4DAJ,4U16


Conserved Protein Domain Family
7tmA_mAChR_M3
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cd15299: 7tmA_mAChR_M3 
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muscarinic acetylcholine receptor subtype M3, 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. The M3 receptor is mainly located in smooth muscle, exocrine glands and vascular endothelium. It induces vomiting in the central nervous system and is a critical regulator of glucose homeostasis by modulating insulin secretion. Generally, M3 receptor causes contraction of smooth muscle resulting in vasoconstriction and increased glandular secretion. 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.
Links
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Statistics
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PSSM-Id: 320426
Aligned: 6 rows
Threshold Bit Score: 389.307
Created: 4-Jul-2013
Updated: 25-Oct-2021
Structure
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Program:
Drawing:
Aligned Rows:
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Conserved site includes 14 residues -Click on image for an interactive view with Cn3D
Feature 1:ligand binding site [chemical binding site]
Evidence:
  • Structure:4DAJ: Human M3 muscarinic acetylcholine receptor binds tiotropium (anticholinergic bronchodilator), contacts at 4A.
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Sequence Alignment
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Format: Row Display: Color Bits: Type Selection: 
Feature 1                                                                                         
4DAJ_A         10 WQVVFIAFLTGFLALVTIIGNILVIVAFKVNKQlktvNNYFLLSLACADLIIGVISMNLFTTYIImnrWALGnlaCDLWL 89  
P20309         66 WQVVFIAFLTGILALVTIIGNILVIVSFKVNKQlktvNNYFLLSLACADLIIGVISMNLFTTYIImnrWALGnlaCDLWL 145  human
P49578        114 WQVVLIAFLTGIIALVTIIGNILVIVSFKVNKQlktvNNYFLLSLACADLIIGVISMNLFTTYIImghWALGnlaCDLWL 193  chicken
CAG10073        9 WQVVLIVLLTGMLSLVTIIGNILVVVSFKVNRQlktvNNYFLLSLAVADLIIGVISMNLYTAYIVmgsWAMGiwaCDLWL 88   spotted green...
XP_002935876   70 WQVFLIASFSGIIALVTVIGNILVILAFKVNKQlktvNNYFLLSLACADLIIGVISMNLFTTYIImdhWIMGslaCDLWL 149  western clawe...
4U16_A         10 WQVVFIAFLTGFLALVTIIGNILVIVAFKVNKQlktvNNYFLLSLACADLIIGVISMNLFTTYIImnrWALGnlaCDLWL 89  

Feature 1           ##  ##                                              #                         
4DAJ_A         90 SIDYVASNASVMNLLVISFDRYFSITRPltYRAKRtTKRAGVMIGLAWVISFVLWAPAILFWqyfvgkrtvppgECFIQf 169 
P20309        146 AIDYVASNASVMNLLVISFDRYFSITRPltYRAKRtTKRAGVMIGLAWVISFVLWAPAILFWqyfvgkrtvppgECFIQf 225  human
P49578        194 SIDYVASNASVMNLLVISFDRYFSITRPltYRAKRtTKRAGVMIGLAWIISFVLWAPAILFWqyfvgkrtvpldECFIQf 273  chicken
CAG10073       89 AIDYVASNASVMNLLVISFDRYLSVTRPltYRAKRtTKRAGIMIGLAWFVSLVLWAPAILLWqyiegkrtvpadQCYIPf 168  spotted green...
XP_002935876  150 MIDYVASNASVMNLLVISFDRYFSITRPltYRTKRtTKRAGIMIGLAWIISFILWAPAILFWqyfvgkrtvpsdECFIQf 229  western clawe...
4U16_A         90 SIDYVASNASVMNLLVISFDRYFSITRPltYRAKRtTKRAGVMIGLAWVISFVLWAPAILFWqyfvgkrtvppgECFIQf 169 

Feature 1               #   #  ##                                                                 
4DAJ_A        170 lsEPTITFGTAIAAFYMPVTIMTILYWRIYKETekmnifemlrideglrlkiykdtegyytigighlltkspslnaakse 249 
P20309        226 lsEPTITFGTAIAAFYMPVTIMTILYWRIYKETekrtkelaglqasgteaetenfvhptgssrscssyelqqqsmkrsnr 305  human
P49578        274 lsEPIITFGTAIAAFYLPVTIMSILYWRIYKETekrtkelaglqasgseaetarfvhqtgssrslssyelqrqstkrssr 353  chicken
CAG10073      169 leQPIITFCTAIAAFYLPVSIMSVLYWRIYRETqnrsrelaglqgsggrggmgdasekarflhqtgssrscssyeltrls 248  spotted green...
XP_002935876  230 ftEPIITFGTAIAAFYLPVSIMTILYWRIYKETekrtkelaglqasggklevpglshrtgnakgnsnykiqrnikfssrt 309  western clawe...
4U16_A        170 lsEPTITFGTAIAAFYMPVTIMTILYWRIYKETekmnifemlridegggsggdeaeklfnqdvdaavrgilrnaklkpvy 249 

