GOAT ANTI HUMAN CD184 (N-TERMINAL)

GWB-F0CDDB

Polyclonal IgGSpecies Cross Reactivity: Reacts with: RatN. B. Antibody reactivity and working conditions may vary between species.

Recognises an epitope within the N-terminal (NT) region of human CD184 otherwise known as CXCR4 (C-X-C chemokine receptor type 4) a transmembrane glycoprotein and member of the G-protein coupled receptor 1 family ubiquitously expressed in blood and tissue cells which acts as a specific receptor for the chemokine SDF-1 (Stromal cell-derived factor 1). Interaction of CD184 with SDF-1 mediates the chemotaxis of progenitor and mature blood cells and is critical for B- lymphopoiesis and myelopoiesis. CD184 is a major co-receptor for infection by T-cell tropic strains of HIV1 and also a primary receptor for some HIV2 isolates.

Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ions levels and enhancing MAPK1/MAPK3 activation. Acts as a receptor for extracellular ubiquitin; leading to enhance intracellular calcium ions and reduce cellular cAMP levels. 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. Ref. 1Ref. 2Ref. 6Ref. 18Ref. 19Ref. 26Ref. 36Ref. 37Ref. 38Subunit structureMonomer. 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. Ref. 26Ref. 36Ref. 37Ref. 38Ref. 23Ref. 25Ref. 27Ref. 28Ref. 29Ref. 32Ref. 35Ref. 39Subcellular locationCell membrane; Multi-pass membrane protein.

The amino-terminus is critical for ligand binding. Residues in all four extracellular regions contribute to HIV-1 coreceptor activity. Ref. 25Post-translational modificationPhosphorylated on agonist stimulation. Rapidly phosphorylated on serine and threonine residues in the C-terminal. Phosphorylation at Ser-324 and Ser-325 leads to recruitment of ITCH ubiquitination and protein degradation. Ref. 36Ref. 35Ref. 33Ref. 34Ubiquitinated by ITCH at the cell membrane on agonist stimulation. The ubiquitin-dependent mechanism endosomal sorting complex required for transport (ESCRT) then targets CXCR4 for lysosomal degradation. This process is dependent also on prior Ser-/Thr-phosphorylation in the C-terminal of CXCR4. Also binding of ARRB1 to STAM negatively regulates CXCR4 sorting to lysosomes though modulating ubiquitination of SFR5S. Ref. 30Sulfation on Tyr-21 is required for efficient binding of CXCL12/SDF-1alpha and promotes its dimerization. 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. Ref. 27Ref. 29Involvement in diseaseDefects in CXCR4 are a cause of WHIM syndrome [MIM:193670]; also known as 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. Ref. 31Miscellaneous: Plerixafor (AMD3100) an antagonist of CXCR4 activity blocks HIV-1 entry interaction with CXCL12 and subsequent CXCR4 signaling. Sequence similaritiesBelongs to the G-protein coupled receptor 1 family. Caution: Was originally (Ref. 1 and Ref. 2) thought to be a receptor for neuropeptide Y type 3 (NPY3R) (NPY3-R). Sequence cautionThe sequence CAA12166. 1 differs from that shown. Reason: Intron retention. 1. Kydd J. H. and Antczak D. F. (1991) Report of the First International Workshop on Equine Leucocyte Antigens Cambridge UK July 1991 Vet Immunol and Immunopathol 42: 3 - 60