Conserved Protein Domain Family
7tmA_TSH-R

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cd15964: 7tmA_TSH-R 
thyroid-stimulating hormone receptor (or thyrotropin receptor), member of the class A family of seven-transmembrane G protein-coupled receptors
The glycoprotein hormone receptors are seven transmembrane domain receptors with a very large extracellular N-terminal domain containing many leucine-rich repeats responsible for hormone recognition and binding. The glycoprotein hormone family includes the three gonadotropins: luteinizing hormone (LH), follicle-stimulating hormone (FSH), chorionic gonadotropin (CG), and a pituitary thyroid-stimulating hormone (TSH). The glycoprotein hormones exert their biological functions by interacting with their cognate GPCRs. Both LH and CG bind to the same receptor, the luteinizing hormone-choriogonadotropin receptor (LHCGR); FSH binds to FSH-R and TSH to TSH-R. TSH-R plays an important role thyroid physiology, and its activation stimulates the production of thyroxine (T4) and triiodothyronine (T3). Defects in TSH-R are a cause of several types of hyperthyroidism. The receptor is predominantly found on the surface of the thyroid epithelial cells and couples to the G(s)-protein and activates adenylate cyclase, thereby promoting cAMP production. TSH and cAMP stimulate thyroid cell proliferation, differentiation, and function.
Statistics
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PSSM-Id: 320630
View PSSM: cd15964
Aligned: 5 rows
Threshold Bit Score: 532.173
Threshold Setting Gi: 13365517
Created: 14-Oct-2014
Updated: 26-Jul-2017
Structure
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Aligned Rows:
  next features
Feature 1:putative peptide ligand binding pocket [polypeptide binding site]
Evidence:
  • Comment:based on the structures of some class A family members with bound ligands (peptides or chemicals), agonists, or antagonists
  • Comment:Small-molecule chemical ligands tend to bind deeper within the receptor core, compared to a peptide ligand neurotensin, which binds towards the extracelllular surface of its receptor.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                               #  ##                   #
gi 62298994  415 KFLRIVVWFVSLLALLGNVFVLLILLTSHYklnVPRFLMCNLAFADFCMGMYLLLIASVDlythseyynhaiDWQTGpGC 494
gi 302191661 414 QFLRIVVWFVNLLAIIGNVFVLFILLTSHYkltVPRFLMCNLAFADFCMGLYLLLIASVDlytrseyynhaiEWQTGpGC 493
gi 512863619 416 NFLRIVVWFVNLLAILGNVFVLFILITSHYkltVPRFLMCNLAFADFCMGIYLLLIASVDvhtrseyynyaiNWQTGpGC 495
gi 556967037 422 KFLRIIVWFVNLLAILGNIFVLLILLTSHYkltVPRFLMCNLAFADFCMGIYLLLIASVDlhtqseyynraiDWQTGpGC 501
gi 13365517  423 GFLRVSVWFVSLLAVLGNVVVLLVLLTSHYklsVSRFLMCHLAFADLCMGIYLLLIASVDlhtraeyfnhaiDWQTGpGC 502
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1        ##### ##  #                                            # #####                  
gi 62298994  495 NTAGFFTVFASELSVYTLTVITLERWYAITFAMrLDRKIrLRHACAIMVGGWVCCFLLALLPLVGissYAKVSICLPmdt 574
gi 302191661 494 NTAGFFTVFASELSVYTLTVITLERWYAITFAMrPNRKIrLRHALVIMLGGWLSCFLLALLPLVRvssYSKVSICLPmdt 573
gi 512863619 496 NAAGFFTVFASELSVYTLTMITLERWYAITFAMrLDRKIrLRHASFIMLGGWTLCFFLALLPLVGissYIKVSICLPmdt 575
gi 556967037 502 NAAGFFTVFASELSVYTLTVITLERWYAITFAMrLDRKIrLRHASAIMLGGWLFCFLLAILPLVGvssYAKVSICLPmdt 581
gi 13365517  503 GLAGFFTVFASELSVYTLTAITLERWYAITFAMrLDRKLhLHHAAAVMLGGWVFCILLALLPLVGvssYQKVSICLPmdt 582
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1           #  ### ### ##                                              #  ## ##  #       
gi 62298994  575 etpLALAYIVFVLTLNIVAFVIVCCCYVKIYITVrnpqynpgDKDTKIAKRMAVLIFTDFICMAPISFYALSAilnkpli 654
gi 302191661 574 etpVAEAYVVFVLICNIIAFVIICACYIKIYITVrnpqyksgDKDTKIAKRMAVLIFTDFLCMAPISFHALSAimnkpli 653
gi 512863619 576 eaaLSQAYIVFVLMLNIIAFIIICACYIKIYITVrnpqyksgDKDTKIAKRMAILIFTDFICMAPISFYALSAimnkpli 655
gi 556967037 582 etlLAQVYVICVLMLNIIAFIIICACYIKIYITVrnphyksgNKDTKIAKRMAILIFTDFICMAPISFYALSAilnkpli 661
gi 13365517  583 estAAQIYIMSVLVLNILAFFIICACYFKIYCTVhnphyhsgSKDTNIAKRMAVLIFTDFLCMAPISFYAISAvldrpli 662
                        250       260       270
                 ....*....|....*....|....*....|....*
Feature 1         ## ###  #  ##                     
gi 62298994  655 tVSNSKILLVLFYPLNSCANPFLYAIFTkaFQRDV 689
gi 302191661 654 tVTNSKILLVLFYPLNSCANPFLYAIFTkaFRRDV 688
gi 512863619 656 tVSNSKILLVLFYPLNSCANPFLYAIFTkaFRRDV 690
gi 556967037 662 tVTNSKILLVLFYPLNSCANPFLYAIFTkaFRRDV 696
gi 13365517  663 tVSNSKILLVLFYPLNSCANPFLYAIFTkaFRGDI 697

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