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Q9QZR5

- HIPK2_MOUSE

UniProt

Q9QZR5 - HIPK2_MOUSE

Protein

Homeodomain-interacting protein kinase 2

Gene

Hipk2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 146 (01 Oct 2014)
      Sequence version 2 (27 Apr 2001)
      Previous versions | rss
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    Functioni

    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.10 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei228 – 2281ATPCurated
    Active sitei324 – 3241Proton acceptorCurated
    Sitei923 – 9242Cleavage; by CASP6By similarity
    Sitei984 – 9852Cleavage; by CASP6By similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi205 – 2139ATPCurated

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. protein binding Source: UniProtKB
    3. protein kinase activity Source: UniProtKB
    4. protein serine/threonine kinase activity Source: BHF-UCL
    5. RNA polymerase II activating transcription factor binding Source: BHF-UCL
    6. transcription corepressor activity Source: UniProtKB
    7. virion binding Source: UniProtKB

    GO - Biological processi

    1. adult locomotory behavior Source: MGI
    2. adult walking behavior Source: MGI
    3. anterior/posterior pattern specification Source: MGI
    4. DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator Source: Ensembl
    5. embryonic camera-type eye morphogenesis Source: DFLAT
    6. embryonic retina morphogenesis in camera-type eye Source: DFLAT
    7. intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: MGI
    8. iris morphogenesis Source: DFLAT
    9. lens induction in camera-type eye Source: DFLAT
    10. negative regulation of BMP signaling pathway Source: Ensembl
    11. negative regulation of neuron apoptotic process Source: MGI
    12. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    13. neuron differentiation Source: DFLAT
    14. peptidyl-serine phosphorylation Source: BHF-UCL
    15. peptidyl-threonine phosphorylation Source: BHF-UCL
    16. positive regulation of angiogenesis Source: Ensembl
    17. positive regulation of cell proliferation Source: MGI
    18. positive regulation of DNA binding Source: UniProtKB
    19. positive regulation of JNK cascade Source: UniProtKB
    20. positive regulation of protein binding Source: BHF-UCL
    21. positive regulation of protein phosphorylation Source: MGI
    22. positive regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
    23. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
    24. positive regulation of transforming growth factor beta receptor signaling pathway Source: UniProtKB
    25. protein phosphorylation Source: UniProtKB
    26. retina layer formation Source: DFLAT
    27. SMAD protein signal transduction Source: Ensembl
    28. smoothened signaling pathway Source: MGI
    29. transcription, DNA-templated Source: UniProtKB-KW
    30. transforming growth factor beta receptor signaling pathway Source: MGI
    31. voluntary musculoskeletal movement Source: MGI

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Apoptosis, DNA damage, Transcription, Transcription regulation

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.11.1. 3474.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Homeodomain-interacting protein kinase 2 (EC:2.7.11.1)
    Alternative name(s):
    Nuclear body-associated kinase 1
    Sialophorin tail-associated nuclear serine/threonine-protein kinase
    Gene namesi
    Name:Hipk2
    Synonyms:Nbak1, Stank
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 6

    Organism-specific databases

    MGIiMGI:1314872. Hipk2.

    Subcellular locationi

    NucleusPML body 5 Publications. Cytoplasm By similarity
    Isoform 2 : Nucleus. Cytoplasm
    Note: Isoform 2 seems to be both nuclear and cytoplasmic.

    GO - Cellular componenti

    1. centrosome Source: Ensembl
    2. cytoplasm Source: MGI
    3. nuclear membrane Source: Ensembl
    4. nucleus Source: UniProtKB
    5. PML body Source: MGI

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    Inhibited terminal erythroid cell proliferation and terminal enucleation, as well as reduced accumulation of hemoglobin. Impaired transcription of many genes involved in cell proliferation and apoptosis, and of erythroid-specific genes involved in hemoglobin biosynthesis, such as HBA and SLC25A37/MFRN. Enhanced stability of CTNNB1; accumulation of beta-catenin leading to the potentiation of beta-catenin-mediated cell proliferation and tumor formation. Small eyes with deficient lens, abnormal retinal lamination, and thickened retinas.3 Publications

