Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9QZR5 (HIPK2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Hipk2
Synonyms:Nbak1, Stank
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1196 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.8 Ref.10 Ref.11 Ref.13 Ref.14 Ref.15 Ref.17 Ref.18 Ref.19 Ref.20

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Subunit 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 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. Ref.1 Ref.2 Ref.7 Ref.8 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15

Subcellular location

NucleusPML body. Cytoplasm By similarity Ref.1 Ref.2 Ref.4 Ref.7 Ref.20.

Isoform 2: Nucleus. Cytoplasm. Note: Isoform 2 seems to be both nuclear and cytoplasmic. Ref.1 Ref.2 Ref.4 Ref.7 Ref.20

Tissue specificity

Ubiquitous. Abundant in muscle, heart, small intestine, stomach, kidney and brain; and low in testis, skin and lung. Ref.2 Ref.4 Ref.9

Developmental stage

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. Ref.9 Ref.14 Ref.19 Ref.20

Induction

During T-cell activation. Ref.2 Ref.16

Post-translational modification

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. Ref.7

Autophosphorylation at Tyr-361 in the activation loop activates the kinase and promotes nuclear localization By similarity.

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.

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.

Disruption phenotype

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. Ref.17 Ref.19 Ref.20

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. HIPK subfamily.

Contains 1 protein kinase domain.

Sequence caution

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

Ontologies

Keywords
   Biological processApoptosis
DNA damage
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   DiseaseTumor suppressor
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator

Inferred from electronic annotation. Source: Ensembl

SMAD protein signal transduction

Inferred from electronic annotation. Source: Ensembl

adult locomotory behavior

Inferred from mutant phenotype PubMed 17159989. Source: MGI

adult walking behavior

Inferred from mutant phenotype PubMed 17159989. Source: MGI

anterior/posterior pattern specification

Inferred from genetic interaction PubMed 16537918. Source: MGI

embryonic camera-type eye morphogenesis

Inferred from mutant phenotype Ref.20. Source: DFLAT

embryonic retina morphogenesis in camera-type eye

Inferred from mutant phenotype Ref.20. Source: DFLAT

intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator

Inferred from genetic interaction PubMed 16537918. Source: MGI

iris morphogenesis

Inferred from mutant phenotype Ref.20. Source: DFLAT

lens induction in camera-type eye

Inferred from mutant phenotype Ref.20. Source: DFLAT

negative regulation of BMP signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of neuron apoptotic process

Inferred from mutant phenotype PubMed 17159989. Source: MGI

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.1. Source: UniProtKB

neuron differentiation

Inferred from mutant phenotype Ref.20. Source: DFLAT

peptidyl-serine phosphorylation

Inferred from direct assay PubMed 16407227. Source: BHF-UCL

peptidyl-threonine phosphorylation

Inferred from direct assay PubMed 16407227. Source: BHF-UCL

positive regulation of DNA binding

Inferred from direct assay Ref.1. Source: UniProtKB

positive regulation of JNK cascade

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of angiogenesis

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell proliferation

Inferred from genetic interaction PubMed 16537918. Source: MGI

positive regulation of protein binding

Inferred from direct assay PubMed 16407227. Source: BHF-UCL

positive regulation of protein phosphorylation

Inferred from genetic interaction PubMed 20360400. Source: MGI

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 16407227. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 16407227. Source: BHF-UCL

positive regulation of transforming growth factor beta receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

protein phosphorylation

Inferred from direct assay Ref.1. Source: UniProtKB

retina layer formation

Inferred from mutant phenotype Ref.20. Source: DFLAT

smoothened signaling pathway

Inferred from genetic interaction PubMed 16537918. Source: MGI

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transforming growth factor beta receptor signaling pathway

