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 |
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