CCR2 C-C motif chemokine receptor 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CCR2provided by HGNC
Official Full Name: C-C motif chemokine receptor 2provided by HGNC
Primary source: HGNC:HGNC:1603
See related: Ensembl:ENSG00000121807 MIM:601267; AllianceGenome:HGNC:1603
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: CKR2; CCR-2; CCR2A; CCR2B; CD192; CKR2A; CKR2B; PCLUD; CMKBR2; MCP-1-R; CC-CKR-2
Summary: The protein encoded by this gene is a receptor for monocyte chemoattractant protein-1, a chemokine which specifically mediates monocyte chemotaxis. Monocyte chemoattractant protein-1 is involved in monocyte infiltration in inflammatory diseases such as rheumatoid arthritis as well as in the inflammatory response against tumors. The encoded protein mediates agonist-dependent calcium mobilization and inhibition of adenylyl cyclase. This protein can also be a coreceptor with CD4 for HIV-1 infection. This gene is located in the chemokine receptor gene cluster region of chromosome 3. [provided by RefSeq, Aug 2017]
Expression: Biased expression in appendix (RPKM 15.2), lymph node (RPKM 5.1) and 12 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3p21.31

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (46354111..46360940)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (46369948..46376777)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (46395602..46402431)

Chromosome 3 - NC_000003.12 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
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?

Nucleus pulposus cells regulate macrophages in degenerated intervertebral discs via the integrated stress response-mediated CCL2/7-CCR2 signaling pathway.
Title: Nucleus pulposus cells regulate macrophages in degenerated intervertebral discs via the integrated stress response-mediated CCL2/7-CCR2 signaling pathway.
[Expression of MCP-1 and CCR2 in Newly Diagnosed Diffuse Large B-Cell Lymphoma and Clinical Significance].
Title: [Expression of MCP-1 and CCR2 in Newly Diagnosed Diffuse Large B-Cell Lymphoma and Clinical Significance].
CCR2 is a potential therapeutic target in peri-implantitis.
Title: CCR2 is a potential therapeutic target in peri-implantitis.
Human inherited CCR2 deficiency underlies progressive polycystic lung disease.
Title: Human inherited CCR2 deficiency underlies progressive polycystic lung disease.
C5a enhances Vdelta1 T cells recruitment via the CCL2-CCR2 axis in IgA nephropathy.
Title: C5a enhances Vδ1 T cells recruitment via the CCL2-CCR2 axis in IgA nephropathy.
Role of MCP-1/CCR2 axis in renal fibrosis: Mechanisms and therapeutic targeting.
Title: Role of MCP-1/CCR2 axis in renal fibrosis: Mechanisms and therapeutic targeting.
The CCL2-CCR2 Axis Contributes to Migration of Cabazitaxel-resistant Prostate Cancer Cells.
Title: The CCL2-CCR2 Axis Contributes to Migration of Cabazitaxel-resistant Prostate Cancer Cells.
Association between CCR2 and CCL2 expression and NET stimulation in adult-onset Still's disease.
Title: Association between CCR2 and CCL2 expression and NET stimulation in adult-onset Still's disease.
Significant association of MCP1 rs1024611 and CCR2 rs1799864 polymorphisms with colorectal cancer and liver metastases susceptibility and aggressiveness: A case-control study.
Title: Significant association of MCP1 rs1024611 and CCR2 rs1799864 polymorphisms with colorectal cancer and liver metastases susceptibility and aggressiveness: A case-control study.
C-C motif chemokine receptor 2 inhibition reduces liver fibrosis by restoring the immune cell landscape.
Title: C-C motif chemokine receptor 2 inhibition reduces liver fibrosis by restoring the immune cell landscape.

