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CCR4

Family: Chemokine receptors

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Agonists
Transduction Mechanisms
Tissue Distribution
Expression Datasets
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Phenotypes, Alleles and Disease Models
References
Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 360 3p24 CCR4 chemokine (C-C motif) receptor 4 16
Mouse 7 360 9 F3 Ccr4 chemokine (C-C motif) receptor 4
Rat 7 360 8q32 Ccr4 chemokine (C-C motif) receptor 4
Previous and Unofficial Names
CC CKR4
CKR4
CC CK4
CC CK4
CC-CKR-4
CMKBR4
k5-5
ChemR13
CD194
C-C chemokine receptor 4
C-C chemokine receptor type 4
chemokine (C-C) receptor 4
CC CKR-4
Sdf1r
Database Links
ChEMBL Target 10579 (Hs), 100858 (Mm)
Ensembl ENSG00000183813 (Hs), ENSMUSG00000047898 (Mm), ENSRNOG00000010315 (Rn)
Entrez Gene 1233 (Hs), 12773 (Mm), 171054 (Rn)
GeneCards CCR4 (Hs)
GenitoUrinary Development Molecular Anatomy Project Ccr4 (Mm)
HomoloGene 21135 (Hs)
Human Protein Reference Database 05324 (Hs)
InterPro P51679 (Hs), P51680 (Mm)
KEGG Gene hsa:1233 (Hs), mmu:12773 (Mm), rno:171054 (Rn)
OMIM 604836 (Hs)
PharmGKB Gene PA26169 (Hs)
PhosphoSitePlus P51679 (Hs), P51680 (Mm)
Protein Ontology (PRO) PRO:000001200 (Hs)
RefSeq Nucleotide NM_005508 (Hs), NM_009916 (Mm), NM_133532 (Rn)
RefSeq Protein NP_005499 (Hs), NP_034046 (Mm), NP_598216 (Rn)
TreeFam ENSG00000183813 (Hs), ENSMUSG00000047898 (Mm), ENSRNOG00000010315 (Rn)
UniGene Hs. 184926 (Hs)
UniProt P51679 (Hs), P51680 (Mm)
Wikipedia CCR4
Chemokine receptors
Search for 3D structures on the PDB
Search by keyword: Chemokine receptors CCR4 Search by accession number: P51679, P51680
Natural/Endogenous Ligand(s)
CCL17 {Sp: Human}
CCL22 {Sp: Human} , CCL22 {Sp: Mouse}
Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
CCL22 {Sp: Human} Hs Full agonist 9.2 pIC50 10
CCL17 {Sp: Human} Hs Full agonist 8.7 pIC50 10
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Calcium channel
References:  14
Tissue Distribution
Glomerular podocytes.
Species:  Human
Technique:  RT-PCR.
References:  8
Tonsil B lymphocytes.
Species:  Human
Technique:  RT-PCR.
References:  6
Blood derived mast cells.
Species:  Human
Technique:  RNase protection assay.
References:  11
Blood dendritic cells.
Species:  Human
Technique:  RT-PCR.
References:  1
Microvascular endothelial cells.
Species:  Human
Technique:  RNase protection assay.
References:  15
Th2-type lymphocytes.
Species:  Human
Technique:  RT-PCR.
References:  13
Primary adult microglia and astrocytes.
Species:  Human
Technique:  Flow cytometry.
References:  7
Skin-associated and intestinal memory T cells.
Species:  Human
Technique:  Immunofluorescence.
References:  2
Platelets.
Species:  Human
Technique:  RT-PCR and flow cytometry.
References:  5
Cortical thymocytes.
Species:  Mouse
Technique:  RT-PCR.
References:  3
Hippocampal neurons.
Species:  Rat
Technique:  RT-PCR.
References:  12
Osteoblasts.
Species:  Rat
Technique:  RT-PCR.
References:  19
Expression Datasets

