Conserved Protein Domain Family
7tmB1_PTH3R

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cd15983: 7tmB1_PTH3R 
parathyroid hormone 3 receptor, member of the class B family of seven-transmembrane G protein-coupled receptors
The parathyroid hormone 3 receptor (PTH3R), one of the three subtypes of PTH receptor family, is found in chicken and fish, but it is absent in mammals. On the other hand, the PTH1R is found in all vertebrate species, whereas PTH2R is found in mammals and fish, but not in chicken or frog. PTH1R is 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. 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. Conversely, PTH3R binds and responds to both PTH and PTHrP, but not the TIP-39. The PTH family 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: 320649
View PSSM: cd15983
Aligned: 4 rows
Threshold Bit Score: 530.265
Threshold Setting Gi: 54035181
Created: 3-Jul-2014
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 359690953 136 FDRLHLMYTIGYSISLASLIVAVCILSYFKRLHCTRNYIHVHLFTSFICRAASIFLKDAVLYsgtlgseaklreeelgae 215
gi 632982912 131 FDRLHLMYTVGYSVSLVSLLVAVFILNYFKRLHCTRNFIHTHLFASFICRAVSIFVKDAVVYsessvdeidrfrved--- 207
gi 18859291  138 FERLYLMYTIGYSISLAALLVAVSILCYFKRLHCTRNYIHIHLFTSFICRAISIFVKDAVLYavtndgeled-------- 209
gi 54035181  145 FERLRLIYTIGYSISLAALLLALCILCYFKRLHCTRNYIHIHLFASFICRAGSIFLKDAILYsgenegaaldeki----- 219
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                          #      #                                                      
gi 359690953 216 lgaelgpspgqrshlvGCKVVVTLFLYFLATNHYWILVEGLYLHSLIFMAFlsnKNYLWVLIIIGWGLPAVFVSIWASVR 295
gi 632982912 208 --lkgdlepgvrpqfvGCKVSVTVFLYFLATNHYWILVEGLYLHSLIFMAFlsdKNYLWALTLIGWGVPAVFVAVWTSVR 285
gi 18859291  210 -------gaveqrpmvGCKAAVTLFLYLLATNHYWILVEGLYLHSLIFMAFlsdKNCLWALTIIGWGIPAVFVSIWVSAR 282
gi 54035181  220 ---efglskrtglqwaGCKVTVTLFLYFLATNHYWILVEGLYLHSLIFMAFlsdRNYFWALIIIGWGLPAVFVSVWASVR 296
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                       ## # #                                                        #  
gi 359690953 296 aslaDTQCWDlsAGNMKWIYQVPILAAVVVNFFLFLNIVRVLASKLWETNtgkpDPRQQYRKLLKSTLVLMPLFGVHYVV 375
gi 632982912 286 aslaDTQCWNlsAGNLKWIYQVPILVAILVNFFLFLNIVRVLASKLWETNagklDPRQQYRKLLKSTLVLMPLFGVHYVV 365
gi 18859291  283 vslaDTQCWDisAGNLKWIYQVPILAAIVVNFFLFLNIIRVLASKLWETNtgklDPRQQYRKLLKSTMVLMPLFGVHYML 362
gi 54035181  297 vslaDTQCWDlsAGHMKWIYQTPILAATLVNFILFLNIVRVLASKLWETNnrkqDPCQQYGKLLKSTLVLMPLFGVHYVL 376
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|...
Feature 1        #                #   #                               
gi 359690953 376 FMAMPYTevsGVLWQIQMHYEMLFNSSQGFFVAFIYCFCNgEVQAEIKKAHFR 428
gi 632982912 366 FMAMPYTdvsGILWQIQMHYEMLFNSSQGFFVAFIYCFCNgEVQAEIKKAWLR 418
gi 18859291  363 FMALPYTdvtGLLWQIQMHYEMLFNSSQGFFVAFIYCFCNgEVQAEVKKAWLR 415
gi 54035181  377 FMAIPYTevtGLLWQIQMHYEMFFNSSQGFFVAIIYCFCNgEVQAEARKFWFR 429

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