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Protein

Homeodomain-interacting protein kinase 2

Gene

HIPK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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.18 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei228ATPCurated1
Active sitei324Proton acceptorCurated1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi205 – 213ATPCurated9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • protein kinase activity Source: UniProtKB
  • protein serine/threonine kinase activity Source: BHF-UCL
  • RNA polymerase II activating transcription factor binding Source: BHF-UCL
  • RNA polymerase II transcription coactivator activity Source: Ensembl
  • SMAD binding Source: UniProtKB
  • transcription corepressor activity Source: UniProtKB
  • virion binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

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

BioCyciZFISH:HS00803-MONOMER.
BRENDAi2.7.11.1. 2681.
ReactomeiR-HSA-2032785. YAP1- and WWTR1 (TAZ)-stimulated gene expression.
R-HSA-5578768. Physiological factors.
R-HSA-6804756. Regulation of TP53 Activity through Phosphorylation.
SignaLinkiQ9H2X6.
SIGNORiQ9H2X6.

Names & Taxonomyi

Protein namesi
Recommended name:
Homeodomain-interacting protein kinase 2 (EC:2.7.11.1)
Short name:
hHIPk2
Gene namesi
Name:HIPK2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:14402. HIPK2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nuclear body Source: UniProtKB
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • PML body Source: UniProtKB-SubCell
  • RNA polymerase II transcription factor complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi228K → A: Locates in the nucleoplasm, no effect on interaction with RANBP9, but loss of kinase activity toward PML, RUNX1 and EP300. 9 Publications1
Mutagenesisi228K → R: Abolishes enzymatic activity, no effect on interaction with TP53 and TP73 or on BMP-induced transcriptional activation. Enhances BMP-induced transcriptional activation; when associated with 359-AAF-361. 9 Publications1
Mutagenesisi359 – 361STY → AAF: Enhances BMP-induced transcriptional activation; when associated with R-228. 1 Publication3
Mutagenesisi803K → A: Impaired nuclear localization; when associated with A-805. 1 Publication1
Mutagenesisi805K → A: Impaired nuclear localization; when associated with A-803. 1 Publication1
Mutagenesisi833R → A: Impaired nuclear localization. 1 Publication1
Mutagenesisi835K → E: Impaired nuclear localization. 1 Publication1
Mutagenesisi885 – 892VSVITISS → KFMHFHRM: Loss of SUMO and CBX4 interaction, and impaired nuclear and PML-nuclear bodies localization. 1 Publication8
Mutagenesisi885 – 888VSVI → KSAK: Loss of SUMO interaction, and impaired nuclear and PML-nuclear bodies localization. 1 Publication4
Mutagenesisi892 – 895SDTD → ADTA: Loss of SUMO interaction, and impaired nuclear and PML-nuclear bodies localization. 1 Publication4
Mutagenesisi893 – 899DTDEEEE → NFNQQQQ: Loss of SUMO and CBX4 interaction, and impaired nuclear and PML-nuclear bodies localization. 1 Publication7

Organism-specific databases

DisGeNETi28996.
OpenTargetsiENSG00000064393.
PharmGKBiPA29291.

Chemistry databases

ChEMBLiCHEMBL4576.
GuidetoPHARMACOLOGYi2034.

Polymorphism and mutation databases

BioMutaiHIPK2.
DMDMi21431782.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000859951 – 1198Homeodomain-interacting protein kinase 2Add BLAST1198

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei16PhosphoserineBy similarity1
Cross-linki32Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication
Modified residuei118PhosphoserineBy similarity1
Modified residuei135PhosphoserineBy similarity1
Modified residuei141PhosphothreonineBy similarity1
Modified residuei252PhosphothreonineBy similarity1
Modified residuei273PhosphothreonineBy similarity1
Modified residuei361Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei441PhosphoserineBy similarity1
Modified residuei482PhosphothreonineBy similarity1
Modified residuei517PhosphothreonineBy similarity1
Modified residuei566PhosphothreonineBy similarity1
Modified residuei634PhosphoserineBy similarity1
Modified residuei668PhosphoserineBy similarity1
Modified residuei687PhosphothreonineBy similarity1
Modified residuei815PhosphoserineBy similarity1
Modified residuei827PhosphoserineBy similarity1
Modified residuei934PhosphoserineBy similarity1
Modified residuei992PhosphoserineBy similarity1
Modified residuei1041PhosphoserineBy similarity1
Modified residuei1155PhosphoserineBy similarity1
Modified residuei1188PhosphoserineBy similarity1
Cross-linki1191Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

Post-translational modificationi

Autophosphorylation at Tyr-361 in the activation loop activates the kinase and promotes nuclear localization.By similarity
Sumoylated. When conjugated it is directed to nuclear speckles. Desumoylated by SENP1 (By similarity). Sumoylation on Lys-32 is promoted by the E3 SUMO-protein ligase CBX4.By similarity4 Publications
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.3 Publications
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.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei923 – 924Cleavage; by CASP62
Sitei984 – 985Cleavage; by CASP62

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ9H2X6.
PaxDbiQ9H2X6.
PeptideAtlasiQ9H2X6.
PRIDEiQ9H2X6.
TopDownProteomicsiQ9H2X6-2. [Q9H2X6-2]

PTM databases

iPTMnetiQ9H2X6.
PhosphoSitePlusiQ9H2X6.

Miscellaneous databases

PMAP-CutDBQ9H2X6.

Expressioni

Tissue specificityi

Highly expressed in heart, muscle and kidney. Weakly expressed in a ubiquitous way. Down-regulated in several thyroid and breast tumors.2 Publications

Inductioni

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.5 Publications

Gene expression databases

BgeeiENSG00000064393.
CleanExiHS_HIPK2.
ExpressionAtlasiQ9H2X6. baseline and differential.
GenevisibleiQ9H2X6. HS.

