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HIPK2 Gene

protein-coding   GIFtS: 61
GCID: GC07M139246

Homeodomain Interacting Protein Kinase 2

(Previous name: homeodomain-interacting protein kinase 2)
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Homeodomain Interacting Protein Kinase 21 2
Homeodomain-Interacting Protein Kinase 21 2
hHIPk22 3
EC 2.7.11.13 8
PRO05932

External Ids:    HGNC: 144021   Entrez Gene: 289962   Ensembl: ENSG000000643937   OMIM: 6068685   UniProtKB: Q9H2X63   

Export aliases for HIPK2 gene to outside databases

Previous GC identifers: GC07M137598 GC07M138657 GC07M138671 GC07M138714 GC07M138907 GC07M133556


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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 pilocytic astrocytoma, and keratoacanthoma. GO annotations related to this gene include protein serine/threonine kinase activity and transcription corepressor activity. An important paralog of this gene is DYRK1A.

UniProtKB/Swiss-Prot: HIPK2_HUMAN, Q9H2X6
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

Gene Wiki entry for HIPK2 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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Regulatory elements:
   Regulatory transcription factor binding sites in the HIPK2 gene promoter:
         STAT1   GATA-3   AML1a   ATF-2   CUTL1   YY1   GATA-1   GATA-2   c-Jun   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 15): HIPK2 promoter sequence
   Search Chromatin IP Primers for HIPK2

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat HIPK2


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 7q32-q34   Ensembl cytogenetic band:  7q34   HGNC cytogenetic band: 7q32-q34

HIPK2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
HIPK2 gene location

GeneLoc information about chromosome 7         GeneLoc Exon Structure

GeneLoc location for GC07M139246:  view genomic region     (about GC identifiers)

Start:
139,246,316 bp from pter      End:
139,477,577 bp from pter
Size:
231,262 bases      Orientation:
minus strand

1 alternative location:
Chr7-,CRA_TCAG 138,590,861-138,806,654     

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: HIPK2_HUMAN, Q9H2X6 (See protein sequence)
Recommended Name: Homeodomain-interacting protein kinase 2  
Size: 1198 amino acids; 130966 Da
Subunit: 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)
Secondary accessions: Q75MR7 Q8WWI4 Q9H2Y1
Alternative splicing: 3 isoforms:  Q9H2X6-1   Q9H2X6-2   Q9H2X6-3   

Explore the universe of human proteins at neXtProt for HIPK2: NX_Q9H2X6

Explore proteomics data for HIPK2 at MOPED

Post-translational modifications: 

  • Autophosphorylation at Tyr-361 in the activation loop activates the kinase and promotes nuclear localization1
  • 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 CBX41
  • 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 damage1
  • 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 machinery1
  • Ubiquitination2 at Lys430, Lys552
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for HIPK2 (Q9H2X6) (see all 13)
     ETLNHPF  SDTDEEE  HLLDFPHS  CGLKRKSEE 


    See HIPK2 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (2 alternative transcripts): 
    NP_001106710.1  NP_073577.3  

    ENSEMBL proteins: 
     ENSP00000385571   ENSP00000413724   ENSP00000343108  

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    Cloud-Clone Corp. ELISAs for HIPK2
    Cloud-Clone Corp. CLIAs for HIPK2


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    IUPHAR Guide to PHARMACOLOGY protein family classification: homeodomain interacting protein kinase 2
    HIPK subfamily

    5 InterPro protein domains:
     IPR017441 Protein_kinase_ATP_BS
     IPR002290 Ser/Thr_dual-sp_kinase_dom
     IPR011009 Kinase-like_dom
     IPR008271 Ser/Thr_kinase_AS
     IPR000719 Prot_kinase_dom

    Graphical View of Domain Structure for InterPro Entry Q9H2X6

    ProtoNet protein and cluster: Q9H2X6

    UniProtKB/Swiss-Prot: HIPK2_HUMAN, Q9H2X6
    Similarity: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. HIPK subfamily
    Similarity: Contains 1 protein kinase domain


