DivIVA is a conserved membrane-associated scaffold protein in Gram-positive bacteria that functions as a polar landmark by sensing negative membrane curvature at cell poles and division septa. The protein forms oligomeric structures through its N-terminal membrane-binding domain (which inserts hydrophobic and positively charged residues into curved membranes) and C-terminal coiled-coil regions that mediate tetramerization and higher-order assembly. During vegetative growth, DivIVA localizes to both sides of the division septum and cell poles, where it recruits MinJ, which in turn positions MinCD to prevent aberrant FtsZ assembly at previous division sites, thereby ensuring proper septum site selection. During sporulation, DivIVA accumulates asymmetrically at the polar septum with forespore bias, associates with SpoIIE phosphatase to promote compartment-specific sigma-F activation, and interacts with Spo0J for chromosome anchoring at the cell pole. DivIVA also recruits ComN to cell poles, facilitating polar localization of comE mRNA during competence development. Loss of DivIVA results in misplacement of division septa leading to minicell formation, while overexpression is lethal.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0009273
peptidoglycan-based cell wall biogenesis
|
IBA
GO_REF:0000033 |
MARK AS OVER ANNOTATED |
Summary: DivIVA is primarily a scaffold protein involved in spatial organization of cell division rather than directly participating in peptidoglycan biosynthesis. While DivIVA localizes to sites of cell wall synthesis (septa and poles), its role is to position other proteins (MinCD via MinJ) that regulate where division occurs, not to directly contribute to peptidoglycan synthesis. In Corynebacterium glutamicum, DivIVA is required for polar peptidoglycan synthesis, but B. subtilis DivIVA localizes to septum rather than directing polar growth when expressed in C. glutamicum (PMID:18296522). This IBA annotation likely reflects functional conservation across Gram-positive bacteria where some DivIVA homologs do directly regulate cell wall synthesis, but in B. subtilis the connection is more indirect.
Reason: DivIVA in B. subtilis functions as a spatial organizer for septum site selection through the MinCD system, not as a direct participant in peptidoglycan biosynthesis. The protein's role is to sense membrane curvature and recruit MinJ/MinCD to prevent inappropriate FtsZ assembly. While this ultimately affects where peptidoglycan synthesis occurs during division, DivIVA itself does not catalyze or directly regulate peptidoglycan synthesis enzymes. This term is too broad and misrepresents the mechanistic role of B. subtilis DivIVA.
Supporting Evidence:
PMID:18296522
DivIVA proteins from Bacillus subtilis or Streptococcus pneumoniae, which localized at the septum of C. glutamicum
|
|
GO:0000917
division septum assembly
|
IEA
GO_REF:0000043 |
MODIFY |
Summary: DivIVA plays a critical role in regulating where division septa form by recruiting the MinJ/MinCD system to previous division sites and cell poles, thereby preventing inappropriate FtsZ assembly. This represents a core function of DivIVA in vegetative B. subtilis cells. Loss of DivIVA results in misplacement of septa and minicell formation. However, the term "division septum assembly" may be slightly broader than DivIVA's actual role, which is more specifically in septum site selection rather than the assembly process itself.
Reason: DivIVA does not directly assemble the division septum but rather controls where septum assembly can occur by positioning the MinCD inhibitor system. The more precise term would be GO:0000918 (division septum site selection), which accurately captures DivIVA's role in marking sites where the septum can or cannot form by recruiting MinJ and MinCD.
Proposed replacements:
division septum site selection
Supporting Evidence:
file:BACSU/divIVA/divIVA-deep-research-falcon.md
DivIVA localizes to both sides of midcell septum and to poles during vegetative growth and, together with MinJ, recruits MinCD to inhibit reassembly of the divisome at old sites
|
|
GO:0005737
cytoplasm
|
IEA
GO_REF:0000044 |
MODIFY |
Summary: DivIVA is annotated to cytoplasm based on UniProt subcellular location mapping. However, DivIVA is specifically a membrane-associated protein that localizes to regions of negative membrane curvature at cell poles and division septa. The protein's N-terminal domain binds directly to the membrane through hydrophobic and positively charged residues. While technically in the cytoplasm, this term is too general and fails to capture DivIVA's specific localization to cell poles and division sites.
Reason: The cytoplasm annotation is technically correct but too general. DivIVA specifically localizes to negatively curved membrane regions at cell poles and division septa. More specific CC terms would better capture DivIVA's localization pattern: GO:0060187 (cell pole) and GO:0000935 (division septum).
Proposed replacements:
cell pole
division septum
Supporting Evidence:
PMID:20502438
DivIVA is a conserved protein in Gram-positive bacteria that localizes at the poles and division sites, presumably through direct sensing of membrane curvature
|
|
GO:0030435
sporulation resulting in formation of a cellular spore
|
IEA
GO_REF:0000043 |
KEEP AS NON CORE |
Summary: DivIVA plays an important role during B. subtilis sporulation, where it accumulates asymmetrically at the polar septum with forespore bias and associates with SpoIIE phosphatase to contribute to compartment-specific sigma-F activation. DivIVA also interacts with Spo0J for chromosome anchoring at the cell pole during sporulation. Mutation of DivIVA causes sporulation defects. However, DivIVA is not a sporulation- specific protein - it functions during both vegetative growth and sporulation.
Reason: While DivIVA plays an important role in sporulation by positioning SpoIIE and anchoring chromosomes, sporulation is not its core function. DivIVA functions primarily as a polar landmark protein that senses membrane curvature, and its sporulation role is a specialized application of this general function. The annotation should be retained but marked as non-core.
Supporting Evidence:
file:BACSU/divIVA/divIVA-deep-research-falcon.md
During sporulation, DivIVA accumulates at the polar septum and becomes biased toward the forespore side as the septum matures. DivIVA associates with the phosphatase SpoIIE, contributing to forespore-specific activation of sigma-F and thus compartment-specific gene expression that initiates the sporulation program
|
|
GO:0051301
cell division
|
IEA
GO_REF:0000043 |
ACCEPT |
Summary: DivIVA is essential for proper cell division in B. subtilis, where it controls the spatial placement of division septa by recruiting MinJ/MinCD to cell poles and previous division sites. Loss of DivIVA leads to aberrant septum placement and minicell formation. This annotation accurately captures DivIVA's involvement in cell division, though a more specific term like GO:0000918 (division septum site selection) would better describe its precise role.
Reason: Cell division is a core function of DivIVA. The protein is essential for proper spatial control of cell division through the Min system. While GO:0000918 would be more specific, GO:0051301 is an appropriate parent term that accurately reflects DivIVA's biological role. This broad annotation should be retained alongside more specific annotations.
Supporting Evidence:
PMID:20502438
DivIVA deletion causes filamentous growth in Bacillus subtilis
file:BACSU/divIVA/divIVA-deep-research-falcon.md
DivIVA localizes to both sides of midcell septum and to poles during vegetative growth and, together with MinJ, recruits MinCD to inhibit reassembly of the divisome at old sites
|
|
GO:0005515
protein binding
|
IPI
PMID:22582279 DivIVA-mediated polar localization of ComN, a posttranscript... |
MODIFY |
Summary: This annotation is based on the interaction between DivIVA and ComN demonstrated by yeast two-hybrid and GST pulldown experiments in PMID:22582279. DivIVA directly binds ComN and is required for its polar localization. However, GO:0005515 (protein binding) is too generic and uninformative - a more specific term describing the scaffold or adapter function would be preferable.
Reason: While DivIVA does bind ComN, the generic term "protein binding" fails to capture the biological significance of this interaction. DivIVA functions as a scaffold protein that recruits multiple partners to cell poles. GO:0097110 (scaffold protein binding) would be more appropriate, or the annotation could be modified to reflect DivIVA's role as a scaffold that recruits other proteins.
Proposed replacements:
scaffold protein binding
Supporting Evidence:
PMID:22582279
Yeast two-hybrid and glutathione S-transferase pulldown experiments showed that ComN interacts directly with DivIVA
|
|
GO:0042802
identical protein binding
|
IPI
PMID:18296522 DivIVA is required for polar growth in the MreB-lacking rod-... |
ACCEPT |
Summary: This annotation reflects DivIVA's ability to form homo-oligomers, a well-established property essential for its scaffold function. The PMID:18296522 study in C. glutamicum demonstrates DivIVA self-interaction, and this property is conserved in B. subtilis DivIVA as shown by crystal structure studies.
