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Information on EC 3.4.22.35 - Histolysain
for references in articles please use BRENDA:EC3.4.22.35
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EC Tree 3 Hydrolases
3.4 Acting on peptide bonds (peptidases)
3.4.22 Cysteine endopeptidases
3.4.22.35 Histolysain
IUBMB Comments
From the protozoan, Entamoeba histolytica. In peptidase family C1 (papain family)
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
- 3.4.22.35
- cathepsins
- lysosomal
- cystatins
- papain
- calpains
- trypanosoma
- plasmodium
- falciparum
-
papain-like
- cruzi
- resorption
- polyproteins
-
antimalarial
- allergen
- caspase-1
- pyogenes
- chagas
- mite
- propeptide
-
calcium-dependent
- osteoclast
- leupeptin
- trophozoite
- m-calpain
-
asparaginyl
- proenzyme
- cruzipain
-
warhead
- nsp2
-
calpain-mediated
-
hexakisphosphate
- pteronyssinus
-
pyrogenic
-
procathepsin
- cpp32
- streptococcal
-
metacercariae
- 3clpro
-
autoprocessing
- bromelain
- kininogens
- calpastatin
- pineapple
-
gingipains
-
l-like
- alln
-
osteoclast-mediated
- legumain
-
collagenolytic
- dermatophagoides
Reaction Schemes
showhydrolysis of proteins, including basement membrane collagen and azocasein. Preferential cleavage: Arg-Arg-/- in small molecule substrates including Z-Arg-Arg-/-NHMec
Synonyms
cysteine protease, ehcp112, ehcp5, ehcp2, ehcp1, cysteine proteinase 1, cysteine proteinase 5, cysteine protease 2, histolysain, ppehcp-b9, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Amebapain
-
-
-
-
CP1
CP2
CP5
CP6
cysteine protease 1
cysteine protease 2
cysteine protease 5
cysteine protease 6
cysteine proteinase 1
cysteine proteinase 5
EhCP1
Entamoeba histolytica 112kDa adhesin
-
together with a protein with an adherence domain EhADH112
Entamoeba histolytica cysteine protease
Entamoeba histolytica cysteine proteinase
Entamoeba histolytica neutral thiol proteinase
-
-
-
-
Histolysin
PCP5
Proteinase, Entamoeba histolytica cysteine
-
-
-
-
additional information
Entamoeba histolytica cysteine protease
-
-
-
-
Entamoeba histolytica cysteine proteinase
-
-
-
-
Histolysin
-
-
-
-
additional information
enzyme is a member of the cysteine proteinase family
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hydrolysis of proteins, including basement membrane collagen and azocasein. Preferential cleavage: Arg-Arg-/- in small molecule substrates including Z-Arg-Arg-/-NHMec
hydrolysis of proteins, including basement membrane collagen and azocasein. Preferential cleavage: Arg-Arg-/- in small molecule substrates including Z-Arg-Arg-/-NHMec
-
-
-
-
hydrolysis of proteins, including basement membrane collagen and azocasein. Preferential cleavage: Arg-Arg-/- in small molecule substrates including Z-Arg-Arg-/-NHMec
from the protozoan, Entamoeba histolytica. In peptidase family C1 (papain family)
-
-
-
hydrolysis of proteins, including basement membrane collagen and azocasein. Preferential cleavage: Arg-Arg-/- in small molecule substrates including Z-Arg-Arg-/-NHMec
cleavage mechanism on mucin substrate, overview
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
hydrolysis of peptide bond
-
-
-
-
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CAS REGISTRY NUMBER
COMMENTARY
92228-52-9
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
Arg-Gly-Phe-Phe + H2O
Arg-Gly + Phe-Phe
-
Substrates: substrate of amoebapain
Products: -
Products: -
?
azocasein + H2O
fragments of azocasein
-
Substrates: -
Products: -
Products: -
?
benzyloxycarbonyl-Ala-Arg-Arg-4-nitroanilide + H2O
benzyloxycarbonyl-Ala-Arg-Arg + 4-nitroaniline
-
Substrates: -
Products: -
Products: -
?
Benzyloxycarbonyl-Arg-Arg 4-methylcoumarin 7-amide + H2O
?
