Conserved Protein Domain Family
7tmB1_PTHR

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cd15265: 7tmB1_PTHR 
parathyroid hormone receptors, member of the class B family of seven-transmembrane G protein-coupled receptors
The parathyroid hormone (PTH) receptor family has three subtypes: PTH1R, PTH2R and PTH3R. PTH1R is expressed in bone and kidney and is activated by two polypeptide ligands: PTH, an endocrine hormone that regulates calcium homoeostasis and bone maintenance, and PTH-related peptide (PTHrP), a paracrine factor that regulates endochondral bone development. PTH1R couples predominantly to a G(s)-protein that in turn activates adenylate cyclase thereby producing cAMP, but it can also couple to several G protein subtypes, including G(q/11), G(i/o), and G(12/13), resulting in activation of multiple intracellular signaling pathways. PTH2R is potently activated by tuberoinfundibular peptide-39 (TIP-39), but not by PTHrP. PTH also strongly activates human PTH2R, but only weakly activates rat and zebrafish PTH2Rs, suggesting that TIP-39 is a natural ligand for PTH2R. On the other hand, PTH3R binds and responds to both PTH and PTHrP, but not the TIP-39. Moreover, the PTH3R is more closely related to the PTH1R than PTH2R. PTH1R is found in all vertebrate species, whereas PTH2R is found in mammals and fish, but not in chicken or frog. The PTH3R is found in chicken and fish, but it is absent in mammals. The PTH receptors are members of the B1 (or secretin-like) subfamily of class B GPCRs, which include receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), and calcitonin gene-related peptide. 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.
Statistics
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PSSM-Id: 320393
View PSSM: cd15265
Aligned: 16 rows
Threshold Bit Score: 396.746
Threshold Setting Gi: 229272176
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 359690951 133 FDRLYLIYTVGYSISLGSLTVAVLILGYFRRLHCTRNYIHMHLFVSFMLRAVSIFVKDAVLysgsaleemeriseedl-- 210
gi 1346906   141 FERLYVMYTVGYSISFGSLAVAILIIGYFRRLHCTRNYIHMHLFVSFMLRATSIFVKDRVVhahigvkeleslimqdd-- 218
gi 229284724 117 FEKVTKLYTVGYSFSLASLTVALAILVYFKRLHCTRNYVHMHLFVSFILRAIFVLVKDAVLysddaidvndvdstlpe-- 194
gi 198419504 127 MKSFIQLYTVGYSFSLVALVFAMIILAYFKRLHCTRNYIHMHLFASFILRAVVIFVKDRVLyygagildintpdgemtle 206
gi 260809309  77 IDNVTKIYTIGYSISLVSLFIAFIILARFKRLHCTRNYVHMHLFVSYMLRAFFILLRDAVLysydtnnstpvprn----- 151
gi 557293460 184 FERLYIMYTVGYSISFSSLAVAIFIIGYFRRLHCTRNYIHMHLFVSFMLRAVSIFIKDKVVhtrigvkeldsllmndl-- 261
gi 301615394 140 FERLYVMYTVGYSISFCSLAVAIFIIGYFRRLHCTRNYIHMHLFVSFMLRAGSIFIKDKVVhthigvkeldavlmg---- 215
gi 190339358 169 FERLHIMYTVGYAVSFSSLLVAIFIIGYFRRLHCTRNYIHMHLFVSFMLRAASIFVKDHVVhtsaglqefdavlmnnf-- 246
gi 6013158   141 FDRLYLIYTVGYSISLGSLMVATVILGYFRRLHCTRNYIHMHLFLSFMLRAISIFVKDVVLysgsalqemeritvedl-- 218
gi 417555    184 FDRLGMIYTVGYSVSLASLTVAVLILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLysgatldeaerlteeelr- 262
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                            #      #                                                    
