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Gene Review

ACKR1  -  atypical chemokine receptor 1 (Duffy blood...

Homo sapiens

Synonyms: Atypical chemokine receptor 1, CCBP1, CD234, DARC, Dfy, ...
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Disease relevance of DARC

  • This suggests a potential role for DARC in the inflammatory processes involved in synovitis [1].
  • Binding of HIV-1 to RBCs involves the Duffy antigen receptors for chemokines (DARC) [2].
  • RESULTS: NSCLC tumor cells that constitutively expressed DARC were generated and their growth characteristics were compared to control transfected cells in vitro and in vivo in SCID animals [3].
  • We demonstrated that DARC overexpression induced inhibition of tumorigenesis and/or metastasis through interfering with the tumor angiogenesis in vivo [4].
  • Our results suggest for the first time that DARC is a negative regulator of growth in breast cancer, mainly by sequestration of angiogenic chemokines and subsequent inhibition of tumor neovascularity.Oncogene (2006) 25, 7201-7211. doi:10.1038/sj.onc.1209703; published online 19 June 2006 [4].

High impact information on DARC


Chemical compound and disease context of DARC


Biological context of DARC

  • Because the Fyx phenotype is not associated with apparent clinical consequences, we discussed these findings in the light of the putative roles of DARC in various tissues [13].
  • The mutation may have implications for some physiological roles of DARC and be of interest in malaria research and in studies of population genetics [14].
  • However, the relationship among the Fy6, Fya/b, and Fy3 epitopes, localized in the first and fourth extracellular domains of DARC, respectively, and the chemokine binding sites remained a matter of controversy [15].
  • There was downregulation of DARC protein and mRNA in rheumatoid samples [1].
  • CONCLUSION: The susceptibility of African American recipients to acute rejection and to DGF was not confirmed to be associated with DARC alleles or genotype [16].

Anatomical context of DARC


Associations of DARC with chemical compounds

  • The Duffy (FY) blood group antigens are carried by the DARC glycoprotein, a widely expressed chemokine receptor [13].
  • The 271C --> T substitution represents a considerable change in chemical nature (Arg91 --> Cys), one which may affect the antigenic determinants of DARC, and thus be of clinical significance [14].
  • It has been demonstrated that the promiscuous chemokine binding profile of the Duffy antigen/receptor for chemokines (DARC) is given by its extracellular NH2-terminal region [15].
  • In a structure-function study, we analysed the binding of chemokines and anti-Fy monoclonal antibodies (mAbs) to K562 cells expressing 39 mutant forms of DARC with alanine substitutions spread out on the four extracellular domains (ECDs) [18].
  • A soluble sulphated amino-terminal domain of DARC, but not one modified to phenylalanine at residue 41, can be used to block the association of PvDBP and PkDaBP with red blood cells, with an IC50 of approximately 5 nM [19].

Physical interactions of DARC

  • To determine the basis for promiscuous chemokine binding by DARC, a chimeric receptor composed of the E1 domain of DARC and hydrophobic helices and loops from IL-8RB (DARCe1/IL-8RB) was constructed [20].
  • Receptor binding and biological studies with the alanine scan mutants of MGSA demonstrate that MGSA binds to DARC and the IL-8RB through distinct binding regions [21].
  • CXCL-8 and CCL-5 chemokine binding analysis indicated that the promiscuous binding profile characteristic of DARC is conserved across species [22].
  • Here we show that a truncated form of HveC directly binds to HSV glycoprotein D (gD) in solution and at the surface of virions [23].
  • Herpes simplex virus glycoprotein D can bind to poliovirus receptor-related protein 1 or herpesvirus entry mediator, two structurally unrelated mediators of virus entry [23].

