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Gene Review

ACKR4  -  atypical chemokine receptor 4

Homo sapiens

Synonyms: Atypical chemokine receptor 4, C-C CKR-11, C-C chemokine receptor type 11, CC chemokine receptor-like 1, CC-CKR-11, ...
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Disease relevance of CCRL1


High impact information on CCRL1

  • An update of the International Union of Pharmacology nomenclature for chemokines is outlined, defining one new receptor type, CXCR6, and disqualifying the putative receptor, CCR11 [6].
  • Few T cells in any mucosal tissue examined express CCR10 [7].
  • Here we demonstrate that CCR10, a receptor for MEC, is selectively expressed by IgA Ab-secreting cells (large s/cIgA(+)CD38(hi)CD19(int/-)CD20(-)), including circulating IgA(+) plasmablasts and almost all IgA(+) plasma cells in the salivary gland, small intestine, large intestine, appendix, and tonsils [7].
  • Unlike other C6 zinc cluster proteins such as GAL4 and PPR1, HAP1 binds selectively to asymmetric DNA sites containing a direct repeat of two CGG triplets [8].
  • These receptor clones will be useful in elucidating the functional role of PP and designing selective PP receptor agonists and antagonists [9].

Biological context of CCRL1

  • We report here on human CCX CKR, previously represented only by noncontiguous expressed sequence tags homologous to bovine PPR1, a putative gustatory receptor [10].
  • However, in man, there are two copies of the CCX-CKR gene, one on chromosome 3 nestled within the ACD homologue, and one on chromosome 6 [11].
  • CCX-CKR cannot couple to typical chemokine receptor signalling pathways or mediate chemotaxis, and its function remains unclear [12].
  • The gene for CCR11 was localized to human chromosome 3q22, which is distinct from most CC chemokine receptor genes at 3p21 [13].
  • CCX CKR transcripts were upregulated in patients (mean +/- SEM); S, 0.82 +/- 0.10; C, 0.44 +/- 0.04; p = 0.01; this upregulation paralleled the disease course as assessed by the chest radiographic stage (p < 0.02) [2].

Anatomical context of CCRL1


Associations of CCRL1 with chemical compounds

  • Unlike most other chemokine receptors, CCX-CKR is unable to mediate Ca(2+) fluxes upon ligand binding when expressed in HEK293 cells [11].

Other interactions of CCRL1

  • However, internalised CCL19 was more efficiently retained and degraded after uptake via CCX-CKR [12].
  • Because these data may identify the receptor as primarily a PP receptor, we have named it PP1 [16].
  • RFamides could act both as ligands of membrane neighbors of the PP receptor, and as competitors of Y5-like NPY receptor epitopes that accommodate the C-terminal aspects of agonist peptides [17].

Analytical, diagnostic and therapeutic context of CCRL1

  • Murine CCX-CKR is expressed predominantly in the heart and lung, but is detectable in most organs using RT-PCR [11].
  • Immunocytochemistry localised the CCX CKR protein to ciliated bronchial cells [2].


