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    CCL2 C-C motif chemokine ligand 2 [ Homo sapiens (human) ]

    Gene ID: 6347, updated on 13-May-2024

    Summary

    Official Symbol
    CCL2provided by HGNC
    Official Full Name
    C-C motif chemokine ligand 2provided by HGNC
    Primary source
    HGNC:HGNC:10618
    See related
    Ensembl:ENSG00000108691 MIM:158105; AllianceGenome:HGNC:10618
    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
    HC11; MCAF; MCP1; MCP-1; SCYA2; GDCF-2; SMC-CF; HSMCR30
    Summary
    This gene is one of several cytokine genes clustered on the q-arm of chromosome 17. Chemokines are a superfamily of secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of N-terminal cysteine residues of the mature peptide. This chemokine is a member of the CC subfamily which is characterized by two adjacent cysteine residues. This cytokine displays chemotactic activity for monocytes and basophils but not for neutrophils or eosinophils. It has been implicated in the pathogenesis of diseases characterized by monocytic infiltrates, like psoriasis, rheumatoid arthritis and atherosclerosis. It binds to chemokine receptors CCR2 and CCR4. Elevated expression of the encoded protein is associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. [provided by RefSeq, Aug 2020]
    Annotation information
    Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in cytokine storm inflammatory response.
    Expression
    Ubiquitous expression in gall bladder (RPKM 117.6), appendix (RPKM 92.3) and 23 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    Location:
    17q12
    Exon count:
    3
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (34255285..34257203)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (35201562..35203480)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (32582304..32584222)

    Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene acid sensing ion channel subunit 2 Neighboring gene uncharacterized LOC105371735 Neighboring gene ReSE screen-validated silencer GRCh37_chr17:32483646-32483804 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:32484104-32484658 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8431 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr17:32505165-32505693 Neighboring gene ReSE screen-validated silencer GRCh37_chr17:32510298-32510505 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:32531127-32531628 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:32531629-32532128 Neighboring gene long intergenic non-protein coding RNA 1989 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr17:32578883-32580082 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr17:32581026-32582000 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr17:32582001-32582975 Neighboring gene C-C motif chemokine ligand 11 Neighboring gene C-C motif chemokine ligand 7

    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?

    Phenotypes

    Associated conditions

    Description Tests
    Mycobacterium tuberculosis, susceptibility to
    MedGen: C1834752 OMIM: 607948 GeneReviews: Not available
    Compare labs
    Neural tube defect
    MedGen: C0027794 OMIM: 182940 GeneReviews: Not available
    Compare labs
    Susceptibility to HIV infection
    MedGen: C1836230 OMIM: 609423 GeneReviews: Not available
    Compare labs

    EBI GWAS Catalog

    Description
    A genome-wide scan of Ashkenazi Jewish Crohn's disease suggests novel susceptibility loci.
    EBI GWAS Catalog
    Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.
    EBI GWAS Catalog
    Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
    EBI GWAS Catalog
    Novel associations for hypothyroidism include known autoimmune risk loci.
    EBI GWAS Catalog