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi228 – 2281K → R: No enzymatic activity, but still interacts with TP53 and NLK. Blocks the ability to induce cell growth arrest. Decreases corepressor activity. 4 Publications
    Mutagenesisi361 – 3611Y → A: Strongly reduced nuclear localization. 1 Publication
    Mutagenesisi1189 – 11891K → R: Inhibits localization to nuclear speckles. 1 Publication

    Keywords - Diseasei

    Tumor suppressor

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 11961196Homeodomain-interacting protein kinase 2PRO_0000085997Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei16 – 161Phosphoserine2 Publications
    Cross-linki32 – 32Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
    Modified residuei118 – 1181Phosphoserine2 Publications
    Modified residuei135 – 1351Phosphoserine2 Publications
    Modified residuei141 – 1411Phosphothreonine2 Publications
    Modified residuei252 – 2521Phosphothreonine2 Publications
    Modified residuei273 – 2731Phosphothreonine2 Publications
    Modified residuei361 – 3611Phosphotyrosine; by autocatalysis2 Publications
    Modified residuei441 – 4411Phosphoserine2 Publications
    Modified residuei482 – 4821Phosphothreonine2 Publications
    Modified residuei517 – 5171Phosphothreonine2 Publications
    Modified residuei566 – 5661Phosphothreonine2 Publications
    Modified residuei634 – 6341Phosphoserine2 Publications
    Modified residuei668 – 6681Phosphoserine2 Publications
    Modified residuei687 – 6871Phosphothreonine2 Publications
    Modified residuei815 – 8151Phosphoserine2 Publications
    Modified residuei827 – 8271Phosphoserine2 Publications
    Modified residuei934 – 9341Phosphoserine2 Publications
    Modified residuei991 – 9911Phosphoserine2 Publications
    Modified residuei993 – 9931Phosphoserine1 Publication
    Modified residuei1042 – 10421Phosphoserine2 Publications
    Modified residuei1153 – 11531Phosphoserine2 Publications
    Modified residuei1186 – 11861Phosphoserine2 Publications
    Cross-linki1189 – 1189Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)

    Post-translational modificationi

    Sumoylated. When conjugated it is directed to nuclear speckles. Desumoylated by SENP1. Sumoylation on Lys-32 is promoted by the E3 SUMO-protein ligase CBX4 By similarity.By similarity
    Autophosphorylation at Tyr-361 in the activation loop activates the kinase and promotes nuclear localization.1 Publication
    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 By similarity.By similarity
    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.

    Keywords - PTMi

    Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiQ9QZR5.
    PRIDEiQ9QZR5.

    PTM databases

    PhosphoSiteiQ9QZR5.

    Expressioni

    Tissue specificityi

    Ubiquitous. Abundant in muscle, heart, small intestine, stomach, kidney and brain; and low in testis, skin and lung.3 Publications

    Developmental stagei

    At E15-E17, mainly in the developing retina, telencephalon and myoblasts. At E12.5, detected in the developing trigeminal and dorsal root ganglia, and in the developing spinal cord (at protein level). Highly induced during primary fetal liver erythropoiesis. Expressed in the inner retina during late embryogenesis, in nucleus. Highest levels at E14.5 for isoform 2 and P12.5 for isoform 1.4 Publications

    Inductioni

    During T-cell activation.2 Publications

    Gene expression databases

    ArrayExpressiQ9QZR5.
    BgeeiQ9QZR5.
    CleanExiMM_HIPK2.
    GenevestigatoriQ9QZR5.

    Interactioni

    Subunit structurei

    Interacts with CREB1, SIAH1, WSB1, CBX4, TRADD, p53/TP53, TP73, TP63, CREBBP, DAXX, P53DINP1, SKI, SMAD1, SMAD2 and SMAD3, but not SMAD4. Interacts with SP100; positively regulates TP53-dependent transcription By similarity. 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.By similarity10 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    MECP2P516083EBI-366905,EBI-1189067From a different organism.
    MybP068762EBI-366905,EBI-366934
    NlkO549492EBI-366905,EBI-366894
    WSB1Q9Y6I75EBI-366905,EBI-1171494From a different organism.

