ACKR3

This gene encodes a member of the G-protein coupled receptor family. Although this protein was earlier thought to be a receptor for vasoactive intestinal peptide (VIP), it is now considered to be an orphan receptor, in that its endogenous ligand has not been identified. The protein is also a coreceptor for human immunodeficiency viruses (HIV). Translocations involving this gene and HMGA2 on chromosome 12 have been observed in lipomas. [provided by RefSeq, Jul 2008]

Atypical Chemokine Receptor 3

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. Acts as coreceptor with CXCR4 for a restricted number of HIV isolates.

Angiogenesis
Calcium-mediated signaling
Cell adhesion
Cell chemotaxis
Chemokine-mediated signaling pathway
G protein-coupled receptor signaling pathway
Immune response
Negative regulation of cell population proliferation
Negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage
Positive regulation of cytosolic calcium ion concentration
Positive regulation of ERK1 and ERK2 cascade
Positive regulation of mesenchymal stem cell migration
Receptor internalization
Vasculogenesis
Viral process

Early endosome; Recycling endosome; Cell membrane; Perinuclear region. 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.

Extracellular: 1-40 aa
Helical: 41-61 aa
Cytoplasmic: 62-81 aa
Helical: 82-102 aa
Extracellular: 103-118 aa
Helical: 119-139 aa
Cytoplasmic: 140-162 aa
Helical: 163-183 aa
Extracellular: 184-213 aa
Helical: 214-234 aa
Cytoplasmic: 235-252 aa
Helical: 253-273 aa
Extracellular: 274-296 aa
Helical: 297-319 aa
Cytoplasmic: 320-362 aa

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.