Alternative titles; symbols
HGNC Approved Gene Symbol: ANKRD28
Cytogenetic location: 3p25.1 Genomic coordinates (GRCh38) : 3:15,667,236-15,859,814 (from NCBI)
By sequencing clones obtained from a size-fractionated human brain cDNA library, Nagase et al. (1997) cloned ANKRD28, which they designated KIAA0379. The deduced 882-amino acid protein shares 30.8% identity with ANKRD3 (605706). RT-PCR analysis detected ubiquitous expression in all human tissues tested.
By searching for PP1 (see 176875)-binding proteins in rabbit skeletal muscle, followed by database analysis, Kwiek et al. (2006) identified ANKRD28, which they called PITK. ANKRD28 contains putative PP1-binding motifs at either terminus and 28 successive ankyrin repeats. Western blot analysis of multiple mouse tissues revealed expression of ANKRD28 at similar levels in all tissues tested. In COS-7 cells, immunofluorescence microscopy localized ANKRD28 to subnuclear bodies with exclusion from nucleoli.
By in vitro studies, Kwiek et al. (2006) showed that recombinant ANKRD28 selectively inhibited the phosphorylase activity of PP1C in a dose-dependent manner. Phosphorylation of ser1013 and ser1017, which lie within the putative PP1-binding motif, negatively regulated ANKRD28 binding to PP1C. Immunoprecipitation studies showed that ANKRD28 bound to hnRNP-K (600712). ANKRD28 selectively regulated phosphorylation of hnRNP-K at ser284, an effect that was enhanced in vivo by an S1013A/S1017A double mutant, suggesting that ANKRD28 targets PP1 in a regulated manner to dephosphorylate hnRNP-K selectively at ser284. Microarray analysis found that expression of ANKRD28 resulted in altered expression of 47 genes, including marked induction of MEK5 (MAP2K5; 602520). Expression of only 2 of these genes was altered by the S1013A/S1017A double mutant, indicating the importance of phosphorylation in ANKRD28 function. In addition, the effects of ANKRD28 and S1013A/S1017A double-mutant ANKRD28 could be modulated by coexpression of hnRNP-K.
By radiation hybrid analysis, Nagase et al. (1997) mapped the ANKRD28 gene to chromosome 3. Kwiek et al. (2006) noted that the ANKRD28 gene maps to chromosome 3p25.1.
Kwiek, N. C., Thacker, D. F., Datto, M. B., Megosh, H. B., Haystead, T. A. J. PITK, a PP1 targeting subunit that modulates the phosphorylation of the transcriptional regulator hnRNP K. Cell. Signal. 18: 1769-1778, 2006. [PubMed: 16564677] [Full Text: https://doi.org/10.1016/j.cellsig.2006.01.019]
Nagase, T., Ishikawa, K., Nakajima, D., Ohira, M., Seki, N., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. DNA Res. 4: 141-150, 1997. [PubMed: 9205841] [Full Text: https://doi.org/10.1093/dnares/4.2.141]