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Information on EC 3.4.21.116 - SpoIVB peptidase and Organism(s) Bacillus subtilis and UniProt Accession P17896
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3.4.21.116 SpoIVB peptidaseSpecify your search results
Word Map
- 3.4.21.116
- forespore
- pro-sigmak
- sigmak
-
checkpoint
- bofa
- spoivfa
- metalloprotease
-
intercompartmental
- ctpb
-
membrane-embedded
-
intramembrane
-
cell-cell
-
engulfment
-
autoproteolysis
- zymogen
The taxonomic range for the selected organisms is: Bacillus subtilis
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
self-cleaves Val52-/-Asn53, Ala62-/-Phe63 and Val74-/-Thr75 at the N-terminus of SpoIVB
N-terminal cleavage of the pro-form of the sporulation protein sigmaK
Synonyms
spoivb, spoivb serine peptidase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
M50.002
SpoIVB
SpolVFB
sporulation protein SpolVFB
-
-
-
-
stage IV sporulation protein FB
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
self-cleaves Val52-/-Asn53, Ala62-/-Phe63 and Val74-/-Thr75 at the N-terminus of SpoIVB
D137 is essential for catalytic activity, mechanism model, enzyme contains conserved metalloprotease sequence motifs HEXXH and NPDG, which are expected to form the catalytic center and are required for catalytic activity
-
self-cleaves Val52-/-Asn53, Ala62-/-Phe63 and Val74-/-Thr75 at the N-terminus of SpoIVB
enzyme contains conserved metalloprotease sequence motif HEXXH
N-terminal cleavage of the pro-form of the sporulation protein sigmaK
enzyme belongs to S2P family of intramembrane-cleaving proteases
-
N-terminal cleavage of the pro-form of the sporulation protein sigmaK
enzyme is a metalloprotease with a transmembrane H43EXXH47 motif, E44 promotes nucleophilic attack by a water molecule on the carbonyl atom of the substrate peptide bond
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
CAS REGISTRY NUMBER
COMMENTARY
258282-12-1
-
296241-18-4
-
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
SpoIVFA + H2O
cleaved SpoIVFA + extracellular domain peptide of SpoIVFA
involved in the regulation of sporulation, cleavage of the extracellular domain, essential for sigmaK processing, cleavage of SpoIVFA activates SpoIVFB which is the enzyme for pro-sigmaK processing
-
-
?
CtpB-His6 + H2O
?
-
effective cleavage to a size similar to that observed during sporulation process
-
-
?
His tagged extracellular domain of SpoIVFA + H2O
?
-
four cleavage sites identified
-
-
?
SpoIIQ + H2O
?
-
protein located in the forespore membrane, cleavage of the extracellular domain, involved in the regulation of sigmaK processing
-
-
?
SpoIVFA + H2O
17 KDa fragment + 14 KDa fragment
-
component of the pro-sigmaK processing complex, cleaves between residues 145 and 175
-
?
SpoIVFA + H2O
cleaved SpoIVFA + extracellular domain peptides of SpoIVFA
-
involved in the regulation of sporulation, cleavage of the extracellular domain, essential for sigmaK processing, cleavage of SpoIVFA at multiple sites activates SpoIVFB which is the enzyme for pro-sigmaK processing, activation of SpoIVFB is suggested to result from conformational changes caused by SpoIVFA cleavage
-
-
?
CtpB + H2O
?
-
cleavage is not required to activate CtpB protease activity
-
-
?
pro-sigmaK
sigmaK + ?
-
enzyme is essential for intercompartmental signalling in the sigmaK-checkpoint, activates poteolytic processing of pro-sigmaK to its mature and active form sigmaK, function in formation of heat-resistant spores
-
?
pro-sigmaK + H2O
sigmaK + 20 amino acid peptide
-
processing of prosigmaK, which is a protein involved in sporulation
-
?
pro-sigmaK + H2O
sigmaK + 20 amino acid peptide
processing of prosigmaK, which is a protein involved in sporulation
-
?
pro-sigmaK + H2O
sigmaK + 20 amino acid peptide
-
amino acids 1-117 are required as a minimum for pro-sigmaK to serve as a substrate, amino acids 1-126 are cleaved much more efficiently. Substitution E13K in pro-sigmaK reduces accumulation of substrate and prevents cleavage by enzmye
-
-
?
pro-sigmaK + H2O
sigmaK + 20 amino acid peptide
-
amino acids 1-126 of substrate pro-sigmaK are sufficient to serve as a substrate
-
-
?
