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

HIPK3 (Q9H422) - Overview - Molecular Target Synopsis

Protein


HIPK3, Homeodomain-interacting protein kinase 3
Enzyme Classification 2.7.11.1
UniProt Q9H422

Also Known as HIPK3_HUMAN, HIPK3, DYRK6, FIST3, PKY

Serine/threonine-protein kinase involved in transcription regulation, apoptosis and steroidogenic gene expression. Phosphorylates JUN and RUNX2. Seems to negatively regulate apoptosis by promoting FADD phosphorylation. Enhances androgen receptor-mediated transcription. May act as a transcriptional corepressor for NK homeodomain transcription factors. The phosphorylation of NR5A1 activates SF1 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation. In osteoblasts, supports transcription activation: phosphorylates RUNX2 that synergizes with SPEN/MINT to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE). Interacts with Nkx1-2. Interacts with FAS and DAXX. Probably part of a complex consisting of HIPK3, FAS and FADD. Interacts with and stabilizes ligand-bound androgen receptor (AR) (By similarity). Interacts with UBL1/SUMO-1. Binds to NR5A1/SF1, SPEN/MINT and RUNX2.

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: HIPK3 is active in the following subcellular-locations: cytoplasm, nucleus.
GO terms: HIPK3 is active in the following subcellular-locations: cytosol, nuclear body, PML body.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project HIPK3 has gain in 2 cell-lines, loss in 1 cell-lines and no signal in 1002 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: T47D, OVCAR_3, SR

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: OVISE, Detroit 562, HCC4006

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: HSMM, HMEC, NHLF

(see details)

RNA Interference


HIPK3 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: MIAPACA2, CAL51. (see details)

3D Structures


At greater than 35% identity similarity to HIPK3 there are:
30 structures (106 chains) solved
30 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

HIPK3 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


HIPK3 has been screened with 343 compounds (560 bioactivities), 16 compounds have bioactivities that show binding affinity of <= 500nM (19 bioactivities). (see details)