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

HIPK2 (Q9H2X6) - Overview - Molecular Target Synopsis

Protein


HIPK2, Homeodomain-interacting protein kinase 2
Enzyme Classification 2.7.11.1
UniProt Q9H2X6

Also Known as HIPK2_HUMAN, HIPK2

Serine/threonine-protein kinase involved in transcription regulation, p53/TP53-mediated cellular apoptosis and regulation of the cell cycle. Acts as a corepressor of several transcription factors, including SMAD1 and POU4F1/Brn3a and probably NK homeodomain transcription factors. Phosphorylates PDX1, ATF1, PML, p53/TP53, CREB1, CTBP1, CBX4, RUNX1, EP300, CTNNB1, HMGA1 and ZBTB4. Inhibits cell growth and promotes apoptosis through the activation of p53/TP53 both at the transcription level and at the protein level (by phosphorylation and indirect acetylation). The phosphorylation of p53/TP53 may be mediated by a p53/TP53-HIPK2-AXIN1 complex. Involved in the response to hypoxia by acting as a transcriptional co-suppressor of HIF1A. Mediates transcriptional activation of TP73. In response to TGFB, cooperates with DAXX to activate JNK. Negative regulator through phosphorylation and subsequent proteasomal degradation of CTNNB1 and the antiapoptotic factor CTBP1. In the Wnt/beta-catenin signaling pathway acts as an intermediate kinase between MAP3K7/TAK1 and NLK to promote the proteasomal degradation of MYB. Phosphorylates CBX4 upon DNA damage and promotes its E3 SUMO-protein ligase activity. Activates CREB1 and ATF1 transcription factors by phosphorylation in response to genotoxic stress. In response to DNA damage, stabilizes PML by phosphorylation. PML, HIPK2 and FBXO3 may act synergically to activate p53/TP53-dependent transactivation. Promotes angiogenesis, and is involved in erythroid differentiation, especially during fetal liver erythropoiesis. Phosphorylation of RUNX1 and EP300 stimulates EP300 transcription regulation activity. Triggers ZBTB4 protein degradation in response to DNA damage. Modulates HMGA1 DNA-binding affinity. In response to high glucose, triggers phosphorylation-mediated subnuclear localization shifting of PDX1. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis. Interacts with CREB1, SIAH1, WSB1, CBX4, TRADD, p53/TP53, TP73, TP63, CREBBP, DAXX, P53DINP1, SKI, SMAD1, SMAD2 and SMAD3, but not SMAD4. Interacts with ATF1, PML, RUNX1, EP300, NKX1-2, NKX2-5, SPN/CD43, UBE2I, HMGA1, CTBP1, AXIN1, NLK, MYB, POU4F1, POU4F2, POU4F3, UBE2I, UBL1 and ZBTB4. Probably part of a complex consisting of p53/TP53, HIPK2 and AXIN1. Interacts with SP100; positively regulates TP53-dependent transcription. Interacts with SUMO1P1/SUMO5 (PubMed:27211601).

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: HIPK2 is active in the following subcellular-locations: cytoplasm, nucleus, pml body.
GO terms: HIPK2 is active in the following subcellular-locations: cytoplasm, nuclear body, nucleoplasm, nucleus, PML body, RNA polymerase II transcription factor complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project HIPK2 has gain in 3 cell-lines, loss in 0 cell-lines and no signal in 1001 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: HOP_92, SR, A498

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: 786-O, SK-MEL-24, HCC1171

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: SK-N-SH, HSMM, AG445

(see details)

RNA Interference


HIPK2 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: T47D, JIMT1. (see details)

3D Structures


At greater than 35% identity similarity to HIPK2 there are:
36 structures (115 chains) solved
35 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

HIPK2 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


HIPK2 has been screened with 379 compounds (598 bioactivities), 23 compounds have bioactivities that show binding affinity of <= 500nM (26 bioactivities). (see details)