Alternative titles; symbols
HGNC Approved Gene Symbol: FABP3
Cytogenetic location: 1p35.2 Genomic coordinates (GRCh38): 1:31,359,588-31,373,076 (from NCBI)
Fatty acid metabolism in mammalian cells depends on a flux of fatty acids, between the plasma membrane and mitochondria or peroxisomes for beta-oxidation, and between other cellular organelles for lipid synthesis. At least 3 different fatty acid-binding proteins (FABPs) play a role as transport vehicles of these hydrophobic compounds throughout the cytoplasm. Different FABPs have been demonstrated in the liver, heart, intestine, skeletal muscle, and brain. Peeters et al. (1991, 1991) determined that a cDNA clone for human skeletal muscle FABP had an open reading frame of 399 nucleotides coding for a protein of 133 amino acid residues with a calculated molecular mass of 14,858 Da. Peptide sequence analysis of human skeletal muscle and heart FABP, after carbamoyl methylation and lysyl endopeptidase digestion followed by automatic Edman degradation, showed that the 2 proteins are identical. No evidence was found for isoproteins in muscle.
The deduced and experimentally determined amino acid sequence of human muscle FABP (Peeters et al., 1991) was reported to be identical to that of human heart FABP as determined by Offner et al. (1988) and Borchers et al. (1990).
Based on the complete cDNA in protein homologies between mouse MDGI and the FABP3 genes, Phelan et al. (1996) assumed that these are the same gene. Independent reports of mapping to the same chromosome region supports their identity.
Phelan et al. (1996) demonstrated that the MDGI/FABP3 gene covers approximately 8 kb of genomic DNA and is divided into 4 exons.
Human FABP3
Peeters et al. (1991) determined the chromosomal localization of the human muscle FABP gene to be 1pter-q31 by the study of human/rodent somatic cell hybrid lines.
Troxler et al. (1993) found, using both a cDNA and a genomic fragment, that the human heart FABP gene (FABP3) mapped to 1p33-p32 by fluorescence in situ hybridization.
Huynh et al. (1995) mapped the MDGI gene to 1p35-p32, a common region of loss in sporadic breast cancer.
Mouse Fabph1
By Southern analysis of mouse-hamster somatic cell hybrids, Heuckeroth et al. (1987) mapped the mouse heart FABP gene to 3 chromosomes, 4, 8, and either 10 or 15. The authors considered that 2 of these loci may represent pseudogenes and/or actively transcribed genes specifying proteins that share a very high degree of sequence homology to heart FABP.
Treuner et al. (1994) placed the mouse Fabph1 gene on chromosome 4 by interspecies crosses. A pseudogene was assigned to mouse chromosome 10 and another one to mouse chromosome 8.
Mammary-derived growth inhibitor (MDGI) was first identified as a growth inhibitor in lactating bovine mammary gland and was shown to play a role in mammary gland differentiation (Bohmer et al. (1987)). Yang et al. (1994) showed that transfection of an MDGI expression construct into breast cancer cell lines reduced proliferation and promoted cellular differentiation; Huynh et al. (1995) showed that it reduced tumor formation in nude mice.
In an attempt to identify possibly inactivating mutations in the MDGI gene in human breast cancer, Phelan et al. (1996) sequenced all 4 exons and their surrounding splice junctions in 30 sporadic breast tumors. Ten of these tumors showed loss of heterozygosity (LOH) in the 1p35-p32 region, with 5 tumors showing LOH in the subregion containing the MDGI gene. They found no mutations in their analysis. Despite experimental evidence that MDGI has tumor suppressor activity, the data suggested to Phelan et al. (1996) that mutations in the coding region are uncommon in human breast tumorigenesis.
Bohmer, F. D., Kraft, R., Otto, A., Wernstedt, C., Hellman, U., Kurtz, A., Muller, T., Rohde, K., Etzold, G., Lehmann, W., Langen, P., Heldin, C., Grosse, R. Identification of a polypeptide growth inhibitor from bovine mammary gland: sequence homology to fatty acid- and retinoid-binding proteins. J. Biol. Chem. 262: 15137-15143, 1987. [PubMed: 3667628]
Borchers, T., Hojrup, P., Nielsen, S. U., Roepstorff, P., Spener, F., Knudsen, J. Revision of the amino acid sequence of human heart fatty acid binding protein. Molec. Cell. Biochem. 98: 127-133, 1990. [PubMed: 2266954] [Full Text: https://doi.org/10.1007/BF00231376]
Heuckeroth, R. O., Birkenmeier, E. H., Levin, M. S., Gordon, J. I. Analysis of the tissue-specific expression, developmental regulation, and linkage relationships of a rodent gene encoding heart fatty acid binding protein. J. Biol. Chem. 262: 9709-9717, 1987. [PubMed: 3036869]
Huynh, H. T., Larsson, C., Narod, S., Pollak, M. Tumor suppressor activity of the gene encoding mammary-derived growth inhibitor. Cancer Res. 55: 2225-2231, 1995. [PubMed: 7757968]
Offner, G. D., Brecher, P., Sawlivich, W. B., Costello, C. E., Troxler, R. F. Characterization and amino acid sequence of a fatty acid-binding protein from human heart. Biochem. J. 252: 191-198, 1988. [PubMed: 3421901] [Full Text: https://doi.org/10.1042/bj2520191]
Peeters, R., Veerkamp, J., Kanda, T., Ono, T., Geurts van Kessel, A. The gene encoding skeletal muscle fatty acid binding protein resides on human chromosome 1, region pter-q31. (Abstract) Cytogenet. Cell Genet. 58: 1861, 1991.
Peeters, R. A., Veerkamp, J. H., Geurts van Kessel, A., Kanda, T., Ono, T. Cloning of the cDNA encoding human skeletal-muscle fatty-acid-binding protein, its peptide sequence and chromosomal localization. Biochem. J. 276: 203-207, 1991. [PubMed: 1710107] [Full Text: https://doi.org/10.1042/bj2760203]
Phelan, C. M., Larsson, C., Baird, S., Futreal, P. A., Ruttledge, M. H., Morgan, K., Tonin, P., Hung, H., Korneluk, R. G., Pollak, M. N., Narod, S. A. The human mammary-derived growth inhibitor (MDGI) gene: genomic structure and mutation analysis in human breast tumors. Genomics 34: 63-68, 1996. Note: Erratum: Genomics 36: 377 only, 1996. [PubMed: 8661024] [Full Text: https://doi.org/10.1006/geno.1996.0241]
Treuner, M., Kozak, C. A., Gallahan, D., Grosse, R., Muller, T. Cloning and characterization of the mouse gene encoding mammary-derived growth inhibitor/heart-fatty acid-binding protein. Gene 147: 237-242, 1994. [PubMed: 7926807] [Full Text: https://doi.org/10.1016/0378-1119(94)90073-6]
Troxler, R. F., Offner, G. D., Jiang, J.-W., Wu, B.-L., Skare, J. C., Milunsky, A., Wyandt, H. E. Localization of the gene for human heart fatty acid binding protein to chromosome 1p32-1p33. Hum. Genet. 92: 563-566, 1993. [PubMed: 8262516] [Full Text: https://doi.org/10.1007/BF00420939]
Yang, Y., Spitzer, E., Kenney, N., Zschiesche, W., Li, M., Kromminga, A., Muller, T., Spener, F., Lezius, A., Veerkamp, J. H., Smith, G., Salomon, D., Grosse, R. Members of the fatty acid binding protein family are differentiation factors for the mammary gland. J. Cell Biol. 124: 1097-1109, 1994.