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Gene Review

Sag  -  S-antigen; retina and pineal gland (arrestin)

Rattus norvegicus

Synonyms: 48 kDa protein, Retinal S-antigen, Rod photoreceptor arrestin, S-AG, S-arrestin, ...
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Disease relevance of Sag


High impact information on Sag

  • The recovered full-length cDNA encodes a 48 kDa protein, NEMO (NF-kappaB Essential MOdulator), which contains a putative leucine zipper motif [6].
  • The 48 kDa antigen is not observed in non-neural epithelial tissues and is detected in cortical and cerebellar tissues only at a developmental period that coincides with the stage of active neuronal cell migration [7].
  • Antibodies raised to a mixture of the 46 and 48 kDa rat CNS 2',3'-cyclic nucleotide 3-phosphodiesterases (CNPs) recognized apparently identical proteins in peripheral nervous system (PNS), thymus, and circulating blood lymphocytes [8].
  • However, the latter binding was more effectively competed by R-2 RNA than by itself, indicating that the homologous sites may be weaker binding sites for the same 48-kDa protein [9].
  • In particular, endosomes were found to harbor a 48-kDa extrinsic membrane protein and two or more integral membrane phosphoproteins of 30-35 kDa [10].

Chemical compound and disease context of Sag


Biological context of Sag

  • Furthermore, antibodies elicited against peptide 384-392 were shown to inhibit the protein kinase C-dependent phosphorylation of the 48-kDa polypeptide [14].
  • The formation of this dimer is particularly sensitive to MSA release on hydrolysis of MDMS because, in the presence of MSA, HCHO preferentially cross-linked an H2a-H2b dimer and a 48-kDa non-histone protein to DNA [15].
  • DC pulsed with either retinal S-antigen or another retinal autoantigen, interphotoreceptor retinoid binding protein (IRBP), were able to stimulate naive T cell proliferation in vitro, but only S-antigen-pulsed DC were able to induce an immune response in vivo and initiate antibody class switching [16].
  • The mutant lacking both glycosylation sites, while poorly secreted, had an apparent molecular mass of 48 kDa, the same size observed for HL after enzymatic removal of N-linked oligosaccharides [17].
  • We show that in PC12 cells overexpression of caspase-2 induces cell death, serum deprivation induces processing (i.e., activation) of the 48-kDa pro-caspase-2, and stable expression of caspase-2 antisense RNA inhibits apoptosis induced by serum deprivation [18].

Anatomical context of Sag

  • Above 48 megarads the radiation inactivation curve of the Tris-HCl-washed microsomes was described by a monoexponential function which gave a target size of 48 kDa [19].
  • A proteoglycan obtained from extracts of Sertoli cells is described which contains heparin (maximum 48 kDa) GAG chains [20].
  • The antibody reacted specifically with a 48 kDa protein in the extract of the parotid glands from untreated rats while no reaction was detected in that of the proliferation-induced ones [21].
  • Liver cytosol contained two poly(A) polymerase species (40 and 48 kDa) [22].
  • PC12 cells were found to contain and release a 70-75-kDa tissue-type plasminogen activator (tPA) and a much less abundant 48-kDa urokinase-type plasminogen activator [23].

Associations of Sag with chemical compounds


Physical interactions of Sag

  • How ATP quenches PDE is not established; however, leading hypotheses favor the intervention of a 48-kDa ATP-binding protein and/or an ATP-utilizing rhodopsin kinase in this reaction [28].

Regulatory relationships of Sag


Other interactions of Sag

  • In addition, antibody RK5 was used to recover a cDNA clone (pRK5) encoding a portion of a 48-kDa keratin-related protein with unique tissue and cellular distribution, designated cytokeratin 21 [31].
  • Intact IGFBP-3 (M(r), approximately 48 kDa) and low molecular IGFBP-3 fragments were not significantly different among the three groups [32].
  • Immunoblotting analyses on SDS gels, using a monoclonal antibody specific to the AT1 receptor, showed two immunoreactive protein species of 45 and 48 kDa [33].
  • The immunoreactivity of types I, III and V collagen, fibronectin and transforming growth factor-beta (TGF-beta) was studied by an immunogold labeling method in retinal vessels of rats with experimental autoimmune uveoretinitis (EAU) induced by retinal S-antigen [34].
  • The molecular mass of the induced form of plasminogen activator was estimated to be approximately 48 kDa [35].

Analytical, diagnostic and therapeutic context of Sag

  • Two subunits of 46 kDa and 48 kDa could be detected in SDS/PAGE, but only one subunit of 41 kDa was present after digestion with N-glycosidase [36].
  • Gel filtration on Sephacryl S-200 using 0.3 M NaCl for elution showed that the major liver poly(A) polymerase had a molecular weight of 156,000, which corresponded to a tetramer of the 38-kDa polypeptide, whereas the hepatoma and minor liver 48-kDa species existed as dimers with a molecular weight of 96,000 [1].
  • The 48-kDa phosphoprotein was analyzed by proteolytic cleavage and peptide mapping in order to localize the site of phosphorylation within the receptor molecule [14].
  • Epididymal 11beta-HSD1 expression was confirmed by Western blot analysis, with immunoreactive species identified at 34 kDa (the expected size for 11beta-HSD1) and at approximately 48 kDa [37].
  • By using the technique of fibrin-agarose zymography, three bands of PA activity were detected at 4 and 7 days after castration: a major band with a molecular mass of approx. 30 kDa and two minor bands of 48 kDa and 64 kDa [38].


