ACKR1
Function
Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Has a promiscuous chemokine-binding profile, interacting with inflammatory chemokines of both the CXC and the CC subfamilies but not with homeostatic chemokines. Acts as a receptor for chemokines including CCL2, CCL5, CCL7, CCL11, CCL13, CCL14, CCL17, CXCL5, CXCL6, IL8/CXCL8, CXCL11, GRO, RANTES, MCP-1, TARC and also for the malaria parasites P.vivax and P.knowlesi. May regulate chemokine bioavailability and, consequently, leukocyte recruitment through two distinct mechanisms: when expressed in endothelial cells, it sustains the abluminal to luminal transcytosis of tissue-derived chemokines and their subsequent presentation to circulating leukocytes; when expressed in erythrocytes, serves as blood reservoir of cognate chemokines but also as a chemokine sink, buffering potential surges in plasma chemokine levels.
Sequence Similarities
Belongs to the G-protein coupled receptor 1 family. Atypical chemokine receptor subfamily.
Tissue Specificity
Found in adult kidney, adult spleen, bone marrow and fetal liver. In particular, it is expressed along postcapillary venules throughout the body, except in the adult liver. Erythroid cells and postcapillary venule endothelium are the principle tissues expressing duffy. Fy(-A-B) individuals do not express duffy in the bone marrow, however they do, in postcapillary venule endothelium.
Cellular localization
- Early endosome
- Recycling endosome
- Membrane
- Multi-pass membrane protein
- Predominantly localizes to endocytic vesicles, and upon stimulation by the ligand is internalized via caveolae. Once internalized, the ligand dissociates from the receptor, and is targeted to degradation while the receptor is recycled back to the cell membrane.
Alternative names
CD234, DARC, FY, GPD, ACKR1, Atypical chemokine receptor 1, Duffy antigen/chemokine receptor, Fy glycoprotein, Glycoprotein D, Plasmodium vivax receptor, GpFy