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:
Feature 1                                                                 #  ##              ####
P70031        69 WVRIVMYSVIFLLSVFGNTLIIIVLVMNKRlr-tiTNSFLLSLALSDLMVAVLCMPFTLIPNlm--enFIFGev-iCRAA 144 African clawed ...
NP_001022844  19 YTIAVTFFMIFLLSVVGNSVVLIVIIKQRAmr-siTNIYLMNLAASDMMLSVVCMPPTLVSMvm--ncWMFGny-mCKIL 94  nematode
NP_491918     14 IMISSIFLLCLILSLLGNAIVILTILGKSHrsrsiTNFYLLNLAFADLLRSIICIPSTLLGElt--qcWLLGaa-mCKIV 90  nematode
ELU06872      15 CVFIVFYTVIMLLSVFGNLFVIIVIAVNVKmr-tvTNTFLVSLAVSDLLIAALNMPLQLKYYvq--neWSLGse-mCKFT 90  Capitella sp. I...
Q96P65        46 LALVLTGVLIFALALFGNALVFYVVTRSKAmr-tvTNIFICSLALSDLLITFFCIPVTMLQNis--dnWLGGaf-iCKMV 121 human
EEN60522     101 IFFIIFYVTIILLAVVGNAMVLWTVWRNKKlr-tvTNYFIMNLAATDLVVGLFVVLFKLLEFatpvavDFFNvp-lCTAL 178 Florida lancelet
EKC20770      47 IIFTVVYSIIMLFALSGNTLVIFVILGNKSlr-nvTNMFLISLAISDIFISGFNIPLGLLYNfn--geWTHGei-lCKFV 122 Pacific oyster
ELU06228       3 VAYLVIYCVVMFLAVAGNILVIWTVYSNKQmr-tvTNYYIVNLATCDFLVAVFVLPLKLLEYvapcswHVFGhdslCAAL 81  Capitella sp. I...
EKC20215      40 ATIIGIYIIVIVLAICGNMLVIWTVWKNNHmh-tvTNYYIVNLAVSDFLVSAIVTPLKLLEFtapcrwNIFRsdglCSFM 118 Pacific oyster
EEN60521      51 VLFMVVYIVVMLLGMGGNAFVCWTIKRNHLlh-naAHYFIANLAVSDLLVSSVVVPMTLVTYig--dpALLSqp-lCTIA 126 Florida lancelet
Feature 1        ## ##  #                                               # #####                  
P70031       145 AYFMGLSVSVSTFNLVAISIERYSAICnplksr---vwqtrsHAYRVIAATWVLSSIIMIPYlvynktvtf-----pmkd 216 African clawed ...
NP_001022844  95 AYLQPVVVTASAYTLAVIAFERYFAICkplhsr---iwqtrsHAYAMITLVWVIAIAANILMlfmyeqq---------ty 162 nematode
NP_491918     91 AFLQPVGVCASAYTLAVIAIERYYAICrplesr---kwqtkkRALITISLVWCFSFSANLTSlflyda------------ 155 nematode
ELU06872      91 KYMQGVTIVASILTLSGIAIDRYYAICnplrar---hvhtaqRAMVLISVFWASAFIVLCPQltiqrieplis-fdaegr 166 Capitella sp. I...
Q96P65       122 PFVQSTAVVTEILTMTCIAVERHQGLVhpfkmk---wqytnrRAFTMLGVVWLVAVIVGSPMwhvqqleiky----dfly 194 human
EEN60522     179 NFLQPVFVGASMLTLVAVSFERFNAICrpldtk----ftskkRIVAMLVAVWVVPMVLCSLQlipaaffrmrl--ssemg 252 Florida lancelet
EKC20770     123 SFATSVNVIASIMTLTAVALERYYAIChplkmr---ylkkttRVVVVMIAIWILALAVSSPFlviqrigkrlkvinelpg 199 Pacific oyster
ELU06228      82 SFTLPVFVFASVLTLVAISLERYYAIVyplkak---iisgksRTRCIIAFTWVIAIVLAVPFlycksyafni---hsqyg 155 Capitella sp. I...
EKC20215     119 SYFQPLFVFVSVLTLVAISIERYYAIVhplsam---kvnsksRTKKIIAATWIIPAILATPYcfsraepfti---sselg 192 Pacific oyster
EEN60521     127 NYLQPVCVSASVLTLVAISLERFYAIVqpirnlansrifpvtRVRNTIIAVWLVPVVVLCPWlvpaevtagcf--ysqlg 204 Florida lancelet
Feature 1                               #  ### ### ##                                            
P70031       217 rrvghQCRlvwp-------skqvQQAWYVLLLTILFFIPGVVMIVAYGLisrelyrgiqfemdlnkeakahkngvstptt 289 African clawed ...
