CCR5受容体、CCR5レセプター

WordNet

a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response

PrepTutorEJDIC

=sense organ / 受信装置

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/07/18 00:03:05」(JST)

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CCR5 receptor (yellow) in cell membrane (grey)

Attachment of HIV to a CD4+ T-helper cell: 1) the gp120 viral protein attaches to CD4. 2) gp120 variable loop attaches to a coreceptor, either CCR5 or CXCR4. 3) HIV enters the cell.

C-C chemokine receptor type 5, also known as CCR5 or CD195, is a protein on the surface of white blood cells that is involved in the immune system as it acts as a receptor for chemokines. This is the process by which T cells are attracted to specific tissue and organ targets. Many forms of HIV, the virus that causes AIDS, initially use CCR5 to enter and infect host cells. A few individuals carry a mutation known as CCR5-Δ32 in the CCR5 gene, protecting them against these strains of HIV.

In humans, the CCR5 gene that encodes the CCR5 protein is located on the short (p) arm at position 21 on chromosome 3. Certain populations have inherited the Delta 32 mutation resulting in the genetic deletion of a portion of the CCR5 gene. Homozygous carriers of this mutation are resistant to M-tropic strains of HIV-1 infection.^[1]^[2]^[3]^[4]^[5]^[6]

Function

The CCR5 protein belongs to the beta chemokine receptors family of integral membrane proteins.^[7]^[8] It is a G protein-coupled receptor^[7] which functions as a chemokine receptor in the CC chemokine group.

The natural chemokine ligands that bind to this receptor are RANTES (a chemotactic cytokine protein also known as CCL5)^[9]^[10]^[11] and macrophage inflammatory protein (MIP) 1α and 1β (also known as CCL3 and CCL4, respectively). A computationally derived structure of CCL5 (RANTES) in complex with CCR5 is reported in ^[12]. The CCL5 : CCR5 structure is in excellent agreement with experimental findings and clarifies the functional role of CCL5 and CCR5 residues which are associated with binding and signaling ^[12]. It also interacts with CCL3L1.^[10]^[13]

CCR5 is predominantly expressed on T cells, macrophages, dendritic cells and microglia. It is likely that CCR5 plays a role in inflammatory responses to infection, though its exact role in normal immune function is unclear.

HIV

HIV most commonly uses CCR5 and/or CXCR4 as a co-receptor to enter its target cells. Several chemokine receptors can function as viral coreceptors, but CCR5 is likely the most physiologically important coreceptor during natural infection. Molecular Dynamics simulations delineated the binding of a specific dual-tropic HIV-1 gp120 V3 loop to CCR5 ^[14]; the computationally derived complex structure exhibits exceptional agreement with previous experimental findings and sheds light into the functional role of HIV-1 gp120 V3 loop and CCR5 residues associated with the HIV-1 coreceptor activity ^[14]. The normal ligands for this receptor, RANTES, MIP-1β, and MIP-1α, are able to suppress HIV-1 infection in vitro. The blocking mechanism of HIV-1 by RANTES is reported in ^[12]. A comparison between the CCL5 (RANTES) : CCR5 ^[12] and the HIV-1 gp120 V3 loop : CCR5 ^[14] complex structures depicts that both RANTES and the virus primarily interact with the same CCR5 residues. In individuals infected with HIV, CCR5-using viruses are the predominant species isolated during the early stages of viral infection,^[15] suggesting that these viruses may have a selective advantage during transmission or the acute phase of disease. Moreover, at least half of all infected individuals harbor only CCR5-using viruses throughout the course of infection.

A number of new experimental HIV drugs, called CCR5 receptor antagonists, have been designed to interfere with the interaction between CCR5 and HIV, including PRO140 (Progenics), Vicriviroc(Phase III trials were cancelled in July 2010) (Schering Plough), Aplaviroc (GW-873140) (GlaxoSmithKline) and Maraviroc (UK-427857) (Pfizer). The blocking mechanism of HIV-1 by Maraviroc was proposed in ^[14]. A problem of this approach is that, while CCR5 is the major co-receptor by which HIV infects cells, it is not the only such co-receptor. It is possible that under selective pressure HIV will evolve to use another co-receptor. However, examination of viral resistance to AD101, molecular antagonist of CCR5, indicated that resistant viruses did not switch to another coreceptor (CXCR4) but persisted in using CCR5, either through binding to alternative domains of CCR5, or by binding to the receptor at a higher affinity.

