ACKR3

Target id: 80

Nomenclature: ACKR3

Family: Chemokine receptors

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

   GtoImmuPdb view: OFF :     ACKR3 has curated GtoImmuPdb data

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 362 2q37.3 ACKR3 atypical chemokine receptor 3
Mouse 7 362 1 D Ackr3 atypical chemokine receptor 3
Rat 7 362 9q35 Ackr3 atypical chemokine receptor 3
Previous and Unofficial Names
chemokine orphan receptor 1
GPR159
chemokine (C-X-C motif) receptor 7
G-protein coupled receptor 159
G-protein coupled receptor RDC1 homolog
CXCR7
Cxcr7
Database Links
Specialist databases
GPCRDB ackr3_human (Hs), ackr3_mouse (Mm), ackr3_rat (Rn)
Other databases
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
CXCL11 {Sp: Human}
CXCL12α {Sp: Human}
Comments: Several lines of evidence have suggested that adrenomedullin is a ligand for ACKR3; however, classical direct binding to the receptor has not yet been convincingly demonstrated.

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
adrenomedullin {Sp: Rat} Rn Agonist 8.1 pEC50 8
pEC50 8.1 (EC50 7x10-9 M) [8]
CXCL12α {Sp: Human} Hs Agonist 7.5 – 7.9 pEC50 5,12
pEC50 7.5 – 7.9 [5,12]
plerixafor Hs Agonist 6.8 pEC50 5,7
pEC50 6.8 [5,7]
TC14012 Hs Agonist 6.5 pEC50 5
pEC50 6.5 [5]
CXCL11 {Sp: Human} Hs Full agonist - -
View species-specific agonist tables
Agonist Comments
Burns et al. show that CXCL12 (SDF-1α) binding of CXCR7 is inhibited by CXCL11 (I-TAC) [3]. CXCR7 is demonstrated to bind to CXCL1 with high affinity. The agonist activity of CXCL12 at CXCR7 has been confirmed [1].
A selective small molecule agonist, CCX771 (chemical structure unavailable) binds hACKR3 with an IC50 of 4.1nM [13].
Tissue Distribution
B cells
Species:  Human
Technique:  FACS, LC-MS and function as scavenger.
References:  6
Primitive erythroid cell
Species:  Mouse
Technique:  Immunohistochemistry, (CXCR7(-/-) used as negative controls)
References:  2
Bone, brain, heart, kidney and vasculature expression detected in neonates; expression in bone and heart in adult mice
Expression level:  High
Species:  Mouse
Technique:  LacZ reporter assay
References:  4
Kidney and testis of adult mice
Expression level:  Low
Species:  Mouse
Technique:  LacZ reporter assay
References:  4
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Physiological Consequences of Altering Gene Expression
Cxcr7 knockout mice displayed myocardial degeneration and fibrosis. Crxcr7 -/- neonates displayed hyperplasia.
Species:  Mouse
Tissue:  Heart tissues
Technique:  Gene knockout
References:  4
Impaired heart valve formation during embryonic development
Species:  Mouse
Tissue:  Heart
Technique:  Gene knockouts
