HGNC Approved Gene Symbol: AKNA
Cytogenetic location: 9q32 Genomic coordinates (GRCh38) : 9:114,330,504-114,398,472 (from NCBI)
The AT hook is a small motif with a typical 9-amino acid signature sequence, in which a glycine-arginine-proline (GRP) tripeptide is the center of the DNA-binding domain. AT-hook proteins such as AKNA bind A/T-rich DNA and are thought to modify DNA architecture, thus enhancing the accessibility of promoters to transcription factors (summary by Siddiqa et al., 2001).
By RT-PCR differential display with RNA from human B-lymphocyte subsets, Siddiqa et al. (2001) isolated a cDNA encoding AKNA. Sequence analysis predicted that the 633-amino acid protein contains an AT-hook motif (RTRGRPADS) and 3 PEST regions. Northern blot analysis detected a 4.0-kb transcript predominantly in lymphoid tissue, with highest expression in spleen, lymph nodes, and peripheral blood leukocytes, lower expression in thymus, and undetectable expression in fetal liver and adult bone marrow. In addition, AKNA was expressed by B and T lymphocytes, natural killer cells, and CD1A (188370)-positive/CD14 (158120)-negative dendritic cells. Immunofluorescence microscopy demonstrated a nuclear localization in a B lymphoma transfected with AKNA-GFP. Immunohistochemical analysis showed expression of AKNA predominantly in germinal centers of secondary lymphoid organs.
Using cDNA expression array, Northern blot, RT-PCR, flow cytometry, and Western blot analyses, Siddiqa et al. (2001) observed AKNA-mediated upregulation of CD40 (109535) expression and downregulation of GSTP1 (134660) expression. Electrophoretic mobility shift analysis showed AKNA binding to A/T-rich regulatory elements of CD40 and CD40 ligand (CD40LG; 300386), supporting a role for AKNA as a transcription factor that coordinately regulates a key receptor-ligand pair during secondary immune responses.
Camargo Ortega et al. (2019) demonstrated that the interphase centrosome protein AKNA has a key role in regulating the length of time that cells stay in the subventricular zone. AKNA localizes at the subdistal appendages of the mother centriole in specific subtypes of neural stem cells, and in almost all basal progenitors. This protein is necessary and sufficient to organize centrosomal microtubules, and promote their nucleation and growth. These features of AKNA are important for mediating the delamination process in the formation of the subventricular zone. Moreover, AKNA regulates the exit from the subventricular zone, which reveals the pivotal role of centrosomal microtubule organization in enabling cells to both enter and remain in the subventricular zone. The epithelial-to-mesenchymal transition is also regulated by AKNA in other epithelial cells, demonstrating its general importance for the control of cell delamination.
Camargo Ortega, G., Falk, S., Johansson, P. A., Peyre, E., Broix, L., Sahu, S. K., Hirst, W., Schlichthaerle, T., De Juan Romero, C., Draganova, K., Vinopal, S., Chinnappa, K., and 18 others. The centrosome protein AKNA regulates neurogenesis via microtubule organization. Nature 567: 113-117, 2019. [PubMed: 30787442] [Full Text: https://doi.org/10.1038/s41586-019-0962-4]
Siddiqa, A., Sims-Mourtada, J. C., Guzman-Rojas, L., Rangel, R., Guret, C., Madrid-Marina, V., Sun, Y., Martinez-Valdez, H. Regulation of CD40 and CD40 ligand by the AT-hook transcription factor AKNA. Nature 410: 383-387, 2001. [PubMed: 11268217] [Full Text: https://doi.org/10.1038/35066602]