4DAJ,4U16


Conserved Protein Domain Family
7tmA_mAChR_M3

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cd15299: 7tmA_mAChR_M3 
Click on image for an interactive view with Cn3D
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.
Statistics
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PSSM-Id: 320426
View PSSM: cd15299
Aligned: 6 rows
Threshold Bit Score: 389.307
Threshold Setting Gi: 301612746
Created: 4-Jul-2013
Updated: 26-Jul-2017
Structure
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Program:
Drawing:
Aligned Rows:
  next features
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.
    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                                                                                         
4DAJ_A         10 WQVVFIAFLTGFLALVTIIGNILVIVAFKVNKQlktvNNYFLLSLACADLIIGVISMNLFTTYIImnrWALGnlaCDLWL 89
gi 113125      66 WQVVFIAFLTGILALVTIIGNILVIVSFKVNKQlktvNNYFLLSLACADLIIGVISMNLFTTYIImnrWALGnlaCDLWL 145
gi 1351855    114 WQVVLIAFLTGIIALVTIIGNILVIVSFKVNKQlktvNNYFLLSLACADLIIGVISMNLFTTYIImghWALGnlaCDLWL 193
gi 47218153     9 WQVVLIVLLTGMLSLVTIIGNILVVVSFKVNRQlktvNNYFLLSLAVADLIIGVISMNLYTAYIVmgsWAMGiwaCDLWL 88
gi 301612746   70 WQVFLIASFSGIIALVTVIGNILVILAFKVNKQlktvNNYFLLSLACADLIIGVISMNLFTTYIImdhWIMGslaCDLWL 149
4U16_A         10 WQVVFIAFLTGFLALVTIIGNILVIVAFKVNKQlktvNNYFLLSLACADLIIGVISMNLFTTYIImnrWALGnlaCDLWL 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1           ##  ##                                              #                         
4DAJ_A         90 SIDYVASNASVMNLLVISFDRYFSITRPltYRAKRtTKRAGVMIGLAWVISFVLWAPAILFWqyfvgkrtvppgECFIQf 169
gi 113125     146 AIDYVASNASVMNLLVISFDRYFSITRPltYRAKRtTKRAGVMIGLAWVISFVLWAPAILFWqyfvgkrtvppgECFIQf 225
gi 1351855    194 SIDYVASNASVMNLLVISFDRYFSITRPltYRAKRtTKRAGVMIGLAWIISFVLWAPAILFWqyfvgkrtvpldECFIQf 273
gi 47218153    89 AIDYVASNASVMNLLVISFDRYLSVTRPltYRAKRtTKRAGIMIGLAWFVSLVLWAPAILLWqyiegkrtvpadQCYIPf 168
gi 301612746  150 MIDYVASNASVMNLLVISFDRYFSITRPltYRTKRtTKRAGIMIGLAWIISFILWAPAILFWqyfvgkrtvpsdECFIQf 229
4U16_A         90 SIDYVASNASVMNLLVISFDRYFSITRPltYRAKRtTKRAGVMIGLAWVISFVLWAPAILFWqyfvgkrtvppgECFIQf 169
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1               #   #  ##                                                                 
4DAJ_A        170 lsEPTITFGTAIAAFYMPVTIMTILYWRIYKETekmnifemlrideglrlkiykdtegyytigighlltkspslnaakse 249
gi 113125     226 lsEPTITFGTAIAAFYMPVTIMTILYWRIYKETekrtkelaglqasgteaetenfvhptgssrscssyelqqqsmkrsnr 305
gi 1351855    274 lsEPIITFGTAIAAFYLPVTIMSILYWRIYKETekrtkelaglqasgseaetarfvhqtgssrslssyelqrqstkrssr 353
gi 47218153   169 leQPIITFCTAIAAFYLPVSIMSVLYWRIYRETqnrsrelaglqgsggrggmgdasekarflhqtgssrscssyeltrls 248
gi 301612746  230 ftEPIITFGTAIAAFYLPVSIMTILYWRIYKETekrtkelaglqasggklevpglshrtgnakgnsnykiqrnikfssrt 309
4U16_A        170 lsEPTITFGTAIAAFYMPVTIMTILYWRIYKETekmnifemlridegggsggdeaeklfnqdvdaavrgilrnaklkpvy 249
