Conserved Protein Domain Family
7tmA_CCKR-like

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cd14993: 7tmA_CCKR-like 
cholecystokinin receptors and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors
This group represents four G-protein coupled receptors that are members of the RFamide receptor family, including cholecystokinin receptors (CCK-AR and CCK-BR), orexin receptors (OXR), neuropeptide FF receptors (NPFFR), and pyroglutamylated RFamide peptide receptor (QRFPR). These RFamide receptors are activated by their endogenous peptide ligands that share a common C-terminal arginine (R) and an amidated phenylanine (F) motif. CCK-AR (type A, alimentary; also known as CCK1R) is found abundantly on pancreatic acinar cells and binds only sulfated CCK-peptides with very high affinity, whereas CCK-BR (type B, brain; also known as CCK2R), the predominant form in the brain and stomach, binds CCK or gastrin and discriminates poorly between sulfated and non-sulfated peptides. CCK is implicated in regulation of digestion, appetite control, and body weight, and is involved in neurogenesis via CCK-AR. There is some evidence to support that CCK and gastrin, via their receptors, are involved in promoting cancer development and progression, acting as growth and invasion factors. 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. The 26RFa, also known as QRFP (Pyroglutamylated RFamide peptide), is a 26-amino acid residue peptide that exerts similar orexigenic activity including the regulation of feeding behavior in mammals. It is the ligand for G-protein coupled receptor 103 (GPR103), which is predominantly expressed in paraventricular (PVN) and ventromedial (VMH) nuclei of the hypothalamus. GPR103 shares significant protein sequence homology with orexin receptors (OX1R and OX2R), which have recently shown to produce a neuroprotective effect in Alzheimer's disease by forming a functional heterodimer with GPR103. Neuropeptide FF (NPFF) is a mammalian octapeptide that has been implicated in a wide range of physiological functions in the brain including pain sensitivity, insulin release, food intake, memory, blood pressure, and opioid-induced tolerance and hyperalgesia. The effects of NPFF are mediated through neuropeptide FF1 and FF2 receptors (NPFF1-R and NPFF2-R) which are predominantly expressed in the brain. NPFF induces pro-nociceptive effects, mainly through the NPFF1-R, and anti-nociceptive effects, mainly through the NPFF2-R.
Statistics
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PSSM-Id: 320124
View PSSM: cd14993
Aligned: 35 rows
Threshold Bit Score: 239.809
Threshold Setting Gi: 212645070
Created: 30-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 2495001    69 WVRIVMYSVIFLLSVFGNTLIIIVLVMNKRlr-tiTNSFLLSLALSDLMVAVLCMPFTLIPNlm--enFIFGev-iCRAA 144
