Conserved Protein Domain Family
7tmB1_PDFR

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cd15261: 7tmB1_PDFR 
The pigment dispersing factor receptor, member of the class B seven-transmembrane G protein-coupled receptors
The pigment dispersing factor receptor (PDFR) is a G protein-coupled receptor that binds the circadian clock neuropeptide PDF, a functional ortholog of the mammalian vasoactive intestinal peptide (VIP), on the pacemaker neurons. The PDFR is implicated in regulating flight circuit development and in modulating acute flight In Drosophila melanogaster. The PDFR activation stimulates adenylate cyclase, thereby increasing cAMP levels in many different pacemakers, and the receptor signaling has been shown to regulate behavioral circadian rhythms and geotaxis in Drosophila. The PDFR belongs to the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. . These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. They play key roles in hormone homeostasis in mammals and are promising drug targets in various human diseases including diabetes, osteoporosis, obesity, neurodegenerative conditions (Alzhemer's and Parkinson's), cardiovascular disease, migraine, and psychiatric disorders (anxiety, depression).
Statistics
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PSSM-Id: 320389
View PSSM: cd15261
Aligned: 8 rows
Threshold Bit Score: 429.095
Threshold Setting Gi: 316978951
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 31340529   164 ARNARKLEFVGLGLSLVSLILAISIFSYFRRLrv--------------fRNLLHLHLMIAMLMVVILRLVLYIDLiftge 229
gi 386763722  306 ARRTRTLEIVGLCLSLFALIVSLLIFCTFRSLrn--------------nRTKIHKNLFVAMVLQVIIRLTLYLDQfrrgn 371
gi 405965483   91 VVGTRTMEIIGLCVSLVSCVTSLFIFCYFRTLrc--------------hRTRIHRNLLLAIIVQVIIRLVLYIDQyiare 156
gi 254553063  140 AKGSRALEIIGLILSLVSLLLSLFIFSYFKFVdfrgpisqpsfrklrnnRTRIHKNLFAAMILQVLVRLILYADQaivrg 219
gi 321479308  133 AQATRVLELTGLTVSLISLMISLFIFTYFRSLqn--------------hRTRIHKNLFAAIGIQVIIRMTLYLDQavfvs 198
gi 195947044  113 ALRTRYLEIFGFTLSFIALSISLYIFIHFRALrn--------------hRTRIHKHLFGAMLVQVLIRLTVYIDQavvrs 178
gi 443720319  188 ARVVKIIEAVGLCTSFVSLAISIIIFCYYRTLrc--------------dRTRMHRNLFVAILIHVSIQLVQMMDAyiers 253
gi 316978951   71 ARGARNLEFVGLALSFVGLITAIIIFSVFRRLrv--------------fRNQVHLQLMLAILLTVVIRLVLYVDQiftqr 136
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                #      #                                                 
gi 31340529   230 ngphtn---saegktintmpIVCEGMFFFLEYFKTVTFCWMFLEGIYLNNQIVFgffnsePKLLPYFIAGYGIPLVHTML 306
gi 386763722  372 keaatn----tslsvientpYLCEASYVLLEYARTAMFMWMFIEGLYLHNMVTVavfqgsFPLKFFSRLGWCVPILMTTV 447
gi 405965483  157 rqshyla-atgsyiaifhtpTFCETIYTLLEYTESVQFMWMLVEGIHLHNIIAVsffsgkPNYIFYYMLGWGAPIPFTIA 235
gi 254553063  220 dstglgtglsterlgidstpILCESFYIFLEYGRSAMFMWMFIEGMYLNNLISVaffqgpPNYSAYYFIGWGIPVFMTAS 299
gi 321479308  199 emva-------aargihetpILCEWFYIVLEYARTTMFVWMFIEGLFLHNLITVmvfrpdTYHKLYLALGWGIPIILTAI 271
gi 195947044  179 sisstdd-nttmtrgidnmpYICEGSYVLLEYATSAMFLWMFMEGLYLHNVVAAnnlrerVPYQWYCVWAWGAPVVITSI 257
gi 443720319  254 tgasigg-stiaegtisstpVLCECLLTLIEYTKTVMFMWMFIEGMYLHNMLVVsvfsgkPNYLLYYIMGWGFPCVPTLA 332
gi 316978951  137 idtikp---gqvgttinsmnYLCEAFYVALEYGKTVAFAWMFIEGFYLHNIVVVtvfegePKMLKYIIAGWGIPLIHVSV 213
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                  ## # #                                                 
gi 31340529   307 WLLVVlikkd-fkverCLGSYyLEPEFWILDGPRMAELVINLFFICNVIRVLYSKVResnn---tseaGLKKSVKAAMML 382
gi 386763722  448 WARCTvmymd-tslgeCLWNYnLTPYYWILEGPRLAVILLNFCFLVNIIRVLVMKLRqsqa---sdieQTRKAVRAAIVL 523
gi 405965483  236 WVVTMldly----qnsCWFPYyFLKQYWIIEAPRVAVIGVNLFFLLNIIRVLVHKLRktrtl-epqvtKVRKAVKAAIVL 310
gi 254553063  300 WAVVMslwm----nvdCWLGYsLTPYYWILEGPRFTVIGANLLFLLNIMRILISKLReasssevqqirPLRRSVRNALFL 375
gi 321479308  272 WAAFTathq---ttsaCWLGYnLTPSYWILEGPRLTIIFINLLYLLNILRVLVTKLRnsqc---seaeQLRKSVKAAMVL 345
gi 195947044  258 WTILTalkyrgekvqtCWYGYnFTGIYWIVQGPRLIVILINFVFLLNILRVLIMKLSksar---reivKVRKAVRAALVL 334
gi 443720319  333 WAITTgilm---kgskCWFGYhFDPYFWIQEGPRAAIITINLFFLLNIIRVLVTKLQenhs---nealQVKKAVKAAIVL 406
gi 316978951  214 WLIVVivknayrktnrCLGNYyLEPEFWIMDGVRLSELLINFIFLLNIIRVLWSKVKethsv--rerqQMKKSVKAALML 291
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
Feature 1                #  #                 #   #                               
gi 31340529   383 LPLLGVPNIMQTIPFAPtrdnimvFAVWTYTASFTYMYQGLMVASIYCFTNkEVNHVLKTFYAR 446
gi 386763722  524 LPLLGITNLLHQLAPLKta---tnFAVWSYGTHFLTSFQGFFIALIYCFLNgEVRAVLLKSLAT 584
gi 405965483  311 LPLLGITNIVNLIDPPAesv--vqFGLWSYSTYFLVQAALKKHWTNYQESKsCSSLQNMKNRRS 372
gi 254553063  376 LPLLGITNAITMIPKPLers-afeFGVWSYGTNLLTSFQGFVVACIYCFFNgDVKRTLCYFWRL 438
gi 321479308  346 LPLLGITNALVMIKAPLdrs-vveFALWSYSSHFLTSFQGFFVALLYCFLNgEVRSTLAKKMRN 408
gi 195947044  335 LPLLGITNIMNMFEAPLssd-pirFAVWSYLTHFLRSFQGFFIALIYCFLNgEVKQCLSKAYTN 397
gi 443720319  407 LPLLGITNFIQMVDPQSpsv--vgFAIWSFAAHFFVPFQGFFIALIYCFLNgEVQNTLRLQWER 468
gi 316978951  292 IPLLGTPNILQTIPFNPttnnivgFAIFTYVASFFYMFQGFMVAVLYCFTNrEVVNVIKCSWER 355

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