    HIPK2 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: HIPK2_HUMAN, Q9H2X6
    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
    Catalytic activity: ATP + a protein = ADP + a phosphoprotein
    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 Number (IUBMB): EC 2.7.11.11 2

         Gene Ontology (GO): Selected molecular function terms (see all 12):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001102RNA polymerase II activating transcription factor binding ISS--
    GO:0001105contributes to RNA polymerase II transcription coactivator activity ISS--
    GO:0003714transcription corepressor activity IDA12874272
    GO:0004672protein kinase activity IDA19448668
    GO:0004674protein serine/threonine kinase activity ISS--
         
    HIPK2 for ontologies           About GeneDecksing


    Phenotypes:
         6 GenomeRNAi human phenotypes for HIPK2:
     Cell cycle / mitosis defect  Decreased nuclei size in G2M  Decreased substrate adherent c  Decreased viability 
     Increased viability with 4OH t  Wnt reporter downregulated 

         9 MGI mutant phenotypes (inferred from 3 alleles(MGI details for Hipk2):
     behavior/neurological  cellular  embryogenesis  growth/size/body  homeostasis/metabolism 
     mortality/aging  muscle  nervous system  vision/eye 

    HIPK2 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-out Hipk2tm1Hko for HIPK2

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for HIPK2
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       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for HIPK2

    miRNA
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    miRTarBase miRNAs that target HIPK2:
    hsa-mir-615-3p (MIRT040268), hsa-mir-18a-3p (MIRT040927), hsa-mir-222-3p (MIRT046799), hsa-mir-760 (MIRT036740), hsa-mir-183-5p (MIRT047166), hsa-mir-296-3p (MIRT038388), hsa-mir-149-5p (MIRT045503), hsa-mir-27a-3p (MIRT005357), hsa-mir-181a-5p (MIRT005577), hsa-mir-423-5p (MIRT038150)

    Block miRNA regulation of human, mouse, rat HIPK2 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate HIPK2 (see all 255):
    hsa-miR-579 hsa-miR-631 hsa-miR-128 hsa-miR-605 hsa-miR-3653 hsa-miR-3074-3p hsa-miR-342-3p hsa-miR-4275
    SwitchGear 3'UTR luciferase reporter plasmidHIPK2 3' UTR sequence
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat HIPK2

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    GenScript: all cDNA clones in your preferred vector (see all 2): HIPK2 (NM_001113239)
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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    HIPK2_HUMAN, Q9H2X6: Nucleus, PML body. Cytoplasm. Note=Concentrated in PML/POD/ND10 nuclear bodies. Small
    amounts are cytoplasmic
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    nucleus5
    cytoskeleton4
    cytosol2

    Gene Ontology (GO): Selected cellular component terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IDA--
    GO:0005737cytoplasm ISS--
    GO:0005813centrosome ----
    GO:0016020membrane ----
    GO:0016604nuclear body TAS14626429

    HIPK2 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for HIPK2 About   (see all 10)                                                                                              See pathways by source

    SuperPathContained pathways About
    1ERK Signaling
    Molecular Mechanisms of Cancer0.51
    2p53 Signaling
    p53 Signaling0.38
    3Wnt signaling pathway (KEGG)
    Wnt Signaling Pathway NetPath0.37
    4Apoptosis Signaling Pathways
    Apoptosis Signaling Pathways0.35
    5Cell Cycle / Checkpoint Control
    DNA Damage0.32

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 R&D Systems Pathway for HIPK2
        Apoptosis Signaling Pathways

    2 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for HIPK2
        Molecular Mechanisms of Cancer
    p53 Signaling

    3 Cell Signaling Technology (CST) Pathways for HIPK2
        Apoptosis and Autophagy
    Translational Control
    DNA Damage

    4 BioSystems Pathways for HIPK2
        Integrated Breast Cancer Pathway
    Wnt Signaling Pathway NetPath
    C-MYB transcription factor network
    p53 pathway



    HIPK2 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including HIPK2: 
              TGFB/BMP Signaling Pathway in human mouse rat
              Apoptosis 384HT in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for HIPK2

