retinol binding proteins


Summary: Proteins which bind with RETINOL. The retinol-binding protein found in plasma has an alpha-1 mobility on electrophoresis and a molecular weight of about 21 kDa. The retinol-protein complex (MW=80-90 kDa) circulates in plasma in the form of a protein-protein complex with prealbumin. The retinol-binding protein found in tissue has a molecular weight of 14 kDa and carries retinol as a non-covalently-bound ligand.

Top Publications

  1. Gonzalez Fernandez F. Interphotoreceptor retinoid-binding protein--an old gene for new eyes. Vision Res. 2003;43:3021-36 pubmed
    ..The present review will summarize what is known about the structure and function of IRBP to anticipate future avenues of research. ..
  2. Peng Y, Han G, Shao H, Wang Y, Kaplan H, Sun D. Characterization of IL-17+ interphotoreceptor retinoid-binding protein-specific T cells in experimental autoimmune uveitis. Invest Ophthalmol Vis Sci. 2007;48:4153-61 pubmed
    ..IL-17(+) T cells can be readily detected among activated autoreactive and bystander T cells and may play a major role in the pathogenesis of EAU. ..
  3. Semenova E, Converse C. Comparison between oleic acid and docosahexaenoic acid binding to interphotoreceptor retinoid-binding protein. Vision Res. 2003;43:3063-7 pubmed
    ..This may imply oleic acid has a key role in the balance and transport of retinoids and fatty acids in the retina. ..
  4. Wu Q, Blakeley L, Cornwall M, Crouch R, Wiggert B, Koutalos Y. Interphotoreceptor retinoid-binding protein is the physiologically relevant carrier that removes retinol from rod photoreceptor outer segments. Biochemistry. 2007;46:8669-79 pubmed
    ..The effect of different concentrations of IRBP on the rate of retinol removal shows no cooperativity and has an EC50 of 40 micromol/L. ..
  5. Otteson D, Liu Y, Lai H, Wang C, Gray S, Jain M, et al. Kruppel-like factor 15, a zinc-finger transcriptional regulator, represses the rhodopsin and interphotoreceptor retinoid-binding protein promoters. Invest Ophthalmol Vis Sci. 2004;45:2522-30 pubmed
  6. Qtaishat N, Wiggert B, Pepperberg D. Interphotoreceptor retinoid-binding protein (IRBP) promotes the release of all-trans retinol from the isolated retina following rhodopsin bleaching illumination. Exp Eye Res. 2005;81:455-63 pubmed
    ..The results suggest that in vivo, IRBP plays a direct role in the release of all-trans retinol from the rods during operation of the visual cycle. ..
  7. Avichezer D, Grajewski R, Chan C, Mattapallil M, Silver P, Raber J, et al. An immunologically privileged retinal antigen elicits tolerance: major role for central selection mechanisms. J Exp Med. 2003;198:1665-76 pubmed
    ..Thus, uveitis-susceptible individuals display a detectable and functionally significant tolerance to their target antigen, in which central mechanisms play a prominent role. ..
  8. Agarwal R, Caspi R. Rodent models of experimental autoimmune uveitis. Methods Mol Med. 2004;102:395-419 pubmed
    ..The ability to induce EAU in various gene-manipulated, including HLA-transgenic, mouse strains makes the EAU model suitable for the study of basic mechanisms as well as in clinically relevant interventions. ..
  9. Tsina E, Chen C, Koutalos Y, Ala Laurila P, Tsacopoulos M, Wiggert B, et al. Physiological and microfluorometric studies of reduction and clearance of retinal in bleached rod photoreceptors. J Gen Physiol. 2004;124:429-43 pubmed

More Information


  1. Wang T, Montell C. Rhodopsin formation in Drosophila is dependent on the PINTA retinoid-binding protein. J Neurosci. 2005;25:5187-94 pubmed
    ..Moreover, our data implicate Drosophila retinal pigment cells as functioning in the conversion of dietary all-trans-retinol to 11-cis-retinal and suggest that these cells are the closest invertebrate equivalent to the RPE. ..
