Conserved Protein Domain Family
7tmB3_Methuselah-like

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cd15039: 7tmB3_Methuselah-like 
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G protein-coupled receptors
The subfamily B3 of class B GPCRs consists of Methuselah (Mth) and its closely related proteins found in bilateria. Mth was originally identified in Drosophila as a GPCR affecting stress resistance and aging. In addition to the seven transmembrane helices, Mth contains an N-terminal extracellular domain involved in ligand binding, and a third intracellular loop (IC3) required for the specificity of G-protein coupling. Drosophila Mth mutants showed an increase in average lifespan by 35% and greater resistance to a variety of stress factors, including starvation, high temperature, and paraquat-induced oxidative toxicity. Moreover, mutations in two endogenous peptide ligands of Methuselah, Stunted A and B, showed an increased in lifespan and resistance to oxidative stress induced by dietary paraquat. These results strongly suggest that the Stunted-Methuselah system plays important roles in stress response and aging.
Statistics
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PSSM-Id: 320167
View PSSM: cd15039
Aligned: 72 rows
Threshold Bit Score: 143.134
Threshold Setting Gi: 19922988
Created: 11-Nov-2013
Updated: 26-Jul-2017
Structure
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Aligned Rows:
  next features
Feature 1:putative polypeptide ligand binding pocket [polypeptide binding site]
Evidence:
  • Comment:based on mutagenesis of human glucagon receptor (GCGR), and modeling studies of GCGR and other related class B GPCRs
  • Comment:Residues in the globular N-terminal extracellular domain and the extracellular loops of the 7TM domain may also be involved in ligand binding.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1               #   #                                         #  ##  #         #      #  
gi 307176254 304 TNHQLTSKPVGLIISLPFLLATFVVYSILPElGNMHGYTLRGYVGSLFVSYTVLVVLQSISpndikksiCITLAFFIHFS 383
gi 212511471 452 GQYMGYITAVGLGVSIVFLVLHLLAFLVVPDlQNLSGKNLASLCVALLLANISFISGQRITtgt---rsCAASGIVTYYG 528
gi 556095271  84 DDVQAILSVIGITLSIIGCVLTICVYLSFKSlRNIPGKIVISLCISLILAYLTMLIGPAMRenf---agCKSFAIMMHYF 160
gi 215507015 422 AGIQDVLSTVVLLISVICLVLHVAAYALAPKlRTGPSRLLLCLAVSVLVAQASFVAGGMLFmpn--tklCAALGIVSHGG 499
gi 443702248 337 DVGLGYLTLVGSALSIFGLLLLLLAYTCLPGlRNTPGKSLMSLAVSLLLAQALYASGLNLMqpr---slCVSMAMFVHFF 413
gi 443700202 443 SSTQTIVSVIGQVISIVCLSLHLLVYSMFRKlRNLPGLNIMSLSACLLIAQLLFLFAGSVSvsy---swCFTIGVLVHYF 519
gi 443718586   3 SVIQTAVSVIGQILSIIGLVIQLTVYSILPKlRNLAGLNLMSLSASLLVAQLLFLLGSSASsvy---elCATMAAVTHFA 79
gi 215505704 331 KDIGGYFTLAGSVVSLSCLLIKMCLYFFTSRvKKLPDHLILMLSVSIFAAQLLFLFILIVEnyq---tlCVAVGLLVHYF 407
gi 321462763  31 STGQHYMSDICLAISVVCLAFHIIVHMILPKlRNLPGKNLLSLSCALFMAQLLFLTGIGLRdtvg-yrlCATLGVLTHWF 109
gi 321468422 532 LIVESYLTLCLMSVSILAMMATIVTYLIFPElRNLAGLAVMNLCLMTSGFQLCIMIGMSLSvhqk-selCVASAILVHYE 610
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
