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atypical chemokine receptor 2; C-C chemokine receptor 10; C-C chemokine receptor D6; chemokine receptor CCR-10; chemokine receptor CCR-9; chemokine-binding protein 2; chemokine-binding protein D6 (ACKR2, CCBP2, CCR10, CMKBR9, D6)

The best characterized of the atypical chemokine receptors [3] Function: - atypical chemokine receptor - controls chemokine levels & localization via high-affinity chemokine binding uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis - also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor - acts as a receptor for chemokines including CCL2, CCL3, CCL3L1, CCL4, CCL5, CCL7, CCL8, CCL11, CCL13, CCL17, CCL22, CCL23, CCL24, SCYA2/MCP-1, SCY3/MIP-1-alpha, SCYA5/RANTES & SCYA7/MCP-3 - upon active ligand stimulation, activates a beta-arrestin 1 (ARRB1)-dependent, G protein-independent signaling pathway that results in the phosphorylation of the actin-binding protein cofilin (CFL1) through a RAC1-PAK1-LIMK1 signaling pathway - activation of this pathway results in up- regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake & degradation - by scavenging chemokines in tissues, on the surfaces of lymphatic vessels, & in placenta, plays a role in the resolution (termination) of the inflammatory response & in regulation of adaptive immune responses - role in immune silencing of macrophages during resolution of inflammation - acts as a regulator of inflammatory leukocyte interactions with lymphatic endothelial cells - required for immature/mature dendritic cells discrimination by lymphatic endothelial cells - phosphorylated on Ser in the C-terminal cytoplasmic tail - suppresses development of chemically induced skin tumors [2] Structure: - the C-terminal cytoplasmic tail controls its phosphorylation, stability, intracellular trafficking itinerary, & chemokine scavenging properties - belongs to the G-protein coupled receptor 1 family atypical chemokine receptor subfamily Compartment: - early endosome. recycling endosome. cell membrane - predominantly localizes to endocytic vesicles - upon ligand stimulation, internalized via clathrin-coated pits - once internalized, the ligand dissociates from the receptor, & is targeted to degradation while the receptor is recycled back to the cell membrane Expression: - found in endothelial cells lining afferent lymphatics in dermis & lymph nodes - also found in lymph nodes subcapsular & medullary sinuses, tonsillar lymphatic sinuses & lymphatics in mucosa & submucosa of small & large intestine & appendix - expressed on apoptotic neutrophils (at protein level) - expressed primarily in placenta & fetal liver, - found at very low levels in the lung & lymph node - induced by interleukin-6 & interferon-gamma Pathology: - found in some malignant vascular tumors - expressed at high levels in Kaposi sarcoma

Related

G-protein coupled receptor 2 (GPR2)

General

atypical chemokine receptor; chemokine-scavenging receptor; chemokine decoy receptor CC chemokine receptor glycoprotein

Properties

SIZE: entity length = 384 aa MW = 43 kD COMPARTMENT: plasma membrane MOTIF: exoplasmic domain {1-50} MOTIF: N-glycosylation site {N19} transmembrane domain {51-71} cytoplasmic loop {72-92} transmembrane domain {93-113} exoplasmic loop {114-118} MOTIF: cysteine residue {C117} MODIFICATION: cysteine residue {C195} transmembrane domain {119-140} cytoplasmic loop {141-162} transmembrane domain {163-183} exoplasmic loop {184-217} MOTIF: cysteine residue {C195} MODIFICATION: cysteine residue {C117} transmembrane domain {218-238} cytoplasmic loop {239-250} transmembrane domain {251-271} exoplasmic loop {272-293} transmembrane domain {294-314} cytoplasmic domain {315-384} MOTIF: C-terminal cytoplasmic tail {327-384}

References

  1. UniProt :accession O00590
  2. Nibbs RJ, Gilchrist DS, King V, Ferra A, Forrow S, Hunter KD, Graham GJ. The atypical chemokine receptor D6 suppresses the development of chemically induced skin tumors. J Clin Invest. 2007 Jul 2;117(7):1884-1892. PMID: 17607362
  3. Graham GJ, Locati M. Regulation of the immune and inflammatory responses by the 'atypical' chemokine receptor D6. J Pathol. 2013 Jan;229(2):168-75. PMID: 23125030

Databases & Figures

OMIM 602648 UniProt O00590 Pfam PF00001 Entrez Gene 1238 Kegg hsa:1238 CC ligand and receptor binding