Information on EC 3.4.24.84 - Ste24 endopeptidase

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The expected taxonomic range for this enzyme is: Eukaryota

EC NUMBER
COMMENTARY
3.4.24.84
-
RECOMMENDED NAME
GeneOntology No.
Ste24 endopeptidase
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
The peptide bond hydrolysed can be designated -C-/-aaX in which C is an S-isoprenylated cysteine residue, a is usually aliphatic and X is the C-terminal residue of the substrate protein, and may be any of several amino acids
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
Terpenoid backbone biosynthesis
-
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
a-factor converting enzyme
-
-
Afc1
-
a-factor converting enzyme
AtSte24
Q8RX88
-
FACE-1
-
-
FACE-1
-
-
Hs Ste24p
-
-
Ste24p
-
-
-
-
Zmpste24
-
-
Zmpste24
O75844
-
Zmpste24
O75844
gene name
Zmpste24
-
-
Zmpste24
Q80W54
-
CAS REGISTRY NUMBER
COMMENTARY
316364-97-3
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GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
defective prelamin A processing induces accelerated features of age-related bone loss including lower osteoblast and osteocyte numbers and higher levels of marrow adipogenesis
physiological function
-
Zmpste24-null progeroid mice exhibit nuclear lamina defects and accumulate unprocessed prelamin A. Defective prelamin A processing induces accelerated features of age-related bone loss including lower osteoblast and osteocyte numbers and higher levels of marrow adipogenesis. There is a significant loss in trabecular and cortical bone between the Zmpste24 -/- mice compared with the wild-type controls. At 3 months of age, Zmpste24 -/- mice show a significant decrease in bone volume/tissue volume, trabecular thickness, and trabecular number compared with their wild-type littermates
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
a-factor + H2O
fragments of a-factor
show the reaction diagram
Q8RX88
-
-
?
a-factor + H2O
fragments of a-factor
show the reaction diagram
-
mating pheromone a-factor
-
?
a-factor + H2O
fragments of a-factor
show the reaction diagram
-
complements yeast ste24DELTA mutant
-
-
a-factor + H2O
fragments of a-factor
show the reaction diagram
-
complements yeast ste24DELTA mutant
-
?
a-factor + H2O
fragments of a-factor
show the reaction diagram
-
Ste24 participates in both N- and C-terminal processing steps of a-factor
-
-
a-factor + H2O
fragments of a-factor
show the reaction diagram
-
Ste24 participates in both N- and C-terminal processing steps of a-factor
-
?
a-factor + H2O
fragments of a-factor
show the reaction diagram
-
Ste24 participates in both N- and C-terminal processing steps of a-factor
-
-
-
a-factor + H2O
fragments of a-factor
show the reaction diagram
-
Ste24 participates in both N- and C-terminal processing steps of a-factor
-
-
a-factor + H2O
fragments of a-factor
show the reaction diagram
-
Ste24 participates in both N- and C-terminal processing steps of a-factor
-
?
a-factor + H2O
fragments of a-factor
show the reaction diagram
-
mutant a-factor, containing a A8G point mutation is not cleaved suggesting that Ste24 N-terminal protease activity is highly discriminating
-
-
a-factor + H2O
fragments of a-factor
show the reaction diagram
-
Ste24 is required for the first of the two N-terminal processing steps of mating pheromone a-factor
-
-
-
a-factor + H2O
?
show the reaction diagram
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the enzyme has CAAX endopeptidase activity towards a-factor substrate
-
-
?
a-factor-CaaX + H2O
a-factor-C + aaX
show the reaction diagram
-
-
endoproteolytic cleavage of a C-terminal tripeptide of prenylated proteins with a CaaX motif
?
a-factor-CaaX + H2O
a-factor-C + aaX
show the reaction diagram
-
endoproteolytic cleavage of a C-terminal tripeptide of prenylated proteins with a CAAX motif, enzyme may also play a role in amino-terminal proteolytic processing of a-factor, endoproteolytic cleavage of a C-terminal tripeptide of prenylated proteins with a CaaX motif
-
?
a-factor-CaaX + H2O
a-factor + aaX
show the reaction diagram
-
removal of the last three amino acids of carboxyl-terminal sequence motif CaaX, enzyme proteolyzes a-factor with A, V, L, I, C or M at the a1 position, V, L, I, C or M at the a2 position or any amino acid at the X position, removal of the last three amino acids of carboxyl-terminal sequence motif CaaX, enzyme proteolyzes a-factor with A,V, L, I, C or M at the a1 position, V, L, I, C or M at the a2 position or any amino acid at the X position
-
?
a-factor-CAMQ + H2O
a-factor-C + AMQ
show the reaction diagram
Q80W54
-
-
?
a-factor-CVIA + H2O
a-factor-C + VIA
show the reaction diagram
Q80W54
-
-
?