    Protein-protein interaction databases

    BioGridi200307. 5 interactions.
    DIPiDIP-31712N.
    IntActiQ9QZR5. 8 interactions.
    STRINGi10090.ENSMUSP00000045457.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9QZR5.
    SMRiQ9QZR5. Positions 125-554.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini199 – 527329Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni97 – 230134Transcriptional corepressionAdd
    BLAST
    Regioni189 – 520332Interaction with DAXXBy similarityAdd
    BLAST
    Regioni539 – 844306Interaction with SKI and SMAD1By similarityAdd
    BLAST
    Regioni752 – 897146Interaction with POU4F1Add
    BLAST
    Regioni774 – 876103Interaction with CTBP1Add
    BLAST
    Regioni787 – 897111Interaction with HMGA1Add
    BLAST
    Regioni802 – 8054Nuclear localization signal 1 (NLS1)By similarity
    Regioni832 – 8354Nuclear localization signal 2 (NLS2)By similarity
    Regioni839 – 93496Interaction with TP53 and TP73Add
    BLAST
    Regioni873 – 980108Localization to nuclear specklesAdd
    BLAST
    Regioni873 – 980108Required for localization to nuclear specklesBy similarityAdd
    BLAST
    Regioni873 – 90735Interaction with UBE2IAdd
    BLAST
    Regioni884 – 90825SUMO interaction motifs (SIM); required for nuclear localization and kinase activityBy similarityAdd
    BLAST
    Regioni935 – 1050116Interaction with AXIN1Add
    BLAST
    Regioni984 – 1196213Autoinhibitory domain (AID)By similarityAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi1089 – 10924Poly-Ala

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00750000117228.
    HOVERGENiHBG051908.
    InParanoidiQ9QZR5.
    KOiK08826.
    OMAiYSFPHNS.
    OrthoDBiEOG7034GK.
    PhylomeDBiQ9QZR5.
    TreeFamiTF105417.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view]
    PfamiPF00069. Pkinase. 1 hit.
    [Graphical view]
    SMARTiSM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequences (5)i

    Sequence statusi: Complete.

    This entry describes 5 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q9QZR5-1) [UniParc]FASTAAdd to Basket

    Also known as: Nbak1b, b

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MAPVYEGMAS HVQVFSPHTL QSSAFCSVKK LKVEPSSNWD MTGYGSHSKV     50
    YSQSKNIPPS QPASTTVSTS LPIPNPSLPY EQTIIFPGST GHIVVTSASS 100
    TSVTGQVLGG PHNLMRRSTV SLLDTYQKCG LKRKSEEIEN TSSVQIIEEH 150
    PPMIQNNASG ATVATATTST ATSKNSGSNS EGDYQLVQHE VLCSMTNTYE 200
    VLEFLGRGTF GQVVKCWKRG TNEIVAIKIL KNHPSYARQG QIEVSILARL 250
    STESADDYNF VRAYECFQHK NHTCLVFEML EQNLYDFLKQ NKFSPLPLKY 300
    IRPVLQQVAT ALMKLKSLGL IHADLKPENI MLVDPSRQPY RVKVIDFGSA 350
    SHVSKAVCST YLQSRYYRAP EIILGLPFCE AIDMWSLGCV IAELFLGWPL 400
    YPGASEYDQI RYISQTQGLP AEYLLSAGTK TTRFFNRDTD SPYPLWRLKT 450
    PDDHEAETGI KSKEARKYIF NCLDDMAQVN MTTDLEGSDM LVEKADRREF 500
    IDLLKKMLTI DADKRVTPIE TLNHPFVTMT HLLDFPHSAH VKSCFQNMEI 550
    CKRRVNMYDT VNQSKTPFIT HVAPSTSTNL TMTFNNQLTT VHNQAPTTSS 600
    ATLSLANPEV SILNYQSALY QPSAASMAAV APRSMPLQTG TAQICARPDP 650
    FQQALIVCPP GFQGLQASPS KHAGYSVRME NAVPIVTQAP GAQPLQIQPG 700
    LLAQQAWPGG AQQILLPPAW QQLTGVATHT SVQHAAVIPE TMAGTQQLAD 750
    WRNTHAHGSH YNPIMQQPAL LTGHVTLPAA QPLNVGVAHV MRQQPTSTTS 800
    SRKSKQHQSS VRNVSTCEVT SSQAISSPQR SKRVKENTPP RCAMVHSSPA 850
    CSTSVTCGWG DVASSTTRER QRQTIVIPDT PSPTVSVITI SSDTDEEEEQ 900
    KHAPTSTVSK QRKNVISCVT VHDSPYSDSS SNTSPYSVQQ RTGHNGTNTL 950
    DTKGGLENHC TGNPRTIIVP PLKTQASEVL VECDSLGPAI SASHHSSSFK 1000
    SKSSSTVTST SGHSSGSSSG AIAYRQQRPG PHFQQQQPLN LSQAQQHMAA 1050
    DRTGSHRRQQ AYITPTMAQA PYTFPHNSPS HGTVHPHLAA AAHLPTQPHL 1100
    YTYTAPTALG STGTVAHLVA SQGSARHTVQ HTAYPASIVH QVPVSMGPRV 1150
    LPSPTIHPSQ YPAQFAHQTY ISASPASTVY TGYPLSPAKV NQYPYI 1196
    Length:1,196
    Mass (Da):130,498
    Last modified:April 27, 2001 - v2
    Checksum:i5C863BE377F3AAEF
    GO
    Isoform 2 (identifier: Q9QZR5-2) [UniParc]FASTAAdd to Basket

