Information on EC 3.4.21.112 - site-1 protease

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY hide
3.4.21.112
-
RECOMMENDED NAME
GeneOntology No.
site-1 protease
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
processes precursors containing basic and hydrophobic/aliphatic residues at P4 and P2, respectively, with a relatively relaxed acceptance of amino acids at P1 and P3
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
cleavage of C-N-linkage
hydrolysis of peptide bond
CAS REGISTRY NUMBER
COMMENTARY hide
167140-48-9
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-aminobenzoic acid-Asp-Ile-Tyr-Ile-Ser-Arg-Arg-Leu-Leu-Gly-Thr-Phe-Thr-(3-nitro)Tyr-Ala + H2O
2-aminobenzoic acid-Asp-Ile-Tyr-Ile-Ser-Arg-Arg-Leu-Leu + Gly-Thr-Phe-Thr-(3-nitro)Tyr-Ala
show the reaction diagram
-
cleaves between Leu and Gly
-
?
2-aminobenzoic acid-Asp-Ile-Tyr-Ile-Ser-Arg-Arg-Leu-Leu-Gly-Thr-Phe-Thr-3-nitrotyrosyl-Ala-CONH2 + H2O
2-aminobenzoic acid-Asp-Ile-Tyr-Ile-Ser-Arg-Arg-Leu-Leu + Gly-Thr-Phe-Thr-3-nitrotyrosyl-Ala-CONH2
show the reaction diagram
-
-
-
-
?
2-aminobenzoyl-ALVLRKPLFLDSY(NO2)-Ala + H2O
?
show the reaction diagram
-
cleaves between Leu and Phe
-
?
2-aminobenzoyl-Arg-Asn-Thr-Pro-Arg-Arg-Glu-Arg-Arg-Arg-Lys-Lys-Arg-Gly-Leu-(3-nitro)Tyr-Ala + H2O
2-aminobenzoyl-Arg-Asn-Thr-Pro-Arg-Arg-Glu-Arg-Arg-Arg-Lys-Lys-Arg-Gly-Leu + (3-nitro)Tyr-Ala
show the reaction diagram
-
cleaves between Leu and 3-nitrotyrosine
-
?
2-aminobenzoyl-Arg-His-Ser-Ser-Arg-Arg-Leu-Leu-Arg-Ala-Ile-(3-nitro)Tyr-Ala + H2O
2-aminobenzoyl-Arg-His-Ser-Ser-Arg-Arg-Leu-Leu + Arg-Ala-Ile-(3-nitro)Tyr-Ala
show the reaction diagram
-
cleaves between Leu and Arg
-
?
2-aminobenzoyl-Arg-Ser-Leu-Lys-Tyr-Ala-Glu-Ser-Asp-(3-nitro)-Tyr-Ala + H2O
2-aminobenzoyl-Arg-Ser-Leu-Lys + Tyr-Ala-Glu-Ser-Asp-(3-nitro)-Tyr-Ala
show the reaction diagram
-
cleaves between Lys and Tyr
-
?
2-aminobenzoyl-Ser-Arg-Arg-Leu-Leu-Arg-Ala-Leu-Glu-(3-nitro)Tyr-Ala + H2O
2-aminobenzoyl-Ser-Arg-Arg-Leu-Leu + Arg-Ala-Leu-Glu-(3-nitro)Tyr-Ala
show the reaction diagram
-
cleaves between Leu and Arg
-
?
2-aminobenzoyl-SSGSRRLLSEESY(NO2)-Ala + H2O
?
show the reaction diagram
-
cleaves between Leu and Ser
-
?
2-aminobenzoyl-Val-Phe-Arg-Ser-Leu-Lys-Tyr-Ala-Glu-Ser-Asp-(3-nitro)Tyr-Ala + H2O
2-aminobenzoyl-Val-Phe-Arg-Ser-Leu-Lys + Tyr-Ala-Glu-Ser-Asp-(3-nitro)Tyr-Ala
show the reaction diagram
-
cleaves between Lys and Tyr
-
?
Abz-Asp-Ile-Tyr-Ile-Ser-Arg-Arg-Leu-Leu-Gly-Thr-Phe-Thr-(3-nitro)Tyr-Ala-CONH2 + H2O
Abz-Asp-Ile-Tyr-Ile-Ser-Arg-Arg-Leu-Leu + Gly-Thr-Phe-Thr-(3-nitro)Tyr-Ala-CONH2
show the reaction diagram
-
i.e. QPC251-263
-
-
?
Abz-Asp-Ile-Tyr-Ile-Ser-Arg-Arg-Leu-Leu-Gly-Thr-Phe-Thr-(3-nitro)Tyr-Ala-NH2 + H2O
?
show the reaction diagram
-
favored quenched fluorogenic substrate
-
-
?
Abz-DIYISRRLL-GTFT-Tyx-A + H2O
Abz-DIYISRRLL + GTFT-Tyx-A
show the reaction diagram
-
-
-
-
?
Abz-DIYISRRLLGTFTY(NO2)A + H2O
?
show the reaction diagram
-
S1P displays pronounced positive cooperativity with this substrate derived from the viral coat glycoprotein of the lassa virus
-
-
?
Ac-AISRRLL-7-amido-4-methylcoumarin + H2O
Ac-AISRRLL + 7-amino-4-methylcoumarin
show the reaction diagram
-
an arenavirus envelope glycoprotein precursor protein-derived peptide substrate
-
-
?
