2R4S,4JKV,4L6R,4OR2,1UAZ


Conserved Protein Domain Family
7tm_GPCRs

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cd14964: 7tm_GPCRs 
seven-transmembrane G protein-coupled receptor superfamily
This hierarchical evolutionary model represents the seven-transmembrane (7TM) receptors, often referred to as G protein-coupled receptors (GPCRs), which transmit physiological signals from the outside of the cell to the inside via G proteins. GPCRs constitute the largest known superfamily of transmembrane receptors across the three kingdoms of life that respond to a wide variety of extracellular stimuli including peptides, lipids, neurotransmitters, amino acids, hormones, and sensory stimuli such as light, smell and taste. All GPCRs share a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes. However, some 7TM receptors, such as the type 1 microbial rhodopsins, do not activate G proteins. Based on sequence similarity, GPCRs can be divided into six major classes: class A (the rhodopsin-like family), class B (the Methuselah-like, adhesion and secretin-like receptor family), class C (the metabotropic glutamate receptor family), class D (the fungal mating pheromone receptors), class E (the cAMP receptor family), and class F (the frizzled/smoothened receptor family). Nearly 800 human GPCR genes have been identified and are involved essentially in all major physiological processes. Approximately 40% of clinically marketed drugs mediate their effects through modulation of GPCR function for the treatment of a variety of human diseases including bacterial infections.
Statistics
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PSSM-Id: 410628
Aligned: 17 rows
Threshold Bit Score: 80.1642
Threshold Setting Gi: 30750138
Created: 9-May-2005
Updated: 25-Oct-2021
Structure
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Program:
Drawing:
Aligned Rows:
  next features
Conserved site includes 25 residues -Click on image for an interactive view with Cn3D
Feature 1:TM helix 1 [structural motif]
Evidence:
  • Comment:All members of this receptor family contain a seven-transmembrane helix domain.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1     #########################                                                       
2R4S_A     13 MGIVMSLIVLAIVFGNVLVITAIAKFErlq---tvtNYFITSLACADLVMGLAvvPFGAahilmkmw------------- 76  human
Q9TX43     10 TYSILVIADFSSIFGCLLVLIAFKKLKl-------lRNHITRVIACFCVSSLLk-DIIStgltlslgpq---------ne 72  Dictyostelium disc...
Q9NYW3      9 LLFLAVGEFSVGILGNAFIGLVNCMDWvkkrkiasiDLILTSLAISRICLLCVi-LLDCfilvlypd------------- 74  human
Q7Z5H5      7 AVGMILSQTVVGVLGSFSVLLHYLSFYctgcrlrstDLIVKHLIVANFLALRCk-GVPQtmaafgvr------------- 72  human
Q6NV75     10 SAVGWLVCGGLSLLANAWGILSVGAKQkkw---kplEFLLCTLAATHMLNVAV--PIATysvvqlrrqr---------pd 75  human
4JKV_A    150 MHSYIAAFGAVTGLCTLFTLATFVADWrnsn--rypAVILFYVNACFFVGSIGw-LAQFmdgarreivcradgtmrlgep 226
4L6R_A    125 FQVMYTVGYSLSLGALLLALAILGGLSklh---ctrNAIHANLFASFVLKASSv-LVIDgllrtrysqkigddlsvstwl 200
Q86SP6     36 LFCLTCLMTFAALVGSIYSLISLLKMQnrt----vvSMLVASWSVDDLMSVLSv-TIFMflqwpnev------------- 97  human
Q16570     61 ALPFFILTSVLGILASSTVLFMLFRPLfrwq-lcpgWPVLAQLAVGSALFSIVv-PVLApglgst--------------- 123 human
4OR2_A    121 ESIIAIAFSCLGILVTLFVTLIFVLYRdtpvvksssRELCYIILAGIFLGYVCp-FTLIakpt----------------- 182
Feature 1                                                                                     
2R4S_A     77 -tfgnfwcEFWTSIDVLCVta--sIETLCVIAVdryfaitspfk-----yqslltknkarVIILMVWIVSGLTSFLPiqm 148 human
Q9TX43     73 agstsfqcYLYAITITYGSla--cWLWTLCLAFsiynlivkr---------epepekyekFYHGVCWTIPLICVIVMlak 141 Dictyostelium disc...
Q9NYW3     75 vyatgkemRIIDFFWTLTNhl--sIWFATCLSIyyffkignffhpl-flwmkwridrvisWILLGCVVLSVFISLPAten 151 human
Q7Z5H5     73 yflnalgcKLVFYLHRVGRgv--sIGTTCLLSVfqvitvssrksrw--aklkekapkhvgFSVLLCWIVCMLVNIIFpmy 148 human
Q6NV75     76 fewneglcKVFVSTFYTLTla--tCFSVTSLSYhrmwmvcwpvn-----yrlsnakkqavHTVMGIWMVSFILSALPavg 148 human