CCR5-Δ32

CCR5-Δ32 (or CCR5-D32 or CCR5 delta 32) is an allele of CCR5.^[16]^[17]

CCR5-Δ32 is a deletion mutation of a gene that has a specific impact on the function of T cells.^[18] At least one copy of CCR5-Δ32 is found in about 4–16% of people of European descent. It has been speculated that this allele was favored by natural selection during the Black Death for Northern Europeans, but further research has revealed that the gene did not protect against the Black Death.^[19] The current hypothesis is of protection vs smallpox throughout Europe,^[19] especially in the major trade cities and in isolated islands and archipelagos, such as Iceland and the Azores.^[20]

In the ancient world in areas such as Corinth in Ancient Greece, prostitution may have led to infection, since a virus similar to HIV existed which had flu-like symptoms and later continued to weaken the immune system of those infected. It was at the time not known how it was spread but the Plague of Athens and many later diseases in the Balkans may have also influenced the genetic mutations.^[21] This coalescence date is contradicted by surported evidence of CCR5-Δ32 in Bronze Age samples, at levels comparable to the modern European population.^[22] Smallpox may be another candidate for the high level of the mutation in the European population.^[16] The highest frequency of the mutation exists in Ashkenazi Jews, with the overall frequency of the CCR5-Delta32 allele is elevated 13.7% on average.^[23]

The allele has a negative effect upon T cell function, but appears to protect against smallpox and HIV. Yersinia pestis (the bubonic plague bacterium) was demonstrated in the laboratory not to associate with CCR5. Individuals with the Δ32 allele of CCR5 are healthy, suggesting that CCR5 is largely dispensable. However, CCR5 apparently plays a role in mediating resistance to West Nile virus infection in humans, as CCR5-Δ32 individuals have shown to be disproportionately at higher risk of West Nile virus in studies,^[24] indicating that not all of the functions of CCR5 may be compensated by other receptors.

While CCR5 has multiple variants in its coding region, the deletion of a 32-bp segment results in a nonfunctional receptor, thus preventing HIV R5 entry; two copies of this allele provide strong protection against HIV infection.^[25] This allele is found in 5–14% of Europeans but is rare in Africans and Asians.^[26] CCR5-Δ32 decreases the number of CCR5 proteins on the outside of the CD4 cell, which can have a large effect on the HIV disease progression rates. Multiple studies of HIV-infected persons have shown that presence of one copy of this allele delays progression to the condition of AIDS by about two years. It is possible that a person with the CCR5-Δ32 receptor allele will not be infected with HIV R5 strains. Several commercial testing companies offer tests for CCR5-Δ32.^[27]

A genetic approach involving intrabodies that block CCR5 expression has been proposed as a treatment for HIV-1 infected individuals.^[28] When T-cells modified so they no longer express CCR5 were mixed with unmodified T-cells expressing CCR5 and then challenged by infection with HIV-1, the modified T-cells that do not express CCR5 eventually take over the culture, as HIV-1 kills the non-modified T-cells. This same method might be used in vivo to establish a virus resistant cell pool in infected individuals.^[28]

This hypothesis was tested in an AIDS patient who had also developed myeloid leukemia, and was treated with chemotherapy to suppress the cancer. A bone marrow transplant containing stem cells from a matched donor was then used to restore the immune system. However, the transplant was performed from a donor with 2 copies of CCR5-Δ32 mutation gene. After 600 days, the patient was healthy and had undetectable levels of HIV in the blood and in examined brain and rectal tissues.^[29]^[2] Before the transplant, low levels of HIV X4, which does not use the CCR5 receptor, were also detected. Following the transplant, however, this type of HIV was not detected either, further baffling doctors.^[2] However, this is consistent with the observation that cells expressing the CCR5-Δ32 variant protein lack both the CCR5 and CXCR4 receptors on their surfaces, thereby conferring resistance to a broad range of HIV variants including HIV X4.^[30] After over six years, the patient has maintained the resistance to HIV and has been pronounced cured of the HIV infection.^[3]

