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Gene Review

RBP2  -  retinol binding protein 2, cellular

Homo sapiens

Synonyms: CRABP-II, CRBP-II, CRBP2, CRBPII, Cellular retinol-binding protein II, ...
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Disease relevance of RBP2

  • RBP2, the form which has lost the two N-terminal Leu is dramatically increased in serum of patients with chronic renal failure (CRF) whereas this form is very low in normal serum [1].
  • Keratinocytes, in the absence of full terminal differentiation, as well as hyperplasia, such as cultured human differentiating keratinocytes, psoriatic plaques, and non-keratinized oral mucosa, contained high levels of CRABP-II [2].
  • Our findings also suggest that CRABP-II may be a potential therapeutic target for neuroblastoma [3].
  • Retinoblastoma-binding protein 2 (Rbp2) was originally identified as a retinoblastoma protein (RB) pocket domain-binding protein [4].
  • Therefore, in this study, we re-established the pRb-modulating function of RBP2-H1 in highly metastatic A375-SM melanoma cells by re-expressing its C-term (cRBP2-H1) [5].

High impact information on RBP2

  • Here we demonstrate that the JARID1 proteins RBP2, PLU1, and SMCX are histone demethylases specific for di- and trimethylated histone 3 lysine 4 (H3K4) [6].
  • RBP2 Belongs to a Family of Demethylases, Specific for Tri-and Dimethylated Lysine 4 on Histone 3 [6].
  • Consistent with a role for the JARID1 Drosophila homolog Lid in regulating expression of homeotic genes during development, we show that RBP2 is displaced from Hox genes during embryonic stem (ES) cell differentiation correlating with an increase of their H3K4me3 levels and expression [6].
  • Our results suggest that promotion of differentiation by pRB involves neutralization of free RBP2 and transcriptional activation of RBP2 targets linked to euchromatin maintenance [7].
  • In analogy with CS, preferential repair of UV-induced cyclobutane pyrimidine dimers in the transcribed strand of the active RBP2 gene is severely impaired [8].

Biological context of RBP2


Anatomical context of RBP2


Associations of RBP2 with chemical compounds

  • RBP2 may have an important physiological role in retinol transport and/or recycling [9].
  • There is strong evidence that RBP2 is formed in vitamin A target tissues, and that after its release into blood circulation, it is cleared by the kidney in healthy people but accumulates in the serum of CRF patients [1].
  • We also measured binding of FA to a retinoic acid (CRABP-I) and a retinol (CRBP-II) binding protein and we have extended to 19 different FA our characterization of the FA-ADIFAB and FA-rat intestinal FABP interactions [16].
  • However, direct sequence analysis and transient transfection experiments indicate that, unlike the rat CRBP II promoter, the human CRBP II promoter is not a direct retinoid X receptor target [14].
  • Retinol uptake and retinyl ester synthesis were increased up to 2-fold by coexpression of CRBP or over-expression of CRBP II [15].

Physical interactions of RBP2

  • Secondly, we found that the truncation resulting in RBP2 does not alter its binding properties for retinol nor those of holo-RBP2 for TTR [17].

Regulatory relationships of RBP2


Other interactions of RBP2

  • Furthermore, we demonstrate that CRABP-II is actually the CRABP previously studied in epidermal cells by a PAGE assay (Siegenthaler & Saurat (1987) Eur. J Biochem. 166, 209-214) and whose levels are dramatically increased by retinoic acid and its analogues in human epidermis [2].
  • Immunohistochemical analysis with the antiserum alpha-PLU-1C confirmed the nuclear localisation of PLU-1. alpha-PLU-1C also reacted with the mouse homologue of PLU-1 (mPlu-1) but not with the closest family member, RBP2 [18].
  • Retinoic acid receptor beta and apolipoprotein A1 regulatory protein-1, two nuclear receptors that bind to the CRBPII promoter, were also induced, whereas other retinoid and orphan receptors were not [19].
  • We found that CRBPII levels were elevated in the residual jejunal segment of rats subjected to jejunal bypass operation, where a concomitant increase in the apoprotein B levels occurred [20].
  • In the 5'-flanking region of rat CRBPII gene, two DR-1 type elements which consist of a direct repeat of the AGGTCA-like motif spaced by a single nucleotide have been identified as putative binding sites for a heterodimer of peroxisome proliferator-activated receptor (PPAR) and retinoid X-receptor (RXR) [20].

