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CCR5

Family: Chemokine receptors

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Agonists
Antagonists
Transduction Mechanisms
Tissue Distribution
Expression Datasets
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Phenotypes, Alleles and Disease Models
Biologically Significant Variants
References
Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 352 3p21 CCR5 chemokine (C-C motif) receptor 5 (gene/pseudogene) 19,44,51,53-54
Mouse 7 354 9 Ccr5 chemokine (C-C motif) receptor 5 37
Rat 7 354 8q32 Ccr5 chemokine (C-C motif) receptor 5 31
Previous and Unofficial Names
Names References
CC CKR5
CKR5
CC CK5
CHEMR13 53
CC CK5
CC CKR5
CMKBR5
CKR-5
CC-CKR-5
CD195
IDDM22
chemokine (C-C motif) receptor 5
C-C CKR-5
C-C chemokine receptor type 5
CCR-5
MIP-1 alpha receptor
chemokine (C-C) receptor 5
Database Links
ChEMBL Target 10580 (Hs), 12406 (Mm)
DrugBank Target 1129 (Hs)
Ensembl ENSG00000160791 (Hs), ENSMUSG00000079227 (Mm), ENSRNOG00000006774 (Rn)
Entrez Gene 1234 (Hs), 12774 (Mm), 117029 (Rn)
GeneCards CCR5 (Hs)
GenitoUrinary Development Molecular Anatomy Project Ccr5 (Mm)
HomoloGene 37325 (Hs)
Human Protein Reference Database 03223 (Hs)
InterPro P51681 (Hs), P51682 (Mm), O08556 (Rn)
KEGG Gene hsa:1234 (Hs), mmu:12774 (Mm), rno:117029 (Rn)
OMIM 601373 (Hs)
PharmGKB Gene PA26170 (Hs)
PhosphoSitePlus P51681 (Hs), P51682 (Mm), O08556 (Rn)
Protein Ontology (PRO) PRO:000001201 (Hs)
RefSeq Nucleotide NM_000579 (Hs), NM_009917 (Mm), NM_053960 (Rn)
RefSeq Protein NP_000570 (Hs), NP_034047 (Mm), NP_446412 (Rn)
TreeFam ENSG00000160791 (Hs), ENSMUSG00000079227 (Mm), ENSRNOG00000006774 (Rn)
UniGene Hs. 546245 (Hs)
UniProt P51681 (Hs), P51682 (Mm), O08556 (Rn)
Wikipedia CCR5
Chemokine receptors
Search for 3D structures on the PDB
Search by keyword: Chemokine receptors CCR5 Search by accession number: O08556, P51681, P51682
Natural/Endogenous Ligand(s)
CCL11 {Sp: Human} , CCL11 {Sp: Rat} , CCL11 {Sp: Mouse}
CCL14 {Sp: Human}
CCL16 {Sp: Human}
CCL3 {Sp: Human} , CCL3 {Sp: Mouse} , CCL3 {Sp: Rat}
CCL4 {Sp: Rat} , CCL4 {Sp: Mouse} , CCL4 {Sp: Human}
CCL5 {Sp: Mouse, Rat} , CCL5 {Sp: Human}
CCL8 {Sp: Mouse} , CCL8 {Sp: Human}
Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[125I]CCL4 (human) Hs Full agonist 9.6 pKd 44
CCL4 {Sp: Human} Hs Full agonist 9.4 – 9.6 pKi 44,52
CCL5 {Sp: Human} Hs Full agonist 9.2 – 9.7 pKi 8,44,52
CCL8 {Sp: Human} Hs Full agonist 9.3 pKi 52
CCL13 {Sp: Human} Hs Full agonist 9.1 pKi 52
CCL3 {Sp: Human} Hs Full agonist 8.0 – 8.9 pKi 44,52,65
BP-CCL3 Hs Full agonist 7.7 pKi 65
Flu-CCL3 Hs Full agonist 7.6 pKi 65
CCL2 {Sp: Human} Hs Full agonist 7.5 pKi 44
CCL14 {Sp: Human} Hs Full agonist 7.2 pKi 44
CCL11 {Sp: Human} Hs Full agonist 7.7 pIC50 15
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]maraviroc Hs Antagonist 9.1 pKd 44
[3H]ancriviroc Hs Antagonist 8.9 pKd 57
vicriviroc Hs Antagonist 9.1 pKi 57
aplaviroc Hs Antagonist 8.5 pKi 38
ancriviroc Hs Antagonist 7.8 – 8.7 pKi 38,49,57
CCL7 {Sp: Human} Hs Antagonist 7.5 pKi 44
TAK-779 Hs Antagonist 7.5 pKi 38
E913 Hs Antagonist 8.7 pIC50 39
TAK-625 Hs Antagonist 8.6 pIC50 9
TAK-220 Hs Antagonist 8.5 pIC50 30
vMIP-II Hs Antagonist 8.3 pIC50 35
maraviroc Hs Antagonist 8.1 pIC50 44
Antagonist Comments
A number of CCR5 receptor antagonists are currently in clinical trials as blockers of HIV entry [32-33,61].

