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Information on EC 3.4.99.B1 - RCE1 and Organism(s) Homo sapiens and UniProt Accession Q9Y256
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3.4.99.B1 RCE1Specify your search results
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The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Proteolytically removes the C-terminal three residues of farnesylated and geranylated proteins
Synonyms
rce1p, hrce1, ras converting enzyme 1, ras-converting enzyme 1, ras converting enzyme, ras and a-factor converting enzyme, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CAS REGISTRY NUMBER
COMMENTARY
148463-92-7
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
farnesyl-Ki-Ras-CaaX + H2O
farnesyl-Ki-Ras-C + aaX
specific for prenylated proteins containing a C-terminal CaaX motif
-
?
geranylgeranyl-Ki-Ras-CaaX + H2O
geranylgeranyl-Ki-Ras-C + aaX
-
-
?
geranylgeranyl-Rab1b-CaaX + H2O
geranylgeranyl-Rab1b-C + aaX
-
-
?
2-aminobenzoyl-KSKTKC(farnesyl)dinitrophenyldiaminopropionic acid-IM + H2O
2-aminobenzoyl-KSKTKC(farnesyl) + dinitrophenyldiaminopropionic acid-IM
-
34% of activity with KSKTKC(farnesyl)VIM
-
?
2-aminobenzoyl-KSKTKC(farnesyl)lysine-epsilon-dinitrophenyl-IM + H2O
2-aminobenzoyl-KSKTKC(farnesyl) + lysine-epsilon-dinitrophenyl-IM
-
50% of activity with KSKTKC(farnesyl)VIM
-
?
2-aminobenzoyl-KSKTKC(farnesyl)QLIM + H2O
?
-
cleavage of a quenched fluorogenic farnesylated peptide that is based on the C-terminal sequence of the K-Ras4b precursor (2-aminobenzoyl-KSKTKC(farnesyl)-K(Dnp)-IM)
-
-
?
2-aminobenzoyl-KSKTKC(farnesyl)VI-dinitrophenyldiaminopropionic acid + H2O
2-aminobenzoyl-KSKTKC(farnesyl) + VI-dinitrophenyldiaminopropionic acid
-
4.8% of activity with KSKTKC(farnesyl)VIM
-
?
2-aminobenzoyl-KSKTKC(farnesyl)VI-lysine-epsilon-dinitrophenyl + H2O
2-aminobenzoyl-KSKTKC(farnesyl) + VI-lysine-epsilon-dinitrophenyl
-
25% of activity with KSKTKC(farnesyl)VIM
-
?
2-aminobenzoyl-KSKTKC(farnesyl)VIM + H2O
2-aminobenzoyl-KSKTKC(farnesyl) + VIM
-
-
-
?
7-methoxycoumarin-4-acetyl-KSKTKC(farnesyl)-dinitrophenyldiaminopropionic acid-IM + H2O
7-methoxycoumarin-4-acetyl-KSKTKC(farnesyl) + dinitrophenyldiaminopropionic acid-IM
-
2.5% of activity with KSKTKC(farnesyl)VIM
-
?
7-methoxycoumarin-4-acetyl-KSKTKC(farnesyl)-VI-dinitrophenyldiaminopropionic acid + H2O
7-methoxycoumarin-4-acetyl-KSKTKC(farnesyl) + VI-dinitrophenyldiaminopropionic acid
-
1% of activity with KSKTKC(farnesyl)VIM
-
?
7-methoxycoumarin-4-acetyl-KSKTKC(farnesyl)lysine-epsilon-dinitrophenyl + H2O
7-methoxycoumarin-4-acetyl-KSKTKC(farnesyl) + lysine-epsilon-dinitrophenyl-IM
-
-
-
?
7-methoxycoumarin-4-acetyl-KSKTKC(farnesyl)VI-lysine-epsilon-dinitrophenyl + H2O
7-methoxycoumarin-4-acetyl-KSKTKC(farnesyl) + VI-lysine-epsilon-dinitrophenyl
-
2% of activity with KSKTKC(farnesyl)VIM
-
?
7-methoxycoumarin-4-acetyl-KSKTKC(farnesyl)VIM + H2O
7-methoxycoumarin-4-acetyl-KSKTKC(farnesyl) + VIM
-
35% of activity with KSKTKC(farnesyl)VIM
-
?
a-factor-CaaX + H2O
a-factor-C + aaX
-
endoproteolytic removal of the last three amino acids by Rce1 (i.e, -aaX)
-
-
?
KSKTKC(farnesyl)VI + H2O
?
-
a better substrate for hRCE1 than a KSKTKC(f)VIM
-
-
?
