Structure and organization of the human transglutaminase 1 gene

Ingyu Kim, O. W. McBride, M. Wang, S. Y. Kim, W. W. Idler, P. M. Steinert

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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.

Original languageEnglish
Pages (from-to)7710-7717
Number of pages8
JournalJournal of Biological Chemistry
Volume267
Issue number11
StatePublished - 1 Jan 1992

Fingerprint

Genes
Transglutaminases
Introns
Human Genome
Southern Blotting
Polymorphism
Dinucleotide Repeats
transglutaminase 1
Genetic Linkage
Gene Duplication
Initiator Codon
Hybrid Cells
Haploidy
Enzymes
Biotin
Sequence Homology
Base Pairing
Restriction Fragment Length Polymorphisms
Population
In Situ Hybridization

Cite this

Kim, I., McBride, O. W., Wang, M., Kim, S. Y., Idler, W. W., & Steinert, P. M. (1992). Structure and organization of the human transglutaminase 1 gene. Journal of Biological Chemistry, 267(11), 7710-7717.
Kim, Ingyu ; McBride, O. W. ; Wang, M. ; Kim, S. Y. ; Idler, W. W. ; Steinert, P. M. / Structure and organization of the human transglutaminase 1 gene. In: Journal of Biological Chemistry. 1992 ; Vol. 267, No. 11. pp. 7710-7717.
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Kim, I, McBride, OW, Wang, M, Kim, SY, Idler, WW & Steinert, PM 1992, 'Structure and organization of the human transglutaminase 1 gene', Journal of Biological Chemistry, vol. 267, no. 11, pp. 7710-7717.

Structure and organization of the human transglutaminase 1 gene. / Kim, Ingyu; McBride, O. W.; Wang, M.; Kim, S. Y.; Idler, W. W.; Steinert, P. M.

In: Journal of Biological Chemistry, Vol. 267, No. 11, 01.01.1992, p. 7710-7717.

Research output: Contribution to journalArticleResearchpeer-review

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Kim I, McBride OW, Wang M, Kim SY, Idler WW, Steinert PM. Structure and organization of the human transglutaminase 1 gene. Journal of Biological Chemistry. 1992 Jan 1;267(11):7710-7717.