spoIIAB

id: P10728
gene_symbol: spoIIAB
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:224308
  label: Bacillus subtilis (strain 168)
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:
- term:
    id: GO:0016989
    label: sigma factor antagonist activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      SpoIIAB is the anti-sigma factor for sigma F, binding sigma F and blocking
      formation of the RNA polymerase holoenzyme.
    action: ACCEPT
    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.
    supported_by:
      - reference_id: file:BACSU/spoIIAB/spoIIAB-uniprot.txt
        supporting_text: "Binds to sigma F and blocks its ability to form an RNA polymerase holoenzyme (E-sigma F)."
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      By binding sigma F and blocking holoenzyme formation, SpoIIAB inhibits
      sigma F-dependent transcription.
    action: ACCEPT
    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.
    supported_by:
      - reference_id: file:BACSU/spoIIAB/spoIIAB-uniprot.txt
        supporting_text: "Binds to sigma F and blocks its ability to form an RNA polymerase holoenzyme (E-sigma F)."
- term:
    id: GO:0000166
    label: nucleotide binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      SpoIIAB is an ATP-dependent kinase with specific ATP-binding motifs.
    action: MODIFY
    reason: >-
      The term "nucleotide binding" is overly broad; SpoIIAB is an ATP-binding
      protein kinase. Use the more specific ATP binding term.
    proposed_replacement_terms:
      - id: GO:0005524
        label: ATP binding
    supported_by:
      - reference_id: file:BACSU/spoIIAB/spoIIAB-uniprot.txt
        supporting_text: "KW   ATP-binding; Direct protein sequencing; Kinase; Nucleotide-binding;"
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000104
  review:
    summary: >-
      SpoIIAB phosphorylates SpoIIAA on a serine residue, functioning as a
      protein serine/threonine kinase.
    action: MODIFY
    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.
    proposed_replacement_terms:
      - id: GO:0004674
        label: protein serine/threonine kinase activity
      - id: GO:0106310
        label: protein serine kinase activity
    supported_by:
      - reference_id: file:BACSU/spoIIAB/spoIIAB-uniprot.txt
        supporting_text: "Phosphorylates SpoIIAA on a serine residue."
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      SpoIIAB is a serine/threonine protein kinase that phosphorylates SpoIIAA.
    action: ACCEPT
    reason: >-
      UniProt assigns EC 2.7.11.1 and reports SpoIIAB phosphorylates SpoIIAA on
      a serine residue, supporting serine/threonine kinase activity.
    supported_by:
      - reference_id: file:BACSU/spoIIAB/spoIIAB-uniprot.txt
        supporting_text: "Phosphorylates SpoIIAA on a serine residue."
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      SpoIIAB binds ATP as part of its kinase catalytic mechanism.
    action: ACCEPT
    reason: >-
      ATP binding is a core feature of SpoIIAB's kinase activity and is noted
      explicitly in UniProt keywords.
    supported_by:
      - reference_id: file:BACSU/spoIIAB/spoIIAB-uniprot.txt
        supporting_text: "KW   ATP-binding; Direct protein sequencing; Kinase; Nucleotide-binding;"
- term:
    id: GO:0010468
    label: regulation of gene expression
  evidence_type: IEA
  original_reference_id: GO_REF:0000104
  review:
    summary: >-
      SpoIIAB regulates expression indirectly by inhibiting sigma F, which
      controls sporulation gene transcription.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The term is too general and adds little beyond the specific sigma factor
      antagonist activity and negative regulation of transcription terms.
    supported_by:
      - reference_id: file:BACSU/spoIIAB/spoIIAB-uniprot.txt
        supporting_text: "Binds to sigma F and blocks its ability to form an RNA polymerase holoenzyme (E-sigma F)."