  2. Stenkamp D, Calderwood J, Van Niel E, Daniels L, Gonzalez Fernandez F. The interphotoreceptor retinoid-binding protein (IRBP) of the chicken (Gallus gallus domesticus). Mol Vis. 2005;11:833-45 pubmed
    ..Expression of chicken IRBP and its mRNA are functionally regulated. This report provides a necessary first step to explore a specific function for IRBP in the cone visual cycle. ..
  3. Grajewski R, Silver P, Agarwal R, Su S, Chan C, Liou G, et al. Endogenous IRBP can be dispensable for generation of natural CD4+CD25+ regulatory T cells that protect from IRBP-induced retinal autoimmunity. J Exp Med. 2006;203:851-6 pubmed
    ..Our data also provide the first evidence that generation of specific T reg cells to a native autoantigen in a mouse with a diverse T cell repertoire requires a cognate interaction. ..
  4. Nickerson J, Frey R, Ciavatta V, Stenkamp D. Interphotoreceptor retinoid-binding protein gene structure in tetrapods and teleost fish. Mol Vis. 2006;12:1565-85 pubmed
    ..We suggest that the two-gene locus in teleost fish arose as a consequence of either the known whole genome duplication or single gene tandem duplication. ..
  5. Gonzalez Fernandez F, Ghosh D. Focus on Molecules: interphotoreceptor retinoid-binding protein (IRBP). Exp Eye Res. 2008;86:169-70 pubmed
  6. Gonzalez Fernandez F, Baer C, Ghosh D. Module structure of interphotoreceptor retinoid-binding protein (IRBP) may provide bases for its complex role in the visual cycle - structure/function study of Xenopus IRBP. BMC Biochem. 2007;8:15 pubmed
  7. Yoshimura T, Sonoda K, Miyazaki Y, Iwakura Y, Ishibashi T, Yoshimura A, et al. Differential roles for IFN-gamma and IL-17 in experimental autoimmune uveoretinitis. Int Immunol. 2008;20:209-14 pubmed
    ..Taken together, our data demonstrated that IL-17/T(h)17 participates in the late phases of EAU and also that T(h)1 and T(h)17 responses are differentially required for EAU...
  8. Cunningham L, Gonzalez Fernandez F. Internalization of interphotoreceptor retinoid-binding protein by the Xenopus retinal pigment epithelium. J Comp Neurol. 2003;466:331-42 pubmed
    ..The role of RPE endocytosis should be explored in relation to the function of IRBP. ..
  9. Folli C, Calderone V, Ramazzina I, Zanotti G, Berni R. Ligand binding and structural analysis of a human putative cellular retinol-binding protein. J Biol Chem. 2002;277:41970-7 pubmed
    ..These results indicate that human CRBP IV belongs to a clearly distinct CRBP subfamily and suggest a relatively different mode of retinol binding for this binding protein. ..
  10. Esteller M, Guo M, Moreno V, Peinado M, Capella G, Galm O, et al. Hypermethylation-associated Inactivation of the Cellular Retinol-Binding-Protein 1 Gene in Human Cancer. Cancer Res. 2002;62:5902-5 pubmed
    ..Epigenetic disruption of CRBP1 is a common event in human cancer that may have important implications for cancer prevention and treatment using retinoids. ..
  11. Xu G, Bochaton Piallat M, Andreutti D, Low R, Gabbiani G, Neuville P. Regulation of alpha-smooth muscle actin and CRBP-1 expression by retinoic acid and TGF-beta in cultured fibroblasts. J Cell Physiol. 2001;187:315-25 pubmed
    ..The characterization of these pathways will be helpful for the design of drugs influencing wound healing. ..