References:  11
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Cxcr7tm1.1Fma Cxcr7tm1.1Fma/Cxcr7tm1.1Fma
involves: BALB/cJ * C57BL/6
MGI:109562  MP:0002747 abnormal aortic valve morphology PMID: 17804806 
Cxcr7+|Cxcr7tm1.1Fma Cxcr7tm1.1Fma/Cxcr7+
involves: BALB/cJ * C57BL/6
MGI:109562  MP:0002747 abnormal aortic valve morphology PMID: 17804806 
Cxcr7tm1Fma|Tg(Tek-cre)12Flv Cxcr7tm1Fma/Cxcr7tm1Fma,Tg(Tek-cre)12Flv/?
involves: C3H * C57BL/6
MGI:109562  MGI:2136409  MP:0002747 abnormal aortic valve morphology PMID: 17804806 
Cxcr7tm1.1Fma Cxcr7tm1.1Fma/Cxcr7tm1.1Fma
involves: BALB/cJ * C57BL/6
MGI:109562  MP:0000266 abnormal heart morphology PMID: 17804806 
Cxcr7tm1Litt Cxcr7tm1Litt/Cxcr7tm1Litt
involves: C57BL/6 * FVB/N
MGI:109562  MP:0000281 abnormal interventricular septum morphology
Cxcr7tm1.1Fma Cxcr7tm1.1Fma/Cxcr7tm1.1Fma
involves: BALB/cJ * C57BL/6
MGI:109562  MP:0006126 abnormal outflow tract development PMID: 17804806 
Cxcr7tm1.1Fma Cxcr7tm1.1Fma/Cxcr7tm1.1Fma
involves: BALB/cJ * C57BL/6
MGI:109562  MP:0002748 abnormal pulmonary valve morphology PMID: 17804806 
Cxcr7tm1Fma|Tg(Tek-cre)12Flv Cxcr7tm1Fma/Cxcr7tm1Fma,Tg(Tek-cre)12Flv/?
involves: C3H * C57BL/6
MGI:109562  MGI:2136409  MP:0002748 abnormal pulmonary valve morphology PMID: 17804806 
Cxcr7tm1Litt Cxcr7tm1Litt/Cxcr7tm1Litt
involves: C57BL/6 * FVB/N
MGI:109562  MP:0002746 abnormal semilunar valve morphology
Cxcr7tm1.1Fma Cxcr7tm1.1Fma/Cxcr7tm1.1Fma
involves: BALB/cJ * C57BL/6
MGI:109562  MP:0006116 aortic valve calcification PMID: 17804806 
Cxcr7tm1.1Fma Cxcr7tm1.1Fma/Cxcr7tm1.1Fma
involves: BALB/cJ * C57BL/6
MGI:109562  MP:0010403 atrial septal defect PMID: 17804806 
Cxcr7tm1Jgo Cxcr7tm1Jgo/Cxcr7tm1Jgo
involves: 129S/SvEvBrd * C57BL/6
MGI:109562  MP:0001855 atrial thrombosis PMID: 18442043 
Cxcr7+|Cxcr7tm1Jgo Cxcr7tm1Jgo/Cxcr7+
involves: 129S/SvEvBrd * C57BL/6
MGI:109562  MP:0003141 cardiac fibrosis PMID: 18442043 
Cxcr7tm1Jgo Cxcr7tm1Jgo/Cxcr7tm1Jgo
involves: 129S/SvEvBrd * C57BL/6
MGI:109562  MP:0003141 cardiac fibrosis PMID: 18442043 
Cxcr7tm1.1Fma Cxcr7tm1.1Fma/Cxcr7tm1.1Fma
involves: BALB/cJ * C57BL/6
MGI:109562  MP:0008182 decreased marginal zone B cell number PMID: 17804806 
Cxcr7tm1Jgo Cxcr7tm1Jgo/Cxcr7tm1Jgo
involves: 129S/SvEvBrd * C57BL/6
MGI:109562  MP:0008770 decreased survivor rate PMID: 18442043 
Cxcr7tm1.1Fma Cxcr7tm1.1Fma/Cxcr7tm1.1Fma
involves: BALB/cJ * C57BL/6
MGI:109562  MP:0002754 dilated heart right ventricle PMID: 17804806 
Cxcr7tm1Fma|Tg(Tek-cre)12Flv Cxcr7tm1Fma/Cxcr7tm1Fma,Tg(Tek-cre)12Flv/?
involves: C3H * C57BL/6
MGI:109562  MGI:2136409  MP:0002754 dilated heart right ventricle PMID: 17804806 
Cxcr7tm1Jgo Cxcr7tm1Jgo/Cxcr7tm1Jgo