Inferred from mutant phenotype PubMed 17159989. Source: MGI

voluntary musculoskeletal movement

Inferred from mutant phenotype PubMed 17159989. Source: MGI

   Cellular_componentPML body

Traceable author statement PubMed 12529400. Source: MGI

centrosome

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay Ref.2. Source: MGI

nuclear membrane

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay Ref.1. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

RNA polymerase II activating transcription factor binding

Inferred from physical interaction PubMed 16407227. Source: BHF-UCL

protein kinase activity

Inferred from direct assay Ref.1. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from direct assay PubMed 16407227. Source: BHF-UCL

transcription corepressor activity

Inferred from direct assay Ref.1. Source: UniProtKB

virion binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

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

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9QZR5-1)

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.
Isoform 2 (identifier: Q9QZR5-2)

Also known as: Nbak1a; a;

The sequence of this isoform differs from the canonical sequence as follows:
     594-620: Missing.
Isoform 3 (identifier: Q9QZR5-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-7: Missing.
     369-1196: Missing.
Isoform 4 (identifier: Q9QZR5-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-7: Missing.
     594-620: Missing.
Isoform 5 (identifier: Q9QZR5-5)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11961196Homeodomain-interacting protein kinase 2
PRO_0000085997

Regions

Domain199 – 527329Protein kinase
Nucleotide binding205 – 2139ATP Probable
Region97 – 230134Transcriptional corepression
Region189 – 520332Interaction with DAXX By similarity
Region539 – 844306Interaction with SKI and SMAD1 By similarity
Region752 – 897146Interaction with POU4F1
Region774 – 876103Interaction with CTBP1
Region787 – 897111Interaction with HMGA1
Region802 – 8054Nuclear localization signal 1 (NLS1) By similarity
Region832 – 8354Nuclear localization signal 2 (NLS2) By similarity
Region839 – 93496Interaction with TP53 and TP73
Region873 – 980108Localization to nuclear speckles
Region873 – 980108Required for localization to nuclear speckles By similarity
Region873 – 90735Interaction with UBE2I
Region884 – 90825SUMO interaction motifs (SIM); required for nuclear localization and kinase activity By similarity
Region935 – 1050116Interaction with AXIN1
Region984 – 1196213Autoinhibitory domain (AID) By similarity
Compositional bias1089 – 10924Poly-Ala

Sites

Active site3241Proton acceptor Probable
Binding site2281ATP Probable
Site923 – 9242Cleavage; by CASP6 By similarity
Site984 – 9852Cleavage; by CASP6 By similarity

Amino acid modifications

Modified residue161Phosphoserine By similarity
Modified residue1181Phosphoserine By similarity
Modified residue1351Phosphoserine By similarity
Modified residue1411Phosphothreonine By similarity
Modified residue2521Phosphothreonine By similarity
Modified residue2731Phosphothreonine By similarity
Modified residue3611Phosphotyrosine By similarity
Modified residue4411Phosphoserine By similarity
Modified residue4821Phosphothreonine By similarity
Modified residue5171Phosphothreonine By similarity
Modified residue5661Phosphothreonine By similarity
Modified residue6341Phosphoserine By similarity
Modified residue6681Phosphoserine By similarity
Modified residue6871Phosphothreonine By similarity
Modified residue8151Phosphoserine By similarity
Modified residue8271Phosphoserine By similarity
Modified residue9341Phosphoserine By similarity
Modified residue9931Phosphoserine By similarity
Modified residue10421Phosphoserine By similarity
Modified residue11531Phosphoserine By similarity
Modified residue11861Phosphoserine By similarity
Cross-link32Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Cross-link1189Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)

Natural variations

Alternative sequence1 – 480480Missing in isoform 5.
VSP_013136
Alternative sequence1 – 77Missing in isoform 3 and isoform 4.
VSP_013135
Alternative sequence369 – 1196828Missing in isoform 3.
VSP_013137
Alternative sequence594 – 62027Missing in isoform 2 and isoform 4.
VSP_004808
Alternative sequence595 – 60511APTTSSATLSL → KSQLIGLSPES in isoform 5.
VSP_013138
Alternative sequence606 – 1196591Missing in isoform 5.
VSP_013139