-
Substrates: -
Products: -
Products: -
?
benzyloxycarbonyl-Arg-Arg-4-nitroanilide + H2O
benzyloxycarbonyl-Arg-Arg + 4-nitroaniline
-
Substrates: -
Products: -
Products: -
?
benzyloxycarbonyl-Arg-Arg-7-amido-4-methylcoumarin + H2O
?
Substrates: -
Products: -
Products: -
?
benzyloxycarbonyl-L-arginyl-L-arginine 4-nitroanilide + H2O
benzyloxycarbonyl-L-arginyl-L-arginine + 4-nitroaniline
Substrates: -
Products: -
Products: -
?
Benzyloxycarbonyl-Phe-Arg 4-methylcoumarin 7-amide + H2O
?
-
Substrates: -
Products: -
Products: -
?
Benzyloxycarbonyl-Phe-L-citrullin 4-methylcoumarin 7-amide + H2O
?
-
Substrates: -
Products: -
Products: -
?
Collagen type I + H2O
?
-
Substrates: digestion with an initial attack at the alpha2-chain
Products: -
Products: -
?
complement factor C3 + H2O
peptides
Substrates: -
Products: product determination
Products: product determination
?
complement factor C9 + H2O
peptides
Substrates: -
Products: product determination
Products: product determination
?
fibronectin + H2O
peptides
Substrates: -
Products: product determination
Products: product determination
?
immunoglobulin G + H2O
peptides derived from immunoglobulin G
Substrates: -
Products: product determination
Products: product determination
?
Kidney glomerular basement-membrane collagen + H2O
?
-
Substrates: -
Products: -
Products: -
?
mucin MUC2 polymer + H2O
?
-
Substrates: enzyme is involved, together with other Entamoeba histolytica cysteine proteinases, in the degradation of mucin in the mucous layer of the colon epithelium, altering the protective function to facilitate parasite attachment
Products: -
Products: -
?
N-benzyloxycarbonyl-L-arginyl-7-amido-4-methylcoumarin + H2O
N-benzyloxycarbonyl-L-arginine + 7-amino-4-methylcoumarin
N-benzyloxycarbonyl-L-arginyl-L-arginyl-7-amido-4-methylcoumarin + H2O
N-benzyloxycarbonyl-L-arginyl-L-arginine + 7-amino-4-methylcoumarin
N-benzyloxycarbonyl-L-phenylalanyl-L-arginyl-7-amido-4-methylcoumarin + H2O
N-benzyloxycarbonyl-L-phenylalanyl-L-arginine + 7-amino-4-methylcoumarin
-
Substrates: 7% of the activity with N-benzyloxycarbonyl-L-arginyl-L-arginyl-7-amido-4-methylcoumarin
Products: -
Products: -
?
pro-interleukin-18 + H2O
?
-
Substrates: protein from human
Products: -
Products: -
?
Z-Arg-Arg-4-methoxy-2-nitroanilide + H2O
Z-Arg-Arg + 4-methoxy-2-nitroaniline
-
Substrates: -
Products: -
Products: -
?
Z-Arg-Arg-4-nitroanilide + H2O
Z-Arg-Arg + 4-nitroaniline
-
Substrates: -
Products: -
Products: -
?
Z-Arg-Arg-7-amido-4-trifluoromethylcoumarin + H2O
?
-
Substrates: -
Products: -
Products: -
?
Z-Arg-Arg-7-amido-4-trifluoromethylcoumarin + H2O
Z-Arg-Arg + 7-amino-4-trifluoromethylcoumarin
Substrates: -
Products: -
Products: -
?
chemokine CCL13 + H2O
?
-
Substrates: Entamoeba histolytica is a human pathogen causing amoebic colitis, the enzyme is involved in the inflammation process modulating human host leucocyte migration by proteolytic cleavage of chemokines CCL2, CCL13, and CXCL8, a mechanism to circumvent host immune response
Products: -
Products: -
?
chemokine CCL2 + H2O
?
-
Substrates: Entamoeba histolytica is a human pathogen causing amoebic colitis, the enzyme is involved in the inflammation process modulating human host leucocyte migration by proteolytic cleavage of chemokines CCL2, CCL13, and CXCL8, a mechanism to circumvent host immune response
Products: -
Products: -
?
chemokine CXCL8 + H2O
?
