PROSITE documentation PDOC00126
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{PDOC00126}
{PS00139; THIOL_PROTEASE_CYS}
{PS00639; THIOL_PROTEASE_HIS}
{PS00640; THIOL_PROTEASE_ASN}
{BEGIN}
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* Eukaryotic thiol (cysteine) proteases active sites *
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Eukaryotic thiol proteases (EC 3.4.22.-) [1] are a family of proteolytic
enzymes which contain an active site cysteine. Catalysis proceeds through a
thioester intermediate and is facilitated by a nearby histidine side chain; an
asparagine completes the essential catalytic triad. The proteases which are
currently known to belong to this family are listed below (references are
only provided for recently determined sequences).
- Vertebrate lysosomal cathepsins B (EC 3.4.22.1), H (EC 3.4.22.16), L
(EC 3.4.22.15), and S (EC 3.4.22.27) [2].
- Vertebrate lysosomal dipeptidyl peptidase I (EC 3.4.14.1) (also known as
cathepsin C) [2].
- Vertebrate calpains (EC 3.4.22.52) (EC 3.4.22.53). Calpains are
intracellular calcium-activated thiol protease that contain both a
N-terminal catalytic domain and a C-terminal calcium-binding domain.
- Mammalian cathepsin K, which seems involved in osteoclastic bone resorption
[3].
- Human cathepsin O [4].
- Bleomycin hydrolase. An enzyme that catalyzes the inactivation of the
antitumor drug BLM (a glycopeptide).
- Plant enzymes: barley aleurain (EC 3.4.22.16), EP-B1/B4; kidney bean EP-C1,
rice bean SH-EP; kiwi fruit actinidin (EC 3.4.22.14); papaya latex papain
(EC 3.4.22.2), chymopapain (EC 3.4.22.6), caricain (EC 3.4.22.30), and
proteinase IV (EC 3.4.22.25); pea turgor-responsive protein 15A; pineapple
stem bromelain (EC 3.4.22.32); rape COT44; rice oryzain alpha, beta, and
gamma; tomato low-temperature induced, Arabidopsis thaliana A494, RD19A and
RD21A.
- House-dust mites allergens DerP1 and EurM1.
- Cathepsin B-like proteinases from the worms Caenorhabditis elegans (genes
gcp-1, cpr-3, cpr-4, cpr-5 and cpr-6), Schistosoma mansoni (antigen SM31)
and Japonica (antigen SJ31), Haemonchus contortus (genes AC-1 and AC-2),
and Ostertagia ostertagi (CP-1 and CP-3).
- Slime mold cysteine proteinases CP1 and CP2.
- Cruzipain from Trypanosoma cruzi and brucei.
- Throphozoite cysteine proteinase (TCP) from various Plasmodium species.
- Proteases from Leishmania mexicana, Theileria annulata and Theileria parva.
- Baculoviruses cathepsin-like enzyme (v-cath).
- Drosophila small optic lobes protein (gene sol), a neuronal protein that
contains a calpain-like domain.
- Yeast thiol protease BLH1/YCP1/LAP3.
- Caenorhabditis elegans hypothetical protein C06G4.2, a calpain-like
protein.
Two bacterial peptidases are also part of this family:
- Aminopeptidase C from Lactococcus lactis (gene pepC) [5].
- Thiol protease tpr from Porphyromonas gingivalis.
Three other proteins are structurally related to this family, but may have
lost their proteolytic activity.
- Soybean oil body protein P34. This protein has its active site cysteine
replaced by a glycine.
- Rat testin, a sertoli cell secretory protein highly similar to cathepsin L
but with the active site cysteine is replaced by a serine. Rat testin
should not be confused with mouse testin which is a LIM-domain protein (see
<PDOC00382>).
- Plasmodium falciparum serine-repeat protein (SERA), the major blood stage
antigen. This protein of 111 Kd possesses a C-terminal thiol-protease-like
domain [6], but the active site cysteine is replaced by a serine.
The sequences around the three active site residues are well conserved and can
be used as signature patterns.
-Consensus pattern: Q-{V}-x-{DE}-[GE]-{F}-C-[YW]-{DN}-x-[STAGC]-[STAGCV]
[C is the active site residue]
-Sequences known to belong to this class detected by the pattern: ALL, except
for P34, testins, SERA antigen, and Theileria annulara protease.
-Other sequence(s) detected in Swiss-Prot: 6.
-Note: The residue in position 4 of the pattern is almost always cysteine; the
only exceptions are calpains (Leu), bleomycin hydrolase (Ser) and yeast YCP1
(Ser).
-Note: The residue in position 5 of the pattern is always Gly except in papaya
protease IV where it is Glu.
-Consensus pattern: [LIVMGSTAN]-{IEVK}-H-[GSACE]-[LIVM]-{GPSI}-[LIVMAT](2)-G-
{SLAG}-[GSADNH]
[H is the active site residue]
-Sequences known to belong to this class detected by the pattern: ALL, except
for calpains, P34 and tpr.
-Other sequence(s) detected in Swiss-Prot: 146.
-Consensus pattern: [FYCH]-[WI]-[LIVT]-x-[KRQAG]-N-[ST]-W-x(3)-[FYW]-G-x(2)-G-
[LFYW]-[LIVMFYG]-x-[LIVMF]
[N is the active site residue]
-Sequences known to belong to this class detected by the pattern: ALL, except
for calpains, bromelain, yeast BLH1, tomato low-temperature induced protease,
cathepsin O, pepC and tpr.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Note: These proteins belong to family C1 (papain-type) and C2 (calpains) in
the classification of peptidases [7,E1].
-Expert(s) to contact by email:
Turk B.;
boris.turk@ijs.si
-Last update: April 2006 / Patterns revised.
[ 1] Dufour E.
"Sequence homologies, hydrophobic profiles and secondary structures of
cathepsins B, H and L: comparison with papain and actinidin."
Biochimie 70:1335-1342(1988).
PubMed=3148320
[ 2] Kirschke H., Barrett A.J., Rawlings N.D.
Protein Prof. 2:1587-1643(1995).
[ 3] Shi G.-P., Chapman H.A., Bhairi S.M., DeLeeuw C., Reddy V.Y., Weiss S.J.
"Molecular cloning of human cathepsin O, a novel endoproteinase and
homologue of rabbit OC2."
FEBS Lett. 357:129-134(1995).
PubMed=7805878
[ 4] Velasco G., Ferrando A.A., Puente X.S., Sanchez L.M., Lopez-Otin C.
"Human cathepsin O. Molecular cloning from a breast carcinoma,
production of the active enzyme in Escherichia coli, and expression
analysis in human tissues."
J. Biol. Chem. 269:27136-27142(1994).
PubMed=7929457
[ 5] Chapot-Chartier M.P., Nardi M., Chopin M.C., Chopin A., Gripon J.C.
Appl. Environ. Microbiol. 59:330-333(1993).
[ 6] Higgins D.G., McConnell D.J., Sharp P.M.
"Malarial proteinase?"
Nature 340:604-604(1989).
PubMed=2671749; DOI=10.1038/340604a0
[ 7] 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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