Alternative products:Additional isoforms seem to exist ,Caution:Was originally (PubMed:8329116 and PubMed:8234909) thought to be a receptor for neuropeptide Y type 3 (NPY3R) (NPY3-R) . ,Disease:Defects in CXCR4 are a cause of WHIM syndrome [MIM:193670]; also called warts , hypogammaglobulinemia , infections , and myelokathexis. WHIM syndrome is an immunodeficiency disease characterized by neutropenia , hypogammaglobulinemia and extensive human papillomavirus (HPV) infection. Despite the peripheral neutropenia , bone marrow aspirates from affected individuals contain abundant mature myeloid cells , a condition termed myelokathexis. ,Domain:The amino-terminus is critical for ligand binding. Residues in all four extracellular regions contribute to HIV-1 coreceptor activity. ,Function:Receptor for the C-X-C chemokine CXCL12/SDF-1. Transduces a signal by increasing the intracellular calcium ions level. Involved in haematopoiesis and in cardiac ventricular septum formation. Plays also an essential role in vascularization of the gastrointestinal tract , probably by regulating vascular branching and/or remodeling processes in endothelial cells. Could be 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. ,online information:CXC chemokine receptors entry ,online information:CXCR4 entry ,online information:CXCR4 mutation db ,PTM:O- and N-glycosylated. Asn-11 is the principal site of N-glycosylation. There appears to be very little or no glycosylation on Asn-176. N-glycosylation masks coreceptor function in both X4 and R5 laboratory-adapted and primary HIV-1 strains through inhibiting interaction with their Env glycoproteins. The O-glycosylation chondroitin sulfate attachment does not affect interaction with CXCL12/SDF-1alpha nor its coreceptor activity. ,PTM:Sulfation on Tyr-21 is required for efficient binding of CXCL12/SDF-1alpha and promotes its dimerization. ,similarity:Belongs to the G-protein coupled receptor 1 family. ,subunit:Monomer. Can form dimers. Interacts with HIV-1 surface protein gp120 and Tat. ,tissue specificity: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. ,
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