-
Substrates: Entamoeba histolytica is a human pathogen causing amoebic colitis, the enzyme is involved in the inflammation process modulating human host leucocyte migration by proteolytic cleavage of chemokines CCL2, CCL13, and CXCL8, a mechanism to circumvent host immune response
Products: -
Products: -
?
immunoglobulin G + H2O
?
-
Substrates: heavy chain, protein from human
Products: -
Products: -
?
immunoglobulin G + H2O
?
-
Substrates: heavy chain, protein from human
Products: -
Products: -
?
MUC2 mucin + H2O
?
-
Substrates: disruption of the protective mucin layer of targeted host cells, entry mechanism of the pathogen, overview
Products: -
Products: -
?
MUC2 mucin + H2O
?
-
Substrates: the enzyme targets two site at the C-terminal cysteine-rich domain, which is less glycosylated and exposes its peptide chain, overview
Products: -
Products: -
?
N-benzyloxycarbonyl-L-arginyl-7-amido-4-methylcoumarin + H2O
N-benzyloxycarbonyl-L-arginine + 7-amino-4-methylcoumarin
-
Substrates: 17% of the activity with N-benzyloxycarbonyl-L-arginyl-L-arginyl-7-amido-4-methylcoumarin
Products: -
Products: -
?
N-benzyloxycarbonyl-L-arginyl-7-amido-4-methylcoumarin + H2O
N-benzyloxycarbonyl-L-arginine + 7-amino-4-methylcoumarin
-
Substrates: 17% of the activity with N-benzyloxycarbonyl-L-arginyl-L-arginyl-7-amido-4-methylcoumarin
Products: -
Products: -
?
N-benzyloxycarbonyl-L-arginyl-L-arginyl-7-amido-4-methylcoumarin + H2O
N-benzyloxycarbonyl-L-arginyl-L-arginine + 7-amino-4-methylcoumarin
-
Substrates: -
Products: -
Products: -
?
N-benzyloxycarbonyl-L-arginyl-L-arginyl-7-amido-4-methylcoumarin + H2O
N-benzyloxycarbonyl-L-arginyl-L-arginine + 7-amino-4-methylcoumarin
-
Substrates: -
Products: -
Products: -
?
protein + H2O
peptides
-
Substrates: -
Products: -
Products: -
?
protein + H2O
peptides
Substrates: enzyme is involved in pathogenic destruction of host tissue by degradation of extracellular matrix proteins
Products: -
Products: -
?
Z-Ala-Arg-Arg-7-amido-4-methylcoumarin + H2O
Z-Ala-Arg-Arg + 7-amino-4-methylcoumarin
-
Substrates: -
Products: -
Products: -
?
Z-Ala-Arg-Arg-7-amido-4-methylcoumarin + H2O
Z-Ala-Arg-Arg + 7-amino-4-methylcoumarin
-
Substrates: -
Products: -
Products: -
?
Z-Arg-Arg-7-amido-4-methylcoumarin + H2O
Z-Arg-Arg + 7-amino-4-methylcoumarin
-
Substrates: -
Products: -
Products: -
?
Z-Arg-Arg-7-amido-4-methylcoumarin + H2O
Z-Arg-Arg + 7-amino-4-methylcoumarin
-
Substrates: -
Products: -
Products: -
?
Insulin B-chain + H2O
additional information
-
-
Substrates: -
Products: the Gly-Phe bond in the insulin B-chain is the major hydrolysis site
Products: the Gly-Phe bond in the insulin B-chain is the major hydrolysis site
?
additional information
?
-
-
Substrates: with unblocked tetrapeptides as substrates, peptidyl dipeptidase activity of the amoeba enzyme requires an arginine at the P2 position. Lysine cannot substitute for arginine
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme causes a loss of adhesion of mammalian cells in culture
Products: -
Products: -
?
additional information
?
-
-
Substrates: plasminogen activator
Products: -
Products: -
?
additional information
?
-
-
Substrates: inactivates aldolase and glyceraldehyde 3-phosphate dehydrogenase from rabbit muscle and glucose 6-phosphate dehydrogenase from yeast, limited proteolysis yielding major cleavage products
Products: -
Products: -
?
additional information
?