KSKTKC(farnesyl)VIM + H2O
KSKTKC(farnesyl) + VIM
-
no activity with unfarnesylated peptides
-
?
additional information
?
-
-
the enzyme is responsible for one step in Ras membrane localization
-
-
?
additional information
?
-
-
when hRCE1 activity is examined on the same K-Ras core peptide with H-Ras (VLS) or N-Ras (VVM) C-terminal AAX sequences, in each case, the CAA peptides are better hRCE1 substrates. For each peptide set the P2' (A) and P3' (X) positions appear independent in influencing hRCE1 activity on peptide substrates. The P3' position methionine is better than serine; while at the P2' position, isoleucine and valine are better than leucine
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
-
the enzyme is responsible for one step in Ras membrane localization
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4-(((1-hydroxynaphthalen-2-yl)(phenyl)methyl)amino)benzoic acid
inhibitor causes a reduction in Rce1 in vitro activity, exhibits low cell toxicity, and induces mislocalization of EGFP-Ras from the plasma membrane in human colon carcinoma cells. FTase activity is not inhibited at concentrations as high as 50 microM
4-(((4-bromo-2,6-difluorophenyl)(1-hydroxynaphthalen-2-yl)methyl)amino)benzoic acid
inhibitor causes a reduction in Rce1 in vitro activity, exhibits low cell toxicity, and induces mislocalization of EGFP-Ras from the plasma membrane in human colon carcinoma cells. FTase activity is not inhibited at concentrations as high as 50 microM
4-(((4-bromophenyl)(1-hydroxynaphthalen-2-yl)methyl)amino)benzoic acid
inhibitor causes a reduction in Rce1 in vitro activity, exhibits low cell toxicity, and induces mislocalization of EGFP-Ras from the plasma membrane in human colon carcinoma cells. FTase activity is not inhibited at concentrations as high as 50 microM
4-(((4-bromophenyl)(8-hydroxyquinolin-7-yl)methyl)amino)benzoate
inhibitor causes a reduction in Rce1 in vitro activity, exhibits low cell toxicity, and induces mislocalization of EGFP-Ras from the plasma membrane in human colon carcinoma cells. FTase activity is not inhibited at concentrations as high as 50 microM
4-(((8-hydroxyquinolin-7-yl)(phenyl)methyl)amino)benzoate
inhibitor causes a reduction in Rce1 in vitro activity, exhibits low cell toxicity, and induces mislocalization of EGFP-Ras from the plasma membrane in human colon carcinoma cells
benzyloxycarbonyl-Phe-Ala-2,4,6-trimethylbenzoyloxymethyl ketone
-
0.25 mM, 12% inhibition of cleavage of a quenched fluorogenic farnesylated peptide that is based on the C-terminal sequence of the K-Ras4b precursor (2-aminobenzoyl-KSKTKC(farnesyl)-K(Dnp)-IM)
benzyloxycarbonyl-Phe-Lys-2,4,6-trimethylbenzoyloxymethyl ketone
-
0.25 mM, 94% inhibition of cleavage of a quenched fluorogenic farnesylated peptide that is based on the C-terminal sequence of the K-Ras4b precursor (2-aminobenzoyl-KSKTKC(farnesyl)-K(Dnp)-IM), inhibition is not readily reversible
N-Boc-Cys(farnesyl)-methylenamin-VIM-OH
-
i.e. isoprenyl protease inhibitor RPI, 0.000058 mM, 50% inhibition
tosyl-L-lysyl-chloromethylketone
-
0.25 mM, 54% inhibition of cleavage of a quenched fluorogenic farnesylated peptide that is based on the C-terminal sequence of the K-Ras4b precursor (2-aminobvenzoyl-KSKTKC(farnesyl)-K(Dnp)-IM)
tosyl-L-phenylalanyl-chloromethylketone
-
0.25 mM, 93% inhibition of cleavage of a quenched fluorogenic farnesylated peptide that is based on the C-terminal sequence of the K-Ras4b precursor (2-aminobenzoyl-KSKTKC(farnesyl)-K(Dnp)-IM)
USP17
-
USP17 deubiquitinates RCE1 and negatively regulates the activity of RCE1. Constitutive expression of USP17 blocks cell growth and decreases Ras activation, knockdown of USP17 expression results in a marked elevation in the level of GTP-bound Ras. USP17 and RCE1 co-localize at the endoplasmic reticulum
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.004
7-methoxycoumarin-4-acetyl-KSKTKC(farnesyl)-dinitrophenyldiaminopropionic acid-IM
-
-
0.005
7-methoxycoumarin-4-acetyl-KSKTKC(farnesyl)-VI-dinitrophenyldiaminopropionic acid
-
-
