Information on EC 3.4.22.41 - cathepsin F

New: Word Map on EC 3.4.22.41
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Search Reference ID:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


The expected taxonomic range for this enzyme is: Bilateria

EC NUMBER
COMMENTARY hide
3.4.22.41
-
RECOMMENDED NAME
GeneOntology No.
cathepsin F
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
The recombinant enzyme cleaves synthetic substrates with Phe and Leu (better than Val) in P2, with high specificity constant (kcat/Km) comparable to that of cathepsin L
show the reaction diagram
Cathepsin F is a lysosomal cysteine endopeptidase of family C1, papain family, most activite at pH 5.9. The enzyme is unstable at neutral pH values and is inhibited by compound E-64. Cathepsin F is expressed in most tissues of human, mouse and rat. Human gene locus: 11q13.1-13.3; endopeptidase
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
CAS REGISTRY NUMBER
COMMENTARY hide
65997-74-2
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Wistar rat
UniProt
Manually annotated by BRENDA team
common abomasal nematode parasite of sheep
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
cathepsin F is implicated in the growth and reproduction regulation
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
Albumin + H2O
?
show the reaction diagram
-
substrate of isozyme CF-4 at pH 6.5 and CF-11 at pH 5.5 but not at neutral pH
-
-
?
apoB-100 + H2O
?
show the reaction diagram
-
apoB-100 is part of LDL particles
-
-
?
benzyloxycarbonyl-Arg-Arg-4-methylcoumaryl-7-amide + H2O
benzyloxycarbonyl-Arg-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
benzyloxycarbonyl-Arg-Arg-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
low activity
-
-
?
benzyloxycarbonyl-L-leucine-L-arginine-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-L-leucine-L-arginine + 7-amino-4-methylcoumarin
show the reaction diagram
-
high catalytic activity with isozymes CF-4 and CF-11
-
-
?
benzyloxycarbonyl-L-leucyl-L-arginyl-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-L-leucyl-L-arginyl + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-L-Phe-L-Arg-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-L-Phe-L-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
benzyloxycarbonyl-L-phenylalanine-L-arginine-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-L-phenylalanine-L-arginine + 7-amino-4-methylcoumarin
show the reaction diagram
-
high catalytic activity with isozymes CF-4 and CF-11
-
-
?
benzyloxycarbonyl-Leu-Arg-4-methylcoumarin-7-amide + H2O
benzyloxycarbonyl-Leu-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
benzyloxycarbonyl-Leu-Arg-4-methylcoumaryl-7-amide + H2O
benzyloxycarbonyl-Leu-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
benzyloxycarbonyl-Leu-Arg-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
high activity
-
-
?
benzyloxycarbonyl-Phe-Arg-4-methylcoumarin-7-amide + H2O
benzyloxycarbonyl-Phe-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
benzyloxycarbonyl-Phe-Arg-4-methylcoumaryl-7-amide + H2O
benzyloxycarbonyl-Phe-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
benzyloxycarbonyl-Phe-Arg-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
high activity
-
-
?
benzyloxycarbonyl-Val-Val-Arg-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
very low activity
-
-
?
Collagen + H2O
?
show the reaction diagram
-
substrate of isozyme CF-4 at pH 6.5 and CF-11 at pH 5.5 but not at neutral pH
-
-
?
Gelatin + H2O
?
show the reaction diagram
purified CtF is capable of hydrolyzing 0.1% gelatin at pH 7.5
-
-
?
Hemoglobin + H2O
?
show the reaction diagram
Ii-MHC class II complex + H2O
?
show the reaction diagram
-
-
-
-
?
immunoglobulin A + H2O
?
show the reaction diagram
-
substrate of isozyme CF-4 at pH 6.5 and CF-11 at pH 5.5 but not at neutral pH
-
-
?
immunoglobulin G + H2O
?
show the reaction diagram
-
substrate of isozyme CF-4 at pH 6.5 and CF-11 at pH 5.5 but not at neutral pH
-
-
?
immunoglobulin M + H2O
?
show the reaction diagram
-
substrate of isozyme CF-4 at pH 6.5 and CF-11 at pH 5.5 but not at neutral pH
-
-
?