    Also known as: Nbak1a, a

    The sequence of this isoform differs from the canonical sequence as follows:
         594-620: Missing.

    Show »
    Length:1,169
    Mass (Da):127,676
    Checksum:iF8C5ED0ADE4CFE4F
    GO
    Isoform 3 (identifier: Q9QZR5-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-7: Missing.
         369-1196: Missing.

    Show »
    Length:361
    Mass (Da):39,990
    Checksum:iF1F5B6095C8BCDA5
    GO
    Isoform 4 (identifier: Q9QZR5-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-7: Missing.
         594-620: Missing.

    Show »
    Length:1,162
    Mass (Da):126,928
    Checksum:i7478F6F1DAF75DE1
    GO
    Isoform 5 (identifier: Q9QZR5-5) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-480: Missing.
         595-605: APTTSSATLSL → KSQLIGLSPES
         606-1196: Missing.

    Show »
    Length:125
    Mass (Da):14,279
    Checksum:i7052092228D50AD5
    GO

    Sequence cautioni

    The sequence AAC63011.1 differs from that shown. Reason: Frameshift at position 2.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti460 – 4601I → T in AAC63011. (PubMed:9748262)Curated
    Sequence conflicti479 – 4791V → G in AAC63011. (PubMed:9748262)Curated
    Sequence conflicti705 – 7051Missing in AAG41237. (PubMed:11267674)Curated
    Sequence conflicti705 – 7051Missing in AAK07649. (PubMed:14990717)Curated
    Sequence conflicti719 – 7191A → T in AAC63011. (PubMed:9748262)Curated
    Sequence conflicti1120 – 11201A → R in AAC63011. (PubMed:9748262)Curated
    Sequence conflicti1132 – 11321T → A in AAK07650. (PubMed:14990717)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 480480Missing in isoform 5. 1 PublicationVSP_013136Add
    BLAST
    Alternative sequencei1 – 77Missing in isoform 3 and isoform 4. 2 PublicationsVSP_013135
    Alternative sequencei369 – 1196828Missing in isoform 3. 1 PublicationVSP_013137Add
    BLAST
    Alternative sequencei594 – 62027Missing in isoform 2 and isoform 4. 4 PublicationsVSP_004808Add
    BLAST
    Alternative sequencei595 – 60511APTTSSATLSL → KSQLIGLSPES in isoform 5. 1 PublicationVSP_013138Add
    BLAST
    Alternative sequencei606 – 1196591Missing in isoform 5. 1 PublicationVSP_013139Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF077659 mRNA. Translation: AAC63011.1. Frameshift.
    AF273680 mRNA. Translation: AAG02078.1.
    AF208292 mRNA. Translation: AAG41237.1.
    AF333791 mRNA. Translation: AAK07649.1.
    AF333792 mRNA. Translation: AAK07650.1.
    AF170301 mRNA. Translation: AAD52566.1.
    AF170302 mRNA. Translation: AAD52567.1.
    AK016742 mRNA. Translation: BAB30405.1.
    AK019821 mRNA. Translation: BAB31866.1.
    CCDSiCCDS20017.2. [Q9QZR5-1]
    PIRiT17088.
    RefSeqiNP_001129537.1. NM_001136065.1.
    NP_034563.2. NM_010433.2. [Q9QZR5-1]
    XP_006505667.1. XM_006505604.1. [Q9QZR5-2]
    XP_006505668.1. XM_006505605.1.
    UniGeneiMm.23790.
    Mm.391962.
    Mm.486937.

