betaTub97EF encodes one of the five beta-tubulins of Drosophila melanogaster, a lineage-specific beta-tubulin isotype conserved across arthropods. It assembles with alpha-tubulin into cytoplasmic microtubules, binds the exchangeable GTP of the heterodimer, and gives the polymer unusually high resistance to depolymerization; the stabilizing property maps mainly to its tubulin core rather than its C-terminal tail. Expression is tissue-restricted, highest in gut epithelia (notably embryonic hindgut boundary cells) and also in hemocytes, wing discs and follicle cells, and is selectively increased at low temperature. Mutually exclusive internal exons (4B, the major cold-induced form, and 4C, a minor form) generate two isoforms that differ at 13 positions between residues 177 and 223. Null mutants are viable and fertile but show mildly reduced embryonic survival in the cold, consistent with a role in cold acclimation through microtubule stabilization.
Summary: Q8MST5 is a full-length beta-tubulin (457 aa, intact tubulin GTPase and C-terminal domains) in the beta-tubulin clade under the tubulin-root PAINT node PTN000172598; within PANTHER it is the sole fly member of subfamily SF490 and its own tree node, sister to the clade holding betaTub56D, betaTub60D and betaTub65B. The IBA is consistent with gene-specific data: betaTub97EF incorporates into cytoplasmic microtubules, and changing its proportion in hemocytes or removing it in the gut alters microtubule stability. Organizing the microtubule cytoskeleton by being polymerized into it is direct participation.
Reason: Q8MST5 is a full-length beta-tubulin (457 aa, intact tubulin GTPase and C-terminal domains) in the beta-tubulin clade under the tubulin-root PAINT node PTN000172598; within PANTHER it is the sole fly member of subfamily SF490 and its own tree node, sister to the clade holding betaTub56D, betaTub60D and betaTub65B. The IBA is consistent with gene-specific data: betaTub97EF incorporates into cytoplasmic microtubules, and changing its proportion in hemocytes or removing it in the gut alters microtubule stability. Organizing the microtubule cytoskeleton by being polymerized into it is direct participation.
Summary: Root-level PAINT inference for tubulins. Paralog-specific immunolabeling places betaTub97EF in mitotic spindles of wing imaginal discs, so it is a constituent of spindle microtubules, but it is a minor beta-tubulin there and null mutants are viable and fertile, so mitosis depends on coexpressed beta-tubulins. Retained as non-core.
Reason: Root-level PAINT inference for tubulins. Paralog-specific immunolabeling places betaTub97EF in mitotic spindles of wing imaginal discs, so it is a constituent of spindle microtubules, but it is a minor beta-tubulin there and null mutants are viable and fertile, so mitosis depends on coexpressed beta-tubulins. Retained as non-core.
Although βTub97EF mutants were viable and fertile at 25°C, their sensitivity within the well-tolerated range was slightly enhanced during embryogenesis specifically at low temperatures.
Summary: The exchangeable GTP of the alpha/beta heterodimer is bound by beta-tubulin (E site) and is hydrolysed after incorporation into the lattice; the catalytic residue is contributed by the alpha-tubulin of the next dimer, so the active site is composite. Q8MST5 has an intact tubulin/FtsZ GTPase domain in the beta-tubulin clade, so it supplies the nucleotide-binding half of the hydrolytic site. Accepted as a conserved family property, noting that no betaTub97EF-specific GTPase rate has been measured and that the activity is realized only in the polymer.
Reason: The exchangeable GTP of the alpha/beta heterodimer is bound by beta-tubulin (E site) and is hydrolysed after incorporation into the lattice; the catalytic residue is contributed by the alpha-tubulin of the next dimer, so the active site is composite. Q8MST5 has an intact tubulin/FtsZ GTPase domain in the beta-tubulin clade, so it supplies the nucleotide-binding half of the hydrolytic site. Accepted as a conserved family property, noting that no betaTub97EF-specific GTPase rate has been measured and that the activity is realized only in the polymer.
