InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Hipk2

Summary

InnateDB Protein

IDBP-534379.3

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Hipk2

Protein Name

homeodomain interacting protein kinase 2

Synonyms

1110014O20Rik; B230339E18Rik; Stank;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000124133

InnateDB Gene

IDBG-137586 (Hipk2)

Protein Structure

UniProt Annotation

Function

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. {ECO:0000269PubMed:11593421, ECO:0000269PubMed:11780126, ECO:0000269PubMed:14567915, ECO:0000269PubMed:15082531, ECO:0000269PubMed:15492043, ECO:0000269PubMed:16917507, ECO:0000269PubMed:20231426, ECO:0000269PubMed:20307497, ECO:0000269PubMed:20579985, ECO:0000269PubMed:20637728}.

Subcellular Localization

Nucleus, PML body {ECO:0000269PubMed:10535925, ECO:0000269PubMed:11078605, ECO:0000269PubMed:14990717, ECO:0000269PubMed:20579985, ECO:0000269PubMed:9748262}. Cytoplasm {ECO:0000250}.Isoform 2: Nucleus. Cytoplasm. Note=Isoform 2 seems to be both nuclear and cytoplasmic.

Disease Associations

Tissue Specificity

Ubiquitous. Abundant in muscle, heart, small intestine, stomach, kidney and brain; and low in testis, skin and lung. {ECO:0000269PubMed:11078605, ECO:0000269PubMed:11798164, ECO:0000269PubMed:14990717}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 18 experimentally validated interaction(s) in this database.
They are also associated with 49 interaction(s) predicted by orthology.

Experimentally validated
Total	18 [view]
Protein-Protein	18 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	49 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001102	RNA polymerase II activating transcription factor binding
GO:0001105	RNA polymerase II transcription coactivator activity
GO:0003714	transcription corepressor activity
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0016773	phosphotransferase activity, alcohol group as acceptor
GO:0046332	SMAD binding
GO:0046790	virion binding

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0001934	positive regulation of protein phosphorylation
GO:0006351	transcription, DNA-templated
GO:0006468	protein phosphorylation
GO:0006978	DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator
GO:0007179	transforming growth factor beta receptor signaling pathway
GO:0007224	smoothened signaling pathway
GO:0007628	adult walking behavior
GO:0008284	positive regulation of cell proliferation
GO:0008344	adult locomotory behavior
GO:0009103	lipopolysaccharide biosynthetic process
GO:0009952	anterior/posterior pattern specification
GO:0010842	retina layer formation
GO:0018105	peptidyl-serine phosphorylation
GO:0018107	peptidyl-threonine phosphorylation
GO:0030182	neuron differentiation
GO:0030511	positive regulation of transforming growth factor beta receptor signaling pathway
GO:0030514	negative regulation of BMP signaling pathway
GO:0032092	positive regulation of protein binding
GO:0042771	intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:0043388	positive regulation of DNA binding
GO:0043524	negative regulation of neuron apoptotic process
GO:0045766	positive regulation of angiogenesis
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0046330	positive regulation of JNK cascade
GO:0048596	embryonic camera-type eye morphogenesis
GO:0050882	voluntary musculoskeletal movement
GO:0051091	positive regulation of sequence-specific DNA binding transcription factor activity
GO:0060059	embryonic retina morphogenesis in camera-type eye
GO:0060235	lens induction in camera-type eye
GO:0060395	SMAD protein signal transduction
GO:0061072	iris morphogenesis

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005813	centrosome
GO:0016020	membrane
GO:0016604	nuclear body
GO:0016605	PML body
GO:0031965	nuclear membrane

Protein Structure and Domains

PDB ID

MGI:1314872

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine- /dual specificity protein kinase, catalytic domain
IPR010440 Lipopolysaccharide kinase
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF06293

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt