Alternative titles; symbols
HGNC Approved Gene Symbol: HIPK3
Cytogenetic location: 11p13 Genomic coordinates (GRCh38) : 11:33,256,672-33,357,023 (from NCBI)
Protein kinases are involved not only in cellular regulation and signaling but also in multidrug resistance (MDR). Using PCR with degenerate primers based on conserved domains of serine-threonine kinases, Begley et al. (1997) isolated an MDR cell cDNA encoding a 1,215-amino acid protein with a calculated molecular mass of 130 kD. The protein contains sequences identical to the catalytic core of many serine-protein kinases and is 54% similar to the yeast protein kinase YAK1, whose normal role is to restrict growth. The authors therefore designated the protein PKY, for homolog of protein kinase YAK1. The authors stated that PKY may be identical to a 170-kD kinase identified in the same cell lines by Sampson et al. (1993), the difference in molecular mass being due to posttranslational modifications. By Northern blot analysis, PKY was expressed at higher levels in MDR cells than in their nonresistant parental lines; in addition, a 7-kb PKY transcript was expressed at high levels in heart and skeletal muscle and at lower levels in placenta, pancreas, and brain.
Using a yeast 2-hybrid screen, Kim et al. (1998) identified in mouse 3 members of a family of cofactors, which they designated homeodomain-interacting protein kinases (HIPKs), that interact with homeoproteins and show the greatest similarity to the yeast YAK1 protein (43% identity in the catalytic domain). The corepressor activity of HIPKs depends on both its homeodomain interaction domain and a corepressor domain that maps to the N terminus. CV-1 cells expressing recombinant HIPK2 showed that HIPKs localize to nuclear speckles. Kim et al. (1998) presented evidence that HIPKs can act as transcriptional corepressors for NK homeodomain transcription factors.
A BLAST search indicated that HIPK3 (GenBank AF07760) is 85% identical to PKY (GenBank AF004849) (Scott, 1999).
Venables et al. (2005) identified a testis-specific HIPK3 splice variant resulting from alternative splicing of the 109 nucleotide 'exon T' located within intron 2. The deduced amino acid sequence is identical for the first 407 amino acids, followed by introduction of 4 novel amino acids and a stop codon, possibly resulting in nonsense-mediated decay.
Zhang et al. (2005) determined that the HIPK3 gene contains 16 exons and spans more than 96 kb.
By fluorescence in situ hybridization, Nupponen and Visakorpi (1999) mapped the HIPK3 gene to chromosome 11p13.
Venables et al. (2005) found that the alternative splicing factor Tra2B (SFRS10; 602719) recapitulated testis-specific splicing of HIPK3 in a concentration-dependent manner and bound specifically to a long purine-rich sequence in exon T. This sequence was also specifically bound by HNRNPA1 (164017), HNRNPH1 (601035), ASF/SF2 (SFRS1; 600812), and SRp40 (SFRS5; 600914). In vitro studies showed that this sequence shifted splicing to a downstream 5-prime splice site within a heterologous pre-mRNA substrate in the presence of Tra2B, ASF/SF2, and SRp40, whereas HNRNPA1 specifically inhibited this choice. By mutating the purine-rich sequence of exon T, the authors showed that purine-rich sequence is the major determinant of Tra2B- and HNRNPA1-mediated regulation.
Begley, D.A., Berkenpas, M. B., Sampson, K. E., Abraham, I. Identification and sequence of human PKY, a putative kinase with increased expression in multidrug-resistant cells, with homology to yeast protein kinase Yak1. Gene 200: 35-43, 1997. [PubMed: 9373137] [Full Text: https://doi.org/10.1016/s0378-1119(97)00350-8]
Kim, Y. H., Choi, C. Y., Lee, S. J., Conti, M. A., Kim, Y. Homeodomain-interacting protein kinases, a novel family of co-repressors for homeodomain transcription factors. J. Biol. Chem. 273: 25875-25879, 1998. [PubMed: 9748262] [Full Text: https://doi.org/10.1074/jbc.273.40.25875]
Nupponen, N. N., Visakorpi, T. Assignment of the protein kinase homolog of YAK1 (HIPK3) to human chromosome band 11p13 by in situ hybridization. Cytogenet. Cell Genet. 87: 102-103, 1999. [PubMed: 10640824] [Full Text: https://doi.org/10.1159/000015404]
Sampson, K. E., McCroskey, M. C., Abraham, I. Identification of a 170 kDa membrane kinase with increased activity in KB-V1 multidrug resistant cells. J. Cell. Biochem. 52: 384-395, 1993. [PubMed: 7693726] [Full Text: https://doi.org/10.1002/jcb.240520403]
Scott, A. F. Personal Communication. Baltimore, Md. 6/21/1999.
Venables, J. P., Bourgeois, C. F., Dalgliesh, C., Kister, L., Stevenin, J., Elliott, D. J. Up-regulation of the ubiquitous alternative splicing factor Tra2-beta causes inclusion of a germ cell-specific exon. Hum. Molec. Genet. 14: 2289-2303, 2005. [PubMed: 16000324] [Full Text: https://doi.org/10.1093/hmg/ddi233]
Zhang, D., Li, K., Erickson-Miller, C. L., Weiss, M., Wojchowski, D. M. DYRK gene structure and erythroid-restricted features of DYRK3 gene expression. Genomics 85: 117-130, 2005. [PubMed: 15607427] [Full Text: https://doi.org/10.1016/j.ygeno.2004.08.021]