2R4S,2VT4,2KS9,2YDO,4DKL,2LNL,3V2Y,2J4Y,4GRV,3VW7,5UNF,3EML,3OE0


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: 341313
View PSSM: cd00637
Aligned: 447 rows
Threshold Bit Score: 63.4506
Threshold Setting Gi: 74762624
Created: 6-Mar-2002
Updated: 26-Jul-2017
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 extracelllular 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: thermo-stabilized 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--------fgnf 81  human
4GRV_A        35 VTAIYLALFVVGTVGNSVTLFTLARKKSlqslqstVHYHLGSLALSDLLILLLamPVELYNFiwvhhpw------afgda 108
P79763       365 LRVLIWFINILAITGNTTVLIILISSQYkl---tvPRFLMCNLAFADLCIGIYl-LFIASVDiqtksryynyaidwqtga 440 chicken
Q8BZL4        44 LTGFLMLEIVLGLGSNLTVLVLYCMKSNlin--svSNIITMNLHVLDVIICVGciPLTIVILllsles--------ntal 113 house mouse
ELT88599      30 FVAFYFVGIILAACGNGYLVYYIIHHRRrtr-knvTALLILNLAFCDLIITLLt-PLRVADIlmprns-------dhgdt 100 Capitella sp. I...
EDV22794      21 AIVILILLAIACILGNLLSIIVIYRNKNmh---dpSGLLMANLATADLCIGLIfmTTTVVYTwkksym--------fnel 89  Trichoplax adha...
EDV22099      27 CSIILTLATLLSLIGNSLVITVIIRNRPlh---tnAGMLMANLAVADFLVGLVimFPTLIAFicqkdi--------ypri 95  Trichoplax adha...
EDV24547      32 LSCFMTLFMLMSCIGNGAVLLVLRYHHDdik--saSNYFITNLALTDFLLGVLcmPCILISClngqwv--------fgqt 101 Trichoplax adha...
XP_001630405  40 ETRLLCAIIVTAIIGNSLILTAIYRFRSlq---tkTNVFVVNLAIADISLAVLamPFTMTSSityewi--------fgdt 108 starlet sea ane...
EDO49789       6 QAVAMIAMIVVSVLANGVVCHCIIKTHSlh---tiTNSFIFNLAATDFCLSALcmPFALVSCitkqwv--------fgkt 74  starlet sea ane...
Feature 1         ###### ##  #                                            # #####                
2R4S_A        82 wCEFWTSIDVLCVtasIETLCVIAVDRYFAITspfkyqslltknKARVIILMVWIVSGLTSFLPiqmhwyrathqeai-- 159 human
4GRV_A       109 gCRGYYFLRDACTyatALNVASLSVARYLAIChpfkaktlmsrsRTKKFISAIWLASALLAIPMlftmglqnrsadgth- 187
P79763       441 gCNAAGFFTVFASelsVYTLTVITLERWHTITyamqlnrkvrlrHAVIIMVFGWMFAFTVALLPifgissymkvs----- 515 chicken
Q8BZL4       114 iCCFHEACVSFASvstAINVFAITLDRYDISVkpanr--iltmgRAVMLMTSIWIFSFFSFLIPfievnffslqsgntwa 191 house mouse
ELT88599     101 yCKIGSFFSLFLAcntYTSIVAISYERLLLICfplqskslltisKTVKVLIISWIFALISALPLpilytfivtiplsnks 180 Capitella sp. I...
EDV22794      90 sCAMRAYLITVIVtvsQFTAAYIAIDRCIYVCkplhypmwitkwKMGSLIIFTWILASLFGSIPlmqleqyglgrytyvs 169 Trichoplax adha...
EDV22099      96 aCVAQGSAITVLVgasTVTILAITADRFISIFlslrynsivttaVIIGTIAFSWLFATVASTIPllglqkyglgryefl- 174 Trichoplax adha...
EDV24547     102 lCSLTGFANSFFCinsMITLAAVSVEKYCAIAspltyhhymsksKVTCVISIIWIHSAINASLPflgwgeyvylp----- 176 Trichoplax adha...
XP_001630405 109 fCKVQGIFNSLFCeasILTLTFVSLERFIAILhplkyqqwmtprTIKIMVVYIWLQSLICATSTflfskfeflkf----- 183 starlet sea ane...
EDO49789      75 vCVVSGFLLSMLCiasILTLVLVAIDRFMAIKyplkytlyvthrACAFMLAYVWFQAAACALLPalgwgsgyvfveq--- 151 starlet sea ane...
Feature 1                              #  ### ### ##                                             
2R4S_A       160 ---------ncyanetccdfftNQAYAIASSIVSFYVPLVIMVFVYSRvfqeakrqlqkidksegrfhvq---------- 220 human
4GRV_A       188 --------pgglvctpivdtatVKVVIQVNTFMSFLFPMLVISILNTViankltvmvnifemlrideglrlkiykdtegy 259
P79763       516 -----------iclpmhietpfSQAYVIFLLVLNVLAFVIICICYICIyftvrn-------------------------- 558 chicken
Q8BZL4       192 ------nktllcvstseyytelGMYYHLLVQIPIFFFTVIVMLITYTKilqalnirigtrfstgqkkkarkkktislath 265 house mouse
ELT88599     181 f-----qfclmnvfpqscdnpgGTAYFMFLFLMYYLIPMIVISICYSKifhtlycgdsll-------------------- 235 Capitella sp. I...