Each tubulin monomer binds a guanine nucleotide, which is nonexchangeable when it is bound in the alpha subunit, or N site, and exchangeable when bound in the beta subunit, or E site.
The exchangeable nucleotide in beta-tubulin is exposed at the plus end of the microtubule, while the proposed catalytic residue in alpha-tubulin is exposed at the minus end.
Summary: Q8MST5 is a full-length beta-tubulin (457 aa, intact tubulin GTPase and C-terminal domains) in the beta-tubulin clade under the tubulin-root PAINT node PTN000172598; within PANTHER it is the sole fly member of subfamily SF490 and its own tree node, sister to the clade holding betaTub56D, betaTub60D and betaTub65B. Structural constituent of cytoskeleton is the core activity of a lattice-forming beta-tubulin, and gene-specific experiments show betaTub97EF is incorporated into microtubules and sets their stability.
Reason: Q8MST5 is a full-length beta-tubulin (457 aa, intact tubulin GTPase and C-terminal domains) in the beta-tubulin clade under the tubulin-root PAINT node PTN000172598; within PANTHER it is the sole fly member of subfamily SF490 and its own tree node, sister to the clade holding betaTub56D, betaTub60D and betaTub65B. Structural constituent of cytoskeleton is the core activity of a lattice-forming beta-tubulin, and gene-specific experiments show betaTub97EF is incorporated into microtubules and sets their stability.
Summary: Q8MST5 is a full-length beta-tubulin (457 aa, intact tubulin GTPase and C-terminal domains) in the beta-tubulin clade under the tubulin-root PAINT node PTN000172598; within PANTHER it is the sole fly member of subfamily SF490 and its own tree node, sister to the clade holding betaTub56D, betaTub60D and betaTub65B. Structural constituent of cytoskeleton is the core activity of a lattice-forming beta-tubulin, and gene-specific experiments show betaTub97EF is incorporated into microtubules and sets their stability.
Reason: Q8MST5 is a full-length beta-tubulin (457 aa, intact tubulin GTPase and C-terminal domains) in the beta-tubulin clade under the tubulin-root PAINT node PTN000172598; within PANTHER it is the sole fly member of subfamily SF490 and its own tree node, sister to the clade holding betaTub56D, betaTub60D and betaTub65B. Structural constituent of cytoskeleton is the core activity of a lattice-forming beta-tubulin, and gene-specific experiments show betaTub97EF is incorporated into microtubules and sets their stability.
Summary: Beta-tubulin carries the exchangeable guanine-nucleotide (E) site of the alpha/beta dimer; Q8MST5 retains the full tubulin GTPase domain within the beta-tubulin clade (tubulin-root PAINT node PTN000172598), supporting GTP binding.
Reason: Beta-tubulin carries the exchangeable guanine-nucleotide (E) site of the alpha/beta dimer; Q8MST5 retains the full tubulin GTPase domain within the beta-tubulin clade (tubulin-root PAINT node PTN000172598), supporting GTP binding.
Each tubulin monomer binds a guanine nucleotide, which is nonexchangeable when it is bound in the alpha subunit, or N site, and exchangeable when bound in the beta subunit, or E site.
Summary: Beta-tubulin carries the exchangeable guanine-nucleotide (E) site of the alpha/beta dimer; Q8MST5 retains the full tubulin GTPase domain within the beta-tubulin clade (tubulin-root PAINT node PTN000172598), supporting GTP binding.
Reason: Beta-tubulin carries the exchangeable guanine-nucleotide (E) site of the alpha/beta dimer; Q8MST5 retains the full tubulin GTPase domain within the beta-tubulin clade (tubulin-root PAINT node PTN000172598), supporting GTP binding.
Each tubulin monomer binds a guanine nucleotide, which is nonexchangeable when it is bound in the alpha subunit, or N site, and exchangeable when bound in the beta subunit, or E site.
Summary: betaTub97EF acts in the cytoplasm: polymerized in cytoplasmic microtubules and, like all tubulins, present as a soluble heterodimer pool. The polymer location is captured more precisely by microtubule (GO:0005874), which this gene already carries; cytoplasm is retained as the correct location of the unpolymerized pool, which is as precise as the evidence allows, and is non-core.
