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(Claim that CCL5 is an HIV-suppressive factor released from CD8+ T-cells needs to site its source for this claim.)
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{{Infobox_gene}}
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'''Chemokine (C-C motif) ligand 5'''  (also '''CCL5''') is a [[protein]] which in humans is encoded by the ''CCL5'' [[gene]].<ref name="pmid1691736">{{cite journal | vauthors = Donlon TA, Krensky AM, Wallace MR, Collins FS, Lovett M, Clayberger C | title = Localization of a human T-cell-specific gene, RANTES (D17S136E), to chromosome 17q11.2-q12 | journal = Genomics | volume = 6 | issue = 3 | pages = 548–53 | date = March 1990 | pmid = 1691736 | doi = 10.1016/0888-7543(90)90485-D | url = }}</ref> It is also known as '''RANTES''' (regulated on activation, normal T cell expressed and secreted).
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image = 1PMI_human_rantes05.png
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1pmi.
| PDB = {{PDB2|1b3a}}, {{PDB2|1eqt}}, {{PDB2|1hrj}}, {{PDB2|1rtn}}, {{PDB2|1rto}}, {{PDB2|1u4l}}, {{PDB2|1u4m}}, {{PDB2|1u4p}}, {{PDB2|1u4r}}
| Name = Chemokine (C-C motif) ligand 5
| HGNCid = 10632
| Symbol = CCL5
| AltSymbols =; D17S136E; MGC17164; RANTES; SCYA5; SISd; TCP228
| OMIM = 187011
| ECnumber = 
| Homologene = 2244
| MGIid = 98262
| GeneAtlas_image1 = PBB_GE_CCL5_1405_i_at_tn.png
| GeneAtlas_image2 = PBB_GE_CCL5_204655_at_tn.png
| Function = {{GNF_GO|id=GO:0004871 |text = signal transducer activity}} {{GNF_GO|id=GO:0008009 |text = chemokine activity}} {{GNF_GO|id=GO:0042056 |text = chemoattractant activity}}
| Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}} {{GNF_GO|id=GO:0005615 |text = extracellular space}}
| Process = {{GNF_GO|id=GO:0006874 |text = cellular calcium ion homeostasis}} {{GNF_GO|id=GO:0006887 |text = exocytosis}} {{GNF_GO|id=GO:0006928 |text = cell motility}} {{GNF_GO|id=GO:0006935 |text = chemotaxis}} {{GNF_GO|id=GO:0006954 |text = inflammatory response}} {{GNF_GO|id=GO:0006955 |text = immune response}} {{GNF_GO|id=GO:0006968 |text = cellular defense response}} {{GNF_GO|id=GO:0006979 |text = response to oxidative stress}} {{GNF_GO|id=GO:0007155 |text = cell adhesion}} {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0007267 |text = cell-cell signaling}} {{GNF_GO|id=GO:0009615 |text = response to virus}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 6352
    | Hs_Ensembl = ENSG00000161570
    | Hs_RefseqProtein = NP_002976
    | Hs_RefseqmRNA = NM_002985
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 17
    | Hs_GenLoc_start = 31222613
    | Hs_GenLoc_end = 31231490
    | Hs_Uniprot = P13501
    | Mm_EntrezGene = 20304
    | Mm_Ensembl = ENSMUSG00000035042
    | Mm_RefseqmRNA = NM_013653
    | Mm_RefseqProtein = NP_038681
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 11
    | Mm_GenLoc_start = 83341978
    | Mm_GenLoc_end = 83346713
    | Mm_Uniprot = Q5XZF2
  }}
}}
'''CCL5''' (earlier called '''RANTES''') is an 8kDa [[protein]] classified as a [[chemotaxis|chemotactic]] [[cytokine]] or [[chemokine]]. CCL5 is chemotactic for [[T cells]], [[eosinophil]]s, and [[basophil]]s, and plays an active role in recruiting [[leukocyte]]s into inflammatory sites. With the help of particular [[cytokine]]s (i.e., [[IL-2]] and [[interferon#Type II IFN|IFN-γ]]) that are released by [[T cell]]s, CCL5 also induces the proliferation and activation of certain natural-killer ([[NK cells|NK]]) cells to form CHAK (CC-Chemokine-activated killer) cells.<ref>Maghazachi et al, CC chemokines induce the generation of killer cells from CD56+ cells, Eur J Immunol. 1996, 26:315-9. PMID 8617297</ref> It is also an [[HIV]]-suppressive factor released from [[Cytotoxic T cell|CD8+ T cell]]s.  This chemokine has been localized to [[chromosome 17]] in humans.<ref>Donlon et al. Localization of a human T-cell-specific gene, CCL5 (D17S136E), to chromosome 17q11.2-q12. Genomics 5: 548-553, 1990. PMID 1691736</ref>