  12. Shaw N, Noy N. Interphotoreceptor retinoid-binding protein contains three retinoid binding sites. Exp Eye Res. 2001;72:183-90 pubmed
    ..The promiscuous 'site 1', and two additional sites with a stricter selectivity. One of the latter sites appears to be selective towards all-trans-retinol, while the other is specific for 11-cis-retinal. ..
  13. Mata N, Radu R, Clemmons R, Travis G. Isomerization and oxidation of vitamin a in cone-dominant retinas: a novel pathway for visual-pigment regeneration in daylight. Neuron. 2002;36:69-80 pubmed
    ..Together these activities comprise a novel pathway that regenerates opsin photopigments at a rate 20-fold faster than the known visual cycle. We suggest that this pathway is responsible for sustained daylight vision in vertebrates. ..
  14. Borst D, Boatright J, Si J, Stodulkova E, Remaley N, Pallansch L, et al. Structural characterization and comparison of promoter activity of mouse and bovine interphotoreceptor retinoid-binding protein (IRBP) gene 5' flanking regions in WERI, Y79, chick retina cells, and transgenic mice. Curr Eye Res. 2001;23:20-32 pubmed
    ..The conservation of sequences far upstream of the transcription start suggest that unknown physiological processes remain to be understood in IRBP transcriptional regulation. ..
  15. Boatright J, Nickerson J, Borst D. Site-specific DNA hypomethylation permits expression of the IRBP gene. Brain Res. 2000;887:211-21 pubmed
    ..This differential DNA methylation may modulate IRBP gene expression since exogenous methylation of the murine sites suppresses reporter gene transcription, apparently by inhibiting DNA:protein binding events. ..
  16. Kuppumbatti Y, Rexer B, Nakajo S, Nakaya K, Mira y Lopez R. CRBP suppresses breast cancer cell survival and anchorage-independent growth. Oncogene. 2001;20:7413-9 pubmed
    ..In conclusion, the data suggest two novel and linked CRBP functions in mammary epithelial cells: inhibition of the PI3K/Akt survival pathway and suppression of anchorage-independent growth. ..
  17. Mohan M, Malayer J, Geisert R, Morgan G. Expression of retinol-binding protein messenger RNA and retinoic acid receptors in preattachment bovine embryos. Mol Reprod Dev. 2001;60:289-96 pubmed
    ..Expression of mRNA for RBP, RARalpha, RARgamma, and of the RARalpha and RARgamma2 receptor proteins in the bovine embryo suggests that RA is likely to directly regulate gene expression during preimplantation development in that species. ..
  18. Gonzalez Fernandez F. Evolution of the visual cycle: the role of retinoid-binding proteins. J Endocrinol. 2002;175:75-88 pubmed
    ..Here we draw lessons from other soluble hormone-binding proteins to anticipate avenues of future research likely to provide insight into the structure and function of IRBP in vision. ..
  19. Arranz V, Dreuillet C, Crisanti P, Tillit J, Kress M, Ernoult Lange M. The zinc finger transcription factor, MOK2, negatively modulates expression of the interphotoreceptor retinoid-binding protein gene, IRBP. J Biol Chem. 2001;276:11963-9 pubmed
    ..Furthermore, we show that Mok2 expression in the developing mouse and in the adult retina seems to be concordant with IRBP expression. ..
  20. Boatright J, Knox B, Jones K, Stodulkova E, Nguyen H, Padove S, et al. Evidence of a tissue-restricting DNA regulatory element in the mouse IRBP promoter. FEBS Lett. 2001;504:27-30 pubmed
    ..In contrast, a -70/+101 fragment was less restrictive in controlling expression, exhibiting activity not only in retina, but also in forebrain, hindbrain, spinal cord, and motor neurons innervating gills. ..