4JKV_A    227 tsnetlscVIIFVIVYYALma--gVVWFVVLTYawhtsfkalgt------tyqplsgktsYFHLLTWSLPFVLTVAIlav 298
4L6R_A    201 sdgavagcRVAAVFMQYGIva--nYCWLLVEGLylhnllgla---------tlpersffsLYLGIGWGAPMLFVVPWavv 269
Q86SP6     98 pgyfqflcTTSALMYLCQGls-snLKATLLVSYnfytmhrgvgs-----qtasrrsgqvlGVVLTVWAASLLLSALPlcg 171 human
Q16570    124 --rssalcSLGYCVWYGSAfaqalLLGCHASLGhrlgagq--------------vpgltlGLTVGIWGVAALLTLPVtla 187 human
4OR2_A    183 ----ttscYLQRLLVGLSSam--cYSALVTKTNriarilagskkkictrkprfmsawaqvIIASILISVQLTLVVTLiim 256
Feature 1                                                                                     
2R4S_A    149 hwyrathqeai------ncyanetccdfftnQAYAIASSIVSFYVPLVIMVFVYSrvfqeakrqlqkidksegrfhvqnl 222 human
Q9TX43    142 ktiep-------------------vgnwcwiSEKYVGYRFGLFYGPFFAIWIISAvlvgltsrytysvi----------- 191 Dictyostelium disc...
Q9NYW3    152 lnadfrfcvkak----rktnltwscrvnktqHASTKLFLNLATLLPFCVCLMSFFllilslrrhirrmq----------- 216 human
Q7Z5H5    149 vtgkwnytnitvnedlgycsgggnnkiaqtlRAMLLSFPDVLCLGLMLWVSSSMVcilhrhkqrvqhid----------- 217 human
Q6NV75    149 whdtserf------------ythgcrfivaeIGLGFGVCFLLLVGGSVAMGVICTaialfqtlavqvgrqadrraftvpt 216 human
4JKV_A    299 aqvdgdsv-------------sgicfvgyknYRYRAGFVLAPIGLVLIVGGYFLIrgvmtlfsiksnhpgl--------- 356
4L6R_A    270 kclfen-----------------vqcwtsndNMGFWWILRFPVFLAILINFFIFVrivqllvaklra------------- 319
Q86SP6    172 wgafvrtpwgc------lvdcsssyvlflsiVYALAFGLLVGLSVPLTHRLLCSEepprlhsnyqeisrgasipgtppta 245 human
Q16570    188 sgasgglct-----------liystelkalqATHTVACLAIFVLLPLGLFGAKGLkkal--------------------- 235 human
4OR2_A    257 eppmpilsy----------psikevylicntSNLGVVAPLGYNGLLIMSCTYYAFktrnvp------------------- 307
Feature 1                                                                                     
2R4S_A    223 s-------------------------------------qveqdgrtghglrrsskfclkehkaLKTLGIIMGTFTLCWLP 265 human
Q9TX43    192 -------------------------------------------------rnsvsdnkdkhmtyQFKLINYIIVFLLCWVF 222 Dictyostelium disc...
Q9NYW3    217 --------------------------------------------------lsatgcrdpsteaHVRALKAVISFLLLFIA 246 human
Q7Z5H5    218 -------------------------------------------------rsdlspraspenraTQSILILVSTFVSSYTL 248 human
Q6NV75    217 --------------------------------------ivvedaqgkrrssidgsepaktslqTTGLVTTIVFIYDCLMG 258 human
4JKV_A    357 -----------------------------------------------lsekaaskinetmlrlGIFGFLAFGFVLITFSC 389
4L6R_A    320 ---------------------------------------------------rqmhhtdykfrlAKSTLTLIPLLGVHEVV 348
Q86SP6    246 grvvslspedapgpslrrsggcspssdtvfgpgapaaagaeacrrenrgtlygtrsftvsvaqKRFALILALTKVVLWLP 325 human
Q16570    236 ------------------------------------------------------------gmgPGPWMNILWAWFIFWWP 255 human
4OR2_A    308 ----------------------------------------------------------anfneAKYIAFTMYTTCIIWLA 329
Feature 1                                                                        
2R4S_A    266 FFIVNIvhviq-------------------------dnlirKEVYILLNWIGYVNSGFNPLIYCRSP 307 human
Q9TX43    223 AIVNRIlngl---------------------------gyypTLPNILHTYFSVSHGFFASVTFIYNN 262 Dictyostelium discoideum AX4
Q9NYW3    247 YYLSFLiatssy------------------------fmpetELAVIFGESIALIYPSSHSFILILGN 289 human
Q7Z5H5    249 SCLFQVcmall--------------------------dnpnSLLVNTSALMSVCFPTLSPFVLMSCD 289 human
Q6NV75    259 FPVLVVsfsslr------------------------adasaPWMALCVLWCSVAQALLLPVFLWACD 301 human
4JKV_A    390 HFYDFFnqaewersfrdyvlcqanvtiglptkqpipdceikNRPSLLVEKINLFAMFGTGIAMSTWV 456
4L6R_A    349 FAFVTDehaq---------------------------gtlrSAKLFFDLFLSSFQGLLVAVLYCFLN 388
Q86SP6    326 MMMHMVvqnvv--------------------------gfqsLPLETFSFLLTLLATTVTPVFVLSKR 366 human
Q16570    256 HGVVLGldflvrsklll--------------lstclaqqalDLLLNLAEALAILHCVATPLLLALFC 308 human
4OR2_A    330 FVPIYFg---------------------------------sNYKIITTCFAVSLSVTVALGCMFTPK 363

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