HIPK2
HIPK2 (homeodomain interacting protein kinase 2) is a nuclear serine/threonine kinase that regulates transcription, the cell cycle and p53-mediated apoptosis. It acts as a corepressor or coactivator depending on the transcription factor it binds and its subcellular localisation. Browse Assay Genie's current range of HIPK2 research reagents below, or read on for the biology behind the target.
HIPK2 is a serine/threonine-protein kinase involved in transcription regulation, p53/TP53-mediated apoptosis and control of the cell cycle. It acts as a corepressor of several transcription factors, including SMAD1 and POU4F1/Brn3a, and probably NK homeodomain transcription factors. It inhibits cell growth and promotes apoptosis by activating p53 at both the transcriptional and protein level, through phosphorylation and indirect acetylation. This phosphorylation may be mediated by a p53-HIPK2-AXIN1 complex, and PML, HIPK2 and FBXO3 may act synergistically to activate p53-dependent transactivation.
The kinase has a broad set of substrates. It phosphorylates PDX1, ATF1, PML, CREB1, CTBP1, CBX4, RUNX1, EP300, CTNNB1, HMGA1, ZBTB4 and DAZAP2. After DNA damage it stabilises PML, activates CREB1 and ATF1, promotes the E3 SUMO-protein ligase activity of CBX4 and triggers degradation of ZBTB4. Phosphorylation of DAZAP2 prevents SIAH1-dependent ubiquitination and proteasomal degradation of HIPK2 itself. In Wnt/beta-catenin signalling it acts as an intermediate kinase between MAP3K7/TAK1 and NLK to promote degradation of MYB, and it also drives phosphorylation-dependent degradation of CTNNB1 and CTBP1. Further roles include co-suppression of HIF1A in the hypoxia response, activation of TP73, JNK activation with DAXX after TGFB, angiogenesis, erythroid differentiation and eye development.
HIPK2 belongs to the CMGC Ser/Thr protein kinase family, HIPK subfamily, within the homeodomain interacting protein kinase family. The HIPK2 gene is conserved, with a mouse ortholog, Hipk2, and multiple transcript variants encode different isoforms. UniProt records localisation to PML bodies in the nucleus, the cytoplasm and stress granules.
HIPK2 activates p53 by phosphorylation and indirect acetylation, making it a focus for studies of growth inhibition and apoptosis.
After DNA damage HIPK2 stabilises PML and phosphorylates CBX4, CREB1, ATF1 and DAZAP2, linking genotoxic stress to transcriptional control.
HIPK2 promotes degradation of CTNNB1 and MYB and cooperates with DAXX to activate JNK after TGFB, so it is studied in these pathways.
HIPK2 contributes to erythropoiesis, angiogenesis, eye and lens development, and hypoxia responses through HIF1A co-suppression.
HIPK2 is a serine/threonine kinase that regulates transcription, the cell cycle and p53-mediated apoptosis. It phosphorylates many substrates, including p53, PML, CREB1, CTBP1 and RUNX1, and can act as a corepressor or coactivator depending on the transcription factor and its localisation.
The approved name is homeodomain interacting protein kinase 2, and no other aliases or previous symbols are listed. It belongs to the HIPK family, which includes HIPK1 and HIPK4. NCBI reports multiple transcript variants encoding different isoforms of the HIPK2 gene.
NCBI describes HIPK2 as a conserved serine/threonine kinase, and a mouse ortholog, Hipk2, is annotated. UniProt notes a role in eye size, lens formation and retinal lamination in late embryogenesis. Check the datasheet of any product for its validated reactivity.
Other members of the homeodomain interacting protein kinase family with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q9H2X6; product specifications from Assay Genie datasheets.