Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

HIPK1 (Q86Z02) - Overview - Molecular Target Synopsis

Protein


HIPK1, Homeodomain-interacting protein kinase 1
Enzyme Classification 2.7.11.1
UniProt Q86Z02

Also Known as HIPK1_HUMAN, HIPK1, KIAA0630, MYAK, NBAK2

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. 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.

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: HIPK1 is active in the following subcellular-locations: cytoplasm, nucleus.
GO terms: HIPK1 is active in the following subcellular-locations: centrosome, cytoplasm, cytosol, nuclear speck, nucleoplasm, nucleus, PML body.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project HIPK1 has gain in 8 cell-lines, loss in 3 cell-lines and no signal in 994 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MCF7, SF_539, KM12

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: MCF-7, MHH-ES-1, BT-20

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: MCF-7, HSMM, HeLa-S3

(see details)

RNA Interference


HIPK1 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: SUM44, CROE33. (see details)

3D Structures


At greater than 35% identity similarity to HIPK1 there are:
39 structures (121 chains) solved
38 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

HIPK1 is solved in complex with the approved drug(s):

2K2/MIDOSTAURIN (4NCT_A, 4NCT_B, 4NCT_C, 4NCT_D).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


HIPK1 has been screened with 729 compounds (1289 bioactivities), 11 compounds have bioactivities that show binding affinity of <= 500nM (11 bioactivities). (see details)