HIPK1
Function
Serine/threonine-protein kinase involved in transcription regulation and TNF-mediated cellular apoptosis. Plays a role as a corepressor for homeodomain transcription factors. Phosphorylates DAXX and MYB. Phosphorylates DAXX in response to stress, and mediates its translocation from the nucleus to the cytoplasm. Inactivates MYB transcription factor activity by phosphorylation. Prevents MAP3K5-JNK activation in the absence of TNF. TNF triggers its translocation to the cytoplasm in response to stress stimuli, thus activating nuclear MAP3K5-JNK by derepression and promoting apoptosis. May be involved in anti-oxidative stress responses. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis. Promotes angiogenesis and to be involved in erythroid differentiation. May be involved in malignant squamous cell tumor formation. Phosphorylates PAGE4 at 'Thr-51' which is critical for the ability of PAGE4 to potentiate the transcriptional activator activity of JUN (PubMed:24559171).
Post-translational modifications
Autophosphorylated. Phosphorylated and activated by JNK1.
Degraded by PARK7 at the protein level.
Sumoylated. When conjugated it is directed to nuclear speckles. SENP1-mediated desumoylation is mediated by TNF in response to stress stimuli, triggering transient translocation from nucleus to cytoplasm.
Sequence Similarities
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. HIPK subfamily.
Tissue Specificity
Ubiquitously expressed with highest levels in skeletal muscle and heart. Overexpressed in breast cancer cell lines. Isoform 2 is highly expressed in testis. Expressed in both androgen-dependent and androgen-independent prostate cancer cells (PubMed:28289210).
Cellular localization
- Nucleus
- Cytoplasm
- Nucleus speckle
- Predominantly nuclear. Translocates from nucleus to cytoplasm in response to stress stimuli via SENP1-mediated desumoylation.
Alternative names
KIAA0630, MYAK, NBAK2, HIPK1, Homeodomain-interacting protein kinase 1, Nuclear body-associated kinase 2