- term:
    id: GO:0016301
    label: kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      SpoIIAB is a protein kinase; however, this term is overly general.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The more specific protein serine/threonine kinase activity is already
      supported. This generic term is redundant.
    supported_by:
      - reference_id: file:BACSU/spoIIAB/spoIIAB-uniprot.txt
        supporting_text: "DE            EC=2.7.11.1;"
- term:
    id: GO:0016740
    label: transferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      SpoIIAB has kinase/transferase activity, but this term is too generic.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Transferase activity is a very broad parent term and is not informative
      relative to the specific kinase annotations.
    supported_by:
      - reference_id: file:BACSU/spoIIAB/spoIIAB-uniprot.txt
        supporting_text: "DE            EC=2.7.11.1;"
- term:
    id: GO:0016989
    label: sigma factor antagonist activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      SpoIIAB antagonizes sigma F by binding to it and blocking holoenzyme formation.
    action: ACCEPT
    reason: >-
      The InterPro-based inference aligns with SpoIIAB's known anti-sigma factor
      role and is supported by UniProt functional annotation.
    supported_by:
      - reference_id: file:BACSU/spoIIAB/spoIIAB-uniprot.txt
        supporting_text: "Binds to sigma F and blocks its ability to form an RNA polymerase holoenzyme (E-sigma F)."
- term:
    id: GO:0030435
    label: sporulation resulting in formation of a cellular spore
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      SpoIIAB is a stage II sporulation protein and part of the sigma F regulatory
      pathway.
    action: ACCEPT
    reason: >-
      UniProt assigns the sporulation keyword and names SpoIIAB as a stage II
      sporulation protein, supporting its role in spore formation.
    supported_by:
      - reference_id: file:BACSU/spoIIAB/spoIIAB-uniprot.txt
        supporting_text: "DE   AltName: Full=Stage II sporulation protein AB;"
      - reference_id: file:BACSU/spoIIAB/spoIIAB-uniprot.txt
        supporting_text: "KW   ATP-binding; Direct protein sequencing; Kinase; Nucleotide-binding; Reference proteome; Serine/threonine-protein kinase; Sporulation; Transferase."
- term:
    id: GO:0030436
    label: asexual sporulation
  evidence_type: IEA
  original_reference_id: GO_REF:0000104
  review:
    summary: >-
      SpoIIAB functions in the asexual sporulation program of B. subtilis.
    action: ACCEPT
    reason: >-
      Sporulation in B. subtilis is an asexual developmental process. SpoIIAB is a
      stage II sporulation protein required for proper sporulation regulation.
    supported_by:
      - reference_id: file:BACSU/spoIIAB/spoIIAB-uniprot.txt
        supporting_text: "DE   AltName: Full=Stage II sporulation protein AB;"
- term:
    id: GO:0042174
    label: negative regulation of sporulation resulting in formation of a cellular
      spore
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      SpoIIAB restrains sigma F activation prior to septation, but this does not
      represent a general negative regulation of sporulation.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
      - reference_id: file:BACSU/spoIIAB/spoIIAB-uniprot.txt
        supporting_text: "Binds to sigma F and blocks its ability to form an RNA polymerase holoenzyme (E-sigma F)."
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      SpoIIAB inhibits sigma F, leading to negative regulation of sigma F-dependent
      transcription.
    action: ACCEPT
    reason: >-
      SpoIIAB directly binds sigma F and blocks RNA polymerase holoenzyme formation,
      which is a direct negative regulatory effect on transcription.
    supported_by:
      - reference_id: file:BACSU/spoIIAB/spoIIAB-uniprot.txt
        supporting_text: "Binds to sigma F and blocks its ability to form an RNA polymerase holoenzyme (E-sigma F)."
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  review:
    summary: >-
      SpoIIAB phosphorylates SpoIIAA on a serine residue, consistent with serine
      protein kinase activity.
    action: ACCEPT
    reason: >-
      UniProt reports SpoIIAB phosphorylates SpoIIAA on serine and assigns EC
      2.7.11.1; this supports protein serine kinase activity.
    supported_by:
      - reference_id: file:BACSU/spoIIAB/spoIIAB-uniprot.txt
        supporting_text: "Phosphorylates SpoIIAA on a serine residue."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25278935
  review:
    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.
    action: UNDECIDED
    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.
    supported_by:
      - reference_id: PMID:25278935
        supporting_text: "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:
  - description: >-
      Binds sigma F to prevent RNA polymerase holoenzyme formation, acting as an
      anti-sigma factor that inhibits sigma F-dependent transcription.
    molecular_function:
      id: GO:0016989
      label: sigma factor antagonist activity
    directly_involved_in:
      - id: GO:0045892
        label: negative regulation of DNA-templated transcription
    supported_by:
      - reference_id: file:BACSU/spoIIAB/spoIIAB-uniprot.txt
        supporting_text: "Binds to sigma F and blocks its ability to form an RNA polymerase holoenzyme (E-sigma F)."