  1. The primate lentiviral receptor Bonzo/STRL33 is coordinately regulated with CCR5 and its expression pattern is conserved between human and mouse. Unutmaz, D., Xiang, W., Sunshine, M.J., Campbell, J., Butcher, E., Littman, D.R. J. Immunol. (2000) [Pubmed]
  2. Expression of CCX CKR in pulmonary sarcoidosis. Kriegova, E., Tsyrulnyk, A., Arakelyan, A., Mrazek, F., Ordeltova, M., Petzmann, S., Zatloukal, J., Kolek, V., du Bois, R.M., Popper, H., Petrek, M. Inflamm. Res. (2006) [Pubmed]
  3. Circulating clonal CLA(+) and CD4(+) T cells in Sezary syndrome express the skin-homing chemokine receptors CCR4 and CCR10 as well as the lymph node-homing chemokine receptor CCR7. Sokolowska-Wojdylo, M., Wenzel, J., Gaffal, E., Lenz, J., Speuser, P., Erdmann, S., Abuzahra, F., Bowman, E., Roszkiewicz, J., Bieber, T., Tüting, T. Br. J. Dermatol. (2005) [Pubmed]
  4. cytoplasmic male sterility of rice with boro II cytoplasm is caused by a cytotoxic peptide and is restored by two related PPR motif genes via distinct modes of mRNA silencing. Wang, Z., Zou, Y., Li, X., Zhang, Q., Chen, L., Wu, H., Su, D., Chen, Y., Guo, J., Luo, D., Long, Y., Zhong, Y., Liu, Y.G. Plant Cell (2006) [Pubmed]
  5. Involvement of a novel chemokine decoy receptor CCX-CKR in breast cancer growth, metastasis and patient survival. Feng, L.Y., Ou, Z.L., Wu, F.Y., Shen, Z.Z., Shao, Z.M. Clin. Cancer Res. (2009) [Pubmed]
  6. International Union of Pharmacology. XXX. Update on chemokine receptor nomenclature. Murphy, P.M. Pharmacol. Rev. (2002) [Pubmed]
  7. CCR10 expression is a common feature of circulating and mucosal epithelial tissue IgA Ab-secreting cells. Kunkel, E.J., Kim, C.H., Lazarus, N.H., Vierra, M.A., Soler, D., Bowman, E.P., Butcher, E.C. J. Clin. Invest. (2003) [Pubmed]
  8. The C6 zinc cluster dictates asymmetric binding by HAP1. Zhang, L., Guarente, L. EMBO J. (1996) [Pubmed]
  9. Cloning and functional expression of cDNAs encoding human and rat pancreatic polypeptide receptors. Yan, H., Yang, J., Marasco, J., Yamaguchi, K., Brenner, S., Collins, F., Karbon, W. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  10. Cutting edge: identification of a novel chemokine receptor that binds dendritic cell- and T cell-active chemokines including ELC, SLC, and TECK. Gosling, J., Dairaghi, D.J., Wang, Y., Hanley, M., Talbot, D., Miao, Z., Schall, T.J. J. Immunol. (2000) [Pubmed]
  11. Characterization of mouse CCX-CKR, a receptor for the lymphocyte-attracting chemokines TECK/mCCL25, SLC/mCCL21 and MIP-3beta/mCCL19: comparison to human CCX-CKR. Townson, J.R., Nibbs, R.J. Eur. J. Immunol. (2002) [Pubmed]
  12. The chemokine receptor CCX-CKR mediates effective scavenging of CCL19 in vitro. Comerford, I., Milasta, S., Morrow, V., Milligan, G., Nibbs, R. Eur. J. Immunol. (2006) [Pubmed]
  13. CCR11 is a functional receptor for the monocyte chemoattractant protein family of chemokines. Schweickart, V.L., Epp, A., Raport, C.J., Gray, P.W. J. Biol. Chem. (2000) [Pubmed]
  14. Cloning of CCRL1, an orphan seven transmembrane receptor related to chemokine receptors, expressed abundantly in the heart. Khoja, H., Wang, G., Ng, C.T., Tucker, J., Brown, T., Shyamala, V. Gene (2000) [Pubmed]
  15. Chemokine receptors and leukocyte trafficking in the mucosal immune system. Williams, I.R. Immunol. Res. (2004) [Pubmed]
  16. Cloning of a human receptor of the NPY receptor family with high affinity for pancreatic polypeptide and peptide YY. Lundell, I., Blomqvist, A.G., Berglund, M.M., Schober, D.A., Johnson, D., Statnick, M.A., Gadski, R.A., Gehlert, D.R., Larhammar, D. J. Biol. Chem. (1995) [Pubmed]
  17. FMRFamides exert a unique modulation of rodent pancreatic polypeptide sensitive neuropeptide Y (NPY) receptors. Parker, S.L., Parker, M.S. Can. J. Physiol. Pharmacol. (2000) [Pubmed]
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