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CCL5 C-C motif chemokine ligand 5 [ Homo sapiens (human) ]

Gene ID: 6352, updated on 10-Oct-2020

Summary

Official Symbol
CCL5provided by HGNC
Official Full Name
C-C motif chemokine ligand 5provided by HGNC
Primary source
HGNC:HGNC:10632
See related
Ensembl:ENSG00000271503 MIM:187011
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
SISd; eoCP; SCYA5; RANTES; TCP228; D17S136E; SIS-delta
Summary
This gene is one of several chemokine genes clustered on the q-arm of chromosome 17. Chemokines form a superfamily of secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of the N-terminal cysteine residues of the mature peptide. This chemokine, a member of the CC subfamily, functions as a chemoattractant for blood monocytes, memory T helper cells and eosinophils. It causes the release of histamine from basophils and activates eosinophils. This cytokine is one of the major HIV-suppressive factors produced by CD8+ cells. It functions as one of the natural ligands for the chemokine receptor chemokine (C-C motif) receptor 5 (CCR5), and it suppresses in vitro replication of the R5 strains of HIV-1, which use CCR5 as a coreceptor. Alternative splicing results in multiple transcript variants that encode different isoforms. [provided by RefSeq, Jul 2013]
Expression
Broad expression in spleen (RPKM 54.1), lymph node (RPKM 46.2) and 17 other tissues See more
Orthologs

Genomic context

See CCL5 in Genome Data Viewer
Location:
17q12
Exon count:
4
Annotation release Status Assembly Chr Location
109.20200815 current GRCh38.p13 (GCF_000001405.39) 17 NC_000017.11 (35871491..35880360, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (34198495..34207377, complement)

Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene TATA-box binding protein associated factor 15 Neighboring gene probable ribosome biogenesis protein RLP24 Neighboring gene HEAT repeat containing 9 Neighboring gene uncharacterized LOC105371744 Neighboring gene uncharacterized LOC105371745 Neighboring gene leucine rich repeat containing 37 member A8, pseudogene

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

HIV-1 interactions

Replication interactions

Interaction Pubs
Clinical samples of serum from patients infected with HIV-1 subtypes B and C exhibited upregulated levels of CXCL10 (IP10) and CCL5 (RANTES) PubMed
HIV-1 infected clinical samples have plasma extracellular vesicles that contain elevated CCL1 (I309), IGFBP1, CCL5 (RANTES), GMCSF, ANG, ADIPOQ (ACRP30), CSF3 (GCSF), CXCL1 (GRO), ICAM1, IL2RA, IL6R, TNFRSF1A, and TIMP1 when compared to healthy donors PubMed
HIV/tuberculosis coinfection upregulates CCL5 expression in pleural fluid mononuclear cells (PFMC) isolated from antiretroviral-naive coinfected patients (relative to patients infected with only tuberculosis) PubMed