Reason: Identical protein binding accurately describes DivIVA's homo-oligomerization, which is essential for its function as a membrane curvature-sensing scaffold. The protein forms tetramers and higher-order oligomers through its C-terminal coiled-coil domain. This is a well-characterized molecular function of DivIVA.
Supporting Evidence:
PMID:18296522
DivIVA from Streptomyces or Mycobacterium localized to the cell poles of DivIVA(Cg)-depleted C. glutamicum and restored polar peptidoglycan synthesis
PMID:20502438
A low-resolution crystal structure of the C-terminal (Ct) domain displays a curved tetramer made from two parallel coiled-coils
|
|
GO:0042802
identical protein binding
|
IPI
PMID:18363795 Control of the cell elongation-division cycle by shuttling o... |
ACCEPT |
Summary: This annotation reflects DivIVA self-interaction demonstrated in the context of PBP1 shuttling studies. DivIVA homo-oligomerization is essential for its scaffold function and is consistently demonstrated across multiple studies.
Reason: This is a duplicate annotation for identical protein binding with different evidence. The homo-oligomerization of DivIVA is well-established and represents a core molecular function. Multiple independent studies supporting this annotation strengthens the evidence base.
Supporting Evidence:
PMID:20502438
A low-resolution crystal structure of the C-terminal (Ct) domain displays a curved tetramer made from two parallel coiled-coils
|
|
GO:0042802
identical protein binding
|
IPI
PMID:20502438 Features critical for membrane binding revealed by DivIVA cr... |
ACCEPT |
Summary: This annotation is strongly supported by the crystal structure of DivIVA reported in PMID:20502438, which definitively demonstrates that DivIVA forms homo-oligomers through its coiled-coil domains. The N-terminal domain forms parallel coiled-coils and the C-terminal domain forms curved tetramers.
Reason: The crystal structure provides definitive evidence for DivIVA homo-oligomerization. The protein forms dimers through its N-terminal domain and tetramers through its C-terminal coiled-coil region. This is a core molecular function essential for DivIVA's role as a membrane-associated scaffold.
Supporting Evidence:
PMID:20502438
We have determined the crystal structure of the N-terminal (Nt) domain of DivIVA, and show that it forms a parallel coiled-coil
|
|
GO:0042802
identical protein binding
|
IPI
PMID:21630458 An expanded protein-protein interaction network in Bacillus ... |
ACCEPT |
Summary: This annotation comes from a large-scale protein-protein interaction study in B. subtilis using yeast two-hybrid. DivIVA was identified as part of a group of highly connected hub proteins. The self-interaction of DivIVA is consistent with its known oligomeric nature.
Reason: While this annotation comes from a high-throughput study, it is consistent with the well-established homo-oligomerization of DivIVA demonstrated by crystal structure and other biochemical studies. Multiple lines of evidence support DivIVA self-interaction as a core molecular function.
Supporting Evidence:
PMID:21630458
We have generated a protein-protein interaction network in Bacillus subtilis focused on several essential cellular processes such as cell division
|
|
GO:0140090
membrane curvature sensor activity
|
IDA
PMID:20502438 Features critical for membrane binding revealed by DivIVA cr... |
NEW |
Summary: DivIVA preferentially localizes to regions of negative membrane curvature at cell poles and division septa. Crystal structure analysis reveals an N-terminal domain with hydrophobic and positively charged residues that insert into curved membranes. This curvature sensing is the fundamental mechanism underlying DivIVA's localization and function as a polar landmark.
Reason: Membrane curvature sensor activity is the core molecular function of DivIVA that underlies all its biological roles. The crystal structure (PMID:20502438) provides structural evidence for how DivIVA binds to curved membranes, and multiple studies confirm its preferential localization to negatively curved membrane regions at poles and septa. This annotation is not currently in the GOA annotations but represents DivIVA's most fundamental molecular activity.
Supporting Evidence:
PMID:20502438
DivIVA is a conserved protein in Gram-positive bacteria that localizes at the poles and division sites, presumably through direct sensing of membrane curvature
file:BACSU/divIVA/divIVA-deep-research-falcon.md
DivIVA preferentially targets regions of high negative membrane curvature, including poles and septal membranes
|
Exported on March 22, 2026 at 03:16 AM
Organism: Bacillus subtilis
Sequence:
MPLTPNDIHNKTFTKSFRGYDEDEVNEFLAQVRKDYEIVLRKKTELEAKVNELDERIGHFANIEETLNKSILVAQEAAEDVKRNSQKEAKLIVREAEKNADRIINESLSKSRKIAMEIEELKKQSKVFRTRFQMLIEAQLDLLKNDDWDHLLEYEVDAVFEEKE
I begin by examining the domain architecture. The protein is defined by IPR007793 (DivIVA family, residues 1–151), a hallmark of bacterial cell-division scaffolds that organize polar and septal assembly. Nested within this is IPR019933 (DivIVA domain, residues 3–36), an N-terminal module that nucleates oligomerization and membrane-proximal assembly. The order—an N-terminal DivIVA domain embedded in a larger DivIVA family scaffold—creates a bipartite architecture: a compact oligomerization/membrane-tethering core (3–36) followed by an extended family region (1–151) that stabilizes higher-order lattices. This architecture causes avid, multivalent protein–protein and protein–membrane interactions rather than catalysis, consistent with a non-enzymatic organizer.
From this scaffold, I infer molecular function as protein binding (GO:0005515). The N-terminal DivIVA domain drives filament formation and docking of divisome factors; the extended family region supplies additional interaction surfaces that concentrate assembly at cell poles and nascent septa. There are no catalytic motifs or transmembrane segments; the functional core is an assembly platform that binds partners with high specificity and cooperativity.
These binding-driven assemblies feed directly into cell-biological roles. By concentrating and positioning the cytokinetic apparatus, the scaffold orchestrates FtsZ-ring maturation and downstream Z-ring–dependent constriction, placing the protein squarely in cytokinesis (GO:0000910). Its polar-targeted assemblies guide the spatial patterning of the division machinery and thereby couple morphogenesis with septal wall synthesis, aligning with the formal concept of cell division.
Cellular location follows from the same architecture and tasking. The absence of transmembrane helices and the presence of membrane-proximal oligomerization favor a soluble, cytoplasmic scaffold that associates peripherally with the inner surface of the membrane and with cortical arrays. This supports a cytoplasmic localization (GO:0005737), with transient enrichment at poles and the division site.
Mechanistically, I propose that the N-terminal DivIVA domain nucleates a curved oligomer that binds acidic phospholipids and recruits early divisome components. This lattice then captures and stabilizes FtsZ polymers and their membrane-tethering adaptors, funneling the assembly toward a mature Z ring at midcell. Likely interaction partners include the tubulin-like FtsZ and its adaptors (FtsA, ZapA), as well as polar/pilus factors that guide spatial assembly in Firmicutes. By concentrating these partners, the scaffold times and places cytokinesis and thereby drives cell division fidelity.
A cytoplasmic scaffold that assembles and positions the cytokinetic machinery in Bacillus subtilis. It oligomerizes through an N-terminal assembly core and uses an extended scaffold to form membrane-proximal lattices that concentrate early cell-division components at poles and nascent septa. By organizing these assemblies and coupling them to the membrane and cortical arrays, it promotes maturation of the division apparatus and coordinates the execution of cytokinesis.
Involved in cell division.
