Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is 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 CXCL11 and CXCL12/SDF1. Chemokine binding does not activate G-protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization and activation of MAPK signaling pathway. Required for regulation of CXCR4 protein levels in migrating interneurons, thereby adapting their chemokine responsiveness. In glioma cells, transduces signals via MEK/ERK pathway, mediating resistance to apoptosis. Promotes cell growth and survival. Not involved in cell migration, adhesion or proliferation of normal hematopoietic progenitors but activated by CXCL11 in malignant hemapoietic cells, leading to phosphorylation of ERK1/2 (MAPK3/MAPK1) and enhanced cell adhesion and migration. Plays a regulatory role in CXCR4-mediated activation of cell surface integrins by CXCL12. Required for heart valve development. Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is 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 CXCL11 and CXCL12/SDF1 (By similarity). Chemokine binding does not activate G-protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization and activation of MAPK signaling pathway (PubMed:20018651). Required for regulation of CXCR4 protein levels in migrating interneurons, thereby adapting their chemokine responsiveness. In glioma cells, transduces signals via MEK/ERK pathway, mediating resistance to apoptosis. Promotes cell growth and survival. Not involved in cell migration, adhesion or proliferation of normal hematopoietic progenitors but activated by CXCL11 in malignant hemapoietic cells, leading to phosphorylation of ERK1/2 (MAPK3/MAPK1) and enhanced cell adhesion and migration. Plays a regulatory role in CXCR4-mediated activation of cell surface integrins by CXCL12. Required for heart valve development. Regulates axon guidance in the oculomotor system through the regulation of CXCL12 levels (By similarity). Homodimer. Can form heterodimers with CXCR4; heterodimerization may regulate CXCR4 signaling activity. Interacts with ARRB1 and ARRB2. Predominantly localizes to endocytic vesicles, and upon stimulation by the ligand is internalized via clathrin-coated pits in a beta-arrestin -dependent manner. Once internalized, the ligand dissociates from the receptor, and is targeted to degradation while the receptor is recycled back to the cell membrane (By similarity). Expressed in vascular smooth muscle cells (at protein level). In brain, expressed in blood vessels, pyramidal cells in hippocampal subfield CA3, mature dentate gyrus granule cells, ventricle walls, olfactory bulb, accumbens shell, supraoptic, lateroanterior and ventromedial hypothalamic nuclei, medial region of thalamus, and motor nuclei, central gray and raphe magnus nucleus of brain stem. Detected in primary neurons, GABAergic neurons, astrocytes, cerebral cortex, ventral striatum and choroid plexus. Not detected in mesencephalon. Expressed in the ventral and dorsal parts of telencephalon at all developmental stages of brain analyzed (E14 to P56). Strong expression detected in the cranial connective tissue surrounding the brain at E14-E15. In the cortex, expressed mainly in the marginal zone at preplate stage (E14), with expression increasing strongly in the marginal zone/layer I between E15 and E18 and declining rapidly in layer I after P0. Expression emerges in the lateral part of cortical plate at E15 and increases in the medial and lateral parts between E15 and E17. Expression not detected in the cortical ventricular and subventricular zones at the early embryonic stages but emerges at E18. Expressed in GABAergic precursors and in some reelin-expressing Cajal-Ratzius cells, in neurons forming the cortical plate and sparsely in the developing dentate gyrus and cerebellar external germinal layer. In the ventral telencephalon, expressed in the germinative zone of the ganglionic eminences and in GABAergic neurons forming the caudate putamen between E14 and E18. By ischemia. Up-regulated in the cingulate, retrosplenial and frontal areas of the cortex ipsilateral to middle cerebral artery occlusion (MCAO) by 163% at 6 hours, 220% at 2 days and 89% at 4 days after ischemia-onset, with expression reduced back to control level at 10 days after MCAO. Expression is almost undetectable in the infarct area between days 2 and 10 after MCAO. The C-terminal cytoplasmic tail, plays a key role in: correct trafficking to the cell membrane, recruitment of beta-arrestin, ubiquitination, and in chemokine scavenging and signaling functions. The Ser/Thr residues and the Lys residues in the C-terminal cytoplasmic tail are essential for beta-arrestin recruitment and ubiquitination respectively. The Ser/Thr residues in the C-terminal cytoplasmic tail may be phosphorylated. Ubiquitinated at the Lys residues in its C-terminal cytoplasmic tail and is essential for correct trafficking from and to the cell membrane. Deubiquitinated by CXCL12-stimulation in a reversible manner. Belongs to the G-protein coupled receptor 1 family. Atypical chemokine receptor subfamily.