CXC chemokine receptor 7, member of the class A family of seven-transmembrane G protein-coupled receptors
ACKR3, also known as CXCR7, is an atypical chemokine receptor for CXCL12 and CXCR11. Unlike the classical chemokine receptors, ACKR3 contains a DRYLSIT-sequence instead of the conserved DRYLAIV motif in the second intracellular loop, which is required for G-protein coupling. Thus, ACKR3 does not activate classical GPCR signaling, instead induces beta-arrestin recruitment which is leading to ligand internalization and MAP-kinase activation. It is acting as a scavenger for CXCL12 and, to a lesser degree, for CXCL11. ACKR3 is highly expressed by blood vascular endothelial cells in brain, in numerous embryonic and neonatal tissues, in inflamed tissues and in a variety of cancers such as lymphomas, sarcomas, prostate and breast cancers, and gliomas. 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.