IPR007793, family) — residues 1-151IPR019933, domain) — residues 3-36Molecular Function: molecular_function (GO:0003674), binding (GO:0005488), protein binding (GO:0005515), identical protein binding (GO:0042802)
Biological Process: biological_process (GO:0008150), cellular process (GO:0009987), cellular component organization or biogenesis (GO:0071840), cell motility (GO:0048870), cilium or flagellum-dependent cell motility (GO:0001539), cellular component organization (GO:0016043), cellular component biogenesis (GO:0044085), archaeal or bacterial-type flagellum-dependent cell motility (GO:0097588), cell projection organization (GO:0030030), organelle organization (GO:0006996), cellular component assembly (GO:0022607), organelle assembly (GO:0070925), cell projection assembly (GO:0030031), bacterial-type flagellum organization (GO:0044781), bacterial-type flagellum-dependent cell motility (GO:0071973), bacterial-type flagellum assembly (GO:0044780), bacterial-type flagellum-dependent swarming motility (GO:0071978), non-membrane-bounded organelle assembly (GO:0140694)
Cellular Component: cellular_component (GO:0005575), protein-containing complex (GO:0032991)
Generated by BioReason
Exported on March 22, 2026 at 03:16 AM
Organism: Bacillus subtilis
Sequence:
MPLTPNDIHNKTFTKSFRGYDEDEVNEFLAQVRKDYEIVLRKKTELEAKVNELDERIGHFANIEETLNKSILVAQEAAEDVKRNSQKEAKLIVREAEKNADRIINESLSKSRKIAMEIEELKKQSKVFRTRFQMLIEAQLDLLKNDDWDHLLEYEVDAVFEEKE
I begin by examining the domain architecture. The protein is defined by IPR007793 (DivIVA family, residues 1–151), a hallmark of bacterial cell-division scaffolds that organize polar and septal assembly. Nested within this is IPR019933 (DivIVA domain, residues 3–36), an N-terminal module that nucleates oligomerization and membrane-proximal assembly. The order—an N-terminal DivIVA domain embedded in a larger DivIVA family scaffold—creates a bipartite architecture: a compact oligomerization/membrane-tethering core (3–36) followed by an extended family region (1–151) that stabilizes higher-order lattices. This architecture causes avid, multivalent protein–protein and protein–membrane interactions rather than catalysis, consistent with a non-enzymatic organizer.
From this scaffold, I infer molecular function as protein binding (GO:0005515). The N-terminal DivIVA domain drives filament formation and docking of divisome factors; the extended family region supplies additional interaction surfaces that concentrate assembly at cell poles and nascent septa. There are no catalytic motifs or transmembrane segments; the functional core is an assembly platform that binds partners with high specificity and cooperativity.
These binding-driven assemblies feed directly into cell-biological roles. By concentrating and positioning the cytokinetic apparatus, the scaffold orchestrates FtsZ-ring maturation and downstream Z-ring–dependent constriction, placing the protein squarely in cytokinesis (GO:0000910). Its polar-targeted assemblies guide the spatial patterning of the division machinery and thereby couple morphogenesis with septal wall synthesis, aligning with the formal concept of cell division.
Cellular location follows from the same architecture and tasking. The absence of transmembrane helices and the presence of membrane-proximal oligomerization favor a soluble, cytoplasmic scaffold that associates peripherally with the inner surface of the membrane and with cortical arrays. This supports a cytoplasmic localization (GO:0005737), with transient enrichment at poles and the division site.
Mechanistically, I propose that the N-terminal DivIVA domain nucleates a curved oligomer that binds acidic phospholipids and recruits early divisome components. This lattice then captures and stabilizes FtsZ polymers and their membrane-tethering adaptors, funneling the assembly toward a mature Z ring at midcell. Likely interaction partners include the tubulin-like FtsZ and its adaptors (FtsA, ZapA), as well as polar/pilus factors that guide spatial assembly in Firmicutes. By concentrating these partners, the scaffold times and places cytokinesis and thereby drives cell division fidelity.
A cytoplasmic scaffold that assembles and positions the cytokinetic machinery in Bacillus subtilis. It oligomerizes through an N-terminal assembly core and uses an extended scaffold to form membrane-proximal lattices that concentrate early cell-division components at poles and nascent septa. By organizing these assemblies and coupling them to the membrane and cortical arrays, it promotes maturation of the division apparatus and coordinates the execution of cytokinesis.
Involved in cell division.
IPR007793, family) — residues 1-151IPR019933, domain) — residues 3-36Molecular Function: molecular_function (GO:0003674), binding (GO:0005488), protein binding (GO:0005515), identical protein binding (GO:0042802)
Biological Process: biological_process (GO:0008150), cellular process (GO:0009987), cellular component organization or biogenesis (GO:0071840), cell motility (GO:0048870), cilium or flagellum-dependent cell motility (GO:0001539), cellular component organization (GO:0016043), cellular component biogenesis (GO:0044085), archaeal or bacterial-type flagellum-dependent cell motility (GO:0097588), cell projection organization (GO:0030030), organelle organization (GO:0006996), cellular component assembly (GO:0022607), organelle assembly (GO:0070925), cell projection assembly (GO:0030031), bacterial-type flagellum organization (GO:0044781), bacterial-type flagellum-dependent cell motility (GO:0071973), bacterial-type flagellum assembly (GO:0044780), bacterial-type flagellum-dependent swarming motility (GO:0071978), non-membrane-bounded organelle assembly (GO:0140694)
Cellular Component: cellular_component (GO:0005575), protein-containing complex (GO:0032991)
Generated by BioReason
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model: Edison Scientific Literature
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start_time: '2025-12-17T23:25:12.061159'
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template_file: templates/gene_research_go_focused.md
template_variables:
organism: BACSU
gene_id: divIVA
gene_symbol: divIVA
uniprot_accession: P71021
protein_description: 'RecName: Full=Septum site-determining protein DivIVA; AltName:
Full=Cell division initiation protein DivIVA; AltName: Full=Minicell-associated
protein DivIVA;'
gene_info: Name=divIVA; Synonyms=ylmJ; OrderedLocusNames=BSU15420;
organism_full: Bacillus subtilis (strain 168).
protein_family: Belongs to the DivIVA family. .
protein_domains: DivIVA_domain. (IPR019933); DivIVA_fam. (IPR007793); DivIVA (PF05103)
provider_config:
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citation_count: 18
BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.
DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'divIVA' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information
Please provide a comprehensive research report on the gene divIVA (gene ID: divIVA, UniProt: P71021) in BACSU.
The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
Question: You are an expert researcher providing comprehensive, well-cited information.
Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies
Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.
BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.
DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'divIVA' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information
Please provide a comprehensive research report on the gene divIVA (gene ID: divIVA, UniProt: P71021) in BACSU.
The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
Comprehensive research report: Bacillus subtilis DivIVA (divIVA; UniProt P71021)
Verification of target identity and family context
- Identity and organism: DivIVA in Bacillus subtilis (strain 168) is a polar/septal scaffold central to cell division topology and sporulation-associated polarity. Its study is well established in B. subtilis, matching the target gene symbol and organism specified (divIVA, BACSU). Recent overviews of B. subtilis cell biology explicitly place DivIVA as a polar scaffold in this organism (Stülke et al., 2023, Journal of Bacteriology; published May 2023) (stulke2023bacillussubtilisa pages 2-5).
- Family and domains: DivIVA proteins are conserved coiled-coil scaffolds that oligomerize and target curved membranes in Gram-positive bacteria, consistent with the DivIVA family/domain annotations. Structural and comparative work highlights N-terminal membrane-binding elements and C-terminal coiled-coils mediating higher-order assemblies, aligning with DivIVA family/domain descriptions (Lubbers et al., 2025, bioRxiv; Chaudhary et al., 2023, Microbiology Spectrum) (lubbers2025definingtheminimal pages 10-12, lubbers2025definingtheminimal pages 1-3, chaudhary2023divivaphosphorylationaffects pages 18-18).
1) Key concepts and definitions with current understanding
- Primary function (vegetative growth): DivIVA is a membrane-associated scaffold that localizes to both sides of the division septum and to cell poles during vegetative growth. Together with MinJ, DivIVA recruits MinCD to previously used division sites, preventing aberrant reassembly of the divisome and ensuring correct spatial control of cytokinesis (Stülke et al., 2023) (stulke2023bacillussubtilisa pages 2-5).