Reason: betaTub97EF acts in the cytoplasm: polymerized in cytoplasmic microtubules and, like all tubulins, present as a soluble heterodimer pool. The polymer location is captured more precisely by microtubule (GO:0005874), which this gene already carries; cytoplasm is retained as the correct location of the unpolymerized pool, which is as precise as the evidence allows, and is non-core.
Summary: Correct but general. betaTub97EF is a microtubule subunit, so the specific cytoskeletal location is microtubule (GO:0005874), already carried by this gene via IBA and InterPro.
Reason: Correct but general. betaTub97EF is a microtubule subunit, so the specific cytoskeletal location is microtubule (GO:0005874), already carried by this gene via IBA and InterPro.
Summary: betaTub97EF is incorporated into microtubules, which it stabilizes in hemocytes and gut; microtubule is the core location of a lattice-forming beta-tubulin.
Reason: betaTub97EF is incorporated into microtubules, which it stabilizes in hemocytes and gut; microtubule is the core location of a lattice-forming beta-tubulin.
Summary: betaTub97EF is incorporated into microtubules, which it stabilizes in hemocytes and gut; microtubule is the core location of a lattice-forming beta-tubulin.
Reason: betaTub97EF is incorporated into microtubules, which it stabilizes in hemocytes and gut; microtubule is the core location of a lattice-forming beta-tubulin.
Summary: Correct but general. The specific microtubule-based process supported for betaTub97EF is microtubule cytoskeleton organization (GO:0000226), already carried via IBA, through its incorporation into and stabilization of the lattice.
Reason: Correct but general. The specific microtubule-based process supported for betaTub97EF is microtubule cytoskeleton organization (GO:0000226), already carried via IBA, through its incorporation into and stabilization of the lattice.
Summary: ARBA machine-learning prediction of a developmental process, not supported for this gene. The only gene-specific loss-of-function data show that null mutants are viable and fertile at 25 C, with slightly reduced embryonic survival at low temperature, mildly reduced fertility and normal hindgut left-right asymmetry; no morphogenetic or organ-development defect is reported. Any role would be an indirect consequence of microtubule stability, which is captured by the microtubule terms.
Reason: ARBA machine-learning prediction of a developmental process, not supported for this gene. The only gene-specific loss-of-function data show that null mutants are viable and fertile at 25 C, with slightly reduced embryonic survival at low temperature, mildly reduced fertility and normal hindgut left-right asymmetry; no morphogenetic or organ-development defect is reported. Any role would be an indirect consequence of microtubule stability, which is captured by the microtubule terms.
Although βTub97EF mutants were viable and fertile at 25°C, their sensitivity within the well-tolerated range was slightly enhanced during embryogenesis specifically at low temperatures.
Summary: ARBA machine-learning prediction of a developmental process, not supported for this gene. The only gene-specific loss-of-function data show that null mutants are viable and fertile at 25 C, with slightly reduced embryonic survival at low temperature, mildly reduced fertility and normal hindgut left-right asymmetry; no morphogenetic or organ-development defect is reported. Any role would be an indirect consequence of microtubule stability, which is captured by the microtubule terms.
Reason: ARBA machine-learning prediction of a developmental process, not supported for this gene. The only gene-specific loss-of-function data show that null mutants are viable and fertile at 25 C, with slightly reduced embryonic survival at low temperature, mildly reduced fertility and normal hindgut left-right asymmetry; no morphogenetic or organ-development defect is reported. Any role would be an indirect consequence of microtubule stability, which is captured by the microtubule terms.
Although βTub97EF mutants were viable and fertile at 25°C, their sensitivity within the well-tolerated range was slightly enhanced during embryogenesis specifically at low temperatures.
