Conserved Protein Domain Family
7tmC_GABA-B-like

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cd15047: 7tmC_GABA-B-like 
gamma-aminobutyric acid type B receptor and related proteins, 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. Also included in this group are orphan receptors, GPR156 and GPR158, which are closely related to the GABA-B receptor family.
Statistics
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PSSM-Id: 320175
View PSSM: cd15047
Aligned: 95 rows
Threshold Bit Score: 141.544
Threshold Setting Gi: 281203204
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 85540945   379 VLRAAVLACQACCMLAIFLSMLVSYRCRRnkrIWASGVVLLETVLFGFLLLYFPVFILYfk-------------psVFRC 445
gi 74857951   392 SIKISILSVSIFCIFICVLGMIFITVLRNariLKSSSPSFLLLILFGCIVIFTGCILFSqp-------------atDKTC 458
gi 281203553  411 GVQLVFTALGVGFAIACGVLIIAVIVLRNerpIRSASPLFCVIILVGGILVFVGCVIWVsy-------------ptTIVC 477
gi 328876451  372 SITLGLSIPSGVFILFAIVSIVVIILFRNakvIKSASPLFSVLILIGCILIFAGIIIWSqn-------------ptTSLC 438
gi 320166213  662 SAFIAVQVVTSLCAVGTIVIFVILRRHLShssIRASSPVLLQFMLASTVLVYAAIFLMGvdsgsddnslvslstvaSNIC 741
gi 182647408  434 TLNIVLGVITGVCVLIVIGIGSVIALQWRk--FRYSSPLFCMFIIIGALMGLASVFTLLpt-------------ptTPLC 498
gi 514485978 1119 ALRYVILAIAVLGALSCVLLLLFIVANREapqMKASSPRFMCIIIGGCIIAFILVATLVpn-------------vtDTTC 1185
gi 514486405 1260 SLRFGFMSVAIIGEACAILLVIFVIRKREepiVKAASPKFCLIVIFGCMLEFALIPTLVpd-------------ltPALC 1326
gi 74857950   383 SMKLGLTIVSGFCILFCIISMVLVIMFRHakiIKSASPIFCLLILFGCIIIFSGCIIFSls-------------ptDGIC 449
gi 281207550  375 SITYGFSIAAGVVGLVAVIILVGLLVFREtkiMRSASPLFCMLIVFGGILIYVAVILWVqs-------------ptTGLC 441
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1           ##  ##  #                                                                     
gi 85540945   446 IALRWVRLLGFAIVYGTIILKLYRVlqlflsrtaq-rsallssgrLLRRLGLLLLPVLGFLAVWTVGALergiqhaplvi 524
gi 74857951   459 QGRVWLLSIGYTIFLGSLLIKNWRVwllfdnkkl--rkrsitnwkLYPWVAGILVVDVLILALWQGLGDiksesriigts 536
gi 281203553  478 HLRYWIPSIGYGLIVGNLVVKNFRIyilfkamk----npritnlkLLPFSIGITSVHVLLLIIWSTVGNtksimdtnddn 553
gi 328876451  439 RSRIWLISLGYTLMIGNLLIKNFRIwllfdnpkl--krrnipnkkLIPWFLGILILDAIILAVWIAVGDikaverlnidg 516
gi 320166213  742 RAIPWLLGLGFDLVYGAMLAKAWRIhkifnnrlr--rrimltdgnLIKHIVIFAMHDIILNAVWVGVDPlgleyhvlsss 819
gi 182647408  499 SGFPWLLGLGYVIVFGTLFTKTWRTwrlfsnarkf-kiiritnkfIITLVGGFVLLESIFMIIWTAVDRpiplaepif-- 575