Ac-Arg-Arg-Leu-Leu-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
Ac-Arg-Ser-Leu-Lys-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
Ac-FISRRLL-7-amido-4-methylcoumarin + H2O
Ac-FISRRLL + 7-amino-4-methylcoumarin
show the reaction diagram
-
an arenavirus envelope glycoprotein precursor protein-derived peptide substrate
-
-
?
Ac-IAVGRTLK-7-amido-4-methylcoumarin + H2O
Ac-IAVGRTLK + 7-amino-4-methylcoumarin
show the reaction diagram
-
an arenavirus envelope glycoprotein precursor protein-derived peptide substrate
-
-
?
Ac-IYISRRLL-7-amido-4-methylcoumarin + H2O
Ac-IYISRRLL + 7-amino-4-methylcoumarin
show the reaction diagram
-
an arenavirus envelope glycoprotein precursor protein-derived peptide substrate
-
-
?
Ac-Leu-4-methyl-coumaryl-7-amide + H2O
?
show the reaction diagram
-
-
-
-
?
Ac-QKSIAVGRTLK-7-amido-4-methylcoumarin + H2O
Ac-QKSIAVGRTLK + 7-amino-4-methylcoumarin
show the reaction diagram
-
an arenavirus envelope glycoprotein precursor protein-derived peptide substrate
-
-
?
Ac-RKLL-7-amido-4-methylcoumarin + H2O
Ac-RKLL + 7-amino-4-methylcoumarin
show the reaction diagram
-
an arenavirus envelope glycoprotein precursor protein-derived peptide substrate
-
-
?
Ac-RRLL-7-amido-4-methylcoumarin + H2O
Ac-RRLL + 7-amino-4-methylcoumarin
show the reaction diagram
-
an arenavirus envelope glycoprotein precursor protein-derived peptide substrate
-
-
?
Ac-RRLQ-7-amido-4-methylcoumarin + H2O
Ac-RRLQ + 7-amino-4-methylcoumarin
show the reaction diagram
-
an arenavirus envelope glycoprotein precursor protein-derived peptide substrate
-
-
?
Ac-RTLK-7-amido-4-methylcoumarin + H2O
Ac-RTLK + 7-amino-4-methylcoumarin
show the reaction diagram
-
an arenavirus envelope glycoprotein precursor protein-derived peptide substrate
-
-
?
Ac-SFITRRLQ-7-amido-4-methylcoumarin + H2O
Ac-SFITRRLQ + 7-amino-4-methylcoumarin
show the reaction diagram
-
an arenavirus envelope glycoprotein precursor protein-derived peptide substrate
-
-
?
Ac-VFRSLK-4-methyl-coumaryl-7-amide + H2O
?
show the reaction diagram
Ac-VFRSLK-4-methylcoumarin 7-amide
?
show the reaction diagram
-
-
-
?
Ac-VFRSLK-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
-
-
?
Ac-YISRRLL-7-amido-4-methylcoumarin + H2O
Ac-YISRRLL + 7-amino-4-methylcoumarin
show the reaction diagram
-
an arenavirus envelope glycoprotein precursor protein-derived peptide substrate
-
-
?
Ac-YSSVSRKLL-7-amido-4-methylcoumarin + H2O
Ac-YSSVSRKLL + 7-amino-4-methylcoumarin
show the reaction diagram
-
an arenavirus envelope glycoprotein precursor protein-derived peptide substrate
-
-
?
arenavirus envelope glycoprotein precursor + H2O
?
show the reaction diagram
ATF6 + H2O
?
show the reaction diagram
ATF6 precursor + H2O
nuclear ATF6
show the reaction diagram
-
rSt-1 and rSt-2 seem to affect the processing of ATF6 by SKI-1
-
-
?
brain-derived neurotrophic factor precursor + H2O
?
show the reaction diagram
-
cleaves at an RGLTLS site between Thr and Ser
-
?
CREB4 + H2O
?
show the reaction diagram
-
i.e. androgen-induced leucine zipper protein, C-terminal domain of CREB4 somehow confers resistance to cleavage by S1P, which can be released either by removal of the region or physiologically by some regulatory signal
-
-
?
Crimean Congo hemorrhagic fever virus glycoprotein + H2O
?
show the reaction diagram
Crimean Congo hemorrhagic fever virus glycoprotein + H2O
glycoprotein precursor Gn + glycoprotein precursor Gc
show the reaction diagram
-
-
-
-
?
Dabcyl-Arg-His-Ser-Ser-Arg-Arg-Leu-Leu-Arg-Ala-Leu-Glu-Gly-Gly-Lys(tetramethylrhodamine)-OH + H2O
?
show the reaction diagram
-
-
-
?
Dabcyl-Ser-Gly-Ser-Gly-Arg-Ser-Val-Leu-Ser-Phe-Glu-Ser-Gly-Ser-Lys(tetramethylrhodamine)-Arg-OH + H2O
?
show the reaction diagram
-
-
-
?
glycoprotein + H2O
?
show the reaction diagram
-
S1P is involved in the processing of the glycoproteins of the genetically more-distant South American hemorrhagic fever viruses Guanarito, Machupo, and Junin
-
-
?
glycoprotein precursor Gc + H2O
?
show the reaction diagram
glycoprotein precursor Gn + H2O
?
show the reaction diagram
-
-
-
-
?
Lassa virus envelope glycoprotein precursor + H2O
?
show the reaction diagram
-
the enzyme recognition motif RRLL is critical for the processing of the Lassa virus envelope glycoprotein in the endoplasmic reticulum/cis-Golgi compartment
-
-
?
