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SLC52A2  -  solute carrier family 52 (riboflavin...

Homo sapiens

Synonyms: BVVLS2, D15Ertd747e, FLJ11856, GPCR41, GPR172A, ...
 
 
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Disease relevance of GPR172A

  • Sequence analysis indicates that PERV-A receptors [human PERV-A receptor (HuPAR)-1, HuPAR-2, baboon PERV-A receptor 2, and porcine PERV-A receptor] are multiple membrane-spanning proteins similar to receptors for other gammaretroviruses [1].
  • PAR-1 and PAR-2 in the cells forming the tumor microenvironment suggest that these receptors mediate the signaling of secreted thrombin and trypsin in the processes of cellular metastasis [2].
  • In the present minireview, we summarize the effects of PAR-1 and PAR-2 stimulation using their activating peptides and agonist proteinases on the calcium signaling and the cell proliferation in DLD-1 cell, a human colon cancer cell line [3].
  • Tissue factor deficiency and PAR-1 deficiency are protective against renal ischemia reperfusion injury [4].
  • In contrast, low-TF, hirudin-treated C57BL/6, and PAR-1(-/-) mice were protected from renal failure and had reduced mortality, tubular injury, neutrophil accumulation, and lower levels of the chemokines KC and MIP-2 [4].
 

High impact information on GPR172A

  • Attachment of a palmitate lipid to peptides based on the third intracellular loop of protease-activated receptor 1 (PAR1) or PAR4 (refs. 3-5) yielded potent inhibitors of thrombin-mediated aggregation of human platelets [5].
  • Although trafficking and degradation of several membrane proteins are regulated by ubiquitination catalyzed by E3 ubiquitin ligases, there has been little evidence connecting ubiquitination with regulation of mammalian G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor (GPCR) function [6].
  • All genes within PAR1 escape X inactivation and are therefore candidates for the etiology of haploinsufficiency disorders including Turner syndrome (45,X) [7].
  • In humans, they reside at the ends of the X and Y chromosomes and encompass roughly 2.7 Mb (PAR1) and 0.33 Mb (PAR2) [7].
  • While PAR2 resembles the overall sequence composition of the X chromosome and exhibits only slightly elevated recombination rates, PAR1 is characterized by a significantly higher GC content and a completely different repeat structure [7].
 

Biological context of GPR172A

 

Anatomical context of GPR172A

  • In striking contrast to most GPCRs, sorting of activated PAR1 to lysosomes rather than recycling is critical for terminating PAR1 signaling-a trafficking solution to a signaling problem [12].
  • This study characterizes the signaling mechanism of Xa in a HeLa cell line that expresses protease-activated receptor 1 (PAR-1) but not PAR-2, -3, or -4 [13].
  • The synthetic PAR-1 tethered ligand sequence SFLLRN-NH2 (0.01 to 10 micromol/L) also caused endothelium-dependent relaxation of U46619-contracted human coronary arteries; however, the equivalent PAR-2 ligand SLIGKV-NH2 caused almost no relaxation [14].
  • Our results demonstrate PAR-1 and PAR-2 expression in the tumor cells, mast cells, macrophages, endothelial cells, and vascular smooth muscle cells of the metastatic tumor microenvironment [2].
  • Human corneal epithelial cells express functional PAR-1 and PAR-2 [15].
 

Associations of GPR172A with chemical compounds

 

Other interactions of GPR172A

  • Thrombin, PAR-1-activating peptide, trypsin, and PAR-2-activating peptide induced no significant contraction in the control [18].
  • Agonist peptides of PAR-1 and PAR-2 stimulate MCP-1 secretion up to 15- and 12.7-fold, respectively [16].
  • Thus, the PAR-1 receptor for thrombin, and receptors for collagen, thromboxane A(2), fibrinogen (GPIIb/IIIa), and ADP appear to function normally on the endoprotease-pretreated platelets [19].
 

Analytical, diagnostic and therapeutic context of GPR172A

  • RESULTS: RT-PCR showed transcripts for PAR-1 and -2 receptors, but not for PAR-4 receptors [20].
  • Here we show conclusively by flow cytometric and Northern blot analysis that human gingival fibroblasts (HGF) express PAR-1 but not PAR-2 [21].
  • CONCLUSIONS: We have demonstrated that PAR-1 agonism causes platelet activation, venous constriction, arterial dilatation, and tPA release in vivo in humans [22].
  • In the present study, we examined if activation of PAR-2 and PAR-1 could alter gastrointestinal transit in mice [23].
  • We describe here the localization of PAR-1 and PAR-2 in mast cells from various normal human tissues using immunohistochemical and double immunofluorescence techniques [24].

