Conserved Protein Domain Family
7tmA_ACKR1_DARC

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cd15010: 7tmA_ACKR1_DARC 
Duffy antigen receptor for chemokines, member of the class A family of seven-transmembrane G protein-coupled receptors
Atypical chemokine receptor 1 (ACKR1), also known as DARC (Duffy antigen receptor for chemokines) or Fy glycoprotein (GpFy), was originally identified on erythrocytes. ACKR1 is also ubiquitously expressed by endothelial cells of venules and is highly promiscuous among all chemokine receptor. It binds many proinflammatory chemokines from both the CC and CXC subfamilies, including CCL2, CCL5, CCL7, CCL11, CXCL1, CXCL2, CXCL3, and CXCL5. Erythrocyte ACKR1 is thought to act as a chemokine sink, limiting the levels of circulating chemokines, thereby controlling leukocyte activation. ACKR1-deficient erythrocytes are shown to confer resistance to the malarial parasite, Plasmodium vivax. On the other hand, ACKR1-expressing endothelial cells can internalize chemokines. ACKR1-internalized chemokines can be moved intact across the endothelium and promotes neutrophil transmigration. Unlike the classical chemokine receptors that contain a conserved DRYLAIV motif in the second intracellular loop, which is required for G-protein coupling, 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, 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: 320138
View PSSM: cd15010
Aligned: 5 rows
Threshold Bit Score: 255.102
Threshold Setting Gi: 701396137
Created: 28-Jul-2013
Updated: 26-Jul-2017
Structure
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Aligned Rows:
  next features
Feature 1:putative peptide ligand binding pocket [polypeptide 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 67476970   60 SALPFFILTSVLGILASSTVLFMLFRPLFRwqLCPGWPVLAQLAVGSALFSIVVPVLAPGLgstr--ssaLCSLGYCVWY 137
gi 27734283   58 SSLPFFMLTSVLGMLASGSILFAILRPFFHwqICPSWPILAELAVGSALFSIAVPILAPGLhsah--staLCNLGYWVWY 135
gi 160332326  54 SSLPFFILVSILGILASGTILYALLRPLFRwqLYQDRSTLVQLAVGSALFSIVVPILARGLsgal--itsLCHLAHLVAY 131
gi 465963031  55 YAFNFLAVVCALGLLSNLALVVALANCQSLwsWPPGRASLFQLTLGSTIFTATLPFFAAGIsqgwvvgdgLCKVAYMLWH 134
gi 701396137  60 VAPPFLAVTCAMAALGAGALLVALTKWPRVwgWPQSRVLVAQLAVGTGVFAALLPLVAVGIkqgwqlgagLCKLTHLLWH 139
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1          #                                     # #####                         #  ### #
gi 67476970  138 GSAFAQALLLGCHASLGHRLGAgqvpgLTLGLTVGIWGVAALLTLPVTLAsgasgglctl---iystelkalQATHTVAC 214
gi 27734283  136 TSAFAQALLIGCYACLNPRLNIgqlrgFTLGLSVGLWGAAALSGLPVALAsdvyngfctf---pssrdmealKYTHYAIC 212
gi 160332326 132 GSAFAQALLIGYHACLGPQLGAgqvpgLRLGVTVGLWGVAALLSLPVVLGsdtsqglctv---tfsgewetlRYIHAAAC 208
gi 465963031 135 GSLFAEGLLVAAGACSAMWGKWvp-srHHWCMAVALWVAAVLLAVPAALLsgteghpqll---cimrdsawwHLAHVTSC 210
gi 701396137 140 WSLFAQGLLVGSSFCSTAWCRWd---pRNQRLAVALWAGALLLAMPAALAsgtvaapetscirrsvdilspaYLLHLALC 216
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1        ## ##                                 #  ## ##  #                  ## ###  #  ##
gi 67476970  215 LAIFVLLPLGLFGAKGLKKALGMGPGPWMNILWAWFIFWWPHGVVLGLDFLVRSKLLLlsTCLAQQALDLLLNLAEALAI 294
gi 27734283  213 FTIFTVLPLTLLAAKGLKIALSKGPGPWVSVLWIWFIFWWPHGMVLIFDALVRSKTVLlyTCQSQKILDAMLNVTEALSM 292
gi 160332326 209 FAIFVLLPLGLLGTKGLKTVLGRAPCPWVDVLWVWFIFWWPQGMTLGLDSLVRSKAIVvsTCPAQQALDMLLDVAEALAI 288
gi 465963031 211 LAVFMLLPAALGVAKAMLTWRRSGWHLRVGVTCLFFLLWVPYGTALLLDLLVRRQLLYt-SCHFQEFLDFFLGLSEGLGI 289
gi 701396137 217 VCLFVLLPVVLLLATLAVPQLRVGWEPGTGASWLFFALWMPYGVGLVVDFLLHARLLQp-TCGTFEHFDYMLGLSEGLGV 295
                        250       260
                 ....*....|....*....|....
Feature 1                                
gi 67476970  295 LHCVATPLLLALFC--HQATRTLL 316
gi 27734283  293 LHCVATPLLLALFC--HQTTRRSL 314
gi 160332326 289 LHCVATPLLLAWVC--YQATHTSP 310
gi 465963031 290 LHCCLGPLLLLGAGlyHQRMHADP 313
gi 701396137 296 LHCCLGPTALLAVRlcHRQASISG 319

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