Lassa virus glycoprotein + H2O
?
show the reaction diagram
-
cleavage at RRLL-sites
-
-
?
Lassa virus glycoprotein precursor GP-C + H2O
Lassa virus glycoprotein GP-2 + ?
show the reaction diagram
-
cleavage at the C-terminal end of the recognition motif R-R-L-L
-
-
?
Lassa virus glycoprotein precursor protein + H2O
peripheral virion attachment protein GP1 + fusion-active transmembrane protein GP2
show the reaction diagram
-
-
Arg-Arg-Leu-Leu + Gly-Thr-Phe
-
?
lymphocytic choriomeningitis virus glycoprotein precursor protein + H2O
peripheral virion attachment protein GP1 + fusion-active transmembrane protein GP2
show the reaction diagram
-
-
Arg-Arg-Leu-Ala + Gly-Thr-Phe
-
?
membrane-associated transcription factor bZIP28 + H2O
?
show the reaction diagram
RsiW + H2O
?
show the reaction diagram
sterol regulatory element-binding protein + H2O
?
show the reaction diagram
sterol regulatory element-binding protein SREBP-2 + H2O
?
show the reaction diagram
-
-
-
-
?
succinyl-YISRRLL-7-amido-4-methylcoumarin + H2O
succinyl-YISRRLL + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
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
Ac-AISRRLL-7-amido-4-methylcoumarin + H2O
Ac-AISRRLL + 7-amino-4-methylcoumarin
show the reaction diagram
-
an arenavirus envelope glycoprotein precursor protein-derived peptide substrate
-
-
?
Ac-FISRRLL-7-amido-4-methylcoumarin + H2O
Ac-FISRRLL + 7-amino-4-methylcoumarin
show the reaction diagram
-
an arenavirus envelope glycoprotein precursor protein-derived peptide substrate
-
-
?
Ac-IAVGRTLK-7-amido-4-methylcoumarin + H2O
Ac-IAVGRTLK + 7-amino-4-methylcoumarin
show the reaction diagram
-
an arenavirus envelope glycoprotein precursor protein-derived peptide substrate
-
-
?
Ac-IYISRRLL-7-amido-4-methylcoumarin + H2O
Ac-IYISRRLL + 7-amino-4-methylcoumarin
show the reaction diagram
-
an arenavirus envelope glycoprotein precursor protein-derived peptide substrate
-
-
?
Ac-QKSIAVGRTLK-7-amido-4-methylcoumarin + H2O
Ac-QKSIAVGRTLK + 7-amino-4-methylcoumarin
show the reaction diagram
-
an arenavirus envelope glycoprotein precursor protein-derived peptide substrate
-
-
?
Ac-RKLL-7-amido-4-methylcoumarin + H2O
Ac-RKLL + 7-amino-4-methylcoumarin
show the reaction diagram
-
an arenavirus envelope glycoprotein precursor protein-derived peptide substrate
-
-
?
Ac-RRLL-7-amido-4-methylcoumarin + H2O
Ac-RRLL + 7-amino-4-methylcoumarin
show the reaction diagram
-
an arenavirus envelope glycoprotein precursor protein-derived peptide substrate
-
-
?
Ac-RRLQ-7-amido-4-methylcoumarin + H2O
Ac-RRLQ + 7-amino-4-methylcoumarin
show the reaction diagram
-
an arenavirus envelope glycoprotein precursor protein-derived peptide substrate
-
-
?
Ac-RTLK-7-amido-4-methylcoumarin + H2O
Ac-RTLK + 7-amino-4-methylcoumarin
show the reaction diagram
-
an arenavirus envelope glycoprotein precursor protein-derived peptide substrate
-
-
?
Ac-SFITRRLQ-7-amido-4-methylcoumarin + H2O
Ac-SFITRRLQ + 7-amino-4-methylcoumarin
show the reaction diagram
-
an arenavirus envelope glycoprotein precursor protein-derived peptide substrate
-
-
?
Ac-YISRRLL-7-amido-4-methylcoumarin + H2O
Ac-YISRRLL + 7-amino-4-methylcoumarin
show the reaction diagram
-
an arenavirus envelope glycoprotein precursor protein-derived peptide substrate
-
-
?
Ac-YSSVSRKLL-7-amido-4-methylcoumarin + H2O
Ac-YSSVSRKLL + 7-amino-4-methylcoumarin
show the reaction diagram
-
an arenavirus envelope glycoprotein precursor protein-derived peptide substrate
-
-
?
arenavirus envelope glycoprotein precursor + H2O
?
show the reaction diagram
Lassa virus glycoprotein precursor protein + H2O
peripheral virion attachment protein GP1 + fusion-active transmembrane protein GP2
show the reaction diagram
-
-
Arg-Arg-Leu-Leu + Gly-Thr-Phe
-
?
lymphocytic choriomeningitis virus glycoprotein precursor protein + H2O
peripheral virion attachment protein GP1 + fusion-active transmembrane protein GP2
show the reaction diagram
-
-
Arg-Arg-Leu-Ala + Gly-Thr-Phe
-
?
membrane-associated transcription factor bZIP28 + H2O
?
show the reaction diagram
-
endoplasmic reticulum stress-induced activation, the RRIL573 site, but not the RVLM373 site, on the lumen-facing domain of bZIP28 is critical for the biological function of bZIP28 under endoplasmic reticulum stress condition
-
-
?