0.006
7-methoxycoumarin-4-acetyl-KSKTKC(farnesyl)lysine-epsilon-dinitrophenyl
-
-
0.004
7-methoxycoumarin-4-acetyl-KSKTKC(farnesyl)VI-lysine-epsilon-dinitrophenyl
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0067
4-(((4-bromophenyl)(8-hydroxyquinolin-7-yl)methyl)amino)benzoate
Homo sapiens
pH 7.0, 30°C
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
RCE1 colocalizes with USP17 in the endoplasmic reticulum
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
-
the deubiquitinating enzyme USP17 negatively regulates the activity of RCE1
physiological function
-
RCE1 is involved in Ras trafficking to the plasma membrane and the Ras/MEK/ERK pathway. USP17 regulation of growth is RCE1-dependent, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
RCE1 is regulated by ubiquination, deubiquitinating enzyme USP17 negatively regulates the activity of RCE1, overview
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
expression of Rce1 is significantly decreased in hepatocellular carcinoma compared with noncancerous tissues, while H-Ras expression is increased in the tumor. The expression of both is a close association with the differentiation and tumor-node-metastasis stage of the tumor. Rce1 is an independent prognostic indicator. Lower expression of Rce1 facilitates epithelial-mesenchymalctransition and promotes the invasion and metastasis of hepatocellular carcinoma
additional information
-
Rce1-mediated removal of of the last three amino acids from isoprenylated Rho GTPases is required for the proteolytic activity of Yersinia enterocolitca outer protein T in living cells
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Hollander, I.; Frommer, E.; Mallon, R.
Human Ras-Converting Enzyme (hRCE1) Endoproteolytic Activity on K-Ras-Derived Peptides
Anal. Biochem.
286
129-137
2000
Homo sapiens
Otto, J.C.; Kim, E.; Young, S.G.; Casey, P.J.
Cloning and characterization of a mammalian prenyl protein-specific protease
J. Biol. Chem.
274
8379-8382
1999
Homo sapiens (Q9Y256), Homo sapiens
Casey, P.J.; Rando, R.R.
Isoprenylated protein peptidase Rce1
Handbook of Proteolytic Enzymes (Barrett, A. J. , Rawlings, N. D. , Woessner, J. F. , eds. )Academic Press
2
2123-2127
2004
Bos taurus, Homo sapiens, Mus musculus, Saccharomyces cerevisiae
-
Fueller, F.; Bergo, M.O.; Young, S.G.; Aktories, K.; Schmidt, G.
Endoproteolytic processing of RhoA by Rce1 is required for the cleavage of RhoA by Yersinia enterocolitica outer protein T
Infect. Immun.
74
1712-1717
2006
Homo sapiens
Plummer, L.J.; Hildebrandt, E.R.; Porter, S.B.; Rogers, V.A.; McCracken, J.; Schmidt, W.K.
Mutational analysis of the ras converting enzyme reveals a requirement for glutamate and histidine residues
J. Biol. Chem.
281
4596-4605
2006
Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Saccharomyces cerevisiae, Schizosaccharomyces pombe
Porter, S.B.; Hildebrandt, E.R.; Breevoort, S.R.; Mokry, D.Z.; Dore, T.M.; Schmidt, W.K.
Inhibition of the CaaX proteases Rce1p and Ste24p by peptidyl (acyloxy)methyl ketones
Biochim. Biophys. Acta
1773
853-862
2007
Arabidopsis thaliana, Homo sapiens, Saccharomyces cerevisiae
Hollander, I.J.; Frommer, E.; Aulabaugh, A.; Mallon, R.
Human Ras converting enzyme endoproteolytic specificity at the P2' and P3' positions of K-Ras-derived peptides
Biochim. Biophys. Acta
1649
24-29
2003
Homo sapiens
Burrows, J.F.; Kelvin, A.A.; McFarlane, C.; Burden, R.E.; McGrattan, M.J.; De la Vega, M.; Govender, U.; Quinn, D.J.; Dib, K.; Gadina, M.; Scott, C.J.; Johnston, J.A.
USP17 regulates Ras activation and cell proliferation by blocking RCE1 activity
J. Biol. Chem.
284
9587-9595
2009
Homo sapiens
Mohammed, I.; Hampton, S.E.; Ashall, L.; Hildebrandt, E.R.; Kutlik, R.A.; Manandhar, S.P.; Floyd, B.J.; Smith, H.E.; Dozier, J.K.; Distefano, M.D.; Schmidt, W.K.; Dore, T.M.
8-Hydroxyquinoline-based inhibitors of the Rce1 protease disrupt Ras membrane localization in human cells
Bioorg. Med. Chem.
24
160-178
2016
Homo sapiens (Q9Y256), Homo sapiens
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