  21. Agarwal R, Sun S, Su S, Chan C, Caspi R. Pertussis toxin alters the innate and the adaptive immune responses in a pertussis-dependent model of autoimmunity. J Neuroimmunol. 2002;129:133-40 pubmed
  22. Loew A, Gonzalez Fernandez F. Crystal structure of the functional unit of interphotoreceptor retinoid binding protein. Structure. 2002;10:43-9 pubmed
  23. Brown J, Eberhardt D, Schrick F, Roberts M, Godkin J. Expression of retinol-binding protein and cellular retinol-binding protein in the bovine ovary. Mol Reprod Dev. 2003;64:261-9 pubmed
    ..Results demonstrate retinoid-binding protein expression by bovine ovaries and provide physical evidence that supports the concept that retinoids play a role in ovarian function. ..
  24. Pennesi G, Mattapallil M, Sun S, Avichezer D, Silver P, Karabekian Z, et al. A humanized model of experimental autoimmune uveitis in HLA class II transgenic mice. J Clin Invest. 2003;111:1171-80 pubmed
    ..Thus, EAU in HLA TG mice offers a new model of uveitis that should represent human disease more faithfully than currently existing models. ..
  25. Folli C, Calderone V, Ottonello S, Bolchi A, Zanotti G, Stoppini M, et al. Identification, retinoid binding, and x-ray analysis of a human retinol-binding protein. Proc Natl Acad Sci U S A. 2001;98:3710-5 pubmed
  26. Swift L, Jovanovska A, Kakkad B, Ong D. Microsomal triglyceride transfer protein expression in mouse intestine. Histochem Cell Biol. 2005;123:475-82 pubmed
    ..In particular, the expression of MTP is not coordinated with the expression of apoB, even though the two proteins are essential for the assembly and secretion of chylomicrons. ..
  27. Poux C, Chevret P, Huchon D, de Jong W, Douzery E. Arrival and diversification of caviomorph rodents and platyrrhine primates in South America. Syst Biol. 2006;55:228-44 pubmed
    ..By contrast, few platyrrhine fossils are known in the Oligocene, and the present-day taxa are the result of a quite recent, Early Miocene diversification. ..
  28. Robinson M, Trujillo E, Mogensen K, Rounds J, McManus K, Jacobs D. Improving nutritional screening of hospitalized patients: the role of prealbumin. JPEN J Parenter Enteral Nutr. 2003;27:389-95; quiz 439 pubmed
    ..PAB screening/assessment may improve identification of those patients requiring nutrition intervention and thus enhance the care of hospitalized individuals. ..
  29. Read R, Vogt S, Barnum S, Szalai A. Experimental autoimmune uveitis in the C57BL/6 mouse. Exp Eye Res. 2006;83:229-30; author reply 231 pubmed
  30. Cabre A, Lazaro I, Girona J, Manzanares J, Marimón F, Plana N, et al. Retinol-binding protein 4 as a plasma biomarker of renal dysfunction and cardiovascular disease in type 2 diabetes. J Intern Med. 2007;262:496-503 pubmed
    ..2 vs. 40.6 +/- 13.9, P = 0.045). The presence of retinopathy or polyneuropathy did not differ across RBP4 quartiles. Plasma RBP4 concentration might be a biomarker of nephropathy and cardiovascular disease in type 2 diabetic subjects. ..
  31. Jin M, Li S, Nusinowitz S, Lloyd M, Hu J, Radu R, et al. The role of interphotoreceptor retinoid-binding protein on the translocation of visual retinoids and function of cone photoreceptors. J Neurosci. 2009;29:1486-95 pubmed publisher
  32. Yapi H, Ahiboh H, Yayo E, Edjeme A, Attoungbre Hauhouot M, Allico J, et al. [Immune, inflammatory, and nutritional protein profile in children with iron deficiency in Côte d'Ivoire]. Sante. 2009;19:25-8 pubmed publisher
    ..The proteins concerned include IgG, TBPA and albumin. The public authorities should pay particular attention to improving children's diets, especially their micronutrient levels, including for iron, vitamin A and zinc. ..