SpoIVFA + H2O
cleaved SpoIVFA + extracellular domain peptide of SpoIVFA
-
involved in the regulation of sporulation, cleavage of the extracellular domain at multiple sides, cleavage is thought to cause a conformational change in the signaling complex that activates SpoIVFB-dependent pro-sigmaK processing, activity of SpoIVB is absolutely essential for sigmaK processing
-
-
?
SpoIVFA + H2O
cleaved SpoIVFA + extracellular domain peptide of SpoIVFA
-
involved in the regulation of sporulation, cleavage of the extracellular domain, absolutely essential for sigmaK processing
-
-
?
SpoIVFA + H2O
cleaved SpoIVFA + extracellular domain peptide of SpoIVFA
-
involved in the regulation of sporulation, cleavage of the extracellular domain, essential for sigmaK processing, cleavage of SpoIVFA activates SpoIVFB which is the enzyme for pro-sigmaK processing
-
-
?
additional information
?
-
self cleavage into at least three distinct species of 46, 45, and 44 kDa
-
-
?
additional information
?
-
-
self cleavage into at least three distinct species of 46, 45, and 44 kDa
-
-
?
additional information
?
-
-
self-cleavage occurs at three different sites: Val52 and Asn53, Ala62 and Phe63, Val74 and Thr75
-
?
additional information
?
-
-
critical component of the intercompartmental signal-transduction pathway that activates the sigma factor, sigmaK, in the mother cell of the sporulating cell, possible non-signalling function in germ cell wall biosynthesis and the formation of heat-resistant spores
-
?
additional information
?
-
-
enzyme is a critical component of the sigmaK regulatory checkpoint during spore formation, PDZ domain can interact with BofC
-
?
additional information
?
-
-
initiates proteolytic processing of pro-sigmaK to its mature and active form in the opposed mother cell chamber of the developing cell, interacts with BofC
-
?
additional information
?
-
-
autoproteolytical activation. PDZ domain of enzyme binds to enzyme N-terminus to maintain its zymogen form. Following secretion across a spore membrane, domain binds in trans to the C-terminus of another enzyme molecule thus facilitating first cleavage event of enzyme near the N-terminus which releases the enzyme from the forespore membrane
-
-
?
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
SpoIVFA + H2O
cleaved SpoIVFA + extracellular domain peptide of SpoIVFA
involved in the regulation of sporulation, cleavage of the extracellular domain, essential for sigmaK processing, cleavage of SpoIVFA activates SpoIVFB which is the enzyme for pro-sigmaK processing
-
-
?
pro-sigmaK
sigmaK + ?
-
enzyme is essential for intercompartmental signalling in the sigmaK-checkpoint, activates poteolytic processing of pro-sigmaK to its mature and active form sigmaK, function in formation of heat-resistant spores
-
?
SpoIIQ + H2O
?
-
protein located in the forespore membrane, cleavage of the extracellular domain, involved in the regulation of sigmaK processing
-
-
?
SpoIVFA + H2O
cleaved SpoIVFA + extracellular domain peptides of SpoIVFA
-
involved in the regulation of sporulation, cleavage of the extracellular domain, essential for sigmaK processing, cleavage of SpoIVFA at multiple sites activates SpoIVFB which is the enzyme for pro-sigmaK processing, activation of SpoIVFB is suggested to result from conformational changes caused by SpoIVFA cleavage
-
-
?
CtpB + H2O
?
-
cleavage is not required to activate CtpB protease activity
-
-
?
pro-sigmaK + H2O
sigmaK + 20 amino acid peptide
-
processing of prosigmaK, which is a protein involved in sporulation
-
?
pro-sigmaK + H2O
sigmaK + 20 amino acid peptide
processing of prosigmaK, which is a protein involved in sporulation
-
?
SpoIVFA + H2O
cleaved SpoIVFA + extracellular domain peptide of SpoIVFA
-
involved in the regulation of sporulation, cleavage of the extracellular domain at multiple sides, cleavage is thought to cause a conformational change in the signaling complex that activates SpoIVFB-dependent pro-sigmaK processing, activity of SpoIVB is absolutely essential for sigmaK processing
-
-
?
SpoIVFA + H2O
cleaved SpoIVFA + extracellular domain peptide of SpoIVFA
-
involved in the regulation of sporulation, cleavage of the extracellular domain, absolutely essential for sigmaK processing
-
-
?
SpoIVFA + H2O
cleaved SpoIVFA + extracellular domain peptide of SpoIVFA
-
involved in the regulation of sporulation, cleavage of the extracellular domain, essential for sigmaK processing, cleavage of SpoIVFA activates SpoIVFB which is the enzyme for pro-sigmaK processing
-
-
?
additional information
?
