spoIIAB

UniProt ID: P10728
Organism: Bacillus subtilis (strain 168)
Review Status: DRAFT
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Gene Description

SpoIIAB is an anti-sigma factor and serine/threonine protein kinase that controls activation of the forespore-specific sigma factor sigma F during Bacillus subtilis sporulation. It binds sigma F to prevent RNA polymerase holoenzyme formation and phosphorylates the anti-anti-sigma factor SpoIIAA on a serine residue, contributing to the partner-switching mechanism that gates sigma F activity.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0016989 sigma factor antagonist activity
IBA
GO_REF:0000033
ACCEPT
Summary: SpoIIAB is the anti-sigma factor for sigma F, binding sigma F and blocking formation of the RNA polymerase holoenzyme.
Reason: This is the defining molecular function of SpoIIAB. UniProt states that SpoIIAB binds sigma F and inhibits holoenzyme formation, consistent with sigma factor antagonist activity.
Supporting Evidence:
file:BACSU/spoIIAB/spoIIAB-uniprot.txt
Binds to sigma F and blocks its ability to form an RNA polymerase holoenzyme (E-sigma F).
GO:0045892 negative regulation of DNA-templated transcription
IBA
GO_REF:0000033
ACCEPT
Summary: By binding sigma F and blocking holoenzyme formation, SpoIIAB inhibits sigma F-dependent transcription.
Reason: SpoIIAB directly antagonizes sigma F and prevents RNA polymerase holoenzyme formation, which is a direct negative regulatory effect on transcription of sigma F-dependent genes.
Supporting Evidence:
file:BACSU/spoIIAB/spoIIAB-uniprot.txt
Binds to sigma F and blocks its ability to form an RNA polymerase holoenzyme (E-sigma F).
GO:0000166 nucleotide binding
IEA
GO_REF:0000043
MODIFY
Summary: SpoIIAB is an ATP-dependent kinase with specific ATP-binding motifs.
Reason: The term "nucleotide binding" is overly broad; SpoIIAB is an ATP-binding protein kinase. Use the more specific ATP binding term.
Proposed replacements: ATP binding
Supporting Evidence:
file:BACSU/spoIIAB/spoIIAB-uniprot.txt
KW ATP-binding; Direct protein sequencing; Kinase; Nucleotide-binding;
GO:0004672 protein kinase activity
IEA
GO_REF:0000104
MODIFY
Summary: SpoIIAB phosphorylates SpoIIAA on a serine residue, functioning as a protein serine/threonine kinase.
Reason: The generic protein kinase activity term is too broad. SpoIIAB is a serine/threonine protein kinase (EC 2.7.11.1), so a more specific kinase term is appropriate.
Supporting Evidence:
file:BACSU/spoIIAB/spoIIAB-uniprot.txt
Phosphorylates SpoIIAA on a serine residue.
GO:0004674 protein serine/threonine kinase activity
IEA
GO_REF:0000120
ACCEPT
Summary: SpoIIAB is a serine/threonine protein kinase that phosphorylates SpoIIAA.
Reason: UniProt assigns EC 2.7.11.1 and reports SpoIIAB phosphorylates SpoIIAA on a serine residue, supporting serine/threonine kinase activity.
Supporting Evidence:
file:BACSU/spoIIAB/spoIIAB-uniprot.txt
Phosphorylates SpoIIAA on a serine residue.
GO:0005524 ATP binding
IEA
GO_REF:0000120
ACCEPT
Summary: SpoIIAB binds ATP as part of its kinase catalytic mechanism.
Reason: ATP binding is a core feature of SpoIIAB's kinase activity and is noted explicitly in UniProt keywords.
Supporting Evidence:
file:BACSU/spoIIAB/spoIIAB-uniprot.txt
KW ATP-binding; Direct protein sequencing; Kinase; Nucleotide-binding;
GO:0010468 regulation of gene expression
IEA
GO_REF:0000104
MARK AS OVER ANNOTATED
Summary: SpoIIAB regulates expression indirectly by inhibiting sigma F, which controls sporulation gene transcription.
Reason: The term is too general and adds little beyond the specific sigma factor antagonist activity and negative regulation of transcription terms.
Supporting Evidence:
file:BACSU/spoIIAB/spoIIAB-uniprot.txt
Binds to sigma F and blocks its ability to form an RNA polymerase holoenzyme (E-sigma F).
GO:0016301 kinase activity
IEA
GO_REF:0000043
MARK AS OVER ANNOTATED
Summary: SpoIIAB is a protein kinase; however, this term is overly general.
Reason: The more specific protein serine/threonine kinase activity is already supported. This generic term is redundant.
Supporting Evidence:
file:BACSU/spoIIAB/spoIIAB-uniprot.txt
DE EC=2.7.11.1;
GO:0016740 transferase activity
IEA
