Atypical chemokine receptor 1 (ACKR1)

Atypical chemokine receptor 1 (ACKR1) is a 7-transmembrane domain protein, structurally related to classical chemokine receptors but lacking the DRYLAIV motif required for G-protein signaling. Unlike classical GPCR chemokine receptors, ACKR1 does not trigger intracellular signaling upon ligand binding, but instead binds more than 20 CC and CXC inflammatory chemokines with high affinity, acting as a sink and buffer especially on erythrocytes and endothelial cells. ACKR1 modulates chemokine gradients and availability, regulates leukocyte trafficking, and plays roles in inflammation, angiogenesis, malaria infection (as an entry point for *Plasmodium vivax* and *P. knowlesi*), and possibly cancer progression. Duffy-null individuals lacking erythrocyte expression of ACKR1 are resistant to *P. vivax* malaria, but display altered systemic chemokine profiles. The receptor is a blood group antigen (FY system) and is also present on brain Purkinje cells, suggesting broader physiological roles. Therapeutic exploitation of ACKR1 is under exploration in cancer and inflammatory disease, but manipulation risks disturbing critical homeostatic chemokine processes.

Other names

Duffy antigen receptor for chemokinesDARCDuffy blood group antigenFy glycoproteinGlycoprotein DCD234CCBP1Plasmodium vivax receptorGPDDfyGpFyWBCQ1Duffy antigen chemokine receptor

Chemokine antagonism (by sequestration), chemokine transcytosis, blockade of chemokine-mediated cell recruitment, inhibition of pathogen (malarial parasite) entry to erythrocytes.