2R4S,2VT4,2KS9,2YDO,4DKL,3V2Y,4GRV,3VW7,5UNF,3OE0,2Z73,3EML


Conserved Protein Domain Family
7tm_classA_rhodopsin-like

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cd00637: 7tm_classA_rhodopsin-like 
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rhodopsin receptor-like class A family of the seven-transmembrane G protein-coupled receptor superfamily
Class A rhodopsin-like receptors constitute about 90% of all GPCRs. The class A GPCRs include the light-sensitive rhodopsin as well as receptors for biogenic amines, lipids, nucleotides, odorants, peptide hormones, and a variety of other ligands. All GPCRs have 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. Based on sequence similarity, GPCRs can be divided into six major classes: class A (rhodopsin-like family), class B (Methuselah-like, adhesion and secretin-like receptor family), class C (metabotropic glutamate receptor family), class D (fungal mating pheromone receptors), class E (cAMP receptor family), and class F (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: 410626
View PSSM: cd00637
Aligned: 449 rows
Threshold Bit Score: 39.194
Threshold Setting Gi: 67476970
Created: 6-Mar-2002
Updated: 17-Aug-2020
Structure
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Program:
Drawing:
Aligned Rows:
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Conserved site includes 41 residues -Click on image for an interactive view with Cn3D
Feature 1:putative ligand binding pocket [chemical binding site]
Evidence:
  • Comment:based on the structures of some class A family members with bound ligands (peptides or chemicals), agonists, or antagonists
  • Comment:Small-molecule chemical ligands tend to bind deeper within the receptor core, compared to a peptide ligand neurotensin, which binds towards the extracellular surface of its receptor.
  • Structure:4GRV: Rattus norvegicus neurotensin receptor Nts1 binds neurotensin peptide (8-13), contacts at 4A.
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  • Structure:3OE0: CXCR4 chemokine receptor in complex with a cyclic peptide antagonist, contacts at 4A.
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  • Structure:2YDO: thermostabilized Human A2A receptor binds adenosine, contacts at 4A.
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  • Structure:2VT4: Meleagris gallopavo beta-1 adrenergic receptor binds high-affinity antagonist cyanopindolol, contacts at 4A.
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  • Structure:3EML: Human A2a adenosine receptor binds antagonist Zm241385, contacts at 4A.
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  • Structure:4DKL: Mouse mu-opiod receptor binds a morphinan antagonist, contacts at 4A.
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  • Structure:3V2Y: sphingosine 1-phosphate receptor 1 binds a sphingolipid mimic antagonist, contacts at 4A.
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                              #  ##                ##
2R4S_A     13 MGIVMSLIVLAIVFGNVLVITAIAKFERlq---tvTNYFITSLACADLVMGLAvvPFGAAHIlmkmwt-----fgnfwCE 84  human
4GRV_A     35 VTAIYLALFVVGTVGNSVTLFTLARKKSlqslqstVHYHLGSLALSDLLILLLamPVELYNFiwvhhpw---afgdagCR 111
P23275     27 FFAVILASYLLTLVGNLTIILLSRLDARlh---tpMYFFLSNLSSLDLAFTTSsvPQMLKNLwgpdkt-----isyggCV 98  house mouse