- Primary function (sporulation): During sporulation, DivIVA accumulates at the polar septum and becomes biased toward the forespore side as the septum matures. DivIVA associates with the phosphatase SpoIIE, contributing to forespore-specific activation of σF and thus compartment-specific gene expression that initiates the sporulation program (Chareyre et al., 2023, bioRxiv, Aug 2023) (chareyre2023celldivisionmachinery pages 15-18, chareyre2023celldivisionmachinery pages 1-6, chareyre2023celldivisionmachinery pages 11-15).
- Localization principle (curvature/poles/septa): DivIVA preferentially targets regions of high negative membrane curvature, including poles and septal membranes, a property underlying its pole/septum localization and scaffolding functions (Chareyre et al., 2023; Chaudhary et al., 2023) (chareyre2023celldivisionmachinery pages 1-6, chaudhary2023divivaphosphorylationaffects pages 18-18).
- Structural features: DivIVA is a coiled-coil oligomer. Evidence indicates an N-terminal membrane-binding/dimerization region and a C-terminal coiled-coil mediating tetramers/higher-order oligomers, which together support lattice-like assemblies at curved membranes (Chaudhary et al., 2023; Lubbers et al., 2025) (chaudhary2023divivaphosphorylationaffects pages 18-18, lubbers2025definingtheminimal pages 10-12, lubbers2025definingtheminimal pages 1-3).
2) Recent developments and latest research (2023–2024 priority)
- Sporulation-specific asymmetric localization and divisome coupling: Chareyre et al. (2023) showed that in B. subtilis the polar septum is thinner than vegetative septa and that DivIVA and SpoIIE exhibit forespore-biased accumulation at the polar septum, while FtsA/FtsZ show mother-cell bias. A DivIVA point mutant (R94N) diminished forespore-biased localization (DivIVAR94N-GFP ~46% forespore bias vs WT ~72%), reduced forespore-specific σF activation (~40% of cells), and impaired sporulation efficiency (~0.18× WT). Mild overproduction of both FtsA and FtsZ rescued DivIVA/SpoIIE asymmetry and septal thickness, supporting a reciprocal coupling between SpoIIE/DivIVA and the cytokinetic machinery (dual-color 3D-SIM and TEM) (bioRxiv preprint, Aug 2023; provides quantitative updates on localization dynamics) (chareyre2023celldivisionmachinery pages 1-6, chareyre2023celldivisionmachinery pages 11-15, chareyre2023celldivisionmachinery pages 15-18).
- Broad context of DivIVA-family regulation and phosphorylation: While centered on D. radiodurans, Chaudhary et al. (2023) comprehensively compile foundational B. subtilis DivIVA literature (polar targeting, crystal-structure insights for membrane binding, Min system regulation), underscoring conserved principles of DivIVA curvature sensing and oligomerization. This 2023 review-style synthesis anchors DivIVA’s structure–function relationships relevant to B. subtilis (Microbiology Spectrum, Apr 2023) (chaudhary2023divivaphosphorylationaffects pages 18-18).
- Model organism perspective in 2023: Stülke et al. (2023) summarize B. subtilis cell biology, explicitly noting DivIVA’s role as a polar scaffold that partners with MinJ to recruit MinCD and prevent reuse of prior division sites, situating DivIVA in current B. subtilis cell-cycle frameworks (Journal of Bacteriology, May 2023) (stulke2023bacillussubtilisa pages 2-5).
3) Current applications and real-world implementations
- Cell biology imaging and localization reporters: DivIVA has been repeatedly used as a localization marker via fluorescent protein fusions (e.g., DivIVA–GFP/mCherry) to visualize poles and septa in B. subtilis. This practical implementation enables tracking of polar/septal dynamics and is widely deployed in studies of division and sporulation (Stülke et al., 2023) (stulke2023bacillussubtilisa pages 2-5).
- Synthetic biology potential: While our gathered sources do not document engineered DivIVA-based “polarity tags” beyond microscopy reporters, the robust polar/septal localization of DivIVA fusions in B. subtilis suggests its utility as a targeting module for engineering spatially controlled processes at poles or septa. Direct engineered applications were not explicitly described in the retrieved 2023–2024 sources (Stülke et al., 2023) (stulke2023bacillussubtilisa pages 2-5).
4) Expert opinions and analysis from authoritative sources
- Authoritative organismal review: Stülke et al. (2023) describe DivIVA as a principal polar scaffold in B. subtilis that, with MinJ, positions MinCD to enforce topological specificity of division—an expert synthesis placing DivIVA at the core of spatial regulation of cytokinesis (Journal of Bacteriology, 2023) (stulke2023bacillussubtilisa pages 2-5).
- Mechanistic synthesis and cross-system grounding: Chaudhary et al. (2023) discuss DivIVA family membrane targeting, structural determinants, and Min regulation, citing foundational B. subtilis work (e.g., Min activity regulation, structural determinants for membrane binding), reinforcing conserved mechanistic principles underpinning DivIVA’s role in B. subtilis (Microbiology Spectrum, 2023) (chaudhary2023divivaphosphorylationaffects pages 18-18).
- Sporulation-specific coupling to the divisome: Chareyre et al. (2023) provide a mechanistic model linking DivIVA/SpoIIE asymmetry to FtsA/FtsZ redeployment and septum architecture during sporulation, highlighting how divisome features drive compartment-specific gene activation via DivIVA-tethered SpoIIE (bioRxiv, 2023) (chareyre2023celldivisionmachinery pages 15-18, chareyre2023celldivisionmachinery pages 1-6, chareyre2023celldivisionmachinery pages 11-15).
5) Relevant statistics and data from recent studies
- Forespore-biased localization: DivIVA-GFP forespore bias at polar septa is ~72% in WT vs ~46% in DivIVAR94N mutant; SpoIIE asymmetry similarly reduced in the mutant and restored by FtsA+FtsZ overexpression (Chareyre et al., 2023) (chareyre2023celldivisionmachinery pages 11-15).
- σF activation and sporulation efficiency: DivIVAR94N exhibits ~40% forespore-specific σF activation and ~0.18× WT sporulation efficiency; both improved substantially upon FtsA+FtsZ overproduction (Chareyre et al., 2023) (chareyre2023celldivisionmachinery pages 11-15).
- Septum architecture: Polar septum thickness increased in DivIVAR94N (~36 nm) compared to WT (~20 nm), and was reduced toward normal (~10 nm) by FtsA+FtsZ overproduction (Chareyre et al., 2023) (chareyre2023celldivisionmachinery pages 11-15).
Interaction partners and pathways (B. subtilis)
- MinJ/MinCD: DivIVA recruits MinJ, which positions MinCD at prior division sites to prevent FtsZ reassembly at old septa, enforcing spatial fidelity of new division events (Stülke et al., 2023) (stulke2023bacillussubtilisa pages 2-5).
- SpoIIE (sporulation): DivIVA associates with SpoIIE at the polar septum; their asymmetric distribution supports forespore-specific σF activation. Coupling to divisome components FtsA and FtsZ influences septal architecture and DivIVA/SpoIIE asymmetry (Chareyre et al., 2023) (chareyre2023celldivisionmachinery pages 15-18, chareyre2023celldivisionmachinery pages 1-6, chareyre2023celldivisionmachinery pages 11-15).
- Other classic partners (RacA, Soj/ParA, ComN): Although these interactions are well known historically for B. subtilis sporulation polarity and chromosome anchoring, specific primary-source details were not captured within our gathered evidence set; thus, we refrain from citing them here to maintain strict source fidelity.
Structural biology and localization mechanism
- Coiled-coil scaffold and oligomerization: DivIVA comprises an N-terminal membrane-binding/dimer interface and C-terminal coiled-coils that assemble into higher-order oligomers, enabling scaffolding at curved membranes. Structural/crystallographic insights and modeling support this modular architecture (Chaudhary et al., 2023; Lubbers et al., 2025) (chaudhary2023divivaphosphorylationaffects pages 18-18, lubbers2025definingtheminimal pages 10-12, lubbers2025definingtheminimal pages 1-3).
- Curvature sensing and pole/septum targeting: DivIVA’s affinity for negatively curved membranes underlies its accumulation at cell poles and septal regions, explaining its role in organizing polar/septal protein complexes (Chareyre et al., 2023; Chaudhary et al., 2023) (chareyre2023celldivisionmachinery pages 1-6, chaudhary2023divivaphosphorylationaffects pages 18-18).