NP_001022844 163 ssngyTCApihp--------piyHFAYQVYMTVVLLVIPLVVMAGLYGNvitslksgikleiasvdpplatatttaivas 234 nematode
NP_491918    156 npgkfTCDstkg--------plvDFIYQLYLTFTLLFVPLALMVGLYGNviitlntainsdhptveqqmiektlpsrasf 227 nematode
ELU06872     167 mrlayVCVefif-------darlAVTYTLFHYIVLYLGPVLIMFITYGKisytlwrrgpige------------------ 221 Capitella sp. I...
Q96P65       195 ekehiCCLeewt-------spvhQKIYTTFILVILFLLPLMVMLILYSKigyelwikkrvgdgs---------------- 251 human
EEN60522     253 tisraRCLddipn------tigdPTWYHVTLFLVLYALPLLFISVVCVRivlrlrametpgs------------------ 308 Florida lancelet
EKC20770     200 lalveVCVehye-------tkalEEAHTLVQFTVFYCVPIGIMLFAYGKiahqlwirkpi-------------------- 252 Pacific oyster
ELU06228     156 tvrrhICTdrfddi----gsgqfRKWFFIFLFLMMYIVPSIIIMYTCVHmticllrpvet-------------------- 211 Capitella sp. I...
EKC20215     193 tltgeLCSdrfdeld--ghtgdfRRIFFVILFVVMYFIPLAIIVVTCTKiaicltrpfvvgns----------------- 253 Pacific oyster
EEN60521     205 evyraRCLdgfylvfdpetagkvAMANQIITLLVMHTFPMVFIAVTCGLvvwrlmklqkp-------------------- 264 Florida lancelet
Feature 1                                                                                        
P70031       290 ipsgdegd--------------------------gcyiqvtkrrntmemstltpsvctkmdrarinnseaklMAKKRVIR 343 African clawed ...
NP_001022844 235 mtdeqklsfwnkl----------------snkltfsqqdktvqhpnfghrksdtsiclenpslrsthtqksaMAKQRVIK 298 nematode
NP_491918    228 sdwfvsavqrvpsmkvvsktfqfkeknslsipqtsglsvrpsrssfssffstprgsfdvtmllrstnqekilIAKKKVTR 307 nematode
ELU06872     222 ------------------------------------------------------------tpdnqrdldrrtREKKKIIR 241 Capitella sp. I...
Q96P65       252 ----------------------------------------------------------vlrtihgkemskiaRKKKRAVI 273 human
EEN60522     309 -----------------------------------------------------------qlvndrdmarkrdKNKKMVTR 329 Florida lancelet
EKC20770     253 --------------------------------------------------------------gdshdwekslKQKKSIIR 270 Pacific oyster
ELU06228     212 -------------------------------------------------------------edggnslrrleENKRKVAR 230 Capitella sp. I...
EKC20215     254 ----------------------------------------------------------atykqdptskrrheVNKRKVAR 275 Pacific oyster
EEN60521     265 -------------------------------------------------------------vtprgtvtrseINRRKVTL 283 Florida lancelet
Feature 1                    #  ## ##  #               ## ###  #  ##                     
P70031       344 MLIVIVAMFFICWMPIFVANTWKafdels----afntlTGAPISFIHLLSYTSACVNPLIYCFMNkrFRKAF 411 African clawed frog
NP_001022844 299 MLIVVVIIFFCCWTPSYIWWLLLiagdsfq-slnlsvwNSDINTFITLLTYISSCTNPITYCFLNkkFRNAV 369 nematode
NP_491918    308 MLITLVIVFAFCWVPSYLYWLLLrmaela----atdlwNPGLNSSLTIMTYISSLANPITYCFMNksFRSSV 375 nematode
ELU06872     242 MLMVIVGLFALSWFPFFTSQVYLvfhssysnpmhgptgLRIVLALFQLIGYSNCCINPIVYCFLNesFQQRF 313 Capitella sp. I Grassle...
Q96P65       274 MMVTVVALFAVCWAPFHVVHMMIeysnfek--eyddvtIKMIFAIVQIIGFSNSICNPIVYAFMNenFKKNV 343 human
EEN60522     330 MVIAVAAAFAVCWTPFYVMNMSAlnpdtn---fiansnLFFWHTLMYGLGFLNSAINPVIYIVMSdkFRRGF 398 Florida lancelet
EKC20770     271 MLIVIVLIFLLSWLPFFAVHIYRfyhyv------pyenFRLVSLVVQVIGFTNSAVNPIIYGFMNqkFKQTF 336 Pacific oyster
ELU06228     231 MIIIVAGAFLVSWTPFYLVNIISqnqsds---flrrsnFLLTMLSTHLFGFLNSCANPFIYCFLSekFRTSF 299 Capitella sp. I Grassle...
EKC20215     276 MVIVVAVAFIVAWSPLYIVSVVSvlqpen---flqksnFIFSMLCAHLFGFINSCVNPFIYTVMSekFRQSF 344 Pacific oyster
EEN60521     284 MVIAVVVAFVVAWTPLHMVSITYlftpqpsefvlaknnFFTGYLILYLLGYLNSLVNPLIYILMSdrFRKDF 355 Florida lancelet

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