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 (By similarity). ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein] ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein] Interacts with Nkx1-2, Nkx2-5, MYB, PARK7, DAXX and p53/TP53. Part of a cytoplasmic complex made of HIPK1, DAB2IP and MAP3K5 in response to TNF. This complex formation promotes MAP3K5-JNK activation and subsequent apoptosis. Predominantly nuclear. Translocates from nucleus to cytoplasm in response to stress stimuli via SENP1-mediated desumoylation. Ubiquitously expressed, with high levels in reproductive tissues. Expressed in the epithelial layer of mammary gland, uterus and epididymis, in the corpus luteum, and in post-meiotic round spermatids. Highest at 12 dpc, where it is expressed primarily in the central nervous system. Highly induced during primary fetal liver erythropoiesis. Expressed in the inner retina during late embryogenesis, predominantly in cytoplasm. Phosphorylated and activated by JNK1 (By similarity). Autophosphorylated. 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. Small eyes with deficient lens, abnormal retinal lamination, and thickened retinas. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. HIPK subfamily.