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Gene Review

RBP3  -  retinol binding protein 3, interstitial

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Disease relevance of RBP3

  • The damage to IRBP seemed to involve photosensitization by the all-trans retinal, which was in turn protected from bleaching by the IRBP [1].
  • Interphotoreceptor retinoid-binding protein (IRBP), a retinal-specific Ag, induces experimental autoimmune uveitis in a variety of animals [2].
  • High levels of cross-reactivity between bovine and monkey IRBP were demonstrated by antibodies as measured by the enzyme-linked immunosorbent assay, and by the radiometric ear test of delayed-type hypersensitivity, by using rats immunized with either one of the IRBP [3].
  • Vasculitis was a predominant feature of IRBP induced disease while chorioretinitis and photoreceptor destruction was more prominent in the S-antigen sensitized animals [4].
  • In Brown Norway (BN) rats, it is known to be difficult to induce experimental autoimmune uveoretinitis (EAU) by the injection of retinal S-antigen (S-Ag) or interphotoreceptor retinoid-binding protein (IRBP) together with complete Freund's adjuvant (CFA), unless intravenous Bordetella Pertussis is used as an additional adjuvant [5].

High impact information on RBP3

  • Initiation of this process involves the signal recognition particle (SRP), which consists of six polypeptide chains and a 7S RNA and interacts with ribosomes carrying nascent secretory polypeptide chains [6].
  • These findings thus suggest that RAT 1181-1191 is not a likely target for lymphocytes sensitized against BOV 1181-1191 in the process in which these cells recognize IRBP in the rat eye and trigger the inflammatory reaction of EAU [7].
  • Interphotoreceptor retinoid-binding protein (IRBP), a glycoprotein specific for the retina and pineal gland, induces inflammatory changes in these two organs in immunized animals [8].
  • In addition, unlike the ocular disease induced by 1158-1180, the disease produced by 1169-1191 resembled that induced by whole IRBP in its kinetics and histopathological features [8].
  • A prominent component of the IPM is a glycoprotein known as interstitial retinol-binding protein (IRBP) [9].

Biological context of RBP3

  • All three of the introns in the IRBP gene fall in the fourth protein repeat [10].
  • The gene for bovine interphotoreceptor retinoid-binding protein (IRBP) has been cloned, and its nucleotide sequence has been determined [10].
  • The amino acid sequence of a tryptic peptide from authentic IRBP has been obtained [11].
  • Bovine retinal extract (RE) is a heterologous mixture of highly uveitogenic proteins including S-Antigen (S-Ag), interphotoreceptor retinol binding protein (IRBP) and rhodopsin, and is a potent inducer of experimental autoimmune uveoretinitis (EAU) [12].
  • Accordingly, it was investigated whether it is possible to reverse the detachment-induced anomalies in rhodopsin kinetics by introducing ligand-free IRBP purified from bovine retina to the subretinal space [13].

Anatomical context of RBP3

  • IRBP labeling was especially associated with the outer segments of photoreceptors and also with the apical surface of the retinal pigment epithelium [14].
  • In vitro translation of bovine retina polyadenylated RNA in a rabbit reticulocyte lysate system yielded an immunoreactive protein that was comparable in size with nonglycosylated, mature IRBP, showing that it is not synthesized from a large precursor, and supporting our finding that the mRNA contains an extensive non-coding region [15].
  • The photoreceptor cells have degenerated at these ages in the RCS animals, and may therefore be the retinal cells responsible for IRBP synthesis [16].
  • Rod outer segments (ROS) or neural retinas were isolated and bleached, then incubated with native RPE (RPE-eyecup) in the presence or absence of IRBP [17].
  • Based on these results and on the additional observation that a steep concentration gradient of docosahexaenoic acid exists between photoreceptor and pigment epithelium cells, a model for the mechanism by which IRBP may target 11-cis-retinal to photoreceptor cells is proposed [18].

