Alternative titles; symbols
HGNC Approved Gene Symbol: KLHL21
Cytogenetic location: 1p36.31 Genomic coordinates (GRCh38): 1:6,590,724-6,602,869 (from NCBI)
During mitosis, KLHL21 functions as an adaptor for CUL3 (603136) E3 ubiquitin ligase and regulates translocation of the chromosomal passenger complex (CPC), which includes the mitotic kinase Aurora B (AURKB; 604970), from chromosomes to the spindle midzone in anaphase. KLHL21 is also required for completion of cytokinesis (Maerki et al., 2009).
By sequencing clones isolated from a size-fractionated human brain cDNA library, Ishikawa et al. (1997) obtained a KLHL21 clone, which they designated KIAA0469. The deduced 539-amino acid protein shares significant similarity with the Drosophila ring canal protein kelch. RT-PCR analysis showed KLHL21 expression in all 14 human tissues examined. SDS-PAGE detected in vitro-translated KLHL21 at an apparent molecular mass of 64 kD.
Using Western blot analysis, Maerki et al. (2009) detected endogenous HeLa cell KLHL21 at an apparent molecular mass of 66 kD.
The BTB proteins KLHL9 (611201) and KLHL13 (300655) form a complex with CUL3 that is required for ubiquitination of Aurora B. Using mass spectrometric analysis, Maerki et al. (2009) found that KLHL21 and KLHL22 (618020) immunoprecipitated with CUL3, KLHL9, and KLHL13 from HeLa cell lysates. KLHL21 also interacted with Aurora B. Deletion analysis revealed that the BTB domain of KLHL21 was required for interaction with CUL3, whereas the kelch domain of KLHL21 was required for interaction with Aurora B. Time-lapse microscopy revealed that knockdown of KLHL21 or KLHL22 via small interfering RNA delayed prometaphase and led to failure of proper metaphase plate formation. Knockdown of KLHL21, but not KLHL22, also caused multinucleation and failure of cytokinesis in a large number of cells. During anaphase, loss of KLHL21 inhibited translocation of Aurora B from segregating chromosomes to the spindle midzone and caused loss of CUL3 localization at the midzone. Likewise, knockdown of CUL3 caused loss of KLHL21 from the midzone. Sucrose gradient and gel filtration experiments revealed that KLHL21 and KLHL9 fractionated into overlapping but distinct CUL3 complexes, suggesting that KLHL21, KLHL9, and KLHL13 assemble distinct CUL3 complexes to regulate CPC localization during mitosis. CUL3-KLHL21 complexes also ubiquitinated Aurora B in vitro. Maerki et al. (2009) concluded that different CUL3 complexes with KLHL9, KLHL13, and KLHL21 may target different pools of Aurora B for mitotic progression.
By radiation hybrid analysis, Ishikawa et al. (1997) mapped the KLHL21 gene to chromosome 1.
Hartz (2015) mapped the KLHL21 gene to chromosome 1p36.31 based on an alignment of the KLHL21 sequence (GenBank AB007938) with the genomic sequence (GRCh38).
Hartz, P. A. Personal Communication. Baltimore, Md. 3/10/2015.
Ishikawa, K., Nagase, T., Nakajima, D., Seki, N., Ohira, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 4: 307-313, 1997. [PubMed: 9455477] [Full Text: https://doi.org/10.1093/dnares/4.5.307]
Maerki, S., Olma, M. H., Staubli, T., Steigemann, P., Gerlich, D. W., Quadroni, M., Sumara, I., Peter, M. The Cul3-KLHL21 E3 ubiquitin ligase targets Aurora B to midzone microtubules in anaphase and is required for cytokinesis. J. Cell Biol. 187: 791-800, 2009. [PubMed: 19995937] [Full Text: https://doi.org/10.1083/jcb.200906117]