Conserved Protein Domain Family
7tmA_GPR135

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cd15212: 7tmA_GPR135 
G protein-coupled receptor 135, member of the class A family of seven-transmembrane G protein-coupled receptors
GPR135, also known as the somastostatin- and angiotensin-like peptide receptor (SALPR), is found in various tissues including eye, brain, cervix, stomach, and testis. Pharmacological studies have shown that relaxin-3 (R3) is a high-affinity endogenous ligand for GPR135. R3 has recently been identified as a new member of the insulin/relaxin family of peptide hormones and is exclusively expressed in the brain neurons. In addition to GPR135, R3 also acts as an agonist for GPR142, a pseudogene in the rat, and can activate LGR7 (leucine repeat-containing G-protein receptor-7), which is the main receptor for relaxin-1 (R1) and relaxin-2 (R2). While R1 and R2 are hormones primarily associated with reproduction and pregnancy, R3 is involved in neuroendocrine and sensory processing. 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: 320340
View PSSM: cd15212
Aligned: 6 rows
Threshold Bit Score: 395.676
Threshold Setting Gi: 62900365
Created: 17-Jul-2013
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 62900365  104 AAQALVLLLIFLLSSLGNCAVMGVIVKHRQLrtvTNAFILSLSLSDLLTALLCLPAAFLDLFtppggsapaaaaGPWRgf 183
gi 32165608   71 AAEALVLLSIFLLSSLGNSAVIVVIIKHRQLrtvTNAFIMSLSLSDFLTAILCLPFSFVMLFskdg----vwmfGDHF-- 144
gi 189442533 101 ACQALLLLAIFLLSCLGNCAVILVIAKHRQLrtvTNAFILSLSVSDLLAALLCLPFSFLLLLrgga-----wpfGDRL-- 173
gi 443721856  27 AVAVAALSAIILLSTLGNIMVLYVVFAHLRFrtvTNTFITTLSLTDLCSTAVCMPMALTTLVrrr------wlfGNAG-- 98
gi 556946628  70 ASQALVLLVIFLLSSLGNCAVIIVIIKHRQLrtvTNAFIMSLSLSDFLTAILCLPFSFIMLFsrdg----fwifGDLF-- 143
gi 637332618  40 ASQALLLLLIFALSALGNGAVVGVIVRHRQLrtvTNAFVLSLALAELLAAVLCLPPAFFSLLsgp------wlfGPRL-- 111
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1        ###### ##  #                                           # #####                  
gi 62900365  184 CAASRFFSSCFGIVSTLSVALISLDRYCAIVrPPREKIGr-RRALQLLAGAWLTALGFSLPWELLGaprelaa------- 255
gi 32165608  145 CVANGFFNTCFGIISTLTMTLISFDRYYAIVrQPQAKMDr-QKATQLLLAVWLTAVIFALPWYLLAsapsqih------- 216
gi 189442533 174 CLASGFLNCCFGIVSSLTMTLISMDRYYAIVrQPQGKIGr-ARALQLLLAAWLLALAFSLPWFLLAreqwqvq------- 245
gi 443721856  99 CLANGTINAALAVLSTIMITFITIDRYFVVVrLPKGRPLavPSAVLAIGVACLLSIVIGAPWHMLSsappyy-------- 170
gi 556946628 144 CIANGFFNSCFGIISTLTMTLISFDRYYAIVrQPQEKIGk-KRAIQLLVAVWLTAVLFSFPWYLLAqaektvvv------ 216
gi 637332618 112 CIASATLHAGLGVAATLTMALLAFDRYCAIVrQPRHKMSr-RRAAQLLAAVWLASLGFSSPWYLLAqeeeeeeeqvavsg 190
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                               #  ### ### ##                                            
gi 62900365  256 ---aqsfhgCLYrtspd--paqlGAAFSVGLVVACYLLPFLLMCFCHYHICKTVRlsdvrvrpvntyarvlrFFSEVRTA 330
gi 32165608  217 ---krgfyhCMYvfhsg--tsrlGTAYSICLIIVCYLLPFSLMCFCHYNICKTVRlseirvrpvttyayllrFYSEMRTA 291
gi 189442533 246 ---rkghyhCLYvfhsa--gsrlGAAYSISLIVLCYLLPFALMCFCHYNICKAVRlseirvrpvttyahllrFYSEMRTA 320
gi 443721856 171 ---klgyqhCNYilhiadspypgGPAFGSVFLLLCFVLPSACMIFCSISLWKIIHnndsqirpatapasairFNGEMRTA 247
gi 556946628 217 --ykkgfyhCMYvfhsg--tsrmGTAYSLALIVVCYLLPFALMCFCHYNICKTVRlseirvrpvttyahllrFYSEMRTA 292
gi 637332618 191 nvaptaadhCLYvlpwg--ssrlGASYGATLIVLCYLLPFSVMCFCHYHICRAVRlsesrvrplttyghllrFYGEMRTA 268
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
Feature 1                     #  ## ##  #          ## ###  #  ##                     
gi 62900365  331 TTVLIMIVFVICCWGPYCFLVLLAaarqaqtmqaPSLLSVVAVWLTWANGAINPVIYAIRNpNISMLL 398
gi 32165608  292 TTVLIMIVFIIFCWGPYCLLGLVTalgs---ytfNPAMDTVAIWLAWANGAINPLIYAMRNpNISMLL 356
gi 189442533 321 TTVLIMIVFIICCWGPYCIMGLVAaagd---ypfTPLMDTVAIWMAWANGAINPLIYAIRNpNISMLL 385
gi 443721856 248 KTVVIMVLLYLVSRVPYLLAASICgaig---vqiPVSVDTSLLWILWGSCAVNPIIYAFRNpTVAQFL 312
gi 556946628 293 TTVLIMIVFIICCWGPYCVMGIVTaage---ysfTPNMDKVAIWMAWANGAINPLIYAVRNpNISMLL 357
gi 637332618 269 TTVLIMIVSIICCWGPYCLLGLAAtvgh---lsfSPTLDAAASWMAWANGAVNPLIYVARNpNISLLL 333

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