CaM53 + H2O
fragments of CaM53
show the reaction diagram
Q8RX88
CaM53 is a prenylated C2+-calmodulin from petunia
-
?
N-(Ac)-Cys-(farnesyl)-Ser-Ile-Met + H2O
?
show the reaction diagram
-
the enzyme can process the prelaminA-specific CAAX sequence
-
-
?
prelamin A + H2O
lamin A
show the reaction diagram
-
cleavage is dependent on processing at the CAAX-box
-
-
?
prelamin A + H2O
?
show the reaction diagram
-
the enzyme removes the farnesylated tail of prelamin A
-
-
?
RACU88402 + H2O
fragments of RACU88402
show the reaction diagram
Q8RX88
RACU88402 is a Rac-like GTPase
-
?
YIIKGVFWDPA(farnesyl)CVIA + H2O
fragments of YIIKGVFWDPA(farnesyl)C + Val-Ile-Ala
show the reaction diagram
-
farnesylated 15-mer peptide containing the mature a-factor sequence and the native a-factor CAAX motif
-
?
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
a-factor + H2O
fragments of a-factor
show the reaction diagram
-
Ste24 participates in both N- and C-terminal processing steps of a-factor
-
-
-
a-factor + H2O
fragments of a-factor
show the reaction diagram
-
Ste24 is required for the first of the two N-terminal processing steps of mating pheromone a-factor
-
-
-
a-factor-CaaX + H2O
a-factor-C + aaX
show the reaction diagram
-
-
endoproteolytic cleavage of a C-terminal tripeptide of prenylated proteins with a CaaX motif
?
a-factor-CaaX + H2O
a-factor-C + aaX
show the reaction diagram
-
endoproteolytic cleavage of a C-terminal tripeptide of prenylated proteins with a CaaX motif
-
?
a-factor-CaaX + H2O
a-factor + aaX
show the reaction diagram
-
removal of the last three amino acids of carboxyl-terminal sequence motif CaaX, enzyme proteolyzes a-factor with A,V, L, I, C or M at the a1 position, V, L, I, C or M at the a2 position or any amino acid at the X position
-
?
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Zn2+
-
the in vitro N-terminal proteolysis of a-factor requires Zn2+ as metal cofactor, inhibition at higher Zn2+ concentrations e.g. 2 mM
Zn2+
-
probably Zn2+-dependent metalloprotease
Zn2+
-
Zn-dependent protease
Zn2+
-
Zn2+-dependent active site
Co2+
-
restores Ste24 CAAX proteolytic activity after 1,10-phenanthroline treatment, reactivation with 0.25 mM Co2+ is 25% of that seen with 0.25 mM Zn2+
additional information
-
Zn-metalloprotease consensus motif HEXXH
additional information
-
Ste24 has a characteristic zinc metalloprotease motif, HEXXH
additional information
-
-
additional information
-
-
additional information
-
C-terminal proteolytic activity of Ste24 requires metall ions
additional information
Q8RX88
zinc metalloprotease motif HEXXH
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1,10-phenanthroline
-
Zn2+ chelator
benzyloxycarbonyl-Phe-Ala-2,4,6-trimethylbenzoyloxymethyl ketone
-
0.25 mM, 21% inhibition, inhibition is not reversible
benzyloxycarbonyl-Phe-Ala-2,4,6-trimethylbenzoyloxymethyl ketone
-
0.25 mM, 41% inhibition, inhibition is not reversible
benzyloxycarbonyl-Phe-Ala-2,4,6-trimethylbenzoyloxymethyl ketone
-
0.25 mM, 22% inhibition, inhibition is not reversible
benzyloxycarbonyl-Phe-Lys-2,4,6-trimethylbenzoyloxymethyl ketone
-
0.25 mM, 76% inhibition, inhibition is not reversible
benzyloxycarbonyl-Phe-Lys-2,4,6-trimethylbenzoyloxymethyl ketone
-
0.25 mM, 68% inhibition, inhibition is not reversible
benzyloxycarbonyl-Phe-Lys-2,4,6-trimethylbenzoyloxymethyl ketone
-
0.25 mM, 76% inhibition, inhibition is not reversible
lopinavir
-
HIV protease inhibitors inhibit ZMPSTE24, leading to an accumulation of farnesyl-prelamin A. The inhibition of ZMPSTE24 by HIV protease inhibitors could play a role in the side effects of these drugs
o-phenanthroline
-
inhibition of recombinant Ste24 CAAX proteolytic activity
tipranavir
-