GO_REF:0000043
MARK AS OVER ANNOTATED
Summary: SpoIIAB has kinase/transferase activity, but this term is too generic.
Reason: Transferase activity is a very broad parent term and is not informative relative to the specific kinase annotations.
Supporting Evidence:
file:BACSU/spoIIAB/spoIIAB-uniprot.txt
DE EC=2.7.11.1;
GO:0016989 sigma factor antagonist activity
IEA
GO_REF:0000002
ACCEPT
Summary: SpoIIAB antagonizes sigma F by binding to it and blocking holoenzyme formation.
Reason: The InterPro-based inference aligns with SpoIIAB's known anti-sigma factor role and is supported by UniProt functional annotation.
Supporting Evidence:
file:BACSU/spoIIAB/spoIIAB-uniprot.txt
Binds to sigma F and blocks its ability to form an RNA polymerase holoenzyme (E-sigma F).
GO:0030435 sporulation resulting in formation of a cellular spore
IEA
GO_REF:0000043
ACCEPT
Summary: SpoIIAB is a stage II sporulation protein and part of the sigma F regulatory pathway.
Reason: UniProt assigns the sporulation keyword and names SpoIIAB as a stage II sporulation protein, supporting its role in spore formation.
Supporting Evidence:
file:BACSU/spoIIAB/spoIIAB-uniprot.txt
DE AltName: Full=Stage II sporulation protein AB;
file:BACSU/spoIIAB/spoIIAB-uniprot.txt
KW ATP-binding; Direct protein sequencing; Kinase; Nucleotide-binding; Reference proteome; Serine/threonine-protein kinase; Sporulation; Transferase.
GO:0030436 asexual sporulation
IEA
GO_REF:0000104
ACCEPT
Summary: SpoIIAB functions in the asexual sporulation program of B. subtilis.
Reason: Sporulation in B. subtilis is an asexual developmental process. SpoIIAB is a stage II sporulation protein required for proper sporulation regulation.
Supporting Evidence:
file:BACSU/spoIIAB/spoIIAB-uniprot.txt
DE AltName: Full=Stage II sporulation protein AB;
GO:0042174 negative regulation of sporulation resulting in formation of a cellular spore
IEA
GO_REF:0000002
MARK AS OVER ANNOTATED
Summary: SpoIIAB restrains sigma F activation prior to septation, but this does not represent a general negative regulation of sporulation.
Reason: SpoIIAB is required for proper timing of sigma F activity and sporulation, not for inhibiting sporulation overall. The term overstates its effect on the overall sporulation outcome.
Supporting Evidence:
file:BACSU/spoIIAB/spoIIAB-uniprot.txt
Binds to sigma F and blocks its ability to form an RNA polymerase holoenzyme (E-sigma F).
GO:0045892 negative regulation of DNA-templated transcription
IEA
GO_REF:0000002
ACCEPT
Summary: SpoIIAB inhibits sigma F, leading to negative regulation of sigma F-dependent transcription.
Reason: SpoIIAB directly binds sigma F and blocks RNA polymerase holoenzyme formation, which is a direct negative regulatory effect on transcription.
Supporting Evidence:
file:BACSU/spoIIAB/spoIIAB-uniprot.txt
Binds to sigma F and blocks its ability to form an RNA polymerase holoenzyme (E-sigma F).
GO:0106310 protein serine kinase activity
IEA
GO_REF:0000116
ACCEPT
Summary: SpoIIAB phosphorylates SpoIIAA on a serine residue, consistent with serine protein kinase activity.
Reason: UniProt reports SpoIIAB phosphorylates SpoIIAA on serine and assigns EC 2.7.11.1; this supports protein serine kinase activity.
Supporting Evidence:
file:BACSU/spoIIAB/spoIIAB-uniprot.txt
Phosphorylates SpoIIAA on a serine residue.
GO:0005515 protein binding
IPI
PMID:25278935
Cross-phosphorylation of bacterial serine/threonine and tyro...
UNDECIDED
Summary: The cited study examines kinase-kinase interactions and phosphorylation networks in B. subtilis and includes SpoIIAB in interaction assays, but the specific binding partner for SpoIIAB is not clearly stated here.
Reason: The PMID describes broad kinase interaction and cross-phosphorylation assays and lists SpoIIAB among the proteins tested, but it does not provide a clear, specific binding interaction for SpoIIAB in the accessible text. More direct binding evidence would be needed to accept a generic protein binding annotation.
Supporting Evidence:
PMID:25278935
The genes encoding the BY-kinases (PtkA, PtkA) Hanks-type serine/threonine-kinases (PrkC, PrkD, YabT), two-component-like serine-kinases (SpoIIAB, RsbT, and RsbW), BY-kinase modulators (TkmA, TkmB)