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 JRFL Env (gp120) binds specifically to polystyrene-immobilized PF4 (CXCL4) and CCL5 (RANTES) as measured through ELISA PubMed
env HIV-1 IIIB Env (gp120) upregulates production of TNF (TNF-a), IL-17A, CCL2 (MCP1), CCL5 (RANTES), IL6, IL10, CXCL8 (IL8), CXCL1 (GRO-a), and CCL1 (I309) in stimulated monocyte derived macrophages PubMed
env Curcumin, a potent and safe anti-inflammatory compound, inhibits HIV-1 gp120-mediated upregulation of the proinflammatory cytokines TNF-alpha and IL-6, and the chemokines IL-8, RANTES, and IP-10 in primary human genital epithelial cells PubMed
env The binding of HIV-1 gp120 to CCR5 and entry of macrophage-tropic HIV-1 isolates into cells is blocked by CCR5 antagonists or the chemokine RANTES, which interacts with CCR5 PubMed
env HIV-1 gp120-induced neurodegeneration is significantly inhibited by overexpression of CCL5 in vivo PubMed
env HIV-1 gp120-mediated upregulation of CCL5 expression requires the NF-kappaB pathway in astrocytes PubMed
env Exposure of macrophages to purified CCR5- or CXCR4-tropic HIV-1 envelope glycoprotein gp120 induces secretion of high levels of macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, RANTES, and tumor necrosis factor alpha PubMed
env NK cells exposed to CXCR4-tropic HIV-1 gp120 produce lower levels of CC chemokines RANTES, MIP-1alpha, and MIP-1beta compared with that produced from untreated NK cells PubMed
env RANTES, stromal derived factor-1alpha (SDF-1alpha), macrophage-derived chemokine (MDC), and their combination attenuate HIV-1 gp120-induced food and water intake decrease in rats PubMed
env HIV-1 gp120 induced cell death is inhibited by a CCR5-mediated neuroprotective pathway that involves protein kinase Akt/PKB as an essential component and can be triggered by the CCR5 agonists MIP-1beta and RANTES PubMed
env CXCR4-tropic HIV-1 gp120 augments the expression of RANTES, IP-10, MCP-1, and LTN in peripheral blood mononuclear cells (PBMCs), while CCR5-tropic HIV-1 gp120 also induces an increase in both IP-10 and MCP-1 production PubMed
env A synthetic peptide domain of the V3 region of HIV-1 gp120 activates the FPRL1 receptor in monocytes and neutrophils and causes reduced response to several chemokines that use multiple cell receptors, including SDF-1alpha and RANTES PubMed
env Chemokines such as fractalkine, macrophage-derived chemokine (MDC), RANTES, and SDF-1alpha are able to block gp120-induced apoptosis of hippocampal neurons; both fractalkine and MDC activate ERK-1/2, while SDF-1alpha activates CREB PubMed
Envelope transmembrane glycoprotein gp41 env A synthetic peptide corresponding to the immunosuppressive domain (amino acids 574-592) of HIV-1 gp41 inhibits activation of PBMCs and upregulates the expression of CCL5 in peptide-treated PBMCs PubMed
env RANTES, MIP-1beta, and anti-CD4 antibodies inhibit CCR5-dependent cell-cell fusion mediated by HIV-1 gp120 and gp41 from macrophage-tropic isolates PubMed
env HIV-1 gp41 stimulates microglial cell production of cytokines (TNF-alpha, IL-1beta, and IL-6) and chemokines (RANTES and MIP-1alpha) PubMed
Nef nef HIV-1 Nef specifically incorporates CSF2, PPBP (NAP2), CCL5, TNF, FAS, CXCL1, IL12B, MIF and OSM into plasma extracellular vesicles from HIV-1 infected patient samples PubMed
nef Knockdown of C/EBPalpha, C/EBPgamma, and AP-1 by siRNA shows significant reduction of CCL5 levels, suggesting that C/EBPalpha, C/EBPgamma, and AP-1 proteins are involved in Nef-mediated upregulation of CCL5 PubMed
nef Knockdown of p38 MAPK alpha or delta by siRNA shows significant reduction of CCL5 levels, suggesting that p38 MAPK alpha and delta proteins are involved in Nef-mediated upregulation of CCL5 PubMed
nef Knockdown of AKT2 and AKT3 by siRNA shows significant reduction of CCL5 levels, suggesting that AKT2 and AKT3 proteins are involved in Nef-mediated upregulation of CCL5 PubMed
nef Knockdown of the p50 and p65 subunits of NF-kappaB shows significant reduction of CCL5 levels, suggesting that NF-kappaB is involved in Nef-mediated upregulation of CCL5 PubMed
nef HIV-1 Nef induces a time-dependent CCL5 upregulation in astrocytes PubMed
nef HIV-1 Nef-pulsed iDCs downregulate MIP-1beta and RANTES expression in NK cells PubMed
nef HIV-1 Nef upregulates the production of RANTES/CCL5 in microglial cells PubMed
Pr55(Gag) gag MVA-gag induces a significant release of cytokines such as IL-2R, IL-6, IL-8, TNF-alpha, IFN-gamma, MCP-1, MIP-1alpha, MIP-1beta, and RANTES by the infected monocyte-derived dendritic cells in comparison with uninfected cells PubMed
Tat tat HIV-1 Tat treatment alone or combination with methadone significantly upregulate RANTES production in mixed-glial cultures PubMed
tat HIV-1 and the viral protein Tat modulate the expression of chemokine (C-C motif) ligand 5 (CCL5; RANTES) in immature dendritic cells and monocyte-derived macrophages PubMed
tat HIV-1 Tat-mediated upregulation of CCL5 involves JAK2/3, AKT2/3, p38delta, NF-kappaB (p65/p50), C/EBP alpha/gamma, and AP-1 proteins PubMed
tat Microarray analysis indicates HIV-1 Tat-induced upregulation of chemokine (C-C motif) ligand 5 (CCL5; RANTES) in primary human brain microvascular endothelial cells PubMed
tat PACAP27-induced release of CCL5 inhibits HIV-1 Tat-mediated toxicity in human astrocytes PubMed
tat Astrocyte cultures treated with morphine and Tat show exaggerated increases in chemokine release, including monocyte chemoattractant protein-1 (MCP-1), RANTES, and IL-6 PubMed
tat HIV-1 Tat upregulates RANTES expression in monocyte-derived dendritic cells (MDDC), thereby driving Th1-type immune responses PubMed
tat RANTES inhibits HIV-1 Tat-induced apoptosis, a protective effect mediated by the induction of MCP-1 PubMed
tat HIV-1 Tat cooperates with RANTES in inducing monocyte migration PubMed
tat RANTES is upregulated by HIV-1 Tat treatment in human epithelial cells PubMed
tat HIV-1 Tat upregulates RANTES expression in human microglial cells, an effect that could contribute to the neuropathogenesis if HIV-1 PubMed
Vpr vpr HIV-1 Vpr upregulates the gene expression of CCL5 (RANTES) in human monocyte-derived dendritic cells PubMed
vpr HIV-1 Vpr-induced upregulation of CCL5 requires p50 and p65 subunits of NF-kappaB, p38delta MAPK, Akt-2 and Akt-3, and AP-1 transcription factor in HIV-1 Vpr transfected astrocytes PubMed
vpr HIV-1 Vpr upregulates expression of CCL5 and causes CCL5 co-localization with GFAP in the cytoplasm of astrocytes PubMed
vpr HIV-1 Vpr regulates expression of RANTES, including upregulation in microglial cells and downregulation in primary lymphocytes and macrophages PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • MGC17164