O95800     45 CTFLLAVIFCLGSYGNFIVFLSFFDPAFrkf-rtnFDFMILNLSFCDLFICGVtaPMFTFVLffssas----sipdafCF 119 human
NP_608986  73 LAVSYGLVVFGGVVGNSTLVLTLCSASSvr----lRNPLLLAVCIADLLVTGIsaPVTLLNLamnrrtr---slplvlCK 145 fruit fly
EDO26227   23 EASISLVVTLLAFGGNLLVCLACSKHQSlr---tiPNILVLNLAVTDIVNSCTslLALTVTLlsgewl-----fgatgCY 94  starlet sea anemone
EDO48607   71 RMTIIVLIFIATGLGNGSILVMIKRFNTlr---ttPNILIANLAFIDLMNVVInlPLVAVLVtlqfqry---vkgrfsSA 144 starlet sea anemone
EEN58549  307 QMVWLAACTVLGVCGNMALLITVSCVQElr---tpGNALLCALACADIFQLVTkvPMAVVFLhyge---------plaCD 374 Florida lancelet
EEN46533   56 VAMVMGLLAVVGTALNGTVIFAVGFNKRlr---taTSWFVVNLAAGDLLETAVylPFGVYTVithrvp-----fhpsvCA 127 Florida lancelet
Q6NV75     10 SAVGWLVCGGLSLLANAWGILSVGAKQKkw---kpLEFLLCTLAATHMLNVAV--PIATYSVvqlrrqrpdfewneglCK 84  human
Feature 1     #### ##  #                                                 # #####              
2R4S_A     85 FWTSIDVLCVta----sIETLCVIAVDRYFAITspfkyq-slltknKARVIILMVWIVSGLTSFLPiqmhwyrathqeai 159 human
4GRV_A    112 GYYFLRDACTya----tALNVASLSVARYLAIChpfkak-tlmsrsRTKKFISAIWLASALLAIPMlftmglqnrsadgt 186
P23275     99 TQLYVFLWLGat----eCILLVVMAFDRYVAVCrplhym-tvmnprLCWGLAAISWLGGLGNSVIQstftlqlpfcghrk 173 house mouse
O95800    120 TFHLTSSGFIim----sLKTVAVIALHRLRMVLgkqpnr--tasfpCTVLLTLLLWATSFTLATLAtlktskshlcl--- 190 human
NP_608986 146 VIHYVQVMPVsa----sTISFFMLSLDRYATVKhprlaq-lrqrryLHVSLALLSWLASAAISTPFlfaykiiaksmvvk 220 fruit fly
EDO26227   95 MQAYTAYTCYaa----tLVTMSATSINRYTMLCapvryr-klftrkKMAIWISVVWIIAFLFGIPPlpwlswgdyvfd-- 167 starlet sea anemone
EDO48607  145 MVASLQSAFVll----nLFDMTLMMIDRYFVIQwgmryk-vwstvdKALWAVLGTWLLTIIIMIPWflylyevdlgdap- 218 starlet sea anemone
EEN58549  375 GVFFIIDTVYltmaqfsINIIAPISIDRYWYICspfkys-dtmtsaRIALLIGLSFLLAMVTMVHPllegennyfhp--- 450 Florida lancelet
EEN46533  128 ALATIGISNKft----sLSCMALIAFHRYMLITkprstykafftarNNVLIVLLAWLVSWTAAIPFvlgygflgml---- 199 Florida lancelet
Q6NV75     85 VFVSTFYTLTla----tCFSVTSLSYHRMWMVCwpvnyr-lsnakkQAVHTVMGIWMVSFILSALPavgwhdtserf--- 156 human
Feature 1                              #  ### ### ##                                          
2R4S_A    160 ------------ncyanetccdfftNQAYAIASSIVSFYVPLVIMVFVYSRvfqeakrqlqkidksegrfhvq------- 220 human
4GRV_A    187 h----------pgglvctpivdtatVKVVIQVNTFMSFLFPMLVISILNTViankltvmvnifemlrideglrlkiykdt 256
P23275    174 vdnf----lcevpamiklacgdtslNEAVLNGVCTFFTVVPVSVILVSYCFiaqavm----------------------- 226 house mouse
O95800    191 ---------------pmssliagkgKAILSLYVVDFTFCVAVVSVSYIMIAqtlrknaqvrkcppvitvdasrpqpfmgv 255 human
NP_608986 221 gggaanttpnpvsisctsdlganamFMSFIIFHTIAVFVLPGIGVLLNHYGvrrklcalsltaraahgelplpipilrrq 300 fruit fly
EDO26227  168 --------------sgyglcvtditNSPSLNNMLFSFLAVNIIVIAFCYVNvykairchrkrvgv--------------- 218 starlet sea anemone
EDO48607  219 ------------nviyrmvyyymigDYMTIIRTVFTALFAVMALMTWYSIRkqtrinekklsl----------------- 269 starlet sea anemone
EEN58549  451 ---------------pyiickylgpARKSRQAMINVCILVPMITMVFCYYKiwgelkrrqkrhnkis------------- 502 Florida lancelet
EEN46533  200 ---------------sigvcvawtgPVLATRAVIGTLYALPLLTMLYSYTAiyrhvrnasyn------------------ 246 Florida lancelet
Q6NV75    157 ---------------ythgcrfivaEIGLGFGVCFLLLVGGSVAMGVICTAialfqtlavqvgrqadrraftv------- 214 human
Feature 1                                                                                     