gi 71993366   19 YTIAVTFFMIFLLSVVGNSVVLIVIIKQRAmr-siTNIYLMNLAASDMMLSVVCMPPTLVSMvm--ncWMFGny-mCKIL 94
gi 392885977  14 IMISSIFLLCLILSLLGNAIVILTILGKSHrsrsiTNFYLLNLAFADLLRSIICIPSTLLGElt--qcWLLGaa-mCKIV 90
gi 443714471  15 CVFIVFYTVIMLLSVFGNLFVIIVIAVNVKmr-tvTNTFLVSLAVSDLLIAALNMPLQLKYYvq--neWSLGse-mCKFT 90
gi 47117904   46 LALVLTGVLIFALALFGNALVFYVVTRSKAmr-tvTNIFICSLALSDLLITFFCIPVTMLQNis--dnWLGGaf-iCKMV 121
gi 229289838 101 IFFIIFYVTIILLAVVGNAMVLWTVWRNKKlr-tvTNYFIMNLAATDLVVGLFVVLFKLLEFatpvavDFFNvp-lCTAL 178
gi 405953036  47 IIFTVVYSIIMLFALSGNTLVIFVILGNKSlr-nvTNMFLISLAISDIFISGFNIPLGLLYNfn--geWTHGei-lCKFV 122
gi 443713309   3 VAYLVIYCVVMFLAVAGNILVIWTVYSNKQmr-tvTNYYIVNLATCDFLVAVFVLPLKLLEYvapcswHVFGhdslCAAL 81
gi 405952398  40 ATIIGIYIIVIVLAICGNMLVIWTVWKNNHmh-tvTNYYIVNLAVSDFLVSAIVTPLKLLEFtapcrwNIFRsdglCSFM 118
gi 229289837  51 VLFMVVYIVVMLLGMGGNAFVCWTIKRNHLlh-naAHYFIANLAVSDLLVSSVVVPMTLVTYig--dpALLSqp-lCTIA 126
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1        ## ##  #                                               # #####                  
gi 2495001   145 AYFMGLSVSVSTFNLVAISIERYSAICnplksr---vwqtrsHAYRVIAATWVLSSIIMIPYlvynktvtf-----pmkd 216
gi 71993366   95 AYLQPVVVTASAYTLAVIAFERYFAICkplhsr---iwqtrsHAYAMITLVWVIAIAANILMlfmyeqq---------ty 162
gi 392885977  91 AFLQPVGVCASAYTLAVIAIERYYAICrplesr---kwqtkkRALITISLVWCFSFSANLTSlflyda------------ 155
gi 443714471  91 KYMQGVTIVASILTLSGIAIDRYYAICnplrar---hvhtaqRAMVLISVFWASAFIVLCPQltiqrieplis-fdaegr 166
gi 47117904  122 PFVQSTAVVTEILTMTCIAVERHQGLVhpfkmk---wqytnrRAFTMLGVVWLVAVIVGSPMwhvqqleiky----dfly 194
gi 229289838 179 NFLQPVFVGASMLTLVAVSFERFNAICrpldtk----ftskkRIVAMLVAVWVVPMVLCSLQlipaaffrmrl--ssemg 252
gi 405953036 123 SFATSVNVIASIMTLTAVALERYYAIChplkmr---ylkkttRVVVVMIAIWILALAVSSPFlviqrigkrlkvinelpg 199
gi 443713309  82 SFTLPVFVFASVLTLVAISLERYYAIVyplkak---iisgksRTRCIIAFTWVIAIVLAVPFlycksyafni---hsqyg 155
gi 405952398 119 SYFQPLFVFVSVLTLVAISIERYYAIVhplsam---kvnsksRTKKIIAATWIIPAILATPYcfsraepfti---sselg 192
gi 229289837 127 NYLQPVCVSASVLTLVAISLERFYAIVqpirnlansrifpvtRVRNTIIAVWLVPVVVLCPWlvpaevtagcf--ysqlg 204
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                               #  ### ### ##                                            
gi 2495001   217 rrvghQCRlvwp-------skqvQQAWYVLLLTILFFIPGVVMIVAYGLisrelyrgiqfemdlnkeakahkngvstptt 289
gi 71993366  163 ssngyTCApihp--------piyHFAYQVYMTVVLLVIPLVVMAGLYGNvitslksgikleiasvdpplatatttaivas 234
gi 392885977 156 npgkfTCDstkg--------plvDFIYQLYLTFTLLFVPLALMVGLYGNviitlntainsdhptveqqmiektlpsrasf 227
gi 443714471 167 mrlayVCVefif-------darlAVTYTLFHYIVLYLGPVLIMFITYGKisytlwrrgpige------------------ 221
gi 47117904  195 ekehiCCLeewt-------spvhQKIYTTFILVILFLLPLMVMLILYSKigyelwikkrvgdgs---------------- 251
