CCR2 (C-C motif chemokine receptor 2)

Gene

• Entrez ID: 729230
• Gene name: C-C motif chemokine receptor 2
• Gene symbol: CCR2
• Synonyms: CC-CKR-2, CCR-2, CCR2A, CCR2B, CD192, CKR2, CKR2A, CKR2B, CMKBR2, MCP-1-R
• Chromosome: 3
• Chromosome location: 3p21.31
• 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]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT018230	hsa-miR-335-5p	Microarray	18185580
MIRT037379	hsa-miR-744-3p	CLASH	23622248
MIRT527312	hsa-miR-6514-3p	PAR-CLIP	22012620
MIRT527313	hsa-miR-6811-3p	PAR-CLIP	22012620
MIRT527314	hsa-miR-4633-5p	PAR-CLIP	22012620
MIRT527315	hsa-miR-214-5p	PAR-CLIP	22012620
MIRT527316	hsa-miR-4539	PAR-CLIP	22012620
MIRT527317	hsa-miR-4680-5p	PAR-CLIP	22012620
MIRT527318	hsa-miR-532-5p	PAR-CLIP	22012620
MIRT527319	hsa-miR-618	PAR-CLIP	22012620

Transcription factors

Transcription factor	Regulation	Reference
NFKB1	Activation	19156404
RELA	Activation	19156404

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001974	Process	Blood vessel remodeling	ISS
GO:0002407	Process	Dendritic cell chemotaxis	TAS	16621978
GO:0002724	Process	Regulation of T cell cytokine production	ISS
GO:0002827	Process	Positive regulation of T-helper 1 type immune response	ISS
GO:0002829	Process	Negative regulation of type 2 immune response	ISS
GO:0004950	Function	Chemokine receptor activity	TAS	10623817
GO:0005515	Function	Protein binding	IPI	23938203
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005737	Component	Cytoplasm	IDA	15995708
GO:0005829	Component	Cytosol	ISS
GO:0005886	Component	Plasma membrane	IDA	15995708, 18587271
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	TAS	8146186
GO:0006874	Process	Cellular calcium ion homeostasis	ISS
GO:0006935	Process	Chemotaxis	TAS	10623817
GO:0006954	Process	Inflammatory response	IBA	21873635
GO:0006955	Process	Immune response	IBA	21873635
GO:0006968	Process	Cellular defense response	TAS	10201901
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS
GO:0007194	Process	Negative regulation of adenylate cyclase activity	TAS	8995400
GO:0007204	Process	Positive regulation of cytosolic calcium ion concentration	IBA	21873635
GO:0007259	Process	Receptor signaling pathway via JAK-STAT	TAS	9670957
GO:0009611	Process	Response to wounding	TAS	8146186
GO:0009897	Component	External side of plasma membrane	IBA	21873635
GO:0010574	Process	Regulation of vascular endothelial growth factor production	ISS
GO:0010820	Process	Positive regulation of T cell chemotaxis	ISS
GO:0016021	Component	Integral component of membrane	TAS	8530354
GO:0016032	Process	Viral process	IEA
GO:0016493	Function	C-C chemokine receptor activity	IBA	21873635
GO:0016525	Process	Negative regulation of angiogenesis	ISS
GO:0019221	Process	Cytokine-mediated signaling pathway	IDA	15995708
GO:0019221	Process	Cytokine-mediated signaling pathway	TAS
GO:0019233	Process	Sensory perception of pain	ISS
GO:0019722	Process	Calcium-mediated signaling	IBA	21873635
GO:0019725	Process	Cellular homeostasis	ISS
GO:0019957	Function	C-C chemokine binding	IBA	21873635
GO:0030425	Component	Dendrite	ISS
GO:0031727	Function	CCR2 chemokine receptor binding	IDA	15995708
GO:0032729	Process	Positive regulation of interferon-gamma production	ISS
GO:0032743	Process	Positive regulation of interleukin-2 production	ISS
GO:0032760	Process	Positive regulation of tumor necrosis factor production	ISS
GO:0035696	Process	Monocyte extravasation	ISS
GO:0035705	Process	T-helper 17 cell chemotaxis	ISS
GO:0042802	Function	Identical protein binding	ISS
GO:0043025	Component	Neuronal cell body	ISS
GO:0043204	Component	Perikaryon	ISS
GO:0043310	Process	Negative regulation of eosinophil degranulation	ISS
GO:0045580	Process	Regulation of T cell differentiation	ISS
GO:0046641	Process	Positive regulation of alpha-beta T cell proliferation	ISS
GO:0048471	Component	Perinuclear region of cytoplasm	ISS
GO:0050727	Process	Regulation of inflammatory response	ISS
GO:0050729	Process	Positive regulation of inflammatory response	ISS
GO:0050870	Process	Positive regulation of T cell activation	ISS
GO:0051968	Process	Positive regulation of synaptic transmission, glutamatergic	ISS
GO:0060326	Process	Cell chemotaxis	IBA	21873635
GO:0070098	Process	Chemokine-mediated signaling pathway	ISS
GO:0090026	Process	Positive regulation of monocyte chemotaxis	IDA	18587271
GO:0090026	Process	Positive regulation of monocyte chemotaxis	ISS
GO:0090265	Process	Positive regulation of immune complex clearance by monocytes and macrophages	ISS
GO:0090594	Process	Inflammatory response to wounding	ISS
GO:0120162	Process	Positive regulation of cold-induced thermogenesis	ISS	24906148
GO:1904783	Process	Positive regulation of NMDA glutamate receptor activity	ISS
GO:1905517	Process	Macrophage migration	ISS
GO:2000412	Process	Positive regulation of thymocyte migration	ISS
GO:2000439	Process	Positive regulation of monocyte extravasation	ISS
GO:2000451	Process	Positive regulation of CD8-positive, alpha-beta T cell extravasation	ISS
GO:2000464	Process	Positive regulation of astrocyte chemotaxis	IDA	12271471
GO:2000473	Process	Positive regulation of hematopoietic stem cell migration	ISS