  1. Structurally and immunologically distinct poly(A) polymerases in rat liver. Occurrence of a tumor-type enzyme in normal liver. Stetler, D.A., Jacob, S.T. J. Biol. Chem. (1984) [Pubmed]
  2. Ocular injection of retinal S antigen: suppression of autoimmune uveitis. Mizuno, K., Clark, A.F., Streilein, J.W. Invest. Ophthalmol. Vis. Sci. (1989) [Pubmed]
  3. The autoantigen La/SSB is a calmodulin-binding protein. Castro, A., Faura, M., Agell, N., Renau-Piqueras, J., Bachs, O. Cell Calcium (1996) [Pubmed]
  4. Experimental autoimmune uveoretinitis in athymic rats: specific IgE response to retinal S-antigen and disease. De Kozak, Y., Mirshahi, M., Sainte-Laudy, J., Thillaye, B., Faure, J.P. Immunol. Lett. (1985) [Pubmed]
  5. Immunization with recombinant Escherichia coli expressing retinal S-antigen-induced experimental autoimmune uveitis (EAU) in Lewis rats. Eto, K., Suzuki, S., Singh, V.K., Shinohara, T. Cell. Immunol. (1993) [Pubmed]
  6. Complementation cloning of NEMO, a component of the IkappaB kinase complex essential for NF-kappaB activation. Yamaoka, S., Courtois, G., Bessia, C., Whiteside, S.T., Weil, R., Agou, F., Kirk, H.E., Kay, R.J., Israël, A. Cell (1998) [Pubmed]
  7. Identification of membrane proteins that comprise the plasmalemmal junction between migrating neurons and radial glial cells. Cameron, R.S., Rakic, P. J. Neurosci. (1994) [Pubmed]
  8. Molecular cloning of a 2',3'-cyclic nucleotide 3'-phosphodiesterase: mRNAs with different 5' ends encode the same set of proteins in nervous and lymphoid tissues. Bernier, L., Alvarez, F., Norgard, E.M., Raible, D.W., Mentaberry, A., Schembri, J.G., Sabatini, D.D., Colman, D.R. J. Neurosci. (1987) [Pubmed]
  9. Identification of an mRNA-binding protein and the specific elements that may mediate the pH-responsive induction of renal glutaminase mRNA. Laterza, O.F., Hansen, W.R., Taylor, L., Curthoys, N.P. J. Biol. Chem. (1997) [Pubmed]
  10. Organelle-specific phosphorylation. Identification of unique membrane phosphoproteins of the endoplasmic reticulum and endosomal apparatus. Rindress, D., Lei, X., Ahluwalia, J.P., Cameron, P.H., Fazel, A., Posner, B.I., Bergeron, J.J. J. Biol. Chem. (1993) [Pubmed]
  11. Local cyclosporine therapy for experimental autoimmune uveitis in rats. Nussenblatt, R.B., Dinning, W.J., Fujikawa, L.S., Chan, C.C., Palestine, A.G. Arch. Ophthalmol. (1985) [Pubmed]
  12. Retinal lipid peroxidation in experimental uveitis. Rao, N.A., Fernandez, M.A., Cid, L.L., Romero, J.L., Sevanian, A. Arch. Ophthalmol. (1987) [Pubmed]
  13. The induction of tolerance by cyclosporine-G in experimental autoimmune uveitis in the Lewis rat. Dinning, W.J., Nussenblatt, R.B., Kuwabara, T., Leake, W. Journal of ocular pharmacology. (1987) [Pubmed]
  14. Phosphorylation of the 48-kDa subunit of the glycine receptor by protein kinase C. Ruiz-Gómez, A., Vaello, M.L., Valdivieso, F., Mayor, F. J. Biol. Chem. (1991) [Pubmed]
  15. Isolation and characterization of proteins cross-linked to DNA by the antitumor agent methylene dimethanesulfonate and its hydrolytic product formaldehyde. O'Connor, P.M., Fox, B.W. J. Biol. Chem. (1989) [Pubmed]
  16. Induction or suppression of a B cell-specific response to self antigen in vivo is dependent upon dendritic cell activation via the TNF-alpha receptor at the time of antigen uptake. Liversidge, J., Dick, A., Daniels, G., Dawson, R. Eur. J. Immunol. (2000) [Pubmed]
  17. Effect of N-linked glycosylation on hepatic lipase activity. Stahnke, G., Davis, R.C., Doolittle, M.H., Wong, H., Schotz, M.C., Will, H. J. Lipid Res. (1991) [Pubmed]
  18. Need for caspase-2 in apoptosis of growth-factor-deprived PC12 cells. Haviv, R., Lindenboim, L., Yuan, J., Stein, R. J. Neurosci. Res. (1998) [Pubmed]
  19. Radiation inactivation of microsomal glutathione S-transferase. Boyer, T.D., Vessey, D.A., Kempner, E. J. Biol. Chem. (1986) [Pubmed]
  20. Structural characterization of proteoglycans produced by testicular peritubular cells and Sertoli cells. Skinner, M.K., Fritz, I.B. J. Biol. Chem. (1985) [Pubmed]