Submit: New GeneRIF Correction See all GeneRIFs (328)

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
Cystic disease of lung MedGen: C0555214 OMIM: 219600 GeneReviews: Not available	not available
Susceptibility to HIV infection MedGen: C1836230 OMIM: 609423 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genome-wide association study of celiac disease in North America confirms FRMD4B as new celiac locus. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-Wide Association Study of CSF Levels of 59 Alzheimer's Disease Candidate Proteins: Significant Associations with Proteins Involved in Amyloid Processing and Inflammation. EBI GWAS Catalog EBI GWAS CatalogPubMed
Multiple common variants for celiac disease influencing immune gene expression. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. 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
HIV/tuberculosis coinfection upregulates CCR2 expression in pleural fluid mononuclear cells (PFMC) isolated from antiretroviral-naive coinfected patients (relative to patients infected with only tuberculosis)	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Treatment of the resting CD4+ T cells with HIV-1 clade B Tat, but not clade C Tat, increases surface CXCR4 expression, which leads to increased function of CXCR4 including increased chemoattraction toward CXCR4-using-gp120	PubMed
	env	Macrophage-tropic HIV-1 can use CCR2b, and to a lesser extent CCR3, STRL33, and APJ, to infect cells; the V1/2 region of HIV-1 gp120 plays a more important role in governing the use of CCR2b, CCR3, STRL33, and APJ than for CXCR4	PubMed
	env	HIV-1 gp120 from CXCR4-tropic subtype E viruses isolated in Thailand associates with and uses at least one of the following coreceptors for virus entry: CCR8, CCR1, CCR2b, or CX3CR1	PubMed
Nef	nef	HIV-1 Nef induces variable levels of CCR2 downregulation in different cell types	PubMed
Tat	tat	HIV-1 Tat upregulates the expression of CCR2,CD16, and TLR-4 in monocyte-derived macrophages	PubMed
	tat	HIV-1 clade B Tat, but not clade C Tat, increases CXCR4 surface expression on resting CD4+ T cells through a CCR2b-dependent mechanism that does not involve de novo protein synthesis	PubMed
	tat	HIV-1 Tat induces CCR2-mediated glial activation	PubMed
	tat	Results from the treatment of microglia with HIV-1 Tat suggest downregulation of CCR2 mRNA expression by HIV-1 Tat, however this was deemed to not be significant	PubMed
	tat	HIV-1 Tat binds to CCR2 and displaces MCP-1 from this beta-chemokine receptor, an effect mediated by Tat amino acids 24-51	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PMC228408P2 (e-PCR)
- UniSTS:272155

