_GABA-B-R1 
gamma-aminobutyric acid type B receptor subunit 1, 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: 320418
View PSSM: cd15291
Aligned: 13 rows
Threshold Bit Score: 386.69
Threshold Setting Gi: 158593719
Created: 10-Dec-2013
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 12643931  589 KLFISVSVLSSLGIVLAVVCLSFNIYNSHvryIQNSQPNLNNLTAVGCSLALAAVFPLGLDGyhig--rsqfPFVCQARL 666
gi 215500755 437 SLFAGMCAVAFIGVVWAVGLLVFNWIFRHsryIQLSHPMCNNIMLIGIILCLVCVCLLGLDGqfvs--efryAHICQARS 514
gi 392925563 416 EFYYPTILFAVLGIAACVFIYLFTQKHHErliIFQSQPECNNILLIGCSLCLFSLFLIGLPSddisiseslfPLLCHARV 495
gi 94732197  555 KLFVSVSVFAGLGILMGIVCLTFNIYNSNvryIQNSQPYLNNMTAVGCMMALAAVFPLGIDGlhvr--nsqfPVVCQFRL 632
gi 121995587 464 PLFVCMCTISSCGIFVAFALIIFNIWNKHrrvIQSSHPVCNTIMLFGVIICLTSVILLGMDGrfvs--peeyPKVCQARA 541
gi 555694655 455 VSFASMCFLAAFGIFCSVFLLVLNAAHRLqmdNQKSRNCMNTVMLLGCLLCFVCIFINGLDArlvs--rltlLKICQAQK 532
gi 283462240 461 NLYAAMCALASLAIIAAVASLTFNIWFRKtryIQLSHPSLNNLIIVGCIVCLSCVFLLGLDGkfvs--pdvyPVICQLNA 538
gi 321475292 459 GLFVTMSLVSSVGIAAAIGLIIFNVVYREqklIELSQPACNNVMLVGIVLLLSSVILLGMDGdtvp--vvhfPVVCQLRA 536
gi 443688992 441 GLFIAMCLLASFGIITAILLLAFNCVNVQrriIRLSQPHVNNAMLVGCIVCFCCIFLQGLDGahiq--rkhfSSLCQVRS 518
gi 312191382 396 KLFISISVLAGLGILLGFVCLSFNIYNSHvryIQNSQPHLNDMTAAGCILSLAAVFPLGLDGrhie--twhfPLVCQARL 473
gi 158593719 480 ELYYAIALLAVIGIFVACIIFIFNVKNSDrviIMESQPQCNNVLLAGCILCCLSLLLLGLPArgitvpkhsfTLLCHSQI 559
gi 12643873  590 KLFISVSVLSSLGIVLAVVCLSFNIYNSHvryIQNSQPNLNNLTAVGCSLALAAVFPLGLDGyhig--rnqfPFVCQARL 667
gi 637273317 599 KLYISVSVLSSIGILLAIICLAFNIYNGHvryIQNSQPYLNNMTAVGCALAQASVFPLGLDGlhis--kelfPFVCQARL 676
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1          ##  #                                                                         
gi 12643931  667 WLLGLGFSLGYGSMFTKIWWVHTvftkkeekk------------ewrktlepWKLYATVGLLVGMDILTLAIWQIVDPlh 734
gi 215500755 515 WFLTIGFTLSFGAMFSKIWRVHRittmsks---------------eskkvesWKLYGMVGAMVLIDAVILTAWQLVDPmk 579
gi 392925563 496 TILLFGFTFAYGSMFAKVWIVHRmgatenqqla---------srqkdepissSKFYVIVAALTAVDVFVCFVWVLIDPlh 566
gi 94732197  633 WLLGLGFSLAYGSMFTKIWWVHTvftkkdekk-----------dkrkqhlepWKLYATVGVLLVIDILSLMIWQIVDPlh 701
gi 121995587 542 WLLSTGFTLAYGAMFSKVWRVHRfttkaktd--------------pkkkvepWKLYTMVSGLLSIDLVILLSWQIFDPlq 607
gi 555694655 533 WIFCFGFTLSYGAMFTKVWSIYRhtirqktg--------------shtvhvtTESFFVIIICLVVDVIILSVWQLINPti 598
gi 283462240 539 WVLCIGFSLAYGAMFSKVWRVHRlstnekasesddkkrrtdskkntkkevedWHLYIVVVIFILVDVVICSVWTVLDPqy 618
gi 321475292 537 WLLCLGFTLAFGAMFSKVWRVHRkmkekks----------------rtqsakAKVDWVLVGLSCIDVIILTIWAIVDPqm 600
gi 443688992 519 WVLCIGFSLAYGSMFSKVWTIYRltthrkk---------------eikalrdWEMYLVLGIFLVIDLIILTAWQVIDPly 583
gi 312191382 474 WLLGLGFSLAYGSMFTKIWWIHTaftkkedkke---------rrklsqtlepWKLYTTVSLLLGLDAITLGIWQIVDPlq 544