-
-
Substrates: not: type I collagen
Products: -
Products: -
?
additional information
?
-
-
Substrates: splits blocked and unblocked peptide analogs with 2-naphthylamide moieties, cleavability is enhanced by the presence of basic residues, such as arginine or lysine, near the acyl end of the substrate
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme permits adhesion of trophozoites to cells via fibronectin binding, which can be inhibited by Zn2+
Products: -
Products: -
?
additional information
?
-
-
Substrates: no activity with benzyloxycarbonyl-Phe-Arg-4-nitroanilide
Products: -
Products: -
?
additional information
?
-
-
Substrates: no activity with N-benzyloxycarbonyl-Val-Lys-Met-7-amido-4-methylcoumarin and succinyl-LLVY-7-amido-4-methylcoumarin
Products: -
Products: -
?
additional information
?
-
Substrates: no activity with peptide substrates containing phenylalanine at P2 position instead of arginine
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme is covalently connected to an adhesin by electrostatic forces which are not broken during phagocytosis
Products: -
Products: -
?
additional information
?
-
-
Substrates: significant pathogenicity factor
Products: -
Products: -
?
additional information
?
-
-
Substrates: role in tissue invasion
Products: -
Products: -
?
additional information
?
-
-
Substrates: appears to be important both for digestion and as a cytotoxic factor
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme can degrade colon cell mucin and destroy epithelial cell layers
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme degrades a number of proteins, including those of the extracellular matrix
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme is involved in host tissue invasion by trophozoites and destroys cell monolayers
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme shows cytopathic effects and destroys cell monolayers
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme degrades a number of proteins, including those of the extracellular matrix, but also acts on small molecule substrates showing endopeptidase and exopeptidase-like activities, amoebapain hydrolyzes unblocked tetrapeptides with basic residues at P2
Products: -
Products: -
?
additional information
?
-
-
Substrates: cysteine proteinases play a central role in tissue invasion and disruption of host defenses by digesting components of the extracellular matrix, immunoglobulins, complement, and cytokines
Products: -
Products: -
?
additional information
?
-
-
Substrates: essential for pathogenicity of Entamoeba histolytica
Products: -
Products: -
?
additional information
?
-
-
Substrates: essential for pathogenicity of Entamoeba histolytica
Products: -
Products: -
?
additional information
?
-
Substrates: essential for pathogenicity of Entamoeba histolytica
Products: -
Products: -
?
additional information
?
-
Substrates: essential for pathogenicity of Entamoeba histolytica
Products: -
Products: -
?
additional information
?
-
-
Substrates: secreted cysteine proteases play an indispensable role in amoebic invasion and tissue destruction due to their hydrolytic and degradative activities towards extracellular matrix proteins
Products: -
Products: -
?
additional information
?
-
Substrates: secreted cysteine proteases play an indispensable role in amoebic invasion and tissue destruction due to their hydrolytic and degradative activities towards extracellular matrix proteins
Products: -
Products: -
?
additional information
?
-
Substrates: secreted cysteine proteases play an indispensable role in amoebic invasion and tissue destruction due to their hydrolytic and degradative activities towards extracellular matrix proteins
Products: -
Products: -
?
additional information
?
-
-
Substrates: no activity with Z-Phe-Arg-4-amido-7-methylcoumarin
Products: -
Products: -
?
additional information
?
-
-
Substrates: the cysteine proteinase EhCP112 and the adhesin EhADH112 assemble to form the EhCPADH complex involved in Entamoeba histolytica virulence
Products: -
Products: -
?
additional information
?
-
-
Substrates: cysteine proteinases play a central role in tissue invasion and disruption of host defenses by digesting components of the extracellular matrix, immunoglobulins, complement, and cytokines
Products: -
Products: -
?
additional information
?
-
-
Substrates: no activity with Z-Phe-Arg-4-amido-7-methylcoumarin
Products: -
Products: -
?
additional information
?
-
-
Substrates: no activity with N-benzyloxycarbonyl-Val-Lys-Met-7-amido-4-methylcoumarin and succinyl-LLVY-7-amido-4-methylcoumarin
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
chemokine CCL13 + H2O
?