==History==
CCL5 is an 8kDa [[protein]] classified as a [[chemotaxis|chemotactic]] [[cytokine]] or [[chemokine]]. CCL5 is chemotactic for [[T cells]], [[eosinophil]]s, and [[basophil]]s, and plays an active role in recruiting [[leukocyte]]s into inflammatory sites. With the help of particular [[cytokine]]s (i.e., [[Interleukin 2|IL-2]] and [[interferon#Type II IFN|IFN-γ]]) that are released by [[T cell]]s, CCL5 also induces the proliferation and activation of certain natural-killer ([[NK cells|NK]]) cells to form CHAK (CC-Chemokine-activated killer) cells.<ref name="pmid8617297">{{cite journal | vauthors = Maghazachi AA, Al-Aoukaty A, Schall TJ | title = CC chemokines induce the generation of killer cells from CD56+ cells | journal = Eur. J. Immunol. | volume = 26 | issue = 2 | pages = 315–9 | date = February 1996 | pmid = 8617297 | doi = 10.1002/eji.1830260207 | url =  | issn =  }}</ref> It is also an [[HIV]]-suppressive factor released from [[Cytotoxic T cell|CD8+ T cell]]s{{Citation needed|reason=Your explanation here|date=September 2017}}.  This chemokine has been localized to [[chromosome 17]] in humans.<ref name="pmid1691736" />
CCL5 was earlier called ''Regulated upon Activation, Normal T-cell Expressed, and Secreted'', abbreviated '''RANTES''.


==References==
RANTES was first identified in a search for genes expressed "late" (3–5 days) after [[T cell]] activation.  It was subsequently determined to be a [[Chemokine#CC chemokines|CC chemokine]] and expressed in more than 100 human diseases.  RANTES expression is regulated in T lymphocytes by Kruppel like factor 13 ([[KLF13]]).<ref name="pmid2456327">{{cite journal | vauthors = Schall TJ, Jongstra J, Dyer BJ, Jorgensen J, Clayberger C, Davis MM, Krensky AM | title = A human T cell-specific molecule is a member of a new gene family | journal = J. Immunol. | volume = 141 | issue = 3 | pages = 1018–25 | date = August 1988 | pmid = 2456327 | doi =  | url = http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=2456327 | issn =  }}</ref><ref name="isbn1-57059-253-5">{{cite book | author = Alan M. Krensky | others = | title = Biology of the Chemokine in Rantes (Molecular Biology Intelligence Unit) | edition = | language = | publisher = R G Landes Co. | location = | year = 1995 | origyear = | pages = | quote = | isbn = 1-57059-253-5 | oclc = | doi = | url = | accessdate = }}</ref><ref name="pmid10023774">{{cite journal | vauthors = Song A, Chen YF, Thamatrakoln K, Storm TA, Krensky AM | title = RFLAT-1: a new zinc finger transcription factor that activates RANTES gene expression in T lymphocytes | journal = Immunity | volume = 10 | issue = 1 | pages = 93–103 | date = January 1999 | pmid = 10023774 | doi = 10.1016/S1074-7613(00)80010-2 | url =  }}</ref><ref name="pmid11138780">{{cite journal | vauthors = Song A, Nikolcheva T, Krensky AM | title = Transcriptional regulation of RANTES expression in T lymphocytes | journal = Immunol. Rev. | volume = 177 | issue =  | pages = 236–45 | date = October 2000 | pmid = 11138780 | doi = 10.1034/j.1600-065X.2000.17610.x | url =  }}</ref> RANTES, along with the related chemokines MIP-1alpha and MIP-1beta, has been identified as a natural HIV-suppressive factor secreted by activated CD8+ T cells and other immune cells.<ref name="pmid8525373">{{cite journal | vauthors = Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P | title = Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells | journal = Science | volume = 270 | issue = 5243 | pages = 1811–5 | date = December 1995 | pmid = 8525373 | doi = 10.1126/science.270.5243.1811 | url = http://www.sciencemag.org/cgi/reprint/270/5243/1811 | issn =  }}</ref> Recently, the RANTES protein has been engineered for in vivo production by Lactobacillus bacteria, and this solution is being developed into a possible HIV entry-inhibiting topical microbicide.<ref name="pmid20479208">{{cite journal | vauthors = Vangelista L, Secchi M, Liu X, Bachi A, Jia L, Xu Q, Lusso P | title = Engineering of Lactobacillus jensenii to secrete RANTES and a CCR5 antagonist analogue as live HIV-1 blockers | journal = Antimicrob. Agents Chemother. | volume = 54 | issue = 7 | pages = 2994–3001 | date = July 2010 | pmid = 20479208 | pmc = 2897324 | doi = 10.1128/AAC.01492-09 | laysummary = http://www.sciencedaily.com/releases/2010/07/100721153305.htm | laysource = Science Daily }}</ref>
{{reflist|2}}
 
