2LNL,4MBS,3OE0,4XT3,4RWS


Conserved Protein Domain Family
7tmA_Chemokine_R

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cd14984: 7tmA_Chemokine_R 
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classical and atypical chemokine receptors, member of the class A family of seven-transmembrane G protein-coupled receptors
Chemokines are principal regulators for leukocyte trafficking, recruitment, and activation. Chemokine family membership is defined on the basis of sequence homology and on the presence of variations on a conserved cysteine motif, which allows the family to further divide into four subfamilies (CC, CXC, XC, and CX3C). Chemokines interact with seven-transmembrane receptors which are typically coupled to G protein for signaling. Currently, there are ten known receptors for CC chemokines, seven for CXC chemokines, and single receptors for the XC and CX3C chemokines. In addition to these classical chemokine receptors, there exists a subfamily of atypical chemokine receptors (ACKRs) that are unable to couple to G-proteins and, instead, they preferentially mediate beta-arrestin dependent processes, such as receptor internalization, after ligand binding. The classical chemokine receptors contain a conserved DRYLAIV motif in the second intracellular loop, which is required for G-protein coupling. However, the ACKRs lack this conserved motif and fail to couple to G-proteins and induce classical GPCR signaling. Five receptors have been identified for the ACKR family, including CC-chemokine receptors like 1 and 2 (CCRL1 and CCRL2), CXCR7, Duffy antigen receptor for chemokine (DARC), and D6. Both ACKR1 (DARC) and ACKR3 (CXCR7) show low sequence homology to the classic chemokine receptors.
Statistics
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PSSM-Id: 341319
View PSSM: cd14984
Aligned: 26 rows
Threshold Bit Score: 221.704
Threshold Setting Gi: 341940330
Created: 23-Sep-2008
Updated: 26-Jul-2017
Structure
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Program:
Drawing:
Aligned Rows:
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Conserved site includes 23 residues -Click on image for an interactive view with Cn3D
Feature 1:chemokine binding site [polypeptide binding site]
Evidence:
  • Comment:based on structures of chemokine receptors with bound ligands (chemokines, peptides, or chemical antagonists/agonists)
  • Structure:4RWS: Human chemokine receptor CXCR4 binds a viral chemokine; contacts at 4A
    View structure with Cn3D
  • Structure:4XT3: Cytomegalovirus GPCR US28 in complex with the chemokine domain of human CX3CL1 (fractalkine), contacts 4A
    View structure with Cn3D
  • Structure:3OE0: Human CXCR4 chemokine receptor in complex with a cyclic peptide antagonist, contacts at 4A.
    View structure with Cn3D
  • Structure:4MBS: Human Ccr5 chemokine receptor binds the HIV entry inhibitor maraviroc, contacts at 4A.
    View structure with Cn3D
  • 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:
Feature 1           #                                                #  #                #  ##
2LNL_A     12 YVVIIAYALVFLLSLLGNSLVMLVILYSRVgrsvTDVYLLNLALADLLFALTLPIWAASKvngwi-fgtflCKVVSLLKE 90  human