Analytical, diagnostic and therapeutic context of RBP2


  1. Extra-and intracellular transport of retinoids: a reappraisal. Siegenthaler, G. Horm. Res. (1996) [Pubmed]
  2. Expression of CRABP-I and -II in human epidermal cells. Alteration of relative protein amounts is linked to the state of differentiation. Siegenthaler, G., Tomatis, I., Chatellard-Gruaz, D., Jaconi, S., Eriksson, U., Saurat, J.H. Biochem. J. (1992) [Pubmed]
  3. Cellular Retinoic Acid-Binding Protein II Is a Direct Transcriptional Target of MycN in Neuroblastoma. Gupta, A., Williams, B.R., Hanash, S.M., Rawwas, J. Cancer Res. (2006) [Pubmed]
  4. Retinoblastoma-binding protein 2 (Rbp2) potentiates nuclear hormone receptor-mediated transcription. Chan, S.W., Hong, W. J. Biol. Chem. (2001) [Pubmed]
  5. Re-expression of the retinoblastoma-binding protein 2-homolog 1 reveals tumor-suppressive functions in highly metastatic melanoma cells. Roesch, A., Becker, B., Schneider-Brachert, W., Hagen, I., Landthaler, M., Vogt, T. J. Invest. Dermatol. (2006) [Pubmed]
  6. RBP2 Belongs to a Family of Demethylases, Specific for Tri-and Dimethylated Lysine 4 on Histone 3. Christensen, J., Agger, K., Cloos, P.A., Pasini, D., Rose, S., Sennels, L., Rappsilber, J., Hansen, K.H., Salcini, A.E., Helin, K. Cell (2007) [Pubmed]
  7. Binding of pRB to the PHD protein RBP2 promotes cellular differentiation. Benevolenskaya, E.V., Murray, H.L., Branton, P., Young, R.A., Kaelin, W.G. Mol. Cell (2005) [Pubmed]
  8. RAD26, the functional S. cerevisiae homolog of the Cockayne syndrome B gene ERCC6. van Gool, A.J., Verhage, R., Swagemakers, S.M., van de Putte, P., Brouwer, J., Troelstra, C., Bootsma, D., Hoeijmakers, J.H. EMBO J. (1994) [Pubmed]
  9. Characterization of two post-translationally processed forms of human serum retinol-binding protein: altered ratios in chronic renal failure. Jaconi, S., Rose, K., Hughes, G.J., Saurat, J.H., Siegenthaler, G. J. Lipid Res. (1995) [Pubmed]
  10. Closing in on the BPES gene on 3q23: mapping of a de Novo reciprocal translocation t(3;4)(q23;p15.2) breakpoint within a 45-kb cosmid and mapping of three candidate genes, RBP1, RBP2, and beta'-COP, distal to the breakpoint. De Baere, E., Van Roy, N., Speleman, F., Fukushima, Y., De Paepe, A., Messiaen, L. Genomics (1999) [Pubmed]
  11. Assignment of the cellular retinol-binding protein 2 gene (RBP2) to human chromosome band 3q23 by in situ hybridization. De Baere, E., Speleman, F., Van Roy, N., Mortier, K., De Paepe, A., Messiaen, L. Cytogenet. Cell Genet. (1998) [Pubmed]
  12. The cellular retinol binding protein II gene. Sequence analysis of the rat gene, chromosomal localization in mice and humans, and documentation of its close linkage to the cellular retinol binding protein gene. Demmer, L.A., Birkenmeier, E.H., Sweetser, D.A., Levin, M.S., Zollman, S., Sparkes, R.S., Mohandas, T., Lusis, A.J., Gordon, J.I. J. Biol. Chem. (1987) [Pubmed]
  13. Identification and structural analysis of a zebrafish apo and holo cellular retinol-binding protein. Calderone, V., Folli, C., Marchesani, A., Berni, R., Zanotti, G. J. Mol. Biol. (2002) [Pubmed]
  14. Analysis of human cellular retinol-binding protein II promoter during enterocyte differentiation. Zhang, L., E, X., Luker, K.E., Shao, J.S., Levin, M.S., Suh, E., Li, E. Am. J. Physiol. Gastrointest. Liver Physiol. (2002) [Pubmed]
  15. Cellular retinol-binding proteins are determinants of retinol uptake and metabolism in stably transfected Caco-2 cells. Levin, M.S. J. Biol. Chem. (1993) [Pubmed]
  16. Fatty acid binding proteins from different tissues show distinct patterns of fatty acid interactions. Richieri, G.V., Ogata, R.T., Zimmerman, A.W., Veerkamp, J.H., Kleinfeld, A.M. Biochemistry (2000) [Pubmed]
  17. Analysis of normal and truncated holo- and apo-retinol-binding protein (RBP) in human serum: altered ratios in chronic renal failure. Jaconi, S., Saurat, J.H., Siegenthaler, G. Eur. J. Endocrinol. (1996) [Pubmed]
  18. PLU-1 nuclear protein, which is upregulated in breast cancer, shows restricted expression in normal human adult tissues: a new cancer/testis antigen? Barrett, A., Madsen, B., Copier, J., Lu, P.J., Cooper, L., Scibetta, A.G., Burchell, J., Taylor-Papadimitriou, J. Int. J. Cancer (2002) [Pubmed]
  19. Retinoic acid increases cellular retinol binding protein II mRNA and retinol uptake in the human intestinal Caco-2 cell line. Levin, M.S., Davis, A.E. J. Nutr. (1997) [Pubmed]
  20. Regulation of vitamin A metabolism-related gene expression. Takase, S., Suruga, K., Goda, T. Br. J. Nutr. (2000) [Pubmed]
  21. Quantitation of human cellular retinoic acid-binding protein II (CRABP-II) RNA from cultured human skin fibroblast cells and human skin biopsies treated with retinoic acid. Zhou, L., Otulakowski, G., Pang, J., Munroe, D.G., Capetola, R.J., Lau, C. Nucleic Acids Res. (1992) [Pubmed]
  22. T-cell oncogene rhombotin-2 interacts with retinoblastoma-binding protein 2. Mao, S., Neale, G.A., Goorha, R.M. Oncogene (1997) [Pubmed]
  23. Cloning of chick cellular retinol-binding protein, type II and comparison to that of some mammals: expression of the gene at different developmental stages, and possible involvement of RXRs and PPAR. Suruga, K., Goda, T., Igarashi, M., Kato, S., Masushige, S., Takase, S. Comp. Biochem. Physiol. A Physiol. (1997) [Pubmed]
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