gi 307176254 384 FLASFFWLNVMCFDIWWTFGgfrslqg-svkqrekKKFIIYSIYAWGSASILTIVCAIMDfvpnvp-kefirPEFGeatC 461
gi 212511471 529 YLASFFWMLTMAFDIWRTLKiatfelr-vssgkqwKKFIVYSIWSWMAPLILMIAAVVTDispsgtvnvyirPFFGvhsC 607
gi 556095271 161 FLVAFFWMNVMAIDVWYTFAyhqagg----ssersTRFRFYVLYVFIMASIPVILSTILNeteia---ddfsPHYGegiC 233
gi 215507015 500 HLAAFFWMNAMAVDIQRTFRagirgs---sragswRSFMGYSLYAWLGPVLLVASASLLDhllpq---splsPAYGrpsC 573
gi 443702248 414 FLSQFCWMNVLAFDVWRSFRmhniglh-srlrtrsRHFVFYCLYAWLLPAVVVLISFLLDlfqa-----sirPAYGqsfC 487
gi 443700202 520 FLASFLWMNVMAFDICRTFVkfskps---lrddysSKFIRYCAYCILVALVIVLSAIVANftlgd---slyrPGYGegiC 593
gi 443718586  80 FLASFSWMHVMAFDIWKTFAkssqpn---sldnstKKYFRYSLYGWGVPLLITTTAITVNfsvae--daayrPAYGemiC 154
gi 215505704 408 FLASFFWTNALAFDLWRSFVsvvrtr----ktnrgKTLCAFNAYCWTMPFLVVCAAGGADfllpr---hsfsPRYGqgiC 480
gi 321462763 110 YLAAFFWMNVMGFDICRTFTgslirhrgmqgrgqrCTFIFYSLYAWGFPTLVVSLGIMLDlthlm---ddyaPEYGtrlC 186
gi 321468422 611 GLASIFWTNVMAIDLFLTLGrwsaa-----prkpsKILPRYSLYAYGLPLAIVSVAVAINfcdct---gefeVEYGklfC 682
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1               ## # #                                                              #  # 
gi 307176254 462 WFntDGAKALYFYGPMSITVICNICLFISTALKILRHKKdtdhhlkg--sesrrhdDNKQWFNLYLKLFIVMGINWSMEI 539
gi 212511471 608 WFghRQALLIFFAAPFAVIMIANIGFFASSAHMIFSTTSttry---------tasgSTQRDFRLYIRLALVMGLTWLTGL 678
gi 556095271 234 WFtrRNALLVFFGLPSLLVLIANVILFLIAANTIYSAQKnsvr---------llgkEDKSMLSIYVRLTIVMGVAYLFGF 304
gi 215507015 574 WLnrPLSLAAFFGAPVLLLLLTNLVLFALTAHSIQRTEQqtkvah-----rqsrrlGDQVRFVLYVKLAVMFGLTWVFGF 648
gi 443702248 488 WLgsRRGLLVLFASPISIMLIFNCGLFSLTARSLCIAGEdsdll-------nlsrrEHRRRLLLYVKLAVVMGLAWVFGF 560
gi 443700202 594 WIknRKALLAFFAAPVAVIVTSNLVYFFITLWSIQKSMEaskma-------agnkkGERDRFWLYVKLSTIMGLTWVFGF 666
gi 443718586 155 WIrsRIGLAIFFATPVAAVLVFNIVFYTLTVVSIYKITKmargv--------tkpkSDQRQLWLYVKLTCIMGLTWIFGF 226
gi 215505704 481 WIsnRMALLVFFAAPIASIIFSNMALFAMSVVRISGTMSrtdq---------arhrASKGRLLIYFKLALVMGMTWTFGF 551
gi 321462763 187 WIsnKTGLGFLFMVPVAVLLLENMILFSLTVFSILKQRRaarfavdkkqsyrkageSKSIRFILYIKLGLIMGMGWIFGF 266
gi 321468422 683 WIsnPTANMVFFGLPLALALVANIVLFVRTVAIIYSSSAcqgkq-------csrrqRALCQLKLYARMSTVMGFAWIFAF 755
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|
Feature 1                       #   #                              
gi 307176254 540 VSWLFkn---ePKYLWYLTDLTNTLQGLIIFIIFVCKK-KVKRLLLKRFG 585
gi 212511471 679 FAGYLd-----IDALWYSFIALNTLQGLFIFLAFTCND-KVIRTIKELIC 722
gi 556095271 305 LVPLYn-----HPAILYIFIILNTLQGLFIFVSFVCTR-KVLGLIRERAN 348
gi 215507015 649 AAAISg-----ISFLWFPFIVLCGLHGAFIFLAFTFKK-SVANMVLETLK 692
gi 443702248 561 LATAFd-----SKILWYIFTALNTFQGLFICISFVFTQ-KVLRLLRKKFT 604
gi 443700202 667 VAAIFd-----VEVLWYLFIIFNSLQGAMICFAFVMTK-QVLSLLRGKFS 710
gi 443718586 227 VAAAFd-----LEVLWYLFIVVNSLQGAFICVAFVCTR-NVVKLLREKFS 270
gi 215505704 552 VAPFAn-----IQALWYVFVILNSLQGAFVLFAFTKLEvRANLETFATWL 596
gi 321462763 267 IAALAk-----IPALWYPFIFFNALQGAFIFVAFCCKR-KIYFMLYQWAT 310
gi 321468422 756 IAACFdpsstaGMIFTFVYVILNSMGGLFIFVAFTCNR-RVYLLYRGWWA 804

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