Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000498
UniProt IDP13501
Primary gene name(s)CCL5
Synonym gene name(s)D17S136E, SCYA5
Protein nameC-C motif chemokine 5
Protein functionChemoattractant 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. {ECO:0000269|PubMed:1380064, ECO:0000269|PubMed:15923218, ECO:0000269|PubMed:16791620, ECO:0000269|PubMed:17001303, ECO:0000269|PubMed:23979485, ECO:0000269|PubMed:8525373, ECO:0000269|PubMed:9516414}.
Subcellular locationSecreted.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P13501
Gene Ontology
(Biological Process)
Complete annatation
activation of phospholipase D activity [GO:0031584];
calcium ion transport [GO:0006816];
cell-cell signaling [GO:0007267];
cellular calcium ion homeostasis [GO:0006874];
cellular protein complex assembly [GO:0043623];
cellular response to fibroblast growth factor stimulus [GO:0044344];
cellular response to interferon-gamma [GO:0071346];
cellular response to interleukin-1 [GO:0071347];
cellular response to organic cyclic compound [GO:0071407];
cellular response to tumor necrosis factor [GO:0071356];
chemokine-mediated signaling pathway [GO:0070098];
chemotaxis [GO:0006935];
dendritic cell chemotaxis [GO:0002407];
eosinophil chemotaxis [GO:0048245];
exocytosis [GO:0006887];
G-protein coupled receptor signaling pathway [GO:0007186];
inflammatory response [GO:0006954];
leukocyte cell-cell adhesion [GO:0007159];
lipopolysaccharide-mediated signaling pathway [GO:0031663];
macrophage chemotaxis [GO:0048246];
MAPK cascade [GO:0000165];
monocyte chemotaxis [GO:0002548];
negative regulation by host of viral transcription [GO:0043922];
negative regulation of G-protein coupled receptor protein signaling pathway [GO:0045744];
negative regulation of macrophage apoptotic process [GO:2000110];
negative regulation of T cell apoptotic process [GO:0070233];
negative regulation of viral genome replication [GO:0045071];
neutrophil activation [GO:0042119];
neutrophil chemotaxis [GO:0030593];
positive regulation of activation of JAK2 kinase activity [GO:0010535];
positive regulation of calcium ion transport [GO:0051928];
positive regulation of cell adhesion [GO:0045785];
positive regulation of cell-cell adhesion mediated by integrin [GO:0033634];
positive regulation of cell migration [GO:0030335];
positive regulation of cellular biosynthetic process [GO:0031328];
positive regulation of epithelial cell proliferation [GO:0050679];
positive regulation of ERK1 and ERK2 cascade [GO:0070374];
positive regulation of GTPase activity [GO:0043547];
positive regulation of homotypic cell-cell adhesion [GO:0034112];
positive regulation of inflammatory response [GO:0050729];
positive regulation of innate immune response [GO:0045089];
positive regulation of JAK-STAT cascade [GO:0046427];
positive regulation of macrophage chemotaxis [GO:0010759];
positive regulation of monocyte chemotaxis [GO:0090026];
positive regulation of natural killer cell chemotaxis [GO:2000503];
positive regulation of phosphatidylinositol 3-kinase signaling [GO:0014068];
positive regulation of phosphorylation [GO:0042327];
positive regulation of smooth muscle cell migration [GO:0014911];
positive regulation of smooth muscle cell proliferation [GO:0048661];
positive regulation of T cell apoptotic process [GO:0070234];
positive regulation of T cell chemotaxis [GO:0010820];
positive regulation of T cell migration [GO:2000406];
positive regulation of T cell proliferation [GO:0042102];
positive regulation of translational initiation [GO:0045948];
positive regulation of tyrosine phosphorylation of STAT protein [GO:0042531];
positive regulation of viral genome replication [GO:0045070];
protein kinase B signaling [GO:0043491];
protein tetramerization [GO:0051262];
regulation of chronic inflammatory response [GO:0002676];
regulation of insulin secretion [GO:0050796];
regulation of neuron death [GO:1901214];
regulation of T cell activation [GO:0050863];
response to toxic substance [GO:0009636];
response to virus [GO:0009615]
Gene Ontology
(Molecular Function)
Complete annatation
CCR1 chemokine receptor binding [GO:0031726];
CCR4 chemokine receptor binding [GO:0031729];
CCR5 chemokine receptor binding [GO:0031730];
chemoattractant activity [GO:0042056];
chemokine activity [GO:0008009];
chemokine receptor antagonist activity [GO:0046817];
chemokine receptor binding [GO:0042379];
heparin binding [GO:0008201];
phosphatidylinositol phospholipase C activity [GO:0004435];
phospholipase activator activity [GO:0016004];
protein homodimerization activity [GO:0042803];
protein kinase activity [GO:0004672];
protein self-association [GO:0043621];
receptor signaling protein tyrosine kinase activator activity [GO:0030298]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
extracellular region [GO:0005576];
extracellular space [GO:0005615]
Protein-protein interaction112255
Phylogenetic treeP13501
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      unknown
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      Postively associated
Interferon-stimulated
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model


DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD3-0.3620826610721930.6228596657340430.723915860729758
AZA vs. DISU-0.1271280541332750.8815504737710150.991771899371402
AZA vs. IL7-0.6831466993568150.461657580622690.999311006273513
AZA vs. SAHA-0.6922763748685860.4692998341743450.8047602553203
DISU vs. CD30.2248612554145190.7322601294433430.812819528072824
DISU vs. IL7-0.5690306785084320.5133247573519520.833769490345522
DISU vs. SAHA-0.5576098437920970.5408828230247660.846195021741247
DMSO vs. AZA-0.08834033470228350.9194383757332891
DMSO vs. CD30.2812927512608060.6883048838368220.770208205823496
DMSO vs. DISU0.04257646070260150.9584762263040020.994105021699463
DMSO vs. IL7-0.5902917598313380.5092656432813990.88780433692056
DMSO vs. SAHA-0.6085142745905420.5116666911299620.820441398235947
HIV vs. Mock in Activation0.8382616282693820.1805216619838080.999983755607037
HIV vs. Mock in Latency2.437526142151211.9559822241888e-060.00039312634729896
IL7 vs. CD3-0.3246497307614250.6646172237832680.770005934846567
SAHA vs. CD3-0.3448336312810850.664988900285370.750900127216423
SAHA vs. IL7-0.005032970719547260.9958655975311850.998085516428942
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
-1.433 0.02865

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
3.3 0.001543671 2.7 0.003982504 3.2 0.001655284
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) TRUE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.169086 0.238681
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
unknown unknown unknown unknown unknown
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB02322 Heparin Disaccharide I-S experimental unknown unknown
DB02353 Heparin Disaccharide Iii-S experimental unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1B3A X-ray 1.6Å A/B=25-91.
1EQT X-ray 1.6Å A/B=26-91.
1HRJ NMR - A/B=24-91.
1RTN NMR - A/B=24-91.
1RTO NMR - A/B=24-91.
1U4L X-ray 2.0Å A/B=24-91.
1U4M X-ray 2.0Å A/B=24-91.
1U4P X-ray 1.7Å A/B=24-91.
1U4R X-ray 2.2Å A/B/C/D=24-91.
2L9H Other - A/B/C/D=24-91.
2VXW X-ray 1.7Å A/B/C/D=33-91.
5CMD X-ray 3.0Å A/B/C/D/E/F=27-91.
5COY X-ray 1.4Å A/B=27-91.
5DNF X-ray 2.5Å A/B/C/D/E/F/G/H/I=27-91.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Envelope surface glycoprotein gp120 downregulates 16393999
Tat upregulates 10964543
11751963
20403075
2389820815630704
16206161
16697675
2424437515857508
24244375
24667918
25760046
Envelope transmembrane glycoprotein gp41 inhibited by 9256481
18663025
Envelope surface glycoprotein gp120 inhibits 10872839
Pr55(Gag) induces release of 25240755
Tat modulates 24742347
Envelope surface glycoprotein gp120 inhibited by 16343773
16841089
25623966
8898753
8976200
9359702
9420238
9576751
10644351
10774549
10775626
10820198
10882583
18706447
257856109826729
Tat inhibited by 12753088
2012116724696163
Tat cooperates with 9517988
19661268
Vpr upregulates 24225433
24225433
26116899
Nef downregulates 17431094
Vpr regulates 10985253
12359436
15142381
15780175
15817944
16354571
17586317
21918813
23728617
Envelope surface glycoprotein gp120 upregulates 11878903
1208933321945445
25856395
Envelope surface glycoprotein gp120 induces release of 11313374
11602715
11878903
12089333
12953261
15481145
17765942
Nef upregulates 12359436
1945546924658403
24658403
24658403
24658403
24658403
Envelope transmembrane glycoprotein gp41 upregulates 10964543
23383108

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04060 Cytokine-cytokine receptor interaction - Homo sapiens (human)
hsa04062 Chemokine signaling pathway - Homo sapiens (human)
hsa04620 Toll-like receptor signaling pathway - Homo sapiens (human)
hsa04621 NOD-like receptor signaling pathway - Homo sapiens (human)
hsa04623 Cytosolic DNA-sensing pathway - Homo sapiens (human)
hsa04668 TNF signaling pathway - Homo sapiens (human)
hsa05020 Prion diseases - Homo sapiens (human)
hsa05120 Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human)
hsa05142 Chagas disease (American trypanosomiasis) - Homo sapiens (human)
hsa05164 Influenza A - Homo sapiens (human)
hsa05168 Herpes simplex infection - Homo sapiens (human)
hsa05323 Rheumatoid arthritis - Homo sapiens (human)
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