Conserved Protein Domain Family
7tmA_SREB2_GPR85

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cd15218: 7tmA_SREB2_GPR85 
super conserved receptor expressed in brain 2 (or GPR85), 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: 320346
View PSSM: cd15218
Aligned: 4 rows
Threshold Bit Score: 581.606
Threshold Setting Gi: 15214045
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 46397434   21 FLKLTSLGFIIGVSVVGNLLISILLVKDKTLHraPYYFLLDLCCSDILRSAICFPFVFNSVKNgstWTYGtltCKVIAFL 100
gi 15214045   22 FLKLTSLGFIIGVGVVGNLLISILLVKDKSLHraPYYFLLDLCASDILRSAICFPFVFTSVKNgsaWTYGtltCKVIAFL 101
gi 147902918  21 FLKLTSLGFIIGVSVVGNLLISILLVKDKTLHraPYYFLLDLCCSDILRSAICFPFVFTSVKNgstWTYGaltCKVIAFL 100
gi 449265737  21 FLKLTSLGFIIGVSVVGNLLISILLVKDKTLHraPYYFLLDLCCSDILRSAICFPFVFTSVKNgstWTYGtltCKVIAFL 100
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1        ##  #                                            # #####                      # 
gi 46397434  101 GVLSCFHTAFMLFCISVTRYLAIAhhrFYTKRLtfWTCLAVICMVWTLSVAMAFPPVLDvgtysFIREEDQCTFQHRsFR 180
gi 15214045  102 GVLSCFHTAFMLFCVSVTRYLAIAhhrFYTKRLtfWTCLAVICMVWTLSVAMAFPPVLDvgtysFIREEDQCTFQHRsFR 181
gi 147902918 101 GVLSCFHTAFMLFCISVTRYLAIAhhrFYTKRLtfWTCLAVICMVWTLSVAMAFPPVLDvgtysFIREEDQCTFQHRsFR 180
gi 449265737 101 GVLSCFHTAFMLFCISVTRYLAIAhhrFYTKRLtfWTCLAVICMVWTLSVAMAFPPVLDvgtysFIREEDQCTFQHRsFR 180
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1         ### ### ##                                                                     
gi 46397434  181 ANDSLGFMLLLALILLATQLVYLKLIFFvhdrRKMKPVQFVAAVSQNWTFHGPGASGQAAANWLAGFGRGPTPPTLLGIR 260
gi 15214045  182 ANDSLGFMLLLALILLATQLVYLKLIFFvhdrRKMKPVQFVPAVSQNWTFHGPGASGQAAANWLAGFGRGPTPPTLLGIR 261
gi 147902918 181 ANDSLGFMLLLALILLATQLVYLKLIFFvhdrRKMKPVQFVAAVSQNWTFHGPGASGQAAANWLAGFGRGPTPPTLLGIR 260
gi 449265737 181 ANDSLGFMLLLALILLATQLVYLKLIFFvhdrRKMKPVQFVAAVSQNWTFHGPGASGQAAANWLAGFGRGPTPPTLLGIR 260
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                             #  ## ##  #        ## ###  #  ##           
gi 46397434  261 qnanttgRRRLLVLDEFKMEKRISRMFYIMTFLFLTLWGPYLVACYWRVFargpvvPGGFLTAAVWMSFAQAGINPFVCI 340
gi 15214045  262 qnsnaagRRRLLVLDEFKTEKRISRMFYIITFFFLSLWGPYLVACYWRVFargpviPGGYLTAAVWMSFAQAGVNPFICI 341
gi 147902918 261 qnanttgRRRLLVLDEFKMEKRISRMFYIMTFLFLTLWGPYLIACYWRVFargpvvPGGFLTAAVWMSFAQAGINPFVCI 340
gi 449265737 261 qnanttgRRRLLVLDEFKMEKRISRMFYIMTFLFLTLWGPYLVACYWRVFargpvvPGGFLTAAVWMSFAQAGINPFVCI 340
                        330
                 ....*....|
Feature 1                  
gi 46397434  341 FSNRELRRCF 350
gi 15214045  342 FSNRELRRCF 351
gi 147902918 341 FSNRELRRCF 350
gi 449265737 341 FSNRELRRCF 350

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