References

  1. Identification of receptors for pig endogenous retrovirus. Ericsson, T.A., Takeuchi, Y., Templin, C., Quinn, G., Farhadian, S.F., Wood, J.C., Oldmixon, B.A., Suling, K.M., Ishii, J.K., Kitagawa, Y., Miyazawa, T., Salomon, D.R., Weiss, R.A., Patience, C. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  2. Differential expression of protease-activated receptors-1 and -2 in stromal fibroblasts of normal, benign, and malignant human tissues. D'Andrea, M.R., Derian, C.K., Santulli, R.J., Andrade-Gordon, P. Am. J. Pathol. (2001) [Pubmed]
  3. Physiology and pathophysiology of proteinase-activated receptors (PARs): PAR-2-mediated proliferation of colon cancer cell. Nishibori, M., Mori, S., Takahashi, H.K. J. Pharmacol. Sci. (2005) [Pubmed]
  4. Tissue factor deficiency and PAR-1 deficiency are protective against renal ischemia reperfusion injury. Sevastos, J., Kennedy, S.E., Davis, D.R., Sam, M., Peake, P.W., Charlesworth, J.A., Mackman, N., Erlich, J.H. Blood (2007) [Pubmed]
  5. Pepducin-based intervention of thrombin-receptor signaling and systemic platelet activation. Covic, L., Misra, M., Badar, J., Singh, C., Kuliopulos, A. Nat. Med. (2002) [Pubmed]
  6. Regulation of receptor fate by ubiquitination of activated beta 2-adrenergic receptor and beta-arrestin. Shenoy, S.K., McDonald, P.H., Kohout, T.A., Lefkowitz, R.J. Science (2001) [Pubmed]
  7. The pseudoautosomal regions, SHOX and disease. Blaschke, R.J., Rappold, G. Curr. Opin. Genet. Dev. (2006) [Pubmed]
  8. Termination of protease-activated receptor-1 signaling by beta-arrestins is independent of receptor phosphorylation. Chen, C.H., Paing, M.M., Trejo, J. J. Biol. Chem. (2004) [Pubmed]
  9. Negative regulation of protease-activated receptor 1-induced Src kinase activity by the association of phosphocaveolin-1 with Csk. Lu, T.L., Kuo, F.T., Lu, T.J., Hsu, C.Y., Fu, H.W. Cell. Signal. (2006) [Pubmed]
  10. Two types of protease-activated receptors (PAR-1 and PAR-2) mediate calcium signaling in rat retinal ganglion cells RGC-5. Luo, W., Wang, Y., Reiser, G. Brain Res. (2005) [Pubmed]
  11. Proteinase-activated receptors in ovine cervical function. Mitchell, S.E., Robinson, J.J., King, M.E., Williams, L.M. Reprod. Fertil. Dev. (2005) [Pubmed]
  12. Termination of signaling by protease-activated receptor-1 is linked to lysosomal sorting. Trejo, J., Hammes, S.R., Coughlin, S.R. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  13. Gene induction by coagulation factor Xa is mediated by activation of protease-activated receptor 1. Riewald, M., Kravchenko, V.V., Petrovan, R.J., O'Brien, P.J., Brass, L.F., Ulevitch, R.J., Ruf, W. Blood (2001) [Pubmed]
  14. Atypical protease-activated receptor mediates endothelium-dependent relaxation of human coronary arteries. Hamilton, J.R., Nguyen, P.B., Cocks, T.M. Circ. Res. (1998) [Pubmed]
  15. Human corneal epithelial cells express functional PAR-1 and PAR-2. Lang, R., Song, P.I., Legat, F.J., Lavker, R.M., Harten, B., Kalden, H., Grady, E.F., Bunnett, N.W., Armstrong, C.A., Ansel, J.C. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
  16. Induction of monocyte chemoattractant protein-1 release from A549 cells by agonists of protease-activated receptor-1 and -2. Wang, H., Yi, T., Zheng, Y., He, S. Eur. J. Cell Biol. (2007) [Pubmed]
  17. Protease-activated receptor (PAR)-1 and PAR-2 participate in the cell growth of alveolar capillary endothelium in primary lung adenocarcinomas. Jin, E., Fujiwara, M., Pan, X., Ghazizadeh, M., Arai, S., Ohaki, Y., Kajiwara, K., Takemura, T., Kawanami, O. Cancer (2003) [Pubmed]
  18. Upregulation of proteinase-activated receptors and hypercontractile responses precede development of arterial lesions after balloon injury. Fukunaga, R., Hirano, K., Hirano, M., Niiro, N., Nishimura, J., Maehara, Y., Kanaide, H. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  19. Responses to aggregating agents after cleavage of GPIb of human platelets by the O-sialoglycoprotein endoprotease from Pasteurella haemolytica- potential surrogates for Bernard-Soulier platelets? Kinlough-Rathbone, R.L., Perry, D.W., Rand, M.L., Packham, M.A. Thromb. Res. (2000) [Pubmed]
  20. Thrombin inhibits intercellular calcium wave propagation in corneal endothelial cells by modulation of hemichannels and gap junctions. D'hondt, C., Ponsaerts, R., Srinivas, S.P., Vereecke, J., Himpens, B. Invest. Ophthalmol. Vis. Sci. (2007) [Pubmed]
  21. Protease-activated receptors and their role in IL-6 and NF-IL-6 expression in human gingival fibroblasts. Hou, L., Ravenall, S., Macey, M.G., Harriott, P., Kapas, S., Howells, G.L. J. Periodont. Res. (1998) [Pubmed]
  22. Direct vascular effects of protease-activated receptor type 1 agonism in vivo in humans. Gudmundsd??ttir, I.J., Megson, I.L., Kell, J.S., Ludlam, C.A., Fox, K.A., Webb, D.J., Newby, D.E. Circulation (2006) [Pubmed]
  23. In vivo evidence that protease-activated receptors 1 and 2 modulate gastrointestinal transit in the mouse. Kawabata, A., Kuroda, R., Nagata, N., Kawao, N., Masuko, T., Nishikawa, H., Kawai, K. Br. J. Pharmacol. (2001) [Pubmed]
  24. Localization of protease-activated receptors-1 and -2 in human mast cells: indications for an amplified mast cell degranulation cascade. D'Andrea, M.R., Rogahn, C.J., Andrade-Gordon, P. Biotechnic & histochemistry : official publication of the Biological Stain Commission. (2000) [Pubmed]
 
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