-
self cleavage into at least three distinct species of 46, 45, and 44 kDa
-
-
?
additional information
?
-
-
self cleavage into at least three distinct species of 46, 45, and 44 kDa
-
-
?
additional information
?
-
-
critical component of the intercompartmental signal-transduction pathway that activates the sigma factor, sigmaK, in the mother cell of the sporulating cell, possible non-signalling function in germ cell wall biosynthesis and the formation of heat-resistant spores
-
?
additional information
?
-
-
enzyme is a critical component of the sigmaK regulatory checkpoint during spore formation, PDZ domain can interact with BofC
-
?
additional information
?
-
-
initiates proteolytic processing of pro-sigmaK to its mature and active form in the opposed mother cell chamber of the developing cell, interacts with BofC
-
?
additional information
?
-
-
autoproteolytical activation. PDZ domain of enzyme binds to enzyme N-terminus to maintain its zymogen form. Following secretion across a spore membrane, domain binds in trans to the C-terminus of another enzyme molecule thus facilitating first cleavage event of enzyme near the N-terminus which releases the enzyme from the forespore membrane
-
-
?
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
secreted by the forespore into the intermembrane space between the forespore and the mother cell membrane
-
during early engulfment, enzyme localizes to discrete foci at the septum and in traces at the mother cell cytoplasmic membrane. After fusion, there is a continuous accumulation in the outer forespore. Proteins SpoIIQ and SpoIIIAGH are required for correct localization of enzyme
-
during early engulfment, enzyme localize to discrete foci at the septum and in traces at the mother cell cytoplasmic membrane
-
-
secreted by the forespore into the intermembrane space between the forespore and the mother cell membrane
belongs to the family of putative membrane metalloproteases
-
catalytic center is located adjacent tot or within the membrane
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
-
a stable association between the membrane-embedded protease SpoIVFB and its substrate requires SpoIVB signaling. The cytoplasmic cystathionine-beta-synthase domain of the SpoIVFB protease is not critical for this interaction or for pro-sigmaK processing. A model explains IVB-dependent cleavage of SpoIVFA on one side of the membrane triggers a conformational change in the membrane-embedded protease from a closed to an open state allowing pro-sigmaK access to the caged interior of the protease
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
38000
-
x * 46000, full-length protein, x * 40000, x * 39000, x * 38000, autoactivation products, SDS-PAGE
39000
-
x * 46000, full-length protein, x * 40000, x * 39000, x * 38000, autoactivation products, SDS-PAGE
40000
-
x * 46000, full-length protein, x * 40000, x * 39000, x * 38000, autoactivation products, SDS-PAGE
42000
-
three predominant species of approximately 45000 Da, 43000 Da and 42000 Da after processing
43000
-
three predominant species of approximately 45000 Da, 43000 Da and 42000 Da after processing
45000
-
three predominant species of approximately 45000 Da, 43000 Da and 42000 Da after processing
46000
-
x * 46000, full-length protein, x * 40000, x * 39000, x * 38000, autoactivation products, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
synthesized as 50 kDa protein at about the second h of the sporulation process, starting at h three enzyme is cleaved into at least three distinct species of 46, 45, and 44 kDa, one of which is the active form of the enzyme, further processing into enzymatically inactive 42 and 40 kDa species
?