  - description: >-
      Phosphorylates the anti-anti-sigma factor SpoIIAA on serine residues,
      contributing to the partner-switching control of sigma F activity during
      sporulation.
    molecular_function:
      id: GO:0106310
      label: protein serine kinase activity
    directly_involved_in:
      - id: GO:0030435
        label: sporulation resulting in formation of a cellular spore
    supported_by:
      - reference_id: file:BACSU/spoIIAB/spoIIAB-uniprot.txt
        supporting_text: "Phosphorylates SpoIIAA on a serine residue."
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings:
  - statement: Maps InterPro anti-sigma-factor family records to sigma factor antagonist
      activity, negative regulation of transcription, and sporulation-related GO terms.
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings:
  - statement: Phylogenetic-tree-based propagation supports SpoIIAB as an anti-sigma
      factor for sigma F, consistent with orthologs across Bacillus and other Firmicutes.
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings:
  - statement: UniProt keywords ATP-binding, Kinase, Nucleotide-binding, Serine/threonine-protein
      kinase, Sporulation, and Transferase map to the corresponding GO terms.
    supporting_text: "KW   ATP-binding; Direct protein sequencing; Kinase; Nucleotide-binding;"
- id: GO_REF:0000104
  title: Electronic Gene Ontology annotations created by transferring manual GO annotations
    between related proteins based on shared sequence features
  findings:
  - statement: Manual annotations from characterized anti-sigma-factor kinases (e.g.
      SpoIIAB, RsbW) are propagated by shared sequence features (ATP-binding kinase
      domain plus anti-sigma-factor fold).
- id: GO_REF:0000116
  title: Automatic Gene Ontology annotation based on Rhea mapping
  findings:
  - statement: UniProt/Rhea catalytic-activity mapping (EC 2.7.11.1; L-seryl/L-threonyl-protein
      + ATP → phospho-form + ADP) supports protein serine/threonine kinase activity.
    supporting_text: "Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP +"
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings:
  - statement: Consensus of multiple IEA pipelines supports serine/threonine kinase
      activity and ATP binding for SpoIIAB, consistent with the manually curated function.
- id: PMID:25278935
  title: Cross-phosphorylation of bacterial serine/threonine and tyrosine protein
    kinases on key regulatory residues.
  findings:
  - statement: SpoIIAB is one of three two-component-like serine/threonine kinases
      in B. subtilis (with RsbT and RsbW) surveyed for cross-phosphorylation with
      Hanks-type and tyrosine kinases.
    supporting_text: "the three two-component-like serine/threonine kinases: RsbT (Kang et al., 1998), RsbW (Yang et al., 1996), and SpoIIAB (Min et al., 1993)"
  - statement: SpoIIAB is among the recipient kinases most readily cross-phosphorylated
      by Hanks-type kinases in this in vitro survey, suggesting integration of SpoIIAB
      activity into a broader kinase network.
    supporting_text: "the BY-kinase PtkA and the two-component-like kinases RsbW and SpoIIAB show the highest propensity to be phosphorylated by other kinases"
suggested_questions:
- question: >-
    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?
- question: >-
    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:
- hypothesis: >-
    Cross-phosphorylation of SpoIIAB by Hanks-type kinases modulates its
    anti-sigma-F activity or ATPase turnover during sporulation.
  description: >-
    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 ΔprkC/ΔprkD/ΔyabT backgrounds
    to test whether removing the donor kinases perturbs sigma F timing.
  experiment_type: Site-directed mutagenesis + reporter assay + genetic epistasis
- hypothesis: >-
    Compartment-specific SpoIIAB degradation contributes to release of sigma F in
    the forespore, in addition to SpoIIE-driven SpoIIAA dephosphorylation.
  description: >-
    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.
  experiment_type: Live-cell fluorescence microscopy + pulse-chase