TBCC (human, Q15814) review notes

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file exists. The notes below come from manual literature research (cached publications,
PubMed E-utilities searches, WebSearch) and the UniProt record.

Identity and domains

• Tubulin-specific chaperone C / tubulin folding cofactor C, 346 aa; UniProt Q15814.
• N-terminal spectrin-like three-helix bundle (TBCC_N, PF16752; NMR structure PDB 2L3L)
  and C-terminal C-CAP/cofactor C-like right-handed beta-helix domain (PF07986, PS51329,
  residues 171-323; PDB 2YUH). The C-terminal domain is shared with RP2 and TBCCD1.
• UniProt MUTAGEN: R262A "R->A: Inhibits stimulation of tubulin GTPase" activity
  (ECO:0000269, PMID:11847227).
• No P-loop, G-box or tubulin/FtsZ GTPase domain: TBCC cannot itself be a GTPase.

Function

• Final step of the post-chaperonin tubulin folding/heterodimer assembly pathway.
  PMID:8706133
• Cofactors act as GAPs for beta-tubulin: PMID:10446175; GTP hydrolysis by beta-tubulin in the supercomplex is the switch that releases
  the native heterodimer PMID:10446175.
• PMID:10831612; ARL2 downregulates this GAP activity.
• PMID:11847227; the conserved arginine (R262 in TBCC) is an arginine finger
  [PMID:11847227 "this residue acts as an \"arginine finger\" to trigger the tubulin GTPase
  activity"]. Human TBCC partially complements yeast cofactor C deletion.
• Alternative/additional GAP target: ARL2. In reconstituted yeast proteins, TBCC binds the
  TBCD-TBCE-ARL2 cage with alpha/beta-tubulin and activates ARL2 GTP hydrolysis
  [PMID:26208336 "forming a ternary complex in which Arl2 GTP hydrolysis is activated to
  alter αβ-tubulin conformation"; "further supporting the idea that TBCC is a true GAP"].
  Fission yeast Tbc1 also acts as an Arl2 GAP PMID:23576550. Either way, the GTP is
  hydrolysed by the GTPase (beta-tubulin or ARL2), and TBCC is the activator.

Conclusion on GO:0003924 GTPase activity (IDA, PMID:11847227, assigned by UniProt)

Flagged by FRR:0010. The cited paper shows TBCC stimulates tubulin GTPase activity; it
does not show that TBCC hydrolyses GTP. GO:0003924 is "Catalysis of the reaction: GTP + H2O
= GDP + H+ + phosphate"; GO:0005096 GTPase activator activity is "Binds to and increases the
activity of a GTPase". MGI already annotates GO:0005096 from the same paper. Action: MODIFY
to GO:0005096, with a WRONG_TERM source_defect against UniProt.

Localization

• Cytoplasm/cytosol; centrosome in HeLa cells PMID:22028797. TBCC depletion causes
  multipolar spindles and mitotic failure PMID:22028797.
• Retina: [PMID:12417528 "cofactor C and Arl3 localized predominantly to the photoreceptor
  connecting cilium in rod and cone photoreceptors"; "Cofactor C was cytoplasmic in
  distribution"].
• No evidence for TBCC as a microtubule (polymer) component; it acts on soluble tubulin.

Cellular phenotypes

• TBCC overexpression in breast cancer cells shifts tubulin to nonpolymerizable pools and
  dampens MT dynamics PMID:20384997; silencing does the reverse PMID:21216936.

Protein-binding rows

PMID:32814053 is a large Y2H neurodegeneration interactome (GSN, FGFR3, CHAT isoform);
uninformative, removed per protein-binding policy.