Limitations and scope note
- While multiple authoritative studies describe interactions of DivIVA with proteins such as RacA, Soj/ParA, and ComN during sporulation and chromosome anchoring in B. subtilis, those specific primary references were not included among the retrieved texts in our evidence set for this report. Accordingly, we have limited claims to those directly supported by the gathered sources.
Embedded summary artifact
| Category | Specific claim | Evidence details (quantitative where present) | Source |
|---|---|---|---|
| Identity & family | DivIVA is a conserved septum/pole scaffold (DivIVA family); coiled-coil protein family member | Conserved DivIVA family protein implicated in septum/pole determination and polarity across Firmicutes; coiled-coil architecture reported (inferred from UniProt-family descriptions and recent reviews) (lubbers2025definingtheminimal pages 10-12, stulke2023bacillussubtilisa pages 2-5). | Stülke et al., 2023; Journal of Bacteriology; https://doi.org/10.1128/jb.00102-23 (stulke2023bacillussubtilisa pages 2-5); Lubbers et al., 2025; bioRxiv; https://doi.org/10.1101/2025.06.24.661030 (lubbers2025definingtheminimal pages 10-12) |
| Vegetative localization & MinJ/MinCD recruitment | Localizes to division septum and cell poles; recruits MinJ which positions MinCD at previous division sites to inhibit aberrant FtsZ assembly | DivIVA localizes to both sides of midcell septum and to poles during vegetative growth and, together with MinJ, recruits MinCD to inhibit reassembly of the divisome at old sites (stulke2023bacillussubtilisa pages 2-5, sutton2023therolesof pages 12-13). | Stülke et al., 2023; Journal of Bacteriology; https://doi.org/10.1128/jb.00102-23 (stulke2023bacillussubtilisa pages 2-5); Sutton et al., 2023; Frontiers in Microbiology; https://doi.org/10.3389/fmicb.2023.1241249 (sutton2023therolesof pages 12-13) |
| Sporulation: asymmetric localization, SpoIIE interaction, σF activation | DivIVA shows forespore-biased localization at the polar septum, binds/associates with SpoIIE and contributes to compartment-specific σF activation; perturbation alters σF activation and sporulation efficiency | Chareyre et al., 2023: WT DivIVA-GFP forespore bias ~72% vs DivIVAR94N-GFP ~46%; DivIVAR94N reduces compartment-specific σF activation (~40% of cells) and lowers sporulation efficiency to ~0.18× WT; overproduction of FtsA+FtsZ rescues localization, σF activation and septum thickness (methods: dual-color 3D SIM, TEM) (chareyre2023celldivisionmachinery pages 1-6, chareyre2023celldivisionmachinery pages 11-15). | Chareyre et al., 2023; bioRxiv; https://doi.org/10.1101/2023.08.10.552768 (chareyre2023celldivisionmachinery pages 1-6, chareyre2023celldivisionmachinery pages 11-15) |
| Curvature / pole targeting | Preferential targeting to negatively curved membranes (poles); curvature acts as localization cue | Multiple studies report DivIVA preference for highly negatively curved membrane regions (poles/septa), supporting curvature-dependent recruitment as a localization mechanism (chareyre2023celldivisionmachinery pages 1-6, chaudhary2023divivaphosphorylationaffects pages 18-18). | Chareyre et al., 2023; bioRxiv; https://doi.org/10.1101/2023.08.10.552768 (chareyre2023celldivisionmachinery pages 1-6); Chaudhary et al., 2023; Microbiology Spectrum; https://doi.org/10.1128/spectrum.03141-22 (chaudhary2023divivaphosphorylationaffects pages 18-18) |
| Structural features (coiled-coils, oligomerization) | N-terminal membrane/dimer interface + C-terminal coiled-coil mediating oligomerization; forms multimers/filaments; C-terminal deletions impair function | Structural/crystal and modeling studies indicate an N-terminal membrane-binding/dimerization region and C-terminal coiled-coil(s) that mediate higher-order oligomerization (tetramers/filaments); mutations/deletions in coiled-coil regions disrupt assembly and morphology (chaudhary2023divivaphosphorylationaffects pages 18-18, lubbers2025definingtheminimal pages 10-12, lubbers2025definingtheminimal pages 1-3). | Chaudhary et al., 2023; Microbiology Spectrum; https://doi.org/10.1128/spectrum.03141-22 (chaudhary2023divivaphosphorylationaffects pages 18-18); Lubbers et al., 2025; bioRxiv; https://doi.org/10.1101/2025.06.24.661030 (lubbers2025definingtheminimal pages 10-12, lubbers2025definingtheminimal pages 1-3) |
| Use as localization tag / reporter | DivIVA has been visualized using fluorescent protein fusions (GFP/mCherry) to report pole/septum localization; explicit engineered 'polarity-tag' applications in B. subtilis not documented in gathered sources | Historical and recent imaging studies use DivIVA–FP fusions to map pole/septum localization, supporting its practical use as a localization reporter; no direct evidence in the gathered set for widespread engineered synthetic-biology 'tag' use beyond microscopy reporters (stulke2023bacillussubtilisa pages 2-5). | Stülke et al., 2023; Journal of Bacteriology; https://doi.org/10.1128/jb.00102-23 (stulke2023bacillussubtilisa pages 2-5) |
Table: Compact, evidence-linked summary of key findings about Bacillus subtilis DivIVA (divIVA, UniProt P71021), including function, localization, structural features, and quantitated sporulation impacts, with direct sources and URLs for each claim.
Citations with URLs and publication dates
- Stülke J, Grüppen A, Bramkamp M, Pelzer S. Bacillus subtilis, a Swiss Army Knife in Science and Biotechnology. Journal of Bacteriology. 205(5):e00102-23. Published May 2023. URL: https://doi.org/10.1128/jb.00102-23 (stulke2023bacillussubtilisa pages 2-5)
- Chareyre S, Li X, Anjuwon-Foster BR, et al. Cell division machinery drives cell-specific gene activation during bacterial differentiation. bioRxiv. Posted Aug 2023. URL: https://doi.org/10.1101/2023.08.10.552768 (chareyre2023celldivisionmachinery pages 15-18, chareyre2023celldivisionmachinery pages 1-6, chareyre2023celldivisionmachinery pages 11-15)
- Chaudhary R, Kota S, Misra HS. DivIVA Phosphorylation Affects Its Dynamics and Cell Cycle in Radioresistant Deinococcus radiodurans. Microbiology Spectrum. 11(2):e03141-22. Published Apr 2023. URL: https://doi.org/10.1128/spectrum.03141-22 (chaudhary2023divivaphosphorylationaffects pages 18-18)
- Lubbers M, Bajramović B, Ongenae V, et al. Defining the minimal structural requirements of DivIVA in filamentous Actinomycetota. bioRxiv. Posted Jun 2025. URL: https://doi.org/10.1101/2025.06.24.661030 (lubbers2025definingtheminimal pages 10-12, lubbers2025definingtheminimal pages 1-3)
- Sutton JAF, Cooke M, Tinajero-Trejo M, et al. The roles of GpsB and DivIVA in Staphylococcus aureus growth and division. Frontiers in Microbiology. Published Aug 2023. URL: https://doi.org/10.3389/fmicb.2023.1241249 (sutton2023therolesof pages 12-13)
References
(stulke2023bacillussubtilisa pages 2-5): Jörg Stülke, Anika Grüppen, Marc Bramkamp, and Stefan Pelzer. Bacillus subtilis, a swiss army knife in science and biotechnology. Journal of Bacteriology, May 2023. URL: https://doi.org/10.1128/jb.00102-23, doi:10.1128/jb.00102-23. This article has 85 citations and is from a peer-reviewed journal.
(lubbers2025definingtheminimal pages 10-12): Maarten Lubbers, Belmin Bajramović, Véronique Ongenae, Joost Willemse, Dieuwertje de Bruin, Niels Mulder, Bastienne Vriesendorp, Francisco Barona-Gómez, Ariane Briegel, Gilles P. van Wezel, Klas Flärdh, and Dennis Claessen. Defining the minimal structural requirements of diviva in filamentous actinomycetota. bioRxiv, Jun 2025. URL: https://doi.org/10.1101/2025.06.24.661030, doi:10.1101/2025.06.24.661030. This article has 0 citations and is from a poor quality or predatory journal.
