8k2w

Structural highlights

Function

C562_ECOLX Electron-transport protein of unknown function.OPRK_HUMAN G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain. Plays a role in mediating reduced physical activity upon treatment with synthetic opioids. Plays a role in the regulation of salivation in response to synthetic opioids. May play a role in arousal and regulation of autonomic and neuroendocrine functions.^{[1] [2] [3] [4]} CXCR3_HUMAN Receptor for the C-X-C chemokine CXCL9, CXCL10 and CXCL11 and mediates the proliferation, survival and angiogenic activity of human mesangial cells (HMC) through a heterotrimeric G-protein signaling pathway (PubMed:12782716). Binds to CCL21. Probably promotes cell chemotaxis response. Upon activation by PF4, induces activated T-lymphocytes migration mediated via downstream Ras/extracellular signal-regulated kinase (ERK) signaling.^{[5] [6] [7]} Receptor for the C-X-C chemokine CXCL4 and also mediates the inhibitory activities of CXCL9, CXCL10 and CXCL11 on the proliferation, survival and angiogenic activity of human microvascular endothelial cells (HMVEC) through a cAMP-mediated signaling pathway (PubMed:12782716). Does not promote cell chemotaxis respons. Interaction with CXCL4 or CXCL10 leads to activation of the p38MAPK pathway and contributes to inhibition of angiogenesis. Overexpression in renal cancer cells down-regulates expression of the anti-apoptotic protein HMOX1 and promotes apoptosis.^[8] Mediates the activity of CXCL11.

References

1. ↑ Li JG, Chen C, Liu-Chen LY. Ezrin-radixin-moesin-binding phosphoprotein-50/Na+/H+ exchanger regulatory factor (EBP50/NHERF) blocks U50,488H-induced down-regulation of the human kappa opioid receptor by enhancing its recycling rate. J Biol Chem. 2002 Jul 26;277(30):27545-52. Epub 2002 May 9. PMID:12004055 doi:http://dx.doi.org/10.1074/jbc.M200058200
2. ↑ Wu H, Wacker D, Mileni M, Katritch V, Han GW, Vardy E, Liu W, Thompson AA, Huang XP, Carroll FI, Mascarella SW, Westkaemper RB, Mosier PD, Roth BL, Cherezov V, Stevens RC. Structure of the human kappa-opioid receptor in complex with JDTic. Nature. 2012 Mar 21;485(7398):327-32. doi: 10.1038/nature10939. PMID:22437504 doi:10.1038/nature10939
3. ↑ Simonin F, Gaveriaux-Ruff C, Befort K, Matthes H, Lannes B, Micheletti G, Mattei MG, Charron G, Bloch B, Kieffer B. kappa-Opioid receptor in humans: cDNA and genomic cloning, chromosomal assignment, functional expression, pharmacology, and expression pattern in the central nervous system. Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):7006-10. PMID:7624359
4. ↑ Mansson E, Bare L, Yang D. Isolation of a human kappa opioid receptor cDNA from placenta. Biochem Biophys Res Commun. 1994 Aug 15;202(3):1431-7. PMID:8060324
5. ↑ Lasagni L, Francalanci M, Annunziato F, Lazzeri E, Giannini S, Cosmi L, Sagrinati C, Mazzinghi B, Orlando C, Maggi E, Marra F, Romagnani S, Serio M, Romagnani P. An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4. J Exp Med. 2003 Jun 2;197(11):1537-49. PMID:12782716 doi:10.1084/jem.20021897
6. ↑ Mueller A, Meiser A, McDonagh EM, Fox JM, Petit SJ, Xanthou G, Williams TJ, Pease JE. CXCL4-induced migration of activated T lymphocytes is mediated by the chemokine receptor CXCR3. J Leukoc Biol. 2008 Apr;83(4):875-82. PMID:18174362 doi:10.1189/jlb.1006645
7. ↑ Van Raemdonck K, Gouwy M, Lepers SA, Van Damme J, Struyf S. CXCL4L1 and CXCL4 signaling in human lymphatic and microvascular endothelial cells and activated lymphocytes: involvement of mitogen-activated protein (MAP) kinases, Src and p70S6 kinase. Angiogenesis. 2014 Jul;17(3):631-40. PMID:24469069 doi:10.1007/s10456-014-9417-6
8. ↑ Lasagni L, Francalanci M, Annunziato F, Lazzeri E, Giannini S, Cosmi L, Sagrinati C, Mazzinghi B, Orlando C, Maggi E, Marra F, Romagnani S, Serio M, Romagnani P. An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4. J Exp Med. 2003 Jun 2;197(11):1537-49. PMID:12782716 doi:10.1084/jem.20021897