Atypical chemokine receptor 3 also known as C-X-C chemokine receptor type 7 (CXCR-7) and G-protein coupled receptor 159 (GPR159) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

that in humans is encoded by the ''ACKR3''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. This gene encodes a member of the

G protein-coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...

family. This protein was earlier thought to be a receptor for vasoactive intestinal peptide (VIP) and was considered to be an orphan receptor. It is now classified as a

chemokine receptor Chemokine receptors are cytokine receptors found on the surface of certain cells that interact with a type of cytokine called a chemokine. There have been 20 distinct chemokine receptors discovered in humans. Each has a rhodopsin-like 7-trans ...

able to bind the chemokines

CXCL12 The stromal cell-derived factor 1 (SDF-1), also known as C-X-C motif chemokine 12 (CXCL12), is a chemokine protein that in humans is encoded by the ''CXCL12'' gene on chromosome 10. It is ubiquitously expressed in many tissues and cell types. Str ...

/SDF-1 and

CXCL11 C-X-C motif chemokine 11 (CXCL11) is a protein that in humans is encoded by the ''CXCL11'' gene. C-X-C motif chemokine 11 is a small cytokine belonging to the CXC chemokine family that is also called ''Interferon-inducible T-cell alpha chemoattra ...

. The protein is also a coreceptor for

human immunodeficiency virus The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immun ...

es (HIV). Translocations involving this gene and HMGA2 on chromosome 12 have been observed in lipomas. Alternatively spliced transcript variants encoding the same protein isoform have been found for this gene. Whereas some reports claim that the receptor induces signaling following ligand binding, recent findings in zebrafish suggest that CXCR7 functions primarily by sequestering the chemokine CXCL12. Another study has provided evidence that ligand binding to CXCR7 activates MAP kinases through Beta-arrestins, and thus has functions beyond ligand sequestration.* ACKR3 has also been shown to sequester endogenous

opioid peptide Opioid peptides are peptides that bind to opioid receptors in the brain; opiates and opioids mimic the effect of these peptides. Such peptides may be produced by the body itself, for example endorphins. The effects of these peptides vary, but t ...

s, and is thought to modulate their activity. Inhibition of ACKR3 by ligands such as the peptide LIH383 (FGGFMRRK-NH₂) increases opioid peptide activity and produces analgesic and antidepressant effects in animal studies.

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Further reading