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

    Gene ID: 6352, updated on 26-Jul-2015
    Official Symbol
    CCL5provided by HGNC
    Official Full Name
    chemokine (C-C motif) ligand 5provided by HGNC
    Primary source
    HGNC:HGNC:10632
    See related
    Ensembl:ENSG00000271503; HPRD:01751; MIM:187011; Vega:OTTHUMG00000188396
    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]
    Orthologs
    See CCL5 in Epigenomics, MapViewer
    Location:
    17q12
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    107 current GRCh38.p2 (GCF_000001405.28) 17 NC_000017.11 (35871491..35880373, 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 TAF15 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 68kDa Neighboring gene HEAT repeat containing 9 Neighboring gene uncharacterized LOC105371744 Neighboring gene uncharacterized LOC105371745 Neighboring gene leucine rich repeat containing 37, member A8, pseudogene

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 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 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 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 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 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-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

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    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Clone Names

    • MGC17164

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    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 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 
    heparin binding IEA
    Inferred from Electronic Annotation
    more info
     
    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 IDA
    Inferred from Direct Assay
    more info
    PubMed 
    MAPK cascade IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    activation of phospholipase D activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    aging IEA
    Inferred from Electronic Annotation
    more info
     
    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 protein complex assembly IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cellular response to alkyl hydroperoxide IEA
    Inferred from Electronic Annotation
    more info
     
    cellular response to amino acid stimulus IEA
    Inferred from Electronic Annotation
    more info
     
    cellular response to ethanol IEA
    Inferred from Electronic Annotation
    more info
     
    cellular response to fibroblast growth factor stimulus IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    cellular response to high density lipoprotein particle stimulus IEA
    Inferred from Electronic Annotation
    more info
     
    cellular response to interferon-gamma IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    cellular response to interleukin-1 IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    cellular response to morphine IEA
    Inferred from Electronic Annotation
    more info
     
    cellular response to organic cyclic compound IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cellular response to transforming growth factor beta stimulus IEA
    Inferred from Electronic Annotation
    more info
     
    cellular response to tumor necrosis factor IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    cellular response to vitamin K IEA
    Inferred from Electronic Annotation
    more info
     
    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 
    chronic inflammatory response IEA
    Inferred from Electronic Annotation
    more info
     
    dendritic cell chemotaxis TAS
    Traceable Author Statement
    more info
    PubMed 
    dibenzo-p-dioxin metabolic process IEA
    Inferred from Electronic Annotation
    more info
     
    eosinophil chemotaxis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    exocytosis IDA
    Inferred from Direct Assay
    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 IEA
    Inferred from Electronic Annotation
    more info
     
    macrophage chemotaxis TAS
    Traceable Author Statement
    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 protein 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 IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of macrophage apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of neuron death 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
     
    positive chemotaxis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of ERK1 and ERK2 cascade IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    positive regulation of GTPase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    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 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 JAK2 kinase activity TAS
    Traceable Author Statement
    more info
    PubMed 
    positive regulation of angiogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    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 fever generation 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 inflammatory response IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    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 mast cell chemotaxis IEA
    Inferred from Electronic Annotation
    more info
     
    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 neuron differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of osteoclast differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    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 IDA
    Inferred from Direct Assay
    more info
    PubMed 
    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 
    protein tetramerization IDA
    Inferred from Direct Assay
    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 activity IEA
    Inferred from Electronic Annotation
    more info
     
    response to cholesterol IEA
    Inferred from Electronic Annotation
    more info
     
    response to drug IEA
    Inferred from Electronic Annotation
    more info
     
    response to estrogen IEA
    Inferred from Electronic Annotation
    more info
     
    response to glucocorticoid IEA
    Inferred from Electronic Annotation
    more info
     
    response to insulin IEA
    Inferred from Electronic Annotation
    more info
     
    response to salt stress IEA
    Inferred from Electronic Annotation
    more info
     
    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
     
    Preferred Names
    C-C motif chemokine 5
    Names
    T-cell specific protein p288
    beta-chemokine RANTES
    eosinophil chemotactic cytokine
    regulated upon activation, normally T-expressed, and presumably secreted
    small inducible cytokine subfamily A (Cys-Cys), member 5

    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
      5001..13883
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001278736.1NP_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
      Conserved Domains (1) summary
      cl00134
      Location:3363
      Chemokine; 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 ...
    2. NM_002985.2NP_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/TrEMBL
      D0EI67
      UniProtKB/Swiss-Prot
      P13501
      Related
      ENSP00000474412, OTTHUMP00000276499, ENST00000603197, OTTHUMT00000477089
      Conserved Domains (1) summary
      cd00272
      Location:3389
      Chemokine_CC; 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. ...

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 107

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

    Reference GRCh38.p2 Primary Assembly

    Genomic

    1. NC_000017.11 Reference GRCh38.p2 Primary Assembly

      Range
      35871491..35880373
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p2 ALT_REF_LOCI_1

    Genomic

    1. NT_187614.1 Reference GRCh38.p2 ALT_REF_LOCI_1

      Range
      106023..114905
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.1

    Genomic

    1. NC_018928.2 Alternate CHM1_1.1

      Range
      34263060..34271942
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)