Conserved Protein Domain Family
7tmC_GPR158-like

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cd15293: 7tmC_GPR158-like 
orphan GPR158 and similar proteins, member of the class C family of seven-transmembrane G protein-coupled receptors
This group includes orphan receptors GPR158, GPR158-like (also called GPR179) and similar proteins. These orphan receptors are closely related to the type B receptor for gamma-aminobutyric acid (GABA-B), which 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: 320420
View PSSM: cd15293
Aligned: 35 rows
Threshold Bit Score: 251.749
Threshold Setting Gi: 328769002
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--psVFRCIALRWVRLLGF 456
gi 405974576  364 VIKVLILILTIIVIVFIIIASGIIFRLKEskaIKSGSPIFLLLMSFGGILMCLQLFVMFpd--anEVLCMLLPWPYHLGF 441
gi 514484580  409 AARITMFTLAGLIVLICLIMGLMTWHFRRiriIQSASPTYLLLILFGAVMSMLWIFLDYsdd-psTAQCTARVWMRHLGF 487
gi 514484806 1227 GARYFFVVLAAIFILIAFGFLLFLMRNWSsriIVASSPTFLALILFGALLSYVWIFLAApt--ptDALCAAMPWVRHLGF 1304
gi 514485650  655 AVIAVILTFTGVLLFLCGVLVVMIVVFRDkkvMRSASPTFLLLMVFGTATSLSSIFLLAvdn-ptNDYCMAAMWIRHMGF 733
gi 320164404  354 ALRIAFVAIACFEVFIFILAAIGVFHYRRvrvILSGSPTFLLLMLLGAVWSMFWIILNYqee-lsESICMARIWARHLGF 432
gi 514487078  411 SLRIAFVILAALLIAFFCVLAAGTFHYRRvrvVLSASPVFLMLMLLGAAWSMFWVILLYdda-ptDAICIARIWARHLGF 489
gi 320164318  404 ALRIAFIVVAAAELALFVLFAFGVIRYRRiraVLSGSPKFLFLMLVGAALSMFWVILSYqee-vtSNLCVARVWARHLGF 482
gi 328769002   43 PFKSMAIAVSVIGALFSLICSILLNRFKKervFRAASRTFMSILVWGTLLMWIGMFLKGlsssatVFTCYGIYFTQYIGF 122
gi 514483820  693 QLRIAFQTIAALLIAMCLLTFYLVYAFRDmkvVLSGNPLFLRIILVGAVIELASVFVVAaeh-vsDELCSARVWTQHLGF 771
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                         
gi 85540945   457 AIVYGTIILKLYRVlqlflsrtaqrsallssgrLLRRLGLLLLPVLGFLAVWTVGALergiqhaplvi----rghtpsgr 532
gi 405974576  442 VLMYGALLLKTWRIsiifrkgqf-kkvhlpdrtLLRHMAMIMAVAFGYLVAWTAANNdfsqmkkt-----------ssgl 509
gi 514484580  488 SIMFSALFLKTYRIarvfkatvt-kssplndrrLFYHFLQMNAVVILILIIWTVVNPphaeqli------------sgne 554
gi 514484806 1305 CFVFGALFLKTYRIdrifnndai-krirmkdtvLFHYMFRIVLMFALYLAIWTGISRpisevrvditsdqtnqgvfvtqq 1383
gi 514485650  734 AIAFGALFLKTYRIaqvfrakssraaralrddrLLLKLFQLCLLFAVYLLIWSLAHPpqvelket-----------pshe 802
gi 320164404  433 VLIYGALFLKTYRIasvfntksstnaghltdrvLLFRFVLIVAYGCVMLVAWSVSHPpqvttmv------------hnne 500
gi 514487078  490 SLVFGALALKTYRIaaifnvkatkkshqltnvrLLVRFGEINLYVCAFLLTWTVAGAptattlv------------shnn 557
gi 320164318  483 AIIFAAIFLKTWRIasvfnikss-kggqltdrvLLYRFLLIVGYATVNLVAWTVSTPpttgtvv------------snne 549
gi 328769002  123 SIVFGTLVVKSLRIvqfskssen-rlprlndyvLLRSLWGYIAAWAVLIVAAIMWQNsirpiglnik------vdsnsql 195
gi 514483820  772 AIMFTALFCKTYQVarvyrvkvd-rratvttraLFKIFAQFLAFFVGYLIVFTIVDPsrpesyli----------rgdti 840
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1              #    #  ##  #                                 #  ##  #   #           ##  # 
gi 85540945   533 hfyLCHHDRWDYIMVVAELLLLCWGSFLCYATRAVLsaFHEPRYMGIALHNELLLSAAFHTARFvlvpslhPDWTLLLFF 612
gi 405974576  510 kfvMCTENWWSYSAYGMEIVMLLFGVYLCFTVRKAPatFNESKHITWSIYNAILLSTFILIVNYftaetvgPDLIYSMTF 589
gi 514484580  555 sylVCNINWWDNAMYILEVVALGGLAVVCFSVRKAPsaFNESKFIALSVYNWLVVAVILQIILRatk--gnATFFFIIES 632
gi 514484806 1384 lvpRCSSNWFDSAILIVELMFLIWGLYLAIKVRHTPtaFNESKYIVVAVYNFVFVAVVLQIILQtai--kdRDIAYVLES 1461
gi 514485650  803 qfhTCDRDWFFFGLLIAELMLLAMSAWLCFITRKAPsaFNELRQQSLAIYNWTLILLILEIVVNtva-nddANAVFALSS 881
gi 320164404  501 syeVCEVTWWDNAMYIQELIAMFITGMLCYRVRKAPsaFNGSKRAAISVYNWIMVGVILQIILNstt--gpADFYFAVQS 578
gi 514487078  558 syaVCSITWWDNAMYLQELAAMLGLAFLSYRVRKAPsaFNECKHMALAVYNWIIIGVILQLILNstt--gtADFYFAIQS 635
gi 320164318  550 sylVCEVTWWDNAIYIEELVAMVALGLLCYRVRKAPsaFNESKHIGLAVYNWIVMGIILQIILNstt--gtADFFFAIQS 627
gi 328769002  196 eyaTCQAKSAEIIWDGFQALSIALGVFVSLQCRGMPsaYNEGTYISLTIYNWALTWTIGKLIRKlwkpsldPGLELFLEI 275
gi 514483820  841 qynGCSRNWWLYSLLLFELLFMGIGVFLAWTVRKAPsaWNESRHVVLSVYNFMFVTVVIEVLLIaas--lePDVQFVLQS 918
                         250       260
                  ....*....|....*....|....
Feature 1          #   #                  
gi 85540945   613 FHTHSTVTTTLALIFIPKFWKLGA 636
gi 405974576  590 LNCQVVVTMTLVLIFVPKFYAVYM 613
gi 514484580  633 LEVLLTVPIIVGLLLVPKLYLTLK 656
gi 514484806 1462 IYVIFTVSAVVLLIFVPKVSLVRN 1485
gi 514485650  882 LELLLTQGFAVMIVLLPKAVAVLR 905
gi 320164404  579 LEVLITVPITMLISFVPKFYLIAR 602
gi 514487078  636 LEVLVPVPIAILLLFVPKFYLTLR 659
gi 320164318  628 LEVLVPVPIAVMILMAPKFYLILR 651
gi 328769002  276 IESFGCVSTVLLMLFAPKVMLMLQ 299
gi 514483820  919 LQIFFTVPVVVVLIFGPKLRMVYR 942

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