Gene Ontology Provided by GOA

Function Evidence Code Pubs
CCR chemokine receptor binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
CCR1 chemokine receptor binding IDA
Inferred from Direct Assay
more info
PubMed 
CCR1 chemokine receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
CCR1 chemokine receptor binding TAS
Traceable Author Statement
more info
PubMed 
CCR4 chemokine receptor binding TAS
Traceable Author Statement
more info
PubMed 
CCR5 chemokine receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
chemoattractant activity IDA
Inferred from Direct Assay
more info
PubMed 
chemokine activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
chemokine activity IDA
Inferred from Direct Assay
more info
PubMed 
chemokine activity NAS
Non-traceable Author Statement
more info
PubMed 
chemokine receptor antagonist activity IDA
Inferred from Direct Assay
more info
PubMed 
chemokine receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
phosphatidylinositol phospholipase C activity IDA
Inferred from Direct Assay
more info
PubMed 
phospholipase activator activity IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein homodimerization activity IDA
Inferred from Direct Assay
more info
PubMed 
protein kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
protein self-association IDA
Inferred from Direct Assay
more info
PubMed 
receptor signaling protein tyrosine kinase activator activity IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
G protein-coupled receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
G protein-coupled receptor signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
G protein-coupled receptor signaling pathway TAS
Traceable Author Statement
more info
 
MAPK cascade IMP
Inferred from Mutant Phenotype
more info
PubMed 
activation of phospholipase D activity IDA
Inferred from Direct Assay
more info
PubMed 
calcium ion transport IDA
Inferred from Direct Assay
more info
PubMed 
cell-cell signaling IDA
Inferred from Direct Assay
more info
PubMed 
cellular calcium ion homeostasis IDA
Inferred from Direct Assay
more info
PubMed 
cellular response to fibroblast growth factor stimulus IEP
Inferred from Expression Pattern
more info
PubMed 
cellular response to interferon-gamma IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cellular response to interferon-gamma IEP
Inferred from Expression Pattern
more info
PubMed 
cellular response to interleukin-1 IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cellular response to interleukin-1 IEP
Inferred from Expression Pattern
more info
PubMed 
cellular response to organic cyclic compound IDA
Inferred from Direct Assay
more info
PubMed 
cellular response to tumor necrosis factor IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cellular response to tumor necrosis factor IEP
Inferred from Expression Pattern
more info
PubMed 
chemokine-mediated signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
chemokine-mediated signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
chemokine-mediated signaling pathway TAS
Traceable Author Statement
more info
PubMed 
chemotaxis NAS
Non-traceable Author Statement
more info
PubMed 
cytokine-mediated signaling pathway TAS
Traceable Author Statement
more info
 
dendritic cell chemotaxis TAS
Traceable Author Statement
more info
PubMed 
eosinophil chemotaxis IDA
Inferred from Direct Assay
more info
PubMed 
exocytosis IDA
Inferred from Direct Assay
more info
PubMed 
inflammatory response IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
inflammatory response IDA
Inferred from Direct Assay
more info
PubMed 
leukocyte cell-cell adhesion IDA
Inferred from Direct Assay
more info
PubMed 
lipopolysaccharide-mediated signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
lymphocyte chemotaxis IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
macrophage chemotaxis TAS
Traceable Author Statement
more info
PubMed 
monocyte chemotaxis IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
monocyte chemotaxis IC
Inferred by Curator
more info
PubMed 
negative regulation by host of viral transcription IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of G protein-coupled receptor signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of T cell apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of chemokine-mediated signaling pathway IEA
Inferred from Electronic Annotation
more info
 