-
Substrates: Entamoeba histolytica is a human pathogen causing amoebic colitis, the enzyme is involved in the inflammation process modulating human host leucocyte migration by proteolytic cleavage of chemokines CCL2, CCL13, and CXCL8, a mechanism to circumvent host immune response
Products: -
Products: -
?
chemokine CCL2 + H2O
?
-
Substrates: Entamoeba histolytica is a human pathogen causing amoebic colitis, the enzyme is involved in the inflammation process modulating human host leucocyte migration by proteolytic cleavage of chemokines CCL2, CCL13, and CXCL8, a mechanism to circumvent host immune response
Products: -
Products: -
?
chemokine CXCL8 + H2O
?
-
Substrates: Entamoeba histolytica is a human pathogen causing amoebic colitis, the enzyme is involved in the inflammation process modulating human host leucocyte migration by proteolytic cleavage of chemokines CCL2, CCL13, and CXCL8, a mechanism to circumvent host immune response
Products: -
Products: -
?
MUC2 mucin + H2O
?
-
Substrates: disruption of the protective mucin layer of targeted host cells, entry mechanism of the pathogen, overview
Products: -
Products: -
?
mucin MUC2 polymer + H2O
?
-
Substrates: enzyme is involved, together with other Entamoeba histolytica cysteine proteinases, in the degradation of mucin in the mucous layer of the colon epithelium, altering the protective function to facilitate parasite attachment
Products: -
Products: -
?
protein + H2O
peptides
-
Substrates: -
Products: -
Products: -
?
protein + H2O
peptides
Substrates: enzyme is involved in pathogenic destruction of host tissue by degradation of extracellular matrix proteins
Products: -
Products: -
?
additional information
?
-
-
Substrates: significant pathogenicity factor
Products: -
Products: -
?
additional information
?
-
-
Substrates: role in tissue invasion
Products: -
Products: -
?
additional information
?
-
-
Substrates: appears to be important both for digestion and as a cytotoxic factor
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme can degrade colon cell mucin and destroy epithelial cell layers
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme degrades a number of proteins, including those of the extracellular matrix
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme is involved in host tissue invasion by trophozoites and destroys cell monolayers
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme shows cytopathic effects and destroys cell monolayers
Products: -
Products: -
?
additional information
?
-
-
Substrates: cysteine proteinases play a central role in tissue invasion and disruption of host defenses by digesting components of the extracellular matrix, immunoglobulins, complement, and cytokines
Products: -
Products: -
?
additional information
?
-
-
Substrates: essential for pathogenicity of Entamoeba histolytica
Products: -
Products: -
?
additional information
?
-
-
Substrates: essential for pathogenicity of Entamoeba histolytica
Products: -
Products: -
?
additional information
?
-
Substrates: essential for pathogenicity of Entamoeba histolytica
Products: -
Products: -
?
additional information
?
-
Substrates: essential for pathogenicity of Entamoeba histolytica
Products: -
Products: -
?
additional information
?
-
-
Substrates: secreted cysteine proteases play an indispensable role in amoebic invasion and tissue destruction due to their hydrolytic and degradative activities towards extracellular matrix proteins
Products: -
Products: -
?
additional information
?
-
Substrates: secreted cysteine proteases play an indispensable role in amoebic invasion and tissue destruction due to their hydrolytic and degradative activities towards extracellular matrix proteins
Products: -
Products: -
?
additional information
?
-
Substrates: secreted cysteine proteases play an indispensable role in amoebic invasion and tissue destruction due to their hydrolytic and degradative activities towards extracellular matrix proteins
Products: -
Products: -
?
additional information
?
-
-
Substrates: the cysteine proteinase EhCP112 and the adhesin EhADH112 assemble to form the EhCPADH complex involved in Entamoeba histolytica virulence
Products: -
Products: -
?
additional information
?
-
-
Substrates: cysteine proteinases play a central role in tissue invasion and disruption of host defenses by digesting components of the extracellular matrix, immunoglobulins, complement, and cytokines
Products: -
Products: -
?
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4-hydroxymercuribenzoate
-
E64 inhibits cell growth and is cytopathic/lethal for E64-sensitive and E64-resistant amoebae
4-[(2S,3S)-carboxyoxiran-2-ylcarbonyl-L-leucylamido]butylguanidine
-
i.e. trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane or E64