    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
    Clinical trophoblast microparticle samples from HIV-1 infected patients decrease CCL2 (MCP-1) expression on dendritic cells upon exposure PubMed
    HIV-1 ADA infection decreases production of CXCL8 (IL8), CCL2 (MCP-1), and IL6 at a basal level or after Fc receptor, complement receptor 3, or bacterial stimulation in primary human macrophages PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 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 HIV-1 CN54, JRFL, and Ada Env (gp120) upregulates IL-6, CCL2, CCL4, CXCL8, and IL-1b through TLR4 and CCR5 induction in monocyte derived macrophages and hepatic stellate cells because treatment with an anti-TLR4 antibody mitigated the response PubMed
    env HIV-1 JRFL (gp120) upregulates CCL2 in ARPE-19 cells PubMed
    env HIV-1 gp120-induced release of IL-6 and MCP-1 is partially responsible for the impairment of barrier function in human retinal pigment epithelial cells 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 Upregulation of the human proteins CCL2, CX3CL1, IL-1beta, and CXCL10 by HIV-1 gp120 involves CB2 receptor in mesencephalic neuronal/glial culture model PubMed
    env HIV-1 gp120 upregulates the expression of chemokine (C-C motif) ligand 2 (CCL2) in human B cells PubMed
    env Nuclear PI-PLC beta 1 plays as a new intermediate in the gp120-triggered PC-PLC-driven signal transduction pathway leading to CCL2 secretion in macrophages PubMed
    env The interaction of HIV-1 gp120 with CCR5 triggers PC-PLC activation and CCL2 secretion in human monocyte-derived macrophages PubMed
    env Phosphatidylcholine-specific phospholipase C (PC-PLC) signaling pathway modulates HIV-1 gp120-induced CCL2 production in human monocyte-derived macrophages PubMed
    env CCL2 upregulates CXCR4 on resting CD4(+) T cells in a CCR2-dependent mechanism, increases the ability of these cells to be chemoattracted to CXCR4 using gp120 and renders them more permissive to X4-tropic HIV-1 infection PubMed
    env Treatment of macrophages (MDM) with recombinant gp120-IIIB results in a specific and dose-dependent enhancement of secretion of monocyte chemoattractant protein-1, macrophage inflammatory protein-1beta, and RANTES PubMed
    env Treatment of human hepatic stellate cells with gp120 significantly increases secretion and gene expression of CCL2, metalloprotease-1 and interleukin-6. Gp120 also induces activation of Akt, NF-kappaB, and p38(MAPK) PubMed
    Envelope transmembrane glycoprotein gp41 env The HIV-1 gp41 transmembrane domain inhibits TLR2-induced activation of ERK1/2, and secretion of TNF-alpha, MCP-1, and IL-6 PubMed
    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 MCP-1 in peptide-treated PBMCs PubMed
    Nef nef Jurkat cells infected with HIV-1 induces a stronger endothelial MCP-1 release and apoptosis in comparison to Nef-deleted HIV-1, suggesting that Nef is responsible for HIV-induced endothelial cell death and activation PubMed
    nef HIV-1 Nef inhibits CCL-2 induced chemotaxis in Jurkat cells, monocytes, and PBMCs, which leads to marked downregulation of F-actin accumulation in cells PubMed
    nef HIV-1 Nef upregulates CCL-2/MCP-1 expression in astrocytes and this upregulation by Nef depends on the myristoylation moiety (residues 2-3) of Nef and requires functional calmodulin PubMed
    Pr55(Gag) gag Neutralization of endogenous CCL2 by Abs induces cellular A3A expression, inhibits HIV-1 Gag+ MDM cells, and impairs HIV-1 DNA accumulation in MDM PubMed
    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 upregulates CCL2 mRNA and protein expression in CRT-MG human astroglioma cells PubMed
    tat HIV-1 Tat upregulates MCP-1 expression, an effect that may contribute to the pathogenesis of Tat associated with AIDS dementia PubMed
    tat HIV-1 Tat inhibitor didehydro-Cortistatin A (dCA), an analog of a natural steroidal alkaloid, potently inhibits Tat-mediated modulation of IL-1beta, TNF-alpha and MCP-1 PubMed
    tat HIV-1 Tat-induced release of CCL2 from human astrocytes is regulated by P2RX7 PubMed
    tat Upregulation of MCP-1 by HIV-1 Tat in astrocytes is inhibited by the MEK1/2 inhibitor UO126, indicating a role for MEK1/2 in Tat-mediated chemokine induction PubMed
    tat Microarray analysis indicates HIV-1 Tat-induced upregulation of chemokine (C-C motif) ligand 2 (CCL2; MCP-1) in primary human brain microvascular endothelial cells PubMed
    tat LRRK2 is involved in HIV-1 Tat-induced cytokine TNF-alpha, IL-6, and MCP-1 expression in microglia cells PubMed
    tat The endogenous PPARgamma ligand 15d-PGJ2 inhibits HIV-1 Tat-induced MCP-1 production in human microglia-like cells PubMed
    tat HIV-1 Tat downregulates the expression of adiponectin protein and upregulates the expression of IL-6, IL-8, and MCP-1 proteins in human SGBS preadipocytes PubMed
    tat Over-expression of PPARalpha or PPARgamma attenuates Tat-induced up-regulation of inflammatory mediators, such as interleukin (IL)-1beta, tumor necrosis factor-alpha, CCL2, and E-selectin PubMed
    tat CDK9 is involved in Tat-induced MCP-1/CCL2 gene expression 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 Upregulation of MCP-1 by HIV-1 Tat is mediated at the transcriptional level and is regulated, at least in part, by NF-kappa B, AP1, Sp1, protein kinase C and PI3 kinase PubMed
    tat HIV-1 Tat is a competitive inhibitor of MCP-1 binding to CCR2 PubMed
    tat MCP-1 and RANTES have been shown to inhibit Tat-induced apoptosis of mixed cultures of human neurons and astrocytes PubMed
    tat The C-terminal MH2 domain of Smad3 can decrease the levels of HIV-1 Tat-induced activation of MCP-1 in astrocytic cells PubMed
    tat Tat-mediated upregulation of MCP-1 transcription is stimulated by Smad-3 and decreased by Smad-4 PubMed
    Vpr vpr Treatment of human primary astrocytes with HIV-1 Vpr upregulates secretion of IL-6, IL-8, MCP-1, and MIF and downregulates secretion of serpin E1, a serine proteinase inhibitor (known as PAI-1) PubMed
    matrix gag Treatment of human PBMCs with HIV-1 MA upregulates the expression of MCP-1, ICAM-1, CD40, CD86 and CD36 and downregulates the expression of nuclear receptors FXR and PPARgamma PubMed
    gag HIV-1 matrix activates monocytes to produce MCP-1, which depends on the binding activity of AP-1 complexes (c-Fos/JunB) in the MCP-1 promoter 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