EDV22794     170 ymyscwldikkfqqngsillllFNTFIGLLLIVSICYIIILYKAKKVHttiqpfrrqfni-------------------- 229 Trichoplax adha...
EDV22099     175 --------hgmsycwldplqvqQNNVIISIIGFYVVLEIFIITTCYLVifiyarqsvrkv-------------------- 226 Trichoplax adha...
EDV24547     177 -----------fetictvawwsFPNYVGFIVGINFGLPTVIMSCTYFLilkiarkhsrr--------------------- 224 Trichoplax adha...
XP_001630405 184 ------------ehictvdwsySIGYTFFFVVTFFFLPFAAMAVCYFVilrkaleqrrkiasit---------------- 235 starlet sea ane...
EDO49789     152 ---------esicrpefgtpskDNGFTSFLFVSSFVIPFSILISIYLSilwtarkqfrqvhhakihlenagttdn----- 217 starlet sea ane...
Feature 1                                                                                        
2R4S_A           -------------------------------------------------------------------------------- human
4GRV_A       260 ytigighlltkspslnaakseldkaigrntngvitkdeaeklfnqdvdaavrgilrnaklkpvydsldavrraalinmvf 339
P79763           -------------------------------------------------------------------------------- chicken
Q8BZL4       266 ettd---------------------------------------------------------------------------- 269 house mouse
ELT88599         -------------------------------------------------------------------------------- Capitella sp. I...
EDV22794         -------------------------------------------------------------------------------- Trichoplax adha...
EDV22099         -------------------------------------------------------------------------------- Trichoplax adha...
EDV24547         -------------------------------------------------------------------------------- Trichoplax adha...
XP_001630405     -------------------------------------------------------------------------------- starlet sea ane...
EDO49789         -------------------------------------------------------------------------------- starlet sea ane...
Feature 1                                                                                        
2R4S_A       221 ----------------------------------------nlsqveqdgrtghglrrsskfcLKEHKALKTLGIIMGTFT 260 human
4GRV_A       340 qmgetgvagftnslrmlnnkrwdeaavnlaksrwynqtpnrakrvittfrtgtwdaygsgsvQALRHGVLVARAVVIAFV 419
P79763       559 --------------------------------------------------------pnvissNSDTKIAKRMAILIFTDF 582 chicken
Q8BZL4       270 ---------------------------msqssggrnvvfgvrtsvsviialrravkrhrerrERQKRVFKMSLLIISTFL 322 house mouse
ELT88599     236 ---------------------------------------------------tssdprqmkmiETRKSLAKMMLFIAVSFT 264 Capitella sp. I...
EDV22794     230 ---------------------------------------------------rqqlptrmvklSWINKPTKTSVILVGVYL 258 Trichoplax adha...
EDV22099     227 --------------------------------------------------ihlsvgdlpkgrPKITKTTKTVMIVVGVFM 256 Trichoplax adha...
EDV24547     225 ----------------------------------------------------igvstrrihyKTHIKATLMLLIVIGSFI 252 Trichoplax adha...
XP_001630405 236 -----------------------------------------------vgeirgqsneeqrktKQEHKATIMIAIVVGTFS 268 starlet sea ane...
EDO49789     218 ------------------------------------ntaamdeitsatnttrgkkmdrasrrRYRARGFKMVLMIVAVFL 261 starlet sea ane...
Feature 1          #  ## ##  #               ## ###  #  ##              
2R4S_A       261 LCWLPFFIVNIVHviqd--------nliRKEVYILLNWIGYVNSGFNPLIYCRSP 307 human
4GRV_A       420 VCWLPYHVRRLMFcyisdeqwttflfdfYHYFYMLTNALAYASSAINPILYNLVS 474
P79763       583 LCMAPISFFAISAslrv-------plitVSKSKILLVLFYPINSCANPFLYAIFT 630 chicken
Q8BZL4       323 LCWTPISVLNTTIlclg-------psdlLVKLRLCFLVMAYGTTIFHPLLYAFTR 370 house mouse
ELT88599     265 LLHGPYFFTFLFLsvgfh------vgnnAVFLLMFIEFLPLISAIINPYVYSVRT 313 Capitella sp. I Grassle & Grassle, 1976
EDV22794     259 ICAAPTAIFGITMtlnfe-----yynvsDAYYRVLLYWCMYANALANPFIFGFSH 308 Trichoplax adhaerens
EDV22099     257 FCWMPSLVNKFLIifkv--------ktlSLSVRLIFTWLTFFNSAANPIIYSIFN 303 Trichoplax adhaerens
EDV24547     253 VCWLPHLISMIYLtiye-------isplPCSFHQITTWLAMANSAFNPIIYGAMD 300 Trichoplax adhaerens
XP_001630405 269 ACWFPHAVGIFCLvsgn--------cewPDSYFIATTWLAMLNSALNSGIYGLMN 315 starlet sea anemone
EDO49789     262 VCWSPHFILIFYGslyq--------iqfPAAVKAVTTWLTFLNSSFNPFLYGFFN 308 starlet sea anemone

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