succinyl-YISRRLL-7-amido-4-methylcoumarin + H2O
succinyl-YISRRLL + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
CaCl2
-
recombinant S1P-1 activity can be stimulated by Ca2+, but is not dependent on Ca2+. Increases activity of recombinant S1P-1 60% at 4 mM, higher concentrations of CaCl2 lowers the activity
K-phosphate buffer
-
-
KCl
-
increases activity of recombinant S1P-1 25% dependent on the substrate used
Na-phosphate buffer
-
-
NaCl
-
increases activity of recombinant S1P-1 25% at 50 mM dependent on the substrate used
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2R,2'R)-2,2'-[(E)-diazene-1,2-diylbis[benzene-2,1-diyloxy(1-oxoethane-2,1-diyl)imino[(2S)-1-oxo-4-phenylbutane-2,1-diyl]imino]]bis(3-phenylpropanoic acid)
-
-
(2S,2'S)-2,2'-[(E)-diazene-1,2-diylbis[benzene-2,1-diyloxy(1-oxoethane-2,1-diyl)imino]]bis(3-methylbutanoic acid)
-
-
(2S,2'S)-2,2'-[(E)-diazene-1,2-diylbis[benzene-2,1-diyloxy(1-oxoethane-2,1-diyl)imino]]bis(4-phenylbutanoic acid)
-
-
(3S,4S,5S,6R)-2-([(2R,3S,4S,5S,6S)-3,5-dihydroxy-2-(hydroxymethyl)-6-methoxytetrahydro-2H-pyran-4-yl]amino)-6-(hydroxymethyl)tetrahydro-2H-thiopyran-3,4,5-triol
-
i.e. BJ-12-26-1, greatly reduces SKI-1 zymogen processing, and abolishes the processing of substrate SREBP-2
(3S,4S,5S,6R)-2-([(2S,3S,4R,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3-yl]amino)-6-(hydroxymethyl)tetrahydro-2H-thiopyran-3,4,5-triol
-
i.e. BJ-12-21-2, greatly reduces SKI-1 zymogen processing, and abolishes the processing of substrate SREBP-2
(R)-4-((diethylamino)methyl)-N-(2-methoxyphenethyl)-N-(pyrrolidin-3-yl)benzamide
-
inhibits endogenous SREBP processing in Chinese hamster ovary cells. Compound down-regulates the signal from an SRE-luciferase reporter gene in human embryonic kidney 293 cells and the expression of endogenous SREBP target genes in cultured HepG2 cells. In mice treated with the compound for 24 h, the expression of hepatic SREBP target genes is suppressed, and the hepatic rates of cholesterol and fatty acid synthesis are reduced
(S)-4-((diethylamino)methyl)-N-(2-methoxyphenethyl)-N-(pyrrolidin-3-yl)benzamide
-
; purified S-enantiomer
1,10-phenanthroline
1-(4-[[2-(2-methoxyphenyl)ethyl](pyrrolidin-3-yl)carbamoyl]benzyl)piperidine-3-carboxamide
-
-
2,2'-[(E)-diazene-1,2-diylbis[benzene-2,1-diyloxy(1-oxoethane-2,1-diyl)imino]]diacetic acid
-
-
3,4-dichloroisocoumarin
-
potent slow binding inhibitor, 100% inhibition by 0.05 mM
4-(2-aminoethyl benzene)sulfonyl fluoride
-
i.e. AEBSF, competitive
4-(2-aminoethyl)-benzenesulfonyl fluoride
-
-
4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride
4-(2-azabicyclo[2.2.1]hept-2-ylmethyl)-N-[2-(2-methoxyphenyl)ethyl]-N-pyrrolidin-3-ylbenzamide
-
-
4-(6-azabicyclo[3.2.1]oct-6-ylmethyl)-N-[2-(2-methoxyphenyl)ethyl]-N-pyrrolidin-3-ylbenzamide
-
-
4-(benzyloxy)-N-[2-(2-chlorophenyl)ethyl]-N-pyrrolidin-3-ylbenzamide
-
-
4-(benzyloxy)-N-[2-(2-methoxyphenyl)ethyl]-N-pyrrolidin-3-ylbenzamide
-
-
4-(benzyloxy)-N-[2-(3-chlorophenyl)ethyl]-N-pyrrolidin-3-ylbenzamide
-
-
4-([[(1S,2S)-2-hydroxycyclohexyl]amino]methyl)-N-[2-(2-methoxyphenyl)ethyl]-N-pyrrolidin-3-ylbenzamide
-
-
4-[(diethylamino)methyl]-N-[2-(2-ethoxyphenyl)ethyl]-N-pyrrolidin-3-ylbenzamide
-
-
4-[(diethylamino)methyl]-N-[2-(2-methoxyphenyl)ethyl]-N-pyrrolidin-3-ylbenzamide
-
-
4-[(diethylamino)methyl]-N-[2-(2-methoxyphenyl)ethyl]-N-[(3R)-pyrrolidin-3-yl]benzamide
-
-
4-[(diethylamino)methyl]-N-[2-(2-methylphenyl)ethyl]-N-pyrrolidin-3-ylbenzamide
-
-
4-[[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]methyl]-N-[2-(2-methoxyphenyl)ethyl]-N-pyrrolidin-3-ylbenzamide
-
-
Ac-VFRSLK-4-(2-aminoethyl benzene)sulfonyl fluoride
-
-
benzyl N-[(2-[(E)-[2-(2-oxo-2-[[(1S)-2-oxo-2-phenoxy-1-phenylethyl]amino]ethoxy)phenyl]diazenyl]phenoxy)acetyl]-L-phenylalaninate
-
competitive. E-isomer is thermally stable