2R4S_A        --------------------------------------------------------------------------------     human
4GRV_A    257 egyytigighlltkspslnaakseldkaigrntngvitkdeaeklfnqdvdaavrgilrnaklkpvydsldavrraalin 336
P23275        --------------------------------------------------------------------------------     house mouse
O95800    256 pvqgggdpiqcampa----------------------------------------------------------------- 270 human
NP_608986 301 thmvivtgcpnaqqaacgggttaddtsngngtgtgggpmav----------------------------------spgdi 346 fruit fly
EDO26227      --------------------------------------------------------------------------------     starlet sea anemone
EDO48607      --------------------------------------------------------------------------------     starlet sea anemone
EEN58549      --------------------------------------------------------------------------------     Florida lancelet
EEN46533      --------------------------------------------------------------------------------     Florida lancelet
Q6NV75        --------------------------------------------------------------------------------     human
Feature 1                                                                                     
2R4S_A    221 -------------------------------------------nlsqveqdgrtghglrrsskfcLKEHKALKTLGIIMG 257 human
4GRV_A    337 mvfqmgetgvagftnslrmlnnkrwdeaavnlaksrwynqtpnrakrvittfrtgtwdaygsgsvQALRHGVLVARAVVI 416
P23275    227 ------------------------------------------------------------kirsvEGRRKAFNTCVSHLV 246 house mouse
O95800    271 ----------------------lyrnqnynklqhvqtrgytkspnqlvtpaasrlqlvsainlstAKDSKAVVTCVIIVL 328 human
NP_608986 347 qlhtlqprqpgsagsalepgsyrssnpispramreirahsqrqrinragrgpatpgiplpqtstlRSRRHLANMLIASAV 426 fruit fly
EDO26227  219 ----------------------------------------------------slrvpsltnshlrPEDVHTSYTIFIIIC 246 starlet sea anemone
EDO48607  270 -----------------------------------------------------hnhglhlkearrRMETHAATTVGLTVG 296 starlet sea anemone
EEN58549  503 --------------------------------------------------pvtrkrigyqispefRARMRSATMVLLIVA 532 Florida lancelet
EEN46533  247 ------------------------------------------------------pnnpsiqnqqkKNMLKVSKNLAVLAC 272 Florida lancelet
Q6NV75    215 --------------------------------------------ptivvedaqgkrrssidgsepAKTSLQTTGLVTTIV 250 human
Feature 1          #  ## ##  #               ## ###  #  ##              
2R4S_A    258 TFTLCWLPFFIVNIVHviqd--------nliRKEVYILLNWIGYVNSGFNPLIYCRSP 307 human
4GRV_A    417 AFVVCWLPYHVRRLMFcyisdeqwttflfdfYHYFYMLTNALAYASSAINPILYNLVS 474
P23275    247 VVFLFYGSAIYGYLLPaks----------snQSQGKFISLFYSVVTPMVNPLIYTLRN 294 house mouse
O95800    329 SVLVCCLPLGISLVQVvlssn------gsfiLYQFELFGFTLIFFKSGLNPFIYSRNS 380 human
NP_608986 427 IFIACWAPHVFCIFYKnfgn-------nqqcSQTSVYFSLLLGYFYSAISPVIYWALN 477 fruit fly
EDO26227  247 LYGFCFLPTFILGIVLfag---------yeiPREAKMFSTLSIATGSAANPLVYASRN 295 starlet sea anemone
EDO48607  297 AYVITCIPLIIYGVLSekasnl----fstnfLRWFGIMSNLFQFISSMCNPFIYMARC 350 starlet sea anemone
EEN58549  533 AYVVSWAPYFAAVIRSnalgde----vstitDGPWQRFAVLFSLLSTFSNPIIYAYRN 586 Florida lancelet
EEN46533  273 VFCVLVGPSCVFVASGmd------------wPPPVSSIVWIMYYANCCINSYLHIRKN 318 Florida lancelet
Q6NV75    251 FIYDCLMGFPVLVVSFsslr-------adasAPWMALCVLWCSVAQALLLPVFLWACD 301 human

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