Core Functions

Binds sigma F to prevent RNA polymerase holoenzyme formation, acting as an anti-sigma factor that inhibits sigma F-dependent transcription.

Supporting Evidence:
  • file:BACSU/spoIIAB/spoIIAB-uniprot.txt
    Binds to sigma F and blocks its ability to form an RNA polymerase holoenzyme (E-sigma F).

Phosphorylates the anti-anti-sigma factor SpoIIAA on serine residues, contributing to the partner-switching control of sigma F activity during sporulation.

Supporting Evidence:
  • file:BACSU/spoIIAB/spoIIAB-uniprot.txt
    Phosphorylates SpoIIAA on a serine residue.

References

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Suggested Questions for Experts

Q: Do cross-phosphorylation events by Hanks-type kinases (e.g. PrkC, PrkD, YabT) on SpoIIAB reported in vitro (PMID:25278935) occur under physiological sporulation conditions in B. subtilis, and do they modulate the timing or amplitude of sigma F activation in the forespore?

Q: How is the septum-localized asymmetric release of sigma F from SpoIIAB coupled to SpoIIE phosphatase activity in the forespore, and what determines the precise threshold of SpoIIAA dephosphorylation required to titrate SpoIIAB and free sigma F?

Suggested Experiments

Experiment: Introduce phospho-mimetic and phospho-null substitutions at SpoIIAB residues identified as cross-phosphorylation targets and measure sigma F activity in vivo (e.g. using a P_spoIIQ-lacZ or fluorescent reporter), SpoIIAA phosphorylation kinetics in vitro, and sporulation efficiency. Include Ξ”prkC/Ξ”prkD/Ξ”yabT backgrounds to test whether removing the donor kinases perturbs sigma F timing.

Hypothesis: Cross-phosphorylation of SpoIIAB by Hanks-type kinases modulates its anti-sigma-F activity or ATPase turnover during sporulation.

Type: Site-directed mutagenesis + reporter assay + genetic epistasis

Experiment: Use fluorescent tags on SpoIIAB and time-lapse microscopy of sporulating cells to quantify SpoIIAB abundance in mother cell versus forespore before and after septation. Combine with pulse-chase and protease-deficient backgrounds (e.g. ClpXP/LonA mutants) to test whether SpoIIAB turnover is asymmetric and protease-dependent.

Hypothesis: Compartment-specific SpoIIAB degradation contributes to release of sigma F in the forespore, in addition to SpoIIE-driven SpoIIAA dephosphorylation.

Type: Live-cell fluorescence microscopy + pulse-chase

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