    Genome annotation databases

    EnsembliENSMUST00000160360; ENSMUSP00000125500; ENSMUSG00000061436.
    ENSMUST00000160962; ENSMUSP00000125572; ENSMUSG00000061436.
    ENSMUST00000161779; ENSMUSP00000124133; ENSMUSG00000061436. [Q9QZR5-1]
    ENSMUST00000162359; ENSMUSP00000125150; ENSMUSG00000061436. [Q9QZR5-2]
    GeneIDi15258.
    KEGGimmu:15258.
    UCSCiuc009bkw.2. mouse. [Q9QZR5-4]
    uc009bkx.2. mouse. [Q9QZR5-1]
    uc009blb.2. mouse. [Q9QZR5-3]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF077659 mRNA. Translation: AAC63011.1 . Frameshift.
    AF273680 mRNA. Translation: AAG02078.1 .
    AF208292 mRNA. Translation: AAG41237.1 .
    AF333791 mRNA. Translation: AAK07649.1 .
    AF333792 mRNA. Translation: AAK07650.1 .
    AF170301 mRNA. Translation: AAD52566.1 .
    AF170302 mRNA. Translation: AAD52567.1 .
    AK016742 mRNA. Translation: BAB30405.1 .
    AK019821 mRNA. Translation: BAB31866.1 .
    CCDSi CCDS20017.2. [Q9QZR5-1 ]
    PIRi T17088.
    RefSeqi NP_001129537.1. NM_001136065.1.
    NP_034563.2. NM_010433.2. [Q9QZR5-1 ]
    XP_006505667.1. XM_006505604.1. [Q9QZR5-2 ]
    XP_006505668.1. XM_006505605.1.
    UniGenei Mm.23790.
    Mm.391962.
    Mm.486937.

    3D structure databases

    ProteinModelPortali Q9QZR5.
    SMRi Q9QZR5. Positions 125-554.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 200307. 5 interactions.
    DIPi DIP-31712N.
    IntActi Q9QZR5. 8 interactions.
    STRINGi 10090.ENSMUSP00000045457.

    PTM databases

    PhosphoSitei Q9QZR5.

    Proteomic databases

    PaxDbi Q9QZR5.
    PRIDEi Q9QZR5.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000160360 ; ENSMUSP00000125500 ; ENSMUSG00000061436 .
    ENSMUST00000160962 ; ENSMUSP00000125572 ; ENSMUSG00000061436 .
    ENSMUST00000161779 ; ENSMUSP00000124133 ; ENSMUSG00000061436 . [Q9QZR5-1 ]
    ENSMUST00000162359 ; ENSMUSP00000125150 ; ENSMUSG00000061436 . [Q9QZR5-2 ]
    GeneIDi 15258.
    KEGGi mmu:15258.
    UCSCi uc009bkw.2. mouse. [Q9QZR5-4 ]
    uc009bkx.2. mouse. [Q9QZR5-1 ]
    uc009blb.2. mouse. [Q9QZR5-3 ]

    Organism-specific databases

    CTDi 28996.
    MGIi MGI:1314872. Hipk2.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00750000117228.
    HOVERGENi HBG051908.
    InParanoidi Q9QZR5.
    KOi K08826.
    OMAi YSFPHNS.
    OrthoDBi EOG7034GK.
    PhylomeDBi Q9QZR5.
    TreeFami TF105417.

    Enzyme and pathway databases

    BRENDAi 2.7.11.1. 3474.

