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Gene Review

Crabp2  -  cellular retinoic acid binding protein II

Mus musculus

Synonyms: AI893628, CRABP-II, Cellular retinoic acid-binding protein 2, Cellular retinoic acid-binding protein II, Crabp-2, ...
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Disease relevance of Crabp2

  • We also show that CRABP-II mRNA levels are induced by at least 50-fold upon treatment of F9 teratocarcinoma cells with retinoic acid [1].
  • Similarly, injection of an adenovirus expressing CRABP-II into mammary carcinomas that spontaneously develop in TgN(MMTVneu)202Mul mice resulted in a significant delay in tumor growth and in prolonged survival rates [2].
  • This study suggests that CRABP-II gene expression may be a more sensitive indicator of retinoid biologic activity in skin than are erythema or changes in epidermal morphology and differentiation [3].
  • Binding to CRABP-II and activation of RARs appear to be important factors for expression of differentiating activity, inhibition of induction of ODC activity and prevention of papillomas on the skin of mice [4].

High impact information on Crabp2


Biological context of Crabp2


Anatomical context of Crabp2

  • Morphological observations of CRBPI- and CRABPI/CRABPII-null mutant fetus at 18.5 dpc do not show any structural modification at the level of the organ of Corti [11].
  • The embryonic structures expressing CRABP II transcripts include those structures that have been shown to be adversely affected by excess of retinoids, such as limbs and hindbrain, but CRABP II transcripts are also found in structures not known to be specifically vulnerable to raised RA levels [8].
  • RAR-beta and CRABP II, which are both RA-inducible, were coexpressed with CRBP I in the choroid plexus and in many other sites, perhaps reflecting the fact that all three genes are RA-inducible [12].
  • CRABP-II expression remains strong in the developing limb bud suggesting a role for this protein in limb patterning [10].
  • We have disrupted the CRABPII gene using homologous recombination in embryonic stem cells, and shown that this disruption results in a null mutation [13].

Associations of Crabp2 with chemical compounds


Regulatory relationships of Crabp2

  • TGF-beta 1 also stimulated a dose-dependent increase in the expression of CRABP-II mRNA [17].
  • RA down-regulated the expression of CRABP-I mRNA and up-regulated the expression of CRABP-II mRNA in a time- and dose-dependent fashion [17].

Other interactions of Crabp2


Analytical, diagnostic and therapeutic context of Crabp2

  • Recombinant wild type and mutant CRABP-II proteins were expressed and purified, and the affinity for retinoids was determined by fluorometric titration and binding of 3H-labeled compounds [19].
  • Crystallographic and site-directed mutagenesis studies of several related proteins have indicated that either one or two conserved amino acid residues, homologous to positions Arg111 and Arg132 of CRABP-II, are important for the binding of the hydrophobic ligand [19].
  • To determine whether RAR and RXR can bind to the human CRABPII RARE, gel retardation assays were performed [15].
  • Localization of CRABP-I and CRABP-II mRNA in the early mouse embryo by whole-mount in situ hybridization: implications for teratogenesis and neural development [20].


