Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt.

PMID:23036704

A novel big protein TPRBK possessing 25 units of TPR motif is essential for the progress of mitosis and cytokinesis.

PMID:39630868

The essential role of TTC28 in maintaining chromosomal stability via HSPA8 chaperone-mediated autophagy.

The tetratricopeptide repeat domains of TTC28 bind the C-terminal PTIEEVD motif of HSPA8, targeting TTC28 for degradation via CMA/microautophagy; TTC28 is thus an HSPA8-mediated CMA substrate.

"The tetratricopeptide repeat domains of TTC28 bind to the C-terminal motif (PTIEEVD) in HSPA8, resulting in the subsequent degradation of TTC28 via CMA/microautophagy."
Loss of TTC28 increases micronuclei frequency ~3-fold, and TTC28 overexpression rescues this, demonstrating TTC28 is required for chromosomal stability.

"the baseline frequency of micronuclei (FMN) in human cancer cells with TTC28 knockout cells was three times greater than that in cells with wild-type TTC28 (7.7% vs. 2.3%, P = 4.86E-09)."
Mechanistically, TTC28 maintains genome integrity by regulating mitosis and cytokinesis, downstream of CMA.

"Mechanistically, TTC28 regulates mitosis and cytokinesis, which are involved in the maintenance of genome integrity by CMA."
TTC28 is a conserved vertebrate gene that is frequently mutated and down-regulated in human cancers, where comprehensive loss may drive chromosomal instability.

"TTC28, a conserved gene in vertebrates, is frequently mutated and down-regulated in numerous human cancers."

file:human/TTC28/TTC28-deep-research-falcon.md

Falcon (Edison Scientific Literature) deep research report on human TTC28 (Q96AY4) function and disease relevance.

TTC28 is a very large (~271 kDa) TPR-containing scaffold protein with ~28 TPR domains and multiple KFERQ-like motifs consistent with recognition by chaperone-mediated autophagy.

"TTC28 as containing **28 TPR domains** and multiple KFERQ-like motifs consistent with recognition by **chaperone-mediated autophagy (CMA)**"
TTC28 is mainly cytoplasmic with perinuclear enrichment, consistent with a TPR scaffold acting where chaperone pathways intersect mitotic machinery.

"Mainly cytoplasmic**, with **perinuclear enrichment**"
The strongest functional phenotype of TTC28 is chromosomal/genome stability, assayed by micronuclei frequency and DNA damage markers.

"The strongest functional phenotype linked to TTC28 is **chromosomal/genome stability** as assayed by micronuclei frequency and DNA damage markers."
TTC28 is best interpreted as a TPR scaffold/adaptor (not an enzyme) coupling chaperone/autophagy machinery to mitotic and cytokinetic fidelity.

"a large TPR scaffold/adaptor that couples chaperone/autophagy machinery to the fidelity of mitotic and cytokinetic processes, likely through protein interaction networks rather than enzymatic catalysis"
TTC28 is not established as an enzyme with defined substrate specificity; the evidence is interaction/scaffold/quality-control centric.

"TTC28 is **not** established here as an enzyme with defined substrate specificity; the evidence is interaction/scaffold/quality-control centric."