Abstract
Membrane-associated transglutaminases (TGase1) have recently been found to be common in mammalian cells, but it is not clear whether these derive from the same or different genes. In order to determine the complexity of this system, we have isolated and characterized the human gene (TGM1). The gene of 14,133 base pairs was found to contain 15 exons spliced by 14 introns. Interestingly, the positions of these introns have been conserved in comparison with the genes of two other transglutaminase-like activities described in the literature, but the TGM1 gene is by far the smallest characterized to date because its introns are relatively smaller. On the other hand, the TGase1 enzyme is the largest known transglutaminase (about 90 kDa), apparently because its gene acquired tracts that encode additional sequences on its amino and carboxyl termini that confer its unique properties. Southern blot analyses of total human genomic DNA cut with several restriction enzymes reveal only one band. Use of human-rodent cell hybrid panels and chromosomal in situ hybridization with biotin-labeled probes revealed that the human TGM1 gene maps to chromosome position 14q11.2-13. Such data suggest there is a single gene copy per haploid human genome. Comparisons of sequence identities and homologies indicate that the transglutaminase family of genes arose by duplications and subsequent divergent evolution from a common ancestor but later became scattered in the human genome. Although our present Southern blot and chromosomal localization studies revealed no restriction fragment length polymorphisms, comparisons of published sequences and our genomic clone indicate there are two sequence variants for TGase1 within the human population. The rare smaller variant contains a two-nucleotide deletion near the 5'-end, uses an alternate initiation codon, and differs from the common larger variant only in the first 15 amino acids. Furthermore, the DNA sequences of intron 14 possess several tracts of dinucleotide repeats that by polymerase chain reaction analysis show wide size polymorphism within the human population. Accordingly, this gene system constitutes a useful polymorphic marker for genetic linkage analyses.
Highlights
Transglutaminases (TGases)’ catalyze the formation of a have recently been found to cboemmon in mammalian bond between the eNH2 group of a lysine and the y-amide cells, but it is not clear whether these derive from thegroup of a glutamine residue, thereby forming ainsodipeptide sameordifferent genes
The catalytic a subunit of largest known transglutaminase, ap- blood-clotting factor XI11 is a soluble protein of about 75 kDa parently because its gene acquired tracts thaetncode [5,6,7]; a protein termed band4.2 is a major constituent of the additional sequences on its amino and carboxyl terminsiubplasma membrane architecture of red cells and probably that confer its unique properties
Our present Southern blot and chro- studies havedescribed both soluble and particulate-associated mosomal localization studies revealed no restriction TGases in different stratified squamous epithelial and nonfragment lengthpolymorphisms, comparisons of pub- epithelial cells and tissues that vary in properties from the lished sequences and ourgenomic cloneindicate there well characterized sources [19,20,21,22], but it has not yet been a r e two sequence variants for TGasel within the hu- proven whether these are different gene products from the man population
Summary
Vol 267, No 11, Issue of April 15, pp. 7710-7717,1992 Printed in U.S.A. In-Gyu Kim, 0.Wesley McBrideS, Mary WangS, Soo-You1Kim, William W. The literature, but the TGMl igsebnyefar thesmallest To date, a family of five human TGase-like proteins, which characterized to datbeecause its intronsare relatively are clearly the productsof different genes, have been described smaller. The abbreviations used are: TGase, transglutaminase; CE, corerase chain reaction analysis show wide size polymor-nified cell envelope; bp, base pairs; kbp, kilobase pairs; PCR, polymphism within the humanpopulation. This erase chain reaction; FITC, fluorescein isothiocyanate; g, genomic; gene system constitutes a useful polymorphic marker CEPH, Centre #Etude du Polymorphisme Humain.
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