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

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: mouse all
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Genomic context

Location:: 17q12

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (34255285..34257203)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (35201562..35203480)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (32582304..32584222)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The CCL2-CCR4 axis promotes Regulatory T cell trafficking to canine glioma tissues.
Title: The CCL2-CCR4 axis promotes Regulatory T cell trafficking to canine glioma tissues.
LRP1 induces anti-PD-1 resistance by modulating the DLL4-NOTCH2-CCL2 axis and redirecting M2-like macrophage polarisation in bladder cancer.
Title: LRP1 induces anti-PD-1 resistance by modulating the DLL4-NOTCH2-CCL2 axis and redirecting M2-like macrophage polarisation in bladder cancer.
Virus-Induced Host Chemokine CCL2 in COVID-19 Pathogenesis: Potential Prognostic Marker and Target of Anti-Inflammatory Strategy.
Title: Virus-Induced Host Chemokine CCL2 in COVID-19 Pathogenesis: Potential Prognostic Marker and Target of Anti-Inflammatory Strategy.
CCL2 mediated IKZF1 expression promotes M2 polarization of glioma-associated macrophages through CD84-SHP2 pathway.
Title: CCL2 mediated IKZF1 expression promotes M2 polarization of glioma-associated macrophages through CD84-SHP2 pathway.
Epithelial cells derived exosomal miR-203a-3p facilitates stromal inflammation of type IIIA chronic prostatitis/chronic pelvic pain syndrome by targeting DUSP5 and increasing MCP-1 generation.
Title: Epithelial cells derived exosomal miR-203a-3p facilitates stromal inflammation of type IIIA chronic prostatitis/chronic pelvic pain syndrome by targeting DUSP5 and increasing MCP-1 generation.
Association of CC-chemokine ligand-2 gene polymorphisms with leprosy reactions.
Title: Association of CC-chemokine ligand-2 gene polymorphisms with leprosy reactions.
Association of MCP-1 promotor polymorphism with disease severity of Crimean-Congo hemorrhagic fever.
Title: Association of MCP-1 promotor polymorphism with disease severity of Crimean-Congo hemorrhagic fever.
Hypoxia-induced miR-210-3p expression in lung adenocarcinoma potentiates tumor development by regulating CCL2 mediated monocyte infiltration.
Title: Hypoxia-induced miR-210-3p expression in lung adenocarcinoma potentiates tumor development by regulating CCL2 mediated monocyte infiltration.
MCP-1 controls IL-17-promoted monocyte migration and M1 polarization in osteoarthritis.
Title: MCP-1 controls IL-17-promoted monocyte migration and M1 polarization in osteoarthritis.
BRG1 mediates epigenetic regulation of TNFalpha-induced CCL2 expression in oral tongue squamous cell carcinoma cells.
Title: BRG1 mediates epigenetic regulation of TNFα-induced CCL2 expression in oral tongue squamous cell carcinoma cells.

Submit: New GeneRIF Correction See all GeneRIFs (1392)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Mycobacterium tuberculosis, susceptibility to MedGen: C1834752 OMIM: 607948 GeneReviews: Not available	Compare labs
Neural tube defect MedGen: C0027794 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 EBI GWAS CatalogPubMed
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel associations for hypothyroidism include known autoimmune risk loci. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D17S1269 (e-PCR)
- UniSTS:149810

CCL2_498 (e-PCR)
- UniSTS:277056

GDB:607769 (e-PCR)
- UniSTS:158283

D17S1988 (e-PCR)
- UniSTS:31585

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 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

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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)

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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

NG_012123.1 RefSeqGene

Range

5009..6927

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_002982.4 → NP_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:34 → 91

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 ...