-
x * 46000, full-length protein, x * 40000, x * 39000, x * 38000, autoactivation products, SDS-PAGE
additional information
-
Enzyme binds specifically to intrinsic protein BofA
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
proteolytic modification
-
enzyme is able to self-cleave in trans into at least three discrete products, zymogen is subject to two levels of proteolysis: autoproteolysis generating intermediate products of 42000 Da, 43000 Da and 45000 Da, at least one of which is proposed to be the active form, followed by processing by one or more enzymes to smaller species of 42000 Da and 40000 Da
proteolytic modification
-
autoproteolytical activation. PDZ domain of enzyme binds to enzyme N-terminus to maintain its zymogen form. Following secretion across a spore membrane, domain binds in trans to the C-terminus of another enzyme molecule thus facilitating first cleavage event of enzyme near the N-terminus which releases the enzyme from the forespore membrane
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D213L
phenotype indistinguishable from wild type, normal spore formation, slight accumulation of the 50 kDa species
D240L
phenotype indistinguishable from wild type, normal spore formation
D242L
phenotype indistinguishable from null mutant, fails to trigger and sigmaK signaling and to form heat and lysozyme resistant spores, production of an unstable protein that is rapidly cleared by secondary proteolysis
D242N
phenotype indistinguishable from wild type, normal spore formation
D363L
phenotype indistinguishable from null mutant, fails to trigger and sigmaK signaling and to form heat and lysozyme resistant spores, self cleavage of enzyme appears to delayed by approximately 30 min, accumulation of the 50 kDa species
D363N
phenotype indistinguishable from wild type, normal spore formation
H236F
phenotype indistinguishable from null mutant, fails to trigger and sigmaK signaling and to form heat and lysozyme resistant spores
H236N
phenotype indistinguishable from null mutant, fails to trigger and sigmaK signaling and to form heat and lysozyme resistant spores, accumulation of the 50 kDa species
H394D
production of approximately 30% fewer spores than wild type, unable to germinate properly at 37°C
K321A
phenotype indistinguishable from wild type, normal spore formation
K387A
phenotype indistinguishable from wild type, normal spore formation, slight accumulation of the 50 kDa species
N290I
production of approximately 30% fewer spores than wild type, unable to germinate properly at 37°C
S378A
phenotype indistinguishable from null mutant, fails to trigger and sigmaK signaling and to form heat and lysozyme resistant spores
S378K
phenotype indistinguishable from null mutant, fails to trigger and sigmaK signaling and to form heat and lysozyme resistant spores, self cleavage of enzyme appears to delayed by approximately 30 min, accumulation of the 50 kDa species
D137A
D137E
-
site-directed mutagenesis, mutant is completely impaired in pro-sigmaK processing
D137N
E44A
E44D
E44Q
G114A
-
self-cleavage and pro-sigmaK processing similar to wild-type enzyme
G126A
-
self-cleavage and pro-sigmaK processing similar to wild-type enzyme
G126Q
-
self-cleavage and pro-sigmaK processing similar to wild-type enzyme
G144A
-
self-cleavage and pro-sigmaK processing similar to wild-type enzyme
G144A/N155D
-
self-cleavage and pro-sigmaK processing similar to wild-type enzyme
G144Q
-
self-cleavage and pro-sigmaK processing similar to wild-type enzyme
H43F
H47F
N122Q
-
site-directed mutagenesis, unaltered activity, similar to wild-type
N155D
-
self-cleavage and pro-sigmaK processing similar to wild-type enzyme
N155Y
-
self-cleavage and pro-sigmaK processing similar to wild-type enzyme
R185H
-
self-cleavage and pro-sigmaK processing similar to wild-type enzyme
R185K
-
self-cleavage and pro-sigmaK processing similar to wild-type enzyme
S378A
T228A
-
can signal processing of pro-sigmaK but is unable to complete its non-signalling function
additional information
D137A
-
site-directed mutagenesis, mutant is completely impaired in pro-sigmaK processing
D137N
-
site-directed mutagenesis, mutant is completely impaired in pro-sigmaK processing
H43F
mutant shows no remaining sporulation activity, no immunologically detectable enzyme protein
H43F
-
site-directed mutagenesis, extremely low enzyme expression, no activity
S378A
-
unable to process self cleavage, unable to trigger the activation of pro-sigmaK processing
additional information
comparison of effects of spoIVFB mutation with spoIVFB mutation on accumulation level of the enzymes in the recombinant strains, overview
additional information
-
cellular localization of enzyme-GFP fusion protein
additional information
-
coexpression of enzyme and its substrate pro-sigmaK in Escherichia coli. Enzyme shows abundant and accurate cleavage of substrate. Coexpression of Bacillus subtilis protein BofA in this system leads to formation of a complex of enzyme and BofA and marked inhibition of pro-sigmaK processing. Inhibition may occur by providing H57 of BofA as metal ligand to the catalytic center of enzyme
additional information
-
N-terminal deletion of residues 1-35, 1-52, 1-62 or 1-74 and additional C-terminal deletion of up to 33 residues. Study on autoactivation process, which involves one trans cleavage by another enzyme protein and two cis cleavages
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of wild-type and enzyme mutants in mutants strain BSL51 and R13
-
functional expression of wild-type, and expression of amino acid exchange mutants in the mutant strain BSL51, lacking spoIVFA and spoIVFB genes, and in the mutant OR745, lacking gene spoIVFB
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Van Hoy, B.E.; Hoch, J.A.
Characterization of the spoIVB and recN loci of Bacillus subtilis
J. Bacteriol.
172
1306-1311
1990
Bacillus subtilis (P17896), Bacillus subtilis
Yu, Y.T.N.; Kroos, L.