Feature 1                                                                                         
4DAJ_A        250 ldkaigrntngvitkdeaeklfnqdvdaavrgilr--------------------------------------------- 284 
P20309        306 rkygrchfwfttkswkpsseqmdqdhsssdswnnndaaaslensassdeedigsetraiysivlkl-------------- 371  human
P49578        354 rkyrrchfwltmkswepntdqgdqehsssdswnnndaaaslensassdeeditaetraiysivlklp------------- 420  chicken
CAG10073      249 qrksmcqefvghlpcwprvrswrpgstrhrdgdldqsssdswnnndtaasldqfgssdeedcggremisqshaifsivls 328  spotted green...
XP_002935876  310 ryswctfrfkpkmcksdkkqieqdqssseswnhndanasldnsgtsdeedapenpraiysi------------------- 370  western clawe...
4U16_A        250 dsldavrraalinm------------------------------------------------------------------ 263 

Feature 1                                                                                         
4DAJ_A        285 ----------------------------------------------------naklkpvydsldavrraalinmvfqmge 312 
P20309        372 ----------------------pghstilnstklpssdnlqvpeeelgmvdlerkadklqaqksvddggsfpksfsklpi 429  human
P49578        421 ---------------------ghsailnstklpssedlnesadelqksdtdsqekkpkklqppksiqdggsfqksfsklp 479  chicken
CAG10073      329 lpgikaavnsqltscedldaaseedplrglgydgerlsalannssagatseganssrssyhqrfcsakiqsmptiqassr 408  spotted green...
XP_002935876  371 ---------------------------vlklpghnsvlsktksqssnqgntskgmqksgpqpkelrfknlnsqrnlqnkd 423  western clawe...
4U16_A        264 --------------------------------------------------------------------------vfqmge 269 

Feature 1                                                                                   #  ## 
4DAJ_A        313 tgvagftnslrmlqqkrwdeaavnlaksrwynqtpnrakrvittfrtgtwdaylIKEKKAAQTLSAILLAFIITWTPYNI 392 
P20309        430 qlesavdtaktsdvnssvgkstatlplsfkeatlakrfalktrsqitkrkrmslVKEKKAAQTLSAILLAFIITWTPYNI 509  human
P49578        480 iqpgsaetatasdgissvtktsaalplsfkeatlakkfalktrsqitkrkrmslIKEKKAAQTLSAILFAFIITWTPYNI 559  chicken
CAG10073      409 rspteptaaagaaededagaksssvpmsfkeaamakrfasrartqitkrkrmslVKEKKAAKTLSAILLAFIITWTPYNI 488  spotted green...
XP_002935876  424 esisvslspqtdhsmntsskttaplpisfkeialakrfaaktrnqitkrkrmslIKEKKAAQTLSAILLAFIITWAPYNI 503  western clawe...
4U16_A        270 tgvagftnslrmlqqkrwdeaavnlaksrwynqtpnrakrvittfrtgtwdaylIKEKKAAQTLSAILLAFIITWTPYNI 349 

Feature 1                             #  #                               
4DAJ_A        393 MVLVNtfcdsciPKTYWNLGYWLCYINSTVNPVCYALCNktFRTTFKTLLLCQCD 447 
P20309        510 MVLVNtfcdsciPKTFWNLGYWLCYINSTVNPVCYALCNktFRTTFKMLLLCQCD 564  human
P49578        560 MVLVNtfc-dcvPKTVWNLGYWLCYINSTVNPVCYALCNkmFRNTFKMLLLCQCD 613  chicken
CAG10073      489 MVLINtfckpciPDTLWAVGYWLCYVNSTVNPMCYALCNktFRTTFKMILLCRWD 543  spotted green pufferfish
XP_002935876  504 MVLVNtfcesciPRIYWNLGYWLCYINSTINPICYALCNktFRTTFKILLLCQCD 558  western clawed frog
4U16_A        350 MVLVNtfcdsciPKTYWNLGYWLCYINSTVNPVCYALCNktFRTTFKTLLLCQCD 404

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