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Aliases for HIPK2 Gene

Aliases for HIPK2 Gene

  • Homeodomain Interacting Protein Kinase 2 2 3
  • Homeodomain-Interacting Protein Kinase 2 2 3
  • EC 2.7.11.1 4 64
  • HHIPk2 3 4
  • PRO0593 3

External Ids for HIPK2 Gene

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. Among its related pathways are ERK Signaling and Translational Control. GO annotations related to this gene include protein serine/threonine kinase activity and transcription corepressor activity. An important paralog of this gene is DYRK1B.

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

Genomic Location for HIPK2 Gene

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

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for HIPK2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HIPK2 Gene

Regulatory Elements 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
  • Ubiquitination at Lys430 and Lys552

Other Protein References for HIPK2 Gene

Domains for HIPK2 Gene

Gene Families for HIPK2 Gene

UniProtKB/Swiss-Prot:

HIPK2_HUMAN
Domain:
  • Contains 1 protein kinase domain.:
    • Q9H2X6
Family:
  • Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. HIPK subfamily.:
    • Q9H2X6
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

Gene Ontology (GO) - Molecular Function for HIPK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001102 RNA polymerase II activating transcription factor binding ISS --
GO:0001105 contributes_to RNA polymerase II transcription coactivator activity ISS --
GO:0003714 transcription corepressor activity IDA 12874272
GO:0004672 protein kinase activity IDA 19448668
GO:0004674 protein serine/threonine kinase activity ISS --
genes like me logo Genes that share ontologies with HIPK2: view
genes like me logo Genes that share phenotypes with HIPK2: view

Animal Models for HIPK2 Gene

MGI Knock Outs for HIPK2:

No data available for Transcription Factor Targeting 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
cytoskeleton 4
cytosol 2

Gene Ontology (GO) - Cellular Components for HIPK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA --
GO:0005737 cytoplasm ISS --
GO:0016020 membrane --
GO:0016604 nuclear body TAS 14626429
GO:0016605 colocalizes_with PML body IDA 14647468
genes like me logo Genes that share ontologies with HIPK2: view

Pathways for HIPK2 Gene

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

Pathways by source for HIPK2 Gene

1 R&D Systems pathway for HIPK2 Gene
2 Qiagen pathways for HIPK2 Gene

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:0001654 eye development ISS 20579985
GO:0001934 positive regulation of protein phosphorylation IEA --
GO:0006351 transcription, DNA-templated IEA --
GO:0006468 protein phosphorylation IDA 19448668
genes like me logo Genes that share ontologies with HIPK2: view

Compounds for HIPK2 Gene

(2) HMDB Compounds for HIPK2 Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
ADP
  • adenosindiphosphorsaeure
58-64-0

(3) Novoseek inferred chemical compound relationships for HIPK2 Gene

Compound -log(P) Hits PubMed IDs
threonine 65.8 14
serine 52.2 13
cisplatin 19.9 8
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 expression in embryonic tissues and stem cells from LifeMap Discovery

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

This gene is overexpressed in Brain - Spinal cord (cervical c-1) (5.7), Brain - Amygdala (5.0), Brain - Substantia nigra (4.6), Brain - Hippocampus (4.4), and Brain - Putamen (basal ganglia) (4.4).

Integrated Proteomics: protein expression 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 expressions with HIPK2: view

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 36
  • 99.5 (n)
  • 99.83 (a)
HIPK2 37
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia HIPK2 37
  • 96 (a)
OneToOne
dog
(Canis familiaris)
Mammalia HIPK2 36
  • 92.8 (n)
  • 97.93 (a)
HIPK2 37
  • 93 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Hipk2 36
  • 90.99 (n)
  • 96.99 (a)
Hipk2 16
Hipk2 37
  • 97 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia HIPK2 37
  • 95 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia HIPK2 37
  • 79 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Hipk2 36
  • 90.93 (n)
  • 96.9 (a)
chicken
(Gallus gallus)
Aves HIPK2 36
  • 84.76 (n)
  • 93.95 (a)
HIPK2 37
  • 93 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia HIPK2 37
  • 93 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia hipk2 36
  • 75.57 (n)
  • 82.6 (a)
Str.10767 36
zebrafish
(Danio rerio)
Actinopterygii hipk2 36
  • 76.23 (n)
  • 81.8 (a)
hipk2 37
  • 80 (a)
OneToOne
wufk56d12 36
fruit fly
(Drosophila melanogaster)
Insecta hipk 37
  • 34 (a)
OneToMany
CG17090 38
  • 55 (a)
worm
(Caenorhabditis elegans)
Secernentea hpk-1 37
  • 41 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes YAK1 37
  • 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

Selected 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 MAF
rs15542 -- 139,563,885(-) CCAAA(A/C)TGCAG utr-variant-3-prime
rs740818 -- 139,752,591(-) CTGAG(A/G)GAATC intron-variant
rs1011017 -- 139,763,766(-) agtgc(C/T)ctgag intron-variant
rs1011018 -- 139,763,465(-) TGTTC(C/T)GGCAA intron-variant
rs1015121 -- 139,755,585(-) GGAGA(A/G)AAAAG intron-variant

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

Relevant External Links for HIPK2 Gene

HapMap Linkage Disequilibrium report
HIPK2

Disorders for HIPK2 Gene

(3) Novoseek inferred disease relationships for HIPK2 Gene

Disease -log(P) Hits PubMed IDs
promyelocytic leukemia 69.5 4
tumors 32.4 37
cancer 17.9 7

Relevant External Links for HIPK2

Genetic Association Database (GAD)
HIPK2
Human Genome Epidemiology (HuGE) Navigator
HIPK2
genes like me logo Genes that share disorders with HIPK2: view

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

Publications for HIPK2 Gene

  1. The serine/threonine kinase HIPK2 interacts with TRADD, but not with CD95 or TNF-R1 in 293T cells. (PMID: 11032752) Li X. … Hug H. (Biochem. Biophys. Res. Commun. 2000) 3 4 23
  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. Isolation and characterization of cDNAs for the protein kinase HIPK2. (PMID: 11267674) Wang Y. … Hug H. (Biochim. Biophys. Acta 2001) 3 4 23
  4. Regulation of p53 activity by its interaction with homeodomain- interacting protein kinase-2. (PMID: 11740489) Hofmann T.G. … Schmitz M.L. (Nat. Cell Biol. 2002) 3 4 23
  5. The homeodomain-interacting protein kinase 2 gene is expressed late in embryogenesis and preferentially in retina, muscle, and neural tissues. (PMID: 11798164) Pierantoni G.M. … Fusco A. (Biochem. Biophys. Res. Commun. 2002) 3 4 23

Products for HIPK2 Gene

  • Addgene plasmids for HIPK2

Sources for HIPK2 Gene

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