HIPK2
Serine/threonine-protein kinase involved in transcription regulation, p53/TP53-mediated cellular apoptosis and regulation of the cell cycle. Acts as a corepressor of several transcription factors, including SMAD1 and POU4F1/Brn3a and probably NK homeodomain transcription factors. Phosphorylates PDX1, ATF1, PML, p53/TP53, CREB1, CTBP1, CBX4, RUNX1, EP300, CTNNB1, HMGA1 and ZBTB4. Inhibits cell growth and promotes apoptosis through the activation of p53/TP53 both at the transcription level and at the protein level (by phosphorylation and indirect acetylation). The phosphorylation of p53/TP53 may be mediated by a p53/TP53-HIPK2-AXIN1 complex. Involved in the response to hypoxia by acting as a transcriptional co-suppressor of HIF1A. Mediates transcriptional activation of TP73. In response to TGFB, cooperates with DAXX to activate JNK. Negative regulator through phosphorylation and subsequent proteasomal degradation of CTNNB1 and the antiapoptotic factor CTBP1. In the Wnt/beta-catenin signaling pathway acts as an intermediate kinase between MAP3K7/TAK1 and NLK to promote the proteasomal degradation of MYB. Phosphorylates CBX4 upon DNA damage and promotes its E3 SUMO-protein ligase activity. Activates CREB1 and ATF1 transcription factors by phosphorylation in response to genotoxic stress. In response to DNA damage, stabilizes PML by phosphorylation. PML, HIPK2 and FBXO3 may act synergically to activate p53/TP53-dependent transactivation. Promotes angiogenesis, and is involved in erythroid differentiation, especially during fetal liver erythropoiesis. Phosphorylation of RUNX1 and EP300 stimulates EP300 transcription regulation activity. Triggers ZBTB4 protein degradation in response to DNA damage. Modulates HMGA1 DNA-binding affinity. In response to high glucose, triggers phosphorylation-mediated subnuclear localization shifting of PDX1. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis. Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. HIPK subfamily. Highly expressed in heart, muscle and kidney. Weakly expressed in a ubiquitous way. Down-regulated in several thyroid and breast tumors. 3 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: CMGC group; DYRK family; EC 2.7.11.1; HIPK subfamily; Kinase, protein; Protein kinase, CMGC; Protein kinase, Ser/Thr (non-receptor)
Molecular Function: ATP binding; DNA binding; kinase activity; nucleotide binding; protein binding; protein kinase activity; protein serine/threonine kinase activity; protein tyrosine kinase activity; RNA polymerase II-specific DNA-binding transcription factor binding; SMAD binding; transcription coactivator activity; transcription corepressor activity; transferase activity; virion binding
Biological Process: adult locomotory behavior; adult walking behavior; anterior/posterior pattern specification; apoptotic process; cell population proliferation; DNA damage response; DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; embryonic camera-type eye morphogenesis; embryonic retina morphogenesis in camera-type eye; gene expression; intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; iris morphogenesis; lens induction in camera-type eye; lung morphogenesis; negative regulation of BMP signaling pathway; negative regulation of neuron apoptotic process; negative regulation of transcription by RNA polymerase II; negative regulation of ubiquitin-dependent protein catabolic process; neuron apoptotic process; neuron differentiation; peptidyl-serine phosphorylation; peptidyl-threonine phosphorylation; phosphorylation; positive regulation of angiogenesis; positive regulation of cell population proliferation; positive regulation of DNA binding; positive regulation of DNA-binding transcription factor activity; positive regulation of DNA-templated transcription; positive regulation of JNK cascade; positive regulation of protein binding; positive regulation of protein phosphorylation; positive regulation of transcription by RNA polymerase II; positive regulation of transforming growth factor beta receptor signaling pathway; protein phosphorylation; respiratory system process; retina layer formation; SMAD protein signal transduction; smoothened signaling pathway; thyroid gland development; transforming growth factor beta receptor signaling pathway; voluntary musculoskeletal movement