Enrollment of HIV-positive patients in a clinical trial was started in 2009 in which the patients' cells were genetically modified with a zinc finger nuclease to carry the CCR5-Δ32 trait and then reintroduced into the body as a potential HIV treatment.^[31]^[32] Results reported in 2014 were promising.^[6]

References

^ de Silva E, Stumpf MP (2004). "HIV and the CCR5-Delta32 resistance allele". FEMS Microbiol. Lett. 241 (1): 1–12. doi:10.1016/j.femsle.2004.09.040. PMID 15556703.
^ ^a ^b ^c Hütter G, Nowak D, Mossner M, Ganepola S, Müssig A, Allers K, Schneider T, Hofmann J, Kücherer C, Blau O, Blau IW, Hofmann WK, Thiel E (2009). "Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation". N. Engl. J. Med. 360 (7): 692–8. doi:10.1056/NEJMoa0802905. PMID 19213682.
^ ^a ^b Allers K, Hütter G, Hofmann J, Loddenkemper C, Rieger K, Thiel E, Schneider T (2011). "Evidence for the cure of HIV infection by CCR5Δ32/Δ32 stem cell transplantation". Blood 117 (10): 2791–9. doi:10.1182/blood-2010-09-309591. PMID 21148083.
^ Zhen A, Kitchen S (2014). "Stem-cell-based gene therapy for HIV infection". Viruses 6 (1): 1–12. doi:10.3390/v6010001. PMC 3917429. PMID 24368413.
^ Kay MA, Walker BD (2014). "Engineering cellular resistance to HIV". N. Engl. J. Med. 370 (10): 968–9. doi:10.1056/NEJMe1400593. PMID 24597871.
^ ^a ^b Tebas P, Stein D, Tang WW, Frank I, Wang SQ, Lee G, Spratt SK, Surosky RT, Giedlin MA, Nichol G, Holmes MC, Gregory PD, Ando DG, Kalos M, Collman RG, Binder-Scholl G, Plesa G, Hwang WT, Levine BL, June CH (2014). "Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV". N. Engl. J. Med. 370 (10): 901–10. doi:10.1056/NEJMoa1300662. PMID 24597865.
^ ^a ^b Genetics Home Reference
^ Samson M, Labbe O, Mollereau C, Vassart G, Parmentier M (March 1996). "Molecular cloning and functional expression of a new human CC-chemokine receptor gene". Biochemistry 35 (11): 3362–7. doi:10.1021/bi952950g. PMID 8639485.
^ Slimani H, Charnaux N, Mbemba E, Saffar L, Vassy R, Vita C, Gattegno L (October 2003). "Interaction of RANTES with syndecan-1 and syndecan-4 expressed by human primary macrophages". Biochim. Biophys. Acta 1617 (1–2): 80–8. doi:10.1016/j.bbamem.2003.09.006. PMID 14637022.
^ ^a ^b Struyf S, Menten P, Lenaerts JP, Put W, D'Haese A, De Clercq E, Schols D, Proost P, Van Damme J (July 2001). "Diverging binding capacities of natural LD78beta isoforms of macrophage inflammatory protein-1alpha to the CC chemokine receptors 1, 3 and 5 affect their anti-HIV-1 activity and chemotactic potencies for neutrophils and eosinophils". Eur. J. Immunol. 31 (7): 2170–8. doi:10.1002/1521-4141(200107)31:7<2170::AID-IMMU2170>3.0.CO;2-D. PMID 11449371.
