CXCR4: Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Acts as a receptor for extracellular ubiquitin; leading to enhanced intracellular calcium ions and reduced cellular cAMP levels. Involved in hematopoiesis and in cardiac ventricular septum formation. Also plays an essential role in vascularization of the gastrointestinal tract, probably by regulating vascular branching and/or remodeling processes in endothelial cells. Involved in cerebellar development. In the CNS, could mediate hippocampal-neuron survival. Acts as a coreceptor (CD4 being the primary receptor) for HIV-1 X4 isolates and as a primary receptor for some HIV-2 isolates. Promotes Env-mediated fusion of the virus. Monomer. Can form dimers. Interacts with CD164. Interacts with HIV-1 surface protein gp120 and Tat. Interacts with ARRB2; the interaction is dependent on the C-terminal phosphorylation of CXCR4 and allows activation of MAPK1 and MAPK3. Interacts with ARRC; the interaction is dependent on the C-terminal phosphorylation of CXCR4 and modulates calcium mobilization. Interacts (via the cytoplasmic C-terminal) with ITCH (via the WW domains I and II); the interaction, enhanced by CXCL12, ubiquitinates CXCR4 and leads to its degradation. Interacts with extracellular ubiquitin. Interacts with human cytomegalovirus/HHV- 5 protein UL78. Expressed in numerous tissues, such as peripheral blood leukocytes, spleen, thymus, spinal cord, heart, placenta, lung, liver, skeletal muscle, kidney, pancreas, cerebellum, cerebral cortex and medulla (in microglia as well as in astrocytes), brain microvascular, coronary artery and umbilical cord endothelial cells. Isoform 1 is predominant in all tissues tested. Belongs to the G-protein coupled receptor 1 family. 2 isoforms of the human protein are produced by alternative splicing.
Protein type: GPCR, family 1; Receptor, GPCR; Membrane protein, integral; Membrane protein, multi-pass
Chromosomal Location of Human Ortholog: 2q21
Cellular Component: cell surface; lysosome; cytoplasmic membrane-bound vesicle; leading edge; early endosome; integral to membrane; intercellular junction; growth cone; cytoplasm; late endosome; plasma membrane; cytoplasmic vesicle; external side of plasma membrane
Molecular Function: viral receptor activity; G-protein coupled receptor activity; ubiquitin binding; protein binding; ubiquitin protein ligase binding; cytokine binding; coreceptor activity; myosin light chain binding; actin binding; C-X-C chemokine receptor activity
Biological Process: entry of virus into host cell; regulation of chemotaxis; neutrophil activation; viral reproduction; activation of MAPK activity; apoptosis; response to virus; calcium-mediated signaling; neuron migration; motor axon guidance; regulation of cell migration; germ cell development; patterning of blood vessels; T cell proliferation; G-protein coupled receptor protein signaling pathway; elevation of cytosolic calcium ion concentration; ameboidal cell migration; germ cell migration; myelin maintenance; response to hypoxia; dendritic cell chemotaxis; entry into host cell; brain development; positive regulation of oligodendrocyte differentiation; inflammatory response
Disease: Whim Syndrome
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