Free for academic non-profit institutions. Other users need a Commercial license

Aliases for HIPK2 Gene

Aliases for HIPK2 Gene

  • Homeodomain Interacting Protein Kinase 2 2 3 5
  • EC 2.7.11.1 4 63
  • HHIPk2 3 4
  • Homeodomain-Interacting Protein Kinase 2 2
  • PRO0593 3

External Ids for HIPK2 Gene

Previous GeneCards Identifiers for HIPK2 Gene

  • GC07M137598
  • GC07M138657
  • GC07M138671
  • GC07M138714
  • GC07M138907
  • GC07M139246
  • GC07M133556

Summaries for HIPK2 Gene

Entrez Gene Summary for HIPK2 Gene

  • This gene encodes a conserved serine/threonine kinase that is a member of the homeodomain-interacting protein kinase family. The encoded protein interacts with homeodomain transcription factors and many other transcription factors such as p53, and can function as both a corepressor and a coactivator depending on the transcription factor and its subcellular localization. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

GeneCards Summary for HIPK2 Gene

HIPK2 (Homeodomain Interacting Protein Kinase 2) is a Protein Coding gene. Diseases associated with HIPK2 include hypoxia and pilocytic astrocytoma. Among its related pathways are Gene Expression and Cardiac conduction. GO annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is HIPK4.

UniProtKB/Swiss-Prot for HIPK2 Gene

  • 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.

Gene Wiki entry for HIPK2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HIPK2 Gene

Genomics for HIPK2 Gene

Regulatory Elements for HIPK2 Gene

Promoters for HIPK2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around HIPK2 on UCSC Golden Path with GeneCards custom track

Genomic Location for HIPK2 Gene

Chromosome:
7
Start:
139,561,570 bp from pter
End:
139,777,894 bp from pter
Size:
216,325 bases
Orientation:
Minus strand

Genomic View for HIPK2 Gene

Genes around HIPK2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HIPK2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HIPK2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HIPK2 Gene

Proteins for HIPK2 Gene

  • Protein details for HIPK2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9H2X6-HIPK2_HUMAN
    Recommended name:
    Homeodomain-interacting protein kinase 2
    Protein Accession:
    Q9H2X6
    Secondary Accessions:
    • Q75MR7
    • Q8WWI4
    • Q9H2Y1

    Protein attributes for HIPK2 Gene

    Size:
    1198 amino acids
    Molecular mass:
    130966 Da
    Quaternary structure:
    • 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.
    Miscellaneous:
    • 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 (PubMed:20514025).

    Alternative splice isoforms for HIPK2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for HIPK2 Gene

Proteomics data for HIPK2 Gene at MOPED

Post-translational modifications for HIPK2 Gene

  • Autophosphorylation at Tyr-361 in the activation loop activates the kinase and promotes nuclear localization.
  • Cleaved at Asp-923 and Asp-984 by CASP6 in a p53/TP53-dependent manner. The cleaved form lacks the autoinhibitory C-terminal domain (AID), resulting in a hyperactive kinase, which potentiates p53/TP53 Ser-46 phosphorylation and subsequent activation of the cell death machinery.
  • Sumoylated. When conjugated it is directed to nuclear speckles. Desumoylated by SENP1 (By similarity). Sumoylation on Lys-32 is promoted by the E3 SUMO-protein ligase CBX4.
  • Ubiquitinated by FBXO3, WSB1 and SIAH1, leading to rapid proteasome-dependent degradation. The degradation mediated by FBXO3, but not ubiquitination, is prevented in the presence of PML. The degradation mediated by WSB1 and SIAH1 is reversibly reduced upon DNA damage.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for HIPK2 Gene

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for HIPK2 (HIPK2)

Domains & Families for HIPK2 Gene

Gene Families for HIPK2 Gene

Suggested Antigen Peptide Sequences for HIPK2 Gene

Graphical View of Domain Structure for InterPro Entry

Q9H2X6

UniProtKB/Swiss-Prot:

HIPK2_HUMAN :
  • Contains 1 protein kinase domain.
  • Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. HIPK subfamily.
Domain:
  • Contains 1 protein kinase domain.
Family:
  • Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. HIPK subfamily.
genes like me logo Genes that share domains with HIPK2: view

Function for HIPK2 Gene

Molecular function for HIPK2 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a protein = ADP + a phosphoprotein.
UniProtKB/Swiss-Prot 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.
UniProtKB/Swiss-Prot Induction:
Unstable in unstressed cells but stabilized upon DNA damage. Induced by UV irradiation and other genotoxic agents (adriamycin ADR, cisplatin CDDP, etoposide, IR, roscovitin), thus triggering p53/TP53 apoptotic response. Consistutively negatively regulated by SIAH1 and WSB1 through proteasomal degradation. This negative regulation is impaired upon genotoxic stress. Repressed upon hypoxia (often associated with tumors), through MDM2- (an E3 ubiquitin ligases) mediated proteasomal degradation, thus inactivating p53/TP53 apoptotic response. This hypoxia repression is reversed by zinc. The stabilization mediated by DNA damage requires the damage checkpoint kinases ATM and ATR.