Experimental info

Mutagenesis2281K → R: No enzymatic activity, but still interacts with TP53 and NLK. Blocks the ability to induce cell growth arrest. Decreases corepressor activity. Ref.1 Ref.8 Ref.10 Ref.13
Mutagenesis11891K → R: Inhibits localization to nuclear speckles. Ref.7
Sequence conflict4601I → T in AAC63011. Ref.1
Sequence conflict4791V → G in AAC63011. Ref.1
Sequence conflict7051Missing in AAG41237. Ref.3
Sequence conflict7051Missing in AAK07649. Ref.4
Sequence conflict7191A → T in AAC63011. Ref.1
Sequence conflict11201A → R in AAC63011. Ref.1
Sequence conflict11321T → A in AAK07650. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Nbak1b) (b) [UniParc].

Last modified April 27, 2001. Version 2.
Checksum: 5C863BE377F3AAEF

FASTA1,196130,498
        10         20         30         40         50         60 
MAPVYEGMAS HVQVFSPHTL QSSAFCSVKK LKVEPSSNWD MTGYGSHSKV YSQSKNIPPS 

        70         80         90        100        110        120 
QPASTTVSTS LPIPNPSLPY EQTIIFPGST GHIVVTSASS TSVTGQVLGG PHNLMRRSTV 

       130        140        150        160        170        180 
SLLDTYQKCG LKRKSEEIEN TSSVQIIEEH PPMIQNNASG ATVATATTST ATSKNSGSNS 

       190        200        210        220        230        240 
EGDYQLVQHE VLCSMTNTYE VLEFLGRGTF GQVVKCWKRG TNEIVAIKIL KNHPSYARQG 

       250        260        270        280        290        300 
QIEVSILARL STESADDYNF VRAYECFQHK NHTCLVFEML EQNLYDFLKQ NKFSPLPLKY 

       310        320        330        340        350        360 
IRPVLQQVAT ALMKLKSLGL IHADLKPENI MLVDPSRQPY RVKVIDFGSA SHVSKAVCST 

       370        380        390        400        410        420 
YLQSRYYRAP EIILGLPFCE AIDMWSLGCV IAELFLGWPL YPGASEYDQI RYISQTQGLP 

       430        440        450        460        470        480 
AEYLLSAGTK TTRFFNRDTD SPYPLWRLKT PDDHEAETGI KSKEARKYIF NCLDDMAQVN 

       490        500        510        520        530        540 
MTTDLEGSDM LVEKADRREF IDLLKKMLTI DADKRVTPIE TLNHPFVTMT HLLDFPHSAH 

       550        560        570        580        590        600 
VKSCFQNMEI CKRRVNMYDT VNQSKTPFIT HVAPSTSTNL TMTFNNQLTT VHNQAPTTSS 

       610        620        630        640        650        660 
ATLSLANPEV SILNYQSALY QPSAASMAAV APRSMPLQTG TAQICARPDP FQQALIVCPP 

       670        680        690        700        710        720 
GFQGLQASPS KHAGYSVRME NAVPIVTQAP GAQPLQIQPG LLAQQAWPGG AQQILLPPAW 

       730        740        750        760        770        780 
QQLTGVATHT SVQHAAVIPE TMAGTQQLAD WRNTHAHGSH YNPIMQQPAL LTGHVTLPAA 

       790        800        810        820        830        840 
QPLNVGVAHV MRQQPTSTTS SRKSKQHQSS VRNVSTCEVT SSQAISSPQR SKRVKENTPP 

       850        860        870        880        890        900 
RCAMVHSSPA CSTSVTCGWG DVASSTTRER QRQTIVIPDT PSPTVSVITI SSDTDEEEEQ 

