Atypical chemokine receptor 3 (IPR001416)

Short name: ACKR3

Overlapping homologous superfamilies


Family relationships


Just like classical chemokine receptors, atypical chemokine receptors (ACKRs) are seven-transmembrane-helix (7TM) receptors that bind chemokines [PMID: 24319779]. However, they lack the canonical DRYLAIV motif necessary for GPCR coupling to G proteins and induction of classical signalling pathways. Instead, ACKRs internalise their chemokine ligands, which may subsequently affect chemokine availability. The ACKR family comprises five members: Duffy Antigen Receptor for Chemokines (DARC, ACKR1), D6 (ACKR2), CXCR7 (ACKR3), CCRL1 (ACKR4) and CCRL2 (ACKR5) [PMID: 24549061].

Atypical chemokine receptor 3 (ACKR3), previously known as CXC chemokine receptor 7 (CXCR7), is regarded as a scavenger for CXCL12 and, to a lesser extent, for CXCL11 [PMID: 20161793]. Unlike other CXC chemokine receptors, ACKR3 does not elicit classical chemokine receptor signalling via typical G protein-mediated pathways [PMID: 20018651], but instead induces beta-arrestin recruitment, leading to ligand internalisation and activation of MAPK signaling pathway [PMID: 19641136, PMID: 20018651].

ACKR3/CXCR7 has been identified on memory B cells and in mammals is found in bone, brain, heart and kidney [PMID: 18442043, PMID: 17804806]. It has been shown to act as a novel coreceptor for several immunodeficiency virus strains, which infect brain-derived cells [PMID: 10623723]. Studies in zebrafish have also revealed a critical role in vascular formation and angiogenesis during development [PMID: 17898181]. ACKR3/CXCR7 is a functional receptor for CXCL12 in astrocytomas/glioblastomas and mediates resistance to drug-induced apoptosis [PMID: 20388803]. It has been shown to promote growth of tumors formed from breast and lung cancer cells [PMID: 16940167].

GO terms

Biological Process

GO:0001525 angiogenesis
GO:0006935 chemotaxis
GO:0001570 vasculogenesis

Molecular Function

GO:0019956 chemokine binding
GO:0015026 coreceptor activity

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.