Regulatory relationships of DARC


Other interactions of DARC


Analytical, diagnostic and therapeutic context of DARC


  1. Expression of the duffy antigen/receptor for chemokines (DARC) by the inflamed synovial endothelium. Patterson, A.M., Siddall, H., Chamberlain, G., Gardner, L., Middleton, J. J. Pathol. (2002) [Pubmed]
  2. Binding of HIV-1 to RBCs involves the Duffy antigen receptors for chemokines (DARC). Lachgar, A., Jaureguiberry, G., Le Buenac, H., Bizzini, B., Zagury, J.F., Rappaport, J., Zagury, D. Biomed. Pharmacother. (1998) [Pubmed]
  3. Overexpression of the duffy antigen receptor for chemokines (DARC) by NSCLC tumor cells results in increased tumor necrosis. Addison, C.L., Belperio, J.A., Burdick, M.D., Strieter, R.M. BMC Cancer (2004) [Pubmed]
  4. Enhanced expression of Duffy antigen receptor for chemokines by breast cancer cells attenuates growth and metastasis potential. Wang, J., Ou, Z.L., Hou, Y.F., Luo, J.M., Shen, Z.Z., Ding, J., Shao, Z.M. Oncogene (2006) [Pubmed]
  5. Interaction of KAI1 on tumor cells with DARC on vascular endothelium leads to metastasis suppression. Bandyopadhyay, S., Zhan, R., Chaudhuri, A., Watabe, M., Pai, S.K., Hirota, S., Hosobe, S., Tsukada, T., Miura, K., Takano, Y., Saito, K., Pauza, M.E., Hayashi, S., Wang, Y., Mohinta, S., Mashimo, T., Iiizumi, M., Furuta, E., Watabe, K. Nat. Med. (2006) [Pubmed]
  6. Herpes simplex virus glycoprotein D: human monoclonal antibody produced by bone marrow cell line. Seigneurin, J.M., Desgranges, C., Seigneurin, D., Paire, J., Renversez, J.C., Jacquemont, B., Micouin, C. Science (1983) [Pubmed]
  7. Detection of antibodies to herpes simplex virus with a continuous cell line expressing cloned glycoprotein D. Berman, P.W., Dowbenko, D., Lasky, L.A., Simonsen, C.C. Science (1983) [Pubmed]
  8. The DARC side of metastasis: Shining a light on KAI1-mediated metastasis suppression in the vascular tunnel. Zijlstra, A., Quigley, J.P. Cancer Cell (2006) [Pubmed]
  9. Effect of nonprotective vaccination on antibody response to subsequent human immunodeficiency virus infection. Pincus, S.H., Messer, K.G., Hu, S.L. J. Clin. Invest. (1994) [Pubmed]
  10. Herpes simplex virus glycoprotein D acquires mannose 6-phosphate residues and binds to mannose 6-phosphate receptors. Brunetti, C.R., Burke, R.L., Kornfeld, S., Gregory, W., Masiarz, F.R., Dingwell, K.S., Johnson, D.C. J. Biol. Chem. (1994) [Pubmed]
  11. Mutations in the N termini of herpes simplex virus type 1 and 2 gDs alter functional interactions with the entry/fusion receptors HVEM, nectin-2, and 3-O-sulfated heparan sulfate but not with nectin-1. Yoon, M., Zago, A., Shukla, D., Spear, P.G. J. Virol. (2003) [Pubmed]
  12. Truncated forms of glycoprotein D of herpes simplex virus 1 capable of blocking apoptosis and of low-efficiency entry into cells form a heterodimer dependent on the presence of a cysteine located in the shared transmembrane domains. Zhou, G., Roizman, B. J. Virol. (2002) [Pubmed]
  13. Arg89Cys substitution results in very low membrane expression of the Duffy antigen/receptor for chemokines in Fy(x) individuals. Tournamille, C., Le Van Kim, C., Gane, P., Le Pennec, P.Y., Roubinet, F., Babinet, J., Cartron, J.P., Colin, Y. Blood (1998) [Pubmed]
  14. A novel mutation in the coding sequence of the FY*B allele of the Duffy chemokine receptor gene is associated with an altered erythrocyte phenotype. Parasol, N., Reid, M., Rios, M., Castilho, L., Harari, I., Kosower, N.S. Blood (1998) [Pubmed]
  15. Close association of the first and fourth extracellular domains of the Duffy antigen/receptor for chemokines by a disulfide bond is required for ligand binding. Tournamille, C., Le Van Kim, C., Gane, P., Blanchard, D., Proudfoot, A.E., Cartron, J.P., Colin, Y. J. Biol. Chem. (1997) [Pubmed]