^ Proudfoot AE, Fritchley S, Borlat F, Shaw JP, Vilbois F, Zwahlen C, Trkola A, Marchant D, Clapham PR, Wells TN (April 2001). "The BBXB motif of RANTES is the principal site for heparin binding and controls receptor selectivity". J. Biol. Chem. 276 (14): 10620–6. doi:10.1074/jbc.M010867200. PMID 11116158.
^ ^a ^b ^c ^d Tamamis P, Floudas CA (Jun 26, 2014). "Elucidating a Key Anti-HIV-1 and Cancer-Associated Axis: The Structure of CCL5 (Rantes) in Complex with CCR5". Sci. Rep. 4: 5447. doi:10.1038/srep05447. PMID 24965094.
^ Miyakawa T, Obaru K, Maeda K, Harada S, Mitsuya H (February 2002). "Identification of amino acid residues critical for LD78beta, a variant of human macrophage inflammatory protein-1alpha, binding to CCR5 and inhibition of R5 human immunodeficiency virus type 1 replication". J. Biol. Chem. 277 (7): 4649–55. doi:10.1074/jbc.M109198200. PMID 11734558.
^ ^a ^b ^c ^d Tamamis P, Floudas CA (Apr 24, 2014). "Molecular recognition of CCR5 by an HIV-1 gp120 V3 loop". PLoS One 9 (4): e95767. doi:10.1371/journal.pone.0095767. PMID 24763408.
^ Anderson J, Akkina R (2007). "Complete knockdown of CCR5 by lentiviral vector-expressed siRNAs and protection of transgenic macrophages against HIV-1 infection". Gene Therapy 14 (17): 1287–97. doi:10.1038/sj.gt.3302958. PMID 17597795.
^ ^a ^b Galvani AP, Slatkin M; Slatkin (December 2003). "Evaluating plague and smallpox as historical selective pressures for the CCR5-Delta 32 HIV-resistance allele". Proc. Natl. Acad. Sci. U.S.A. 100 (25): 15276–9. Bibcode:2003PNAS..10015276G. doi:10.1073/pnas.2435085100. PMC 299980. PMID 14645720.
^ Stephens JC, Reich DE, Goldstein DB, Shin HD, Smith MW, Carrington M, Winkler C, Huttley GA, Allikmets R, Schriml L, Gerrard B, Malasky M, Ramos MD, Morlot S, Tzetis M, Oddoux C, di Giovine FS, Nasioulas G, Chandler D, Aseev M, Hanson M, Kalaydjieva L, Glavac D, Gasparini P, Kanavakis E, Claustres M, Kambouris M, Ostrer H, Duff G, Baranov V, Sibul H, Metspalu A, Goldman D, Martin N, Duffy D, Schmidtke J, Estivill X, O'Brien SJ, Dean M (June 1998). "Dating the origin of the CCR5-Delta32 AIDS-resistance allele by the coalescence of haplotypes". Am. J. Hum. Genet. 62 (6): 1507–15. doi:10.1086/301867. PMC 1377146. PMID 9585595.
^ Buseyne F, Janvier G, Teglas JP, Ivanoff S, Burgard M, Bui E, Mayaux MJ, Blanche S, Rouzioux C, Rivière Y (October 1998). "Impact of heterozygosity for the chemokine receptor CCR5 32-bp-deleted allele on plasma virus load and CD4 T lymphocytes in perinatally human immunodeficiency virus-infected children at 8 years of age". J. Infect. Dis. 178 (4): 1019–23. doi:10.1086/515660. PMID 9806029.
^ ^a ^b Faure E, Royer-Carenzi M (December 2008). "Is the European spatial distribution of the HIV-1-resistant CCR5-Delta32 allele formed by a breakdown of the pathocenosis due to the historical Roman expansion?". Infect. Genet. Evol. 8 (6): 864–74. doi:10.1016/j.meegid.2008.08.007. PMID 18790087.
