{PDOC00473}
{PS00547; TRANSGLUTAMINASES}
{BEGIN}
*********************************
* 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  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.

-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 known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: December 2004 / Pattern and text revised.

[ 1] Ichinose A., Bottenus R.E., Davie E.W.
     "Structure of transglutaminases."
     J. Biol. Chem. 265:13411-13414(1990).
     PubMed=1974250
[ 2] Greenberg C.S., Birckbichler P.J., Rice R.H.
     "Transglutaminases: multifunctional cross-linking enzymes that
     stabilize tissues."
     FASEB J. 5:3071-3077(1991).
     PubMed=1683845

--------------------------------------------------------------------------------
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and
distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives
(CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html
--------------------------------------------------------------------------------

{END}