Click here to show/hide data

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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Functional Assays
Measurement of Ca2+ levels in the murine pre-B cell line L1.2 transfected with the human CCR4 receptor.
Species:  Human
Tissue:  L1.2 cells.
Response measured:  Ca2+ influx.
References:  10
Measurement of chemotaxis in the murine pre-B cell line L1.2 transfected with the human CCR4 receptor.
Species:  Human
Tissue:  L1.2 cells.
Response measured:  Chemotaxis.
References:  10
Measurement of Ca2+ levels in HEK 293 cells transfected with the human CCR4 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Ca2+ flux.
References:  18
Measurement of chemotaxis of HEK 293 cells transfected with the human CCR4 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Chemotaxis.
References:  18
Measurement of chemotaxis of blood-derived mast cells endogenously expressing the CCR4 receptor.
Species:  Human
Tissue:  Mast cells.
Response measured:  Chemotaxis.
References:  11
Measurement of Ca2+ currents in HEK 293 cells stably expressing N-type calcium channels and the rat CCR4 receptor, using Ba2+ as the charge carrier (IBa).
Species:  Rat
Tissue:  HEK 293 cells.
Response measured:  IBa inhibition.
References:  14
Physiological Functions
Chemotaxis.
Species:  Human
Tissue:  Mast cells.
References:  11
Chemotaxis.
Species:  Human
Tissue:  Blood CD4+CD25+ cytotoxic T lymphocyte antigen (CTLA)-4+ regulatory T cells (Treg).
References:  9
Physiological Consequences of Altering Gene Expression
CCR4 receptor knockout mice exhibit decreased mortality upon administration of high or low dose bacterial lipopolysaccharide.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  4
Following infection with A. fumigatus spores, CCR4 receptor knockout mice exhibit increased numbers of airway neutrophils and macrophages, as well as reduced numbers of peribronchial and airway eosinophils. Cholinergic stimulation induces airway hyperresponsiveness, which then subsides to a lower level in the knockout mice than wild-type. The elimination of the pathogen from the knockout mice was more rapid compared to the wild-type.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  17
Phenotypes, Alleles and Disease Models Mouse data from MGI

Click here to show/hide data

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Ccr4tm1Pwr Ccr4tm1Pwr/Ccr4tm1Pwr
involves: 129P2/OlaHsd * C57BL/6		 MGI:107824  MP:0008722 abnormal chemokine secretion PMID: 10811868 
Ccr4tm1Pwr Ccr4tm1Pwr/Ccr4tm1Pwr
involves: 129P2/OlaHsd * C57BL/6		 MGI:107824  MP:0009333 abnormal splenocyte physiology PMID: 10811868 
Ccr4tm1Pwr Ccr4tm1Pwr/Ccr4tm1Pwr
involves: 129P2/OlaHsd * C57BL/6		 MGI:107824  MP:0008658 decreased interleukin-1 beta secretion PMID: 10811868 
Ccr4tm1Pwr Ccr4tm1Pwr/Ccr4tm1Pwr
involves: 129P2/OlaHsd * C57BL/6		 MGI:107824  MP:0005016 decreased lymphocyte cell number PMID: 10811868 
Ccr4tm1Pwr Ccr4tm1Pwr/Ccr4tm1Pwr
involves: 129P2/OlaHsd * C57BL/6		 MGI:107824  MP:0003884 decreased macrophage cell number PMID: 10811868 
Ccr4tm1Pwr Ccr4tm1Pwr/Ccr4tm1Pwr
involves: 129P2/OlaHsd * C57BL/6		 MGI:107824  MP:0008734 decreased susceptibility to endotoxin shock PMID: 10811868 
Ccr4tm1Pwr Ccr4tm1Pwr/Ccr4tm1Pwr
involves: 129P2/OlaHsd * C57BL/6		 MGI:107824  MP:0008561 decreased tumor necrosis factor secretion PMID: 10811868 

REFERENCES

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1. Ayehunie, S., Garcia-Zepeda, E. A., Hoxie, J. A., Horuk, R., Kupper, T. S., Luster, A. D. and Ruprecht, R. M. (1997) Human immunodeficiency virus-1 entry into purified blood dendritic cells through CC and CXC chemokine coreceptors. Blood, 90: 1379-1386. [PMID:9269754]

2. Campbell, J. J., Haraldsen, G., Pan, J., Rottman, J., Qin, S., Ponath, P., Andrew, D. P., Warnke, R., Ruffing, N., Kassam, N., Wu, L. and Butcher, E. C. (1999) The chemokine receptor CCR4 in vascular recognition by cutaneous but not intestinal memory T cells. Nature, 400: 776-780. [PMID:10466728]

3. Campbell, J. J., Pan, J. and Butcher, E. C. (1999) Cutting edge: developmental switches in chemokine responses during T cell maturation. J. Immunol., 163: 2353-2357. [PMID:10452965]

4. Chvatchko, Y., Hoogewerf, A. J., Meyer, A., Alouani, S., Juillard, P., Buser, R., Conquet, F., Proudfoot, A. E., Wells, T. N. and Power, C. A. (2000) A key role for CC chemokine receptor 4 in lipopolysaccharide-induced endotoxic shock. J Exp Med, 191: 1755-1764. [PMID:10811868]

5. Clemetson, K. J., Clemetson, J. M., Proudfoot, A. E., Power, C. A., Baggiolini, M. and Wells, T. N. (2000) Functional expression of CCR1, CCR3, CCR4, and CXCR4 chemokine receptors on human platelets. Blood, 96: 4046-4054. [PMID:11110672]