LAMP 2 protein + H2O
?
show the reaction diagram
-
-
-
-
?
N-acetyl-DEVD-7-amido-4-triflurormethylcoumarin + H2O
N-acetyl-DEVD + 7-amino-4-triflurormethylcoumarin
show the reaction diagram
-
-
-
-
?
N-benzyloxycarbonyl-L-Arg-L-Arg-4-methylcoumarin 7-amide + H2O
N-benzyloxycarbonyl-L-Arg-L-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
?
N-benzyloxycarbonyl-L-Leu-L-Arg-4-methylcoumarin 7-amide + H2O
N-benzyloxycarbonyl-L-Leu-L-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
N-benzyloxycarbonyl-L-Phe-L-Arg-4-methylcoumarin 7-amide + H2O
N-benzyloxycarbonyl-L-Phe-L-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
N-benzyloxycarbonyl-L-Val-L-Arg-4-methylcoumarin 7-amide + H2O
N-benzyloxycarbonyl-L-Val-L-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
?
Pro-Arg-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
very low activity
-
-
?
tert-butyloxycarbonyl-Ala-Gly-Pro-Arg-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
very low activity
-
-
?
tert-butyloxycarbonyl-Leu-Arg-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
highest activity
-
-
?
tert-butyloxycarbonyl-Val-Pro-Arg-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
very low activity
-
-
?
tosyl-Gly-Pro-Arg-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
very low activity
-
-
?
tosyl-Gly-Pro-Lys-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
very low activity
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
Hemoglobin + H2O
?
show the reaction diagram
-
cathepsin F and cathepsin B can work in concert to hydrolyse hemoglobin at low pH
-
-
?
Ii-MHC class II complex + H2O
?
show the reaction diagram
-
-
-
-
?
LAMP 2 protein + H2O
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
149.95% relative activity at 1 mM
K+
143.7% relative activity at 1 mM
Mg2+
133.38% relative activity at 1 mM
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,10-phenanthroline
15.28% inhibition at 0.1 mM
antipain
complete inhibition at 0.1 mM
Aprotinin
36.94% inhibition at 0.1 mM
Chloroquine
-
-
chymostatin
35.42% inhibition at 0.1 mM
Co2+
6.85% residual activity at 5 mM
Cu2+
11.6% residual activity at 5 mM
cystatin B
-
-
-
EDTA
6.52% inhibition at 0.1 mM
EGTA
4.72% inhibition at 0.1 mM
Hg2+
0.81% residual activity at 5 mM
JPM565
-
radioactive-labeling by 125I, irrevrsible inhibitor of papin-type cathepsins, active site labeling
leupeptine
complete inhibition at 0.1 mM
-
morpholine urea-Leu-homophenylalaninevinyl sulfone-phenyl
NEM
44.59% inhibition at 0.1 mM
phenylmethylsufonyl fluoride
13.22% inhibition at 0.1 mM
SDS
complete inhibition at 0.05% (w/v)
trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane
Z-VAD(OMe)-fluoromethylketone
-
-
-
Zn2+
5.94% residual activity at 1 mM
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Brij 35
273.6% relative activity at 0.01% (v/v)
chondroitin-4-sulfate
-
activates apoB-100/LDL degradation by cathepsin F
chondroitin-6-sulfate
-
activates apoB-100/LDL degradation by cathepsin F
dermatan sulfate
-
activates apoB-100/LDL degradation by cathepsin F
heparan sulfate
-
activates apoB-100/LDL degradation by cathepsin F
human aortic proteoglycans
-
activates apoB-100/LDL degradation by cathepsin F
-
Triton X-100
310.29% relative activity at 0.01% (v/v)
Tween 20
282.7% relative activity at 0.01% (v/v)
additional information
-
cathepsin F is secreted as an inactive zymogen that autocatalytically processes and activates to a mature enzyme at pH 4.5 (after 6 h incubation) via an intermolecular cleavage at the prosegment-mature domain junction, the active cathepsin B1 zymogen is capable of trans-activating cathepsin F by proteolytic removal of its prosegment at pH 5.5
