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.  
19
  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB KW
Protein bindingdefinition[GO:0005515]  
7
  • IntAct
  • UniProtKB
  • BHF-UCL
Protein kinase activitydefinition[GO:0004672]  
1
  • UniProtKB
Protein serine/threonine kinase activitydefinition[GO:0004674]  
1
  • Ortholog Curator
RNA polymerase II activating transcription factor bindingdefinition[GO:0001102]  
1
  • Ortholog Curator
Contributes to RNA polymerase II transcription coactivator activitydefinition[GO:0001105]  
1
  • Ortholog Curator
SMAD bindingdefinition[GO:0046332]  
1
  • UniProtKB
Transcription corepressor activitydefinition[GO:0003714]  
1
  • UniProtKB
Virion bindingdefinition[GO:0046790]  
1
  • UniProtKB
GO biological process 
Adult walking behaviordefinition[GO:0007628] silver  
1
  • Ortholog Compara
Anterior/posterior pattern specificationdefinition[GO:0009952] silver  
1
  • Ortholog Compara
Cellular response to hypoxiadefinition[GO:0071456]  
1
  • UniProtKB
DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediatordefinition[GO:0006978]  
1
  • BHF-UCL
Embryonic camera-type eye morphogenesisdefinition[GO:0048596] silver  
1
  • Ortholog Compara
Embryonic retina morphogenesis in camera-type eyedefinition[GO:0060059] silver  
1
  • Ortholog Compara
Erythrocyte differentiationdefinition[GO:0030218]  
1
  • UniProtKB
Eye developmentdefinition[GO:0001654]  
1
  • UniProtKB
Intrinsic apoptotic signaling pathwaydefinition[GO:0097193]  
1
  • UniProtKB
Intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediatordefinition[GO:0042771]  
1
  • UniProtKB
Iris morphogenesisdefinition[GO:0061072] silver  
1
  • Ortholog Compara
Lens induction in camera-type eyedefinition[GO:0060235] silver  
1
  • Ortholog Compara
Modulation by virus of host morphology or physiologydefinition[GO:0019048]  
1
  • UniProtKB
Negative regulation of BMP signaling pathwaydefinition[GO:0030514]  
1
  • UniProtKB
Negative regulation of neuron apoptotic processdefinition[GO:0043524] silver  
1
  • Ortholog Compara
Negative regulation of transcription from RNA polymerase II promoterdefinition[GO:0000122] silver  
1
  • Ortholog Compara
Neuron differentiationdefinition[GO:0030182] silver  
1
  • Ortholog Compara
Peptidyl-serine phosphorylationdefinition[GO:0018105]  
1
  • Ortholog Curator
Peptidyl-threonine phosphorylationdefinition[GO:0018107]  
1
  • Ortholog Curator
PML body organizationdefinition[GO:0030578]  
1
  • UniProtKB
Positive regulation of angiogenesisdefinition[GO:0045766]  
1
  • UniProtKB
Positive regulation of cell proliferationdefinition[GO:0008284] silver  
1
  • Ortholog Compara
Positive regulation of DNA bindingdefinition[GO:0043388] silver  
1
  • Ortholog Compara
Positive regulation of JNK cascadedefinition[GO:0046330]  
1
  • UniProtKB
Positive regulation of protein bindingdefinition[GO:0032092]  
1
  • Ortholog Curator
Positive regulation of protein phosphorylationdefinition[GO:0001934] silver  
1
  • Ortholog Compara
Positive regulation of sequence-specific DNA binding transcription factor activitydefinition[GO:0051091]  
1
  • Ortholog Curator
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944]  
1
  • Ortholog Curator
Positive regulation of transcription, DNA-templateddefinition[GO:0045893]  
1
  • BHF-UCL
Positive regulation of transforming growth factor beta receptor signaling pathwaydefinition[GO:0030511]  
1
  • UniProtKB
Protein phosphorylationdefinition[GO:0006468]  
1
  • UniProtKB
Regulation of cell cycledefinition[GO:0051726]  
1
  • UniProtKB
Retina layer formationdefinition[GO:0010842] silver  
1
  • Ortholog Compara
SMAD protein signal transductiondefinition[GO:0060395]  
1
  • UniProtKB
Smoothened signaling pathwaydefinition[GO:0007224] silver  
1
  • Ortholog Compara
Transcription, DNA-templateddefinition[GO:0006351]  
1
  • UniProtKB KW
Transforming growth factor beta receptor signaling pathwaydefinition[GO:0007179] silver  
1
  • Ortholog Compara
Voluntary musculoskeletal movementdefinition[GO:0050882] silver  
1
  • Ortholog 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.  
1
  • UniProtKB
 
More information is available from:
Pathways 
According to Reactome, this protein belongs to the following pathway:
YAP1- and WWTR1 (TAZ)-stimulated gene expression  REACT_118713  
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).  
2
  • UniProtKB
 

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