    Selected Interacting proteins for HIPK2 (Q9H2X61, 2, 3) via UniProtKB, MINT, STRING, and/or I2D (see all 63)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    DCAF7P619621, 2, 3EBI-348345,EBI-359808 MINT-8084976 MINT-8085254 MINT-8085171 MINT-8088896 MINT-8085240 MINT-8085226 MINT-8084962 MINT-8084992 MINT-8084886 MINT-8084902 MINT-8085008 I2D: score=1 
    RUNX1Q011961, 2, 3EBI-348345,EBI-925904 MINT-2982465 MINT-2982510 MINT-2982487 MINT-2984544 I2D: score=3 
    EP300Q094721, 2, 3EBI-348345,EBI-447295 MINT-2982635 MINT-2982535 MINT-2982577 MINT-2984574 I2D: score=2 
    MECP2P516081, 2, 3EBI-348345,EBI-1189067 MINT-7308929 MINT-7308914 I2D: score=1 
    MDM2Q009872, 3MINT-68740 MINT-68741 MINT-68739 MINT-68745 MINT-68746 I2D: score=2 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 38):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000122negative regulation of transcription from RNA polymerase II promoter IEA--
    GO:0001654eye development ISS--
    GO:0006468protein phosphorylation IDA19448668
    GO:0006978DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator IDA14647468
    GO:0007179transforming growth factor beta receptor signaling pathway IEA--

    HIPK2 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
    About This Section

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    Browse Small Molecules at EMD Millipore
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      Browse compounds at ApexBio 

    Browse Tocris compounds for HIPK2

    2 HMDB Compounds for HIPK2    About this table
    CompoundSynonyms CAS #PubMed Ids
    ADPadenosindiphosphorsaeure (see all 8)58-64-0--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--

    3 Novoseek inferred chemical compound relationships for HIPK2 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    threonine 65.8 27 15122315 (1), 15708980 (1), 15897882 (1), 18981727 (1) (see all 14)
    serine 52.2 25 11532197 (2), 15708980 (1), 15897882 (1), 11740489 (1) (see all 12)
    cisplatin 19.9 12 14729469 (5), 15897882 (1), 18395248 (1), 11925430 (1)



    HIPK2 for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for HIPK2 gene (2 alternative transcripts): 
    NM_001113239.2  NM_022740.4  

    3 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000406875(uc003vvd.4 uc003vvf.4) ENST00000428878 ENST00000342645

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      QuantiTect SYBR Green Assays in human, mouse, rat HIPK2
      QuantiFast Probe-based Assays in human, mouse, rat HIPK2

    Selected AceView cDNA sequences (see all 425):

    BM995735 AL833223 CA418359 BQ938536 T34485 BG059872 BX955135 BQ083195 
    BM707936 CD722561 AI288943 BM679184 AA364909 AI421394 CA868458 AL706915 
    AI493318 AI868491 H94216 BU177127 BQ639019 BQ227272 Z41203 BX647377 

    GeneLoc Exon Structure

    3 Alternative Splicing Database (ASD) splice patterns (SP) for HIPK2    About this scheme

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


    ECgene alternative splicing isoforms for HIPK2

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    HIPK2 expression in normal human tissues (normalized intensities)      HIPK2 embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: ACGTCGTGTG
    HIPK2 Expression
    About this image


    HIPK2 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 13) fully expand
     
     Brain (Nervous System)    fully expand to see all 9 entries
             Cerebral Cortex
     
     Neural Tube (Nervous System)    fully expand to see all 3 entries
             Metencephalon
     
     Ovary (Reproductive System)    fully expand to see all 2 entries
             Ovarian Mesenchymal Stroma Cells Ovary Interstitium
             Oviduct
     
     Primitive Streak (Early Embryonic Tissues)
             Primitive streak-like cells
     
     Bone (Muscoskeletal System)
             Bone Marrow
    HIPK2 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    HIPK2 Protein Expression

    UniProtKB/Swiss-Prot: HIPK2_HUMAN, Q9H2X6
    Tissue specificity: Highly expressed in heart, muscle and kidney. Weakly expressed in a ubiquitous way.
    Down-regulated in several thyroid and breast tumors

        Pathway & Disease-focused RT2 Profiler PCR Arrays including HIPK2: 
              TGFB/BMP Signaling Pathway in human mouse rat
              Apoptosis 384HT in human mouse rat

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    In Situ
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for HIPK2

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals and fungi.

