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    CCL3 C-C motif chemokine ligand 3 [ Homo sapiens (human) ]

    Gene ID: 6348, updated on 27-Nov-2024

    Summary

    Official Symbol
    CCL3provided by HGNC
    Official Full Name
    C-C motif chemokine ligand 3provided by HGNC
    Primary source
    HGNC:HGNC:10627
    See related
    Ensembl:ENSG00000277632 MIM:182283; AllianceGenome:HGNC:10627
    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
    SCI; LD78; MIP1A; SCYA3; G0S19-1; LD78ALPHA; MIP-1-alpha
    Summary
    This locus represents a small inducible cytokine. The encoded protein, also known as macrophage inflammatory protein 1 alpha, plays a role in inflammatory responses through binding to the receptors CCR1, CCR4 and CCR5. Polymorphisms at this locus may be associated with both resistance and susceptibility to infection by human immunodeficiency virus type 1.[provided by RefSeq, Sep 2010]
    Annotation information
    Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in cytokine storm inflammatory response.
    Expression
    Biased expression in bone marrow (RPKM 81.4), liver (RPKM 17.1) and 10 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See CCL3 in Genome Data Viewer
    Location:
    17q12
    Exon count:
    2
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (36088256..36090143, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (37036142..37038029, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (34415602..34417489, complement)

    Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105371746 Neighboring gene C-C motif chemokine ligand 18 Neighboring gene CCL3 antisense RNA 1 Neighboring gene MPRA-validated peak2824 silencer Neighboring gene C-C motif chemokine ligand 4 Neighboring gene RNA, 7SL, cytoplasmic 301, 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 cerebrospinal fluid from patients infected with HIV-1 subtypes B and C exhibited upregulated levels of IL7, IL10, CXCL10 (IP10), CCL2 (MCP1), and CCL3 (MIP1A) PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env Vaccine with CCL3 inserted in the targeting unit induces a higher number of HIV-1 gp120-reactive T cells in vivo compared to gp120 only PubMed
    env HIV-1 gp120 induces the release of cytokines MIP-1 alpha, MIP-1 beta, IL-6, IL10, and TNF-alpha in immature dentritic cells PubMed
    env The CCR5 chemokine receptor is required for the entry of macrophage-tropic HIV-1 into target cells; the HIV-1 gp120-CD4 complex binds CCR5, which inhibits the binding of the natural CCR5 ligands macrophage inflammatory protein (MIP)-1alpha and MIP-1beta PubMed
    env HIV-1 gp120 binding causes increased expression of CCL3 in T cells 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 HIV-1 gp120 from a T-cell-tropic virus causes CD4-dependent antagonism of CXCR4 response to SDF-1alpha, whereas gp120 from macrophage-tropic viruses causes CD4-dependent antagonism of CCR5 response to MIP-1alpha PubMed
    env The neuroprotective action of VIP on gp120-induced neuronal cell death is attenuated by co-treatment with anti-MIP-1alpha, suggesting that the neuroprotective action of VIP is linked in part to its release of MIP-1alpha PubMed
    env The chemokine receptor CCR5 is posttranslationally modified by sulfation of its N-terminal tyrosines; sulfated tyrosines contribute to the binding of CCR5 to MIP-1 alpha, MIP-1 beta, and HIV-1 gp120/CD4 complexes and to the ability of HIV-1 to enter cells PubMed
    env N-formyl-methionyl-leucylphenyl-alanine binding to formyl peptide receptor (FPR) results in significant attenuation of cell responses to CCR5 ligands and in inhibition of HIV-1 gp120-mediated fusion and infection of cells expressing CD4, CCR5, and FPR PubMed
    Envelope surface glycoprotein gp160, precursor env A significant level of MIP1A is upregulated when PBMCs are stimulated with HIV-1 gp140 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 MIP-1alpha in peptide-treated PBMCs 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 The expression of HIV-1 Nef in primary human monocyte-derived macrophages (MDM) increases the concentration of MIP-1alpha PubMed
    nef HIV-1 Nef-stimulated CD8+ T cells upregulate mRNAs expression for IFN-gamma, MIP-1alpha, MIP-1alphaP, MIP-1beta, TNFRSF9, XCL1, and GM-CSF compared to unstimulated cells PubMed
    nef HIV-1 Nef impairs the mobility of primary CD4+ lymphocytes and inhibits chemotaxis of primary T cells to CCL3 PubMed
    nef HIV-1 Nef expression by immature human and macaque dendritic cells (DCs) upregulates IL-6, IL-12, TNF-alpha, CXCL8, CCL3, and CCL4 release, but without upregulating co-stimulatory and other molecules characteristic of mature DCs 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
    gag HIV-1 Gag virus-like particles expressed by recombinant baculoviruses activate human PBMC to release GM-CSF and MIP-1alpha in a dose-and time-dependent manner PubMed
    Tat tat HIV-1 and the viral protein Tat modulate the expression of chemokine (C-C motif) ligand 3 (CCL3; MIP-1-alpha) in immature dendritic cells and monocyte-derived macrophages PubMed
    tat HIV-1 Tat upregulates MIP-1alpha expression in microglia, MDDC, and T and B cell lines, an effect that suggests Tat plays an important role in the pathogenesis of HIV encephalitis and AIDS associated progressive multifocal leukoencephalopathy (PML) PubMed
    tat HIV-1 Tat enhances the NFkappaB activity and promotes the transcriptional activation of MIP-1alpha by interacting with IkappaB-alpha and p65 RelA PubMed
    tat Wild-type Tat but not Cys-22 and oxidized Tat induces CD1A-expressing monocyte-derived dendritic cells (MDDC) maturation and increases the production of cytokines TNF-alpha, IL-12, MIP-1alpha, and MIP-1beta PubMed
    tat HIV-1 Tat downregulates MIP-1alpha expression in Jurkat T-cells by inducing MNP-1 PubMed
    Vpr vpr HIV-1 Vpr downregulates the expression of beta chemokines in primary lymphocytes and macrophage, including MIP-1 alpha, MIP-1 beta, and RANTES PubMed
    capsid gag HIV-1 CA-stimulated CD8+ T cells upregulate mRNAs expression for IFN-gamma, MIP-1alpha, MIP-1alphaP, MIP-1beta, TNFRSF9, XCL1, and GM-CSF compared to unstimulated cells PubMed
    matrix gag HIV-1 Matrix is able to reduce MIP-1alpha secretion from IL-15-stimulated monocyte cells 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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables CCR chemokine receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables CCR1 chemokine receptor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables CCR5 chemokine receptor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables chemoattractant activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables chemokine activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables chemokine activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables phospholipase activator activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Process Evidence Code Pubs
    involved_in MAPK cascade IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in T cell chemotaxis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in antimicrobial humoral immune response mediated by antimicrobial peptide IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in astrocyte cell migration ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in calcium ion transport IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in calcium-mediated signaling IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in cell activation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in cell chemotaxis IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in cell-cell signaling IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in cellular response to interleukin-1 IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in cellular response to tumor necrosis factor IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in cellular response to type II interferon IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in chemokine-mediated signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in chemotaxis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in cytoskeleton organization IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in eosinophil chemotaxis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in eosinophil degranulation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in exocytosis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in granulocyte chemotaxis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in inflammatory response IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in inflammatory response IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in intracellular calcium ion homeostasis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in lymphocyte chemotaxis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in macrophage chemotaxis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in monocyte chemotaxis IC
    Inferred by Curator
    more info
    PubMed 
    involved_in monocyte chemotaxis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation by host of viral transcription IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of bone mineralization IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of gene expression IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of osteoclast differentiation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in neutrophil chemotaxis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in osteoblast differentiation IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in positive chemotaxis IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of ERK1 and ERK2 cascade IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of calcium ion import TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in positive regulation of calcium ion transport IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of calcium-mediated signaling IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of cell migration IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in positive regulation of cell migration IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of gene expression IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of inflammatory response ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of interleukin-1 beta production ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of microglial cell activation TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in positive regulation of microglial cell migration TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in positive regulation of natural killer cell chemotaxis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of neuron apoptotic process ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in positive regulation of tumor necrosis factor production ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of behavior IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of cell shape IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of sensory perception of pain IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in release of sequestered calcium ion into cytosol by sarcoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in response to cholesterol IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in response to toxic substance IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in signaling IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    Component Evidence Code Pubs
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in extracellular region IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
     