benzyl N-[(2-[(E)-[2-(2-[[(2S)-3-methyl-1-oxo-1-phenoxybutan-2-yl]amino]-2-oxoethoxy)phenyl]diazenyl]phenoxy)acetyl]-L-leucinate
-
competitive. E-isomer is thermally stable
brefeldin A
-
abrogates St-2 production
Ca2+
-
inhibition above 3 mM
Co2+
-
-
CuSO4
-
complete inactivation at 1 mM
decanoyl-RRLL-chloromethylketone
-
the selective and cell-permeable small-peptide inhibitor inhibits the enzyme and leads to suppression of proliferation and metabolic activity of melanoma cells in vitro. The inhibitor induces classical apoptosis of melanoma cells in vitro and affects expression of several SKI-1 target genes including activating transcription factor 6. The compound induces cell death in an ATF6-independent manner
decanoyl-RVKR-chlorometylketone
-
66% inhibition at 0.05 mM
dibenzyl (2R,2'S)-2,2'-[(E)-diazene-1,2-diylbis[benzene-2,1-diyloxy(1-oxoethane-2,1-diyl)imino]]bis(3-methylbutanoate)
-
-
dibenzyl (2R,2'S)-2,2'-[(E)-diazene-1,2-diylbis[benzene-2,1-diyloxy(1-oxoethane-2,1-diyl)imino]]bis(3-phenylpropanoate)
-
-
dithiothreitol
-
partial inhibition at very high concentrations
ethanolamine
-
supresses cleavage by dS1P
gabexate mesylate
-
8% inhibition at 0.05 mM
N-(2-chlorobenzyl)-4-(1-methylethoxy)-N-pyrrolidin-3-ylbenzamide
-
-
N-[(2-[(E)-[2-(2-[[(1S)-1-carboxy-2-methylpropyl]amino]-2-oxoethoxy)phenyl]diazenyl]phenoxy)acetyl]-L-leucine
-
competitive. E-isomer is thermally stable
N-[2-(2,6-dichlorophenyl)ethyl]-4-[(diethylamino)methyl]-N-pyrrolidin-3-ylbenzamide
-
-
N-[2-(2-chlorophenyl)ethyl]-4-(1-methylethoxy)-N-pyrrolidin-3-ylbenzamide
-
-
N-[2-(2-chlorophenyl)ethyl]-4-[(diethylamino)methyl]-N-pyrrolidin-3-ylbenzamide
-
-
N-[2-(2-chlorophenyl)ethyl]-4-[[3-(2-methylphenyl)piperidin-1-yl]methyl]-N-pyrrolidin-3-ylbenzamide
-
-
N-[2-(2-fluorophenyl)ethyl]-4-(1-methylethoxy)-N-pyrrolidin-3-ylbenzamide
-
-
N-[2-(2-methoxyphenyl)ethyl]-4-(piperidin-1-ylmethyl)-N-pyrrolidin-3-ylbenzamide
-
-
N-[2-(2-methoxyphenyl)ethyl]-4-[[3-(2-methylphenyl)piperidin-1-yl]methyl]-N-pyrrolidin-3-ylbenzamide
-
-
N-[2-(3-chlorophenyl)ethyl]-4-(1-methylethoxy)-N-pyrrolidin-3-ylbenzamide
-
-
N-[2-(4-chlorophenyl)ethyl]-4-[(diethylamino)methyl]-N-pyrrolidin-3-ylbenzamide
-
-
Ni2+
-
-
palmitate
-
supresses cleavage by dS1P
Pefabloc SC
-
at high concentrations
PF-429242
-
potent S1P inhibitor both in vitro and in cell-based assays, PF-429242 inhibits S1P-mediated processing of arenavirus arenavirus glycoprotein precursor protein
PMSF
-
12% inhibition at 0.05 mM
prosegment of SKI-1
-
-
-
Zn2+
-
-
ZnSO4
-
complete inactivation at 1 mM
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
EDTA
-
increase in activity about 40% at 10 mM
EGTA
-
increase in activity about 40% at 10 mM
N-acetyl-leucinal-leucinal-norleucinal
-
increases the level of St-1
additional information
-
cellular stress induced by tunicamycin does not regulate the production of St-2
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0051
2-aminobenzoic acid-SSGSRRLLSEESY(NO2)-Ala-NH2
-
pH 7.4
0.028
2-aminobenzoyl-Arg-Asn-Thr-Pro-Arg-Arg-Glu-Arg-Arg-Arg-Lys-Lys-Arg-Gly-Leu-(3-nitro)Tyr-Ala
-
pH 7.4, 37C
0.02
2-aminobenzoyl-Arg-His-Ser-Ser-Arg-Arg-Leu-Leu-Arg-Ala-Ile-(3-nitro)Tyr-Ala
-
pH 7.4, 37C
0.00096
2-aminobenzoyl-Arg-Ser-Leu-Lys-Tyr-Ala-Glu-Ser-Asp-(3-nitro)Tyr-Ala
-
pH 7.4, 37C
0.0044
2-aminobenzoyl-Asp-Ile-Tyr-Ile-Ser-Arg-Arg-Leu-Leu-Gly-Thr-Phe-Thr-(3-nitro)Tyr-Ala
-
pH 7.4, 37C
0.023
2-aminobenzoyl-Ser-Arg-Arg-Leu-Leu-Arg-Ala-Leu-Glu-(3-nitro)Tyr-Ala
-
pH 7.4, 37C
0.00428
2-aminobenzoyl-Val-Phe-Arg-Ser-Leu-Lys-Tyr-Ala-Glu-Ser-Asp-(3-nitro)Tyr-Ala
-
pH 7.4, 37C
0.0031
Abz-DIYISRRLLGTFTY(NO2)A
-
-
0.0504 - 0.067
Ac-AISRRLL-7-amido-4-methylcoumarin
0.0255
Ac-Arg-Arg-Leu-Leu-p-nitroanilide
-
-
0.1335
Ac-Arg-Ser-Leu-Lys-p-nitroanilide
-
-
0.0123 - 0.015
Ac-FISRRLL-7-amido-4-methylcoumarin
0.0226 - 0.0846
Ac-IAVGRTLK-7-amido-4-methylcoumarin
0.0047 - 0.0074
Ac-IYISRRLL-7-amido-4-methylcoumarin
0.0025 - 0.0156
Ac-QKSIAVGRTLK-7-amido-4-methylcoumarin
