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	PROSITE documentation PDOC00473

Transglutaminases active site

Transglutaminases (EC 2.3.2.13) (TGase) [1,2] are calcium-dependent enzymes that catalyze the cross-linking of proteins by promoting the formation of isopeptide bonds between the γ-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.

Last update:

December 2004 / Pattern and text revised.

PROSITE method (with tools and information) covered by this documentation:

TRANSGLUTAMINASES, PS00547; Transglutaminases active site  (PATTERN)

• Consensus pattern:
  [GT]-Q-[CA]-W-V-x-[SA]-[GAS]-[IVT]-x(2)-T-x-[LMSC]-R-[CSAG]-[LV]-G
  The first C is the active site residue
• Sequences in UniProtKB/Swiss-Prot known to belong to this class: 31
  • detected by PS00547: 30 (true positives)
  • undetected by PS00547: 1 (0 false negative and 1 'partial')
• Other sequence(s) in UniProtKB/Swiss-Prot detected by PS00547:
  NONE.
• Retrieve an alignment of UniProtKB/Swiss-Prot true positive hits:
  Clustal format, color, condensed view  /  Clustal format, color  /  Clustal format, plain text  /  Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic distribution of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS00547
• Retrieve a list of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS00547
• Scan UniProtKB (Swiss-Prot and/or TrEMBL) entries against PS00547
• View ligand binding statistics of PS00547
• Matching PDB structures: 1EVU 1EX0 1F13 1FIE ... [ALL]

1	Authors	Ichinose A., Bottenus R.E., Davie E.W.
	Title	Structure of transglutaminases.
	Source	J. Biol. Chem. 265:13411-13414(1990).
	PubMed ID	1974250

2	Authors	Greenberg C.S., Birckbichler P.J., Rice R.H.
	Title	Transglutaminases: multifunctional cross-linking enzymes that stabilize tissues.
	Source	FASEB J. 5:3071-3077(1991).
	PubMed ID	1683845

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