InterPro : IPR005384

Name  Duffy antigen/chemokine receptor Short Name  Duffy_chemokine_rcpt
Type  Family Description  Chemokines (chemotactic cytokines) are a family of chemoattractant molecules. They attract leukocytes to areas of inflammation and lesions, and play a key role in leukocyte activation. Originally defined as host defense proteins, chemokines are now known to play a much broader biological role []. They have a wide range of effects in many different cell types beyond the immune system, including, for example, various cells of the central nervous system [], and endothelial cells, where they may act as either angiogenic or angiostatic factors [].The chemokine family is divided into four classes based on the number and spacing of their conserved cysteines: 2 Cys residues may be adjacent (the CC family); separated by an intervening residue (the CXC family); have only one of the first two Cys residues (C chemokines); or contain both cysteines, separated by three intervening residues (CX3C chemokines).Chemokines exert their effects by binding to rhodopsin-like G protein-coupled receptors on the surface of cells. Following interaction with their specific chemokine ligands, chemokine receptors trigger a flux in intracellular calcium ions, which cause a cellular response, including the onset of chemotaxis. There are over fifty distinct chemokines and least 18 human chemokine receptors []. Although the receptors bind only a single class of chemokines, they often bind several members of the same class with high affinity. Chemokine receptors are preferentially expressed on important functional subsets of dendritic cells, monocytes and lymphocytes, including Langerhans cells and T helper cells [, ]. Chemokines and their receptors can also be subclassified into homeostatic leukocyte homing molecules (CXCR4, CXCR5, CCR7, CCR9) versus inflammatory/inducible molecules (CXCR1, CXCR2, CXCR3, CCR1-6, CX3CR1).This entry represents the Duffy antigen/chemokine receptor, DARC (Duffy Antigen for Chemokines). It is also known as Fy protein [, ], and was originally identified as a blood group antigen. DARC has been found to act as a multi-specific receptor for chemokines of both the C-C and C-X-C families including CCL2, CCL5, CXCL1 and CXCL4 [, , , , ], it has also been shown to internalise chemokines but not scavenge them []. Although DARC is a 7-transmembrane protein, sharing a high content of alpha-helical secondary structure typical of chemokine structures [], the characteristic rhodopsin-like signature is virtually absent. As a result, unlike classical chemokine receptors DARC does not signal through G-proteins, so is regarded as an atypical chemokine receptor. DARC was initially described on red blood cells, but subsequent studies have demonstrated DARC protein expression on renal endothelial and epithelial cells and in Purkinje cells of the cerebellum, even in Duffy-negative individuals whose red cells lack DARC [, , , , ]. DARC is believed to play an important role in endothelial cells, since expression on these cell types is highly conserved, whereas the function on RBCs appears to be dispensable in order to confer resistance to malaria []. There is evidence suggesting a role for DARC in neutrophil migration from the blood into the tissues []and in modulating inflammatory response [, , , , ].
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25 Publications

First Author Title Year Journal Volume Pages
Horuk R Chemokine receptors. 2001 Cytokine Growth Factor Rev 12 313-35
Zlotnik A Chemokines: a new classification system and their role in immunity. 2000 Immunity 12 121-7
Charbonnier AS Macrophage inflammatory protein 3alpha is involved in the constitutive trafficking of epidermal langerhans cells. 1999 J Exp Med 190 1755-68
Sallusto F Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes. 1998 J Exp Med 187 875-83
Ma Q Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. 1998 Proc Natl Acad Sci U S A 95 9448-53
Strieter RM The functional role of the ELR motif in CXC chemokine-mediated angiogenesis. 1995 J Biol Chem 270 27348-57
Murphy PM International union of pharmacology. XXII. Nomenclature for chemokine receptors. 2000 Pharmacol Rev 52 145-76
Hadley TJ From malaria to chemokine receptor: the emerging physiologic role of the Duffy blood group antigen. 1997 Blood 89 3077-91
Chaudhuri A Cloning of glycoprotein D cDNA, which encodes the major subunit of the Duffy blood group system and the receptor for the Plasmodium vivax malaria parasite. 1993 Proc Natl Acad Sci U S A 90 10793-7
Tournamille C Disruption of a GATA motif in the Duffy gene promoter abolishes erythroid gene expression in Duffy-negative individuals. 1995 Nat Genet 10 224-8
Horuk R A receptor for the malarial parasite Plasmodium vivax: the erythrocyte chemokine receptor. 1993 Science 261 1182-4
Chaudhuri A Expression of the Duffy antigen in K562 cells. Evidence that it is the human erythrocyte chemokine receptor. 1994 J Biol Chem 269 7835-8
Horuk R Identification and characterization of a promiscuous chemokine-binding protein in a human erythroleukemic cell line. 1994 J Biol Chem 269 17730-3
McMorran BJ Platelet factor 4 and Duffy antigen required for platelet killing of Plasmodium falciparum. 2012 Science 338 1348-51
Pruenster M The Duffy antigen receptor for chemokines transports chemokines and supports their promigratory activity. 2009 Nat Immunol 10 101-8
Grodecka M One-step immunopurification and lectinochemical characterization of the Duffy atypical chemokine receptor from human erythrocytes. 2012 Glycoconj J 29 93-105
Horuk R Expression of chemokine receptors by subsets of neurons in the central nervous system. 1997 J Immunol 158 2882-90
Hadley TJ Postcapillary venule endothelial cells in kidney express a multispecific chemokine receptor that is structurally and functionally identical to the erythroid isoform, which is the Duffy blood group antigen. 1994 J Clin Invest 94 985-91
Lee JS Duffy antigen facilitates movement of chemokine across the endothelium in vitro and promotes neutrophil transmigration in vitro and in vivo. 2003 J Immunol 170 5244-51
Dawson TC Exaggerated response to endotoxin in mice lacking the Duffy antigen/receptor for chemokines (DARC). 2000 Blood 96 1681-4
Patterson AM Expression of the duffy antigen/receptor for chemokines (DARC) by the inflamed synovial endothelium. 2002 J Pathol 197 108-16
Rot A Contribution of Duffy antigen to chemokine function. 2005 Cytokine Growth Factor Rev 16 687-94
Brühl H Expression of DARC, CXCR3 and CCR5 in giant cell arteritis. 2005 Rheumatology (Oxford) 44 309-13
Peiper SC The Duffy antigen/receptor for chemokines (DARC) is expressed in endothelial cells of Duffy negative individuals who lack the erythrocyte receptor. 1995 J Exp Med 181 1311-7
Liu XH Up-regulation of Duffy antigen receptor expression in children with renal disease. 1999 Kidney Int 55 1491-500



To cite PlanMine, please refer to the following publication:

Rozanski, A., Moon, H., Brandl, H., Martín-Durán, J. M., Grohme, M., Hüttner, K., Bartscherer, K., Henry, I., & Rink, J. C.
PlanMine 3.0—improvements to a mineable resource of flatworm biology and biodiversity
Nucleic Acids Research, gky1070. doi:10.1093/nar/gky1070 (2018)