  33. Fu T, Yang P, Huang X, Zheng H, Zhou H, Zhong H. [Effect of endotoxin-induced uveitis on GATA-3 expression and ACAID development]. Zhonghua Yi Xue Za Zhi. 2003;83:1615-8 pubmed
    ..In ocular inflammation, the up-regulation of GATA-3 expression is inhibited and ACAID development is blocked after antigen was injected into anterior chamber. Once GATA-3 is up-regulated, LPS injection cannot affect ACAID development. ..
  34. Weksler M. Phylogeny of Neotropical oryzomyine rodents (Muridae: Sigmodontinae) based on the nuclear IRBP exon. Mol Phylogenet Evol. 2003;29:331-49 pubmed
    ..No conflict is observed between IRBP results and previous robust hypotheses from mitochondrial data, while a single case of incongruence is present between the IRBP topology and robust hypothesis from morphological studies...
  35. Shiraishi T, Kawahara K, Yamamoto S, Maekawa T, Shirakusa T. Postoperative nutritional management after esophagectomy: is TPN the standard of nutritional care?. Int Surg. 2005;90:30-5 pubmed
    ..No major complications due to early enteral diet occurred in ENT patients. We conclude that early enteral diet is nutritionally adequate and might be recommended as standard nutritional care after subtotal esophagectomy. ..
  36. Erikstrup C, Mortensen O, Pedersen B. Retinol-binding protein 4 and insulin resistance. N Engl J Med. 2006;355:1393-4; author reply 1394-5 pubmed
  37. Oh J. Retinol-binding protein 4 and insulin resistance. N Engl J Med. 2006;355:1394; author reply 1394-5 pubmed
  38. Luo L, Chen W, Pretlow T. CpG island methylation in aberrant crypt foci and cancers from the same patients. Int J Cancer. 2005;115:747-51 pubmed
  39. Farias E, Ong D, Ghyselinck N, Nakajo S, Kuppumbatti Y, Mira y Lopez R. Cellular retinol-binding protein I, a regulator of breast epithelial retinoic acid receptor activity, cell differentiation, and tumorigenicity. J Natl Cancer Inst. 2005;97:21-9 pubmed
    ..Physiologic RAR activation is dependent on CRBP-I-mediated retinol storage, and CRBP-I downregulation chronically compromises RAR activity, leading to loss of cell differentiation and tumor progression. ..
  40. Kawaguchi R, Yu J, Honda J, Hu J, Whitelegge J, Ping P, et al. A membrane receptor for retinol binding protein mediates cellular uptake of vitamin A. Science. 2007;315:820-5 pubmed
    ..It is widely expressed in embryonic development and in adult organ systems. The RBP receptor represents a major physiological mediator of cellular vitamin A uptake. ..
  41. Takebayashi K, Suetsugu M, Wakabayashi S, Aso Y, Inukai T. Retinol binding protein-4 levels and clinical features of type 2 diabetes patients. J Clin Endocrinol Metab. 2007;92:2712-9 pubmed
    ..The addition of pioglitazone for 12 wk to other diabetic medications the patients were already taking did not affect serum RBP4 levels. ..
  42. Ho J, Cheung S, Poon W, Lee Y, Ng I, Fan S. Down-regulation of retinol binding protein 5 is associated with aggressive tumor features in hepatocellular carcinoma. J Cancer Res Clin Oncol. 2007;133:929-36 pubmed
    ..02), and was an independent prognostic factor for HCC. Our study revealed that RBP5 down-regulation in HCC was associated with aggressive tumor features, suggesting an important role of RPB5 in HCC progression. ..
  43. Cia D, Bonhomme B, Azaïs Braesco V, Cluzel J, Doly M. Uptake and esterification of vitamin A by RCS rat retinal pigment epithelial cells in primary culture. Vision Res. 2004;44:247-55 pubmed
    ..Our results provide evidence of a functional retinol esterifying enzyme in cultured RCS RPE cells and suggest that CRBP-I could play a role in the uptake and esterification of ROL in the RPE cells. ..
