{PDOC50203}
{PS50203; CALPAIN_CAT}
{BEGIN}
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* Cysteine proteinase, calpain-type, catalytic domain profile *
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Calpains are  a  family  of  cytosolic cysteine proteinases (see <PDOC00126>).
Members of  the  calpain family are believed to function in various biological
processes, including    integrin-mediated    cell    migration,   cytoskeletal
remodeling, cell differentiation and apoptosis [1,2].

The  calpain  family  includes numerous members from C. elegans to mammals and
with homologs in yeast and bacteria. The best characterized members are the m-
and  mu-calpains,  both proteins are heterodimer composed of a large catalytic
subunit  and  a  small  regulatory  subunit.  The large subunit comprises four
domains  (dI-dIV)  while the small subunit has two domains (dV-dVI). Domain dI
is  a  short region cleaved by autolysis, dII is the catalytic core, dIII is a
C2-like domain, dIV consists of five calcium binding EF-hand motifs [2].

The  crystal  structure of calpain has been solved (see <PDB:1DF0>) [3,4]. The
catalytic  region consists of two distinct structural domains (dIIa and dIIb).
dIIa  contains  a  central  helix  flanked  on  three  faces  by  a cluster of
alpha-helices  and  is  entirely  unrelated to the corresponding domain in the
typical  thiol  proteinases.  The fold of dIIb is similar to the corresponding
domain   in   other   cysteine  proteinases  and  contains  two three-stranded
anti-parallel beta-sheets. The catalytic triad residues (C,H,N) are located in
dIIa and dIIb. The activation of the domain is dependent on the binding of two
calcium atoms  in  two  non  EF-hand  calcium  binding  sites  located  in the
catalytic core, one close to the Cys active site in dIIa and one at the end of
dIIb. Calcium-binding  induced  conformational changes in the catalytic domain
which align the active site [4,5].

The profile we developed covers the whole catalytic domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: August 2003 / First entry.

-Note: These  proteins belong to family C2 in the classification of peptidases
 [6,E1].

[ 1] Glading A., Lauffenburger D.A., Wells A.
     "Cutting to the chase: calpain proteases in cell motility."
     Trends Cell Biol. 12:46-54(2002).
     PubMed=11854009
[ 2] Perrin B.J., Huttenlocher A.
     "Calpain."
     Int. J. Biochem. Cell Biol. 34:722-725(2002).
     PubMed=11950589
[ 3] Hosfield C.M., Elce J.S., Davies P.L., Jia Z.
     "Crystal structure of calpain reveals the structural basis for
     Ca(2+)-dependent protease activity and a novel mode of enzyme
     activation."
     EMBO J. 18:6880-6889(1999).
     PubMed=10601010; DOI=10.1093/emboj/18.24.6880
[ 4] Moldoveanu T., Hosfield C.M., Lim D., Elce J.S., Jia Z., Davies P.L.
     "A Ca(2+) switch aligns the active site of calpain."
     Cell 108:649-660(2002).
     PubMed=11893336
[ 5] Khorchid A., Ikura M.
     "How calpain is activated by calcium."
     Nat. Struct. Biol. 9:239-241(2002).
     PubMed=11914728; DOI=10.1038/nsb0402-239
[ 6] Rawlings N.D., Barrett A.J.
     "Families of cysteine peptidases."
     Methods Enzymol. 244:461-486(1994).
     PubMed=7845226
[E1] https://www.uniprot.org/docs/peptidas

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