25% fewer mutants completed embryogenesis at 14°C; normal hindgut left/right asymmetry in n=100
GO:0160108 animal gross anatomical part developmental process
IEA GO_REF:0000117
REMOVE
Summary: ARBA machine-learning prediction of a developmental process, not supported for this gene. The only gene-specific loss-of-function data show that null mutants are viable and fertile at 25 C, with slightly reduced embryonic survival at low temperature, mildly reduced fertility and normal hindgut left-right asymmetry; no morphogenetic or organ-development defect is reported. Any role would be an indirect consequence of microtubule stability, which is captured by the microtubule terms.
Reason: ARBA machine-learning prediction of a developmental process, not supported for this gene. The only gene-specific loss-of-function data show that null mutants are viable and fertile at 25 C, with slightly reduced embryonic survival at low temperature, mildly reduced fertility and normal hindgut left-right asymmetry; no morphogenetic or organ-development defect is reported. Any role would be an indirect consequence of microtubule stability, which is captured by the microtubule terms.
Although βTub97EF mutants were viable and fertile at 25°C, their sensitivity within the well-tolerated range was slightly enhanced during embryogenesis specifically at low temperatures.
25% fewer mutants completed embryogenesis at 14°C; normal hindgut left/right asymmetry in n=100
Core Functions
Lattice-forming beta-tubulin subunit of cytoplasmic microtubules that confers increased microtubule stability, notably in gut epithelia and hemocytes, and is upregulated at low temperature.
βTub97EF is required for normal microtubule stability in the gut.
Binds the exchangeable GTP of the alpha/beta-tubulin heterodimer (E site), whose hydrolysis in the lattice, completed by the alpha subunit of the adjacent dimer, drives microtubule dynamics.
Each tubulin monomer binds a guanine nucleotide, which is nonexchangeable when it is bound in the alpha subunit, or N site, and exchangeable when bound in the beta subunit, or E site.
The exchangeable nucleotide in beta-tubulin is exposed at the plus end of the microtubule, while the proposed catalytic residue in alpha-tubulin is exposed at the minus end.
Q: Does betaTub97EF upregulation contribute causally to cellular cold acclimation (e.g. GO:0070417 cellular response to cold), or is the cold-induced expression a regulatory feature of the locus with the protein simply stabilizing whatever microtubules it joins?
Q: Which UniProt accession (Q8MST5/E1JIZ8 versus Q9VAX7) corresponds to the exon-4B versus exon-4C splice form described by Myachina et al. 2017?
Suggested Experiments
Experiment: Purify recombinant betaTub97EF-4B and -4C heterodimers (or betaTub56D/97EF chimeras) and measure dynamic instability parameters (catastrophe and rescue frequencies, GTP hydrolysis rate) in vitro across 14-30 C to identify the core residues responsible for stabilization.
External Prediction Reviews
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
A broad microtubule role is supported for both internal splice variants; microtubule-based process is less precise than the supported organization annotation.
Review rationale: A microtubule-based process is supported by the intact beta-tubulin architecture and primary experiments on both internal splice variants. Both forms partially rescue loss of the major betaTub56D paralog; the detailed stabilization and cold-induction results specifically concern the major exon-4B form. Exact correspondence of Q8MST5 to the paper’s exon names remains unresolved, but this does not undermine the broad structural microtubule role. Existing microtubule-cytoskeleton organization is a more precise supported process, so the prediction is LSP.
Supporting Evidence:
PMID:29084803: "Changing β-tubulin isoform ratios in hemocytes demonstrated that β-Tubulin 97EF has a pronounced microtubule stabilizing effect."
PMID:29084803: "βTub97EF is required for normal microtubule stability in the gut."
FlyBase gene description for betaTub97EF (DROME)FlyBase
FlyBase gene description for betaTub97EF (DROME)
&bgr;-Tubulin at 97EF (&bgr;Tub97EF) is one of five distinct paralogs that codes for a &bgr;-tubulin protein. &bgr;-tubulin protein can polymerize into microtubules after heterodimerization with an &agr;-tubulin protein. &bgr;Tub97EF expression is tissue-specific and up-regulated at low temperature. Microtubules containing this beta-tubulin are relatively stable.