homeodomain-interacting protein kinase 1; nuclear body-associated kinase 2 (HIPK1, KIAA0630, MYAK, NBAK2)

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 - complex formation promotes MAP3K5-JNK activation & subsequent apoptosis 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

General

endoribonuclease nuclear protein serine/threonine kinase

Properties

SIZE: entity length = 1210 aa MW = 131 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: kinase domain SITE: 190-518 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 196-204 ATP-binding site NAME: ATP-binding site SITE: 219-219 aspartate residue {D315} Tyr phosphorylation site {Y352} nuclear translocation signal {844-847} Ser phosphorylation site {S872} TP53 interaction {885-1093} MOTIF: nuclear speckles {891-998} SUMO interaction {902-926} STATE: active state

Database Correlations

OMIM 608003 UniProt Q86Z02 Pfam PF00069 Entrez Gene 204851 Kegg hsa:204851 ENZYME 2.7.11.1

References

UniProt :accession Q86Z02