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                         
4DAJ_A        250 ldkaigrntngvitkdeaeklfnqdvdaavrgilr--------------------------------------------- 284
gi 113125     306 rkygrchfwfttkswkpsseqmdqdhsssdswnnndaaaslensassdeedigsetraiysivlkl-------------- 371
gi 1351855    354 rkyrrchfwltmkswepntdqgdqehsssdswnnndaaaslensassdeeditaetraiysivlklp------------- 420
gi 47218153   249 qrksmcqefvghlpcwprvrswrpgstrhrdgdldqsssdswnnndtaasldqfgssdeedcggremisqshaifsivls 328
gi 301612746  310 ryswctfrfkpkmcksdkkqieqdqssseswnhndanasldnsgtsdeedapenpraiysi------------------- 370
4U16_A        250 dsldavrraalinm------------------------------------------------------------------ 263
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                         
4DAJ_A        285 ----------------------------------------------------naklkpvydsldavrraalinmvfqmge 312
gi 113125     372 ----------------------pghstilnstklpssdnlqvpeeelgmvdlerkadklqaqksvddggsfpksfsklpi 429
gi 1351855    421 ---------------------ghsailnstklpssedlnesadelqksdtdsqekkpkklqppksiqdggsfqksfsklp 479
gi 47218153   329 lpgikaavnsqltscedldaaseedplrglgydgerlsalannssagatseganssrssyhqrfcsakiqsmptiqassr 408
gi 301612746  371 ---------------------------vlklpghnsvlsktksqssnqgntskgmqksgpqpkelrfknlnsqrnlqnkd 423
4U16_A        264 --------------------------------------------------------------------------vfqmge 269
                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                   #  ## 
4DAJ_A        313 tgvagftnslrmlqqkrwdeaavnlaksrwynqtpnrakrvittfrtgtwdaylIKEKKAAQTLSAILLAFIITWTPYNI 392
gi 113125     430 qlesavdtaktsdvnssvgkstatlplsfkeatlakrfalktrsqitkrkrmslVKEKKAAQTLSAILLAFIITWTPYNI 509
gi 1351855    480 iqpgsaetatasdgissvtktsaalplsfkeatlakkfalktrsqitkrkrmslIKEKKAAQTLSAILFAFIITWTPYNI 559
gi 47218153   409 rspteptaaagaaededagaksssvpmsfkeaamakrfasrartqitkrkrmslVKEKKAAKTLSAILLAFIITWTPYNI 488
gi 301612746  424 esisvslspqtdhsmntsskttaplpisfkeialakrfaaktrnqitkrkrmslIKEKKAAQTLSAILLAFIITWAPYNI 503
4U16_A        270 tgvagftnslrmlqqkrwdeaavnlaksrwynqtpnrakrvittfrtgtwdaylIKEKKAAQTLSAILLAFIITWTPYNI 349
                         490       500       510       520       530
                  ....*....|....*....|....*....|....*....|....*....|....*
Feature 1                             #  #                               
4DAJ_A        393 MVLVNtfcdsciPKTYWNLGYWLCYINSTVNPVCYALCNktFRTTFKTLLLCQCD 447
gi 113125     510 MVLVNtfcdsciPKTFWNLGYWLCYINSTVNPVCYALCNktFRTTFKMLLLCQCD 564
gi 1351855    560 MVLVNtfc-dcvPKTVWNLGYWLCYINSTVNPVCYALCNkmFRNTFKMLLLCQCD 613
gi 47218153   489 MVLINtfckpciPDTLWAVGYWLCYVNSTVNPMCYALCNktFRTTFKMILLCRWD 543
gi 301612746  504 MVLVNtfcesciPRIYWNLGYWLCYINSTINPICYALCNktFRTTFKILLLCQCD 558
4U16_A        350 MVLVNtfcdsciPKTYWNLGYWLCYINSTVNPVCYALCNktFRTTFKTLLLCQCD 404

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