During mitosis, may be involved in the condensation of spindle midzone microtubules, leading to the formation of midbody. (updated: Sept. 12, 2018)
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
No sequence conservation computed yet.
Total structural coverage: 0%
No model available.
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The reference OMIM entry for this protein is 615098
Tetratricopeptide repeat domain-containing protein 28; ttc28
Tprbk
Kiaa1043
DESCRIPTION
TTC28 is a large protein required during the cell cycle for condensation of spindle midzone microtubules, formation of the midbody, and completion of cytokinesis (Izumiyama et al., 2012).
CLONING
By sequencing clones amplified from a size-fractionated fetal brain cDNA library, Kikuno et al. (1999) obtained a partial TTC28 clone, which they designated KIAA1043. RT-PCR ELISA detected highest TTC28 expression in adult ovary and lung, followed by kidney and liver. Lower expression was detected in all other adult and fetal tissues examined except testis, which showed no expression. By PCR and 5-prime RACE of a human fetal brain cDNA library, Izumiyama et al. (2012) cloned full-length TTC28, which they called 'tetratricopeptide repeat-containing big gene cloned at Keio University,' or TPRBK. The N-terminal half of the deduced 2,481-amino acid protein contains 25 tetratricopeptide repeats (TPRs) of about 34 residues each. The 25 TPRs in TPRBK are significantly different from one another. Orthologs of TPRBK are present in most animal species, but not in nematode, fungi, plants, and lower organisms. Mouse and human TPRBK share 92% amino acid identity. Northern blot analysis detected transcripts of 11, 9, and 7 kb in most fetal human tissues examined and in adult testis and ovary, with lower expression in adult kidney and pancreas. In mouse, a major 11-kb transcript and a minor 9-kb transcript were detected in embryos at all stages examined and in adult heart, with lower expression in adult kidney and testis. Western blot analysis detected an endogenous TPRBK protein with an apparent molecular mass of 270 kD in human, monkey, and mouse cell lines. Immunofluorescence analysis of synchronized COS-7 cells revealed Tprbk localization at centrosomes during interphase, along spindle microtubules and spindle poles during prometaphase, in the midzone at anaphase, and at the central spindles at telophase.
GENE FUNCTION
Using immunoprecipitation analysis and chemical cross-linking experiments, Izumiyama et al. (2012) found that TPRBK interacted with Aurora B (AURKB;
604970), a serine/threonine protein kinase that facilitates proper chromosome segregation. In COS-7 cells, the 2 proteins colocalized during anaphase and translocated together toward the midbody. Pharmacologic inhibition of cytokinesis resulted in localization of TPRBK and Aurora B at the postmitotic spindle between the 2 nuclei. Small interfering RNA-mediated knockdown of TPRBK arrested HeLa cell proliferation at G2+M phase and caused failure of cytokinesis, leaving cells at a 2-nucleated state. Izumiyama et al. (2012) concluded that TPRBK is necessary for condensation of spindle midzone microtubules, formation of the midbody, and completion of cytokinesis.
GENE STRUCTURE
Izumiyama et al. (2012) determined that the TTC28 gene contains 23 exons and spans 702 kb.
MAPPING
By radiation hybrid analysis, Kikuno et al. (1999) mapped the TTC28 gene to chromosome 22. Izumiyama et al. (2012) mapped the TTC28 gene to chromosome 22q12.1 by genomic sequence analysis. ...
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Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 615098 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).