Alternative titles; symbols
HGNC Approved Gene Symbol: CRABP1
Cytogenetic location: 15q25.1 Genomic coordinates (GRCh38): 15:78,340,353-78,348,225 (from NCBI)
Cellular retinoic acid-binding protein is assumed to play an important role in retinoic acid-mediated differentiation and proliferation processes. The gene is strongly conserved in evolution. Mouse and bovine CRABP, for example, share 90% homology at the nucleotide level and 100% homology at the amino acid level. Vaessen et al. (1989) partially cloned and sequenced the human gene.
The physiologic forms of vitamin A are water insoluble, and this property is circumvented by a number of specific binding or carrier proteins for these compounds. Six such proteins have been well characterized: serum retinol-binding protein (180250); cellular retinol-binding protein (CRBP; 180260); cellular retinoic acid-binding protein; cellular retinol-binding protein, unique to visual tissue; interphotoreceptor retinol-binding protein, also unique to visual tissue; and cellular retinol-binding protein, type II (CRBP2; 180280), present in small intestine. Ong (1987) discussed the likely function of CRABP in epithelial tissues.
The fusion proteins PLZF (176797)/RARA (180240) and RARA/PLZF are formed by the t(11;17)(q23;q21) translocation associated with retinoic acid-resistant acute promyelocytic leukemia. Guidez et al. (2007) identified CRABP1 as a target of both PLZF and the RARA/PLZF fusion protein. PLZF repressed CRABP1 through propagation of chromatin condensation from a remote intronic binding element, culminating in silencing of the CRABP1 promoter. Although the canonical PLZF/RARA oncoprotein had no effect on PLZF-mediated repression, the reciprocal translocation product, RARA/PLZF, bound to this remote binding site, recruited p300 (EP300; 602700), and induced promoter hypomethylation and CRABP1 upregulation. Similarly, retinoic acid-resistant murine blasts that expressed both fusion proteins expressed much higher levels of Crabp1 than retinoic acid-sensitive cells expressing Plzf/Rara alone. RARA/PLZF conferred retinoic acid resistance to a retinoid-sensitive acute myeloid leukemia cell line in a CRABP1-dependent fashion. Guidez et al. (2007) concluded that upregulation of CRABP1 by RARA/PLZF contributes to retinoid resistance in leukemia.
Using hamster-human somatic cell hybrids, Vaessen et al. (1989) assigned the CRABP gene to chromosome 15. Geurts van Kessel et al. (1991) assigned a human genomic fragment comprising the CRABP gene to human chromosome 15 by analysis of a panel of somatic cell hybrids. In cells carrying the 15;17 translocation of acute promyelocytic leukemia (APL), they demonstrated that the CRABP gene was transposed; however, they observed no gross CRABP rearrangement in a series of APL patients. The observations indicate that CRABP maps to the region 15q22-qter. The cellular retinol-binding protein maps to chromosome 3, and the interstitial retinol-binding protein (IRBP; 180290) maps to chromosome 10. In the mouse, CRABP and 2 cellular retinol-binding proteins, CRBP and CRBP2, are all located on chromosome 9. The murine equivalent of CRABP2 (180231) is located on mouse chromosome 2 (MacGregor et al., 1992). By fluorescence in situ hybridization, Flagiello et al. (1997) narrowed the assignment of CRABP1 to 15q24.
Flagiello, D., Apiou, F., Gibaud, A., Poupon, M. F., Dutirllaux, B., Malfoy, B. Assignment of the genes for cellular retinoic acid binding protein 1 (CRABP1) and 2 (CRABP2) to human chromosome band 15q24 and 1q21.3, respectively, by in situ hybridization. Cytogenet. Cell Genet. 76: 17-18, 1997. [PubMed: 9154115] [Full Text: https://doi.org/10.1159/000134502]
Geurts van Kessel, A., de Leeuw, H., Dekker, E. J., Rijks, L., Spurr, N., Ledbetter, D., Kootwijk, E., Vaessen, M. J. Localization of the cellular retinoic acid binding protein (CRABP) gene relative to the acute promyelocytic leukemia-associated breakpoint on human chromosome 15. Hum. Genet. 87: 201-204, 1991. [PubMed: 1648546] [Full Text: https://doi.org/10.1007/BF00204182]
Guidez, F., Parks, S., Wong, H., Jovanovic, J. V., Mays, A., Gilkes, A. F., Mills, K. I., Guillemin, M.-C., Hobbs, R. M., Pandolfi, P. P., de The, H., Solomon, E., Grimwade, D. RAR-alpha-PLZF overcomes PLZF-mediated repression of CRABPI, contributing to retinoid resistance in t(11;17) acute promyelocytic leukemia. Proc. Nat. Acad. Sci. 104: 18694-18699, 2007. [PubMed: 18000064] [Full Text: https://doi.org/10.1073/pnas.0704433104]
MacGregor, T. M., Copeland, N. G., Jenkins, N. A., Giguere, V. The murine gene for cellular retinoic acid-binding protein type II: genomic organization, chromosomal localization, and post-transcriptional regulation by retinoic acid. J. Biol. Chem. 267: 7777-7783, 1992. [PubMed: 1313808]
Ong, D. E. Cellular retinoid-binding proteins. Arch. Derm. 123: 1693-1695, 1987. [PubMed: 2825608]
Vaessen, M. J., Rijks, L., Dekker, E. J., Kootwijk, E., Bootsma, D., Westerveld, A., Geurts van Kessel, A. H. M. Localization of the human cellular retinoic acid-binding protein (CRABP) on chromosome 15. (Abstract) Cytogenet. Cell Genet. 51: 1094 only, 1989.