0.0274 - 0.0564
Ac-RKLL-7-amido-4-methylcoumarin
0.0153 - 0.0228
Ac-RRLL-7-amido-4-methylcoumarin
0.0971 - 0.2263
Ac-RRLQ-7-amido-4-methylcoumarin
0.0967 - 0.2167
Ac-RTLK-7-amido-4-methylcoumarin
0.0443 - 0.0784
Ac-SFITRRLQ-7-amido-4-methylcoumarin
0.1
Ac-VFRSLK-4-methyl-coumaryl-7-amide
-
pH 8, 37C
0.0028 - 0.0057
Ac-YISRRLL-7-amido-4-methylcoumarin
0.0212 - 0.0281
Ac-YSSVSRKLL-7-amido-4-methylcoumarin
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.046
Abz-DIYISRRLLGTFTY(NO2)A
Homo sapiens
-
-
0.03
Ac-Arg-Arg-Leu-Leu-p-nitroanilide
Homo sapiens
-
-
0.005
Ac-Arg-Ser-Leu-Lys-p-nitroanilide
Homo sapiens
-
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.14
(2R,2'R)-2,2'-[(E)-diazene-1,2-diylbis[benzene-2,1-diyloxy(1-oxoethane-2,1-diyl)imino[(2S)-1-oxo-4-phenylbutane-2,1-diyl]imino]]bis(3-phenylpropanoic acid)
-
in 25 mM Tris, 25 mM MES, 2 mM CaCl2, pH 7.4, at 37C
0.075
(2S,2'S)-2,2'-[(E)-diazene-1,2-diylbis[benzene-2,1-diyloxy(1-oxoethane-2,1-diyl)imino]]bis(3-methylbutanoic acid)
-
in 25 mM Tris, 25 mM MES, 2 mM CaCl2, pH 7.4, at 37C
0.225
(2S,2'S)-2,2'-[(E)-diazene-1,2-diylbis[benzene-2,1-diyloxy(1-oxoethane-2,1-diyl)imino]]bis(4-phenylbutanoic acid)
-
in 25 mM Tris, 25 mM MES, 2 mM CaCl2, pH 7.4, at 37C
0.265
2,2'-[(E)-diazene-1,2-diylbis[benzene-2,1-diyloxy(1-oxoethane-2,1-diyl)imino]]diacetic acid
-
in 25 mM Tris, 25 mM MES, 2 mM CaCl2, pH 7.4, at 37C
231
4-(2-aminoethyl benzene)sulfonyl fluoride
-
substrate Abz-DIYISRRLL-GTFT-Tyx-A, 37C, pH 7.4
57.7
Ac-VFRSLK-4-(2-aminoethyl benzene)sulfonyl fluoride
-
substrate Abz-DIYISRRLL-GTFT-Tyx-A, 37C, pH 7.4
0.0118
benzyl N-[(2-[(E)-[2-(2-oxo-2-[[(1S)-2-oxo-2-phenoxy-1-phenylethyl]amino]ethoxy)phenyl]diazenyl]phenoxy)acetyl]-L-phenylalaninate
-
pH 7.4, 37C
0.125
benzyl N-[(2-[(E)-[2-(2-[[(2S)-3-methyl-1-oxo-1-phenoxybutan-2-yl]amino]-2-oxoethoxy)phenyl]diazenyl]phenoxy)acetyl]-L-leucinate
-
pH 7.4, 37C
0.125
dibenzyl (2R,2'S)-2,2'-[(E)-diazene-1,2-diylbis[benzene-2,1-diyloxy(1-oxoethane-2,1-diyl)imino]]bis(3-methylbutanoate)
-
in 25 mM Tris, 25 mM MES, 2 mM CaCl2, pH 7.4, at 37C
0.0118
dibenzyl (2R,2'S)-2,2'-[(E)-diazene-1,2-diylbis[benzene-2,1-diyloxy(1-oxoethane-2,1-diyl)imino]]bis(3-phenylpropanoate)
-
in 25 mM Tris, 25 mM MES, 2 mM CaCl2, pH 7.4, at 37C
0.0758
N-[(2-[(E)-[2-(2-[[(1S)-1-carboxy-2-methylpropyl]amino]-2-oxoethoxy)phenyl]diazenyl]phenoxy)acetyl]-L-leucine
-
pH 7.4, 37C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000175 - 0.0005
(R)-4-((diethylamino)methyl)-N-(2-methoxyphenethyl)-N-(pyrrolidin-3-yl)benzamide
0.000393 - 0.000971
(S)-4-((diethylamino)methyl)-N-(2-methoxyphenethyl)-N-(pyrrolidin-3-yl)benzamide
0.00016
1-(4-[[2-(2-methoxyphenyl)ethyl](pyrrolidin-3-yl)carbamoyl]benzyl)piperidine-3-carboxamide
Homo sapiens
-
-
0.000095
4-(2-azabicyclo[2.2.1]hept-2-ylmethyl)-N-[2-(2-methoxyphenyl)ethyl]-N-pyrrolidin-3-ylbenzamide
Homo sapiens
-
-
0.000029
4-(6-azabicyclo[3.2.1]oct-6-ylmethyl)-N-[2-(2-methoxyphenyl)ethyl]-N-pyrrolidin-3-ylbenzamide
Homo sapiens
-
-
0.00059
4-(benzyloxy)-N-[2-(2-chlorophenyl)ethyl]-N-pyrrolidin-3-ylbenzamide
Homo sapiens
-
-
0.00031
4-(benzyloxy)-N-[2-(2-methoxyphenyl)ethyl]-N-pyrrolidin-3-ylbenzamide
Homo sapiens
-
-
0.00051
4-(benzyloxy)-N-[2-(3-chlorophenyl)ethyl]-N-pyrrolidin-3-ylbenzamide
Homo sapiens
-
-
0.0001
4-([[(1S 2S)-2-hydroxycyclohexyl]amino]methyl)-N-[2-(2-methoxyphenyl)ethyl]-N-pyrrolidin-3-ylbenzamide
Homo sapiens
-
-
0.016
4-[(diethylamino)methyl]-N-[2-(2-ethoxyphenyl)ethyl]-N-pyrrolidin-3-ylbenzamide
Homo sapiens
-
-
0.00054
4-[(diethylamino)methyl]-N-[2-(2-methoxyphenyl)ethyl]-N-pyrrolidin-3-ylbenzamide
Homo sapiens
-
-
0.00017
4-[(diethylamino)methyl]-N-[2-(2-methoxyphenyl)ethyl]-N-[(3R)-pyrrolidin-3-yl]benzamide
Homo sapiens
-
-
0.0016
4-[(diethylamino)methyl]-N-[2-(2-methylphenyl)ethyl]-N-pyrrolidin-3-ylbenzamide
Homo sapiens
-
-
0.00014
