Atypical chemokine receptor 3
Also known as: ACKR3, CMKOR1, CXCR7, GPR159, RDC1
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. Acts as a receptor for chemokines CXCL11 and CXCL12/SDF1. Chemokine binding does not activate G protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization and activation of MAPK signaling pathway. Required for regulation of CXCR4 protein levels in migrating interneurons, thereby adapting their chemokine responsiveness. In glioma cells, transduces signals via MEK/ERK pathway, mediating resistance to apoptosis. Promotes cell growth and survival. Not involved in cell migration, adhesion or proliferation of normal hematopoietic progenitors but activated by CXCL11 in malignant hemapoietic cells, leading to phosphorylation of ERK1/2 (MAPK3/MAPK1) and enhanced cell adhesion and migration. Plays a regulatory role in CXCR4-mediated activation of cell surface integrins by CXCL12. Required for heart valve development. Regulates axon guidance in the oculomotor system through the regulation of CXCL12 levels. Acts as a receptor for SHLP2, mediating its effects on activation of proopiomelanocortin neurons in the arcuate nucleus of the hypothalamus which leads to suppression of food intake and increased energy expenditure.
Classification
- Family (Pfam)
- PF00001 7tm_1
- InterPro
- ACKR3, GPCR_Rhodpsn, GPCR_Rhodpsn_7TM, GPER1-like
- Functional cluster
- G Protein-Coupled Receptors
Experimental structures · PDB · 14
- 6K3F X-ray 2.30A
- 7SK3 EM 3.80A
- 7SK4 EM 3.30A
- 7SK5 EM 4.00A
- 7SK6 EM 4.00A
- 7SK7 EM 3.30A
- 7SK8 EM 3.30A
- 7SK9 EM 3.70A
- 8TII EM 3.00A
- 8TIL EM 3.80A
- 8TIN EM 4.00A
- 8TIO EM 3.60A
- … and 2 more
A predicted model is available from AlphaFold.
Gene Ontology · 26
- GO:0009986 cell surface
- GO:0005905 clathrin-coated pit
- GO:0005769 early endosome
- GO:0005768 endosome
- GO:0009897 external side of plasma membrane
- GO:0005886 plasma membrane
- GO:0055037 recycling endosome
- GO:0019957 C-C chemokine binding
- GO:0016493 C-C chemokine receptor activity
- GO:0019958 C-X-C chemokine binding
- GO:0016494 C-X-C chemokine receptor activity
- GO:0015026 coreceptor activity
- GO:0005044 scavenger receptor activity
- GO:0001525 angiogenesis
- GO:0019722 calcium-mediated signaling
- GO:0007155 cell adhesion
- GO:0060326 cell chemotaxis
- GO:0070098 chemokine-mediated signaling pathway
- GO:0006955 immune response
- GO:1902230 negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage
- GO:0021557 oculomotor nerve development
- GO:0007204 positive regulation of cytosolic calcium ion concentration
- GO:0070374 positive regulation of ERK1 and ERK2 cascade
- GO:1905322 positive regulation of mesenchymal stem cell migration
- GO:0031623 receptor internalization
- GO:0001570 vasculogenesis
Disease associations
- oculomotor-abducens synkinesis MONDO:0030976
Neighborhood · nearest proteins
Related proteins · sequence + function similarity
- Atypical chemokine receptor 3 1.00
- Atypical chemokine receptor 3 1.00
- Atypical chemokine receptor 3 0.99
- G protein-coupled receptor 15 0.94
- G protein-coupled receptor 15 0.94
- Type-1 angiotensin II receptor A 0.94
- G protein-coupled receptor 15 0.93
- G protein-coupled receptor 15 0.93
- Type-1 angiotensin II receptor B 0.93
- Type-2 angiotensin II receptor 0.93
- Type-1 angiotensin II receptor B 0.93
- C-X-C chemokine receptor type 3-2 0.93
Co-cited proteins · studied together in the literature
- Atypical chemokine receptor 3 4 shared papers
- Atypical chemokine receptor 3 2 shared papers
- Stromal cell-derived factor 1 3 shared papers
- Small humanin-like peptide 2 1 shared papers
- Atypical chemokine receptor 4 3 shared papers
- Viral macrophage inflammatory protein 2 1 shared papers
- Atypical chemokine receptor 2 3 shared papers
- Atypical chemokine receptor 1 3 shared papers
- Beta-arrestin-2 2 shared papers
- Beta-arrestin-1 1 shared papers
Literature · 27 cited papers
- Mitochondria-derived peptide SHLP2 regulates energy homeostasis through the activation of hypothalamic neurons. Nat. Commun. · 2023
- Decreased ACKR3 (CXCR7) function causes oculomotor synkinesis in mice and humans. Hum. Mol. Genet. · 2019
- Human herpesvirus 8-encoded chemokine vCCL2/vMIP-II is an agonist of the atypical chemokine receptor ACKR3/CXCR7. Biochem. Pharmacol. · 2016
- Atypical chemokine receptors: from silence to sound. Biochem. Soc. Trans. · 2013
- CXCR7 impact on CXCL12 biology and disease. Trends Mol. Med. · 2013
- The biochemistry and biology of the atypical chemokine receptors. Immunol. Lett. · 2012
- Ubiquitination of CXCR7 controls receptor trafficking. PLoS ONE · 2012
- Carboxy-terminus of CXCR7 regulates receptor localization and function. Int. J. Biochem. Cell Biol. · 2012
- CXCR7 protein expression in human adult brain and differentiated neurons. PLoS ONE · 2011
- CXCR7: a new SDF-1-binding receptor in contrast to normal CD34(+) progenitors is functional and is expressed at higher level in human malignant hematopoietic cells. Eur. J. Haematol. · 2010
- The chemokine receptor CXCR7 is highly expressed in human glioma cells and mediates antiapoptotic effects. Cancer Res. · 2010
- Chemokine decoy receptors: structure-function and biological properties. Curr. Top. Microbiol. Immunol. · 2010
- … and 15 more in the literature graph