involves: 129S/SvEvBrd * C57BL/6
MGI:109562  MP:0000275 heart hyperplasia PMID: 18442043 
Cxcr7+|Cxcr7tm1Jgo Cxcr7tm1Jgo/Cxcr7+
involves: 129S/SvEvBrd * C57BL/6
MGI:109562  MP:0001861 lung inflammation PMID: 18442043 
Cxcr7tm1Jgo Cxcr7tm1Jgo/Cxcr7tm1Jgo
involves: 129S/SvEvBrd * C57BL/6
MGI:109562  MP:0001861 lung inflammation PMID: 18442043 
Cxcr7+|Cxcr7tm1Jgo Cxcr7tm1Jgo/Cxcr7+
involves: 129S/SvEvBrd * C57BL/6
MGI:109562  MP:0004566 myocardial fiber degeneration PMID: 18442043 
Cxcr7tm1Jgo Cxcr7tm1Jgo/Cxcr7tm1Jgo
involves: 129S/SvEvBrd * C57BL/6
MGI:109562  MP:0004566 myocardial fiber degeneration PMID: 18442043 
Cxcr7tm1.1Fma Cxcr7tm1.1Fma/Cxcr7tm1.1Fma
involves: BALB/cJ * C57BL/6
MGI:109562  MP:0002058 neonatal lethality PMID: 17804806 
Cxcr7tm1.1Fma Cxcr7tm1.1Fma/Cxcr7tm1.1Fma
involves: BALB/cJ * C57BL/6
MGI:109562  MP:0000273 overriding aorta PMID: 17804806 
Cxcr7tm1Litt Cxcr7tm1Litt/Cxcr7tm1Litt
involves: C57BL/6 * FVB/N
MGI:109562  MP:0002081 perinatal lethality
Cxcr7tm1Jgo Cxcr7tm1Jgo/Cxcr7tm1Jgo
involves: 129S/SvEvBrd * C57BL/6
MGI:109562  MP:0002082 postnatal lethality PMID: 18442043 
Cxcr7tm1.1Fma Cxcr7tm1.1Fma/Cxcr7tm1.1Fma
involves: BALB/cJ * C57BL/6
MGI:109562  MP:0002083 premature death PMID: 17804806 
Cxcr7+|Cxcr7tm1Jgo Cxcr7tm1Jgo/Cxcr7+
involves: 129S/SvEvBrd * C57BL/6
MGI:109562  MP:0006050 pulmonary fibrosis PMID: 18442043 
Cxcr7tm1Jgo Cxcr7tm1Jgo/Cxcr7tm1Jgo
involves: 129S/SvEvBrd * C57BL/6
MGI:109562  MP:0006050 pulmonary fibrosis PMID: 18442043 
Cxcr7tm1.1Fma Cxcr7tm1.1Fma/Cxcr7tm1.1Fma
involves: BALB/cJ * C57BL/6
MGI:109562  MP:0010402 ventricular septal defect PMID: 17804806 
Gene Expression and Pathophysiology
CXCR7 is expressed on lymphatic endothelial cells during renal allograft rejection
Tissue or cell type:  Kidney
Pathophysiology:  renal allograft rejection
Species:  Human
Technique:  RT-PCR
References:  10
CXCR7 modulates adrenomedullin-mediated cardiac and lymphatic vascular development.
Tissue or cell type:  Heart.
Pathophysiology:  Myocyte hyperplasia.
Species:  Mouse
Technique:  Gene kockout.
References:  9
Immunopharmacology Comments
ACKR3 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation.
Immuno Process Associations
Immuno Process:  Antigen presentation
Immuno Process ID:  3
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  scavenger receptor activity (GO:0005044) IMP
receptor internalization (GO:0031623) IMP
References: 
Immuno Process:  Cytokine production & signalling
Immuno Process ID:  9
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  C-X-C chemokine receptor activity (GO:0016494) IMP
chemokine-mediated signaling pathway (GO:0070098) IMP
References: 