4XT3_A     42 PVTLFLYGVVFLFGSIGNFLVIFTITWRRRiqcsGDVYFINLAAADLLFVCTLPLWMQYLldhns-lasvpCTLLTACFY 120 Cytomegalovirus
4RWS_A     48 IFLPTIYSIIFLTGIVGNGLVILVMGYQKKlrsmTDKYRLHLSVADLLFVITLPFWAVDAvanwy-fgnflCKAVHVIYT 126
P46094     32 LATTVLYCLVFLLSLVGNSLVLWVLVKYESleslTNIFILNLCLSDLVFACLLPVWISPYhwgwv-lgdflCKLLNMIFS 110 human
P51679     40 LFLPPLYSLVFVFGLLGNSVVVLVLFKYKRlrsmTDVYLLNLAISDLLFVFSLPFWGYYAadqwv-fglglCKMISWMYL 118 human
AAH82709   34 KFLVPVYIFVFLLGIIGNALVIIILIQYKKlrnmTDIYLLNLAISDLLFVISLPFWAYYItkdwv-fgdalCKILSGLYL 112 African clawed frog
P32246     35 QLLPPLYSLVFVIGLVGNILVVLVLVQYKRlknmTSIYLLNLAISDLLFLFTLPFWIDYKlkddwvfgdamCKILSGFYY 114 human
P49238     32 VFLSIFYSVIFAIGLVGNLLVVFALTNSKKpksvTDIYLLNLALSDLLFVATLPFWTHYLinekg-lhnamCKFTTAFFF 110 human
P51685     36 LLLAVFYCLLFVFSLLGNSLVILVLVVCKKlrsiTDVYLLNLALSDLLFVFSFPFQTYYLldqwv-fgtvmCKVVSGFYY 114 human
P51677     35 QFVPPLYSLVFTVGLLGNVVVVMILIKYRRlrimTNIYLLNLAISDLLFLVTLPFWIHYVrghnwvfghgmCKLLSGFYH 114 human
Feature 1                                                                          ######     
2LNL_A     91 VNFYSGILLLACISVDRYLAIVHatrtl-tqkrHLVKFVCLGCWGLSMNLSLPFFLFrqayhpnnsspVCYEVLGndt-a 168 human
4XT3_A    121 VAMFASLCFITEIALDRYYAIVYmry----rpvKQACLFSIFWWIFAVIIAIPHFMVvtk-----kdnQCMTDYDyle-v 190 Cytomegalovirus
4RWS_A    127 VNLYSSVWILAFISLDRYLAIVHatnsqrprklLAEKVVYVGVWIPALLLTIPDFIFanvse-addryICCRFYPnd--- 202
P46094    111 ISLYSSIFFLTIMTIHRYLSVVSplstlrvptlRCRVLVTMAVWVASILSSILDTIFhkv-----lssGCDYSELt---- 181 human
P51679    119 VGFYSGIFFVMLMSIDRYLAIVHavfslrartlTYGVITSLATWSVAVFASLPGFLFstcyt-ernhtYCKTKYSlns-t 196 human
AAH82709  113 TGFYGASFFIILLTLDRYLAIVHvifamkvrtvKFSIFTSIVLWGIAVLFSLPGFIFykaek-qidvwTCSPYYTga--- 188 African clawed frog
P32246    115 TGLYSEIFFIILLTIDRYLAIVHavfalrartvTFGVITSIIIWALAILASMPGLYFsktqw-efthhTCSLHFPheslr 193 human
P49238    111 IGFFGSIFFITVISIDRYLAIVLaansmnnrtvQHGVTISLGVWAAAILVAAPQFMFtkq-----kenECLGDYPevlqe 185 human
P51685    115 IGFYSSMFFITLMSVDRYLAVVHavyalkvrtiRMGTTLCLAVWLTAIMATIPLLVFyqvas-edgvlQCYSFYNqqt-l 192 human
P51677    115 TGLYSEIFFIILLTIDRYLAIVHavfalrartvTFGVITSIVTWGLAVLAALPEFIFyetee-lfeetLCSALYPedtvy 193 human
Feature 1       #  ##                                                                         
2LNL_A    169 kwRMVLRILPHTFGFIVPLFVMLFCYGFTLRTlfk--------------------------------------------- 203 human
4XT3_A    191 syPIILNVELMLGAFVIPLSVISYCYYRISRIvav--------------------------------------------- 225 Cytomegalovirus
4RWS_A    203 lwVVVFQFQHIMVGLILPGIVILSCYCIIISKlshnifemlrideglrlkiykdtegyytigighlltkspslnaaksel 282
P46094    182 --WYLTSVYQHNLFFLLSLGIILFCYVEILRTlfr--------------------------------------------- 214 human
P51679    197 twKVLSSLEINILGLVIPLGIMLFCYSMIIRTlqh--------------------------------------------- 231 human
AAH82709  189 -wKTIFTLVMSILGLFIPLVVMIFCYSRIIYTllrc-------------------------------------------- 223 African clawed frog
P32246    194 ewKLFQALKLNLFGLVLPLLVMIICYTGIIKIllr--------------------------------------------- 228 human
P49238    186 iwPVLRNVETNFLGFLLPLLIMSYCYFRIIQTlfs--------------------------------------------- 220 human
P51685    193 kwKIFTNFKMNILGLLIPFTIFMFCYIKILHQlkr--------------------------------------------- 227 human