    Miscellaneous databases

    ChiTaRSi HIPK2. mouse.
    NextBioi 287877.
    PROi Q9QZR5.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9QZR5.
    Bgeei Q9QZR5.
    CleanExi MM_HIPK2.
    Genevestigatori Q9QZR5.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view ]
    Pfami PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SMARTi SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Homeodomain-interacting protein kinases, a novel family of co-repressors for homeodomain transcription factors."
      Kim Y.H., Choi C.Y., Lee S.-J., Conti M.A., Kim Y.
      J. Biol. Chem. 273:25875-25879(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, INTERACTION WITH NKX1-2 AND NKX2-5, MUTAGENESIS OF LYS-228.
      Strain: BALB/c.
    2. "Identification and cloning of a CD43-associated serine/threonine kinase."
      Wang W., Link V., Green J.M.
      Cell. Immunol. 205:34-39(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INTERACTION WITH SPN, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INDUCTION.
      Strain: BALB/c.
      Tissue: Heart.
    3. "Isolation and characterization of cDNAs for the protein kinase HIPK2."
      Wang Y., Hofmann T.G., Runkel L., Haaf T., Schaller H., Debatin K.-M., Hug H.
      Biochim. Biophys. Acta 1518:168-172(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
    4. "US11 of herpes simplex virus type 1 interacts with HIPK2 and antagonizes HIPK2-induced cell growth arrest."
      Giraud S., Diaz-Latoud C., Hacot S., Textoris J., Bourette R.P., Diaz J.-J.
      J. Virol. 78:2984-2993(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
      Tissue: Heart.
    5. "Protein kinases associated with PML/CBP nuclear bodies and filamentous threads regulate transcription and inhibit cell growth."
      Sather S.L., Johnson N.L., Johnson G.L.
      Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
    6. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 5).
      Strain: C57BL/6J.
      Tissue: Testis.
    7. "Covalent modification of the homeodomain-interacting protein kinase 2 (HIPK2) by the ubiquitin-like protein SUMO-1."
      Kim Y.H., Choi C.Y., Kim Y.
      Proc. Natl. Acad. Sci. U.S.A. 96:12350-12355(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, INTERACTION WITH UBE2I, SUMOYLATION, MUTAGENESIS OF LYS-1189.
    8. "High mobility group I (Y) proteins bind HIPK2, a serine-threonine kinase protein which inhibits cell growth."
      Pierantoni G.M., Fedele M., Pentimalli F., Benvenuto G., Pero R., Viglietto G., Santoro M., Chiariotti L., Fusco A.
      Oncogene 20:6132-6141(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HMGA1, FUNCTION, PHOSPHORYLATION, AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-228.
    9. "The homeodomain-interacting protein kinase 2 gene is expressed late in embryogenesis and preferentially in retina, muscle, and neural tissues."
      Pierantoni G.M., Bulfone A., Pentimalli F., Fedele M., Iuliano R., Santoro M., Chiariotti L., Ballabio A., Fusco A.
      Biochem. Biophys. Res. Commun. 290:942-947(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
    10. "Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis."
      D'Orazi G., Cecchinelli B., Bruno T., Manni I., Higashimoto Y., Saito S., Gostissa M., Coen S., Marchetti A., Del Sal G., Piaggio G., Fanciulli M., Appella E., Soddu S.
      Nat. Cell Biol. 4:11-19(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH TP53, AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-228.
    11. "Homeodomain interacting protein kinase 2 promotes apoptosis by downregulating the transcriptional corepressor CtBP."
      Zhang Q., Yoshimatsu Y., Hildebrand J., Frisch S.M., Goodman R.H.
      Cell 115:177-186(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH CTBP1.
    12. "Axin stimulates p53 functions by activation of HIPK2 kinase through multimeric complex formation."
      Rui Y., Xu Z., Lin S., Li Q., Rui H., Luo W., Zhou H.-M., Cheung P.-Y., Wu Z., Ye Z., Li P., Han J., Lin S.-C.
