C-C motif chemokine 5 (CCL5)
The protein contains 91 amino acids for an estimated molecular weight of 9990 Da.
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). (updated: Sept. 12, 2018)
Protein identification was indicated in the following studies:
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| Antagonist of the chemokine receptors CCR1 and CCR3 |
No binding partner found
Biological Process
Activation of phospholipase D activity
Calcium ion transport
Cell-cell signaling
Cellular calcium ion homeostasis
Cellular response to fibroblast growth factor stimulus
Cellular response to interferon-gamma
Cellular response to interleukin-1
Cellular response to organic cyclic compound
Cellular response to tumor necrosis factor
Cellular response to virus
Chemokine-mediated signaling pathway
Chemotaxis
Cytokine-mediated signaling pathway
Dendritic cell chemotaxis
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 G protein-coupled receptor signaling pathway
Negative regulation of macrophage apoptotic process
Negative regulation of T cell apoptotic process
Negative regulation of viral genome replication
Neutrophil activation
Neutrophil chemotaxis
Positive regulation of activation of Janus kinase activity
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 GTPase activity
Positive regulation of homotypic cell-cell adhesion
Positive regulation of innate immune response
Positive regulation of macrophage chemotaxis
Positive regulation of monocyte chemotaxis
Positive regulation of natural killer cell chemotaxis
Positive regulation of phosphatidylinositol 3-kinase signaling
Positive regulation of phosphorylation
Positive regulation of receptor signaling pathway via JAK-STAT
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
Regulation of chronic inflammatory response
Regulation of insulin secretion
Regulation of neuron death
Regulation of T cell activation
Response to toxic substance
Response to virus
Molecular Function
CCR chemokine receptor binding
CCR1 chemokine receptor binding
CCR4 chemokine receptor binding
CCR5 chemokine receptor binding
Chemoattractant activity
Chemokine activity
Chemokine receptor antagonist activity
Chemokine receptor binding
Identical protein binding
Phosphatidylinositol phospholipase C activity
Phospholipase activator activity
Protein homodimerization activity
Protein kinase activity
Protein self-association
Receptor signaling protein tyrosine kinase activator activity
The reference OMIM entry for this protein is 187011
Chemokine, cc motif, ligand 5; ccl5
Small inducible cytokine a5; scya5
Regulated upon activation, normally t-expressed, and presumably secreted; rantes
T cell-specific rantes
T cell-specific protein p228; tcp228
CLONING
Using a human cDNA library that was enriched by subtractive hybridization for sequences expressed by T lymphocytes but not B lymphocytes, Schall et al. (1988) isolated a gene (D17S136E), which they designated RANTES, that encodes a novel T cell-specific molecule. (RANTES is an acronym for 'Regulated upon Activation, Normally T-Expressed, and presumably Secreted.') The gene product was predicted to be a 10-kD protein which, after cleavage of the signal peptide, could be expected to be approximately 8 kD. Of the 68 residues, 4 are cysteines, and there are no sites for N-linked glycosylation. Significant homology (30 to 70%) was found between the RANTES sequence and several other T-cell genes, suggesting that they constitute a family of small, secreted T-cell molecules. Schall et al. (1988) found that RANTES, also designated p228 (TCP228), was expressed in 10 functional T-cell lines, but not in 8 hematopoietic tumor lines or in 6 T-cell tumor lines. Its expression was increased more than 10-fold in peripheral blood lymphocytes 3 to 5 days following mitogenic or antigenic stimulation.GENE FUNCTION
CD8-positive T lymphocytes are involved in the control of human immunodeficiency virus (HIV) infection in vivo (see 609423). Cocchi et al. (1995) demonstrated that the chemokines RANTES, MIP-1-alpha (182283), and MIP-1-beta (182284) are the major HIV-suppressive factors produced by CD8-positive T cells. HIV-suppressive factor activity produced by either immortalized or primary CD8-positive T cells was completely blocked by a combination of neutralizing antibodies against these 3 cytokines. On the other hand, recombinant forms of the 3 human cytokines induced a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). Cocchi et al. (1995) speculated that chemokine-mediated control of HIV may occur either directly, through their inherent anti-lentiretroviral activity, or indirectly, through their ability to chemoattract T cells and monocytes to the proximity of the infection foci. However, this latter mechanism may also have the opposite effect of providing new, uninfected targets for HIV infection. The authors noted that the findings may be relevant for the prevention and therapy of AIDS. Arenzana-Seisdedos et al. (1996) investigated a derivative of RANTES as a possible therapeutic agent for inhibition of HIV infection. The derivative, called RANTES(9-68), lacks the first 8 N-terminal amino acids and has no chemotactic or leukocyte-activating properties. RANTES(9-68) was a potent receptor antagonist and inhibited infection of macrophage-tropic HIV. The anti-HIV activity was somewhat lower than that of RANTES itself, which correlated with its lower affinity for CC chemokine receptors. Arenzana-Seisdedos et al. (1996) found that the anti-HIV activity of RANTES and RANTES(9-68) showed some variability depending on the donor cells. The authors concluded that structural modification of a chemokine can yield variants lacking activation properties but retaining both high-affinity for chemokine receptors and the ability to block HIV infection. Using astrocytes obtained from 5- to 10-week-old fetal forebrains and in situ hybridization and immunohistochemical analyses, Bakhiet et al. (2001) showed that expression of RANTES mRNA and protein, but not of other chemokines, increases with age. Responses to RANTES in cultured astrocytes differed with age. Stimulation of 5-week-old astroc ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 187011 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).