Alternative titles; symbols
HGNC Approved Gene Symbol: HIPK1
Cytogenetic location: 1p13.2 Genomic coordinates (GRCh38) : 1:113,929,324-113,977,869 (from NCBI)
By sequencing clones obtained from a size-fractionated brain cDNA library, Ishikawa et al. (1998) obtained a partial HIPK1 cDNA clone, which they designated KIAA0630. Over 295 amino acids, the deduced sequence shares 32.2% identity with a serine/threonine protein kinase. RT-PCR detected expression in all tissues examined.
Ecsedy et al. (2003) cloned mouse Hipk1. Northern blot analysis detected expression in all mouse and human tissues examined. RNA dot-blot analysis of human tissues detected expression in all adult and fetal tissues. Immunolocalization of Hipk1 in mouse fibroblasts detected punctate nuclear staining. Hipk1 also localized throughout the nucleus and was excluded only from nucleoli. In addition, there was a diffuse cytoplasmic staining.
Using p53 (191170) as bait in a yeast 2-hybrid screen, Kondo et al. (2003) cloned rat Hipk1, and using the rat cDNA as probe, they cloned human HIPK1 from a skeletal muscle cDNA library. The deduced 1,210-amino acid protein contains a putative serine/threonine kinase domain. Northern blot analysis detected expression of a 9-kb transcript in heart, brain, placenta, skeletal muscle, and pancreas.
Ecsedy et al. (2003) found that HIPK1, but not a kinase-dead mutant (lys219 to ala), underwent autophosphorylation and was able to phosphorylate substrate proteins in vitro. Endogenous HIPK1 immunoprecipitated with DAXX (603186) from human embryonic kidney cells and phosphorylated DAXX in vitro and in vivo. HIPK1 phosphorylated DAXX on ser669, and phosphorylation diminished DAXX transcriptional repression in 3 of 4 reporters assayed. In human embryonic kidney cells, interaction with HIPK1 resulted in the relocalization of DAXX from promyelocytic leukemia protein (PML; 102578) oncogenic domains (PODs). The relocalization required the HIPK1 kinase domain, but it was independent of DAXX phosphorylation.
Kondo et al. (2003) confirmed interaction between HIPK1 and p53 by immunoprecipitation assays. Deletion analysis showed that amino acids 100 to 370 of p53 and 885 to 1093 of HIPK1 were sufficient for the interaction. HIPK1 serine phosphorylated p53 and was able to autophosphorylate. Kondo et al. (2003) found HIPK1 expression elevated in 12 of 14 breast cancer cell lines. In 2 of these cell lines, HIPK1 was expressed at more than 10 times the control levels. Oncogenically transformed mouse embryonic fibroblasts developed from Hipk1-null mice showed reduced transcription of Mdm2 (164785) and were more susceptible to apoptosis induced by DNA damage. Carcinogen-treated Hipk1-null mice developed fewer and smaller skin tumors than wildtype mice.
By radiation hybrid analysis, Ishikawa et al. (1998) mapped the HIPK1 gene to chromosome 1. By in situ hybridization, Kondo et al. (2003) mapped the HIPK1 gene to chromosome 1p13.
Ecsedy, J. A., Michaelson, J. S., Leder, P. Homeodomain-interacting protein kinase 1 modulates Daxx localization, phosphorylation, and transcriptional activity. Molec. Cell. Biol. 23: 950-960, 2003. [PubMed: 12529400] [Full Text: https://doi.org/10.1128/MCB.23.3.950-960.2003]
Ishikawa, K., Nagase, T., Suyama, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. DNA Res. 5: 169-176, 1998. [PubMed: 9734811] [Full Text: https://doi.org/10.1093/dnares/5.3.169]
Kondo, S., Lu, Y., Debbas, M., Lin, A. W., Sarosi, I., Itie, A., Wakeham, A., Tuan, J., Saris, C., Elliott, G., Ma, W., Benchimol, S., Lowe, S. W., Mak, T. W., Thukral, S. K. Characterization of cells and gene-targeted mice deficient for the p53-binding kinase homeodomain-interacting protein kinase-1 (HIPK1). Proc. Nat. Acad. Sci. 100: 5431-5436, 2003. [PubMed: 12702766] [Full Text: https://doi.org/10.1073/pnas.0530308100]