Associations of RBP3 with chemical compounds

  • To prove the identity of the genomic clone, we determined the protein sequence of several tryptic and cyanogen bromide fragments of purified bovine IRBP protein and localized them in the protein predicted from its nucleotide sequence [10].
  • The putative function of IRBP in the extracellular transport of retinoids during the visual cycle is consistent with a defect in retinol transport in the RCS rat reported by others [16].
  • Interstitial retinol-binding protein (IRBP) is a soluble glycoprotein in the interphotoreceptor matrix of bovine, human, monkey, and rat eyes [16].
  • Analysis of IRBP-supplemented Ringer's solution incubated in the RPE-eyecup showed 11-cis-retinal to be virtually the only retinoid withdrawn from the RPE [17].
  • The transport of retinoids in the interphotoreceptor matrix is believed to be mediated by the interphotoreceptor retinoid-binding protein (IRBP), a protein that, in addition to possessing two retinoid-binding sites, associates in vivo with long chain fatty acids [18].

Physical interactions of RBP3

  • Early expression and localization of rhodopsin and interphotoreceptor retinoid-binding protein (IRBP) in the developing fetal bovine retina [19].

Regulatory relationships of RBP3

  • Supplementation with IRBP enhanced the formation of rhodopsin in both the ROS/RPE-eyecup and retina/RPE-eyecup preparations [17].

Other interactions of RBP3

  • In light-reared Royal College of Surgeons (RCS) and RCS retinal dystrophy gene (rdy)+ rats, the amount of IRBP in the interphotoreceptor matrix increased in corresponding proportion to the amount of total rhodopsin through postnatal day 22 (P22) [16].
  • The extent of regeneration was graded with the quantities of IRBP and opsin introduced into the RPE-eyecup [17].

