The human and rodent intestinal fatty acid binding protein genes. A comparative analysis of their structure, expression, and linkage relationships

• Published in: The Journal of biological chemistry Vol. 262; no. 33; pp. 16060 - 16071
• Main Authors: Sweetser, D A, Birkenmeier, E H, Klisak, I J, Zollman, S, Sparkes, R S, Mohandas, T, Lusis, A J, Gordon, J I
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 25.11.1987; American Society for Biochemistry and Molecular Biology
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Biological and medical sciences; Biotechnology; Carrier Proteins - genetics; Chromosome Mapping; Chromosomes, Human, Pair 2; Chromosomes, Human, Pair 4; DNA Restriction Enzymes; Fatty Acid-Binding Protein 7; Fatty Acid-Binding Proteins; Fundamental and applied biological sciences. Psychology; Gene expression; Genes; Genetic engineering; Genetic Linkage; Genetic technics; Humans; Intestine, Small - metabolism; Liver - metabolism; Methods. Procedures. Technologies; Mice; Molecular and cellular biology; Molecular cloning; Molecular genetics; Molecular Sequence Data; Neoplasm Proteins; Nerve Tissue Proteins; Species Specificity; Transcription, Genetic; Tumor Suppressor Proteins; Human; Cell culture; Hybrid cell; Gut; Rodentia; Chromosome; Homology; Primary structure; Gene expression; Fatty acids; Binding protein; Vertebrata; Mammalia; Gene; Localization; Southern blotting; Intestinal fatty acid binding protein; Comparative study
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)47696-X

Intestinal fatty acid binding protein (I-FABP) is believed to participate in the uptake, intracellular metabolism, and/or transport of long chain fatty acids within enterocytes. The 15.1-kDA rodent proteins is a member of a family of low Mr cytoplasmic proteins that have evolved to bind different ligands. We have now determined the nucleotide sequence of the gene encoding human I-FABP and defined the primary structure of its protein product. The human I-FABP gene spans 3382 nucleotides and contains 4 exons (103 or 128, 173, 108, and 312 base pairs). interrupted by 3 introns (1194, 1023, and 444 base pairs). The 132-residue rat and human I-FABPs have 82% amino acid sequence identity. Blot hybridization studies of RNAs prepared from a variety of adult rhesus monkey tissues as well as human intestine and liver indicate that I-FABP mRNA is confined to the intestine. I-FABP mRNA was not detectable in a number of cultured human enterocyte-like cell lines, suggesting it may be a sensitive marker for differentiated, villus-associated, small intestinal lining cells. Given the similar patterns of tissue-specific expression exhibited by the rat and human genes, we compared their 5' nontranscribed regions. Optimal alignments of the two sequences disclosed 64% identity among the 260 nucleotides immediately 5' to the start site of transcription. Matrix plots revealed a 14-nucleotide long repeated sequence (5'-TGAACTTTGAACTT-3') in the 5' nontranscribed region of both genes as well as in a comparable region of another family member that is expressed in enterocytes, cellular retinol binding protein II. The linkage relationships between I-FABP and the homologous liver FABP (L-FABP) gene were defined in mice and humans. The mouse genes were mapped using restriction fragment length polymorphisms and recombinant inbred strains. The I-FABP gene is located on mouse chromosome 3 between the amylase 1,2 (Amy 1,2) and alcohol dehydrogenase 3 (Adh-3) loci while the L-FABP gene is on mouse chromosome 6 within 3 centimorgans of the lymphocyte antigen-2 (Ly-2) locus. Mouse L-FABP may be identical to the major liver protein-1 (Lvp-1) which is encoded by a gene situated within a centimorgan of Ly-2. Human gene mapping studies were carried out using a panel of mouse-human somatic cell hybrid clones as well as in situ hybridization to metaphase chromosomes.