References

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1. Balabanian K, Lagane B, Infantino S, Chow KY, Harriague J, Moepps B, Arenzana-Seisdedos F, Thelen M, Bachelerie F. (2005) The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes. J. Biol. Chem.280 (42): 35760-6. [PMID:16107333]

2. Berahovich RD, Zabel BA, Penfold ME, Lewén S, Wang Y, Miao Z, Gan L, Pereda J, Dias J, Slukvin II, McGrath KE, Jaen JC, Schall TJ. (2010) CXCR7 Protein Is Not Expressed on Human or Mouse Leukocytes. J. Immunol.185 (9): 5130-9. [PMID:20889540]

3. Burns JM, Summers BC, Wang Y, Melikian A, Berahovich R, Miao Z, Penfold ME, Sunshine MJ, Littman DR, Kuo CJ, Wei K, McMaster BE, Wright K, Howard MC, Schall TJ. (2006) A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development. J. Exp. Med.203 (9): 2201-13. [PMID:16940167]

4. Gerrits H, van Ingen Schenau DS, Bakker NE, van Disseldorp AJ, Strik A, Hermens LS, Koenen TB, Krajnc-Franken MA, Gossen JA. (2008) Early postnatal lethality and cardiovascular defects in CXCR7-deficient mice. Genesis46 (5): 235-45. [PMID:18442043]

5. Gravel S, Malouf C, Boulais PE, Berchiche YA, Oishi S, Fujii N, Leduc R, Sinnett D, Heveker N. (2010) The peptidomimetic CXCR4 antagonist TC14012 recruits {beta}-arrestin to CXCR7 roles of receptor domains. J Biol Chem,  [Epub ahead of print]. [PMID:20956518]

6. Humpert ML, Tzouros M, Thelen S, Bignon A, Levoye A, Arenzana-Seisdedos F, Balabanian K, Bachelerie F, Langen H, Thelen M. (2012) Complementary methods provide evidence for the expression of CXCR7 on human B cells. Proteomics12 (12): 1938-48. [PMID:22623068]

7. Kalatskaya I, Berchiche YA, Gravel S, Limberg BJ, Rosenbaum JS, Heveker N. (2009) AMD3100 is a CXCR7 ligand with allosteric agonist properties. Mol. Pharmacol.75 (5): 1240-7. [PMID:19255243]

8. Kapas S, Catt KJ, Clark AJ. (1995) Cloning and expression of cDNA encoding a rat adrenomedullin receptor. J. Biol. Chem.270 (43): 25344-7. [PMID:7592696]

9. Klein KR, Karpinich NO, Espenschied ST, Willcockson HH, Dunworth WP, Hoopes SL, Kushner EJ, Bautch VL, Caron KM. (2014) Decoy receptor CXCR7 modulates adrenomedullin-mediated cardiac and lymphatic vascular development. Dev. Cell30 (5): 528-40. [PMID:25203207]

10. Neusser MA, Kraus AK, Regele H, Cohen CD, Fehr T, Kerjaschki D, Wüthrich RP, Penfold ME, Schall T, Segerer S. (2010) The chemokine receptor CXCR7 is expressed on lymphatic endothelial cells during renal allograft rejection. Kidney Int.77 (9): 801-8. [PMID:20164826]

11. Sierro F, Biben C, Martínez-Muñoz L, Mellado M, Ransohoff RM, Li M, Woehl B, Leung H, Groom J, Batten M, Harvey RP, Martínez-A C, Mackay CR, Mackay F. (2007) Disrupted cardiac development but normal hematopoiesis in mice deficient in the second CXCL12/SDF-1 receptor, CXCR7. Proc. Natl. Acad. Sci. U.S.A.104 (37): 14759-64. [PMID:17804806]

12. Southern C, Cook JM, Neetoo-Isseljee Z, Taylor DL, Kettleborough CA, Merritt A, Bassoni DL, Raab WJ, Quinn E, Wehrman TS et al.. (2013) Screening β-Arrestin Recruitment for the Identification of Natural Ligands for Orphan G-Protein-Coupled Receptors. J Biomol Screen18 (5): 599-609. [PMID:23396314]

13. Zabel BA, Wang Y, Lewén S, Berahovich RD, Penfold ME, Zhang P, Powers J, Summers BC, Miao Z, Zhao B, Jalili A, Janowska-Wieczorek A, Jaen JC, Schall TJ. (2009) Elucidation of CXCR7-mediated signaling events and inhibition of CXCR4-mediated tumor cell transendothelial migration by CXCR7 ligands. J. Immunol.183 (5): 3204-11. [PMID:19641136]

Contributors

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How to cite this page

Francoise Bachelerie, Adit Ben-Baruch, Israel F. Charo, Christophe Combadiere, Joshua M. Farber, Reinhold Förster, Gerard J. Graham, Richard Horuk, Massimo Locati, Andrew D. Luster, Alberto Mantovani, Georgios L Moschovakis, Philip M. Murphy, Robert J. B. Nibbs, Hisayuki Nomiyama, Joost J. Oppenheim, Christine A. Power, Amanda E. I. Proudfoot , Mette M. Rosenkilde, Antal Rot, Silvano Sozzani, Marcus Thelen, Osamu Yoshie, Albert Zlotnik.
Chemokine receptors: ACKR3. Last modified on 22/02/2017. Accessed on 20/07/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=80.