ACKR1 | Chemokine receptors | IUPHAR/BPS Guide to PHARMACOLOGY

ACKR1

Target id: 316

Nomenclature: ACKR1

Family: Chemokine receptors

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     ACKR1 has curated GtoImmuPdb data

Gene and Protein Information
class A G protein-coupled receptor: Non-signalling 7TM chemokine-binding protein
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 336 1q21-q22 ACKR1 atypical chemokine receptor 1 (Duffy blood group)
Mouse 7 334 1 H3 Ackr1 atypical chemokine receptor 1 (Duffy blood group)
Rat - - 13q24 Ackr1 atypical chemokine receptor 1
Previous and Unofficial Names
Duffy antigen/chemokine receptor | atypical chemokine receptor 1 | CD234 | Dfy | Duffy blood group, atypical chemokine receptor | Darc
Database Links
Specialist databases
GPCRDB ackr1_human (Hs), ackr1_mouse (Mm)
Other databases
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Endogenous ligands (Human)
CXCL5 (CXCL5, P42830), CXCL6 (CXCL6, P80162), CXCL8 (CXCL8, P10145), CXCL11 (CXCL11, O14625), CCL2 (CCL2, P13500), CCL5 (CCL5, P13501), CCL7 (CCL7, P80098), CCL11 (CCL11, P51671), CCL14 (CCL14, Q16627), CCL17 (CCL17, Q92583)
Immunopharmacology Comments
ACKR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. Studies in ACKR1 null mice, and analysis of ACKR1 SNPs in asthmatic patients with poorly controlled symptoms, suggest a role for this cytokine receptor in the temporal regulation of asthma pathophysiology and symptoms [1].
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes
GO:0006954 inflammatory response IBA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 2 GO processes
GO:0032642 regulation of chemokine production IBA
click arrow to show/hide IEA associations
GO:0070098 chemokine-mediated signaling pathway IEA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes
GO:0032642 regulation of chemokine production IBA
Immuno Disease Associations
Disease Name:  Asthma
Disease Synonyms:  no synonynms
Comment:  ACKR1 may play a role in the temporal regulation of asthma pathophysiology and symptoms.
Disease X-refs:  Disease Ontology: DOID:2841
OMIM: 600807
References:  1
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
Mice with targeted disruption of the ACKR1 gene show increased airway hyperresponsiveness to allergen challenge at 24 hours (post last exposure) compared to WT mice. By 7 days post exposure the hyperresponsiveness had resolved in ACKR1 deficient mice but not in WT mice.
Species:  Mouse
Tissue:  Airways.
Technique: 
References:  1
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Darctm1Pogo Darctm1Pogo/Darctm1Pogo
involves: 129P2/OlaHsd * C57BL/6J
MGI:1097689  MP:0000065 abnormal bone marrow cavity morphology PMID: 17416748 
Darctm1Pogo Darctm1Pogo/Darctm1Pogo
involves: 129P2/OlaHsd * C57BL/6J
MGI:1097689  MP:0000130 abnormal cancellous bone morphology PMID: 17416748 
Darctm1Skmz Darctm1Skmz/Darctm1Skmz
involves: 129P2/OlaHsd * C57BL/6J
MGI:1097689  MP:0008721 abnormal chemokine level PMID: 12646177 
Darctm1Scp Darctm1Scp/Darctm1Scp
involves: 129P2/OlaHsd
MGI:1097689  MP:0010209 abnormal circulating chemokine level PMID: 20643340 
Cxcl5tm1Gscw|Darctm1Scp Cxcl5tm1Gscw/Cxcl5tm1Gscw,Darctm1Scp/Darctm1Scp
involves: 129/Sv * 129P2/OlaHsd * C57BL/6
MGI:1096868  MGI:1097689  MP:0010209 abnormal circulating chemokine level PMID: 20643340 
Darctm1Skmz Darctm1Skmz/Darctm1Skmz
involves: 129P2/OlaHsd * C57BL/6J
MGI:1097689  MP:0001764 abnormal homeostasis PMID: 12646177 
Darctm1Pogo Darctm1Pogo/Darctm1Pogo
involves: 129P2/OlaHsd * C57BL/6J
MGI:1097689  MP:0010120 increased bone mineral density PMID: 17416748 
Darctm1Scp Darctm1Scp/Darctm1Scp
involves: 129P2/OlaHsd * C57BL/6
MGI:1097689  MP:0001846 increased inflammatory response PMID: 10961863 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Plasmodium vivax malaria
Disease Ontology: DOID:12978
OMIM: 611162
Role: 
Biologically Significant Variant Comments
The Duffy blood group system, associated with complete resistance to the malarial parasite Plasmodium vivax, and white blood cell count as a quantitative trait are based on variation in the DARC gene. For more information see OMIM entries 110700 and 611862.

References

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1. Chapman DG, Mougey EB, Van der Velden JL, Lahue KG, Aliyeva M, Daphtary N, George KL, Hoffman SM, Schneider RW, Tracy RP et al.. (2017) The Duffy antigen receptor for chemokines regulates asthma pathophysiology. Clin. Exp. Allergy, 47 (9): 1214-1222. [PMID:28471517]

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: ACKR1. Last modified on 29/09/2017. Accessed on 17/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=316.