gi 229289838 253 tisraRCLddipn------tigdPTWYHVTLFLVLYALPLLFISVVCVRivlrlrametpgs------------------ 308
gi 405953036 200 lalveVCVehye-------tkalEEAHTLVQFTVFYCVPIGIMLFAYGKiahqlwirkpi-------------------- 252
gi 443713309 156 tvrrhICTdrfddi----gsgqfRKWFFIFLFLMMYIVPSIIIMYTCVHmticllrpvet-------------------- 211
gi 405952398 193 tltgeLCSdrfdeld--ghtgdfRRIFFVILFVVMYFIPLAIIVVTCTKiaicltrpfvvgns----------------- 253
gi 229289837 205 evyraRCLdgfylvfdpetagkvAMANQIITLLVMHTFPMVFIAVTCGLvvwrlmklqkp-------------------- 264
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
gi 2495001   290 ipsgdegd--------------------------gcyiqvtkrrntmemstltpsvctkmdrarinnseaklMAKKRVIR 343
gi 71993366  235 mtdeqklsfwnkl----------------snkltfsqqdktvqhpnfghrksdtsiclenpslrsthtqksaMAKQRVIK 298
gi 392885977 228 sdwfvsavqrvpsmkvvsktfqfkeknslsipqtsglsvrpsrssfssffstprgsfdvtmllrstnqekilIAKKKVTR 307
gi 443714471 222 ------------------------------------------------------------tpdnqrdldrrtREKKKIIR 241
gi 47117904  252 ----------------------------------------------------------vlrtihgkemskiaRKKKRAVI 273
gi 229289838 309 -----------------------------------------------------------qlvndrdmarkrdKNKKMVTR 329
gi 405953036 253 --------------------------------------------------------------gdshdwekslKQKKSIIR 270
gi 443713309 212 -------------------------------------------------------------edggnslrrleENKRKVAR 230
gi 405952398 254 ----------------------------------------------------------atykqdptskrrheVNKRKVAR 275
gi 229289837 265 -------------------------------------------------------------vtprgtvtrseINRRKVTL 283
                        330       340       350       360       370       380       390
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
Feature 1                    #  ## ##  #               ## ###  #  ##                     
gi 2495001   344 MLIVIVAMFFICWMPIFVANTWKafdels----afntlTGAPISFIHLLSYTSACVNPLIYCFMNkrFRKAF 411
gi 71993366  299 MLIVVVIIFFCCWTPSYIWWLLLiagdsfq-slnlsvwNSDINTFITLLTYISSCTNPITYCFLNkkFRNAV 369
gi 392885977 308 MLITLVIVFAFCWVPSYLYWLLLrmaela----atdlwNPGLNSSLTIMTYISSLANPITYCFMNksFRSSV 375
gi 443714471 242 MLMVIVGLFALSWFPFFTSQVYLvfhssysnpmhgptgLRIVLALFQLIGYSNCCINPIVYCFLNesFQQRF 313
gi 47117904  274 MMVTVVALFAVCWAPFHVVHMMIeysnfek--eyddvtIKMIFAIVQIIGFSNSICNPIVYAFMNenFKKNV 343
gi 229289838 330 MVIAVAAAFAVCWTPFYVMNMSAlnpdtn---fiansnLFFWHTLMYGLGFLNSAINPVIYIVMSdkFRRGF 398
gi 405953036 271 MLIVIVLIFLLSWLPFFAVHIYRfyhyv------pyenFRLVSLVVQVIGFTNSAVNPIIYGFMNqkFKQTF 336
gi 443713309 231 MIIIVAGAFLVSWTPFYLVNIISqnqsds---flrrsnFLLTMLSTHLFGFLNSCANPFIYCFLSekFRTSF 299
gi 405952398 276 MVIVVAVAFIVAWSPLYIVSVVSvlqpen---flqksnFIFSMLCAHLFGFINSCVNPFIYTVMSekFRQSF 344
gi 229289837 284 MVIAVVVAFVVAWTPLHMVSITYlftpqpsefvlaknnFFTGYLILYLLGYLNSLVNPLIYILMSdrFRKDF 355

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