Other IDs

• MIM: 601267
• HGNC: 1603
• e!Ensembl: ENSG00000121807

Protein

• UniProt ID: P41597
• Protein name: C-C chemokine receptor type 2 (C-C CKR-2) (CC-CKR-2) (CCR-2) (CCR2) (Monocyte chemoattractant protein 1 receptor) (MCP-1-R) (CD antigen CD192)
• Protein function: Key functional receptor for CCL2 but can also bind CCL7 and CCL12 (PubMed:8146186, PubMed:8048929, PubMed:23408426). Its binding with CCL2 on monocytes and macrophages mediates chemotaxis and migration induction through the activation of the PI3K cascade, the small G protein Rac and lamellipodium protrusion (Probable). Also acts as a receptor for the beta-defensin DEFB106A/DEFB106B (PubMed:23938203). Regulates the expression of T-cell inflammatory cytokines and T-cell differentiation, promoting the differentiation of T-cells into T-helper 17 cells (Th17) during inflammation (By similarity). Facilitates the export of mature thymocytes by enhancing directional movement of thymocytes to sphingosine-1-phosphate stimulation and up-regulation of S1P1R expression; signals through the JAK-STAT pathway to regulate FOXO1 activity leading to an increased expression of S1P1R (By similarity). Plays an important role in mediating peripheral nerve injury-induced neuropathic pain (By similarity). Increases NMDA-mediated synaptic transmission in both dopamine D1 and D2 receptor-containing neurons, which may be caused by MAPK/ERK-dependent phosphorylation of GRIN2B/NMDAR2B (By similarity). Mediates the recruitment of macrophages and monocytes to the injury site following brain injury (By similarity). ; (Microbial infection) Alternative coreceptor with CD4 for HIV-1 infection.
• PDB: 1KAD, 1KP1, 2MLO, 2MLQ, 5T1A
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00001	7tm_1	59 → 305	7 transmembrane receptor (rhodopsin family)	Family

• Sequence:

  MLSTSRSRFIRNTNESGEEVTTFFDYDYGAPCHKFDVKQIGAQLLPPLYSLVFIFGFVGN
  MLVVLILINCKKLKCLTDIYLLNLAISDLLFLITLPLWAHSAANEWVFGNAMCKLFTGLY
  HIGYFGGIFFIILLTIDRYLAIVHAVFALKARTVTFGVVTSVITWLVAVFASVPGIIFTK
  CQKEDSVYVCGPYFPRGWNNFHTIMRNILGLVLPLLIMVICYSGILKTLLRCRNEKKRHR
  AVRVIFTIMIVYFLFWTPYNIVILLNTFQEFFGLSNCESTSQLDQATQVTETLGMTHCCI
  NPIIYAFVGEKFRSLFHIALGCRIAPLQKPVCGGPGVRPGKNVKVTTQGLLDGRGKGKSI
  GRAPEASLQDKEGA

• Sequence length: 374

Pathways

KEGG:

Cytokine-cytokine receptor interaction
Viral protein interaction with cytokine and cytokine receptor
Chemokine signaling pathway

Reactome:

Beta defensins
Chemokine receptors bind chemokines
G alpha (i) signalling events
Interleukin-10 signaling

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Pulmonary fibrosis	Pulmonary Fibrosis	rs121918666, rs199422300, rs121917737, rs121917834, rs199422294, rs201159197, rs199422297, rs199422305, rs751381953, rs876661305, rs878853260, rs863223336, rs786205702, rs1555811762, rs1060502990, rs1555903332, rs1554038539, rs1554042899, rs938938578	14609568
Dermatitis	Dermatitis, Allergic Contact	rs61816761, rs150597413, rs138726443, rs201356558, rs149484917, rs372754256, rs747301529, rs567795279, rs745915174	17374397

Unknown
Disease name	Disease term	dbSNP ID	References
Alveolitis	Alveolitis, Fibrosing		14609568
Grand mal status epilepticus	Grand Mal Status Epilepticus		19490431, 20034406
Nonconvulsive status epilepticus	Non-Convulsive Status Epilepticus		19490431, 20034406
Petit mal status	Petit mal status		20034406, 19490431
Status epilepticus	Status Epilepticus, Complex Partial Status Epilepticus, Status Epilepticus, Subclinical		19490431, 20034406