  21. Isoproterenol downregulation of statin-related gene expression in the rat parotid gland. Ann, D.K., Wechsler, A., Lin, H.H., Wang, E. J. Cell. Sci. (1991) [Pubmed]
  22. Comparison of cytosolic and nuclear poly(A) polymerases from rat liver and a hepatoma: structural and immunological properties and response to NI-type protein kinases. Stetler, D.A., Jacob, S.T. Biochemistry (1985) [Pubmed]
  23. Modulation of proteolytic activity during neuritogenesis in the PC12 nerve cell: differential control of plasminogen activator and plasminogen activator inhibitor activities by nerve growth factor and dibutyryl-cyclic AMP. Leprince, P., Rogister, B., Delrée, P., Rigo, J.M., André, B., Moonen, G. J. Neurochem. (1991) [Pubmed]
  24. Reconstitution of the immunopurified 49-kDa sodium-dependent bile acid transport protein derived from hepatocyte sinusoidal plasma membranes. von Dippe, P., Levy, D. J. Biol. Chem. (1990) [Pubmed]
  25. Cloning and expression of the Gal beta 1, 3GalNAc alpha 2,3-sialyltransferase. Gillespie, W., Kelm, S., Paulson, J.C. J. Biol. Chem. (1992) [Pubmed]
  26. Degradation of nuclear matrix and DNA cleavage in apoptotic thymocytes. Weaver, V.M., Carson, C.E., Walker, P.R., Chaly, N., Lach, B., Raymond, Y., Brown, D.L., Sikorska, M. J. Cell. Sci. (1996) [Pubmed]
  27. Membrane dipeptidase and glutathione are major components of pig pancreatic zymogen granules. Höfken, T., Linder, D., Kleene, R., Göke, B., Wagner, A.C. Exp. Cell Res. (1998) [Pubmed]
  28. 8-Azido-ATP (alpha 32P) binding to rod outer segment proteins. Shuster, T.A., Nagy, A.K., Farber, D.B. Exp. Eye Res. (1988) [Pubmed]
  29. Protein phosphorylation in rat hippocampal synaptic plasma membranes in response to neurohypophyseal peptides. Hinko, A., Kim, Y., Pearlmutter, A.F. Brain Res. (1986) [Pubmed]
  30. Effect of antioxidant enzymes on experimental uveitis in rats. de Kozak, Y., Nordman, J.P., Faure, J.P., Rao, N.A., Marak, G.E. Ophthalmic Res. (1989) [Pubmed]
  31. Identification and characterization of rat intestinal keratins. Molecular cloning of cDNAs encoding cytokeratins 8, 19, and a new 49-kDa type I cytokeratin (cytokeratin 21) expressed by differentiated intestinal epithelial cells. Chandler, J.S., Calnek, D., Quaroni, A. J. Biol. Chem. (1991) [Pubmed]
  32. Decreased hepatic insulin-like growth factor (IGF)-I and increased IGF binding protein-1 and -2 gene expression in experimental uremia. Tönshoff, B., Powell, D.R., Zhao, D., Durham, S.K., Coleman, M.E., Domené, H.M., Blum, W.F., Baxter, R.C., Moore, L.C., Kaskel, F.J. Endocrinology (1997) [Pubmed]
  33. Charge heterogeneity of the AT1 angiotensin II receptor subtype in the rat lung. Montiel, M., Quesada, J., Jiménez, E. J. Endocrinol. (1995) [Pubmed]
  34. Increased immunoreactivity of collagen types I, III and V, fibronectin and TGF-beta in retinal vessels of rats with experimental autoimmune uveoretinitis. Mahalak, S.M., Lin, W.L., Essner, E., Shichi, H. Curr. Eye Res. (1991) [Pubmed]
  35. Induction of urokinase-type plasminogen activator in rat facial nucleus by axotomy of the facial nerve. Nakajima, K., Reddington, M., Kohsaka, S., Kreutzberg, G.W. J. Neurochem. (1996) [Pubmed]
  36. Rat acid phosphatase: overexpression of active, secreted enzyme by recombinant baculovirus-infected insect cells, molecular properties, and crystallization. Vihko, P., Kurkela, R., Porvari, K., Herrala, A., Lindfors, A., Lindqvist, Y., Schneider, G. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  37. Localization of 11beta-hydroxysteroid dehydrogenase types 1 and 2 in the male reproductive tract. Waddell, B.J., Hisheh, S., Krozowski, Z.S., Burton, P.J. Endocrinology (2003) [Pubmed]
  38. Urokinase- and tissue-type plasminogen activators are suppressed by cortisol in the involuting prostate of castrated rats. Freeman, S.N., Rennie, P.S., Chao, J., Lund, L.R., Andreasen, P.A. Biochem. J. (1990) [Pubmed]
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