PROSITE documentation PDOC00864

{PDOC00864}
{PS01121; CASPASE_HIS}
{PS01122; CASPASE_CYS}
{PS50207; CASPASE_P10}
{PS50208; CASPASE_P20}
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* Caspase family signatures and profiles *
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Interleukin-1 beta converting enzyme (EC 3.4.22.36) (ICE) [1,2] is responsible
for the cleavage of the IL-1 beta precursor at an Asp-Ala bond to generate the
mature biologically  active  cytokine.  ICE  a  thiol protease composed of two
subunits of 10 (p10) and 20 Kd (p20), both derived by the autocleavage of a 45
Kd precursor  (p45). Two residues are implicated in the catalytic mechanism: a
cysteine and an histidine. They are located  in the P20 subunit after cleavage
of  the  precursor.  ICE  belongs  to  a family  of  peptidases  [3] which  is
implicated in  programmed  cell  death  (apoptosis)  and which has been termed
'caspase' for cysteine aspase. ICE is known as Caspase-1 and the other members
of this family [4] are:

 - Caspase-2 (ICH-1, NEDD-2).
 - Caspase-3 (also  known  as apopain, CPP32, Yama), a protease which,  at the
   onset of  apoptosis,  proteolytically  cleaves  poly(ADP-ribose) polymerase
   (see <PDOC00360>) at an Asp-Gly bond.
 - Caspase-4 (ICH-2, TX, ICErel-II).
 - Caspase-5 (ICH-3, TY, ICErel-III).
 - Caspase-6 (MCH-2).
 - Caspase-7 (MCH-3, ICE-LAP3, CMH-1, SCA-2, LICE2).
 - Caspase-8 (MCH-5, MACH, FLICE).
 - Caspase-9 (MCH-6, ICE-LAP6).
 - Caspase-10 (MCH-4, FLICE2).
 - Caspase-11.
 - Caspase-12.
 - Caspase-13 (ERICE).
 - Caspase-14.
 - Caenorhabditis elegans ced-3 involved in the initiation of apoptosis.
 - Drosophila Ice.

We have  developed  signature  patterns for both active site residues. We also
developed  two  profiles, one specific for the caspase P10 subunit and one for
the caspase P20 subunit.

-Consensus pattern: H-x(2,4)-[SC]-x(2)-{A}-x-[LIVMF](2)-[ST]-H-G
                    [The second H is an active site residue]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: 5.

-Consensus pattern: K-P-K-[LIVMF]-[LIVMFY]-[LIVMF](2)-[QP]-[AF]-C-[RQG]-[GE]
                    [C is the active site residue]
-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.

-Note: These proteins belong to family C14 in the classification of peptidases
 [5,E1].

-Last update: December 2004 / Patterns and text revised.

[ 1] Thornberry N.A., Molineaux S.M.
     "Interleukin-1 beta converting enzyme: a novel cysteine protease
     required for IL-1 beta production and implicated in programmed cell
     death."
     Protein Sci. 4:3-12(1995).
     PubMed=7773174
[ 2] Kumar S.
     "ICE-like proteases in apoptosis."
     Trends Biochem. Sci. 20:198-202(1995).
     PubMed=7610484
[ 3] Nicholson D.W., Thornberry N.A.
     "Caspases: killer proteases."
     Trends Biochem. Sci. 22:299-306(1997).
     PubMed=9270303
[ 4] Alnemri E.S., Livingston D.J., Nicholson D.W., Salvesen G.,
     Thornberry N.A., Wong W.W., Yuan J.
     "Human ICE/CED-3 protease nomenclature."
     Cell 87:171-171(1996).
     PubMed=8861900
[ 5] Rawlings N.D., Barrett A.J.
     "Evolutionary families of peptidases."
     Biochem. J. 290:205-218(1993).
     PubMed=8439290
[E1] https://www.uniprot.org/docs/peptidas

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