CCL5

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

CCL5
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1B3A, 1EQT, 1HRJ, 1RTN, 1RTO, 1U4L, 1U4M, 1U4P, 1U4R, 2L9H, 2VXW, 5CMD, 5DNF, 5COY
Identifiers
Aliases	CCL5, D17S136E, RANTES, SCYA5, SIS-delta, SISd, TCP228, eoCP, C-C motif chemokine ligand 5
External IDs	OMIM: 187011 MGI: 98262 HomoloGene: 2244 GeneCards: CCL5
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17q12 Start 35,871,491 bp[1] End 35,880,793 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11 C|11 50.66 cM Start 83,525,778 bp[2] End 83,530,518 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • CCR5 chemokine receptor binding • receptor signaling protein tyrosine kinase activator activity • chemokine activity • protein self-association • CCR4 chemokine receptor binding • phosphatidylinositol phospholipase C activity • protein kinase activity • cytokine activity • CCR1 chemokine receptor binding • phospholipase activator activity • chemokine receptor binding • protein homodimerization activity • chemokine receptor antagonist activity • GO:0001948 protein binding • chemoattractant activity • identical protein binding • CCR chemokine receptor binding Cellular component • cytoplasm • extracellular region • extracellular • cell Biological process • leukocyte cell-cell adhesion • positive regulation of cell-cell adhesion mediated by integrin • regulation of T cell activation • positive regulation of smooth muscle cell migration • activation of phospholipase D activity • negative regulation of viral genome replication • positive regulation of ERK1 and ERK2 cascade • positive regulation of innate immune response • cellular response to interferon-gamma • positive regulation of macrophage chemotaxis • calcium ion transport • exocytosis • positive regulation of calcium ion transport • response to cytokine • regulation of insulin secretion • chemokine-mediated signaling pathway • positive regulation of cellular biosynthetic process • response to virus • positive regulation of monocyte chemotaxis • cellular response to fibroblast growth factor stimulus • neutrophil chemotaxis • response to tumor necrosis factor • negative regulation of T cell apoptotic process • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity • negative regulation of macrophage apoptotic process • positive regulation of T cell proliferation • positive regulation of phosphorylation • inflammatory response • positive regulation of translational initiation • response to toxic substance • positive regulation of epithelial cell proliferation • positive regulation of tyrosine phosphorylation of STAT protein • cellular response to organic cyclic compound • cellular calcium ion homeostasis • protein tetramerization • chemotaxis • positive regulation of homotypic cell-cell adhesion • cellular response to interleukin-1 • immune response • positive regulation of viral genome replication • positive regulation of JAK-STAT cascade • lipopolysaccharide-mediated signaling pathway • positive regulation of T cell migration • regulation of chronic inflammatory response • positive regulation of smooth muscle cell proliferation • neutrophil activation • protein kinase B signaling • positive regulation of cell migration • positive regulation of natural killer cell chemotaxis • cell-cell signaling • eosinophil chemotaxis • dendritic cell chemotaxis • MAPK cascade • macrophage chemotaxis • positive regulation of T cell chemotaxis • regulation of neuron death • positive regulation of phosphatidylinositol 3-kinase signaling • negative regulation of G-protein coupled receptor protein signaling pathway • positive regulation of T cell apoptotic process • positive regulation of cell adhesion • negative regulation of chemokine-mediated signaling pathway • monocyte chemotaxis • positive chemotaxis • positive regulation of protein tyrosine kinase activity • cellular response to tumor necrosis factor • positive regulation of activation of Janus kinase activity • regulation of receptor activity • G-protein coupled receptor signaling pathway • cytokine-mediated signaling pathway • lymphocyte chemotaxis Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	6352	20304
Ensembl	ENSG00000271503 ENSG00000274233	ENSMUSG00000035042
UniProt	P13501	P30882
RefSeq (mRNA)	NM_002985 NM_001278736	NM_013653
RefSeq (protein)	NP_001265665 NP_002976	NP_038681
Location (UCSC)	Chr 17: 35.87 – 35.88 Mb	Chr 11: 83.53 – 83.53 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[6] It is also an HIV-suppressive factor released from CD8+ T cells. This chemokine has been localized to chromosome 17 in humans.[5]

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).[7][8][9][10] 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.[11] 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.[12]

Interactions

CCL5 has been shown to interact with CCR3, [13][14] CCR5[14][15][16] and CCR1.[14][16]

CCL5 also activates the G-protein coupled receptor GPR75. [17]

See also

• Chemotaxis
• Chemokine

References

1. ENSG00000274233 GRCh38: Ensembl release 89: ENSG00000271503, ENSG00000274233 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000035042 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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" (PDF). Genomics. 6 (3): 548–53. doi:10.1016/0888-7543(90)90485-D. hdl:2027.42/28717. PMID 1691736.
6. 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.
7. 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.
8. Alan M. Krensky (1995). Biology of the Chemokine in Rantes (Molecular Biology Intelligence Unit). R G Landes Co. ISBN 978-1-57059-253-9.
9. 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.
10. 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.
11. 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" (PDF). Science. 270 (5243): 1811–5. doi:10.1126/science.270.5243.1811. PMID 8525373.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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

• Human CCL5 genome location and CCL5 gene details page in the UCSC Genome Browser.
• Overview of all the structural information available in the PDB for UniProt: P13501 (C-C motif chemokine 5) at the PDBe-KB.

Further reading

• Muthumani K, Desai BM, Hwang DS, Choo AY, Laddy DJ, Thieu KP, Rao RG, Weiner DB (2004). "HIV-1 Vpr and anti-inflammatory activity". DNA Cell Biol. 23 (4): 239–47. doi:10.1089/104454904773819824. PMID 15142381.
• Zhao RY, Elder RT (2005). "Viral infections and cell cycle G2/M regulation". Cell Res. 15 (3): 143–9. doi:10.1038/sj.cr.7290279. PMID 15780175.
• Zhao RY, Bukrinsky M, Elder RT (2005). "HIV-1 viral protein R (Vpr) & host cellular responses". Indian J. Med. Res. 121 (4): 270–86. PMID 15817944.
• Li L, Li HS, Pauza CD, Bukrinsky M, Zhao RY (2006). "Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions". Cell Res. 15 (11–12): 923–34. doi:10.1038/sj.cr.7290370. PMID 16354571.
• Ignatov A, Robert J, Gregory-Evans C, Schaller HC (Nov 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.