Explore drug-target interactions for this set of compounds using iPHACE

Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Calcium channel
References:  46
Secondary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
References:  6
Tissue Distribution
CD4+ T lymphocytes.
Species:  Human
Technique:  Flow cytometry.
References:  34
Testes.
Species:  Human
Technique:  RT-PCR.
References:  26
Blood and cerebrospinal fluid B lymphocytes.
Species:  Human
Technique:  Flow cytometry.
References:  58
Microglia.
Species:  Human
Technique:  Flow cytometry.
References:  2,21
Basophils.
Species:  Human
Technique:  RT-PCR and flow cytometry.
References:  29
Blood dendritic cells.
Species:  Human
Technique:  RT-PCR.
References:  7
Th1-type lymphocytes.
Species:  Human
Technique:  RT-PCR.
References:  43
Testicular macrophages.
Species:  Human
Technique:  Northern blotting and RT-PCR.
References:  26
Tonsil B lymphocytes.
Species:  Human
Technique:  RT-PCR.
References:  20
Bone marrow dendritic cells.
Species:  Mouse
Technique:  Ribonuclease protection assay.
References:  45
Hippocampal neurons.
Species:  Rat
Technique:  RT-PCR.
References:  41
Lung, spleen, kidney, thymus, macrophages.
Species:  Rat
Technique:  RNase protection assay.
References:  31
Osteoblasts.
Species:  Rat
Technique:  RT-PCR.
References:  62
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
Detection of HIV-1 fusion in HeLa cells transfected with CD4 and the human CCR5 receptor.
Species:  Human
Tissue:  HeLa cells expressing CD4 and CCR5.
Response measured:  HIV-1 fusion and infection.
References:  18
Measurement of cAMP levels in CHO and NG108-15 cells transfected with the human CCR5 receptor.
Species:  Human
Tissue:  CHO and NG108-15 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  63
Measurement of Ca2+ levels in CHO cells transfected with the human CCR5 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Ca2+ influx.
References:  8
Measurement of chemotaxis of skin natural killer (NK) cells endogenously expressing the CCR5 receptor.
Species:  Human
Tissue:  Skin NK lymphocytes.
Response measured:  Chemotaxis.
References:  48
Detection of cell death of SH-SY5Y neuroblastoma cells induced to express the CCR5 receptor by lentiviral transduction.
Species:  Human
Tissue:  SH-SY5Y neuroblastoma cells.
Response measured:  Apoptosis by caspase-3 activation.
References:  16
Measurement of Ca2+ currents in HEK 293 cells stably expressing N-type calcium channels and the rat CCR5 receptor, using Ba2+ as the charge carrier (IBa).
Species:  Rat
Tissue:  HEK 293 cells.
Response measured:  IBa inhibition.
References:  46
Physiological Functions
T-cell and eosinophil trafficking.
Species:  Mouse
Tissue:  In vivo.
References:  56
HIV coreceptor.
Species:  Human
Tissue:  Microglia.
References:  2
Chemotaxis.
Species:  Human
Tissue:  NK lymphocytes.
References:  48
Angiogenesis.
Species:  Mouse
Tissue:  Cornea.
References:  4
Leukocyte trafficking.
Species:  Mouse
Tissue:  In vivo.
References:  13
Physiological Consequences of Altering Gene Expression
CCR5 receptor knockout mice exhibit defective clearence of Listeria monocytogenes infection as well as having a protective effect against lipopolysaccharide-induced endotoxemia.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  64
CCR5 receptor knockout mice infected with Cryptococcus neoformans exhibit reduced survival compared to wild-type, defective leukocyte recruitment to the brain and defective clearence of extracellular cryptococcal polysaccharide capsules which accumulate in the brain.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  28