P51677    194 swRHFHTLRMTIFCLVLPLLVMAICYTGIIKTllr--------------------------------------------- 228 human
Feature 1                                                                                     
2LNL_A        -------------------------------------------------------------------------------- human
4XT3_A        -------------------------------------------------------------------------------- Cytomegalovirus
4RWS_A    283 dkaigrntngvitkdeaeklfnqdvdaavrgilrnaklkpvydsldavrraalinmvfqmgetgvagftnslrmlqqkrw 362
P46094        -------------------------------------------------------------------------------- human
P51679        -------------------------------------------------------------------------------- human
AAH82709      -------------------------------------------------------------------------------- African clawed frog
P32246        -------------------------------------------------------------------------------- human
P49238        -------------------------------------------------------------------------------- human
P51685        -------------------------------------------------------------------------------- human
P51677        -------------------------------------------------------------------------------- human
Feature 1                                                                   #      #  #       
2LNL_A    204 ------------------------------------ahmGQKHRAMRVIFAVVLIFLLCWLPYNLVLLADTLMrtqviqe 247 human
4XT3_A    226 ------------------------------------sqsRHKGRIVRVLIAVVLVFIIFWLPYHLTLFVDTLKllkwiss 269 Cytomegalovirus
4RWS_A    363 deaavnlaksrwynqtpnrakrvittfrtgtwdaysgsgHQKRKALKPTVILILAFFACWLPYYIGISIDSFIlleiikq 442
P46094    215 ------------------------------------srsKRRHRTVKLIFAIVVAYFLSWGPYNFTLFLQTLFrtqii-r 257 human
P51679    232 ------------------------------------cknEKKNKAVKMIFAVVVLFLGFWTPYNIVLFLETLVelevl-q 274 human
AAH82709  224 ------------------------------------kseRKKHKAVKLIFIIMVVFFIFWMPYNIVYIMHSFQdsdsi-n 266 African clawed frog
P32246    229 ------------------------------------rpnEKKSKAVRLIFVIMIIFFLFWTPYNLTILISVFQdflft-h 271 human
P49238    221 ------------------------------------cknHKKAKAIKLILLVVIVFFLFWTPYNVMIFLETLKlydff-p 263 human
P51685    228 ------------------------------------cqnHNKTKAIRLVLIVVIASLLFWVPFNVVLFLTSLHsmhil-d 270 human
P51677    229 ------------------------------------cpsKKKYKAIRLIFVIMAVFFIFWTPYNVAILLSSYQsilfg-n 271 human
Feature 1         #   #  ##  #                         
2LNL_A    248 scerRNNIGRALDATEILGFLHSCLNPIIYAFIGqnFRHGF 288 human
4XT3_A    270 scefERSLKRALILTESLAFCHCCLNPLLYVFVGtkFRQEL 310 Cytomegalovirus
4RWS_A    443 gcefENTVHKWISITEALAFFHCCLNPILYAFLGakFKTSA 483
P46094    258 sceaKQQLEYALLICRNLAFSHCCFNPVLYVFVGvkFRTHL 298 human
P51679    275 dctfERYLDYAIQATETLAFVHCCLNPIIYFFLGekFRKYI 315 human
AAH82709  267 ackmNKKLDEAVQWAEAISYFHCCLNPVIYAFVGekFRKYL 307 African clawed frog
P32246    272 eceqSRHLDLAVQVTEVIAYTHCCVNPVIYAFVGerFRKYL 312 human
P49238    264 scdmRKDLRLALSVTETVAFSHCCLNPLIYAFAGekFRRYL 304 human
P51685    271 gcsiSQQLTYATHVTEIISFTHCCVNPVIYAFVGekFKKHL 311 human
P51677    272 dcerSKHLDLVMLVTEVIAYSHCCMNPVIYAFVGerFRKYL 312 human

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