{PDOC00351}
{PS00427; DISINTEGRIN_1}
{PS50214; DISINTEGRIN_2}
{BEGIN}
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* Disintegrin domain signature and profile *
********************************************

Disintegrins [1,2]  are  snake  venom   proteins   which  inhibit   fibrinogen
interaction  with  platelet  receptors  expressed on the glycoprotein IIb-IIIa
complex. They act by binding to the integrin glycoprotein IIb-IIIa receptor on
the  platelet  surface and  inhibit  aggregation  induced  by  ADP,  thrombin,
platelet-activating factor and collagen.

Disintegrins are peptides of about  70 amino  acid residues that contain  many
cysteines all  involved  in disulfide bonds [3].  Disintegrins contain an Arg-
Gly-Asp (RGD) sequence, a recognition site of many adhesion proteins.  The RGD
sequence  of disintegrins is postulated to interact with the glycoprotein IIb-
IIIa complex.

The sequences of disintegrins from  different  snake  species are known. These
proteins  are  known  as:  albolabrin,   applagin,  barbourin,  batroxostatin,
bitistatin, echistatin, elegantin, eristicophin, flavoridin, halysin, kistrin,
tergeminin and triflavin.

Some other proteins are known to contain a disintegrin domain:

 - Some  snake    venom  zinc metalloproteinases [4]  consist of an N-terminal
   catalytic domain  fused  to  a  disintegrin  domain.  Such  is the case for
   trimerelysin I    (HR1B),   atrolysin e (Ht-e)  and  trigramin. It has been
   suggested  that  these proteinases  are  able to cleave themselves from the
   disintegrin domains  and  that  the  latter  may  arise  from  such a post-
   translational processing.
 - ADAM type metalloproteases (see <PDOC50215>).
 - Mammalian epididymial protein 1 (EAP I) [6].  EAP I is  associated with the
   sperm membrane and may play a role in sperm maturation. Structurally, EAP I
   consists of  an  N-terminal  domain,  followed  by a zinc metalloproteinase
   domain, a disintegrin domain, and a large C-terminal domain that contains a
   transmembrane region.

The schematic  representation of the structure of a typical disintegrin domain
is shown below:

                              +-----+
                +-------------|-----|--+        +------------------+
                |             |     |  |        |                  |
  xxxxxCxCxxxxxxCCxxxxCxxxxxxxCxxxxCCxxCxxxxxxxxCxxxRGDxxxxxCxxxxxxCxxxxxxx
       | |       |    |       *****|**************          |
       +-|-------|----+            +------------------------+
         +-------+

'C': conserved cysteine involved in a disulfide bond.
'*': position of the pattern.

Short disintegrins lack the N-terminal of the domain.

As a    signature  pattern for the disintegrin domain, we selected a conserved
central region  that  contains  five  of  the  cysteines involved in disulfide
bonds. A profile was also developed that spans the whole domain.

-Consensus pattern: C-x(2)-[GS]-x-C-C-x(1,2)-[NQRSEKD]-C-x-[FMYLVI]-x(6)-C-
                    [RKNQ]
                    [The 5 C's are involved in disulfide bonds]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: April 2006 / Pattern revised.

[ 1] Williams J., Rucinski B., Holt J., Niewiarowski S.
     "Elegantin and albolabrin purified peptides from viper venoms:
     homologies with the RGDS domain of fibrinogen and von Willebrand
     factor."
     Biochim. Biophys. Acta 1039:81-89(1990).
     PubMed=2191722
[ 2] Dennis M.S., Henzel W.J., Pitti R.M., Lipari M.T., Napier M.A.,
     Deisher T.A., Bunting S., Lazarus R.A.
     "Platelet glycoprotein IIb-IIIa protein antagonists from snake venoms:
     evidence for a family of platelet-aggregation inhibitors."
     Proc. Natl. Acad. Sci. U.S.A. 87:2471-2475(1990).
     PubMed=2320569
[ 3] Calvete J.J., Schafer W., Soszka T., Lu W.Q., Cook J.J., Jameson B.A.,
     Niewiarowski S.
     "Identification of the disulfide bond pattern in albolabrin, an
     RGD-containing peptide from the venom of Trimeresurus albolabris:
     significance for the expression of platelet aggregation inhibitory
     activity."
     Biochemistry 30:5225-5229(1991).
     PubMed=2036389
[ 4] Hite L.A., Fox J.W., Bjarnason J.B.
     "A new family of proteinases is defined by several snake venom
     metalloproteinases."
     Biol. Chem. Hoppe-Seyler 373:381-385(1992).
     PubMed=1515064
[ 5] Blobel C.P., Wolfsberg T.G., Turck C.W., Myles D.G., Primakoff P.,
     White J.M.
     "A potential fusion peptide and an integrin ligand domain in a protein
     active in sperm-egg fusion."
     Nature 356:248-252(1992).
     PubMed=1552944; DOI=10.1038/356248a0
[ 6] Perry A.C.F., Jones R., Barker P.J., Hall L.
     "A mammalian epididymal protein with remarkable sequence similarity to
     snake venom haemorrhagic peptides."
     Biochem. J. 286:671-675(1992).
     PubMed=1417724

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