4-[[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]methyl]-N-[2-(2-methoxyphenyl)ethyl]-N-pyrrolidin-3-ylbenzamide
Homo sapiens
-
-
0.005
N-(2-chlorobenzyl)-4-(1-methylethoxy)-N-pyrrolidin-3-ylbenzamide
Homo sapiens
-
-
0.00043
N-[2-(2 6-dichlorophenyl)ethyl]-4-[(diethylamino)methyl]-N-pyrrolidin-3-ylbenzamide
Homo sapiens
-
-
0.0014
N-[2-(2-chlorophenyl)ethyl]-4-(1-methylethoxy)-N-pyrrolidin-3-ylbenzamide
Homo sapiens
-
-
0.00084
N-[2-(2-chlorophenyl)ethyl]-4-[(diethylamino)methyl]-N-pyrrolidin-3-ylbenzamide
Homo sapiens
-
-
0.000008
N-[2-(2-chlorophenyl)ethyl]-4-[[3-(2-methylphenyl)piperidin-1-yl]methyl]-N-pyrrolidin-3-ylbenzamide
Homo sapiens
-
most potent inhibitor
0.009
N-[2-(2-fluorophenyl)ethyl]-4-(1-methylethoxy)-N-pyrrolidin-3-ylbenzamide
Homo sapiens
-
-
0.00025
N-[2-(2-methoxyphenyl)ethyl]-4-(piperidin-1-ylmethyl)-N-pyrrolidin-3-ylbenzamide
Homo sapiens
-
-
0.000037
N-[2-(2-methoxyphenyl)ethyl]-4-[[3-(2-methylphenyl)piperidin-1-yl]methyl]-N-pyrrolidin-3-ylbenzamide
Homo sapiens
-
-
0.0096
N-[2-(3-chlorophenyl)ethyl]-4-(1-methylethoxy)-N-pyrrolidin-3-ylbenzamide
Homo sapiens
-
-
0.0037
N-[2-(4-chlorophenyl)ethyl]-4-[(diethylamino)methyl]-N-pyrrolidin-3-ylbenzamide
Homo sapiens
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.007
-
first 997 amino acids of human S1P lacking the C-terminal transmembrane region prepared from Trichoplusia ni egg, High Five cells
0.022
-
first 997 amino acids of human S1P lacking the C-terminal transmembrane region prepared from Sf21 cells, 103fold purified
0.2
-
first 997 amino acids of human S1P lacking the C-terminal transmembrane region prepared from Sf21 cells
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 8
-
-
7.5
-
assay at
8
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
the enzyme SKI-1 is constitutively expressed in human pigment cells with higher SKI activity in seven out of eight melanoma cell lines compared with normal melanocytes, also detectable in tumor cells of melanoma metastases
Manually annotated by BRENDA team
-
osteosarcoma cell line used. Mineralizing UMR 106 cells express a 98 kDa active, soluble form of SKI-1 within biomineralization foci. Non-mineralizing UMR cells differentially process SKI-1 into smaller immunoreactive fragments
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
additional information
-
the truncated mutant DELTA AC SKI-1/S1P BTMD, truncated before the transmembrane domain, stays in the endoplasmic reticulum
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8500
-
St-2 protein, time-of-flight mass spectrometry
35000
-
SDS-PAGE, predominant form in non-mineralizing cultures are smaller than 35 kDa
91000
-
gel filtration
92300
-
sequence analysis
100000
-
x * 100000, about, SDS-PAGE
148000
-
zymogen, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 100000, about, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
proteolytic modification
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80C, 40% (v/v) glycerol
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
first 997 amino acids of human S1P lacking the C-terminal transmembrane region 103fold purified by immobilised metal affinity chromatography on Co2+ column
-
recombinant C-terminally His6-tagged wild-type mutant enzyme from HEK-293T cell medium by immobilized metal affinity chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cDNA encoding amino acids 17 to 997, encompassing the prodomain, catalytic domain, and cysteine-rich domain of soluble site 1 protease (sS1P) is expressed in CHO cells
-
expressed in Escherichia coli
-
expression in CHO K1 and SRD-12B cells
-
first 997 amino acids of human S1P lacking the C-terminal transmembrane region. Full-length sequence of human S1P. Both tagged with a C-terminal 8 x His-tag, subcloned into the entry vector pDONR201 and expressed by baculovirus expression vector system in Sf9 cells. Additionally, first 997 amino acids of human S1P lacking the C-terminal transmembrane region expressed in Sf21 cells and Trichoplusia ni egg, High Five cells
