CXCR4 peptide

製品の性状

製品の状態

Lyophilized

一般的な情報

機能

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 (PubMed : 10074102, PubMed : 10452968, PubMed : 10644702, PubMed : 10825158, PubMed : 18799424, PubMed : 20048153, PubMed : 20505072, PubMed : 24912431, PubMed : 28978524, PubMed : 8752280, PubMed : 8752281). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed : 16725153, PubMed : 17197449, PubMed : 18799424, PubMed : 39093700). CXCR4 is coupled to G(i) G alpha proteins and mediates inhibition of adenylate cyclase (PubMed : 17197449, PubMed : 39093700). Involved in the AKT signaling cascade (PubMed : 24912431). Plays a role in regulation of cell migration, e.g. during wound healing (PubMed : 28978524). Also acts as a receptor for extracellular ubiquitin; leading to enhanced intracellular calcium ions and reduced cellular cAMP levels (PubMed : 20228059). Binds bacterial lipopolysaccharide (LPS) et mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed : 11276205). Involved in hematopoiesis and in cardiac ventricular septum formation (By similarity). Also plays an essential role in vascularization of the gastrointestinal tract, probably by regulating vascular branching and/or remodeling processes in endothelial cells (By similarity). Involved in cerebellar development; in the CNS, could mediate hippocampal-neuron surviva (By similarity).. (Microbial infection) Acts as a coreceptor (CD4 being the primary receptor) for human immunodeficiency virus-1/HIV-1 X4 isolates and as a primary receptor for some HIV-2 isolates. Promotes Env-mediated fusion of the virus (PubMed : 10074122, PubMed : 10756055, PubMed : 8849450, PubMed : 8929542, PubMed : 9427609).

配列の類似性

Belongs to the G-protein coupled receptor 1 family.

翻訳後修飾

Phosphorylated on agonist stimulation (PubMed:20048153, PubMed:37209686). Phosphorylation of the P-X-P-P motif promotes association with beta-arrestin ARRB1, leading to receptor desensitization and negative regulation of G-protein coupled receptor signaling (PubMed:37209686). Phosphorylation at Ser-324 and Ser-325 leads to recruitment of ITCH, ubiquitination and protein degradation (PubMed:14602072, PubMed:19116316).. Ubiquitinated after ligand binding, leading to its degradation (PubMed:28978524). Ubiquitinated by ITCH at the cell membrane on agonist stimulation (PubMed:14602072, PubMed:34927784). 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.. Sulfation on Tyr-21 is required for efficient binding of CXCL12/SDF-1alpha and promotes its dimerization. Tyr-7 and Tyr-12 are sulfated in a sequential manner after Tyr-21 is almost fully sulfated, with the binding affinity for CXCL12/SDF-1alpha increasing with the number of sulfotyrosines present. Sulfotyrosines Tyr-7 and Tyr-12 occupy clefts on opposing CXCL12 subunits, thus bridging the CXCL12 dimer interface and promoting CXCL12 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.

細胞内局在性

Early endosome