  44. Josephs T, Waugh H, Kokay I, Grattan D, Thompson M. Fasting-induced adipose factor identified as a key adipokine that is up-regulated in white adipose tissue during pregnancy and lactation in the rat. J Endocrinol. 2007;194:305-12 pubmed
    ..2- to 2.5-fold higher throughout pregnancy and lactation. The marked induction of FIAF identifies this adipokine as a potential regulator of the metabolic adaptations that occur during pregnancy and lactation. ..
  45. Laube G, Russell Eggitt I, van t Hoff W. Early proximal tubular dysfunction in Lowe's syndrome. Arch Dis Child. 2004;89:479-80 pubmed
    ..Measurement of these urine parameters is recommended in suspected cases. ..
  46. Saraswathy S, Nguyen A, Rao N. The role of TLR4 in photoreceptor {alpha}a crystallin upregulation during early experimental autoimmune uveitis. Invest Ophthalmol Vis Sci. 2010;51:3680-6 pubmed publisher
    ..Such crystallin upregulation may prevent oxidative stress-mediated apoptosis of photoreceptors in uveitis. ..
  47. Maiti P, Gollapalli D, Rando R. Specificity of binding of all-trans-retinyl ester to RPE65. Biochemistry. 2005;44:14463-9 pubmed
    ..Other isoprenoid analogues also bind, as do truncated retinoids in the beta-ionone series. Therefore, mRPE65 is a moderately specific retinoid binding protein directed at long chain all-trans-retinyl esters. ..
  48. Gollapalli D, Maiti P, Rando R. RPE65 operates in the vertebrate visual cycle by stereospecifically binding all-trans-retinyl esters. Biochemistry. 2003;42:11824-30 pubmed
    ..This work provides further evidence that RPE65 functions by binding to and mobilizing the highly hydrophobic all-trans-retinyl esters, allowing them to enter the visual cycle. ..
  49. Matsukawa T, Sugitani K, Mawatari K, Koriyama Y, Liu Z, Tanaka M, et al. Role of purpurin as a retinol-binding protein in goldfish retina during the early stage of optic nerve regeneration: its priming action on neurite outgrowth. J Neurosci. 2004;24:8346-53 pubmed
    ..Thus, purpurin with retinol is the first candidate molecule of priming neurite outgrowth in the early stage of optic nerve regeneration in fish. ..
  50. Villani M, Appierto V, Cavadini E, Valsecchi M, Sonnino S, Curley R, et al. Identification of the fenretinide metabolite 4-oxo-fenretinide present in human plasma and formed in human ovarian carcinoma cells through induction of cytochrome P450 26A1. Clin Cancer Res. 2004;10:6265-75 pubmed
    ..Moreover evidence was provided that 4-HPR up-modulates the expression of CRBP-I transcript, which is lost during ovarian carcinogenesis. ..
  51. Zhang P, Sun D, Ke Y, Kaplan H, Shao H. The net effect of costimulatory blockers is dependent on the subset and activation status of the autoreactive T cells. J Immunol. 2007;178:474-9 pubmed
    ..Our results show that anti-costimulatory molecule treatment can have diverse actions on autoreactive T cell subsets, the net effect being determined by the subset of immune cells affected and the type and dose of treatment used. ..
  52. Chen L, Zhou Q, Yang J. [Protective effects of astragali injection on tubular in patients with primary nephrotic syndrome]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2004;29:152-3 pubmed
    ..After the one month treatment, sALB was significantly higher, and ubeta2MG, uNAG, uRBP, and 24 huP were significantly lower in astragali group (P <0.01, P < 0.05). Astragali injection on tubular plays a protective role in PNS. ..
  53. Huang J, Vieira A. Evidence for a specific cell membrane retinol-binding protein transport mechanism in a human keratinocyte line. Int J Mol Med. 2006;17:627-31 pubmed
    ..Overall, the data establish membrane transport parameters for RBP, and provide a basis for examining modulation of vitamin A endocytosis that may accompany changes in proliferation or differentiation state of epidermal cells. ..