5DSG


Conserved Protein Domain Family
7tmA_mAChR_M4

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cd15298: 7tmA_mAChR_M4 
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muscarinic acetylcholine receptor subtype M4, 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 G(i/o) types of G proteins. The M4 receptor is mainly found in the CNS and function as an inhibitory autoreceptor regulating acetycholine release. 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: 341344
Aligned: 17 rows
Threshold Bit Score: 422.891
Created: 4-Jul-2013
Updated: 25-Oct-2021
Structure
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Program:
Drawing:
Aligned Rows:
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Conserved site includes 16 residues -Click on image for an interactive view with Cn3D
Feature 1:ligand binding site [chemical binding site]
Evidence:
  • Structure:5DSG: Human M4 muscarinic acetylcholine receptor binds an inverse agonist (Tiotropium); contacts at 4A

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                                                       #
5DSG_A        14 VFIATVTGSLSLVTVVGNILVMLSIKVNRQLQtvNNYFLFSLACADLIIGAFSMNLYTVYIIKGYWPLGaVVCDLWLALD 93 
XP_002200150  43 VFIATVTGSLSLVTVVGNILVMLSIKVNRQLQtvNNYFLFSLACADLIIGVFSMNLYTVYIIKGYWPLGaVVCDLWLALD 122 zebra finch
P17200        43 VFIATVTGSLSLVTVVGNILVMLSIKVNRQLQtvNNYFLFSLACADLIIGVFSMNLYTVYIIKGYWPLGaVVCDLWLALD 122 chicken
P08485        32 VFIATVTGSLSLVTVVGNILVMLSIKVNRQLQtvNNYFLFSLGCADLIIGAFSMNLYTLYIIKGYWPLGaVVCDLWLALD 111 Norway rat
P30544        34 IFIATVTGSLSLVTVVGNILVMLSIKVNRQLQtvNNYFLFSLACADLIIGVFSMNLYSLYIIKGYWPLGpIVCDLWLALD 113 African clawed ...
P32211        32 VFIATVTGSLSLVTVVGNILVMLSIKVNRQLQtvNNYFLFSLACADLIIGAFSMNLYTLYIIKGYWPLGaVVCDLWLALD 111 house mouse
NP_113735     32 VFIATVTGSLSLVTVVGNILVMLSIKVNRQLQtvNNYFLFSLACADLIIGAFSMNLYTLYIIKGYWPLGaVVCDLWLALD 111 Norway rat
AAI54721      28 IFIATVTGSLSLVTVVGNILVMLSIKVNRQLQtvNNYFLFSLACADLIIGVFSMNLYSLYIIKGYWPLGpIVCDLWLALD 107 western clawed ...
XP_002755204  33 VFIATVTGSLSLVTVVGNILVMLSIKVNRQLQtvNNYFLFSLACADLIIGAFSMNLYTVYIIKGYWPLGaVVCDLWLALD 112 white-tufted-ea...
XP_003122876  32 VFIATVTGSLSLVTVVGNILVMLSIKVNRQLQtvNNYFLFSLACADLIIGAFSMNLYTVYIIKGYWPLGaVVCDLWLALD 111 pig
Feature 1        #  ##                                              #                            
5DSG_A        94 YVVSNASVMNLLIISFDRYFCVTKPltYPARRtTKMAGLMIAAAWVLSFVLWAPAILFWQFVVGKRTVPDNQCFIQflSN 173
XP_002200150 123 YVVSNASVMNLLIISFDRYFCVTKPltYPARRtTKMAGLMIAAAWILSFILWAPAILFWQFIVGKRTVPERECYIQflSN 202 zebra finch
P17200       123 YVVSNASVMNLLIISFDRYFCVTKPltYPARRtTKMAGLMIAAAWILSFILWAPAILFWQFIVGKRTVHERECYIQflSN 202 chicken
P08485       112 YVVSNASVMNLLIISFDRYFCVTKPltYPARRtTKMAGLMIAAAWVLSFVLWAPAILFWQFVVGKRTVPDNQCFIQflSN 191 Norway rat
P30544       114 YVVSNASVMNLLIISLERXFCVTKPltYPARRtTKMAGLMIAAAWLLSFELWAPAILFWQFIVGQRTVPSGECYIQflSN 193 African clawed ...