^ Freitas T, Brehm A, Fernandes AT (December 2006). "Frequency of the CCR5-delta32 mutation in the Atlantic island populations of Madeira, the Azores, Cabo Verde, and São Tomé e Príncipe". Hum. Biol. 78 (6): 697–703. doi:10.1353/hub.2007.0011. PMID 17564248.
^ Mirko D. Grmek (March 1991). Diseases in the Ancient Greek World.
^ Hedrick PW, Verrelli BC (June 2006). ""Ground truth" for selection on CCR5-Delta32". Trends Genet. 22 (6): 293–6. doi:10.1016/j.tig.2006.04.007. PMID 16678299.
^ Lucotte G, Smets P (2003). "CCR5-Delta32 allele frequencies in Ashkenazi Jews". Genet. Test. 7 (4): 333–7. doi:10.1089/109065703322783716. PMID 15000812.
^ Glass WG, McDermott DH, Lim JK, Lekhong S, Yu SF, Frank WA, Pape J, Cheshier RC, Murphy PM (January 2006). "CCR5 deficiency increases risk of symptomatic West Nile virus infection". J. Exp. Med. 203 (1): 35–40. doi:10.1084/jem.20051970. PMC 2118086. PMID 16418398.
^ Duncan SR, Scott S, Duncan CJ (March 2005). "Reappraisal of the historical selective pressures for the CCR5-Delta32 mutation". J. Med. Genet. 42 (3): 205–8. doi:10.1136/jmg.2004.025346. PMC 1736018. PMID 15744032. Lay summary – PhysOrg.com.
^ Sabeti PC, Walsh E, Schaffner SF, Varilly P, Fry B, Hutcheson HB, Cullen M, Mikkelsen TS, Roy J, Patterson N, Cooper R, Reich D, Altshuler D, O'Brien S, Lander ES (November 2005). "The case for selection at CCR5-Delta32". PLoS Biol. 3 (11): e378. doi:10.1371/journal.pbio.0030378. PMC 1275522. PMID 16248677.
^ "Delta32 Genetic Testing". Briefing paper for AFAO members. Australian Federation of AIDS Organisations. 2007-06-01. Retrieved 2011-01-22.
^ ^a ^b Steinberger P, Andris-Widhopf J, Bühler B, Torbett BE, Barbas CF (January 2000). "Functional deletion of the CCR5 receptor by intracellular immunization produces cells that are refractory to CCR5-dependent HIV-1 infection and cell fusion". Proc. Natl. Acad. Sci. U.S.A. 97 (2): 805–10. Bibcode:2000PNAS...97..805S. doi:10.1073/pnas.97.2.805. PMC 15412. PMID 10639161.
^ Schoofs M (2008-11-07). "A Doctor, a Mutation and a Potential Cure for AIDS". The Wall Street Journal. Retrieved 2010-12-15.
^ Agrawal L, Lu X, Qingwen J, VanHorn-Ali Z, Nicolescu IV, McDermott DH, Murphy PM, Alkhatib G (March 2004). "Role for CCR5Delta32 protein in resistance to R5, R5X4, and X4 human immunodeficiency virus type 1 in primary CD4+ cells". J. Virol. 78 (5): 2277–87. doi:10.1128/JVI.78.5.2277-2287.2004. PMC 369216. PMID 14963124.
^ "Autologous T-Cells Genetically Modified at the CCR5 Gene by Zinc Finger Nucleases SB-728 for HIV (Zinc-Finger)". U.S. National Institutes of Health. 2009-12-09. Retrieved 2009-12-30.
^ Wade, Nicholas (2009-12-28). "Zinc Fingers Could Be Key to Reviving Gene Therapy". The New York Times. Retrieved 2009-12-30.