  1. Molecular cloning of cDNA encoding a second cellular retinoic acid-binding protein. Giguère, V., Lyn, S., Yip, P., Siu, C.H., Amin, S. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  2. Mammary carcinoma suppression by cellular retinoic acid binding protein-II. Manor, D., Shmidt, E.N., Budhu, A., Flesken-Nikitin, A., Zgola, M., Page, R., Nikitin, A.Y., Noy, N. Cancer Res. (2003) [Pubmed]
  3. Comparison of CD271 (adapalene) and all-trans retinoic acid in human skin: dissociation of epidermal effects and CRABP-II mRNA expression. Griffiths, C.E., Elder, J.T., Bernard, B.A., Rossio, P., Cromie, M.A., Finkel, L.J., Shroot, B., Voorhees, J.J. J. Invest. Dermatol. (1993) [Pubmed]
  4. Biochemical characteristics and differentiating activity of 4-oxo analogs of retinoic acid. Sani, B.P., Venepally, P., Zhang, X.K., Hill, D.L., Shealy, Y.F. Anticancer Res. (1996) [Pubmed]
  5. Retinoids: effects on growth, differentiation, and nuclear receptor expression in human pancreatic carcinoma cell lines. Rosewicz, S., Stier, U., Brembeck, F., Kaiser, A., Papadimitriou, C.A., Berdel, W.E., Wiedenmann, B., Riecken, E.O. Gastroenterology (1995) [Pubmed]
  6. Direct channeling of retinoic acid between cellular retinoic acid-binding protein II and retinoic acid receptor sensitizes mammary carcinoma cells to retinoic acid-induced growth arrest. Budhu, A.S., Noy, N. Mol. Cell. Biol. (2002) [Pubmed]
  7. Targeted disruption of retinoic acid receptor alpha (RAR alpha) and RAR gamma results in receptor-specific alterations in retinoic acid-mediated differentiation and retinoic acid metabolism. Boylan, J.F., Lufkin, T., Achkar, C.C., Taneja, R., Chambon, P., Gudas, L.J. Mol. Cell. Biol. (1995) [Pubmed]
  8. Differential distribution patterns of CRABP I and CRABP II transcripts during mouse embryogenesis. Ruberte, E., Friederich, V., Morriss-Kay, G., Chambon, P. Development (1992) [Pubmed]
  9. Mouse conceptuses have a limited capacity to elevate the mRNA level of cellular retinoid binding proteins in response to teratogenic doses of retinoic acid. Harnish, D.C., Soprano, K.J., Soprano, D.R. Teratology (1992) [Pubmed]
  10. Postaxial polydactyly in forelimbs of CRABP-II mutant mice. Fawcett, D., Pasceri, P., Fraser, R., Colbert, M., Rossant, J., Giguère, V. Development (1995) [Pubmed]
  11. Spatio-temporal distribution of cellular retinoid binding protein gene transcripts in the developing and the adult cochlea. Morphological and functional consequences in CRABP- and CRBPI-null mutant mice. Romand, R., Sapin, V., Ghyselinck, N.B., Avan, P., Le Calvez, S., Dollé, P., Chambon, P., Mark, M. Eur. J. Neurosci. (2000) [Pubmed]
  12. Retinoic acid receptors and cellular retinoid binding proteins. III. Their differential transcript distribution during mouse nervous system development. Ruberte, E., Friederich, V., Chambon, P., Morriss-Kay, G. Development (1993) [Pubmed]
  13. Mice deficient in cellular retinoic acid binding protein II (CRABPII) or in both CRABPI and CRABPII are essentially normal. Lampron, C., Rochette-Egly, C., Gorry, P., Dollé, P., Mark, M., Lufkin, T., LeMeur, M., Chambon, P. Development (1995) [Pubmed]
  14. Antisense oligonucleotides to CRABP I and II alter the expression of TGF-beta 3, RAR-beta, and tenascin in primary cultures of embryonic palate cells. Nugent, P., Greene, R.M. In Vitro Cell. Dev. Biol. Anim. (1995) [Pubmed]
  15. Retinoic acid induction of human cellular retinoic acid-binding protein-II gene transcription is mediated by retinoic acid receptor-retinoid X receptor heterodimers bound to one far upstream retinoic acid-responsive element with 5-base pair spacing. Aström, A., Pettersson, U., Chambon, P., Voorhees, J.J. J. Biol. Chem. (1994) [Pubmed]
  16. Replacement of proline with valine does not remove an apparent proline isomerization-dependent folding event in CRABP I. Burns-Hamuro, L.L., Dalessio, P.M., Ropson, I.J. Protein Sci. (2004) [Pubmed]
  17. Interactions between the transforming growth factor beta (TGF beta) and retinoic acid signal transduction pathways in murine embryonic palatal cells. Nugent, P., Greene, R.M. Differentiation (1994) [Pubmed]
  18. Correlations of RAR isoforms and cellular retinoid-binding proteins mRNA levels with retinoid-induced teratogenesis. Soprano, D.R., Harnish, D.C., Soprano, K.J., Kochhar, D.M., Jiang, H. J. Nutr. (1993) [Pubmed]
  19. Arginine 132 of cellular retinoic acid-binding protein (type II) is important for binding of retinoic acid. Chen, L.X., Zhang, Z.P., Scafonas, A., Cavalli, R.C., Gabriel, J.L., Soprano, K.J., Soprano, D.R. J. Biol. Chem. (1995) [Pubmed]
  20. Localization of CRABP-I and CRABP-II mRNA in the early mouse embryo by whole-mount in situ hybridization: implications for teratogenesis and neural development. Lyn, S., Giguère, V. Dev. Dyn. (1994) [Pubmed]
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