P32211       112 YVVSNASVMNLLIISFDRYFCVTKPltYPARRtTKMAGLMIAAAWVLSFVLWAPAILFWQFVVGKRTVPDNQCFIQflSN 191 house mouse
NP_113735    112 YVVSNASVMNLLIISFDRYFCVTKPltYPARRtTKMAGLMIAAAWVLSFVLWAPAILFWQFVVGKRTVPDNQCFIQflSN 191 Norway rat
AAI54721     108 YVVSNASVMNLLIISFDRYFCVTKPltYPARRtTKMAGLMIAAAWLLSFVLWAPAILFWQFIVGERTVASGECYIQflSN 187 western clawed ...
XP_002755204 113 YVVSNASVMNLLIISFDRYFCVTKPltYPARRtTKMAGLMIAAAWVLSFVLWAPAILFWQFVVGKRTVPDNQCFIQflSN 192 white-tufted-ea...
XP_003122876 112 YVVSNASVMNLLIISFDRYFCVTKPltYPARRtTKMAGLMIAAAWVLSFVLWAPAILFWQFVVGKRTVPDNQCFIQflSN 191 pig
Feature 1           #  ##  ##                                                                    
5DSG_A       174 PAVTFGTAIAAFYLPVVIMTVLYIHISLASrsrvnifemlridegggsggdeaeklfnqdvdaavrgilrnaklkpvyds 253
XP_002200150 203 PAVTFGTAIAAFYLPVVIMTVLYIHISLASrsrvrrhkpesrkerkakslrflkgpvvkqnnnnspkravevkeevrngk 282 zebra finch
P17200       203 PAVTFGTAIAAFYLPVVIMTVLYIHISLASrsrvrrhkpesrkerkgkslsffkappvkqnnnnspkravevkeevrngk 282 chicken
P08485       192 PAVTFGTAIAAFYLPVVIMTVLYIHISLASrsrvhkhrpegpkekkaktlaflksplmkpsikkpppggasreelrngkl 271 Norway rat
P30544       194 PAVTFGTAIAAFYLPVVIMTILYIHISLASrsrvrrhcpetrqekkkpissmksllikqtknipkqdagdkvvekkngvs 273 African clawed ...
P32211       192 PAVTFGTAIAAFYLPVVIMTVLYIHISLASrsrvhkhrpegpkekkaktlaflksplmkpsikkpppggasreelrngkl 271 house mouse
NP_113735    192 PAVTFGTAIAAFYLPVVIMTVLYIHISLASrsrvhkhrpegpkekkaktlaflksplmkpsikkpppggasreelrngkl 271 Norway rat
AAI54721     188 PVVTFGTAIAAFYLPVVIMTILYIHISLASrsrvrrhctetrqekkkpissmksplikqtknlpkqdpgdeavkkengvr 267 western clawed ...
XP_002755204 193 PAVTFGTAIAAFYLPVVIMTVLYIHISLASrsrvhkhrpegpkekkaktlaflksplmkhsvkkpppreaareelrngkl 272 white-tufted-ea...
XP_003122876 192 PAVTFGTAIAAFYLPVVIMTVLYVHISLASrsrvhkhrpegpkekkakplaflksplmkqsvkkpppgeaaargelrngk 271 pig
Feature 1                                                                                        
5DSG_A       254 ldavrraalinm--------------------------------------------------vfqmgetgvagftnslrm 283
XP_002200150 283 vddqpsaqteatghqeeketsnesstvsmtqttkd-----kptaevlpagqgqspakprvnptskwskikivtkqtgtec 357 zebra finch
P17200       283 vddqpsaqteatgqqeeketsnesstvsmtqttkdk---ptteilpagqgqspahprvnptskwskikivtkqtgtesvt 359 chicken
P08485       272 eeapppalpppprpvpdkdtsnesssgsatqntke----rpptelstaeattpalpaptlqprtlnpaskwskiqivtkq 347 Norway rat
P30544       274 ngkieksmtnlqtaeeketsnesssaslshnppekqplseassgvvlaptqsmpplpakantaskwskikivtkqtgnec 353 African clawed ...