    Clone Names

    • MGC9434

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables CCR chemokine receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables CCR2 chemokine receptor binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables CCR2 chemokine receptor binding TAS
    Traceable Author Statement
    more info
    PubMed 
    enables chemokine activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein kinase activity TAS
    Traceable Author Statement
    more info
    PubMed 
    enables signaling receptor binding TAS
    Traceable Author Statement
    more info
    PubMed 
    Process Evidence Code Pubs
    involved_in G protein-coupled receptor signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in angiogenesis TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in animal organ morphogenesis TAS
    Traceable Author Statement
    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 IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in cell adhesion TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in cell surface receptor signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in cell surface receptor signaling pathway via JAK-STAT TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in cellular homeostasis TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in cellular response to fibroblast growth factor stimulus IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in cellular response to interleukin-1 IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in cellular response to interleukin-1 ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in cellular response to lipopolysaccharide ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in cellular response to tumor necrosis factor IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in cellular response to tumor necrosis factor ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in cellular response to type II interferon IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in cellular response to type II interferon ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in chemokine-mediated signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in chemotaxis TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in cytokine-mediated signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in cytoskeleton organization IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in eosinophil chemotaxis IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in helper T cell extravasation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in humoral immune response TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in inflammatory response IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in macrophage chemotaxis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in monocyte chemotaxis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of G1/S transition of mitotic cell cycle IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of glial cell apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of natural killer cell chemotaxis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of neuron apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of vascular endothelial cell proliferation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of GTPase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in positive regulation of NMDA glutamate receptor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of T cell activation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of apoptotic cell clearance ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of calcium ion import IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of cell migration IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in positive regulation of endothelial cell apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of nitric-oxide synthase biosynthetic process ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of synaptic transmission, glutamatergic ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in protein phosphorylation TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in regulation of cell shape IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in response to bacterium NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in sensory perception of pain ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in signal transduction NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in viral genome replication TAS
    Traceable Author Statement
    more info
    PubMed 
    Component Evidence Code Pubs
    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
     

    General protein information

    Preferred Names
    C-C motif chemokine 2
    Names
    chemokine (C-C motif) ligand 2
    monocyte chemoattractant protein-1
    monocyte chemotactic and activating factor
    monocyte chemotactic protein 1
    monocyte secretory protein JE
    small inducible cytokine A2 (monocyte chemotactic protein 1, homologous to mouse Sig-je)
    small inducible cytokine subfamily A (Cys-Cys), member 2
    small-inducible cytokine A2

    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_012123.1 RefSeqGene

      Range
      5009..6927
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_002982.4NP_002973.1  C-C motif chemokine 2 precursor

      See identical proteins and their annotated locations for NP_002973.1

      Status: REVIEWED

      Source sequence(s)
      BC009716, BG530064
      Consensus CDS
      CCDS11277.1
      UniProtKB/Swiss-Prot
      B2R4V3, P13500, Q9UDF3
      Related
      ENSP00000225831.4, ENST00000225831.4
      Conserved Domains (1) summary
      cd00272
      Location:3491
      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: GCF_000001405.40-RS_2023_10

    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
      34255285..34257203
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060941.1 Alternate T2T-CHM13v2.0

      Range
      35201562..35203480
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)