External links

Video and text from a PBS documentary about the discovery of CCR5
"Chemokine Receptors: CCR5". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
HuGENavigator literature on HIV Infections and CCR5 from CDC - (note, authors may not be CDC employees, and there is no public domain notice on the page, so this cannot be assumed to be public domain)
Schering-Plough Initiates Phase III Studies with CCR5-Vicriviroc in Treatment- Experienced HIV Patients.
HIVcoPred A server for prediction of HIV coreceptor usage (CCR5). PLoS ONE 8(4): e61437

UpToDate Contents

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English Journal

Structural insight into the binding complex: β-arrestin/CCR5 complex.

Stambouli N1, Dridi M, Wei NN, Jlizi A, Bouraoui A, Elgaaied AB.Author information 1a Laboratory of Genetics, Immunology and Human Pathology, Faculty of Sciences , Tunis , Tunisia .AbstractThe chemokine receptor 5 (CCR5) belongs to the superfamily of serpentine G protein-coupled receptors (GPCRs). The DRY motif (Asp, Arg, Tyr) of the intracellular loop 2 (ICL2), which is highly conserved in the GPCRs has been shown to be essential for the stability of folding of CCR5 and the interaction with β-arrestin. But the molecular mechanism by which it recognizes and interacts with β-arrestin has not been elucidated. In the present study, we described the active state of the β-arrestin structure using normal mode analysis and characterized the binding cleft of CCR5-ICL2 with β-arrestin using SABRE© docking tool and molecular dynamics simulation. Based on our computational results, we proposed a mode of binding between the ICL2 loop of CCR5 and β-arrestin structure, and modeled the energetically stable β-arrestin/CCR5 complex. In view of CCR5's importance as a therapeutic target for the treatment of HIV, this observation provides novel insight into the β-arrestin/CCR5 pathway. As a result, the current computational study of the detailed β-arrestin/CCR5 binding complex could provide the rationale for the development of next generation of HIV peptide inhibitors as therapeutic agents.
Journal of biomolecular structure & dynamics.J Biomol Struct Dyn.2014 Jun;32(6):866-75. doi: 10.1080/07391102.2013.794373. Epub 2013 Jun 19.
The chemokine receptor 5 (CCR5) belongs to the superfamily of serpentine G protein-coupled receptors (GPCRs). The DRY motif (Asp, Arg, Tyr) of the intracellular loop 2 (ICL2), which is highly conserved in the GPCRs has been shown to be essential for the stability of folding of CCR5 and the interacti
PMID 24404772

Plasma membrane signaling in HIV-1 infection.

Abbas W1, Herbein G2.Author information 1Department of Virology, EA 4266 "Pathogens & Inflammation", SFR FED4234, University of Franche-Comte, CHRU Besançon, F-25030 Besançon, France. Electronic address: wazim_cemb@hotmail.com.2Department of Virology, EA 4266 "Pathogens & Inflammation", SFR FED4234, University of Franche-Comte, CHRU Besançon, F-25030 Besançon, France. Electronic address: georges.herbein@univ-fcomte.fr.AbstractPlasma membrane is a multifunctional structure that acts as the initial barrier against infection by intracellular pathogens. The productive HIV-1 infection depends upon the initial interaction of virus and host plasma membrane. Immune cells such as CD4+ T cells and macrophages contain essential cell surface receptors and molecules such as CD4, CXCR4, CCR5 and lipid raft components that facilitate HIV-1 entry. From plasma membrane HIV-1 activates signaling pathways that prepare the grounds for viral replication. Through viral proteins HIV-1 hijacks host plasma membrane receptors such as Fas, TNFRs and DR4/DR5, which results in immune evasion and apoptosis both in infected and uninfected bystander cells. These events are hallmark in HIV-1 pathogenesis that leads towards AIDS. The interplay between HIV-1 and plasma membrane signaling has much to offer in terms of viral fitness and pathogenicity, and a better understanding of this interplay may lead to development of new therapeutic approaches. This article is part of a Special Issue entitled: Viral Membrane Proteins - Channels for Cellular Networking.
Biochimica et biophysica acta.Biochim Biophys Acta.2014 Apr;1838(4):1132-1142. doi: 10.1016/j.bbamem.2013.06.020. Epub 2013 Jun 24.
Plasma membrane is a multifunctional structure that acts as the initial barrier against infection by intracellular pathogens. The productive HIV-1 infection depends upon the initial interaction of virus and host plasma membrane. Immune cells such as CD4+ T cells and macrophages contain essential cel
PMID 23806647

Temporal Course of Changes in Gene Expression Suggests a Cytokine-Related Mechanism for Long-Term Hippocampal Alteration after Controlled Cortical Impact.