HIV protease inhibitors inhibit ZMPSTE24, leading to an accumulation of farnesyl-prelamin A. The inhibition of ZMPSTE24 by HIV protease inhibitors could play a role in the side effects of these drugs
lovastatin
-
abolishes the conversion of prelamin A into lamin A
additional information
-
HIV protease inhibitors inhibit ZMPSTE24
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0184
-
lopinavir
-
-
0.0012
-
tipranavir
-
-
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
hydropathy analysis predicts multiple membrane spanning segments
-
Manually annotated by BRENDA team
-
Ste24 has a lumenal N-terminus and a cytosolic C-terminus indicativ of an odd number of transmembrane spans, hydropathy analysis suggests 7 membrane spans
-
Manually annotated by BRENDA team
Q8RX88
hydropathy blot analysis suggests 7 membrane-spanning domains
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
54000
-
-
SDS-PAGE or immunoblot analyis
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 52300, deduced from nucleotide sequence
?
Q8RX88
x * 48455, deduced from nucleotide sequence
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
Ni-bead-purified
-
recombinant His-tagged Ste24, nickel chelate chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression of AtSte24 in Sacchromyces cerevisiae ste24DELTA mutant
Q8RX88
expressed in Sf-21 insect cells; expression in CHO-K1 cells; Zmpste24, fused N-terminally to a His6 tag, cloned into the (5')-NheI-(3')-BamHI site of the pcDNA3.1 construct using reverse transcriptase-PCR on HeLa RNA, when cloned into pBacpak8
-
expression of Ste24 in Sacchromyces cerevisiae ste24DELTA mutant
-
cloning of cDNA
Q80W54
complementation of a ste24 mutant
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
L362F
-
the mutation is associated with restrictive dermopathy
E298A
-
ability to complement the mating-defective phenotype of ste24-1 is lost
E298D
-
ability to complement the mating-defective phenotype of ste24-1 is lost
H297A
-
ability to complement the mating-defective phenotype of ste24-1 is lost
L647R
-
prelaminaAct mutant, cannot be cleaved by Zmpste24
additional information
-
identification of compound heterozygous frameshifting mutations in exon 1, c.50delA, and exon 5, c.584_585delAT of the ZMPSTE24 gene in two brothers affected with restrictive dermopathy, who died in the neonatal period. Both deletions are frameshifting and are predicted to cause the appearance of premature termination codons
additional information
-
neonates with restrictive dermopathy have homozygous or compound heterozygous null mutations in the ZMPSTE24 gene
W302X
-
the mutation is associated with restrictive dermopathy
additional information
-
Zmste24-deficient mice, Zmpste24 deficiency elicits a stress signaling pathway that is evidenced by a marked upregulation of p53 target genes, accompanied by a senescence phenotype at the cellular level and accelerated ageing at the organismal level
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
restrictive dermopathy is an autosomal recessive laminopathy caused by inactivating Zmpste24 mutations that result in defective processing and nuclear accumulation of prelamin A
medicine
-
identification of compound heterozygous frameshifting mutations in exon 1, c.50delA, and exon 5, c.584_585delAT of the ZMPSTE24 gene in two brothers affected with restrictive dermopathy, who died in the neonatal period. Both deletions are frameshifting and are predicted to cause the appearance of premature termination codons
medicine
-
existence of a checkpoint response activated by the nuclear abnormalities caused by prelamin A accumulation, hyperactivation of the tumour suppressor p53 may cause accelerated ageing