(lubbers2025definingtheminimal pages 1-3): Maarten Lubbers, Belmin Bajramović, Véronique Ongenae, Joost Willemse, Dieuwertje de Bruin, Niels Mulder, Bastienne Vriesendorp, Francisco Barona-Gómez, Ariane Briegel, Gilles P. van Wezel, Klas Flärdh, and Dennis Claessen. Defining the minimal structural requirements of diviva in filamentous actinomycetota. bioRxiv, Jun 2025. URL: https://doi.org/10.1101/2025.06.24.661030, doi:10.1101/2025.06.24.661030. This article has 0 citations and is from a poor quality or predatory journal.
(chaudhary2023divivaphosphorylationaffects pages 18-18): Reema Chaudhary, Swathi Kota, and Hari S. Misra. Diviva phosphorylation affects its dynamics and cell cycle in radioresistant deinococcus radiodurans. Microbiology Spectrum, Apr 2023. URL: https://doi.org/10.1128/spectrum.03141-22, doi:10.1128/spectrum.03141-22. This article has 8 citations and is from a domain leading peer-reviewed journal.
(chareyre2023celldivisionmachinery pages 15-18): Sylvia Chareyre, Xuesong Li, Brandon R. Anjuwon-Foster, Sarah Clifford, Anna Brogan, Yijun Su, Hari Shroff, and Kumaran S. Ramamurthi. Cell division machinery drives cell-specific gene activation during bacterial differentiation. bioRxiv, Aug 2023. URL: https://doi.org/10.1101/2023.08.10.552768, doi:10.1101/2023.08.10.552768. This article has 0 citations and is from a poor quality or predatory journal.
(chareyre2023celldivisionmachinery pages 1-6): Sylvia Chareyre, Xuesong Li, Brandon R. Anjuwon-Foster, Sarah Clifford, Anna Brogan, Yijun Su, Hari Shroff, and Kumaran S. Ramamurthi. Cell division machinery drives cell-specific gene activation during bacterial differentiation. bioRxiv, Aug 2023. URL: https://doi.org/10.1101/2023.08.10.552768, doi:10.1101/2023.08.10.552768. This article has 0 citations and is from a poor quality or predatory journal.
(chareyre2023celldivisionmachinery pages 11-15): Sylvia Chareyre, Xuesong Li, Brandon R. Anjuwon-Foster, Sarah Clifford, Anna Brogan, Yijun Su, Hari Shroff, and Kumaran S. Ramamurthi. Cell division machinery drives cell-specific gene activation during bacterial differentiation. bioRxiv, Aug 2023. URL: https://doi.org/10.1101/2023.08.10.552768, doi:10.1101/2023.08.10.552768. This article has 0 citations and is from a poor quality or predatory journal.
(sutton2023therolesof pages 12-13): Joshua A. F. Sutton, Mark Cooke, Mariana Tinajero-Trejo, Katarzyna Wacnik, Bartłomiej Salamaga, Callum Portman-Ross, Victoria A. Lund, Jamie K. Hobbs, and Simon J. Foster. The roles of gpsb and diviva in staphylococcus aureus growth and division. Frontiers in Microbiology, Aug 2023. URL: https://doi.org/10.3389/fmicb.2023.1241249, doi:10.3389/fmicb.2023.1241249. This article has 14 citations and is from a poor quality or predatory journal.
Source: divIVA-deep-research-bioreason-rl.md
The BioReason functional summary reads:
A cytoplasmic scaffold that assembles and positions the cytokinetic machinery in Bacillus subtilis. It oligomerizes through an N-terminal assembly core and uses an extended scaffold to form membrane-proximal lattices that concentrate early cell-division components at poles and nascent septa. By organizing these assemblies and coupling them to the membrane and cortical arrays, it promotes maturation of the division apparatus and coordinates the execution of cytokinesis.
The summary correctly identifies DivIVA as a scaffold involved in cell division that oligomerizes and localizes to poles and septa. However, several significant errors and omissions reduce accuracy:
Missed core molecular function: The curated review identifies membrane curvature sensor activity (GO:0140090) as the fundamental molecular function of DivIVA. This is what drives its localization to negatively curved membrane regions at cell poles and division septa. BioReason misses this entirely, defaulting to generic "protein binding" (GO:0005515).
Wrong mechanism: BioReason describes DivIVA as directly promoting "maturation of the division apparatus" and orchestrating "FtsZ-ring maturation." The curated review clarifies that DivIVA's actual role in B. subtilis is division septum site selection (GO:0000918) -- it recruits MinJ/MinCD to prevent inappropriate FtsZ assembly at old division sites, rather than directly promoting FtsZ ring maturation. This is a conceptually different mechanism.
Missing localization specificity: BioReason assigns cytoplasm (GO:0005737); the curated review specifically notes cell pole (GO:0060187) and division septum (GO:0000935) as more appropriate localizations.
Missing sporulation role: The curated review describes DivIVA's role during sporulation (asymmetric polar septum localization, SpoIIE association, chromosome anchoring via Spo0J), which BioReason completely omits.
Erroneous GO predictions: The BioReason GO term predictions include flagellum-related terms (bacterial-type flagellum assembly, swarming motility) which are completely wrong for DivIVA.
Comparison with interpro2go:
The interpro2go annotations for divIVA map to protein binding and identical protein binding, plus flagellum-related BP terms. BioReason's GO predictions closely mirror these interpro2go mappings, including the erroneous flagellum terms. The flagellar annotations likely derive from the IPR007793 DivIVA family being associated with some flagellar terms in InterPro2GO through organisms where DivIVA homologs play flagellar roles. BioReason recapitulates these interpro2go errors without correction and adds no insight beyond interpro2go.
The trace correctly identifies the DivIVA domain architecture and infers an oligomeric scaffold function. However, the inference that DivIVA "captures and stabilizes FtsZ polymers" misrepresents its actual function as a negative spatial regulator of FtsZ via the Min system, rather than a direct FtsZ stabilizer. The assignment of cytokinesis (GO:0000910) as the primary BP, while broadly correct, obscures the more specific septum site selection role.
id: P71021
gene_symbol: divIVA
product_type: PROTEIN
status: DRAFT
taxon:
id: NCBITaxon:224308
label: Bacillus subtilis (strain 168)
description: DivIVA is a conserved membrane-associated scaffold protein in Gram-positive
bacteria that functions as a polar landmark by sensing negative membrane curvature
at cell poles and division septa. The protein forms oligomeric structures through
its N-terminal membrane-binding domain (which inserts hydrophobic and positively
charged residues into curved membranes) and C-terminal coiled-coil regions that
mediate tetramerization and higher-order assembly. During vegetative growth, DivIVA
localizes to both sides of the division septum and cell poles, where it recruits
MinJ, which in turn positions MinCD to prevent aberrant FtsZ assembly at previous
division sites, thereby ensuring proper septum site selection. During sporulation,
DivIVA accumulates asymmetrically at the polar septum with forespore bias, associates
with SpoIIE phosphatase to promote compartment-specific sigma-F activation, and
interacts with Spo0J for chromosome anchoring at the cell pole. DivIVA also recruits
ComN to cell poles, facilitating polar localization of comE mRNA during competence
development. Loss of DivIVA results in misplacement of division septa leading to
minicell formation, while overexpression is lethal.
existing_annotations:
- term:
id: GO:0009273
label: peptidoglycan-based cell wall biogenesis
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: DivIVA is primarily a scaffold protein involved in spatial organization
of cell division rather than directly participating in peptidoglycan biosynthesis.
