功能Protein kinase acting as a corepressor of several transcription factors, including SMAD1 and POU4F1/Brn3a and probably NK homeodomain transcription factors. Inhibits cell growth and promotes apoptosis. Involved in transcriptional activation of TP53 and TP73. Phosphorylation of TP53 may be mediated by a TP53-HIPK2-AXIN1 complex. In response to TGFB, cooperates with DAXX to activate JNK. Phosphorylates the antiapoptotic factor CTBP1 and promotes its proteasomal degradation. In the Wnt/beta-catenin signaling pathway acts as an intermediate kinase between TAK1 and NLK to promote the proteasomal degradation of MYB (By similarity). Phosphorylates CBX4 upon DNA damage and promotes its E3 SUMO-protein ligase activity. PML, HIPK2 and FBXO3 may act synergically to activate p53/TP53-dependent transactivation.
组织特异性Highly expressed in heart, muscle and kidney. Weakly expressed in a ubiquitous way. Down-regulated in several thyroid and breast tumors.
序列相似性Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. HIPK subfamily. Contains 1 protein kinase domain.
翻译后修饰Phosphorylated on tyrosines (By similarity). Autophosphorylated. Sumoylated. When conjugated it is directed to nuclear speckles. Desumoylated by SENP1 (By similarity). Sumoylation on Lys-32 is promoted by the E3 SUMO-protein ligase CBX4. Ubiquitinated by FBXO3, leading to rapid proteasome-dependent degradation. This degradation, but not ubiquitination, is prevented in the presence of PML.
细胞定位Nucleus > PML body. Cytoplasm. Concentrated in PML/POD/ND10 nuclear bodies. Small amounts are cytoplasmic.