{PDOC00109}
{PS00118; PA2_HIS}
{PS00119; PA2_ASP}
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* Phospholipase A2 active sites signatures *
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Phospholipase A2 (EC 3.1.1.4) (PA2) [1,2] is  an  enzyme  which releases fatty
acids  from  the  second  carbon group of glycerol.  PA2's are small and rigid
proteins of  120  amino-acid residues that have four to seven disulfide bonds.
PA2 binds a calcium ion which is required for activity. The side chains of two
conserved residues,  a  histidine  and  an  aspartic  acid,  participate  in a
'catalytic network'.

Many PA2's  have been sequenced from snakes, lizards, bees and mammals. In the
latter, there are at least four forms: pancreatic, membrane-associated as well
as two less characterized forms. The venom of most  snakes  contains  multiple
forms of   PA2.  Some  of  them  are  presynaptic  neurotoxins  which  inhibit
neuromuscular transmission  by  blocking  acetylcholine release from the nerve
termini.

We derived  two  different signature patterns for PA2's. The first is centered
on the  active  site  histidine  and  contains  three  cysteines  involved  in
disulfide bonds.  The  second is centered on the active site aspartic acid and
also contains three cysteines involved in disulfide bonds.

-Consensus pattern: C-C-{P}-x-H-{LGY}-x-C
                    [H is the active site residue]
-Sequences known to belong to this class detected by the pattern: ALL    known
 functional PA2's.     However, this pattern will not detect some snake toxins
 homologous with PA2 but which have lost their catalytic  activity  as well as
 otoconin-22, a  Xenopus  protein  from  the aragonitic otoconia which is also
 unlikely to be enzymatically active.
-Other sequence(s) detected in Swiss-Prot: 15.

-Consensus pattern: [LIVMA]-C-{LIVMFYWPCST}-C-D-{GS}-{G}-{N}-x-{QS}-C
                    [D is the active site residue]
-Sequences known to belong to this class detected by the pattern: the majority
 of functional  and  non-functional PA2's.  Undetected sequences are  bee PA2,
 gila monster PA2's, PA2 PL-X from habu and PA2 PA-5 from mulga.
-Other sequence(s) detected in Swiss-Prot: 13.
-Last update: April 2006 / Pattern revised.

[ 1] Davidson F.F., Dennis E.A.
     "Evolutionary relationships and implications for the regulation of
     phospholipase A2 from snake venom to human secreted forms."
     J. Mol. Evol. 31:228-238(1990).
     PubMed=2120459
[ 2] Gomez F., Vandermeers A., Vandermeers-Piret M.-C., Herzog R., Rathe J.,
     Stievenart M., Winand J., Christophe J.
     "Purification and characterization of five variants of phospholipase
     A2 and complete primary structure of the main phospholipase A2 variant
     in Heloderma suspectum (Gila monster) venom."
     Eur. J. Biochem. 186:23-33(1989).
     PubMed=2480893

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