While DivIVA localizes to sites of cell wall synthesis (septa and poles), its
role is to position other proteins (MinCD via MinJ) that regulate where division
occurs, not to directly contribute to peptidoglycan synthesis. In Corynebacterium
glutamicum, DivIVA is required for polar peptidoglycan synthesis, but B. subtilis
DivIVA localizes to septum rather than directing polar growth when expressed
in C. glutamicum (PMID:18296522). This IBA annotation likely reflects functional
conservation across Gram-positive bacteria where some DivIVA homologs do directly
regulate cell wall synthesis, but in B. subtilis the connection is more indirect.
action: MARK_AS_OVER_ANNOTATED
reason: DivIVA in B. subtilis functions as a spatial organizer for septum site
selection through the MinCD system, not as a direct participant in peptidoglycan
biosynthesis. The protein's role is to sense membrane curvature and recruit
MinJ/MinCD to prevent inappropriate FtsZ assembly. While this ultimately affects
where peptidoglycan synthesis occurs during division, DivIVA itself does not
catalyze or directly regulate peptidoglycan synthesis enzymes. This term is
too broad and misrepresents the mechanistic role of B. subtilis DivIVA.
supported_by:
- reference_id: PMID:18296522
supporting_text: DivIVA proteins from Bacillus subtilis or Streptococcus pneumoniae,
which localized at the septum of C. glutamicum
- term:
id: GO:0000917
label: division septum assembly
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: DivIVA plays a critical role in regulating where division septa form
by recruiting the MinJ/MinCD system to previous division sites and cell poles,
thereby preventing inappropriate FtsZ assembly. This represents a core function
of DivIVA in vegetative B. subtilis cells. Loss of DivIVA results in misplacement
of septa and minicell formation. However, the term "division septum assembly"
may be slightly broader than DivIVA's actual role, which is more specifically
in septum site selection rather than the assembly process itself.
action: MODIFY
reason: DivIVA does not directly assemble the division septum but rather controls
where septum assembly can occur by positioning the MinCD inhibitor system. The
more precise term would be GO:0000918 (division septum site selection), which
accurately captures DivIVA's role in marking sites where the septum can or cannot
form by recruiting MinJ and MinCD.
proposed_replacement_terms:
- id: GO:0000918
label: division septum site selection
supported_by:
- reference_id: file:BACSU/divIVA/divIVA-deep-research-falcon.md
supporting_text: DivIVA localizes to both sides of midcell septum and to poles
during vegetative growth and, together with MinJ, recruits MinCD to inhibit
reassembly of the divisome at old sites
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
summary: DivIVA is annotated to cytoplasm based on UniProt subcellular location
mapping. However, DivIVA is specifically a membrane-associated protein that
localizes to regions of negative membrane curvature at cell poles and division
septa. The protein's N-terminal domain binds directly to the membrane through
hydrophobic and positively charged residues. While technically in the cytoplasm,
this term is too general and fails to capture DivIVA's specific localization
to cell poles and division sites.
action: MODIFY
reason: 'The cytoplasm annotation is technically correct but too general. DivIVA
specifically localizes to negatively curved membrane regions at cell poles and
division septa. More specific CC terms would better capture DivIVA''s localization
pattern: GO:0060187 (cell pole) and GO:0000935 (division septum).'
proposed_replacement_terms:
- id: GO:0060187
label: cell pole
- id: GO:0000935
label: division septum
supported_by:
- reference_id: PMID:20502438
supporting_text: DivIVA is a conserved protein in Gram-positive bacteria that
localizes at the poles and division sites, presumably through direct sensing
of membrane curvature
- term:
id: GO:0030435
label: sporulation resulting in formation of a cellular spore
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: DivIVA plays an important role during B. subtilis sporulation, where
it accumulates asymmetrically at the polar septum with forespore bias and associates
with SpoIIE phosphatase to contribute to compartment-specific sigma-F activation.
DivIVA also interacts with Spo0J for chromosome anchoring at the cell pole during
sporulation. Mutation of DivIVA causes sporulation defects. However, DivIVA
is not a sporulation- specific protein - it functions during both vegetative
growth and sporulation.
action: KEEP_AS_NON_CORE
reason: While DivIVA plays an important role in sporulation by positioning SpoIIE
and anchoring chromosomes, sporulation is not its core function. DivIVA functions
primarily as a polar landmark protein that senses membrane curvature, and its
sporulation role is a specialized application of this general function. The
annotation should be retained but marked as non-core.
supported_by:
- reference_id: file:BACSU/divIVA/divIVA-deep-research-falcon.md
supporting_text: During sporulation, DivIVA accumulates at the polar septum
and becomes biased toward the forespore side as the septum matures. DivIVA
associates with the phosphatase SpoIIE, contributing to forespore-specific
activation of sigma-F and thus compartment-specific gene expression that initiates
the sporulation program
- term:
id: GO:0051301
label: cell division
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: DivIVA is essential for proper cell division in B. subtilis, where it
controls the spatial placement of division septa by recruiting MinJ/MinCD to
cell poles and previous division sites. Loss of DivIVA leads to aberrant septum
placement and minicell formation. This annotation accurately captures DivIVA's
involvement in cell division, though a more specific term like GO:0000918 (division
septum site selection) would better describe its precise role.
action: ACCEPT
reason: Cell division is a core function of DivIVA. The protein is essential for
proper spatial control of cell division through the Min system. While GO:0000918
would be more specific, GO:0051301 is an appropriate parent term that accurately
reflects DivIVA's biological role. This broad annotation should be retained
alongside more specific annotations.
supported_by:
- reference_id: PMID:20502438
supporting_text: DivIVA deletion causes filamentous growth in Bacillus subtilis
- reference_id: file:BACSU/divIVA/divIVA-deep-research-falcon.md
supporting_text: DivIVA localizes to both sides of midcell septum and to poles
during vegetative growth and, together with MinJ, recruits MinCD to inhibit
reassembly of the divisome at old sites
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:22582279
review:
summary: This annotation is based on the interaction between DivIVA and ComN demonstrated
by yeast two-hybrid and GST pulldown experiments in PMID:22582279. DivIVA directly
binds ComN and is required for its polar localization. However, GO:0005515 (protein
binding) is too generic and uninformative - a more specific term describing
the scaffold or adapter function would be preferable.
action: MODIFY
reason: While DivIVA does bind ComN, the generic term "protein binding" fails
to capture the biological significance of this interaction. DivIVA functions
as a scaffold protein that recruits multiple partners to cell poles. GO:0097110
(scaffold protein binding) would be more appropriate, or the annotation could
be modified to reflect DivIVA's role as a scaffold that recruits other proteins.
proposed_replacement_terms:
- id: GO:0097110
label: scaffold protein binding
supported_by:
- reference_id: PMID:22582279
supporting_text: Yeast two-hybrid and glutathione S-transferase pulldown experiments
showed that ComN interacts directly with DivIVA
- term:
id: GO:0042802
label: identical protein binding
evidence_type: IPI
original_reference_id: PMID:18296522
review:
summary: This annotation reflects DivIVA's ability to form homo-oligomers, a well-established
property essential for its scaffold function. The PMID:18296522 study in C.
glutamicum demonstrates DivIVA self-interaction, and this property is conserved
in B. subtilis DivIVA as shown by crystal structure studies.
action: ACCEPT
reason: Identical protein binding accurately describes DivIVA's homo-oligomerization,
which is essential for its function as a membrane curvature-sensing scaffold.
The protein forms tetramers and higher-order oligomers through its C-terminal
coiled-coil domain. This is a well-characterized molecular function of DivIVA.
supported_by:
- reference_id: PMID:18296522
supporting_text: DivIVA from Streptomyces or Mycobacterium localized to the
cell poles of DivIVA(Cg)-depleted C. glutamicum and restored polar peptidoglycan
synthesis
- reference_id: PMID:20502438
supporting_text: A low-resolution crystal structure of the C-terminal (Ct) domain
displays a curved tetramer made from two parallel coiled-coils
- term:
id: GO:0042802
label: identical protein binding
evidence_type: IPI
original_reference_id: PMID:18363795
review:
summary: This annotation reflects DivIVA self-interaction demonstrated in the
context of PBP1 shuttling studies. DivIVA homo-oligomerization is essential
for its scaffold function and is consistently demonstrated across multiple studies.
action: ACCEPT
reason: This is a duplicate annotation for identical protein binding with different
evidence. The homo-oligomerization of DivIVA is well-established and represents
a core molecular function. Multiple independent studies supporting this annotation
strengthens the evidence base.
supported_by:
- reference_id: PMID:20502438
supporting_text: A low-resolution crystal structure of the C-terminal (Ct) domain
displays a curved tetramer made from two parallel coiled-coils
- term:
id: GO:0042802
label: identical protein binding
evidence_type: IPI
original_reference_id: PMID:20502438
review:
summary: This annotation is strongly supported by the crystal structure of DivIVA
reported in PMID:20502438, which definitively demonstrates that DivIVA forms
homo-oligomers through its coiled-coil domains. The N-terminal domain forms
parallel coiled-coils and the C-terminal domain forms curved tetramers.
action: ACCEPT
reason: The crystal structure provides definitive evidence for DivIVA homo-oligomerization.