CCR5 receptor knockout mice exhibit decreased IFN-γ responses and defective granuloma formation.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  55
CCR5 receptor knockout mice infected with mouse hepatitis virus exhibit reduced macrophage infiltration to the CNS and subsequent decrease in demyelination.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  24
CCR5 receptor knockout mice infected with live Aspergillus fumigatus (model of chronic fungal asthma) exhibit an initial reduced airway hyperresponsiveness to cholinergic stimulation compared to wild-type mice also infected with the fungus. The knockout mice initially show reduced peribronchial T-cell and eosinophil accumulation as well as reduced goblet cell hyperplasia and peribronchial fibrosis. However, 12 days after infection both the wild-type and the knockout mice exhibit similar allergic airway disease.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  56
CCR5 receptor knockout mice exhibit reduced corneal neovascularization and expression of vascular endothelial growth factor (VEGF).
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  4
Few CCR5 receptor knockout mice infected with Plasmodium berghei ANKA (PbA) develop the the characteristic neurologic signs of cerebral malaria (CM) as seen in wild-type mice infected with the parasite. The knockout mice that did not exhibit CM had defective leukocyte accumulation in the brain and reduced Th1 cytokine production.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  13
CCR5 receptor knockout mice exhibit delayed dendritic cell tumour growth following injection of melanoma cells. In addition, the knockout mice injected with tumour followed by a vaccination of matured DCs from wild-type mice lack significant tumour growth hence exhibit protective antitumor immunity.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  45
CCR5 receptor knockout mice infected with Mycobacterium tuberculosis exhibit immune cell trafficking to the lungs and control of infection. Infact, the knockout mice exhibit increased leukocyte migration to the lungs, increased numbers of inflammatory cytokines, increased levels of dendritic cells in the lung-draining lymph nodes, an increase in the amount of primed T lymphocytes and an increase in bacterial numbers in the lymph nodes compared to wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  3
CCR5 receptor knockout mice infected with Trypanosoma cruzi exhibit reduced migration of T lymphocytes to the heart and increased susceptibility to infection.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  27,36
CCR5 receptor knockout mice exhibit fewer lung metastases than wild-type mice following injection of B16-F10 melanoma cells.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  59
CCR5 receptor knockout mice are protected from dextran sodium sulfate (DSS)-mediated colitis. They have increased levels of CD4+ and NK1.1+ lymphocytes in the colonic lamina propria as well as increased Il-4, Il-5 and Il-10 expression and decreased IFN-γ expression.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  5
CCR5 receptor knockout mice administered with Con A develop fulminant liver failure (FLF) by reduced apoptosis of CD1d-restricted NKT cells.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  1
CCR5 receptor knockout mice have a reduced incidence of collagen-induced arthritis following collagen II-immunisation. They exhibit reduced IgG levels as well as increased levels of Il-10 on splenocytes and overproduction of MIP-1β.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  10