6. Corcione, A., Tortolina, G., Bonecchi, R., Battilana, N., Taborelli, G., Malavasi, F., Sozzani, S., Ottonello, L., Dallegri, F. and Pistoia, V. (2002) Chemotaxis of human tonsil B lymphocytes to CC chemokine receptor (CCR) 1, CCR2 and CCR4 ligands is restricted to non-germinal center cells. Int Immunol, 14: 883-892. [PMID:12147625]

7. Flynn, G., Maru, S., Loughlin, J., Romero, I. A. and Male, D. (2003) Regulation of chemokine receptor expression in human microglia and astrocytes. J Neuroimmunol, 136: 84-93. [PMID:12620646]

8. Huber, T. B., Reinhardt, H. C., Exner, M., Burger, J. A., Kerjaschki, D., Saleem, M. A. and Pavenstädt, H. (2002) Expression of functional CCR and CXCR chemokine receptors in podocytes. J Immunol, 168: 6244-6252. [PMID:12055238]

9. Iellem, A., Mariani, M., Lang, R., Recalde, H., Panina-Bordignon, P., Sinigaglia, F. and D'Ambrosio, D. (2001) Unique chemotactic response profile and specific expression of chemokine receptors CCR4 and CCR8 by CD4(+)CD25(+) regulatory T cells. J Exp Med, 194: 847-853. [PMID:11560999]

10. Imai, T., Chantry, D., Raport, C. J., Wood, C. L., Nishimura, M., Godiska, R., Yoshie, O. and Gray, P. W. (1998) Macrophage-derived chemokine is a functional ligand for the CC chemokine receptor 4. J Biol Chem, 273: 1764-1768. [PMID:9430724]

11. Juremalm, M., Olsson, N. and Nilsson, G. (2002) Selective CCL5/RANTES-induced mast cell migration through interactions with chemokine receptors CCR1 and CCR4. Biochem Biophys Res Commun, 297: 480-485. [PMID:12270118]

12. Meucci, O., Fatatis, A., Simen, A. A., Bushell, T. J., Gray, P. W. and Miller, R. J. (1998) Chemokines regulate hippocampal neuronal signaling and gp120 neurotoxicity. Proc Natl Acad Sci U S A, 95: 14500-14505. [PMID:9826729]

13. Nanki, T. and Lipsky, P. E. (2000) Lack of correlation between chemokine receptor and T(h)1/T(h)2 cytokine expression by individual memory T cells. Int Immunol, 12: 1659-1667. [PMID:11099305]

14. Oh, S. B., Endoh, T., Simen, A. A., Ren, D. and Miller, R. J. (2002) Regulation of calcium currents by chemokines and their receptors. J Neuroimmunol, 123: 66-75. [PMID:11880151]

15. Salcedo, R., Young, H. A., Ponce, M. L., Ward, J. M., Kleinman, H. K., Murphy, W. J. and Oppenheim, J. J. (2001) Eotaxin (CCL11) induces in vivo angiogenic responses by human CCR3+ endothelial cells. J Immunol, 166: 7571-7578. [PMID:11390513]

16. Samson, M., Soularue, P., Vassart, G. and Parmentier, M. (1996) The genes encoding the human CC-chemokine receptors CC-CKR1 to CC-CKR5 (CMKBR1-CMKBR5) are clustered in the p21.3-p24 region of chromosome 3. Genomics, 36: 522-526. [PMID:8884276]

17. Schuh, J. M., Power, C. A., Proudfoot, A. E., Kunkel, S. L., Lukacs, N. W. and Hogaboam, C. M. (2002) Airway hyperresponsiveness, but not airway remodeling, is attenuated during chronic pulmonary allergic responses to Aspergillus in CCR4-/- mice. FASEB J, 16: 1313-1315. [PMID:12154006]

18. Wang, Y., Zhang, Y., Yang, X., Han, W., Liu, Y., Xu, Q., Zhao, R., Di, C., Song, Q. and Ma, D. (2006) Chemokine-like factor 1 is a functional ligand for CC chemokine receptor 4 (CCR4). Life Sci, 78: 614-621. [PMID:16137713]

19. Yano, S., Mentaverri, R., Kanuparthi, D., Bandyopadhyay, S., Rivera, A., Brown, E. M. and Chattopadhyay, N. (2005) Functional expression of beta-chemokine receptors in osteoblasts: role of regulated upon activation, normal T cell expressed and secreted (RANTES) in osteoblasts and regulation of its secretion by osteoblasts and osteoclasts. Endocrinology, 146: 2324-2335. [PMID:15718270]

To cite this database page, please use the following:

Israel F. Charo, Rebecca Hills, Richard Horuk, Kouji Matsushima, Philip M. Murphy, Joost J. Oppenheim.
Chemokine receptors: CCR4. Last modified on 31/01/2013. Accessed on 25/05/2013. IUPHAR database (IUPHAR-DB), http://iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=61.


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