D3S4500 (e-PCR)
- UniSTS:474431

SHGC-78976 (e-PCR)
- UniSTS:101976

NoName (e-PCR)
- UniSTS:481891

NoName (e-PCR)
- UniSTS:491153

SHGC-76910 (e-PCR)
- UniSTS:38106

SHGC-76923 (e-PCR)
- UniSTS:41442

WI-9314 (e-PCR)
- UniSTS:51178

Clone Names

FLJ78302, MGC103828, MGC111760, MGC168006

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables C-C chemokine binding	IBA Inferred from Biological aspect of Ancestor more info
enables C-C chemokine receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables CCR2 chemokine receptor binding	IDA Inferred from Direct Assay more info	PubMed
enables chemokine (C-C motif) ligand 12 binding	IEA Inferred from Electronic Annotation more info
enables chemokine (C-C motif) ligand 2 binding	IEA Inferred from Electronic Annotation more info
enables chemokine (C-C motif) ligand 7 binding	IEA Inferred from Electronic Annotation more info
enables chemokine receptor activity	TAS Traceable Author Statement more info	PubMed
enables identical protein binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in T-helper 17 cell chemotaxis	ISS Inferred from Sequence or Structural Similarity more info
involved_in blood vessel remodeling	ISS Inferred from Sequence or Structural Similarity more info
involved_in calcium-mediated signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell chemotaxis	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell surface receptor signaling pathway via JAK-STAT	TAS Traceable Author Statement more info	PubMed
involved_in cellular defense response	IEA Inferred from Electronic Annotation more info
involved_in cellular homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in chemokine-mediated signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in chemotaxis	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within cytokine-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in dendritic cell chemotaxis	TAS Traceable Author Statement more info	PubMed
involved_in hemopoiesis	IEA Inferred from Electronic Annotation more info
involved_in homeostasis of number of cells within a tissue	IEA Inferred from Electronic Annotation more info
involved_in humoral immune response	IEA Inferred from Electronic Annotation more info
involved_in immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in inflammatory response	IBA Inferred from Biological aspect of Ancestor more info
involved_in inflammatory response to wounding	ISS Inferred from Sequence or Structural Similarity more info
involved_in intracellular calcium ion homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in leukocyte adhesion to vascular endothelial cell	IEA Inferred from Electronic Annotation more info
involved_in macrophage migration	ISS Inferred from Sequence or Structural Similarity more info
involved_in monocyte chemotaxis	IEA Inferred from Electronic Annotation more info
involved_in monocyte extravasation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of adenylate cyclase activity	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of angiogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of eosinophil degranulation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of type 2 immune response	ISS Inferred from Sequence or Structural Similarity more info
involved_in neutrophil clearance	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of CD8-positive, alpha-beta T cell extravasation	ISS Inferred from Sequence or Structural Similarity 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 T cell chemotaxis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of T-helper 1 type immune response	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of alpha-beta T cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of astrocyte chemotaxis	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cold-induced thermogenesis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of cytosolic calcium ion concentration	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of hematopoietic stem cell migration	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of immune complex clearance by monocytes and macrophages	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of inflammatory response	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of interleukin-2 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of leukocyte tethering or rolling	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of monocyte chemotaxis	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of monocyte chemotaxis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of monocyte extravasation	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 positive regulation of thymocyte migration	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of tumor necrosis factor production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of type II interferon production	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of T cell cytokine production	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of T cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of inflammatory response	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of macrophage migration	IEA Inferred from Electronic Annotation more info
involved_in regulation of vascular endothelial growth factor production	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to wounding	TAS Traceable Author Statement more info	PubMed
involved_in sensory perception of pain	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	ISS Inferred from Sequence or Structural Similarity more info
located_in dendrite	ISS Inferred from Sequence or Structural Similarity more info
is_active_in external side of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in fibrillar center	IDA Inferred from Direct Assay more info
located_in membrane	TAS Traceable Author Statement more info	PubMed
located_in neuronal cell body	ISS Inferred from Sequence or Structural Similarity more info
located_in perikaryon	ISS Inferred from Sequence or Structural Similarity more info
located_in perinuclear region of cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: C-C chemokine receptor type 2

Names: MCP-1 receptor; chemokine (C-C motif) receptor 2; monocyte chemoattractant protein 1 receptor; monocyte chemotactic protein 1 receptor

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_021428.1 RefSeqGene

Range

5368..12197

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001123041.3 → NP_001116513.2 C-C chemokine receptor type 2 isoform A

See identical proteins and their annotated locations for NP_001116513.2

Status: REVIEWED

Description

Transcript Variant: This variant (A) represents the longer transcript and encodes the longer isoform (A).

Source sequence(s)

AC098613, AV715904, BC126452, BQ027284, BX101672, DC418358

Consensus CDS

CCDS43078.1

UniProtKB/Swiss-Prot

A0AVQ3, B2RMT0, O95950, P41597, Q4VBL2

UniProtKB/TrEMBL

L7REX9

Related

ENSP00000383681.2, ENST00000400888.2

Conserved Domains (1) summary

cd15184
Location:43 → 316

7tmA_CCR5_CCR2; CC chemokine receptor types 5 and 2, member of the class A family of seven-transmembrane G protein-coupled receptors
NM_001123396.4 → NP_001116868.1 C-C chemokine receptor type 2 isoform B

See identical proteins and their annotated locations for NP_001116868.1

Status: REVIEWED

Description

Transcript Variant: This variant (B) differs in the 3' UTR and 3' coding region, compared to variant A. The resulting isoform (B) is shorter and contains a distinct C-terminus, compared to isoform A.

Source sequence(s)

AC098613, AC138069

Consensus CDS

CCDS46813.1

UniProtKB/TrEMBL

L7REX9

Related

ENSP00000399285.2, ENST00000445132.3

Conserved Domains (2) summary

pfam00001
Location:59 → 305

7tm_1; 7 transmembrane receptor (rhodopsin family)

pfam06417
Location:245 → 283

DUF1077; Protein of unknown function (DUF1077)