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

Gene ID: 6347, updated on 29-Mar-2020

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
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. [provided by RefSeq, Jul 2013]
Expression
Ubiquitous expression in gall bladder (RPKM 117.6), appendix (RPKM 92.3) and 23 other tissues See more
Orthologs

Genomic context

See CCL2 in Genome Data Viewer
Location:
17q12
Exon count:
3
Annotation release Status Assembly Chr Location
109.20200228 current GRCh38.p13 (GCF_000001405.39) 17 NC_000017.11 (34255285..34257203)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (32582296..32584222)

Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105371735 Neighboring gene long intergenic non-protein coding RNA 1989 Neighboring gene C-C motif chemokine ligand 7 Neighboring gene C-C motif chemokine ligand 11

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
Human immunodeficiency virus type 1, susceptibility to
MedGen: C1836230 OMIM: 609423 GeneReviews: Not available
Compare labs
Mycobacterium tuberculosis, susceptibility to
MedGen: C1834752 OMIM: 607948 GeneReviews: Not available
Compare labs
Neural tube defect
MedGen: C3891448 OMIM: 182940 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

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

Homology

Clone Names

  • MGC9434

Gene Ontology Provided by GOA

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

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
    P13500
    Related
    ENSP00000225831.4, ENST00000225831.4
    Conserved Domains (1) summary
    cd00272
    Location:3491
    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 Updated Annotation Release 109.

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