== Interactions ==
CCL5 has been shown to [[Protein-protein interaction|interact]] with [[CCR3 (gene)|CCR3]], <ref name="pmid8642344">{{cite journal | vauthors = Daugherty BL, Siciliano SJ, DeMartino JA, Malkowitz L, Sirotina A, Springer MS | title = Cloning, expression, and characterization of the human eosinophil eotaxin receptor | journal = J. Exp. Med. | volume = 183 | issue = 5 | pages = 2349–54 | date = May 1996 | pmid = 8642344 | pmc = 2192548 | doi = 10.1084/jem.183.5.2349 | url =  | issn =  }}</ref> <ref name="pmid11449371">{{cite journal | vauthors = Struyf S, Menten P, Lenaerts JP, Put W, D'Haese A, De Clercq E, Schols D, Proost P, Van Damme J | title = 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 | journal = Eur. J. Immunol. | volume = 31 | issue = 7 | pages = 2170–8 | date = July 2001 | pmid = 11449371 | doi = 10.1002/1521-4141(200107)31:7<2170::AID-IMMU2170>3.0.CO;2-D | url =  | issn =  }}</ref> [[CCR5]]<ref name=pmid11449371/><ref name="pmid14637022">{{cite journal | vauthors = Slimani H, Charnaux N, Mbemba E, Saffar L, Vassy R, Vita C, Gattegno L | title = Interaction of RANTES with syndecan-1 and syndecan-4 expressed by human primary macrophages | journal = Biochim. Biophys. Acta | volume = 1617 | issue = 1–2 | pages = 80–8 | date = October 2003 | pmid = 14637022 | doi = 10.1016/j.bbamem.2003.09.006 | url =  | issn =  }}</ref><ref name="pmid11116158">{{cite journal | vauthors = Proudfoot AE, Fritchley S, Borlat F, Shaw JP, Vilbois F, Zwahlen C, Trkola A, Marchant D, Clapham PR, Wells TN | title = The BBXB motif of RANTES is the principal site for heparin binding and controls receptor selectivity | journal = J. Biol. Chem. | volume = 276 | issue = 14 | pages = 10620–6 | date = April 2001 | pmid = 11116158 | doi = 10.1074/jbc.M010867200 | url =  | issn =  }}</ref> and [[CCR1]].<ref name=pmid11449371/><ref name=pmid11116158 />
 
CCL5 also activates the G-protein coupled receptor [[GPR75]]. <ref name="pmid17001303">{{cite journal | vauthors = Ignatov A, Robert J, Gregory-Evans C, Schaller HC | title = RANTES stimulates Ca2+ mobilization and inositol trisphosphate (IP3) formation in cells transfected with G protein-coupled receptor 75 | journal = Br. J. Pharmacol. | volume = 149 | issue = 5 | pages = 490–7 | date = November 2006 | pmid = 17001303 | pmc = 2014681 | doi = 10.1038/sj.bjp.0706909 | url =  | issn = }}</ref>


==See also==
==See also==
*[[Chemotaxis]]
*[[Chemotaxis]]
*[[chemokine]]
*[[Chemokine]]
 
