homeodomain-interacting protein kinase 1; nuclear body-associated kinase 2 (HIPK1, KIAA0630, MYAK, NBAK2)
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Function
- serine/threonine protein kinase
- role in transcription regulation & TNF-mediated apoptosis
- role as a corepressor for homeodomain transcription factors
- phosphorylates DAXX & MYB
- phosphorylates DAXX in response to stress, & 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 & promoting apoptosis
- may be involved in anti- oxidative stress responses
- role in regulation of eye size, lens formation & retinal lamination during late embryogenesis
- promotes angiogenesis
- role in erythroid differentiation
- autophosphorylated. phosphorylated & activated by JNK1
- degraded by PARK7
- sumoylated
- when sumoylated HIPK1 is directed to nuclear speckles
- SENP1-mediated desumoylation is mediated by TNF in response to stress stimuli, triggering transient translocation from nucleus to cytoplasm
- interacts with Nkx1-2, Nkx2-5, MYB, PARK7, DAXX & p53/TP53
- part of a cytoplasmic complex made of HIPK1, DAB2IP & MAP3K5 in response to TNF
Structure
- belongs to the protein kinase superfamily, CMGC Ser/Thr protein kinase family, HIPK subfamily
- contains 1 protein kinase domain
Compartment
- nucleus, predominantly nuclear
- translocates from nucleus to cytoplasm in response to stress stimuli via SENP1-mediated desumoylation
Alternative splicing
named isoforms=4
Expression
- ubiquitously expressed
- highest levels in skeletal muscle & heart
- isoform 2 is highly expressed in testis
Pathology
- may play role in malignant squamous cell tumor formation
- overexpressed in breast cancer cell lines