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MGP005585

UniProt Annotations

Entry Information

Gene Name	atypical chemokine receptor 3
Protein Entry	ACKR3_HUMAN
UniProt ID	P25106
Species	Human

Comments

Comment type	Description
Caution	Was originally thought to be the receptor for VIP. {ECO:0000305\|PubMed:1675791}.
Domain	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.
Function	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. {ECO:0000269\|PubMed:16107333, ECO:0000269\|PubMed:16940167, ECO:0000269\|PubMed:17804806, ECO:0000269\|PubMed:18653785, ECO:0000269\|PubMed:19255243, ECO:0000269\|PubMed:19380869, ECO:0000269\|PubMed:19641136, ECO:0000269\|PubMed:20018651, ECO:0000269\|PubMed:20161793, ECO:0000269\|PubMed:20388803, ECO:0000269\|PubMed:20887389, ECO:0000269\|PubMed:22300987}.
Induction	Up-regulated during cell differentiation in glioma cells. {ECO:0000269\|PubMed:20388803}.
Ptm	The Ser/Thr residues in the C-terminal cytoplasmic tail may be phosphorylated.
Ptm	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. {ECO:0000269\|PubMed:22457824}.
Similarity	Belongs to the G-protein coupled receptor 1 family. Atypical chemokine receptor subfamily. {ECO:0000255\|PROSITE- ProRule:PRU00521}.
Subcellular Location	Cell membrane; Multi-pass membrane protein. Cytoplasm, perinuclear region. Early endosome. Recycling endosome {ECO:0000250}. Note=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.
Subunit	Homodimer. Can form heterodimers with CXCR4; heterodimerization may regulate CXCR4 signaling activity. Interacts with ARRB1 and ARRB2. {ECO:0000269\|PubMed:19255243, ECO:0000269\|PubMed:19380869, ECO:0000269\|PubMed:22300987, ECO:0000269\|PubMed:22457824}.
Tissue Specificity	Expressed in monocytes, basophils, B-cells, umbilical vein endothelial cells (HUVEC) and B-lymphoblastoid cells. Lower expression detected in CD4+ T-lymphocytes and natural killer cells. In the brain, detected in endothelial cells and capillaries, and in mature neurons of the frontal cortex and hippocampus. Expressed in tubular formation in the kidney. Highly expressed in astroglial tumor endothelial, microglial and glioma cells. Expressed at low levels in normal CD34+ progenitor cells, but at very high levels in several myeloid malignant cell lines. Expressed in breast carcinomas but not in normal breast tissue (at protein level). {ECO:0000269\|PubMed:16107333, ECO:0000269\|PubMed:16455976, ECO:0000269\|PubMed:19641136, ECO:0000269\|PubMed:20388803, ECO:0000269\|PubMed:20887389, ECO:0000269\|PubMed:21655198}.
Web Resource	Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/CMKOR1ID40108ch2q37.html";
Web Resource	Name=Wikipedia; Note=CXC chemokine receptors entry; URL="http://en.wikipedia.org/wiki/CXC_chemokine_receptors";