gi 514485978 1186 TVHIWFGHIAFTVTFGALFFKSYRIavifnnrklkrqlsrtsdrfLLTMVSLIVGGMVTYLIIWTAVDRpvrdfhiv--- 1262
gi 514486405 1327 VTHIWIGHLGFAVAFGALFAKTHRIaaifnnknlarklrgtsdsfLMSRIAIVVSAVSLYLLVWSVVDKpdvvgttevg- 1405
gi 74857950   450 GARVWLLSIGYTIFLGSLLVKNWRIwllfdnpkl--kkrsitnwkLYPFVAGILAADVLILALWQGLGDirsesrigids 527
gi 281207550  442 RSRIWLMSLGYTIMLGNMVIKNFRIwlifdnpll--kklritnakLMPWLGGIILLNCLILAIMTGVGEvhsqrnygfeg 519
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                       #    #  ##  #                                  #  ##  #   #       
gi 85540945   525 -rghtpsgrhfyLCHHDRWDYIMVVAELLLLCWGSFLCYATRAVls-aFHEPRYMGIALHNELLLSAAFHTARFvlvp-- 600
gi 74857951   537 --fyqytnvctnNDQGSIALYILLAFHGLKLLGTCFISFKIKLVdieeFNESKPITTSVFIILFCIFTIILLIApsssss 614
gi 281203553  554 igkyefvrkchlTTAGDIIFYAILVIHGLILLVGCFVSFQIRAVdieeFNESKSIAAFLYAVMFALFIIIPLFVss---- 629
gi 328876451  517 lgtyesmnacssSHAGDVVLYILLIFHGIMLLVGCFISFKIRSVdikeFNECGPVSTCLYAIAFCLFIVIPLMVsp---- 592
gi 320166213  820 -ssgttvtsqcrSDNFGIYLAIYLAFKGAVLLAGIYLAIACRNVad-qFNESKQLGFAIYNLTFISCIIIPLVLaiq--- 894
gi 182647408  576 ---kageaqlqcTSDSEAWWYVFVFYKVFYILFGVFLAFKTRNVvd-sLNESKPITLALYNLTFVMVVAIALGFilr--- 648
gi 514485978 1263 ----gsevrvlcSSSSTLWVVAVYIAEALLLAFGAIVAFKSRRAps-rWNESKFLAFAIWNIFVVVVIVMPLNYlvd--- 1334
gi 514486405 1406 ---etisvyymcKSSNDSWSVGLYALEAVGLLYGCWLAWQVRNAps-rFRESKFIVMAVWNILVVSIIILPLNYaln--- 1478
gi 74857950   528 ltkyqyanvcssNDQGSVALYILLVFHGIKLLAACFISFKIKAVdieeFNESKPIASSIYIITFCLFIVIPLMVsp---- 603
gi 281207550  520 lfeydyrvtcdmNKSGNIVLYILLIYHAILLLVGCFVSWKIRIVdiaeFNESKSIANTLYAISFCLFIIIPLMVsq---- 595
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
Feature 1                   ##  #  #   #                  
gi 85540945   601 ----slhPDWTLLLFFFHTHSTVTTTLALIFIPKFWKLGA 636
gi 74857951   615 sasspqpIASLETIICICSVTTTAISIGLLFGDKIYFITT 654
gi 281203553  630 -----tsTFNHIIILCVAFLFTAGSGLAIIFIPKFLMIKR 664
gi 328876451  593 -----qsIANQTIIICACGIFTTFSSMAILFLPKFGEMYT 627
gi 320166213  895 -----asATVVYLIAAFGTLLALVMTIAIIFVPKIVLVYS 929
gi 182647408  649 -----dnPIAIIVIQTIAILLGFTVTVSVLFLPKVWMILS 683
gi 514485978 1335 ----tsnPDTQFLLTCIGVLLAAFGTLGLCIVPKVHSVVS 1370
gi 514486405 1479 ----tdnPDTQFMFTALGILLATFGTLGLIFIPKMYGLVT 1514
gi 74857950   604 -----qsVASQVITIVVCAIVTTLISISLLFGSKFYMMAT 638
gi 281207550  596 -----ttYDSQIIIICASAIFTTASTLTILFLPKFWRLYT 630

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