gi 359690951 211 ---ksiteappadksqfvgCKVAVTFFLYFLATNYYWILVEGLYLHSLIFmaffseKKYLWGFTLFGWGLPAVFVTAWAS 287
gi 1346906   219 --pqnsieatsvdksqyigCKIAVVMFIYFLATNYYWILVEGLYLHNLIFvaffsdTKYLWGFILIGWGFPAAFVAAWAV 296
gi 229284724 195 --qlggplnidhgqrntwtCKLAMSLFMYFMATNYYWVLVEGLYLHNLIFisvfseKKFLRWFIAIGWGFPLTFVIPWVL 272
gi 198419504 207 alknrvdeidadrssylvgCKLVMTLFHYFVATNYYWILVEALYLHSLIFvaffsdKKYLWRFSVTGWGVPILFVVPWAI 286
gi 260809309 152 -----tvrnskiykvpqvgCKLLYTCFMYFMATNYFWILVEGLYLHNLIFvsvfseRKFFYGFIAIGWVFPLTFVVPWVV 226
gi 557293460 262 ---qsvvvapaidksqyvgCKIIVVMFIYFLATNYYWILVEGLYLHSLIFvaffsdTKYLWGFILTGWGFPAVFVMAWAV 338
gi 301615394 216 ----dlmispvldksqyvgCKIAVVMFIYFLATNYYWILVEGLYLHSLIFvaffsdTKYLWGFTLIGWGFPAVFVVIWAV 291
gi 190339358 247 ---tnavdvapvdtsqymgCKVTVLLFIYFLATNYYWILVEGLYLHSLIFmaflsdSKYLWGFTLIGWGVPAVFVAAWAV 323
gi 6013158   219 ---ksiteappanktqfigCKVAVTLFLYFLATNYYWILVEGLYLHSLIFmtffsdRKYLWGFTLIGWGVPAMFVTIWAS 295
gi 417555    263 -aiaqappppataaagyagCRVAVTFFLYFLATNYYWILVEGLYLHSLIFmaffseKKYLWGFTVFGWGLPAVFVAVWVS 341
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                            ## # #                                                      
gi 359690951 288 VRatla-dteCWDl--sAGNLKWIIQVPILAAIVVNFILFINIIRVLATKLRetnagr-cdsrqQYRKLLKSTLVLMPLF 363
gi 1346906   297 ARatla-darCWEl--sAGDIKWIYQAPILAAIGLNFILFLNTVRVLATKIWetnavg-hdtrkQYRKLAKSTLVLVLVF 372
gi 229284724 273 TNlvflycfrCWDysepTTGYLWIYRGPIVAAILINFLLFVNILRIVVQKLRmta------avgADQKLAKSTLVLIPLF 346
gi 198419504 287 VRakld-dtaCWDi--aVTEYKWIYNGPIVVANVINFLLFLNIIRVLWYKMRergpigktdnrrQYKKLAKSTLVLIPMF 363
gi 260809309 227 VRatme-dtgCWDt---DTVYKWIYKAPIVVSIVVNFLLFLNILRVLVKKLReiqqh---stssLCRKLAKSTMVLIPLF 299
gi 557293460 339 VRavla-darCWEl--sAGDIKWIYQAPILAAIGLNFILFLNTVRVLATKIWetnavg-ydtrkQYRKLAKSTLVLILVF 414
gi 301615394 292 ARatla-darCWEl--sAGDIKWIYQAPILAAIGLNFILFLNTVRVLATKIWesnavg-ydtrkQYRKLAKSTLVLILVF 367
gi 190339358 324 VRatla-darCWEl--sAGNIKWIYQVPILTAIGLNFILFVNIVRVLATKIRetnagr-ydtrkQYRKLAKSTLVLVFVF 399
gi 6013158   296 VRatla-dteCWDl--sAGNLKWIVQIPILTAIVVNFLLFLNIIRVLATKLRetnagr-cdtrqQYRKLLKSTLVLMPLF 371
gi 417555    342 VRatla-ntgCWDl--sSGNKKWIIQVPILASIVLNFILFINIVRVLATKLRetnagr-cdtrqQYRKLLKSTLVLMPLF 417
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*....
Feature 1           #  #                #   #                               
gi 359690951 364 GVHYIVFMAMPYTdvsgilWQVQMHYEMLFNSFQGFFVAIIYCFCNgEVQAEIKKSWSR 422
gi 1346906   373 GVHYIVFVCLPHSftg-lgWEIRMHCELFFNSFQGFFVSIIYCYCNgEVQAEVKKMWSR 430
gi 229284724 347 GVHYIVFVGMPDNvgg-vaYEARLYFDLFFNSFQGFFVAILYCFLNgEVRAEFQKRWER 404
gi 198419504 364 GVHAIVFIGMPDDissgtwWDIRMSFDLFFNSFQGFFVAIIYCFCNgEVQAEFRKAWER 422
gi 260809309 300 GVHYIVFVGMPDDtkg-laQEIRLYFELFFNSFQGFFVSILYCFLNgEVRAEFKRRWER 357
gi 557293460 415 GVHYIVFVCLPHTftg-lgWEIRMHCELFFNSFQGFFVSIIYCYCNgEVQTEIKKMWTR 472
gi 301615394 368 GVHYIVFVCLPHTftg-laWEIRMHCELFFNSFQGFFVSIIYCYCNgEVQTEIKKTWTR 425
gi 190339358 400 GVHYIVFVGMPHTfeg-lgWEVRMYCELFFNSFQGFFVSIIYCYCNgEVQTEIKKTWTR 457
gi 6013158   372 GVHYIVFMAMPYTevsgvlWQIQMHYEMLFNSVQGFFVAIIYCFCNgEVQAEIKKAWNR 430
gi 417555    418 GVHYIVFMATPYTevsgtlWQVQMHYEMLFNSFQGFFVAIIYCFCNgEVQAEIKKSWSR 476

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