Conserved Protein Domain Family
7tmC_RAIG_GPRC5

?
cd15043: 7tmC_RAIG_GPRC5 
retinoic acid-inducible orphan G-protein-coupled receptors; class C family of seven-transmembrane G protein-coupled receptors, group 5
Retinoic acid-inducible G-protein-coupled receptors (RAIGs), also referred to as GPCR class C group 5, are a group consisting of four orphan receptors RAIG1 (GPRC5A), RAIG2 (GPRC5B), RAIG3 (GPRC5C), and RAIG4 (GPRC5D). Unlike other members of the class C GPCRs which contain a large N-terminal extracellular domain, RAIGs have a shorter N-terminus. Thus, it is unlikely that RAIGs bind an agonist at its N-terminus domain. Instead, agonists may bind to the seven-transmembrane domain of these receptors. In addition, RAIG2 and RAIG3 contain a cleavable signal peptide whereas RAIG1 and RAIG4 do not. Although their expression is induced by retinoic acid (vitamin A analog), their biological function is not clearly understood. To date, no ligand is known for the members of RAIG family. Three receptor types (RAIG1-3) are found in vertebrates, while RAIG4 is only present in mammals. They show distinct tissue distribution with RAIG1 being primarily expressed in the lung, RAIG2 in the brain and placenta, RAIG3 in the brain, kidney and liver, and RAIG4 in the skin. RAIG1 is evolutionarily conserved from mammals to fish. RAIG1 has been to shown to act as a tumor suppressor in non-small cell lung carcinoma as well as oral squamous cell carcinoma, but it could also act as an oncogene in breast cancer, colorectal cancer, and pancreatic cancer. Studies have shown that overexpression of RAIG1 decreases intracellular cAMP levels. Moreover, knocking out RAIG1 induces the activation of the NF-kB and STAT3 signaling pathways leading to cell proliferation and resistance to apoptosis. RAIG2 (GPRC5B), a mammalian Boss (Bride of sevenless) homolog, activates obesity-associated inflammatory signaling in adipocytes, and GPRC5B knockout mice show resistance to high-fat diet-induced obesity and insulin resistance. The specific functions of RAIG3 and RAIG4 are unknown; however, they may play roles in mediating the effects of retinoic acid on embryogenesis, differentiation, and tumorigenesis through interactions with G-protein signaling pathways.
Statistics
?
PSSM-Id: 320171
View PSSM: cd15043
Aligned: 3 rows
Threshold Bit Score: 329.527
Threshold Setting Gi: 46396016
Created: 2-Feb-2014
Updated: 26-Jul-2017
Structure
?
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
?
Format: Row Display: Color Bits: Type Selection:
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                  #           ##  ##  #
gi 46396943  26 AWGIVLETVATAGVVTSVAFMLTLPILVCkvqdsNRRKMLPTQFLFLLGVLGIFGLTFAFIigldGSTGPTRFFLFGILF 105
gi 46396016  54 IWGIVVEAVAGAGALITLLLMLILLVRLPfikekEKKSPVGLHFLFLLGTLGLFGLTFAFIiqedETICSVRRFLWGVLF 133
gi 46396014  48 AWGIVLEAVAGAGIVTTFVLTIILVASLPfvqdtKKRSLLGTQVFFLLGTLGLFCLVFACVvkpdFSTCASRRFLFGVLF 127
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                   #   
gi 46396943 106 SICFSCLLAHAVSLtklvrgrkplsllvILGLAVGFSLVQDVIAIEYIVLTMnrtnvn----------vfselsAPRRNE 175
gi 46396016 134 ALCFSCLLSQAWRVrrlvrhgtgpagwqLVGLALCLMLVQVIIAVEWLVLTVlrdt---------------rpaCAYEPM 198
gi 46396014 128 AICFSCLAAHVFALnflarknhgprgwvIFTVALLLTLVEVIINTEWLIITLvrgsgeggpqgnssagwavaspCAIANM 207
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1        #  ##  #                                   #  ##  #   #             ##  #  #   
gi 46396943 176 DFVLLLTYVLFLMALTFLMSSFTFCGSFtgwKRHGAHIYLTMLLSIAIWVAWITLLMlpd----fdRRWDDTILSSALAA 251
gi 46396016 199 DFVMALIYDMVLLVVTLGLALFTLCGKFkrwKLNGAFLLITAFLSVLIWVAWMTMYLfgnvklqqgDAWNDPTLAITLAA 278
gi 46396014 208 DFVMALIYVMLLLLGAFLGAWPALCGRYkrwRKHGVFVLLTTATSVAIWVVWIVMYTygnk-qhnsPTWDDPTLAIALAA 286
                       250
                ....*....|....*....
Feature 1       #                  
gi 46396943 252 NGWVFLLAYVSPEFWLLTK 270
gi 46396016 279 SGWVFVIFHAIPEIHCTLL 297
gi 46396014 287 NAWAFVLFYVIPEVSQVTK 305

| Disclaimer | Privacy statement | Accessibility |
NCBI Home NCBI Search NCBI SiteMap