atypical chemokine receptor 4; C-C chemokine receptor type 11; C-C CKR-11; CC-CKR-11; CCR-11; CC chemokine receptor-like 1; CCRL1; CCX CKR (ACKR4, CCBP2, CCR11, CCRL1 ,VSHK1)
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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 CCL2, CCL8, CCL13, CCL19, CCL21 & CCL25
- chemokine-binding does not activate G-protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization.
- role in controlling the migration of immune & cancer cells that express chemokine receptors CCR7 & CCR9, by reducing the availability of CCL19, CCL21, & CCL25 through internalization
- negatively regulates CXCR3-induced chemotaxis
- regulates T-cell development in the thymus
- the Ser/Thr residues in the C-terminal cytoplasmic tail may be phosphorylated
- forms heteromers with CXCR3
- interacts with ARRB1 & ARRB2
Structure
- 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 stimulation by the ligand is internalized via caveolae
- once internalized, the ligand dissociates from the receptor, & is targeted to degradation while the receptor is recycled back to the cell membrane
Expression
- predominantly expressed in heart.
- lower expression in lung, pancreas, spleen, colon, skeletal muscle & small intestine