C-C chemokine receptor type 2

UniProt P41597 Organism Homo sapiens Gene CCR2, CMKBR2

Also known as: CCR2, CMKBR2

Function

Key functional receptor for CCL2 but can also bind CCL7, and CCL12. Also transduces signaling mediated by CCL13. 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. Also acts as a receptor for the beta-defensin DEFB106A/DEFB106B. 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).

Classification

Family (Pfam): PF00001 7tm_1
InterPro: CCR1-9-like, Chemokine_CCR2, Chemokine_rcpt, GPCR_Rhodpsn, GPCR_Rhodpsn_7TM
Functional cluster: G Protein-Coupled Receptors

Experimental structures · PDB · 7

2MLO NMR
2MLQ NMR
5T1A X-ray 2.81A
6GPS X-ray 3.30A
6GPX X-ray 2.70A
7P8X X-ray 1.40A
7XA3 EM 2.90A

A predicted model is available from AlphaFold.

Gene Ontology · 62

Disease associations

cystic disease of lung MONDO:0009060
susceptibility to HIV infection MONDO:0004951

Drugs targeting this protein · 8

PF-4136309 antagonist
CENICRIVIROC antagonist
ILACIRNON antagonist
JNJ-41443532 antagonist
MK-0812 antagonist
BMS-741672 antagonist
BMS-813160 antagonist
PF-04634817 antagonist

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

C-C chemokine receptor type 3 2 shared papers
Nuclear pore complex protein Nup85 1 shared papers
C-C chemokine receptor type 1 2 shared papers
Beta-defensin 1 1 shared papers
Beta-defensin 106 1 shared papers
Nuclear pore complex protein Nup85 1 shared papers
G protein-coupled receptor kinase 2 1 shared papers
Cyclic AMP-responsive element-binding protein 3 1 shared papers
Viral macrophage inflammatory protein 2 1 shared papers
C-C chemokine receptor type 5 1 shared papers
Protein Tat 1 shared papers
Beta-arrestin-1 1 shared papers

Literature · 22 cited papers

Human inherited CCR2 deficiency underlies progressive polycystic lung disease. Cell · 2024
Molecular insights into ligand recognition and activation of chemokine receptors CCR2 and CCR3. Cell Discov. · 2022
Structure of CC chemokine receptor 2 with orthosteric and allosteric antagonists. Nature · 2016
Structural basis for the binding of the membrane-proximal C-terminal region of chemokine receptor CCR2 with the cytosolic regulator FROUNT. FEBS J. · 2014
Structural basis for the interaction of human beta-defensin 6 and its putative chemokine receptor CCR2 and breast cancer microvesicles. J. Mol. Biol. · 2013
Tyrosine sulfation of chemokine receptor CCR2 enhances interactions with both monomeric and dimeric forms of the chemokine monocyte chemoattractant protein-1 (MCP-1). J. Biol. Chem. · 2013
Human LZIP induces monocyte CC chemokine receptor 2 expression leading to enhancement of monocyte chemoattractant protein 1/CCL2-induced cell migration. Exp. Mol. Med. · 2008
The DNA sequence, annotation and analysis of human chromosome 3. Nature · 2006
Pivotal function for cytoplasmic protein FROUNT in CCR2-mediated monocyte chemotaxis. Nat. Immunol. · 2005
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
Monocyte chemotactic protein-1 receptor CCR2B is a glycoprotein that has tyrosine sulfation in a conserved extracellular N-terminal region. J. Immunol. · 2000
… and 10 more in the literature graph

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