==References==
{{reflist}}
 
==External links==
* {{UCSC gene info|CCL5}}


==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
*{{cite journal | vauthors = Muthumani K, Desai BM, Hwang DS, Choo AY, Laddy DJ, Thieu KP, Rao RG, Weiner DB | title = HIV-1 Vpr and anti-inflammatory activity. | journal = DNA Cell Biol. | volume = 23 | issue = 4 | pages = 239–47 | year = 2004 | pmid = 15142381 | doi = 10.1089/104454904773819824 }}
| citations =
*{{cite journal | vauthors = Zhao RY, Elder RT | title = Viral infections and cell cycle G2/M regulation. | journal = Cell Res. | volume = 15 | issue = 3 | pages = 143–9 | year = 2005 | pmid = 15780175 | doi = 10.1038/sj.cr.7290279 }}
*{{cite journal | author=Muthumani K, Desai BM, Hwang DS, ''et al.'' |title=HIV-1 Vpr and anti-inflammatory activity. |journal=DNA Cell Biol. |volume=23 |issue= 4 |pages= 239-47 |year= 2004 |pmid= 15142381 |doi= 10.1089/104454904773819824 }}
*{{cite journal | vauthors = Zhao RY, Bukrinsky M, Elder RT | title = HIV-1 viral protein R (Vpr) & host cellular responses. | journal = Indian J. Med. Res. | volume = 121 | issue = 4 | pages = 270–86 | year = 2005 | pmid = 15817944 | doi =  }}
*{{cite journal | author=Zhao RY, Elder RT |title=Viral infections and cell cycle G2/M regulation. |journal=Cell Res. |volume=15 |issue= 3 |pages= 143-9 |year= 2005 |pmid= 15780175 |doi= 10.1038/sj.cr.7290279 }}
*{{cite journal | vauthors = Li L, Li HS, Pauza CD, Bukrinsky M, Zhao RY | title = Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions | journal = Cell Res. | volume = 15 | issue = 11–12 | pages = 923–34 | year = 2006 | pmid = 16354571 | doi = 10.1038/sj.cr.7290370 }}
*{{cite journal | author=Zhao RY, Bukrinsky M, Elder RT |title=HIV-1 viral protein R (Vpr) & host cellular responses. |journal=Indian J. Med. Res. |volume=121 |issue= 4 |pages= 270-86 |year= 2005 |pmid= 15817944 |doi=  }}
* {{cite journal | vauthors = Ignatov A, Robert J, Gregory-Evans C, Schaller HC | title = RANTES stimulates Ca2+ mobilization and inositol trisphosphate (IP3) formation in cells transfected with G protein-coupled receptor 75 | journal = Br J Pharmacol | volume = 149 | issue = 5 | pages = 490–7 | date = Nov 2006 | pmid = 17001303 | pmc = 2014681 | doi = 10.1038/sj.bjp.0706909 | url =  }}
*{{cite journal | author=Li L, Li HS, Pauza CD, ''et al.'' |title=Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions. |journal=Cell Res. |volume=15 |issue= 11-12 |pages= 923-34 |year= 2006 |pmid= 16354571 |doi= 10.1038/sj.cr.7290370 }}
}}
{{refend}}
{{refend}}


{{PDB Gallery|geneid=6352}}
{{Chemokines}}
{{Chemokines}}
{{Chemokine receptor modulators}}


{{protein-stub}}
[[Category:Cytokines]]
[[category:cytokines]]
 
[[pl:RANTES]]
{{WikiDoc Sources}}

Revision as of 16:20, 25 September 2017

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Identifiers
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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Chemokine (C-C motif) ligand 5 (also CCL5) is a protein which in humans is encoded by the CCL5 gene.[1] It is also known as RANTES (regulated on activation, normal T cell expressed and secreted).

