Conserved Protein Domain Family
7tmB1_PTH2R

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cd15982: 7tmB1_PTH2R 
parathyroid hormone 2 receptor, member of the class B family of seven-transmembrane G protein-coupled receptors
The parathyroid hormone 2 receptor (PTH2R), one of the three subtypes of PTH receptor family, is found in mammals and fish, but not in chicken or frog. PTH2R is potently activated by tuberoinfundibular peptide-39 (TIP-39) but not by PTH-related peptide (PTHrP), a paracrine factor that regulates endochondral bone development. PTH, an endocrine hormone that regulates calcium homoeostasis and bone maintenance, strongly activates human PTH2R, but only weakly activates rat and zebrafish PTH2Rs. These results suggest that TIP-39 is a natural ligand for PTH2R. Conversely, PTH1R is activated by PTH and PTHrP, but not by 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: 320648
View PSSM: cd15982
Aligned: 4 rows
Threshold Bit Score: 555.315
Threshold Setting Gi: 190339358
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 1346906   141 FERLYVMYTVGYSISFGSLAVAILIIGYFRRLHCTRNYIHMHLFVSFMLRATSIFVKDRVVHAHIGvkeleslimqddpq 220
gi 557293460 184 FERLYIMYTVGYSISFSSLAVAIFIIGYFRRLHCTRNYIHMHLFVSFMLRAVSIFIKDKVVHTRIGvkeldsllmnd-lq 262
gi 301615394 140 FERLYVMYTVGYSISFCSLAVAIFIIGYFRRLHCTRNYIHMHLFVSFMLRAGSIFIKDKVVHTHIGvkeldavlm----g 215
gi 190339358 169 FERLHIMYTVGYAVSFSSLLVAIFIIGYFRRLHCTRNYIHMHLFVSFMLRAASIFVKDHVVHTSAGlqefdavlmnn-ft 247
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                        #      #                                                        
gi 1346906   221 nsieatsvDKSQYIGCKIAVVMFIYFLATNYYWILVEGLYLHNLIFvaffsDTKYLWGFILIGWGFPAAFVAAWAVARat 300
gi 557293460 263 svvvapaiDKSQYVGCKIIVVMFIYFLATNYYWILVEGLYLHSLIFvaffsDTKYLWGFILTGWGFPAVFVMAWAVVRav 342
gi 301615394 216 dlmispvlDKSQYVGCKIAVVMFIYFLATNYYWILVEGLYLHSLIFvaffsDTKYLWGFTLIGWGFPAVFVVIWAVARat 295
gi 190339358 248 navdvapvDTSQYMGCKVTVLLFIYFLATNYYWILVEGLYLHSLIFmaflsDSKYLWGFTLIGWGVPAVFVAAWAVVRat 327
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                     ## # #                                                        #  # 
gi 1346906   301 laDARCWElsAGDIKWIYQAPILAAIGLNFILFLNTVRVLATKIWEtnavghDTRKQYRKLAKSTLVLVLVFGVHYIVFV 380
gi 557293460 343 laDARCWElsAGDIKWIYQAPILAAIGLNFILFLNTVRVLATKIWEtnavgyDTRKQYRKLAKSTLVLILVFGVHYIVFV 422
gi 301615394 296 laDARCWElsAGDIKWIYQAPILAAIGLNFILFLNTVRVLATKIWEsnavgyDTRKQYRKLAKSTLVLILVFGVHYIVFV 375
gi 190339358 328 laDARCWElsAGNIKWIYQVPILTAIGLNFILFVNIVRVLATKIREtnagryDTRKQYRKLAKSTLVLVFVFGVHYIVFV 407
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|
Feature 1                      #   #                               
gi 1346906   381 CLPHSFtglgWEIRMHCELFFNSFQGFFVSIIYCYCNgEVQAEVKKMWSR 430
gi 557293460 423 CLPHTFtglgWEIRMHCELFFNSFQGFFVSIIYCYCNgEVQTEIKKMWTR 472
gi 301615394 376 CLPHTFtglaWEIRMHCELFFNSFQGFFVSIIYCYCNgEVQTEIKKTWTR 425
gi 190339358 408 GMPHTFeglgWEVRMYCELFFNSFQGFFVSIIYCYCNgEVQTEIKKTWTR 457

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