The protein forms dimers through its N-terminal domain and tetramers through
its C-terminal coiled-coil region. This is a core molecular function essential
for DivIVA's role as a membrane-associated scaffold.
supported_by:
- reference_id: PMID:20502438
supporting_text: We have determined the crystal structure of the N-terminal
(Nt) domain of DivIVA, and show that it forms a parallel coiled-coil
- term:
id: GO:0042802
label: identical protein binding
evidence_type: IPI
original_reference_id: PMID:21630458
review:
summary: This annotation comes from a large-scale protein-protein interaction
study in B. subtilis using yeast two-hybrid. DivIVA was identified as part of
a group of highly connected hub proteins. The self-interaction of DivIVA is
consistent with its known oligomeric nature.
action: ACCEPT
reason: While this annotation comes from a high-throughput study, it is consistent
with the well-established homo-oligomerization of DivIVA demonstrated by crystal
structure and other biochemical studies. Multiple lines of evidence support
DivIVA self-interaction as a core molecular function.
supported_by:
- reference_id: PMID:21630458
supporting_text: We have generated a protein-protein interaction network in
Bacillus subtilis focused on several essential cellular processes such as
cell division
- term:
id: GO:0140090
label: membrane curvature sensor activity
evidence_type: IDA
original_reference_id: PMID:20502438
review:
summary: DivIVA preferentially localizes to regions of negative membrane curvature
at cell poles and division septa. Crystal structure analysis reveals an N-terminal
domain with hydrophobic and positively charged residues that insert into curved
membranes. This curvature sensing is the fundamental mechanism underlying DivIVA's
localization and function as a polar landmark.
action: NEW
reason: Membrane curvature sensor activity is the core molecular function of DivIVA
that underlies all its biological roles. The crystal structure (PMID:20502438)
provides structural evidence for how DivIVA binds to curved membranes, and multiple
studies confirm its preferential localization to negatively curved membrane
regions at poles and septa. This annotation is not currently in the GOA annotations
but represents DivIVA's most fundamental molecular activity.
supported_by:
- reference_id: PMID:20502438
supporting_text: DivIVA is a conserved protein in Gram-positive bacteria that
localizes at the poles and division sites, presumably through direct sensing
of membrane curvature
- reference_id: file:BACSU/divIVA/divIVA-deep-research-falcon.md
supporting_text: DivIVA preferentially targets regions of high negative membrane
curvature, including poles and septal membranes
core_functions:
- molecular_function:
id: GO:0140090
label: membrane curvature sensor activity
description: DivIVA preferentially localizes to regions of negative membrane curvature
at cell poles and division septa. Crystal structure analysis reveals an N-terminal
domain with hydrophobic and positively charged residues that insert into curved
membranes. This curvature sensing is the fundamental mechanism underlying DivIVA's
localization and function as a polar landmark.
supported_by:
- reference_id: PMID:20502438
supporting_text: DivIVA is a conserved protein in Gram-positive bacteria that
localizes at the poles and division sites, presumably through direct sensing
of membrane curvature
- reference_id: file:BACSU/divIVA/divIVA-deep-research-falcon.md
supporting_text: DivIVA preferentially targets regions of high negative membrane
curvature, including poles and septal membranes
locations:
- id: GO:0060187
label: cell pole
- id: GO:0000935
label: division septum
directly_involved_in:
- id: GO:0000918
label: division septum site selection
- molecular_function:
id: GO:0042802
label: identical protein binding
description: DivIVA forms homo-oligomers essential for its scaffold function. Crystal
structures show the N-terminal domain forms parallel coiled-coils and the C-terminal
domain forms curved tetramers, enabling assembly into extended ~30 nm scaffolds.
supported_by:
- reference_id: PMID:20502438
supporting_text: A low-resolution crystal structure of the C-terminal (Ct) domain
displays a curved tetramer made from two parallel coiled-coils
references:
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
- id: GO_REF:0000043
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
findings: []
- id: GO_REF:0000044
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
vocabulary mapping, accompanied by conservative changes to GO terms applied by
UniProt
findings: []
- id: PMID:18296522
title: DivIVA is required for polar growth in the MreB-lacking rod-shaped actinomycete
Corynebacterium glutamicum.
findings:
- statement: DivIVA from B. subtilis localizes to the septum rather than poles when
expressed in C. glutamicum
supporting_text: DivIVA proteins from Bacillus subtilis or Streptococcus pneumoniae,
which localized at the septum of C. glutamicum
- statement: DivIVA proteins show functional divergence between actinomycetes and
firmicutes
supporting_text: This confirmed that DivIVAs from actinomycetes are involved in
polarized cell growth
- id: PMID:18363795
title: Control of the cell elongation-division cycle by shuttling of PBP1 protein
in Bacillus subtilis.
findings: []
- id: PMID:20502438
title: Features critical for membrane binding revealed by DivIVA crystal structure.
findings:
- statement: N-terminal domain forms parallel coiled-coil with membrane-binding
loop
supporting_text: We have determined the crystal structure of the N-terminal (Nt)
domain of DivIVA, and show that it forms a parallel coiled-coil
- statement: Hydrophobic and positively charged residues essential for membrane
binding
supporting_text: exposing hydrophobic and positively charged residues that we
show here are essential for membrane binding
- statement: C-terminal domain forms curved tetramer from two parallel coiled-coils
supporting_text: A low-resolution crystal structure of the C-terminal (Ct) domain
displays a curved tetramer made from two parallel coiled-coils
- statement: Full-length DivIVA protein is approximately 30 nm long
supporting_text: The Nt and Ct parts were then merged into a model of the full
length, 30 nm long DivIVA protein
- statement: DivIVA deletion causes filamentous growth in B. subtilis
supporting_text: DivIVA deletion causes filamentous growth in Bacillus subtilis
- id: PMID:21630458
title: 'An expanded protein-protein interaction network in Bacillus subtilis reveals
a group of hubs: Exploration by an integrative approach.'
findings:
- statement: DivIVA identified as part of highly connected protein hub group
supporting_text: A striking feature of the network is a group of highly connected
hubs (GoH) linking many different cellular processes
- statement: Self-interaction detected by yeast two-hybrid
supporting_text: We have generated a protein-protein interaction network in Bacillus
subtilis focused on several essential cellular processes such as cell division
- id: PMID:22582279
title: DivIVA-mediated polar localization of ComN, a posttranscriptional regulator
of Bacillus subtilis.
findings:
- statement: ComN directly interacts with DivIVA via yeast two-hybrid and GST pulldown
supporting_text: Yeast two-hybrid and glutathione S-transferase pulldown experiments
showed that ComN interacts directly with DivIVA
- statement: ComN localization to poles and division sites is DivIVA-dependent
supporting_text: ComN localizes to the division site and cell poles in a DivIVA-dependent
fashion
- statement: DivIVA functions as versatile promoter of bacterial pole differentiation
supporting_text: Our results underscore the versatility of DivIVA as a promoter
of the differentiation of bacterial poles
- id: file:BACSU/divIVA/divIVA-deep-research-falcon.md
title: Deep research synthesis on DivIVA function
findings:
- statement: DivIVA recruits MinJ which positions MinCD at previous division sites
- statement: During sporulation DivIVA shows forespore-biased localization
- statement: DivIVA associates with SpoIIE for compartment-specific sigma-F activation
- statement: DivIVA targets negatively curved membrane regions at poles and septa
tags:
- bacsu