HIPK1

The protein encoded by this gene belongs to the Ser/Thr family of protein kinases and HIPK subfamily. It phosphorylates homeodomain transcription factors and may also function as a co-repressor for homeodomain transcription factors. Alternative splicing results in four transcript variants encoding four distinct isoforms. [provided by RefSeq]

Full Name

homeodomain interacting protein kinase 1

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).

Biological Process

Adherens junction assembly Source: Ensembl
Anterior/posterior pattern specification Source: Ensembl
Definitive hemopoiesis Source: UniProtKB
Embryonic camera-type eye morphogenesis Source: Ensembl
Embryonic retina morphogenesis in camera-type eye Source: Ensembl
Endothelial cell apoptotic process Source: UniProtKB
Extrinsic apoptotic signaling pathway Source: UniProtKB
Eye development Source: UniProtKB
Intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: GO_Central
Iris morphogenesis Source: Ensembl
Lens induction in camera-type eye Source: Ensembl
Neuron differentiation Source: Ensembl
Peptidyl-serine phosphorylation Source: GO_Central
Peptidyl-threonine phosphorylation Source: GO_Central
Positive regulation of angiogenesis Source: UniProtKB
Positive regulation of cell population proliferation Source: Ensembl
Protein phosphorylation Source: UniProtKB
Regulation of tumor necrosis factor-mediated signaling pathway Source: UniProtKB
Retina layer formation Source: Ensembl
Smoothened signaling pathway Source: GO_Central

Cellular Location

Nucleus; Nucleus speckle; Cytoplasm. Predominantly nuclear. Translocates from nucleus to cytoplasm in response to stress stimuli via SENP1-mediated desumoylation.

PTM

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.