      EMBO J. 23:4583-4594(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH AXIN1, IDENTIFICATION IN A COMPLEX WITH TP53 AND AXIN1.
    13. "Wnt-1 signal induces phosphorylation and degradation of c-Myb protein via TAK1, HIPK2, and NLK."
      Kanei-Ishii C., Ninomiya-Tsuji J., Tanikawa J., Nomura T., Ishitani T., Kishida S., Kokura K., Kurahashi T., Ichikawa-Iwata E., Kim Y., Matsumoto K., Ishii S.
      Genes Dev. 18:816-829(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN WNT SIGNALING, INTERACTION WITH NLK AND MYB, MUTAGENESIS OF LYS-228.
    14. "Interaction of Brn3a and HIPK2 mediates transcriptional repression of sensory neuron survival."
      Wiggins A.K., Wei G., Doxakis E., Wong C., Tang A.A., Zang K., Luo E.J., Neve R.L., Reichardt L.F., Huang E.J.
      J. Cell Biol. 167:257-267(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH POU4F1; POU4F2 AND POU4F3, DEVELOPMENTAL STAGE.
    15. "Roles of HIPK1 and HIPK2 in AML1- and p300-dependent transcription, hematopoiesis and blood vessel formation."
      Aikawa Y., Nguyen L.A., Isono K., Takakura N., Tagata Y., Schmitz M.L., Koseki H., Kitabayashi I.
      EMBO J. 25:3955-3965(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS KINASE AND IN ANGIOGENESIS, INTERACTION WITH RUNX1 AND EP300.
    16. "Targeting hypoxia in cancer cells by restoring homeodomain interacting protein-kinase 2 and p53 activity and suppressing HIF-1alpha."
      Nardinocchi L., Puca R., Sacchi A., Rechavi G., Givol D., D'Orazi G.
      PLoS ONE 4:E6819-E6819(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION BY ZINC DURING HYPOXIA.
    17. "Homeodomain-interacting protein kinase 2 (HIPK2) targets beta-catenin for phosphorylation and proteasomal degradation."
      Kim E.-A., Kim J.E., Sung K.S., Choi D.W., Lee B.J., Choi C.Y.
      Biochem. Biophys. Res. Commun. 394:966-971(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS CTNNB1 KINASE, DISRUPTION PHENOTYPE.
    18. "Pancreatic and duodenal homeobox 1 (PDX1) phosphorylation at serine-269 is HIPK2-dependent and affects PDX1 subnuclear localization."
      An R., da Silva Xavier G., Semplici F., Vakhshouri S., Hao H.X., Rutter J., Pagano M.A., Meggio F., Pinna L.A., Rutter G.A.
      Biochem. Biophys. Res. Commun. 399:155-161(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS PDX1 KINASE.
    19. "Homeodomain-interacting protein kinase 2 plays an important role in normal terminal erythroid differentiation."
      Hattangadi S.M., Burke K.A., Lodish H.F.
      Blood 115:4853-4861(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE.
    20. "Involvement of the Hipk family in regulation of eyeball size, lens formation and retinal morphogenesis."
      Inoue T., Kagawa T., Inoue-Mochita M., Isono K., Ohtsu N., Nobuhisa I., Fukushima M., Tanihara H., Taga T.
      FEBS Lett. 584:3233-3238(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN EYE DEVELOPMENT, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE.
    21. "HIPK2 catalytic activity and subcellular localization are regulated by activation-loop Y354 autophosphorylation."
      Siepi F., Gatti V., Camerini S., Crescenzi M., Soddu S.
      Biochim. Biophys. Acta 1833:1443-1453(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-16; SER-118; SER-135; THR-141; THR-252; THR-273; TYR-361; SER-441; THR-482; THR-517; THR-566; SER-634; SER-668; THR-687; SER-815; SER-827; SER-934; SER-991; SER-991; SER-1042; SER-1153 AND SER-1186, ENZYME REGULATION, MUTAGENESIS OF TYR-361.

    Entry informationi

    Entry nameiHIPK2_MOUSE
    AccessioniPrimary (citable) accession number: Q9QZR5
    Secondary accession number(s): O88905
    , Q99P45, Q99P46, Q9D2E6, Q9D474, Q9EQL2, Q9QZR4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 27, 2001
    Last sequence update: April 27, 2001
    Last modified: October 1, 2014
    This is version 146 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3