Analytical, diagnostic and therapeutic context of RBP3


  1. Photosensitized light-induced damage of IRBP (interphotoreceptor retinoid-binding protein): effects on binding properties. Fedorovich, I.B., Semenova, E.M., Grant, K., Converse, C.A., Ostrovsky, M.A. Curr. Eye Res. (2000) [Pubmed]
  2. Analysis of the pivotal residues of the immunodominant and highly uveitogenic determinant of interphotoreceptor retinoid-binding protein. Kotake, S., de Smet, M.D., Wiggert, B., Redmond, T.M., Chader, G.J., Gery, I. J. Immunol. (1991) [Pubmed]
  3. Dissociation between lymphocyte activation for proliferation and for the capacity to adoptively transfer uveoretinitis. Fox, G.M., Redmond, T.M., Wiggert, B., Kuwabara, T., Chader, G.J., Gery, I. J. Immunol. (1987) [Pubmed]
  4. Experimental autoimmune uveoretinitis and pinealitis induced by interphotoreceptor retinoid-binding protein and S-antigen: induction of intraretinal and subretinal neovascularization. al-Mahdawi, S., McGettrick, P.M., Lee, W.R., Graham, D.I., Shallal, A., Converse, C.A. Journal of clinical & laboratory immunology. (1990) [Pubmed]
  5. Experimental autoimmune uveoretinitis in brown Norway rats induced by bovine interphotoreceptor retinoid-binding protein and renal cryosurgery. Shimmoto, K. Jpn. J. Ophthalmol. (1991) [Pubmed]
  6. The signal sequence of nascent preprolactin interacts with the 54K polypeptide of the signal recognition particle. Kurzchalia, T.V., Wiedmann, M., Girshovich, A.S., Bochkareva, E.S., Bielka, H., Rapoport, T.A. Nature (1986) [Pubmed]
  7. A pathogenic autoimmune process targeted at a surrogate epitope. Kozhich, A.T., Kawano, Y., Egwuagu, C.E., Caspi, R.R., Maturi, R.K., Berzofsky, J.A., Gery, I. J. Exp. Med. (1994) [Pubmed]
  8. Identification of an immunodominant and highly immunopathogenic determinant in the retinal interphotoreceptor retinoid-binding protein (IRBP). Sanui, H., Redmond, T.M., Kotake, S., Wiggert, B., Hu, L.H., Margalit, H., Berzofsky, J.A., Chader, G.J., Gery, I. J. Exp. Med. (1989) [Pubmed]
  9. Endocytosis and degradation of interstitial retinol-binding protein: differential capabilities of cells that border the interphotoreceptor matrix. Hollyfield, J.G., Varner, H.H., Rayborn, M.E., Liou, G.I., Bridges, C.D. J. Cell Biol. (1985) [Pubmed]
  10. Interphotoreceptor retinoid-binding protein. Gene characterization, protein repeat structure, and its evolution. Borst, D.E., Redmond, T.M., Elser, J.E., Gonda, M.A., Wiggert, B., Chader, G.J., Nickerson, J.M. J. Biol. Chem. (1989) [Pubmed]
  11. cDNA clones encoding bovine interphotoreceptor retinoid binding protein. Barrett, D.J., Redmond, T.M., Wiggert, B., Oprian, D.D., Chader, G.J., Nickerson, J.M. Biochem. Biophys. Res. Commun. (1985) [Pubmed]
  12. Intranasal administration of retinal antigens suppresses retinal antigen-induced experimental autoimmune uveoretinitis. Dick, A.D., Cheng, Y.F., Liversidge, J., Forrester, J.V. Immunology (1994) [Pubmed]
  13. Interphotoreceptor retinoid binding protein (IRBP) enhances rhodopsin regeneration in the experimentally detached retina. Duffy, M., Sun, Y., Wiggert, B., Duncan, T., Chader, G.J., Ripps, H. Exp. Eye Res. (1993) [Pubmed]
  14. Confocal immunolocalization of bovine serum albumin, serum retinol-binding protein, and interphotoreceptor retinoid-binding protein in bovine retina. Duncan, T., Fariss, R.N., Wiggert, B. Mol. Vis. (2006) [Pubmed]
  15. Bovine interstitial retinol-binding protein (IRBP)--isolation and sequence analysis of cDNA clones, characterization and in vitro translation of mRNA. Liou, G.I., Fong, S.L., Beattie, W.G., Cook, R.G., Leone, J., Landers, R.A., Alvarez, R.A., Wang, C., Li, Y., Bridges, C.D. Vision Res. (1986) [Pubmed]
  16. An extracellular retinol-binding glycoprotein in the eyes of mutant rats with retinal dystrophy: development, localization, and biosynthesis. Gonzalez-Fernandez, F., Landers, R.A., Glazebrook, P.A., Fong, S.L., Liou, G.I., Lam, D.M., Bridges, C.D. J. Cell Biol. (1984) [Pubmed]
  17. Interphotoreceptor retinoid-binding protein promotes rhodopsin regeneration in toad photoreceptors. Okajima, T.I., Pepperberg, D.R., Ripps, H., Wiggert, B., Chader, G.J. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  18. Docosahexaenoic acid modulates the interactions of the interphotoreceptor retinoid-binding protein with 11-cis-retinal. Chen, Y., Houghton, L.A., Brenna, J.T., Noy, N. J. Biol. Chem. (1996) [Pubmed]
  19. Early expression and localization of rhodopsin and interphotoreceptor retinoid-binding protein (IRBP) in the developing fetal bovine retina. Hauswirth, W.W., Langerijt, A.V., Timmers, A.M., Adamus, G., Ulshafer, R.J. Exp. Eye Res. (1992) [Pubmed]
  20. Properties of an interphotoreceptor retinoid-binding protein from bovine retina. Saari, J.C., Teller, D.C., Crabb, J.W., Bredberg, L. J. Biol. Chem. (1985) [Pubmed]
  21. Synthesis of an immunopathogenic fusion protein derived from a bovine interphotoreceptor retinoid-binding protein cDNA clone. Redmond, T.M., Si, J.S., Barrett, D.J., Borst, D.E., Rainier, S., Kotake, S., Gery, I., Nickerson, J.M. Gene (1989) [Pubmed]
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