    Orthologs for HIPK2 gene from Selected species (see all 16)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Hipk21 , 5 homeodomain interacting protein kinase 21, 5 90.99(n)1
    96.99(a)1
      6 (17.85 cM)5
    152581  NM_010433.21  NP_034563.21 
     386943905 
    chicken
    (Gallus gallus)
    Aves HIPK21 homeodomain interacting protein kinase 2 84.76(n)
    93.95(a)
      374138  XM_004937847.1  XP_004937904.1 
    lizard
    (Anolis carolinensis)
    Reptilia HIPK26
    homeodomain interacting protein kinase 2
    93(a)
    1 ↔ 1
    5(16673140-16845817)
    African clawed frog
    (Xenopus laevis)
    Amphibia BJ071036.12   -- 78.38(n)    BJ071036.1 
    zebrafish
    (Danio rerio)
    Actinopterygii wufk56d122 Transcribed sequence with weak similarity to protein more 79.37(n)    BG306073.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta CG170903 protein amino acid phosphorylation
    protein kinase
    55(a)     --
    worm
    (Caenorhabditis elegans)
    Secernentea hpk-16
    Protein HPK-1, isoform c (hpk-1) mRNA, complete cd...
    41(a)
    1 → many
    X(4210654-4217290) WBGene00001994
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes YAK16
    Serine-threonine protein kinase; component of a gl...
    25(a)
    1 → many
    X(147967-150390) YJL141C


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for HIPK2 gene
    DYRK1A2  DYRK22  DYRK32  HIPK12  ENSG000002729212  DYRK42  HIPK32  HIPK42  
    DYRK1B2  
    7 SIMAP similar genes for HIPK2 using alignment to 4 protein entries:     HIPK2_HUMAN (see all proteins):
    HIPK1    HIPK4    HIPK3    MAPK14    CDK4    DYRK1A
    CLK1

    HIPK2 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for HIPK2 (see all 4106)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 7 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1176742531,2
    F--138590376(+) ACTGCA/TTGGGA 2 -- int11Minor allele frequency- T:0.01NA 120
    rs745644451,2
    C--138590405(+) CAAGG-/CCCCCC 2 -- int10--------
    rs1925480361,2
    --138590503(+) TGCCTA/GTAATC 2 -- int10--------
    rs1848456001,2
    --138590716(+) AGGATC/TGTGCC 2 -- int10--------
    rs1134510411,2
    C,F--138590857(+) AGGCAG/AGTGTA 2 -- int12Minor allele frequency- A:0.02CSA WA 120
    rs1894452191,2
    --138591026(+) ATAACA/GTAGTT 2 -- ut310--------
    rs114775341,2
    C--138591045(+) TGGGA-/CCCCCC 2 -- ut310--------
    rs2001354371,2
    --138591055(+) CCCCC-/TTTTTC 2 -- ut310--------
    rs2011252661,2
    C--138591073(+) TACAG-/TAGAGTAA 2 -- cds10--------
    rs1453781591,2
    C--138591288(+) TTTCTC/TGTAAA 2 -- ut310--------

    HapMap Linkage Disequilibrium report for HIPK2 (139246316 - 139477577 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 6 variations for HIPK2:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2663283CNV Deletion23128226
    esv2735212CNV Deletion23290073
    esv271548CNV Insertion20981092
    nsv824317CNV Loss20364138
    nsv824316CNV Gain20364138
    nsv464732CNV Gain19166990

    Site Specific Mutation Identification with PCR Assays
    1 Copy Number PCR Panel containing HIPK2:
    Glioma
    Search QIAGEN SeqTarget long-range PCR primers for resequencing HIPK2
    DNA2.0 Custom Variant and Variant Library Synthesis for HIPK2

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 606868    OMIM disorders: --