CCR5 receptor knockout mice infected with Chlamydia trachomatis have an increased susceptibility to infection compared to infected wild-type mice. Infected wild-type mice had a significantly lower pregnancy rate than infected knockout mice, suggesting that the inflammatory response by the host may be involved in the development of tubal infertility.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  12
West Nile virus (WNV) infection is uniformly fatal in CCR5 knockout mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  23
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Ccr5tm1Kuz Ccr5tm1Kuz/Ccr5tm1Kuz
involves: 129P2/OlaHsd * C57BL/6		 MGI:107182  MP:0002432 abnormal CD4-positive T cell morphology PMID: 10843684 
Ccr5tm1Kuz Ccr5tm1Kuz/Ccr5tm1Kuz
involves: 129P2/OlaHsd * C57BL/6		 MGI:107182  MP:0005010 abnormal CD8-positive T cell morphology PMID: 10843684 
Ccr5tm1Blck Ccr5tm1Blck/Ccr5tm1Blck
B6.129P2-Ccr5		 MGI:107182  MP:0009858 abnormal cellular extravasation PMID: 16275892 
Ccr5tm1Kuz Ccr5tm1Kuz/Ccr5tm1Kuz
B6.129P2-Ccr5		 MGI:107182  MP:0002805 abnormal conditioned taste aversion behavior PMID: 16105698 
Ccr5tm1Kuz Ccr5tm1Kuz/Ccr5tm1Kuz
involves: 129P2/OlaHsd * C57BL/6		 MGI:107182  MP:0008713 abnormal cytokine level PMID: 10843684 
Ccr5tm1Brv Ccr5tm1Brv/Ccr5tm1Brv
either: (involves: 129S1/Sv * ICR) or (involves: 129S1/Sv * 129X1/SvJ * ICR)		 MGI:107182  MP:0003009 abnormal cytokine secretion PMID: 9558111 
Ccr5tm1Blck Ccr5tm1Blck/Ccr5tm1Blck
B6.129P2-Ccr5		 MGI:107182  MP:0003628 abnormal leukocyte adhesion PMID: 16275892 
Ccr5tm1Sush Ccr5tm1Sush/Ccr5tm1Sush
B6.129P2-Ccr5		 MGI:107182  MP:0002442 abnormal leukocyte physiology PMID: 12524535 
Ccr5tm1Kuz Ccr5tm1Kuz/Ccr5tm1Kuz
involves: 129P2/OlaHsd * C57BL/6		 MGI:107182  MP:0001392 abnormal locomotor activity PMID: 10843684 
Ccr5tm1Blck Ccr5tm1Blck/Ccr5tm1Blck
B6.129P2-Ccr5		 MGI:107182  MP:0000343 altered response to myocardial infarction PMID: 16275892 
Ccr5tm1Brv Ccr5tm1Brv/Ccr5tm1Brv
either: (involves: 129S1/Sv * ICR) or (involves: 129S1/Sv * 129X1/SvJ * ICR)		 MGI:107182  MP:0008658 decreased interleukin-1 beta secretion PMID: 9558111 
Ccr5tm1Brv Ccr5tm1Brv/Ccr5tm1Brv
either: (involves: 129S1/Sv * ICR) or (involves: 129S1/Sv * 129X1/SvJ * ICR)		 MGI:107182  MP:0008706 decreased interleukin-6 secretion PMID: 9558111 
Ccr5tm1Brv Ccr5tm1Brv/Ccr5tm1Brv
either: (involves: 129S1/Sv * ICR) or (involves: 129S1/Sv * 129X1/SvJ * ICR)		 MGI:107182  MP:0008734 decreased susceptibility to endotoxin shock PMID: 9558111 
Ccr5tm1Kuz Ccr5tm1Kuz/Ccr5tm1Kuz
involves: 129P2/OlaHsd * C57BL/6		 MGI:107182  MP:0008539 decreased susceptibility to induced colitis PMID: 10843684 
Ccr5tm1Sush Ccr5tm1Sush/Ccr5tm1Sush
B6.129P2-Ccr5		 MGI:107182  MP:0005095 decreased T cell proliferation PMID: 12524535 
Ccr5tm1Kuz Ccr5tm1Kuz/Ccr5tm1Kuz
involves: 129P2/OlaHsd * C57BL/6		 MGI:107182  MP:0005496 impaired macrophage recruitment PMID: 10528159  12618265 
Ccr5tm1Kuz Ccr5tm1Kuz/Ccr5tm1Kuz
B6.129P2-Ccr5		 MGI:107182  MP:0003545 increased alcohol consumption PMID: 16105698 
Ccr5tm1Kuz Ccr5tm1Kuz/Ccr5tm1Kuz
B6.129P2-Ccr5		 MGI:107182  MP:0003911 increased drinking behavior PMID: 16105698 
Ccr5tm1Brv Ccr5tm1Brv/Ccr5tm1Brv
either: (involves: 129S1/Sv * ICR) or (involves: 129S1/Sv * 129X1/SvJ * ICR)		 MGI:107182  MP:0008499 increased IgG1 level PMID: 9558111 
Ccr5tm1Brv Ccr5tm1Brv/Ccr5tm1Brv
