Active Site

Transglutaminase, active site (IPR013808)

Short name: Transglutaminase_AS


Transglutaminases (EC (TGase) [PMID: 1974250, PMID: 1683845] are calcium-dependent enzymes that catalyze the cross-linking of proteins by promoting the formation of isopeptide bonds between the gamma-carboxyl group of a glutamine in one polypeptide chain and the epsilon-amino group of a lysine in a second polypeptide chain. TGases also catalyze the conjugation of polyamines to proteins.

The best known transglutaminase is blood coagulation factor XIII, a plasma tetrameric protein composed of two catalytic A subunits and two non-catalytic B subunits. Factor XIII is responsible for cross-linking fibrin chains, thus stabilizing the fibrin clot.

Other forms of transglutaminases are widely distributed in various organs, tissues and body fluids. Sequence data is available for the following forms of TGase:

  • Transglutaminase K (Tgase K), a membrane-bound enzyme found in mammalian epidermis and important for the formation of the cornified cell envelope (gene TGM1).
  • Tissue transglutaminase (TGase C), a monomeric ubiquitous enzyme located in the cytoplasm (gene TGM2).
  • Transglutaminase 3, responsible for the later stages of cell envelope formation in the epidermis and the hair follicle (gene TGM3).
  • Transglutaminase 4 (gene TGM4).
  • Transglutaminase X (Tgase X) (gene TGM5).
  • Transglutaminase Z (Tgase Z) (gene TGM7).

A conserved cysteine is known to be involved in the catalytic mechanism of TGases.

The erythrocyte membrane band 4.2 protein, which probably plays an important role in regulating the shape of erythrocytes and their mechanical properties, is evolutionary related to TGases. However the active site cysteine is substituted by an alanine and the 4.2 protein does not show TGase activity.

GO terms

Biological Process

GO:0018149 peptide cross-linking

Molecular Function

No terms assigned in this category.

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE patterns