HIPK2 - Homeodomain-interacting protein kinase 2 - human protein (Function)
 
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HIPK2 »  Homeodomain-interacting protein kinase 2   [ EC 2.7.11.1 ]
 
Gene name:  HIPK2
Entry whose protein(s) existence is based on evidence at protein level
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1 112 3
GENE REF ISO

Function

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Overview 
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.  
18
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Protein bindingdefinition[GO:0005515]  
7
  • IPIIntAct
  • IPIUniProtKB
  • IPIBHF-UCL
Protein kinase activitydefinition[GO:0004672]  
1
  • IDAUniProtKB
Protein serine/threonine kinase activitydefinition[GO:0004674]  
  • ISSOrtholog Curator
RNA polymerase II activating transcription factor bindingdefinition[GO:0001102]  
  • ISSOrtholog Curator
Contributes to RNA polymerase II transcription coactivator activitydefinition[GO:0001105]  
  • ISSOrtholog Curator
SMAD bindingdefinition[GO:0046332]  
1
  • IPIUniProtKB
Transcription corepressor activitydefinition[GO:0003714]  
1
  • IDAUniProtKB
Virion bindingdefinition[GO:0046790]  
1
  • IPIUniProtKB
GO biological process 
Adult walking behaviordefinition[GO:0007628] silver  
  • IEAOrtholog Compara
Anterior/posterior pattern specificationdefinition[GO:0009952] silver  
  • IEAOrtholog Compara
Cellular response to hypoxiadefinition[GO:0071456]  
1
  • TASUniProtKB
DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediatordefinition[GO:0006978]  
1
  • IDABHF-UCL
Embryonic camera-type eye morphogenesisdefinition[GO:0048596] silver  
  • IEAOrtholog Compara
Embryonic retina morphogenesis in camera-type eyedefinition[GO:0060059] silver  
  • IEAOrtholog Compara
Erythrocyte differentiationdefinition[GO:0030218]  
1
  • ISSUniProtKB
Eye developmentdefinition[GO:0001654]  
1
  • ISSUniProtKB
Intrinsic apoptotic signaling pathwaydefinition[GO:0097193]  
1
  • NASUniProtKB
Intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediatordefinition[GO:0042771]  
1
  • TASUniProtKB
Iris morphogenesisdefinition[GO:0061072] silver  
  • IEAOrtholog Compara
Lens induction in camera-type eyedefinition[GO:0060235] silver  
  • IEAOrtholog Compara
Modulation by virus of host morphology or physiologydefinition[GO:0019048]  
1
  • NASUniProtKB
Negative regulation of BMP signaling pathwaydefinition[GO:0030514]  
1
  • IMPUniProtKB
Negative regulation of neuron apoptotic processdefinition[GO:0043524] silver  
  • IEAOrtholog Compara
Negative regulation of transcription from RNA polymerase II promoterdefinition[GO:0000122] silver  
  • IEAOrtholog Compara
Neuron differentiationdefinition[GO:0030182] silver  
  • IEAOrtholog Compara
Peptidyl-serine phosphorylationdefinition[GO:0018105]  
  • ISSOrtholog Curator
Peptidyl-threonine phosphorylationdefinition[GO:0018107]  
  • ISSOrtholog Curator
PML body organizationdefinition[GO:0030578]  
1
  • TASUniProtKB
Positive regulation of angiogenesisdefinition[GO:0045766]  
1
  • IDAUniProtKB
Positive regulation of cell proliferationdefinition[GO:0008284] silver  
  • IEAOrtholog Compara
Positive regulation of DNA bindingdefinition[GO:0043388] silver  
  • IEAOrtholog Compara
Positive regulation of JNK cascadedefinition[GO:0046330]  
1
  • IMPUniProtKB
Positive regulation of protein bindingdefinition[GO:0032092]  
  • ISSOrtholog Curator
Positive regulation of sequence-specific DNA binding transcription factor activitydefinition[GO:0051091]  
  • ISSOrtholog Curator
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944]  
  • ISSOrtholog Curator
Positive regulation of transcription, DNA-templateddefinition[GO:0045893]  
1
  • IMPBHF-UCL
Positive regulation of transforming growth factor beta receptor signaling pathwaydefinition[GO:0030511]  
1
  • IMPUniProtKB
Protein phosphorylationdefinition[GO:0006468]  
1
  • IDAUniProtKB
Regulation of cell cycledefinition[GO:0051726]  
1
  • TASUniProtKB
Retina layer formationdefinition[GO:0010842] silver  
  • IEAOrtholog Compara
SMAD protein signal transductiondefinition[GO:0060395]  
1
  • IDAUniProtKB
Smoothened signaling pathwaydefinition[GO:0007224] silver  
  • IEAOrtholog Compara
Transcription, DNA-templateddefinition[GO:0006351]  
  • IEAUniProtKB KW
Transforming growth factor beta receptor signaling pathwaydefinition[GO:0007179] silver  
  • IEAOrtholog Compara
Voluntary musculoskeletal movementdefinition[GO:0050882] silver  
  • IEAOrtholog Compara
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.1: ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
 
More information is available from:
Note 
Interesting targets for cancer therapy. HIPK2 deregulation would end up in a multifactorial response leading to tumor chemoresistance by affecting p53/TP53 activity on one hand and to angiogenesis and cell proliferation by affecting HIF1A activity on the other hand. May provide important insights in the process of tumor progression, and may also serve as the crucial point in the diagnostic and therapeutical aspects of cancer. Tumor treatment may potential be improved by zinc supplementation in combination with chemotherapy to address hypoxia (PubMed20514025).  
1
  • CuratedUniProtKB
 

Keywords

Biological process 
Apoptosis  definition   [KW-0053]
DNA damage  definition   [KW-0227]
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: HIPK2
GenomeRNAi: 28996
PRO: PR:Q9H2X6
Chemistry
GuidetoPHARMACOLOGY: 2034