-
full length SKI-1 and its H249A mutant expressed in HEK-293 cells, M19 cells, HuH7 cells and Hep-G2 cells. Wild-type SKI-1 and mutants H249A, L925A and K948A expressed in SRD-12B and CHO-K1 cells. Wild-type SKI-1 or a secretable form of St-1 containing a signal peptide followed by a FLAG tag at the N terminus and a V5 tag at the C terminus overexpressed in CHO-K1 cells. rSt-1 coexpressed with protease inhibitors in CHO-K1 and Neuro-2a cells. Mutants I985A, I989L, M990L, M990A, M990I, Y994A, N995A, and double mutant Y994A/N995A expressed in CHO-K1 cells
-
functional expression of full-length wild-type enzyme, which undergoes complete autoprocessing, in SRD12B cells. Recombinant expression HEK-293T and CHO cells, real-time quantitative PCR expression analysis
-
into pcMV-S1P-Myc
-
overexpression of proSKI variants in HepG2 cells
-
pCDNA3.1-SKI/S1P expressed in CHO-K1, BHK, Vero, or SRD-12B cells
-
prsW+ and mutant E95K expressed in Escherichia coli. PrsW active-site mutants expressed in Bacillus subtilis
-
SKI-1/S1P deficient SRD12B cells transiently transfected with SKI-1/S1P-containing vector
-
transient expression of C-terminally His6-tagged full-length wild-type enzyme and a soluble enzyme variant truncated before the transmembrane domain, the catalytically inactive mutant H249A, B'/B, B' mutants of enzyme in HEK-293T cells, secretion of proteins. Wild-type and the DELTA AC SKI-1/S1P FL mutant are expressed in the SKI-I/S1P-deficient CHO cell line SRD12B, which lacks active endogenous enzyme
-
transient expression of wild-type and mutant enzymes in enzyme-deficient SRD12B cells
-
truncated from lacking the COOH-terminal membrane anchor, expressed in CHO cells
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E75A/E76A
-
is catalytically inactive and traps RsiW in a complex in which the anti-sigma factor is protected from undergoing proteolysis
E95K
-
missense mutant with a a dominant (gain-of-function) mutation. Exhibits heightened resistance to the SdpC toxin in cells lacking the SdpI immunity protein. Is locked in a state that causes constitutive activation of sigmaW
H175A
-
is catalytically inactive and traps RsiW in a complex in which the anti-sigma factor is protected from undergoing proteolysis
E75A/E76A
-
is catalytically inactive and traps RsiW in a complex in which the anti-sigma factor is protected from undergoing proteolysis
-
E95K
-
missense mutant with a a dominant (gain-of-function) mutation. Exhibits heightened resistance to the SdpC toxin in cells lacking the SdpI immunity protein. Is locked in a state that causes constitutive activation of sigmaW
-
H175A
-
is catalytically inactive and traps RsiW in a complex in which the anti-sigma factor is protected from undergoing proteolysis
-
S414A
-
inactive mutant, no autocatalytic processing to generate S1P-C
I985A
-
has no effect on generation of St-2
I989L
-
results in more than 90% reduction in the generation of St-2
K948A
-
shedding site mutant
L952A
-
shedding site mutant
M990A
-
fails to generate St-2
M990I
-
fails to generate St-2
M990L
-
fails to generate St-2
N995A
-
has no effect on generation of St-2
R130A/K131A
-
proSKI variant that exhibits no basic residue at the P4 position, has no effect on HMG-CoA reductase mRNA levels
R130E/R134E
-
site-directed mutagenesis, the double mutations at the B'/B site prevents autoprocessing
R160E
-
site-directed mutagenesis
R163E/R164E
-
site-directed mutagenesis
Y285A
-
site-directed mutagenesis, molecular modeling
Y994A
-
has no effect on generation of St-2
Y994A/N995A
-
has no effect on generation of St-2
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
degradation
-
S1P reduces the size of the luminal domain to prepare ATF6 to be an optimal S2P substrate
medicine
additional information