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    PubMed 

    General protein information

    Preferred Names
    C-C motif chemokine 3
    Names
    G0/G1 switch regulatory protein 19-1
    PAT 464.1
    SIS-beta
    macrophage inflammatory protein 1-alpha
    small inducible cytokine A3 (homologous to mouse Mip-1a)
    tonsillar lymphocyte LD78 alpha protein

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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_027730.2 RefSeqGene

      Range
      5000..6887
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_002983.3NP_002974.1  C-C motif chemokine 3 precursor

      See identical proteins and their annotated locations for NP_002974.1

      Status: REVIEWED

      Source sequence(s)
      BX103455, M23452
      Consensus CDS
      CCDS11307.1
      UniProtKB/Swiss-Prot
      P10147
      UniProtKB/TrEMBL
      A0N0R1, Q14745
      Related
      ENSP00000477908.1, ENST00000613922.2
      Conserved Domains (1) summary
      smart00199
      Location:3088
      SCY; Intercrine alpha family (small cytokine C-X-C) (chemokine CXC)

    RNA

    1. NR_168494.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC243829
      Related
      ENST00000614051.1
    2. NR_168495.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC243829
    3. NR_168496.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC243829

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000017.11 Reference GRCh38.p14 Primary Assembly

      Range
      36088256..36090143 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_1

    Genomic

    1. NT_187614.1 Reference GRCh38.p14 ALT_REF_LOCI_1

      Range
      323130..325017 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_2

    Genomic

    1. NT_187661.1 Reference GRCh38.p14 ALT_REF_LOCI_2

      Range
      42353..44240 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060941.1 Alternate T2T-CHM13v2.0

      Range
      37036142..37038029 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)