gi 158593719 560 SLLMVGFTFAYGSMFAKVWVVHRlgstenqhlis--------kpttgqpvpaCKFYLVVTAFFVVDIIIIACWFTFDPiq 631
gi 12643873  668 WLLGLGFSLGYGSMFTKIWWVHTvftkkeekk------------ewrktlepWKLYATVGLLVGMDVLTLAIWQIVDPlh 735
gi 637273317 677 WLLGLGFSLGYGSMFTKIWWVHTvftkkeekk------------errktlepWKLYATVGLLVGLDFVILAIWQIVSPlk 744
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                       #    #  ##  #                                  # 
gi 12643931  735 rtietfakeepk--edidvsilpqlehCSSKKMNTWLGIFYGYKGLLLLLGIFLAYETKSVstekINDHRAVGMAIYNVA 812
gi 215500755 580 releifpledpe-msdedvkiepalehCESKNHAIWLGVMYSYKGLLLIFGIFLAYETRSVkikqLNDSRLVGMSIYNVV 658
gi 392925563 567 lteqkfplftpa-dseedemimpvlqqCQSNQQEVWIGIIMGFKCLLLVFGTFLSYETRNLklrfINDSRFVGLAIYNVA 645
gi 94732197  702 itvekftkeapk--gdvdeliepllqhCSSEKMNTWLGVVYGYKGLLLLLGIFLAYETKSVstekINDHRAVGMAIYNVS 779
gi 121995587 608 ryletfpledpv-sttddikirpelehCESQRNSMWLGLVYGFKGLILVFGLFLAYETRSIkvkqINDSRYVGMSIYNVV 686
gi 555694655 599 ielelftlenklniykddteviyelehCSSHNYSTWFGIMAGFKGILLLFGLLLAYEIRNIklneANESRFVCVSIYNTV 678
gi 283462240 619 rsiqelqkiepv--gkedveilplleyCDSRQSAVWLGVIFGAKGLLLIFGLFLAYETRNMsvkeLNDSRFVGMSIYNVV 696
gi 321475292 601 rmvenfqlenpt-dtekdikirpsmehCESKHQNIWLGVVYGYKGLLLIFGLFLAYETRSMkvrsINDSRYVGMSIYNVV 679
gi 443688992 584 vdiemfpletpe-vadkdmqyepqlefCTSKYLNIWLGVVFSYKGILLLFGILLAYETRNVkvvqVNDSRFVGMSIYNIV 662
gi 312191382 545 rsieeftkeepr--gdldvlilpqlehCSSLKMNTWLGIVYGSKGLLLLLGIFLAYETKSVstekINDHRAVGMAIYNVA 622
gi 158593719 632 rveqrfplqeppmgteedimllpilelCQSERQEMWTGLVMGYKCLLLVLGLFLAYETRNLkplfVNDLRFVGLAIYNVA 711
gi 12643873  736 rtietfakeepk--edidvsilpqlehCSSRKMNTWLGIFYGYKGLLLLLGIFLAYETKSVstekINDHRAVGMAIYNVA 813
gi 637273317 745 rtteeftkedpk--sdidvqilpklehCSSEKMNTWLGIFYGFKGLLLLLGIFLAYETKGVstekINDHRAVGMAIYNVA 822
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|
Feature 1         ##  #   #          ##  #  #   #                  
gi 12643931  813 VLCLITAPVTMils-sqQDAAFAFASLAIVFSSYITLVVLFVPKMRRLIT 861
gi 215500755 659 VLCLITAPVTLvig-sqQDATFAFVALAIIFCSFLSMALIFVPKIIELVR 707
gi 392925563 646 VMTLVTAPVVTllihgkVDANFAFISLTVLICTYISVGLIYGPKIRHIIK 695
gi 94732197  780 VLCMITAPVTMils-skQDASFAFASLAIIFSVYITLVVLFVPKMRRLIT 828
gi 121995587 687 VLCLITAPVGMvia-sqQDASFAFVALAVIFCCFLSMLLIFVPKVIEVIR 735
gi 555694655 679 ILCVITVPAAWiir-shQDATYLFVSIAILLGNLFFMFVIFVPKIKEMQN 727
gi 283462240 697 VLCIITAPVTLiir-tqQNATFAFVSLAIIFCCVVTLVLIFIPKVVEIKR 745
gi 321475292 680 VLCLITAPVSLvis-sqADASFAFVTAALAFCCFISMALIFLPKVVEVVR 728
gi 443688992 663 VLCIITAPVTLiig-shQDASFAFVAVAILLSSFLAMGLIFVPKIMEVMR 711
gi 312191382 623 VLCLITAPVTMils-rqQDASFAFSSLAIVFSAYITLVVLFVPKMRRLIT 671
gi 158593719 712 VLSLITGPIVTflirsqSDANFAFISITVLLSTYITLGLIFLPKIVHIRR 761
gi 12643873  814 VLCLITAPVTMils-sqQDAAFAFASLAIVFSSYITLVVLFVPKMRRLIT 862
gi 637273317 823 VLCLITAPVTMils-sqQDAAFAFASLAIVFSSYITLVVLFVPKMRRLIT 871

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