{PDOC00440}
{PS00477; ALPHA_2_MACROGLOBULIN}
{BEGIN}
************************************************************
* Alpha-2-macroglobulin family thiolester region signature *
************************************************************

The proteinase-binding alpha-macroglobulins (A2M) [1] are  large glycoproteins
found in the plasma of vertebrates, in  the  hemolymph  of  some invertebrates
and in  reptilian and avian egg white.  A2M-like  proteins are able to inhibit
all four  classes  of  proteinases  by  a  'trapping' mechanism.  They have  a
peptide  stretch,  called  the 'bait region', which contains specific cleavage
sites for different proteinases.  When a proteinase cleaves the bait region, a
conformational change is induced in the protein, thus trapping the proteinase.
The entrapped enzyme  remains active  against low molecular weight substrates,
whilst its  activity    toward   larger  substrates is greatly reduced, due to
steric hindrance.   Following cleavage in the bait region, a thiol ester bond,
formed between the side chains of a  cysteine and  a glutamine, is cleaved and
mediates the covalent binding of the A2M-like protein to the proteinase.

The proteins which are known to belong to this family are:

 - Alpha-2-macroglobulin from mammals, lobster, and crayfish.
 - Alpha-1-inhibitor III from rat.
 - Pregnancy zone protein (PZP) from human.
 - Ovostatin from birds.

 - Complement components C3,  C4  and  C5.   These  proteins  do  not  inhibit
   proteinases.  C3 plays a  central role in the  activation of both classical
   and alternative complement pathways.  After C3 is  cleaved to  form C3b, it
   can bind covalently,  via its  reactive  thiol ester bond,  to cell surface
   carbohydrates  or immune aggregates.  Similarily C4, once activated to C4b,
   can bind to various molecules.

As a  signature  pattern  for  this  family  of proteins, we have selected the
region containing the two residues involved in the thiol ester bond.

-Consensus pattern: [PG]-x-[GS]-C-[GA]-E-[EQ]-x-[LIVM]
                    [C and E/Q are involved in the thiol ester bond]
-Sequences known to belong to this class detected by the pattern: ALL,  except
 for complement component C5  which  has  lost  the residues implicated in the
 thiol ester bond.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Expert(s) to contact by email:
           van Leuven F.; fred@blekul13.bitnet

-Last update: May 1991 / First entry.

[ 1] Sottrup-Jensen L.
     "Alpha-macroglobulins: structure, shape, and mechanism of proteinase
     complex formation."
     J. Biol. Chem. 264:11539-11542(1989).
     PubMed=2473064;

--------------------------------------------------------------------------------
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}