{PDOC50215}
{PS50215; ADAM_MEPRO}
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* ADAM type metalloprotease domain profile *
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ADAMs are   transmembrane   proteins   containing   both  a  disintegrin  (see
<PDOC00351>) and a metalloprotease domain [1]. About two third of the proteins
with an  ADAM  type  metalloprotease  domain  also  contain  the zinc protease
pattern (see <PDOC00129>) which locates the active site of these proteases. As
they contain   an  adhesion  domain  and  a  protease  domain,  ADAM  proteins
potentially have  both cell adhesion and protease activities. They play a role
in various   biological   processes,  including  fertilization,  neurogenesis,
myogenesis, embryonic TGF-alpha release and inflammatory response [2].

ADAMTS proteins  [3]  form  a  closely  related  family of proteases. In these
proteins, the   metalloprotease   and   disintegrin  domains  are  flanked  by
thrombospondin type  I  (TSP1)  repeat  (see <PDOC50092>). ADAMTS proteins are
soluble, extracellular  matrix    proteases  those  known substrates are other
extracellular matrix proteins [2].

ADAM proteins  also share the metalloprotease and disintegrin domains with the
disintegrin class of peptides that are present in snake venom [2,4]. Together,
they form  the  adamlysin/reprolysin subfamily of the metzincin superfamily of
Zn-dependent metalloproteinases [4].

Some proteins  known  to  contain  an  ADAM  metalloprotease domain are listed
below:

 - Human  ADAM  1 and 2 (fertilin alpha and beta). Fertilins are sperm surface
   membrane proteins  that  may  be  involved  in  sperm-egg  plasma  membrane
   adhesion and fusion during fertilization. They lack proteolytic activity.
 - Human ADAM 8. It may be involved in immune function.
 - Drosophila  Kuzbanian.  It  is  involved  in  neurogenesis.  Kuzbanian is a
   sheddase that  has  been  found to release a soluble form of Delta, a Notch
   ligand.
 - Vertebrate ADAM 10, the homologue of Kuzbanian.
 - Caenorhabditis  elegans  Sup-17, the homologue of Kuzbanian. It is involved
   in Lin-12/NOTCH signaling.
 - Human ADAM 12 (meltrin alpha). It may be involved in myogenesis.
 - Several  snake venom metalloproteinases of the disintegrin family. They are
   not transmembrane proteins.
 - Mammalian    ADAMTS-1.  Protease  those expression is associated with acute
   inflammation as well as development of cancer cachexia.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: December 2001 / First entry.

[ 1] Wolfsberg T.G., Straight P.D., Gerena R.L., Huovila A.P.,
     Primakoff P., Myles D.G., White J.M.
     "ADAM, a widely distributed and developmentally regulated gene family
     encoding membrane proteins with a disintegrin and metalloprotease
     domain."
     Dev. Biol. 169:378-383(1995).
     PubMed=7750654
[ 2] Primakoff P., Myles D.G.
     "The ADAM gene family: surface proteins with adhesion and protease
     activity."
     Trends Genet. 16:83-87(2000).
     PubMed=10652535
[ 3] Tang B.L., Hong W.
     "ADAMTS: a novel family of proteases with an ADAM protease domain and
     thrombospondin 1 repeats."
     FEBS Lett. 445:223-225(1999).
     PubMed=10094461
[ 4] Black R.A., White J.M.
     "ADAMs: focus on the protease domain."
     Curr. Opin. Cell Biol. 10:654-659(1998).
     PubMed=9818177

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