Conserved Protein Domain Family
7tmA_SREB3_GPR173

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cd15217: 7tmA_SREB3_GPR173 
super conserved receptor expressed in brain 3 (or GPR173), member of the class A family of seven-transmembrane G protein-coupled receptors
The SREB (super conserved receptor expressed in brain) subfamily consists of at least three members, named SREB1 (GPR27), SREB2 (GPR85), and SREB3 (GPR173). They are very highly conserved G protein-coupled receptors throughout vertebrate evolution, however no endogenous ligands have yet been identified. SREB2 is greatly expressed in brain regions involved in psychiatric disorders and cognition, such as the hippocampal dentate gyrus. Genetic studies in both humans and mice have shown that SREB2 influences brain size and negatively regulates hippocampal adult neurogenesis and neurogenesis-dependent cognitive function, all of which are suggesting a potential link between SREB2 and schizophrenia. All three SREB genes are highly expressed in differentiated hippocampal neural stem cells. Furthermore, all GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.
Statistics
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PSSM-Id: 320345
View PSSM: cd15217
Aligned: 5 rows
Threshold Bit Score: 659.718
Threshold Setting Gi: 15214315
Created: 28-Mar-2014
Updated: 26-Jul-2017
Structure
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Aligned Rows:
  next features
Feature 1:putative ligand binding pocket [chemical 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 15214315   23 YVKLVLLGLIMCVSLAGNAILSLLVLKERAlhkaPYYFLLDLCLADGIRSAVCFPFVLASVrhgssWTFSalsCKIVAFM 102
gi 15214314   37 YVKLVLLGLIICISLVGNLVVSLLVLRDRAlhkaPYYFLLDLCLADTIRSAVCFPFVLVSIkngsaWTYSvlsCKVVAFM 116
gi 301623422  23 HLKLVLLGFIICASLAGNLLVSLLVLKDRSlhkaPYYFLLDLCLADAVRSSACFPFVLLSIrngsaWAYSllsCKVVAFM 102
gi 637264902  21 YAKLLLLGLIICVSLAGNLSLSLLVLKERGlhkaPYYFLLDLCLADVIRSAVCFPFVLVSIrhgsaWTYSvlsCKIVAFM 100
gi 556995371  23 YIKLVLLGLIICISLAGNLMISVLVLKDRTlhkaPYYFLLDLCLADTIRSAVCFPFVLVSIkngsaWTYSmlsCKIIAFM 102
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1        ##  #                                            # #####                      # 
gi 15214315  103 AVLFCFHAAFMLFCISVTRYMAIAhhrFYAKRMtlWTCAAVICMAWTLSVAMAFPPVFdvgtykfIREEDQCIFEHRyFK 182
gi 15214314  117 AVLFCFHAAFMLFCISVTRYMAIAhhrFYSKRMtfWTCVAVVCMVWTLSVAMAFPPVFdvgtykfIREEDQCIFEHRyFK 196
gi 301623422 103 AVLFCFHASFMLFCISVTRYMAIAhhrFYSKRMtlWTCIAVICMVWTLSVAMAFPPVFdvgtykfIREEDQCIFEHRyFK 182
gi 637264902 101 AVLFCFHAAFLLFCISVTRYMAVAhhrFYAKRMtfWTCIAVICMVWTLSVAMAFPPVFdvgtykfIREEDQCIFEHRyFK 180
gi 556995371 103 AVLFCFHAAFMLFCISVTRYMAIAhhrFYCKRMtfWTCIAIVCMVWTLSVAMAFPPVFdvgtykfIREEDQCIFEHRyFK 182
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1         ### ### ##                                                                     
gi 15214315  183 ANDTLGFMLMLAVLMAATHAVYGKLLLFeyrhRKMKPVQMVPAISQNWTFHGPGATGQAAANWIAGFGRGPMPPTLLGIR 262
gi 15214314  197 ANDTLGFMLMLAVLILATHVVYMKLLLFeykhRKMKPVQMVPAISQNWTFHGPGATGQAAANWIAGFGRGPMPPTLLGIR 276
gi 301623422 183 ANDTLGFMLMLAVLIVATHIVYAKLLLFeyrhRKMKPVQMVPAISQNWTFHGPGATGQAAANWIAGFGRGPMPPTLLGIR 262
gi 637264902 181 ANDTLGFMLMLAVLIFATHVVYIKLLLFeyrhRKMKPVQMVPAISQNWTFHGPGATGQAAANWIAGFGRGPMPPTLLGIR 260
gi 556995371 183 ANDTLGFMLMLAVLIVATHIVYVKLILFeykhRKMKPVQMVPAISQNWTFHGPGATGQAAANWIAGFGRGPMPPTLLGIR 262
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                            #  ## ##  #        ## ###  #  ##            
gi 15214315  263 qnghaaSRRLLGMDEVKGEKQLGRMFYAITLLFLLLWSPYIVACYWRVFvkacavPHRYLATAVWMSFAQAAVNPIVCFL 342
gi 15214314  277 qnlhnqNRRLLGMEEFKAEKQLGRMFYVITLFFLVLWSPYIVACYWRVFvkactiPHRYLSTTVWMSFAQAGVNPIICFF 356
gi 301623422 263 qnthtaNRRLLGMDEFKSEKRLGRMFYGITLSFLVLWSPYIVACYWRVFvktcsiPHRYLSTAVWMTFTQAGVNPIMCFL 342
gi 637264902 261 qnahaaNRRLLGMEEFKAEKRLGRMFYVITLLFLVLWSPYIVACYWRVFvkacsiPHRYLSTAVWMSFAQAAVNPIVCFL 340
gi 556995371 263 qnahtqNRRLLGMEELKVEKRLGRMFYIITLSFLILWSPYIVACYWRVFvkactiPHRYLSTAVWMSFAQAGVNPIICFL 342

                 ....*....
Feature 1                 
gi 15214315  343 LNKDLKKCL 351
gi 15214314  357 LNKDLKKGL 365
gi 301623422 343 LNKDLKSCL 351
gi 637264902 341 LNKDLKKGL 349
gi 556995371 343 LNKDLKKCL 351

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