P32211       272 eeapppalpppprpvadkdtsnesssgsatqntker---pptelstteaattpalpaptlqprtlnpaskwskiqivtkq 348 house mouse
NP_113735    272 eeapppalpppprpvpdkdtsnesssgsatqntke----rpptelstaeattpalpaptlqprtlnpaskwskiqivtkq 347 Norway rat
AAI54721     268 ngkieksmtnlqtaeeketsnesssaslshnppekqpvsdassgvvlaptqnmpplpskvnvaskwskikivtkqtgnec 347 western clawed ...
XP_002755204 273 eeapppvlpppprpmadkdtsnesssgsatqntke----rpatelstteattpampapplqpralnpaskwskiqivtkq 348 white-tufted-ea...
XP_003122876 272 leeapppvlpppprpvadkdtsnesssgsatqntke---rpptelstteattpaapapplqprtlnpaskwskiqivtkq 348 pig
Feature 1                                                                        #  ##           
5DSG_A       284 lqqkrwdeaavnlaksrwynqtpnrakrvittfrtgtwdayqmaARERKVTRTIFAILLAFILTWTPYNVMVLVNTFCqs 363
XP_002200150 358 vtaieivpaksgasnslansrpvnvarkfasiarsqvrkkrqmaAREKKVTRTIFAILLAFILTWTPYNVMVLINTFCet 437 zebra finch
P17200       360 aieivpakagasdhnslsnsrpanvarkfasiarsqvrkkrqmaAREKKVTRTIFAILLAFILTWTPYNVMVLINTFCet 439 chicken
P08485       348 tgnecvtaieivpatpagmrpaanvarkfasiarnqvrkkrqmaARERKVTRTIFAILLAFILTWTPYNVMVLVNTFCqs 427 Norway rat
P30544       354 vtaieivpecaiplpeqannrpvnvarkfasiarnqvrkkrqmaAREKKVTRTIFAILLAFIITWTPYNVMVLINTFCqt 433 African clawed ...
P32211       349 tgsecvtaieivpatpagmrpaanvarkfasiarnqvrkkrqmaARERKVTRTIFAILLAFILTWTPYNVMVLVNTFCqs 428 house mouse
NP_113735    348 tgnecvtaieivpatpagmrpaanvarkfasiarnqvrkkrqmaARERKVTRTIFAILLAFILTWTPYNVMVLVNTFCqs 427 Norway rat
AAI54721     348 vtaieivpecaiplpqqannrpgnvarkfasiarnqvrkkrqmaAREKKVTRTIFAILLAFIITWTPYNVMVLINTFCqt 427 western clawed ...
XP_002755204 349 tgnecvtaieivpatpasmrpaanvarkfasiasnqvrkkrqmaARERKVTRTIFAILLAFILTWTPYNVMVLVNTFCqs 428 white-tufted-ea...
XP_003122876 349 tgnecvtaieivpatpagmrpaanvarkfasiarnqvrkkrqmaARERKVTRTIFAILLAFILTWTPYNVMVLVNTFCqs 428 pig
Feature 1                  #  ##                      
5DSG_A       364 CIPDTVWSIGYWLCYVNSTINPACYALCNa-tFKKTF 399
XP_002200150 438 CVPETVWSIGYWLCYVNSTINPACYALCNa-tFKKTF 473 zebra finch
P17200       440 CVPETVWSIGYWLCYVNSTINPACYALCNa-tFKKTF 475 chicken
P08485       428 CIPERVWSIGYWLCYVNSTINPACYALCNa-tFKKTF 463 Norway rat
P30544       434 CIPETIWYIGYWLCYVNSTINPACYALCNa-tFKKTF 469 African clawed frog
P32211       429 CIPERVWSIGYWLCYVNSTINPACYALCNa-tFKKTF 464 house mouse
NP_113735    428 CIPERVWSIGYWLCYVNSTINPACYALCNa-tFKKTF 463 Norway rat
AAI54721     428 CIPETVWYIGYWLCYVNSTINPACYALCNa-tFKKTF 463 western clawed frog
XP_002755204 429 CIPDTVWSIGYWLCYVNSTINPACYALCKchlLKRPS 465 white-tufted-ear marmoset
XP_003122876 429 CIPDTVWSIGYWLCYVNSTINPACYALCNa-tFKKTF 464 pig

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