3UON


Conserved Protein Domain Family
7tmA_mAChR_M2

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cd15297: 7tmA_mAChR_M2 
Click on image for an interactive view with Cn3D
muscarinic acetylcholine receptor subtype M2, member of the class A family of seven-transmembrane G protein-coupled receptors
Muscarinic acetylcholine receptors (mAChRs) regulate the activity of many fundamental central and peripheral functions. The mAChR family consists of 5 subtypes M1-M5, which can be further divided into two major groups according to their G-protein coupling preference. The M1, M3 and M5 receptors selectively interact with G proteins of the G(q/11) family, whereas the M2 and M4 receptors preferentially link to the G(i/o) types of G proteins. Activation of M2 receptor causes a decrease in cAMP production, generally leading to inhibitory-type effects. This causes an outward current of potassium in the heart, resulting in a decreased heart rate. 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.
Statistics
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PSSM-Id: 320424
View PSSM: cd15297
Aligned: 7 rows
Threshold Bit Score: 450.572
Threshold Setting Gi: 374414662
Created: 4-Jul-2013
Updated: 26-Jul-2017
Structure
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Program:
Drawing:
Aligned Rows:
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Conserved site includes 17 residues -Click on image for an interactive view with Cn3D
Feature 1:ligand binding site [chemical binding site]
Evidence:
  • Structure:3UON: Human M2 muscarinic acetylcholine bound an antagonist (3-quinuclidinyl-benzilate), contact at 4A.
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                       #
3UON_A        24 VFIVLVAGSLSLVTIIGNILVMVSIKVNRHLQTVNNYFLFSLACADLIIGVFSMNLYTLYTViGYWPLGPVVCDLWLALD 103
gi 113122     24 VFIVLVAGSLSLVTIIGNILVMVSIKVNRHLQTVNNYFLFSLACADLIIGVFSMNLYTLYTViGYWPLGPVVCDLWLALD 103
gi 231489     27 VFIVLVAGSLSLVTIIGNILVMVSIKVNRHLQTVNNYFLFSLACADLIIGIFSMNLYTLYTViGYWPLGPVVCDLWLALD 106
gi 189537413  32 VLIVLGLSILSLITIIGNVLVMLSIKVNRNLQTVNNYFLFSLACADLFIGVFSMNLYTVYIVtGHWPLGALVCDLWLALD 111
gi 301627367  27 VFIVIVAGSLSLVTIIGNILVMVSIKVNRHLQTVNNYFLFSLACADLIIGVFSMNLYTLYTViGYWPIGPVVCDLWLALD 106
gi 190338621  32 VFIVLVAGSLSLVTVIGNILVMLSIKVNRSLQTVNNYFLFSLACADLIIGLCSMNLYTVYIViGYWPLGPVVCDLWLALD 111
gi 47219776    7 VLIVAVAGSLSLITVIGNILVMLSIKVNRNLQTVNNYFLFSLACADLIIGLCSMNLYTVYIViGHWPLGAVVCDLWLAVD 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1        #  ##                                              #                         #  
3UON_A       104 YVVSNASVMNLLIISFDRYFCVTKPltYPVKRtTKMAGMMIAAAWVLSFILWAPAILFWQFIVGVRTVedGECYIQFFsN 183
gi 113122    104 YVVSNASVMNLLIISFDRYFCVTKPltYPVKRtTKMAGMMIAAAWVLSFILWAPAILFWQFIVGVRTVedGECYIQFFsN 183
gi 231489    107 YVVSNASVMNLLIISFDRYFCVTKPltYPVKRtTKMAGMMIAAAWVLSFILWAPAILFWQFIVGGRTVpdKDCYIQFFsN 186
gi 189537413 112 YVVSNASVMNLLIISFDRYFCVTKPlsYPVKRtHKMAGMMIAAAWILSFILWAPAILFWQFITGSRTVpeGECYIQFFsN 191
gi 301627367 107 YVVSNASVMNLLIISFDRYFCVTKPltYPVRRtTKMAGMMIAAAWVLSFILWAPAILFWQFIVGGRTVpeGECYIQFFsN 186
gi 190338621 112 YVVSNASVMNLLIISFDRYFCVTKPlsYPVKRtTKMAGMMIAAAWVLSFILWAPAILFWQFIVGGRTVpeKECYIQFFsN 191