  16. Duffy antigen receptor and genetic susceptibility of African Americans to acute rejection and delayed function. Mange, K.C., Prak, E.L., Kamoun, M., Du, Y., Goodman, N., Danoff, T., Hoy, T., Newman, M., Joffe, M.M., Feldman, H.I. Kidney Int. (2004) [Pubmed]
  17. Upregulation of interleukin 8 by oxygen-deprived cells in glioblastoma suggests a role in leukocyte activation, chemotaxis, and angiogenesis. Desbaillets, I., Diserens, A.C., Tribolet, N., Hamou, M.F., Van Meir, E.G. J. Exp. Med. (1997) [Pubmed]
  18. Structure-function analysis of the extracellular domains of the Duffy antigen/receptor for chemokines: characterization of antibody and chemokine binding sites. Tournamille, C., Filipe, A., Wasniowska, K., Gane, P., Lisowska, E., Cartron, J.P., Colin, Y., Le Van Kim, C. Br. J. Haematol. (2003) [Pubmed]
  19. Sulphated tyrosines mediate association of chemokines and Plasmodium vivax Duffy binding protein with the Duffy antigen/receptor for chemokines (DARC). Choe, H., Moore, M.J., Owens, C.M., Wright, P.L., Vasilieva, N., Li, W., Singh, A.P., Shakri, R., Chitnis, C.E., Farzan, M. Mol. Microbiol. (2005) [Pubmed]
  20. The promiscuous chemokine binding profile of the Duffy antigen/receptor for chemokines is primarily localized to sequences in the amino-terminal domain. Lu, Z.H., Wang, Z.X., Horuk, R., Hesselgesser, J., Lou, Y.C., Hadley, T.J., Peiper, S.C. J. Biol. Chem. (1995) [Pubmed]
  21. A mutant of melanoma growth stimulating activity does not activate neutrophils but blocks erythrocyte invasion by malaria. Hesselgesser, J., Chitnis, C.E., Miller, L.H., Yansura, D.G., Simmons, L.C., Fairbrother, W.J., Kotts, C., Wirth, C., Gillece-Castro, B.L., Horuk, R. J. Biol. Chem. (1995) [Pubmed]
  22. Sequence, evolution and ligand binding properties of mammalian Duffy antigen/receptor for chemokines. Tournamille, C., Blancher, A., Le Van Kim, C., Gane, P., Apoil, P.A., Nakamoto, W., Cartron, J.P., Colin, Y. Immunogenetics (2004) [Pubmed]
  23. Herpes simplex virus glycoprotein D can bind to poliovirus receptor-related protein 1 or herpesvirus entry mediator, two structurally unrelated mediators of virus entry. Krummenacher, C., Nicola, A.V., Whitbeck, J.C., Lou, H., Hou, W., Lambris, J.D., Geraghty, R.J., Spear, P.G., Cohen, G.H., Eisenberg, R.J. J. Virol. (1998) [Pubmed]
  24. The Duffy antigen/receptor for chemokines (DARC) is expressed in endothelial cells of Duffy negative individuals who lack the erythrocyte receptor. Peiper, S.C., Wang, Z.X., Neote, K., Martin, A.W., Showell, H.J., Conklyn, M.J., Ogborne, K., Hadley, T.J., Lu, Z.H., Hesselgesser, J., Horuk, R. J. Exp. Med. (1995) [Pubmed]
  25. Antigen-specific cytokine and antibody isotype profiles induced by mucosal and systemic immunization with recombinant adenoviruses. Papp, Z., Babiuk, L.A., Baca-Estrada, M.E. Viral Immunol. (1999) [Pubmed]
  26. The Duffy antigen receptor for chemokines is up-regulated during acute renal transplant rejection and crescentic glomerulonephritis. Segerer, S., Regele, H., MacK, M., Kain, R., Cartron, J.P., Colin, Y., Kerjaschki, D., Schlöndorff, D. Kidney Int. (2000) [Pubmed]
  27. Molecular cloning and characterization of a mouse gene with homology to the Duffy-antigen receptor for chemokines. Tang, T., Owen, J.D., Du, J., Walker, C.L., Richmond, A. DNA Seq. (1998) [Pubmed]
  28. Mapping binding residues in the Plasmodium vivax domain that binds Duffy antigen during red cell invasion. Hans, D., Pattnaik, P., Bhattacharyya, A., Shakri, A.R., Yazdani, S.S., Sharma, M., Choe, H., Farzan, M., Chitnis, C.E. Mol. Microbiol. (2005) [Pubmed]
  29. 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. Chaudhuri, A., Polyakova, J., Zbrzezna, V., Williams, K., Gulati, S., Pogo, A.O. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
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