Almeida-Suhett CP1, Li Z, Marini AM, Braga MF, Eiden LE.Author information 11 Program in Neuroscience, F. Edward Hébert School of Medicine Uniformed Services University of the Health Sciences , Bethesda, Maryland.AbstractAbstract Mild traumatic brain injury (mTBI) often has long-term effects on cognitive function and social behavior. Altered gene expression may be predictive of long-term psychological effects of mTBI, even when acute clinical effects are minimal or transient. Controlled cortical impact (CCI), which causes concussive, but nonpenetrant, trauma to underlying (non-cortical) brain, resulting in persistent changes in hippocampal synaptic function, was used as a model of mTBI. The hippocampal transcriptomes of sham-operated or injured male rats at 1, 7, and 30 days postinjury were examined using microarrays comprising a comprehensive set of expressed genes, subsequently confirmed by quantitative reverse-transcriptase polymerase chain reaction. Transcripts encoding the chemokines, chemokine (C-C motif) ligand (Ccl)2 and Ccl7, inflammatory mediators lipocalin-2 (Lcn2) and tissue inhibitor of metalloproteinase 1 (Timp1), immunocyte activators C-C chemokine receptor type 5 (Ccr5) and Fc fragment of IgG, low affinity IIb, receptor (CD32) (Fcgr2b), the major histocompatibility complex II immune response-related genes, Cd74 and RT1 class II, locus Da (RT1-Da), the complement component, C3, and the transcription factor, Kruppel-like factor 4 (Klf4), were identified as early (Ccl2, Ccl7, Lcn2, and Timp1), intermediate (Ccr5, Fcgr2b, Cd74, RT1-Da, and C3), and late (Klf4) markers for bilateral hippocampal response to CCI. Ccl2 and Ccl7 transcripts were up-regulated within 24 h after CCI, and their elevation subsided within 1 week of injury. Other transcriptional changes occurred later and were more stable, some persisting for at least 1 month, suggesting that short-term inflammatory responses trigger longer-term alteration in the expression of genes previously associated with injury, aging, and neuronal function in the brain. These transcriptional responses to mTBI may underlie long-term changes in excitatory and inhibitory neuronal imbalance in hippocampus, leading to long-term behavioral consequences of mTBI.
Journal of neurotrauma.J Neurotrauma.2014 Mar 3. [Epub ahead of print]
Abstract Mild traumatic brain injury (mTBI) often has long-term effects on cognitive function and social behavior. Altered gene expression may be predictive of long-term psychological effects of mTBI, even when acute clinical effects are minimal or transient. Controlled cortical impact (CCI), which
PMID 24344922

Japanese Journal

脳梗塞におけるケモカインRANTESについて

脳循環代謝（日本脳循環代謝学会機関誌） 28(2), 327-331, 2017
NAID 130006008215

Essential roles of the interaction between cancer cell-derived chemokine, CCL4, and intra-bone CCR5-expressing fibroblasts in breast cancer bone metastasis

Cancer Letters 378(1), 23-32, 2016-08-01
NAID 120005764205

CCR5による脂肪組織マクロファージの動態制御 : CCR5とインスリン抵抗性 (第1土曜特集代謝調節における免疫細胞の役割) -- (脂肪組織炎症性マクロファージを調節する分子)

医学のあゆみ 257(6), 620-626, 2016-05-07
NAID 40020812627

「CCR5受容体」

Chemokine (C-C motif) receptor 5 (gene/pseudogene)
	; PDB rendering based on 1poz.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	2L87, 2RLL, 2RRS, 4MBS
Identifiers
Symbols	CCR5 ; CC-CKR-5; CCCKR5; CCR-5; CD195; CKR-5; CKR5; CMKBR5; IDDM22
External IDs	OMIM: 601373 MGI: 88338 HomoloGene: 37325 GeneCards: CCR5 Gene
Gene ontology
Molecular function	• actin binding; • phosphatidylinositol phospholipase C activity; • chemokine receptor activity; • protein binding; • coreceptor activity; • C-C chemokine receptor activity; • C-C chemokine binding; • chemokine (C-C motif) ligand 5 binding;
Cellular component	• cytoplasm; • endosome; • plasma membrane; • integral to plasma membrane; • external side of plasma membrane; • cell surface;
Biological process	• MAPK cascade; • dendritic cell chemotaxis; • calcium ion transport; • chemotaxis; • inflammatory response; • immune response; • cellular defense response; • cell surface receptor signaling pathway; • G-protein coupled receptor signaling pathway; • elevation of cytosolic calcium ion concentration; • cell-cell signaling; • release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; • viral reproduction; • virus-host interaction; • calcium-mediated signaling; • viral reproductive process; • signaling; • entry into host cell; • negative regulation of cAMP biosynthetic process; • chemokine-mediated signaling pathway; • response to cholesterol; • cellular response to lipopolysaccharide;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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