Conserved Protein Domain Family
7tmA_OXR

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cd15208: 7tmA_OXR 
orexin receptors, member of the class A family of seven-transmembrane G protein-coupled receptors
Orexins (OXs, also referred to as hypocretins) are neuropeptide hormones that regulate the sleep-wake cycle and potently influence homeostatic systems regulating appetite and feeding behavior or modulating emotional responses such as anxiety or panic. OXs are synthesized as prepro-orexin (PPO) in the hypothalamus and then proteolytically cleaved into two forms of isoforms: orexin-A (OX-A) and orexin-B (OX-B). OXA is a 33 amino-acid peptide with N-terminal pyroglutamyl residue and two intramolecular disulfide bonds, whereas OXB is a 28 amino-acid linear peptide with no disulfide bonds. OX-A binds orexin receptor 1 (OX1R) with high-affinity, but also binds with somewhat low-affinity to OX2R, and signals primarily to Gq coupling, whereas OX-B shows a strong preference for the orexin receptor 2 (OX2R) and signals through Gq or Gi/o coupling. Thus, activation of OX1R or OX2R will activate phospholipase activity and the phosphatidylinositol and calcium signaling pathways. Additionally, OX2R activation can also lead to inhibition of adenylate cyclase.
Statistics
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PSSM-Id: 320336
View PSSM: cd15208
Aligned: 13 rows
Threshold Bit Score: 413.324
Threshold Setting Gi: 405975375
Created: 29-Sep-2008
Updated: 26-Jul-2017
Structure
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Aligned Rows:
  next features
Feature 1:putative peptide ligand binding pocket [polypeptide binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                #  ##           ###### #
gi 56201263   57 WALIAGYIVVFIVALVGNVLVCIAVWKNHHMRtvTNYFIVNLSLADILVTITCLPATLVVDItetWFFGhhlCKAIPYLQ 136
gi 120300948  55 WVLIAGYILVFLVSLVGNTLVCFAVWKNHHMRtvTNYFIVNLSFADILVTITCLPASLVVDItetWFFGqtlCKILPYLQ 134
gi 206729885  55 WVLIAGYIIVFVVALIGNVLVCVAVWKNHHMRtvTNYFIVNLSLADVLVTITCLPATLVVDItetWFFGqslCKVIPYLQ 134
gi 205804177  47 WVLIAAYVAVFVVALVGNTLVCLAVWRNHHMRtvTNYFIVNLSLADVLVTAICLPASLLVDItesWLFGhalCKVIPYLQ 126
gi 315258322  53 WVLIVGYIIVFIIALIGNILVCVAVWKNHHMRtvTNYFIVNLSLADVLVTIICLPATLLVDItetWFFGktlCKVIPYLQ 132
gi 268054247  54 WVLISAYFLVFILALGGNVLVCYAVLRNPQMRtvTNYYILNLSIADILVSLICLPITVVFETsetWFFGnlaCKLIPYFQ 133
gi 197209900  73 WILIATHTFVFITGLFGNALVCVAVYRNHSMRtvTNYFIVNLAVADFMVILFCLPATVLWDVtetWFLGeglCKVLPYFQ 152
gi 443730780  65 WCLIVLYLIVFTLGLVGNFLVVFVVVRNKHMRtiTNLFIVNLSVADFLVLLICLPASVLTDVtetWFMGrvmCKLVHYLQ 144
gi 443734978  32 WILILLYGMIFVIGLVGNFLVCFAVWRNPSMRtvTNYFIVNLALADFLVILICLPSTVIEDVamtWFFGrimCKIVKYLQ 111