Enzyme Numbers (IUBMB) for HIPK2 Gene

genes like me logo Genes that share phenotypes with HIPK2: view

Animal Models for HIPK2 Gene

MGI Knock Outs for HIPK2:

Animal Model Products

  • Taconic Biosciences Mouse Models for HIPK2

No data available for Gene Ontology (GO) - Molecular Function , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for HIPK2 Gene

Localization for HIPK2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for HIPK2 Gene

Nucleus, PML body. Cytoplasm. Note=Concentrated in PML/POD/ND10 nuclear bodies. Small amounts are cytoplasmic.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for HIPK2 Gene COMPARTMENTS Subcellular localization image for HIPK2 gene
Compartment Confidence
nucleus 5
cytosol 2

Gene Ontology (GO) - Cellular Components for HIPK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005654 nucleoplasm TAS --
GO:0090575 RNA polymerase II transcription factor complex ISS --
genes like me logo Genes that share ontologies with HIPK2: view

Pathways & Interactions for HIPK2 Gene

genes like me logo Genes that share pathways with HIPK2: view

SIGNOR curated interactions for HIPK2 Gene

Activates:
Inactivates:
Is inactivated by:

Gene Ontology (GO) - Biological Process for HIPK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription from RNA polymerase II promoter IEA --
GO:0006351 transcription, DNA-templated IEA --
GO:0006468 protein phosphorylation IEA,IDA 19448668
GO:0007179 transforming growth factor beta receptor signaling pathway IEA --
GO:0007628 adult walking behavior IEA --
genes like me logo Genes that share ontologies with HIPK2: view

Drugs & Compounds for HIPK2 Gene

(5) Drugs for HIPK2 Gene - From: HMDB, Novoseek, and DGIdb

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Adenosine triphosphate Approved Nutra 0
Vadimezan Pharma Vascular disrupting agents (VDA) 18

(1) Additional Compounds for HIPK2 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
genes like me logo Genes that share compounds with HIPK2: view

Transcripts for HIPK2 Gene

Unigene Clusters for HIPK2 Gene

Homeodomain interacting protein kinase 2:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for HIPK2 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8a · 8b ^ 9 ^ 10 ^ 11 ^ 12a · 12b ^ 13a · 13b ^ 14 ^ 15
SP1: - -
SP2: -
SP3:

Relevant External Links for HIPK2 Gene

GeneLoc Exon Structure for
HIPK2
ECgene alternative splicing isoforms for
HIPK2

Expression for HIPK2 Gene

mRNA expression in normal human tissues for HIPK2 Gene

mRNA differential expression in normal tissues according to GTEx for HIPK2 Gene

This gene is overexpressed in Brain - Spinal cord (cervical c-1) (x5.7), Brain - Amygdala (x5.0), Brain - Substantia nigra (x4.6), Brain - Hippocampus (x4.4), and Brain - Putamen (basal ganglia) (x4.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for HIPK2 Gene



SOURCE GeneReport for Unigene cluster for HIPK2 Gene Hs.731417

mRNA Expression by UniProt/SwissProt for HIPK2 Gene

Q9H2X6-HIPK2_HUMAN
Tissue specificity: Highly expressed in heart, muscle and kidney. Weakly expressed in a ubiquitous way. Down-regulated in several thyroid and breast tumors.
genes like me logo Genes that share expression patterns with HIPK2: view

Primer Products

In Situ Assay Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Protein differential expression in normal tissues and Protein tissue co-expression partners for HIPK2 Gene

Orthologs for HIPK2 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for HIPK2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia HIPK2 35
  • 99.5 (n)
  • 99.83 (a)
HIPK2 36
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia HIPK2 36
  • 96 (a)
OneToOne
dog
(Canis familiaris)
Mammalia HIPK2 36
  • 93 (a)
OneToOne
HIPK2 35
  • 92.8 (n)
  • 97.93 (a)
mouse
(Mus musculus)
Mammalia Hipk2 16
Hipk2 35
  • 90.99 (n)
  • 96.99 (a)
Hipk2 36
  • 97 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia HIPK2 36
  • 95 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia HIPK2 36
  • 79 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Hipk2 35
  • 90.93 (n)
  • 96.9 (a)
chicken
(Gallus gallus)
Aves HIPK2 36
  • 93 (a)
OneToOne
HIPK2 35
  • 84.76 (n)
  • 93.95 (a)
lizard
(Anolis carolinensis)
Reptilia HIPK2 36
  • 93 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia hipk2 35
  • 75.57 (n)
  • 82.6 (a)
Str.10767 35
zebrafish
(Danio rerio)
Actinopterygii hipk2 36
  • 80 (a)
OneToOne
hipk2 35
  • 76.23 (n)
  • 81.8 (a)
wufk56d12 35
fruit fly
(Drosophila melanogaster)
Insecta hipk 36
  • 34 (a)
OneToMany
CG17090 37
  • 55 (a)
worm
(Caenorhabditis elegans)
Secernentea hpk-1 36
  • 41 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes YAK1 36
  • 25 (a)
OneToMany
Species with no ortholog for HIPK2:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for HIPK2 Gene

ENSEMBL:
Gene Tree for HIPK2 (if available)
TreeFam:
Gene Tree for HIPK2 (if available)

Paralogs for HIPK2 Gene

(7) SIMAP similar genes for HIPK2 Gene using alignment to 4 proteins:

genes like me logo Genes that share paralogs with HIPK2: view

Variants for HIPK2 Gene

Sequence variations from dbSNP and Humsavar for HIPK2 Gene

SNP ID Clin Chr 07 pos Sequence Context AA Info Type
VAR_040547 -
VAR_040548 -
rs1077374 -- 139,751,580(+) gatgg(A/T)tggat intron-variant
rs1015122 -- 139,755,044(-) CATGC(C/T)GGAAG intron-variant
rs1045888 -- 139,566,196(-) ACCCT(G/T)TGCCA utr-variant-3-prime

Structural Variations from Database of Genomic Variants (DGV) for HIPK2 Gene

Variant ID Type Subtype PubMed ID
esv2735212 CNV Deletion 23290073
nsv824316 CNV Gain 20364138
esv2663283 CNV Deletion 23128226
esv271548 CNV Insertion 20981092
nsv824317 CNV Loss 20364138
nsv464732 CNV Gain 19166990

Variation tolerance for HIPK2 Gene

Gene Damage Index Score: 2.04; 37.42% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for HIPK2 Gene

HapMap Linkage Disequilibrium report
HIPK2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HIPK2 Gene

Disorders for HIPK2 Gene

MalaCards: The human disease database

(2) MalaCards diseases for HIPK2 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
hypoxia
pilocytic astrocytoma
  • grade i astrocytic tumor
- elite association - COSMIC cancer census association via MalaCards
Search HIPK2 in MalaCards View complete list of genes associated with diseases

Relevant External Links for HIPK2

Genetic Association Database (GAD)
HIPK2
Human Genome Epidemiology (HuGE) Navigator
HIPK2
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
HIPK2
genes like me logo Genes that share disorders with HIPK2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for HIPK2 Gene

Publications for HIPK2 Gene

  1. Targeting hypoxia in cancer cells by restoring homeodomain interacting protein-kinase 2 and p53 activity and suppressing HIF- 1alpha. (PMID: 19714248) Nardinocchi L. … D'Orazi G. (PLoS ONE 2009) 3 4 23 67
  2. Human homeodomain-interacting protein kinase-2 (HIPK2) is a member of the DYRK family of protein kinases and maps to chromosome 7q32-q34. (PMID: 11120354) Hofmann T.G. … Schmitz M.L. (Biochimie 2000) 2 3 23
  3. Homeodomain interacting protein kinase 2: a target for Alzheimer's beta amyloid leading to misfolded p53 and inappropriate cell survival. (PMID: 20418953) Lanni C. … Racchi M. (PLoS ONE 2010) 3 23
  4. Inhibition of HIF-1alpha activity by homeodomain-interacting protein kinase-2 correlates with sensitization of chemoresistant cells to undergo apoptosis. (PMID: 19128456) Nardinocchi L. … D'Orazi G. (Mol. Cancer 2009) 3 23
  5. How cells switch HIPK2 on and off. (PMID: 18974774) Sombroek D. … Hofmann T.G. (Cell Death Differ. 2009) 3 23

Products for HIPK2 Gene

Sources for HIPK2 Gene

Back to Top

Content