C-C motif chemokine 5

Details

Name
C-C motif chemokine 5
Synonyms
  • D17S136E
  • EoCP
  • Eosinophil chemotactic cytokine
  • SCYA5
  • SIS-delta
  • Small-inducible cytokine A5
  • T cell-specific protein P228
  • T-cell-specific protein RANTES
  • TCP228
Gene Name
CCL5
Organism
Humans
Amino acid sequence
>lcl|BSEQ0021283|C-C motif chemokine 5
MKVSAAALAVILIATALCAPASASPYSSDTTPCCFAYIARPLPRAHIKEYFYTSGKCSNP
AVVFVTRKNRQVCANPEKKWVREYINSLEMS
Number of residues
91
Molecular Weight
9989.52
Theoretical pI
9.3
GO Classification
Functions
CCR1 chemokine receptor binding / CCR4 chemokine receptor binding / CCR5 chemokine receptor binding / chemoattractant activity / chemokine activity / chemokine receptor antagonist activity / chemokine receptor binding / heparin binding / phosphatidylinositol phospholipase C activity / phospholipase activator activity / protein homodimerization activity / protein kinase activity / protein self-association / receptor signaling protein tyrosine kinase activator activity
Processes
activation of phospholipase D activity / aging / calcium ion transport / cell-cell signaling / cellular calcium ion homeostasis / cellular protein complex assembly / cellular response to alkyl hydroperoxide / cellular response to amino acid stimulus / cellular response to ethanol / cellular response to fibroblast growth factor stimulus / cellular response to high density lipoprotein particle stimulus / cellular response to interferon-gamma / cellular response to interleukin-1 / cellular response to morphine / cellular response to organic cyclic compound / cellular response to transforming growth factor beta stimulus / cellular response to tumor necrosis factor / cellular response to vitamin K / chemokine-mediated signaling pathway / chemotaxis / chronic inflammatory response / dendritic cell chemotaxis / dibenzo-p-dioxin metabolic process / eosinophil chemotaxis / exocytosis / G-protein coupled receptor signaling pathway / inflammatory response / leukocyte cell-cell adhesion / lipopolysaccharide-mediated signaling pathway / lymphocyte chemotaxis / macrophage chemotaxis / MAPK cascade / monocyte chemotaxis / negative regulation by host of viral transcription / negative regulation of chemokine-mediated signaling pathway / negative regulation of G-protein coupled receptor protein signaling pathway / negative regulation of macrophage apoptotic process / negative regulation of neuron death / negative regulation of T cell apoptotic process / negative regulation of viral genome replication / neutrophil activation / neutrophil chemotaxis / positive chemotaxis / positive regulation of activation of JAK2 kinase activity / positive regulation of angiogenesis / positive regulation of calcium ion transport / positive regulation of cell adhesion / positive regulation of cell migration / positive regulation of cell-cell adhesion mediated by integrin / positive regulation of cellular biosynthetic process / positive regulation of epithelial cell proliferation / positive regulation of ERK1 and ERK2 cascade / positive regulation of fever generation / positive regulation of GTPase activity / positive regulation of homotypic cell-cell adhesion / positive regulation of inflammatory response / positive regulation of innate immune response / positive regulation of JAK-STAT cascade / positive regulation of macrophage chemotaxis / positive regulation of mast cell chemotaxis / positive regulation of monocyte chemotaxis / positive regulation of natural killer cell chemotaxis / positive regulation of neuron differentiation / positive regulation of osteoclast differentiation / positive regulation of phosphatidylinositol 3-kinase signaling / positive regulation of phosphorylation / positive regulation of protein tyrosine kinase activity / positive regulation of smooth muscle cell migration / positive regulation of smooth muscle cell proliferation / positive regulation of T cell apoptotic process / positive regulation of T cell chemotaxis / positive regulation of T cell migration / positive regulation of T cell proliferation / positive regulation of translational initiation / positive regulation of tyrosine phosphorylation of STAT protein / positive regulation of viral genome replication / protein kinase B signaling / protein tetramerization / regulation of chronic inflammatory response / regulation of insulin secretion / regulation of neuron death / regulation of T cell activation / response to activity / response to cholesterol / response to drug / response to estrogen / response to glucocorticoid / response to insulin / response to salt stress / response to toxic substance / response to virus
Components
cytoplasm / extracellular region / extracellular space
General Function
Receptor signaling protein tyrosine kinase activator activity
Specific Function
Chemoattractant for blood monocytes, memory T-helper cells and eosinophils. Causes the release of histamine from basophils and activates eosinophils. May activate several chemokine receptors including CCR1, CCR3, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant RANTES protein induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). The processed form RANTES(3-68) acts as a natural chemotaxis inhibitor and is a more potent inhibitor of HIV-1-infection. The second processed form RANTES(4-68) exhibits reduced chemotactic and HIV-suppressive activity compared with RANTES(1-68) and RANTES(3-68) and is generated by an unidentified enzyme associated with monocytes and neutrophils (PubMed:16791620, PubMed:1380064, PubMed:8525373, PubMed:9516414, PubMed:15923218). May also be an agonist of the G protein-coupled receptor GPR75, stimulating inositol trisphosphate production and calcium mobilization through its activation. Together with GPR75, may play a role in neuron survival through activation of a downstream signaling pathway involving the PI3, Akt and MAP kinases. By activating GPR75 may also play a role in insulin secretion by islet cells (PubMed:23979485).
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
>lcl|BSEQ0001940|276 bp
ATGAAGGTCTCCGCGGCACGCCTCGCTGTCATCCTCATTGCTACTGCCCTCTGCGCTCCT
GCATCTGCCTCCCCATATTCCTCGGACACCACACCCTGCTGCTTTGCCTACATTGCCCGC
CCACTGCCCCGTGCCCACATCAAGGAGTATTTCTACACCAGTGGCAAGTGCTCCAACCCA
GCAGTCGTCTTTGTCACCCGAAAGAACCGCCAAGTGTGTGCCAACCCAGAGAAGAAATGG
GTTCGGGAGTACATCAACTCTTTGGAGATGAGCTAG
Chromosome Location
Not Available
Locus
17q11.2-q12
External Identifiers
ResourceLink
UniProtKB IDP13501
UniProtKB Entry NameCCL5_HUMAN
GenBank Protein ID339421
GenBank Gene IDM21121
GenAtlas IDCCL5
HGNC IDHGNC:10632
General References
  1. Schall TJ, Jongstra J, Dyer BJ, Jorgensen J, Clayberger C, Davis MM, Krensky AM: A human T cell-specific molecule is a member of a new gene family. J Immunol. 1988 Aug 1;141(3):1018-25. [Article]
  2. Nomiyama H, Fukuda S, Iio M, Tanase S, Miura R, Yoshie O: Organization of the chemokine gene cluster on human chromosome 17q11.2 containing the genes for CC chemokine MPIF-1, HCC-2, HCC-1, LEC, and RANTES. J Interferon Cytokine Res. 1999 Mar;19(3):227-34. [Article]
  3. Capoulade-Metay C, Ayouba A, Kfutwah A, Lole K, Petres S, Dudoit Y, Deterre P, Menu E, Barre-Sinoussi F, Debre P, Theodorou I: A natural CCL5/RANTES variant antagonist for CCR1 and CCR3. Immunogenetics. 2006 Jul;58(7):533-41. Epub 2006 Jun 22. [Article]
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  5. Kameyoshi Y, Dorschner A, Mallet AI, Christophers E, Schroder JM: Cytokine RANTES released by thrombin-stimulated platelets is a potent attractant for human eosinophils. J Exp Med. 1992 Aug 1;176(2):587-92. [Article]
  6. Schroder JM, Kameyoshi Y, Christophers E: Platelets secrete an eosinophil-chemotactic cytokine which is a member of the C-C-chemokine family. Adv Exp Med Biol. 1993;351:119-28. [Article]
  7. Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P: Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science. 1995 Dec 15;270(5243):1811-5. [Article]
  8. Proost P, De Meester I, Schols D, Struyf S, Lambeir AM, Wuyts A, Opdenakker G, De Clercq E, Scharpe S, Van Damme J: Amino-terminal truncation of chemokines by CD26/dipeptidyl-peptidase IV. Conversion of RANTES into a potent inhibitor of monocyte chemotaxis and HIV-1-infection. J Biol Chem. 1998 Mar 27;273(13):7222-7. [Article]
  9. Lim JK, Burns JM, Lu W, DeVico AL: Multiple pathways of amino terminal processing produce two truncated variants of RANTES/CCL5. J Leukoc Biol. 2005 Aug;78(2):442-52. Epub 2005 May 27. [Article]
  10. Ignatov A, Robert J, Gregory-Evans C, Schaller HC: RANTES stimulates Ca2+ mobilization and inositol trisphosphate (IP3) formation in cells transfected with G protein-coupled receptor 75. Br J Pharmacol. 2006 Nov;149(5):490-7. Epub 2006 Sep 25. [Article]
  11. Liu B, Hassan Z, Amisten S, King AJ, Bowe JE, Huang GC, Jones PM, Persaud SJ: The novel chemokine receptor, G-protein-coupled receptor 75, is expressed by islets and is coupled to stimulation of insulin secretion and improved glucose homeostasis. Diabetologia. 2013 Nov;56(11):2467-76. doi: 10.1007/s00125-013-3022-x. Epub 2013 Aug 27. [Article]
  12. Skelton NJ, Aspiras F, Ogez J, Schall TJ: Proton NMR assignments and solution conformation of RANTES, a chemokine of the C-C type. Biochemistry. 1995 Apr 25;34(16):5329-42. [Article]
  13. Chung CW, Cooke RM, Proudfoot AE, Wells TN: The three-dimensional solution structure of RANTES. Biochemistry. 1995 Jul 25;34(29):9307-14. [Article]
  14. Wilken J, Hoover D, Thompson DA, Barlow PN, McSparron H, Picard L, Wlodawer A, Lubkowski J, Kent SB: Total chemical synthesis and high-resolution crystal structure of the potent anti-HIV protein AOP-RANTES. Chem Biol. 1999 Jan;6(1):43-51. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB02322Heparin Disaccharide I-SexperimentalunknownDetails
DB02353Heparin Disaccharide Iii-SexperimentalunknownDetails