Evolution of transglutaminase genes: identification of a transglutaminase gene cluster on human chromosome 15q15. Structure of the gene encoding transglutaminase X and a novel gene family member, transglutaminase Z

• Published in: The Journal of biological chemistry 2001-08, Vol.276 (35), p.33066-33078
• Main Authors: Grenard, P, Bates, M K, Aeschlimann, D
• Format: Article
• Language: English
• Subjects: 5' Untranslated Regions - genetics; Alternative Splicing; Amino Acid Sequence; Animals; Base Sequence; Blood Proteins - genetics; Blotting, Northern; chromosome 15; chromosome 2; chromosome 20; Chromosome Mapping; Chromosomes, Human, Pair 15; Cytoskeletal Proteins; EPB42 gene; Evolution, Molecular; Female; Fetus; Genetic Markers; Genetic Variation; Genomic Library; Humans; Introns; Invertebrates; Isoenzymes - genetics; Male; Membrane Proteins; Molecular Sequence Data; Molecular Weight; Multigene Family; Phylogeny; Polymerase Chain Reaction; Protein Structure, Secondary; Protein Subunits; TGM6 gene; TGM7 gene; Transcription, Genetic; Transglutaminases - chemistry; Transglutaminases - genetics; Vertebrates
• ISSN: 0021-9258
• DOI: 10.1074/jbc.M102553200

We isolated and characterized the gene encoding human transglutaminase (TG)(X) (TGM5) and mapped it to the 15q15.2 region of chromosome 15 by fluorescence in situ hybridization. The gene consists of 13 exons separated by 12 introns and spans about 35 kilobases. Further sequence analysis and mapping showed that this locus contained three transglutaminase genes arranged in tandem: EPB42 (band 4.2 protein), TGM5, and a novel gene (TGM7). A full-length cDNA for the novel transglutaminase (TG(Z)) was obtained by anchored polymerase chain reaction. The deduced amino acid sequence encoded a protein with 710 amino acids and a molecular mass of 80 kDa. Northern blotting showed that the three genes are differentially expressed in human tissues. Band 4.2 protein expression was associated with hematopoiesis, whereas TG(X) and TG(Z) showed widespread expression in different tissues. Interestingly, the chromosomal segment containing the human TGM5, TGM7, and EPB42 genes and the segment containing the genes encoding TG(C),TG(E), and another novel gene (TGM6) on chromosome 20q11 are in mouse all found on distal chromosome 2 as determined by radiation hybrid mapping. This finding suggests that in evolution these six genes arose from local duplication of a single gene and subsequent redistribution to two distinct chromosomes in the human genome.