Function

CCL5 is an 8kDa protein classified as a chemotactic cytokine or chemokine. CCL5 is chemotactic for T cells, eosinophils, and basophils, and plays an active role in recruiting leukocytes into inflammatory sites. With the help of particular cytokines (i.e., IL-2 and IFN-γ) that are released by T cells, CCL5 also induces the proliferation and activation of certain natural-killer (NK) cells to form CHAK (CC-Chemokine-activated killer) cells.[2] It is also an HIV-suppressive factor released from CD8+ T cells[citation needed]. This chemokine has been localized to chromosome 17 in humans.[1]

RANTES was first identified in a search for genes expressed "late" (3–5 days) after T cell activation. It was subsequently determined to be a CC chemokine and expressed in more than 100 human diseases. RANTES expression is regulated in T lymphocytes by Kruppel like factor 13 (KLF13).[3][4][5][6] RANTES, along with the related chemokines MIP-1alpha and MIP-1beta, has been identified as a natural HIV-suppressive factor secreted by activated CD8+ T cells and other immune cells.[7] Recently, the RANTES protein has been engineered for in vivo production by Lactobacillus bacteria, and this solution is being developed into a possible HIV entry-inhibiting topical microbicide.[8]

Interactions

CCL5 has been shown to interact with CCR3, [9] [10] CCR5[10][11][12] and CCR1.[10][12]

CCL5 also activates the G-protein coupled receptor GPR75. [13]

See also

References

  1. ↑ 1.0 1.1 Donlon TA, Krensky AM, Wallace MR, Collins FS, Lovett M, Clayberger C (March 1990). "Localization of a human T-cell-specific gene, RANTES (D17S136E), to chromosome 17q11.2-q12". Genomics. 6 (3): 548–53. doi:10.1016/0888-7543(90)90485-D. PMID 1691736.
  2. ↑ Maghazachi AA, Al-Aoukaty A, Schall TJ (February 1996). "CC chemokines induce the generation of killer cells from CD56+ cells". Eur. J. Immunol. 26 (2): 315–9. doi:10.1002/eji.1830260207. PMID 8617297.
  3. ↑ Schall TJ, Jongstra J, Dyer BJ, Jorgensen J, Clayberger C, Davis MM, Krensky AM (August 1988). "A human T cell-specific molecule is a member of a new gene family". J. Immunol. 141 (3): 1018–25. PMID 2456327.
  4. ↑ Alan M. Krensky (1995). Biology of the Chemokine in Rantes (Molecular Biology Intelligence Unit). R G Landes Co. ISBN 1-57059-253-5.
  5. ↑ Song A, Chen YF, Thamatrakoln K, Storm TA, Krensky AM (January 1999). "RFLAT-1: a new zinc finger transcription factor that activates RANTES gene expression in T lymphocytes". Immunity. 10 (1): 93–103. doi:10.1016/S1074-7613(00)80010-2. PMID 10023774.
  6. ↑ Song A, Nikolcheva T, Krensky AM (October 2000). "Transcriptional regulation of RANTES expression in T lymphocytes". Immunol. Rev. 177: 236–45. doi:10.1034/j.1600-065X.2000.17610.x. PMID 11138780.
  7. ↑ Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P (December 1995). "Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells". Science. 270 (5243): 1811–5. doi:10.1126/science.270.5243.1811. PMID 8525373.
  8. ↑ Vangelista L, Secchi M, Liu X, Bachi A, Jia L, Xu Q, Lusso P (July 2010). "Engineering of Lactobacillus jensenii to secrete RANTES and a CCR5 antagonist analogue as live HIV-1 blockers". Antimicrob. Agents Chemother. 54 (7): 2994–3001. doi:10.1128/AAC.01492-09. PMC 2897324. PMID 20479208. Lay summary – Science Daily.
  9. ↑ Daugherty BL, Siciliano SJ, DeMartino JA, Malkowitz L, Sirotina A, Springer MS (May 1996). "Cloning, expression, and characterization of the human eosinophil eotaxin receptor". J. Exp. Med. 183 (5): 2349–54. doi:10.1084/jem.183.5.2349. PMC 2192548. PMID 8642344.
  10. ↑ 10.0 10.1 10.2 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.
  11. ↑ 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.
  12. ↑ 12.0 12.1 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.
  13. ↑ Ignatov A, Robert J, Gregory-Evans C, Schaller HC (November 2006). "RANTES stimulates Ca2+ mobilization and inositol trisphosphate (IP3) formation in cells transfected with G protein-coupled receptor 75". Br. J. Pharmacol. 149 (5): 490–7. doi:10.1038/sj.bjp.0706909. PMC 2014681. PMID 17001303.

External links

Further reading


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