TGM5
TGM5 encodes transglutaminase 5, a Ca2+-dependent enzyme that catalyzes protein cross-linking through intermolecular isopeptide bonds[1]. Mechanistically, TGase 5 cross-links loricrin, involucrin, and small proline-rich proteins during keratinocyte differentiation, supporting cornified envelope biology[2]. In disease models, TGM5 mutations abolish or reduce epidermal transglutaminase 5 activity and cause acral peeling skin syndrome[3][4]. Compared with related epidermal transglutaminases, TGase 5 is differently regulated during differentiation and includes active and low-activity splice isoforms[2]. For experimental applications, GTP and ATP inhibit TGase 5 cross-linking activity in vitro, whereas Ca2+ reverses this inhibition[1].
References:
- [1]. Candi E, et al. Transglutaminase 5 is regulated by guanine-adenine nucleotides. Biochem J. 2004 Jul 1;381(Pt 1):313-9. [Content Brief]
- [2]. Candi E, et al. Transglutaminase 5 cross-links loricrin, involucrin, and small proline-rich proteins in vitro. J Biol Chem. 2001 Sep 14;276(37):35014-23. [Content Brief]
- [3]. Cassidy AJ, et al. A homozygous missense mutation in TGM5 abolishes epidermal transglutaminase 5 activity and causes acral peeling skin syndrome. Am J Hum Genet. 2005 Dec;77(6):909-17. [Content Brief]
- [4]. Pigors M, et al. TGM5 mutations impact epidermal differentiation in acral peeling skin syndrome. J Invest Dermatol. 2012 Oct;132(10):2422-2429. [Content Brief]
