Conserved Protein Domain Family
7tmC_CaSR

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cd15282: 7tmC_CaSR 
calcium-sensing receptor, member of the class C of seven-transmembrane G protein-coupled receptors
CaSR is a widely expressed GPCR that is involved in sensing small changes in extracellular levels of calcium ion to maintain a constant level of the extracellular calcium via modulating the synthesis and secretion of calcium regulating hormones, such as parathyroid hormone (PTH), in order to regulate Ca(2+)transport into or out of the extracellular fluid via kidney, intestine, and/or bone. For instance, when Ca2+ is high, CaSR downregulates PTH synthesis and secretion, leading to an increase in renal Ca2+ excretion, a decrease in intestinal Ca2+ absorption, and a reduction in release of skeletal Ca2+. CaSR is coupled to both G(q/11)-dependent activation of phospholipase and, subsequently, intracellular calcium mobilization and protein kinase C activation as well as G(i/o)-dependent inhibition of adenylate cyclase leading to inhibition of cAMP formation. CaSR is closely related to GRPC6A (GPCR, class C, group 6, subtype A), which is an amino acid-sensing GPCR that is most potently activated by the basic amino acids L-arginine, L-lysine, and L-ornithine. These receptors contain a large extracellular Venus flytrap-like domain in the N-terminus, cysteine-rich domain (CRD), and seven-transmembrane (7TM) domain, which are characteristics of the class C GPCRs. The Venus flytrap-like domain shares strong sequence homology to bacterial periplasmic binding proteins and possess the orthosteric amino acid and calcium binding sites for members of the class C, including CaSR, GABA-B1, GPRC6A, mGlu, and TASR1 receptors.
Statistics
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PSSM-Id: 320409
View PSSM: cd15282
Aligned: 4 rows
Threshold Bit Score: 458.26
Threshold Setting Gi: 483501373
Created: 10-Dec-2013
Updated: 26-Jul-2017
Structure
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Aligned Rows:
  next features
Feature 1:putative allosteric modulator binding site [chemical binding site]
Evidence:
  • Comment:based on the binding of human mGluR1 receptor to a negative allosteric modulator FITM (contacts at 4A)

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                  #           ##  ##  #  
gi 82080581   596 PFGIALAICAVLGVVLTAFVIGVFVRFRNTPiVKATNRELSYVLLFSLICCFSSSLIFIGEPQDWTCRLRQPAFGVSFVL 675
gi 408359999  611 PFGIALTLFAVLGIFLTAFVLGVFIKFRNTPiVKATNRELSYLLLFSLLCCFSSSLFFIGEPQDWTCRLRQPAFGISFVL 690
gi 483501373  610 PFGIALTLFAVLGIFLTSFVLGVFTKFRNTPiVKATNRELSYLLLFSLLCCFSSSLFFIGEPQNWTCRLRQPAFGISFVL 689
gi 512881648  616 PFGIALTMFAILGICLTSFVLGVFIKFRNTPiVKATNRELSYLLLFSLICCFSSSLIFLGEPQDWTCRLRQPAFGISFVL 695
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                      #  
gi 82080581   676 CISCILVKTNRVLLVFEAKIPtslhRKWWGLNLQFLLVFLCTFVQVMICVVWLYNAPPSSYqnh-diDEIIFITCNEGSV 754
gi 408359999  691 CISCILVKTNRVLLVFEAKIPtsfhRKWWGLNLQFLLVFLCTFMQIVICIIWLYTAPPSSYrnheleDEIIFITCHEGSL 770
gi 483501373  690 CISCILVKTNRVLLVFEAKIPtslhRKWWGLNLQFLLVFLCTFVQIVICVIWLYTAPPSSYrnheleDEIIFITCHEGSL 769
gi 512881648  696 CISCILVKTNRILLVFEAKIPtsfqRKWWGLNLQFLLVFLCTFVQIVTCIIWLYTAPPWSYrnqdleDEIIFITCNEGSL 775
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1           #  ##  #                                 #  ##  #   #       ##  #  #   #      
gi 82080581   755 MALGFLIGYTCILAAICFFFAFKSRKLPeNFTEAKFITFSMLIFFIVWISFIPAYFstYGKFVSAVEVIAILASSFGMLA 834
gi 408359999  771 MALGSLIGYTCLLAAICFFFAFKSRKLPeNFNEAKFITFSMLIFFIVWISFIPAYAstYGKFVSAVEVIAILAASFGLLA 850
gi 483501373  770 MALGFLIGYTCLLAAICFFFAFKSRKLPeNFNEAKFITFSMLIFFIVWISFIPAYAstYGKFVSAVEVIAILAASFGLLA 849
gi 512881648  776 MALGFLIGYTCLLAAICFFFAFKARKLPeNFNEAKFITFSMLIFFIVWISFIPAYAstYGKFVSAVEVIAILASSFGLLA 855
                         250
                  ....*....|..
Feature 1                     
gi 82080581   835 CIFFNKVYIILF 846
gi 408359999  851 CIFFNKVYIILF 862
gi 483501373  850 CIFFNKVYIILF 861
gi 512881648  856 CIFFNKVYIILF 867

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