negative regulation of macrophage apoptotic process IEA
Inferred from Electronic Annotation
more info
 
negative regulation of viral genome replication IDA
Inferred from Direct Assay
more info
PubMed 
neutrophil activation IDA
Inferred from Direct Assay
more info
PubMed 
neutrophil chemotaxis IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive chemotaxis IEA
Inferred from Electronic Annotation
more info
 
positive regulation of ERK1 and ERK2 cascade IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of GTPase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of JAK-STAT cascade TAS
Traceable Author Statement
more info
PubMed 
positive regulation of T cell apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of T cell chemotaxis IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of T cell chemotaxis IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of T cell migration IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of T cell proliferation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of activation of Janus kinase activity TAS
Traceable Author Statement
more info
PubMed 
positive regulation of calcium ion transport IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of cell adhesion IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of cell migration IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of cell-cell adhesion mediated by integrin IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of cellular biosynthetic process IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of epithelial cell proliferation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of homotypic cell-cell adhesion IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of innate immune response TAS
Traceable Author Statement
more info
PubMed 
positive regulation of macrophage chemotaxis IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of monocyte chemotaxis IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of natural killer cell chemotaxis IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of phosphatidylinositol 3-kinase signaling IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of protein tyrosine kinase activity IEA
Inferred from Electronic Annotation
more info
 
positive regulation of smooth muscle cell migration IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of smooth muscle cell proliferation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of translational initiation NAS
Non-traceable Author Statement
more info
PubMed 
positive regulation of tyrosine phosphorylation of STAT protein IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of viral genome replication TAS
Traceable Author Statement
more info
PubMed 
protein kinase B signaling IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of T cell activation IDA
Inferred from Direct Assay
more info
PubMed 
regulation of chronic inflammatory response TAS
Traceable Author Statement
more info
PubMed 
regulation of insulin secretion IDA
Inferred from Direct Assay
more info
PubMed 
regulation of neuron death IDA
Inferred from Direct Assay
more info
PubMed 
response to toxic substance IDA
Inferred from Direct Assay
more info
PubMed 
response to virus TAS
Traceable Author Statement
more info
PubMed 
Component Evidence Code Pubs
cytoplasm IEA
Inferred from Electronic Annotation
more info
 
extracellular region TAS
Traceable Author Statement
more info
 
extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 

General protein information

Preferred Names
C-C motif chemokine 5
Names
T-cell specific protein p288
beta-chemokine RANTES
chemokine (C-C motif) ligand 5
eosinophil chemotactic cytokine
regulated upon activation, normally T-expressed, and presumably secreted
small inducible cytokine subfamily A (Cys-Cys), member 5

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_015990.1 RefSeqGene

    Range
    5014..13883
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001278736.2NP_001265665.1  C-C motif chemokine 5 isoform 2 precursor

    See identical proteins and their annotated locations for NP_001265665.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate exon in the 3' coding region, which results in a frameshift, compared to variant 1. The encoded isoform (2) has a longer and distinct C-terminus, compared to isoform 1.
    Source sequence(s)
    AA443491, AW769950, BG272739, CB111656, CD695497, CR980938, GD136908, HY265548
    Related
    ENSP00000499138.1, ENST00000651122.1
    Conserved Domains (1) summary
    cl00134
    Location:3363
    Chemokine; small cytokines, including a number of secreted growth factors and interferons involved in mitogenic, chemotactic, and inflammatory activity; distinguished from other cytokines by their receptors, which are G-protein coupled receptors; divided into 4 ...
  2. NM_002985.3NP_002976.2  C-C motif chemokine 5 isoform 1 precursor

    See identical proteins and their annotated locations for NP_002976.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the shorter transcript and encodes isoform 1.
    Source sequence(s)
    AA443491, AA486131, AW769950, BC008600, BG272739, CD695497
    Consensus CDS
    CCDS11300.1
    UniProtKB/Swiss-Prot
    P13501
    UniProtKB/TrEMBL
    D0EI67
    Related
    ENSP00000475057.1, ENST00000605140.6
    Conserved Domains (1) summary
    cd00272
    Location:3389
    Chemokine_CC; 1 of 4 subgroup designations based on the arrangement of the two N-terminal cysteine residues; includes a number of secreted growth factors and interferons involved in mitogenic, chemotactic, and inflammatory activity; some members (e.g. 2HCC) contain an ...

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20200815

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000017.11 Reference GRCh38.p13 Primary Assembly

    Range
    35871491..35880360 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p13 ALT_REF_LOCI_1

Genomic

  1. NT_187614.1 Reference GRCh38.p13 ALT_REF_LOCI_1

    Range
    106023..114892 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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