CCL5

Chemokine (C-C motif) ligand 5
PDB rendering based on 1eqt.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1B3A​, 1EQT​, 1HRJ​, 1RTN​, 1RTO​, 1U4L​, 1U4M​, 1U4P​, 1U4R​, 2L9H​, 2VXW​
Identifiers
Symbols	CCL5 ; D17S136E; RANTES; SCYA5; SIS-delta; SISd; TCP228; eoCP
External IDs	OMIM: 187011 MGI: 98262 HomoloGene: 2244 ChEMBL: 1275217 GeneCards: CCL5 Gene
Gene ontology Molecular function • phosphatidylinositol phospholipase C activity • protein kinase activity • protein binding • chemokine activity • heparin binding • phospholipase activator activity • receptor signaling protein tyrosine kinase activator activity • CCR1 chemokine receptor binding • CCR4 chemokine receptor binding • CCR5 chemokine receptor binding • chemoattractant activity • chemokine receptor binding • protein homodimerization activity • protein self-association • chemokine receptor antagonist activity Cellular component • extracellular region • extracellular space • cytoplasm Biological process • MAPK cascade • dendritic cell chemotaxis • chronic inflammatory response • monocyte chemotaxis • regulation of chronic inflammatory response • calcium ion transport • cellular calcium ion homeostasis • exocytosis • chemotaxis • inflammatory response • leukocyte cell-cell adhesion • G-protein coupled receptor signaling pathway • cell-cell signaling • aging • response to virus • response to toxic substance • response to salt stress • positive regulation of activation of JAK2 kinase activity • positive regulation of macrophage chemotaxis • positive regulation of T cell chemotaxis • positive regulation of phosphatidylinositol 3-kinase signaling • response to activity • positive regulation of smooth muscle cell migration • dibenzo-p-dioxin metabolic process • positive regulation of cell migration • neutrophil chemotaxis • positive regulation of cellular biosynthetic process • activation of phospholipase D activity • positive regulation of fever generation • lipopolysaccharide-mediated signaling pathway • response to insulin • positive regulation of cell-cell adhesion mediated by integrin • positive regulation of homotypic cell-cell adhesion • positive regulation of T cell proliferation • neutrophil activation • positive regulation of phosphorylation • response to drug • positive regulation of tyrosine phosphorylation of STAT protein • protein kinase B signaling • positive regulation of GTPase activity • cellular protein complex assembly • response to estrogen • negative regulation by host of viral transcription • cellular response to fibroblast growth factor stimulus • positive regulation of viral genome replication • negative regulation of viral genome replication • positive regulation of innate immune response • positive regulation of neuron differentiation • positive regulation of osteoclast differentiation • negative regulation of G-protein coupled receptor protein signaling pathway • positive regulation of angiogenesis • positive regulation of cell adhesion • positive regulation of translational initiation • positive regulation of JAK-STAT cascade • eosinophil chemotaxis • macrophage chemotaxis • lymphocyte chemotaxis • positive regulation of smooth muscle cell proliferation • positive regulation of epithelial cell proliferation • positive regulation of inflammatory response • regulation of insulin secretion • regulation of T cell activation • positive chemotaxis • protein tetramerization • response to glucocorticoid • positive regulation of calcium ion transport • positive regulation of mast cell chemotaxis • positive regulation of protein tyrosine kinase activity • chemokine-mediated signaling pathway • negative regulation of chemokine-mediated signaling pathway • negative regulation of T cell apoptotic process • positive regulation of T cell apoptotic process • positive regulation of ERK1 and ERK2 cascade • response to cholesterol • cellular response to amino acid stimulus • cellular response to vitamin K • cellular response to morphine • cellular response to interferon-gamma • cellular response to interleukin-1 • cellular response to tumor necrosis factor • cellular response to ethanol • cellular response to high density lipoprotein particle stimulus • cellular response to organic cyclic compound • cellular response to alkyl hydroperoxide • cellular response to transforming growth factor beta stimulus • positive regulation of monocyte chemotaxis • regulation of neuron death • negative regulation of neuron death • negative regulation of macrophage apoptotic process • positive regulation of T cell migration • positive regulation of natural killer cell chemotaxis Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6352	20304
Ensembl	ENSG00000271503	ENSMUSG00000035042
UniProt	P13501	P30882
RefSeq (mRNA)	NM_001278736	NM_013653
RefSeq (protein)	NP_001265665	NP_038681
Location (UCSC)	Chr 17: 35.87 – 35.88 Mb	Chr 11: 83.53 – 83.53 Mb
PubMed search

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. 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

• Chemotaxis
• Chemokine

References

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. 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. 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.

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.