       910        920        930        940        950        960 
KHAPTSTVSK QRKNVISCVT VHDSPYSDSS SNTSPYSVQQ RTGHNGTNTL DTKGGLENHC 

       970        980        990       1000       1010       1020 
TGNPRTIIVP PLKTQASEVL VECDSLGPAI SASHHSSSFK SKSSSTVTST SGHSSGSSSG 

      1030       1040       1050       1060       1070       1080 
AIAYRQQRPG PHFQQQQPLN LSQAQQHMAA DRTGSHRRQQ AYITPTMAQA PYTFPHNSPS 

      1090       1100       1110       1120       1130       1140 
HGTVHPHLAA AAHLPTQPHL YTYTAPTALG STGTVAHLVA SQGSARHTVQ HTAYPASIVH 

      1150       1160       1170       1180       1190 
QVPVSMGPRV LPSPTIHPSQ YPAQFAHQTY ISASPASTVY TGYPLSPAKV NQYPYI 

« Hide

Isoform 2 (Nbak1a) (a) [UniParc].

Checksum: F8C5ED0ADE4CFE4F
Show »

FASTA1,169127,676
Isoform 3 [UniParc].

Checksum: F1F5B6095C8BCDA5
Show »

FASTA36139,990
Isoform 4 [UniParc].

Checksum: 7478F6F1DAF75DE1
Show »

FASTA1,162126,928
Isoform 5 [UniParc].

Checksum: 7052092228D50AD5
Show »

FASTA12514,279

References

« Hide 'large scale' references
[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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRT17088.
RefSeqNP_001129537.1. NM_001136065.1.
NP_034563.2. NM_010433.2.
XP_006505667.1. XM_006505604.1.
XP_006505668.1. XM_006505605.1.
UniGeneMm.23790.
Mm.391962.
Mm.486937.

3D structure databases

ProteinModelPortalQ9QZR5.
SMRQ9QZR5. Positions 125-526.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid200307. 5 interactions.
DIPDIP-31712N.
IntActQ9QZR5. 8 interactions.
STRING10090.ENSMUSP00000045457.

PTM databases

PhosphoSiteQ9QZR5.

Proteomic databases

PaxDbQ9QZR5.
PRIDEQ9QZR5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000160360; ENSMUSP00000125500; ENSMUSG00000061436.
ENSMUST00000160962; ENSMUSP00000125572; ENSMUSG00000061436.
ENSMUST00000161779; ENSMUSP00000124133; ENSMUSG00000061436. [Q9QZR5-1]
ENSMUST00000162359; ENSMUSP00000125150; ENSMUSG00000061436. [Q9QZR5-2]
GeneID15258.
KEGGmmu:15258.
UCSCuc009bkw.2. mouse. [Q9QZR5-4]
uc009bkx.2. mouse. [Q9QZR5-1]
uc009blb.2. mouse. [Q9QZR5-3]

Organism-specific databases

CTD28996.
MGIMGI:1314872. Hipk2.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00750000117228.
HOVERGENHBG051908.
InParanoidQ9QZR5.
KOK08826.
OMAYSFPHNS.
OrthoDBEOG7034GK.
PhylomeDBQ9QZR5.
TreeFamTF105417.

Enzyme and pathway databases

BRENDA2.7.11.1. 3474.

Gene expression databases

ArrayExpressQ9QZR5.
BgeeQ9QZR5.
CleanExMM_HIPK2.
GenevestigatorQ9QZR5.

Family and domain databases

InterProIPR011009. 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]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSHIPK2. mouse.
NextBio287877.
PROQ9QZR5.
SOURCESearch...

Entry information

Entry nameHIPK2_MOUSE
AccessionPrimary (citable) accession number: Q9QZR5
Secondary accession number(s): O88905 expand/collapse secondary AC list , Q99P45, Q99P46, Q9D2E6, Q9D474, Q9EQL2, Q9QZR4
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: April 27, 2001
Last modified: April 16, 2014
This is version 142 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot