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: 410631
Aligned: 5 rows
Threshold Bit Score: 255.101
Threshold Setting Gi: 701396137
Created: 28-Jul-2013
Updated: 17-Aug-2020
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 extracellular surface of its receptor.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                                #  ##          ###### ##
Q16570        60 SALPFFILTSVLGILASSTVLFMLFRPLFRwqLCPGWPVLAQLAVGSALFSIVVPVLAPGLgstr--ssaLCSLGYCVWY 137 human
Q9QUI6        58 SSLPFFMLTSVLGMLASGSILFAILRPFFHwqICPSWPILAELAVGSALFSIAVPILAPGLhsah--staLCNLGYWVWY 135 house mouse
Q9GLX0        54 SSLPFFILVSILGILASGTILYALLRPLFRwqLYQDRSTLVQLAVGSALFSIVVPILARGLsgal--itsLCHLAHLVAY 131 cattle
EMP29974      55 YAFNFLAVVCALGLLSNLALVVALANCQSLwsWPPGRASLFQLTLGSTIFTATLPFFAAGIsqgwvvgdgLCKVAYMLWH 134 green sea turtle
XP_009995662  60 VAPPFLAVTCAMAALGAGALLVALTKWPRVwgWPQSRVLVAQLAVGTGVFAALLPLVAVGIkqgwqlgagLCKLTHLLWH 139 chimney swift
Feature 1          #                                     # #####                         #  ### #
Q16570       138 GSAFAQALLLGCHASLGHRLGAGQvpgLTLGLTVGIWGVAALLTLPVTLAsgasgglctl---iystelkalQATHTVAC 214 human
Q9QUI6       136 TSAFAQALLIGCYACLNPRLNIGQlrgFTLGLSVGLWGAAALSGLPVALAsdvyngfctf---pssrdmealKYTHYAIC 212 house mouse
Q9GLX0       132 GSAFAQALLIGYHACLGPQLGAGQvpgLRLGVTVGLWGVAALLSLPVVLGsdtsqglctv---tfsgewetlRYIHAAAC 208 cattle
EMP29974     135 GSLFAEGLLVAAGACSAMWGKWVPs-rHHWCMAVALWVAAVLLAVPAALLsgteghpqll---cimrdsawwHLAHVTSC 210 green sea turtle
XP_009995662 140 WSLFAQGLLVGSSFCSTAWCRWDP---RNQRLAVALWAGALLLAMPAALAsgtvaapetscirrsvdilspaYLLHLALC 216 chimney swift
Feature 1        ## ##                                 #  ## ##  #                  ## ###  #  ##
Q16570       215 LAIFVLLPLGLFGAKGLKKALGMGPGPWMNILWAWFIFWWPHGVVLGLDFLVRSKLLLlsTCLAQQALDLLLNLAEALAI 294 human
Q9QUI6       213 FTIFTVLPLTLLAAKGLKIALSKGPGPWVSVLWIWFIFWWPHGMVLIFDALVRSKTVLlyTCQSQKILDAMLNVTEALSM 292 house mouse
Q9GLX0       209 FAIFVLLPLGLLGTKGLKTVLGRAPCPWVDVLWVWFIFWWPQGMTLGLDSLVRSKAIVvsTCPAQQALDMLLDVAEALAI 288 cattle
EMP29974     211 LAVFMLLPAALGVAKAMLTWRRSGWHLRVGVTCLFFLLWVPYGTALLLDLLVRRQLLYt-SCHFQEFLDFFLGLSEGLGI 289 green sea turtle
XP_009995662 217 VCLFVLLPVVLLLATLAVPQLRVGWEPGTGASWLFFALWMPYGVGLVVDFLLHARLLQp-TCGTFEHFDYMLGLSEGLGV 295 chimney swift
Feature 1                                
Q16570       295 LHCVATPLLLALFC--HQATRTLL 316 human
Q9QUI6       293 LHCVATPLLLALFC--HQTTRRSL 314 house mouse
Q9GLX0       289 LHCVATPLLLAWVC--YQATHTSP 310 cattle
EMP29974     290 LHCCLGPLLLLGAGlyHQRMHADP 313 green sea turtle
XP_009995662 296 LHCCLGPTALLAVRlcHRQASISG 319 chimney swift

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