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.043
benzyloxycarbonyl-Phe-Arg-4-methylcoumarin 7-amide
-
pH 6.5, room temperature, mutant enzyme N97Q/N108Q/N170Q
0.017
benzyloxycarbonyl-Phe-Arg-4-methylcoumaryl-7-amide
-
pH 6.5, room temperature, wild-type enzyme
0.00287
N-benzyloxycarbonyl-L-Arg-L-Arg-4-methylcoumarin 7-amide
-
0.00023
N-benzyloxycarbonyl-L-Leu-L-Arg-4-methylcoumarin 7-amide
-
0.00044
N-benzyloxycarbonyl-L-Phe-L-Arg-4-methylcoumarin 7-amide
-
0.00124
N-benzyloxycarbonyl-L-Val-L-Arg-4-methylcoumarin 7-amide
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.5 - 2.9
benzyloxycarbonyl-Phe-Arg-4-methylcoumaryl-7-amide
0.2
N-benzyloxycarbonyl-L-Arg-L-Arg-4-methylcoumarin 7-amide
Homo sapiens
Q9UBX1
-
1.3
N-benzyloxycarbonyl-L-Leu-L-Arg-4-methylcoumarin 7-amide
Homo sapiens
Q9UBX1
-
2.5
N-benzyloxycarbonyl-L-Phe-L-Arg-4-methylcoumarin 7-amide
Homo sapiens
Q9UBX1
-
1.3
N-benzyloxycarbonyl-L-Val-L-Arg-4-methylcoumarin 7-amide
Homo sapiens
Q9UBX1
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5.3 - 7.6
benzyloxycarbonyl-L-leucine-L-arginine-7-amido-4-methylcoumarin
6 - 8.2
benzyloxycarbonyl-L-phenylalanine-L-arginine-7-amido-4-methylcoumarin
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.2 - 6.8
-
6
-
about
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.5 - 6
modest enzyme activity, substrates hemoglobin and gelatin
4.5 - 8
substrate benzyloxycarbonyl-Phe-Arg-4-methylcoumarin-7-amide
additional information
-
slightly acidic pH optimum, rapid inactivation at neutral pH
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.8
calculated from amino acid sequence
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
distribution, overview
Manually annotated by BRENDA team
-
overexpression of cathepsin F
Manually annotated by BRENDA team
immunostaining using anti-PoCtF antibody was strongest on the epidermal mucus in the fin
Manually annotated by BRENDA team
immunohistochemistry
Manually annotated by BRENDA team
-
cervical cancer cell lines, CTSF expression profile
Manually annotated by BRENDA team
immunohistochemistry
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
immunofluorescence microscopy, fluorescence-labeled peptide substrate (benzyloxycarbonyl-Leucin-Arginin-4-methylcoumaryl-7-amide) with excitation wavelength 380 nm and emission wavelength 460 nm; Western blot, immunofluorescence microscopy, fluorescence-labeled peptide substrate (benzyloxycarbonyl-Leu-Arg-4-methylcoumaryl-7-amide) with excitation wavelength 380 nm and emission wavelength 460 nm
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
23590
mature enzyme, calculation from sequence of cDNA
23810
predicted from amino acid sequence, 213 residues
24000
-
fully matured enzymes CF-4 and CF-11, SDS-PAGE
33860
302 amino acid protein composed of a 88 residue propeptide and a 214 residue mature enzyme
41000
-
cathepsin F proenzyme in the yeast medium is present as two major protein bands migrating at 41000 Da and 47000 Da as a result of differential addition of N-linked glycans
47000
-
cathepsin F proenzyme in the yeast medium is present as two major protein bands migrating at 41000 Da and 47000 Da as a result of differential addition of N-linked glycans
50000
recombinant His-tag fusion protein, SDS-APGE
additional information
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
additional information
recombinant expression results in zymogen which needs to be activated, recombinant Ov-CF-1 does not autocatalytically process and activate at pH 4.5, activation can be accomplished by Fasciola hepatica cathepsin L1