Evidence that SpoIVFB is a novel type of membrane metalloprotease governing intercompartmental communication during Bacillus subtilis sporulation
J. Bacteriol.
182
3305-3309
2000
Bacillus subtilis (P26937), Bacillus subtilis PY79 (P26937)
Hoa, N.T.; Brannigan, J.A.; Cutting, S.M.
The PDZ domain of the SpoIVB serine peptidase facilitates multiple functions
J. Bacteriol.
183
4364-4373
2001
Bacillus subtilis
Hoa, N.T.; Brannigan, J.A.; Cutting, S.M.
The Bacillus subtilis signaling protein SpoIVB defines a new family of serine peptidases
J. Bacteriol.
184
191-199
2002
Bacillus subtilis (P17896), Bacillus subtilis, Bacillus subtilis PY79 (P17896)
Oke, V.; Shchepetov, M.; Cutting, S.
SpoIVB has two distinct functions during spore formation in Bacillus subtilis
Mol. Microbiol.
23
223-230
1997
Bacillus subtilis
Wakeley, P.R.; Dorazi, R.; Hoa, N.T.; Bowyer, J.R.; Cutting, S.M.
Proteolysis of SpoIVB is a critical determinant in signalling of Pro-sK processing in Bacillus subtilis
Mol. Microbiol.
36
1336-1348
2000
Bacillus subtilis
Wakeley, P.; Hoa, N.T.; Cutting, S.
BofC negatively regulates SpoIVB-mediated signalling in the Bacillus subtilis sigmaK-checkpoint
Mol. Microbiol.
36
1415-1424
2000
Bacillus subtilis
Dong, T.C.; Cutting, S.M.
SpoIVB-mediated cleavage of SpoIVFA could provide the intercellular signal to activate processing of Pro-sigmaK in Bacillus subtilis
Mol. Microbiol.
49
1425-1434
2003
Bacillus subtilis
Rudner, D.Z.; Fawcett, P.; Losick, R.
A family of membrane-embedded metalloproteases involved in regulated proteolysis of membrane-associated transcription factors
Proc. Natl. Acad. Sci. USA
96
14765-14770
1999
Bacillus subtilis
Prince, H.; Zhou, R.; Kroos, L.
Substrate requirements for regulated intramembrane proteolysis of Bacillus subtilis pro-sigmaK
J. Bacteriol.
187
961-971
2005
Bacillus subtilis
Dong, T.C.; Cutting, S.M.
The PDZ domain of the SpoIVB transmembrane signaling protein enables cis-trans interactions involving multiple partners leading to the activation of the pro-sigmaK processing complex in Bacillus subtilis
J. Biol. Chem.
279
43468-43478
2004
Bacillus subtilis
Jiang, X.; Rubio, A.; Chiba, S.; Pogliano, K.
Engulfment-regulated proteolysis of SpoIIQ: evidence that dual checkpoints control sigma activity
Mol. Microbiol.
58
102-115
2005
Bacillus subtilis, Bacillus subtilis PY79
Zhou, R.; Kroos, L.
Serine proteases from two cell types target different components of a complex that governs regulated intramembrane proteolysis of pro-sigmaK during Bacillus subtilis development
Mol. Microbiol.
58
835-846
2005
Bacillus subtilis, Bacillus subtilis PY79
Zhou, R.; Kroos, L.
BofA protein inhibits intramembrane proteolysis of pro-sigmaK in an intercompartmental signaling pathway during Bacillus subtilis sporulation
Proc. Natl. Acad. Sci. USA
101
6385-6390
2004
Bacillus subtilis
Campo N.; Rudner D.Z.
SpoIVB and CtpB are both forespore signals in the activation of the sporulation transcription factor sigmaK in Bacillus subtilis
J. Bacteriol.
189
6021-6027
2007
Bacillus subtilis, Bacillus subtilis PY79
Campo, N.; Rudner, D.Z.
A branched pathway governing the activation of a developmental transcription factor by regulated intramembrane proteolysis
Mol. Cell
23
25-35
2006
Bacillus subtilis, Bacillus subtilis PY79
Ramixadrez-Guadiana, F.; Rodrigues, C.; Marquis, K.; Campo, N.; Barajas-Ornelas, R.; Brock, K.; Marks, D.; Kruse, A.; Rudner, D.
Evidence that regulation of intramembrane proteolysis is mediated by substrate gating during sporulation in Bacillus subtilis
PLoS Genet.
14
e1007753
2018
Bacillus subtilis, Bacillus subtilis PY79
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