gi 405966368  50 WGIIILYALTFIVGLSGNVLVCFAVWRNRSMRtvTNIFIVNLAIADLAVIIICLPPTLLSDVtetWYFGfamCKIALFLQ 129
gi 405975375  35 WILIGLFVVVFLLGISGNLLVCLAVWRNRNLRtlTNVHLVNLAVADFMVIAVCLPPTLLHDAlesWFLGtvgCKIVTYLQ 114
gi 557015016  91 WALIAGYIIVFIVALFGNILVCVAVWKNHHMRtvTNYFIVNLSLADVLVTITCLPASLVVDItetWFFGqtlCKVIPYLQ 170
gi 632953204  57 WVLIAAYIAVFVVALVGNVLVCVAVWKNHHMRtvTNYFIVNLSFADVLVTIICLPASLVVDItetWFFGqifCKVIPYLQ 136
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1        #  #                                          # #####                           
gi 56201263  137 TVSVSVSVLTLSCIALDRWYAICHPlmFKSTAkRARNSIIIIWIVSCIIMIPQAIVMecssvfpglankttlFTVCDehw 216
gi 120300948 135 TISVSVSVLTLSCIAQDRWYAICHPlkFKSTAkRARKSIVLIWLVSCIMMIPQAVVMessslmpeltnktslFTVCDeqw 214
gi 206729885 135 TVSVSVSVLTLSCIALDRWYAICHPlmFKSTAkRARNSIVIIWIVSCIIMIPQAIVMecstvfpglankttlFTVCDerw 214
gi 205804177 127 AVSVSVAVLTLSFIALDRWYAICHPllFKSTArRARGSILGIWAVSLAIMVPQAAVMecssvlpelanrtrlFSVCDerw 206
gi 315258322 133 TVSVSVSVLTLSCIALDRWYAICHPlmFKSTAkRAQQSIVIIWIVSCVIMIPQAIVMecrsvfpelanktilFTVCDerw 212
gi 268054247 134 VVSMSVSVLTLCAIAVDRYFAICHPlmFKSTAkRAITVIFSIWITSFLVPIPQAVVYeterpiy--tknyiyLTKCFern 211
gi 197209900 153 SVSVTVSVLTLTFISVDRWYAICFPlkFKSTTgRAKTAILIIWLVSLCFNIPELVVLklvrfvp-lrfelpyLLQCYgtw 231
gi 443730780 145 AVSVSVSVLTLTVISIERYYAICHPlsFKSTHtRARLMIILVWVISLAIVIPELVILdlfphk----pytdlLMACKpsw 220
gi 443734978 112 AVSVAVSVFTLSCISLERFYAICYPlsFKSTPrRAKVMIVVTWVLALLMAIPDLICLdtqhnsg-lpadfslLTTCKptw 190
gi 405966368 130 TTSVAVSVFTLSAISVERWYAICYPlrFKSTKrRAKIIILVIWIIAFLLALPEVIVAdltrfvk--rqyidlLIFCGpqw 207
gi 405975375 115 KVSVLVSVLTLTTIGIERYLGICHPmsDFLPRiKTRVALLGIWVVAMVTAIPDAYYMtvipdnv-ipptinlLKSCRpsd 193
gi 557015016 171 TVSVSVSVLTLSCIALDRWYAICHPlmFKSTAkRARNSIIIIWIVSCVIMIPQAIVMecsnlvpelanktnlFTVCDeqw 250
gi 632953204 137 TVSVSVSVLTLSCIALDRWYAICHPlmFKSTAkRARNSIIIIWIVSCVLMTPQAIVMecsimvpelvnktilFTVCDehw 216
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1              #  ### ### ##                                                             
gi 56201263  217 g-aevyPKMYHTCFFLVTYMAPLCLMVLAYLQIFRKLWcrqipgtssvvqkkwkslqssaq--qrglgqstkskisavaa 293
gi 120300948 215 p-deiyPKVYHTCFFIVTYFAPLCLMVLAYIQICHKLWcqqipgsssvlqrqwkslqcsah--avgsgesvkvrtstvsa 291
gi 206729885 215 g-geiyPKMYHICFFLVTYMAPLCLMVLAYLQIFRKLWcrqipgtssvvqrkwkplqpvsq--prgpgqptksrmsavaa 291
gi 205804177 207 a-ddlyPKIYHSCFFIVTYLAPLGLMAMAYFQIFRKLWgrqipgttsalvrnwkrpsdqlgdleqglsgepqprarafla 285
gi 315258322 213 e-gqiySKVYHICFFFITYMVPLCLMILAYLQIFRKLWcrqipgtssvvqrkwkplqcsi---hskgqqstksrnnavaa 288
gi 268054247 212 wfgsiqQKVYHIALVLVIYVIPLVMIIIAYVFICRQLWakipgsyescdskkna---------------sngnshvstka 276
