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FLASH GENE
Symbol HIPK2 contributors: mct - updated : 13-07-2016
HGNC name homeodomain interacting protein kinase 2
HGNC id 14402
Location 7q34      Physical location : 139.246.316 - 139.477.693
Synonym symbol(s) PRO0593, HIK2, DKFZp686K02111, FLJ23711
EC.number 2.7.11.1
DNA
TYPE functioning gene
STRUCTURE 96.05 kb     14 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
14 - 15245 131 1198 - 2009 19043406
isoform 1
14 - 15164 - 1171 - 2009 19043406
isoform 2
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart    
Endocrineneuroendocrinepituitary  highly
 parathyroid   highly
Nervousbrain   highly
Urinarykidney    
cell lineage
cell lines
fluid/secretion
at STAGE
Text expressed in the inner retina during late embryogenesis, and found in neural tissues, including optic vesicles
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal kinase domain
  • serine-threonine protein kinases, catalytic domain
  • DYRK consensus motif within the kinase domain
  • an interaction domain for homeodomain transcription factors
  • an autoinhibitory domain
  • HOMOLOGY
    interspecies homolog to murine Hipk2
    intraspecies homolog to HIPK3
    Homologene
    FAMILY
  • protein kinase superfamily
  • CMGC Ser/Thr protein kinase family
  • HIPK subfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    text
  • colocalized with TP73 and TP53 in nuclear bodies
  • predominant localization in subnuclear HIPK domains, and small amounts in the cytosol and nucleoplasm
  • colocalizes with ZYX at the cytoskeleton and in the cell nucleus
  • HIPK2 colocalizes with its ubiquitin ligase SIAH1 at nuclear bodies, suggesting that these nuclear domains are the site of HIPK2 ubiquitination
  • basic FUNCTION
  • playing a role as corepressor for homeodomain transcription factor
  • modulating functions of the TP53 family
  • phosphorylating the antiapoptotic factor CTBP1 and promoting its proteasomal degradation
  • in the Wnt/beta-catenin signaling pathway acting as an intermediate kinase between TAK1 and NLK to promote
  • the proteasomal degradation of c-Myb
  • contributes to drug-induced modulation of MDM2 activity at transcriptional and posttranscriptional levels
  • implicated in regulating various intracellular signalings, such as TGF-beta, BMP, Notch and Wnt signaling
  • tumor suppressor that controls proliferation by antagonizing LEF1/CTNNB1-mediated transcription
  • having an important role as a negative regulator of gene expression, its elimination from promoter-associated repressor complexes allows the induction of a substantial fraction of hypoxia-induced genes
  • implicated in restraining tumor progression by more than one mechanism, involving both its catalytic and transcriptional co-repressor functions
  • phosphorylates ZBTB4 undern ormal condition sof cell growth and down-regulates it
  • phosphorylating MECP2
  • function as a novel negative regulator of beta-catenin through its phosphorylation and proteasomal degradation
  • negative regulator of Wnt signaling operating via the direct phosphorylation and degradation of beta-catenin, a key component of the Wnt signaling pathway
  • with HIPK1, are involved in regulation of eye size, lens formation and retinal lamination during late embryogenesis
  • may function as cell-intrinsic determinants of cell migration in the retina
  • emerging player in cell response to genotoxic agents that senses damage intensity and contributes to the cell choice between cell cycle arrest and apoptosis
  • serine/threonine kinase that acts as a coregulator of an increasing number of factors involved in cell survival and proliferation during development and in response to different types of stress
  • stabilizes CDKN1B by its phosphorylation at serine 10 and contributes to cell motility
  • role of HIPK1, HIPK2 in connecting TGFB1 signaling pathway with the transcriptional programs critical for angiogenesis in early embryonic development
  • plays a key role in radiosensitivity and chemosensitivity
  • conserved function of HIPK2 and PIN1 in the DNA damage-induced apoptosis response
  • is an essential regulator of white fat development
  • HIPK1, HIPK2, HIPK3 share the mechanism of activation by tyrosine autophosphorylation with the closely related DYRK family (dual-specificity tyrosine phosphorylation regulated kinase)
  • is required to complete cytokinesis and impaired HIPK2 expression results in cytokinesis failure and tetraploidization
  • acts as a caretaker gene, whose inactivation increases tumorigenicity and causes chromosomal instability (CIN) by cytokinesis failure
  • highly conserved serine/threonine kinase and is involved in transcriptional regulation
  • importance of HIPK2 in stress mediated cell death, and is a generic stress kinase that gets activated by diverse set of physiological stressors
  • functions as a regulator of developmental processes and as a signal integrator of a wide variety of stress signals, such as DNA damage, hypoxia, and reactive oxygen intermediates
  • role of HIPK2 activation in ER-stress-mediated neurodegeneration
  • regulates malignant growth via phosphorylation of NOTCH1
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • TRADD
  • interacting with TP53 and TP73, playing a role in cell cycle regulation and apoptosis
  • interacting with TP53INP1
  • interaction with CHMP4B
  • interacts with MDM2 and promotes its nuclear export and proteasomal degradation, in p53-null cellular context
  • interacting PML
  • regulated interaction between the serine/threonine kinase HIPK2 and the ubiquitin E3 ligase SIAH2 as a mechanism controlling the hypoxic response
  • interacting with PML and phosphorylating PML at serines 8 and 38 (contribute to the DNA damage-induced PML SUMOylation and are required for the ability of PML to cooperate with HIPK2 for the induction of cell death)
  • phosphorylates HMGA1 at Ser-35, Thr-52, and Thr-77 and modulates its DNA binding affinity
  • DCAF7 is an interactor of the kinase homeodomain-interacting protein kinase 2 (HIPK2)
  • interacting with ZYX, a novel regulator of the HIPK2-TP53 signaling axis in response to DNA damage
  • HIPK2, a proapoptotic kinase, is involved in AATF degradation (HIPK2 interacts with AATF and, upon genotoxic stress, phosphorylates it at specific residues)
  • PIN1 couples HIPK2 activation to its stabilization and is essential for DNA damage-induced apoptosis in cancer cells
  • PIN1 regulates SIAH1–mediated HIPK2 ubiquitination and degradation
  • SIRT1 negatively regulates the protein stability of HIPK2
  • accumulation of HIPK2 in nuclear speckles and association with promyelocytic leukemia protein (PML) in response to DNA damage were also dependent on ABL1 activity
  • complex regulation of CREBBP activity by HIPK2, which might be relevant for the control of specific sets of target genes involved in cellular proliferation, differentiation and apoptosis
  • HIPK2 and HIPK1 restrict CNOT2-dependent mRNA decay
  • cell & other
    REGULATION
    activated by activated in response to morphogenic signals or DNA damage
    ABL1 (ABL1 protected HIPK2 from degradation mediated by the ubiquitin E3 ligase SIAH1)
    Other HIPK2 activity and apoptotic function is modulated by autophosphorylation at Thr880/Ser882
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral        
    synergizes with activation of H-ras to induce tumorigenesis, and leads to an expansion of epidermal stem cells due to increased proliferation
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker potential role as a biomarker and therapeutic target for ALS
    Therapy target
    ANIMAL & CELL MODELS