    Selected diseases for HIPK2 (see all 32):    About MalaCards
    pilocytic astrocytoma    keratoacanthoma    astrocytoma    idiopathic pulmonary fibrosis
    duodenitis    epididymitis    pulmonary fibrosis    myelodysplastic syndromes
    herpes simplex    labyrinthitis    down syndrome    hypoxia
    cervical cancer    acute myeloid leukemia    kidney disease    cervicitis
    myeloid leukemia    leukemia    neuroblastoma    retinitis


    HIPK2 for disorders           About GeneDecksing

    3 Novoseek inferred disease relationships for HIPK2 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    promyelocytic leukemia 69.5 7 14647468 (1), 14678985 (1), 12851404 (1), 16253240 (1)
    tumors 32.4 63 19714248 (4), 19046997 (3), 18644116 (3), 19794125 (3) (see all 21)
    cancer 17.9 7 19828042 (1), 16467083 (1), 19714248 (1), 18395248 (1) (see all 7)

    Genetic Association Database (GAD): HIPK2
    Human Genome Epidemiology (HuGE) Navigator: HIPK2 (1 document)

    Export disorders for HIPK2 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for HIPK2 gene, integrated from 10 sources (see all 165):
    (articles sorted by number of sources associating them with HIPK2)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Targeting hypoxia in cancer cells by restoring homeodomain interacting protein-kinase 2 and p53 activity and suppressing HIF- 1alpha. (PubMed id 19714248)1, 2, 9 Nardinocchi L.... D'Orazi G. (PLoS ONE 2009)
    2. HIPK2 regulates transforming growth factor-beta-induced c-Jun NH(2)- terminal kinase activation and apoptosis in human hepatoma cells. (PubMed id 14678985)1, 2, 9 Hofmann T.G.... Will H. (Cancer Res. 2003)
    3. How cells switch HIPK2 on and off. (PubMed id 18974774)1, 2, 9 Sombroek D. and Hofmann T.G. (Cell Death Differ. 2009)
    4. Desumoylation of homeodomain-interacting protein kinase 2 (HIPK2) through the cytoplasmic-nuclear shuttling of the SUMO-specific protease SENP1. (PubMed id 16253240)1, 2, 9 Kim Y.H.... Kim Y. (FEBS Lett. 2005)
    5. TP53INP1s and homeodomain-interacting protein kinase-2 (HIPK2) are partners in regulating p53 activity. (PubMed id 12851404)1, 2, 9 Tomasini R.... Dusetti N.J. (J. Biol. Chem. 2003)
    6. Identification and characterization of HIPK2 interacting with p73 and modulating functions of the p53 family in vivo. (PubMed id 11925430)1, 2, 9 Kim E.-J.... Um S.-J. (J. Biol. Chem. 2002)
    7. The human protein kinase HIPK2 phosphorylates and downregulates the methyl-binding transcription factor ZBTB4. (PubMed id 19448668)1, 2, 9 Yamada D.... Defossez P.A. (Oncogene 2009)
    8. Control of HIPK2 stability by ubiquitin ligase Siah-1 and checkpoint kinases ATM and ATR. (PubMed id 18536714)1, 2, 9 Winter M.... Hofmann T.G. (Nat. Cell Biol. 2008)
    9. Transcriptional regulation of hypoxia-inducible factor 1alpha by HIPK2 suggests a novel mechanism to restrain tumor growth. (PubMed id 19046997)1, 2, 9 Nardinocchi L.... D'Orazi G. (Biochim. Biophys. Acta 2009)
    10. PML activates transcription by protecting HIPK2 and p300 from SCFFbx3-mediated degradation. (PubMed id 18809579)1, 2, 9 Shima Y....Kitabayashi I. (Mol. Cell. Biol. 2008)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 28996 HGNC: 14402 AceView: HIPK2 Ensembl:ENSG00000064393 euGenes: HUgn28996
    ECgene: HIPK2 H-InvDB: HIPK2

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for HIPK2 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for HIPK2 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section

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    Patent Information for HIPK2 gene:
    Search GeneIP for patents involving HIPK2

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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