gi 47219776   87 YVVSNASVMNLLIISFDRYFCVTKPlsYPVRRsTKMAGLMIAAAWVLSFVLWAPAILFWQFIVGGRTVprGKCYIQFFsN 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1           #  ##  ##                                                                    
3UON_A       184 AAVTFGTAIAAFYLPVIIMTVLYWHISRASksrinifemlrideglrlkiykdtegyytigighlltkspslnaakseld 263
gi 113122    184 AAVTFGTAIAAFYLPVIIMTVLYWHISRASksrikkdkkepvanqdpvspslvqgrivkpnnnnmpssddglehnkiqng 263
gi 231489    187 PAVTFGTAIAAFYLPVIIMTVLYWQISRASksrikkgkkeaaqnqdpvspslvqgkivkpnnnniptssdglehnkvqng 266
gi 189537413 192 AVVTFGTAIAAFYLPVITMTILYWQISKASrsrvrrrdnrrvsrvsndggqaglgnernmdrkstqegeemvsrkqsasd 271
gi 301627367 187 AAVTFGTAIAAFYLPVIIMTVLYWQISRASksrikkgkkeaapnqdpispsnvqgkivkpnnnnvsanedgldhgkiqng 266
gi 190338621 192 AAVTFGTAIAAFYLPVIIMMVLYWQVSRASksrvkkdnrkpsggnldvassnqirensankptnnnltaeetdrgqtqlt 271
gi 47219776  167 PVVTFGTAIAAFYLPVAIMVHLYWRISKASrsrvkrdsrktsgtslgdgpdhsqedrcesqsnprgdrphgtggkedaeq 246
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
3UON_A       264 kaigrntngvitkdeaeklfnqdvdaavrgilrn--------------------aklkpvydsldavrraalinmvfqmg 323
gi 113122    264 kaprdpvtencvqgeekessndstsvsavasnm---------------------rddeitqdentvstslghskdenskq 322
gi 231489    267 kttgesvmencvqgeekdssndstsvsvvpsn------------------------tkedeaakdasqisasqdhlkven 322
gi 189537413 272 tttgeerdsendsisgsvlassnqrdde-------------------------------avsistngdirarqnqsasla 320
gi 301627367 267 kvtsnsgiencvqaegeekeisndstsvsvvntk--------------------degaakdvpqasgsqanpktensklt 326
gi 190338621 272 ddtinqhdaklqngkapstasgeaeeagqancipaeekessndstsgsgavtnqkeeaappssaaandsqtstrhrakag 351
gi 47219776  247 qqnggapcrnnsrgqgdst-------------------------------------------------rdsvhpftsedt 277
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                     #  
3UON_A       324 etgvagftnslrmlqqkrwdeaavnlaksrwynqtpnrakrvittfrtgtwdaypppSREKKVTRTILAILLAFIITWAP 403
gi 113122    323 tcirigtktpksdsctptnttvevvgssgqngdekqnivarkivkmtkqpakkkpppSREKKVTRTILAILLAFIITWAP 402
gi 231489    323 skltcirivtksqkgdccaptnttveivgtngdekqnsvarkivkmtkqpakkkpppSREKKVTRTILAILLAFIITWTP 402
gi 189537413 321 teswvrftcfktasqkdlqntykvnsesqgmtngkerlslvsqkiisphsqkrksssSREKKVTRTIMAILVAFATTWTP 400
gi 301627367 327 cirivtkspkgdcsnatgttveivpgangrngedkqnivarkivkmtkqppkkklppSREKKVTRTILAILLAFIITWTP 406
gi 190338621 352 gskltcikiitkspkgdcyapsnatveivpaverqnhvarkivkmtkqppkkkkapsSREKKVTRTIMAILVAFVATWTP 431
gi 47219776  278 tvtvaspkgpdagtktapthppspghsaadrqslvtrtlfkvtkqnavakwrrkgvsSREKKVTRTIMAILVAFVVTWTP 357
                        410       420       430       440
                 ....*....|....*....|....*....|....*....|....*....
Feature 1        ##                     #  ##                     
3UON_A       404 YNVMVLINTFCapCIPNTVWTIGYWLCYINSTINPACYALCNatFKKTF 452
gi 113122    403 YNVMVLINTFCapCIPNTVWTIGYWLCYINSTINPACYALCNatFKKTF 451
gi 231489    403 YNVMVLINSFCasCIPGTVWTIGYWLCYINSTINPACYALCNatFKKTF 451
gi 189537413 401 YNVMVLINTFCsdCIPNTVWIFGYWLCYINSTVNPACYALCNvtFKNTF 449
gi 301627367 407 YNVMVLINTFCavCVPNTVWTIGYWLCYINSTINPACYALCNttFKKTF 455
gi 190338621 432 YNVMVLINTFCssCIPNTVWTIGYWLCYINSTINPACYALCNitFKKTF 480
gi 47219776  358 YNVMVLINTFCssCIPNSLWTIGYWLCYINSTINPACYALCNasFKNTF 406

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