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hanging-drop vapour diffusion method, 1.7 A structure of the mature domain of cathepsin F associated with an irreversible vinyl sulfone inhibitor
-
hanging-drop vapour diffusion method, mutant cathepsin F, N97Q/N108Q/N170Q, complexed with an irreversible vinyl sulfone inhibitor
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4 - 8
-
isozyme CF-4 is relatively stable at slight acidic and neutral pHs, but is comparatively unstable in acidic pHs, isozyme CF-11 is stable at acidic pHs, but is highly unstable in neutral and alkaline pH values
709866
5.5
-
cathepsin F zymogen is inactive at pH 5.5
708053
7.2
half-life 2 min
137262
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, crude extract 2 years stable
-
4°C, purified enzyme, 24 h, 50% loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
glutathione-Sepharose column chromatography
Ni-NTA column chromatography
-
Ni-NTA column chromatography, gel filtration
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cDNA cloned from primary HSCs using RACE-PCR
chromosomal localization of the gene endocing cathepsin F at 11q13
-
DNA and amino acid sequence determination and analysis
-
DNA and amino acid sequence determination and analysis, sequence comparison and phylogenetic analysis
enhanced production and release of cathepsins in tumor cells leads to tumor cell growth, invasion and metastasis
-
expressed in Escherichia coli DH5alphaMCR cells using the pGEX-4 T-1 expression vector system
expressed in Escherichia coli HEK-293T cells
-
expressed in Escherichia coli M15 (pREP4) cells
-
expressed in Escherichia coli M15 [pREP4] cells
-
expression of mature enzyme in Escherichia coli
-
PCR with primers specific for the Camellia sinensis cathepsin F gene, 5'- and 3'-RACE used to clone and identify a coding sequence of 981 bp (AY821800). The Ov-cf-1 gene is organized into 7 exons. Phylogenetic analysis confirms relationship of Ov-CF-1 with other cathepsin F proteases.
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
CtF expressions increases significantly in gill at 3 h post-injection with lipopolysaccharide
the accumulation of cathepsin F mRNA in early stage of development increases with development
the isozymes CF-4, CF-6, and CF-11 are expressed throughout various developmental stages of the parasite and the transcripts increased gradually in accordance with the maturation of the parasite
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
N97Q/N108Q/N170Q
-
KM-value for benzyloxycarbonyl-Phe-Arg-4-methylcoumaryl-7-amide is 2fold higher than that of the wild-type enzyme, the turnover number is 2fold lower
additional information
-
generation of cat F-deficient mice by homologous recombination, the mutation leads to weight loss and death within 6 months, deficient neurons accumulate eosiniophilic granules causing neuronal ceroid lipofuscinosis beginning as early as 6 weeks of age, overview
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
for isozyme CF-4, the purified recombinant protein (10 mg) is slowly added to 1 l of 100 mM Tris-HCl (pH 8.0) containing 1 mM EDTA, 250 mM L-arginine, 5 mM reduced glutathione, and 1 mM oxidized glutathione and gently stirred at 4°C for 20 h. Isozyme CF-11 is refolded in 100 mM Tris-HCl (pH 8.0) containing 1 mM EDTA, 250 mM L-arginine, 10 mM reduced glutathione, and 1 mM oxidized glutathione with the same method
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
food industry
medicine
the enzyme is immunogenic and a possible target for development of vaccines for teladorsagiosis