gi 197209900 232 s--pssELVWHILKVLLIYTLPLVLMAVAYHQIARVLWssngipgqadt-------------------------kklata 284
gi 443730780 221 s--ytsQAAFQIVLIVALFFLPFCLMGFAYIRIALCLWsdfiptescecnkpl-----------------nadgksshhe 281
gi 443734978 191 s--hsiQVGVQCFNLLVMYLLPLGFMFCTYFRIVRCLWsnniptessrdql---------------------hsngsnsa 247
gi 405966368 208 s-dktnQVVYQSVIIVLMYLLPLVLMTVTYSMIAVVLWtgkipgaiesanrp--------------------mmdgnvnr 266
gi 405975375 194 ---sqvEVTQQLVIFFVFFIIPLAIMGFAYTNIFLCLWrstqslpnin----------------------------neha 242
gi 557015016 251 g-deiyPKVYHICFFLVTYMAPLCLMILAYLQIFHKLWcrqipgtssvvqrkwkplqcslq--prgsgfknkpkvnavaa 327
gi 632953204 217 g-dtvyPKVYHICFFIVTYMGPLCLMILAYFQIFRKLWcrqipgtssvvqrkwkplalqcs-sqraaglqtkprinavaa 294
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                 #  ## ##  #               ## ###  #  ##                
gi 56201263  294 eikqiRARRKTARMLMVVLLVFALCYLPISILNILKrvfgmfn-haddretVYAWFTFSHWLVYANSAANPIIYNFLSgk 372
gi 120300948 292 eakqvKARRKTARMLMVVLFVFALCYLPISILNIMKrvfgafk-ntgnretVYAWFTFSHWLIYANSAANPIIYNFLSgk 370
gi 206729885 292 eikqiRARRKTARMLMIVLLVFAICYLPISILNVLKrvfgmfa-htedretVYAWFTFSHWLVYANSAANPIIYNFLSgk 370
gi 205804177 286 evkqmRARRKTAKMLMVVLLVFALCYLPISVLNVLKrvfgmfr-qasdreaVYACFTFSHWLVYANSAANPIIYNFLSgk 364
gi 315258322 289 eikqiHTRRKTARMLMVVLLVFALCYLPISILNILKrvfgmft-htndretVYAWFTFSHWLVYANSAANPIIYNFLSgk 367
gi 268054247 277 sesqlKSRRKVAKMLIIVVVIFTICYLPLHLLNILRqfsffddvvhntrssFHIPFLIAHWLAFANSGVNPIIYNFLSak 356
gi 197209900 285 eltqlRSRRKAAKMLVSVVIMFAVCYFPVHLLSVMRytidm-----gqtefITIWALVSHVMCYANSAINPLIYNLMSdk 359
gi 443730780 282 vrqqvTSRRNVAKMLIAVVIMFGICYLPVHLLNILRyakal-----mngvaAVNFALIAHWLCYFNSAINPLIYNFMSak 356
gi 443734978 248 aenqlRGRRNAAKMLIAVVVMFCICYLPVHLLNILGyanald----ligdyITLLALMSHWLSYLNSAINPVIYNYMSmp 323
gi 405966368 267 aeeqlESRKKAAKMLITVVIGFAVCYFPVHLFNILRyadalr---fvaprmIQVLSMISHWLPYLNSSINPIIYNFMSvq 343
gi 405975375 243 antviQNRKITAKMLIVVVAAFFACNLPVYILNILRyvgvlf---tvdhakIKSFALSSHLLLYTSSAINPVIYTIMSgh 319
gi 557015016 328 eikqiHARRKTARMLMVVLFIFALCYLPISILNILKrvfgmfk-ssndretVYAWFTFSHWLVYANSAANPIIYNFLSgk 406
gi 632953204 295 eikqiRARRKTARMLMVVLFFFAVCYLPISILNVLKrvfgmfd-niddratVYAWFMFSHWLVYANSAANPIIYNFLSgk 373

                 ....*
Feature 1             
gi 56201263  373 FREEF 377
gi 120300948 371 FREEF 375
gi 206729885 371 FREEF 375
gi 205804177 365 FREQF 369
gi 315258322 368 FREEF 372
gi 268054247 357 FRREF 361
gi 197209900 360 FRREF 364
gi 443730780 357 FRKEF 361
gi 443734978 324 IAPSA 328
gi 405966368 344 TKGAF 348
gi 405975375 320 SQTTD 324
gi 557015016 407 FREEF 411
gi 632953204 374 FREEF 378

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