either: (involves: 129S1/Sv * ICR) or (involves: 129S1/Sv * 129X1/SvJ * ICR)		 MGI:107182  MP:0008566 increased interferon-gamma secretion PMID: 9558111 
Ccr5tm1Brv Ccr5tm1Brv/Ccr5tm1Brv
either: (involves: 129S1/Sv * ICR) or (involves: 129S1/Sv * 129X1/SvJ * ICR)		 MGI:107182  MP:0008699 increased interleukin-4 secretion PMID: 9558111 
Ccr5tm1Blck Ccr5tm1Blck/Ccr5tm1Blck
B6.129P2-Ccr5		 MGI:107182  MP:0004751 increased length of allograft survival PMID: 15307189 
Ccr5tm1Kuz Ccr5tm1Kuz/Ccr5tm1Kuz
involves: 129P2/OlaHsd * C57BL/6		 MGI:107182  MP:0008039 increased NK T cell number PMID: 10843684 
Ccr5tm1Brv Ccr5tm1Brv/Ccr5tm1Brv
either: (involves: 129S1/Sv * ICR) or (involves: 129S1/Sv * 129X1/SvJ * ICR)		 MGI:107182  MP:0002412 increased susceptibility to bacterial infection PMID: 9558111 
Ccr5tm1Kuz Ccr5tm1Kuz/Ccr5tm1Kuz
involves: 129P2/OlaHsd * C57BL/6		 MGI:107182  MP:0005399 increased susceptibility to fungal infection PMID: 10528159 
Ccr5tm1Brv Ccr5tm1Brv/Ccr5tm1Brv
either: (involves: 129S1/Sv * ICR) or (involves: 129S1/Sv * 129X1/SvJ * ICR)		 MGI:107182  MP:0005617 increased susceptibility to type IV hypersensitivity reaction PMID: 9558111 
Biologically Significant Variants
A 32 bp deletion in the CCR5 gene gives rise to the CCR5Δ32 receptor variant. Individuals homozygous for the CCR5Δ32 allele are highly resistant to HIV-1 infection and heterozygotes have delayed AIDS progression.
Type:  Naturally occurring mutation.
Species:  Human
References:  14,42,47
The CCR5Δ32 receptor variant identified in Dutch Caucasian women is thought to be linked to a lower incidence of tubal pathology following Chlamydia trachomatis genital infection.
Type:  Naturally occurring mutation.
Species:  Human
References:  12
The CCR5Δ32 variant may be linked to an increased age of multiple sclerosis (MS) onset but a higher mortality rate among MS sufferers.
Type:  Naturally occurring mutation.
Species:  Human
References:  11,22
The CCR5Δ32 variant may be associated with an increased risk of the development of sarcoidosis.
Type:  Naturally occurring mutation.
Species:  Human
References:  50
The CCR5Δ32 variant may contribute to the control of the chronic inflammation state present in sickle cell disease sufferers.
Type:  Naturally occurring mutation.
Species:  Human
References:  17,60
The CCR5Δ32 variant may be linked to an increased risk of symptomatic West Nile virus (WNV) infection.
Type:  Naturally occurring mutation.
Species:  Human
References:  25
Gene promotor polymorphisms have been associated with risk of HIV disease progression.
Type:  Single nucleotide polymorphism.
Species:  Human
References:  40

REFERENCES

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12. Barr, E. L., Ouburg, S., Igietseme, J. U., Morré, S. A., Okwandu, E., Eko, F. O., Ifere, G., Belay, T., He, Q., Lyn, D., Nwankwo, G., Lillard, J., Black, C. M. and Ananaba, G. A. (2005) Host inflammatory response and development of complications of Chlamydia trachomatis genital infection in CCR5-deficient mice and subfertile women with the CCR5delta32 gene deletion. J Microbiol Immunol Infect, 38: 244-254. [PMID:16118671]

13. Belnoue, E., Kayibanda, M., Deschemin, J. C., Viguier, M., Mack, M., Kuziel, W. A. and Rénia, L. (2003) CCR5 deficiency decreases susceptibility to experimental cerebral malaria. Blood, 101: 4253-4259. [PMID:12560237]

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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: CCR5. Last modified on 31/01/2013. Accessed on 18/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=62.


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