Organism-specific databases

HPAiHPA007611.

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 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.16 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
DCAF7P6196210EBI-348345,EBI-359808
EP300Q094724EBI-348345,EBI-447295
MECP2P516082EBI-348345,EBI-1189067
RUNX1Q011964EBI-348345,EBI-925904

GO - Molecular functioni

  • RNA polymerase II activating transcription factor binding Source: BHF-UCL
  • SMAD binding Source: UniProtKB

Protein-protein interaction databases

BioGridi118815. 60 interactors.
DIPiDIP-31716N.
IntActiQ9H2X6. 19 interactors.
MINTiMINT-234689.
STRINGi9606.ENSP00000385571.

Chemistry databases

BindingDBiQ9H2X6.

Structurei

3D structure databases

ProteinModelPortaliQ9H2X6.
SMRiQ9H2X6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini199 – 527Protein kinasePROSITE-ProRule annotationAdd BLAST329

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni97 – 230Transcriptional corepressionBy similarityAdd BLAST134
Regioni189 – 520Interaction with DAXX1 PublicationAdd BLAST332
Regioni539 – 844Interaction with SKI and SMAD11 PublicationAdd BLAST306
Regioni752 – 897Interaction with POU4F1By similarityAdd BLAST146
Regioni774 – 876Interaction with CTBP1By similarityAdd BLAST103
Regioni787 – 897Interaction with HMGA1By similarityAdd BLAST111
Regioni846 – 941Interaction with TP53 and TP731 PublicationAdd BLAST96
Regioni873 – 980Required for localization to nuclear specklesBy similarityAdd BLAST108
Regioni873 – 907Interaction with UBE2IBy similarityAdd BLAST35
Regioni884 – 908SUMO interaction motifs (SIM); required for nuclear localization and kinase activityAdd BLAST25
Regioni935 – 1049Interaction with AXIN1By similarityAdd BLAST115
Regioni984 – 1198Autoinhibitory domain (AID)Add BLAST215

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi802 – 805Nuclear localization signal 1 (NLS1)4
Motifi832 – 835Nuclear localization signal 2 (NLS2)4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1088 – 1094Poly-Ala7

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0667. Eukaryota.
ENOG410XPET. LUCA.
GeneTreeiENSGT00760000119032.
HOGENOMiHOG000231785.
HOVERGENiHBG051908.
InParanoidiQ9H2X6.
KOiK08826.
OMAiMIQNNAS.
OrthoDBiEOG091G0UMX.
PhylomeDBiQ9H2X6.
TreeFamiTF105417.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
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 (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Experimental confirmation may be lacking for some isoforms.
Isoform 1 (identifier: Q9H2X6-1) [UniParc]FASTAAdd to basket

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

        10         20         30         40         50
MAPVYEGMAS HVQVFSPHTL QSSAFCSVKK LKIEPSSNWD MTGYGSHSKV
60 70 80 90 100
YSQSKNIPLS QPATTTVSTS LPVPNPSLPY EQTIVFPGST GHIVVTSASS
110 120 130 140 150
TSVTGQVLGG PHNLMRRSTV SLLDTYQKCG LKRKSEEIEN TSSVQIIEEH
160 170 180 190 200
PPMIQNNASG ATVATATTST ATSKNSGSNS EGDYQLVQHE VLCSMTNTYE
210 220 230 240 250
VLEFLGRGTF GQVVKCWKRG TNEIVAIKIL KNHPSYARQG QIEVSILARL
260 270 280 290 300
STESADDYNF VRAYECFQHK NHTCLVFEML EQNLYDFLKQ NKFSPLPLKY
310 320 330 340 350
IRPVLQQVAT ALMKLKSLGL IHADLKPENI MLVDPSRQPY RVKVIDFGSA
360 370 380 390 400
SHVSKAVCST YLQSRYYRAP EIILGLPFCE AIDMWSLGCV IAELFLGWPL
410 420 430 440 450
YPGASEYDQI RYISQTQGLP AEYLLSAGTK TTRFFNRDTD SPYPLWRLKT
460 470 480 490 500
PDDHEAETGI KSKEARKYIF NCLDDMAQVN MTTDLEGSDM LVEKADRREF
510 520 530 540 550
IDLLKKMLTI DADKRITPIE TLNHPFVTMT HLLDFPHSTH VKSCFQNMEI
560 570 580 590 600
CKRRVNMYDT VNQSKTPFIT HVAPSTSTNL TMTFNNQLTT VHNQAPSSTS
610 620 630 640 650
ATISLANPEV SILNYPSTLY QPSAASMAAV AQRSMPLQTG TAQICARPDP
660 670 680 690 700
FQQALIVCPP GFQGLQASPS KHAGYSVRME NAVPIVTQAP GAQPLQIQPG
710 720 730 740 750
LLAQQAWPSG TQQILLPPAW QQLTGVATHT SVQHATVIPE TMAGTQQLAD
760 770 780 790 800
WRNTHAHGSH YNPIMQQPAL LTGHVTLPAA QPLNVGVAHV MRQQPTSTTS
810 820 830 840 850
SRKSKQHQSS VRNVSTCEVS SSQAISSPQR SKRVKENTPP RCAMVHSSPA
860 870 880 890 900
CSTSVTCGWG DVASSTTRER QRQTIVIPDT PSPTVSVITI SSDTDEEEEQ
910 920 930 940 950
KHAPTSTVSK QRKNVISCVT VHDSPYSDSS SNTSPYSVQQ RAGHNNANAF
960 970 980 990 1000
DTKGSLENHC TGNPRTIIVP PLKTQASEVL VECDSLVPVN TSHHSSSYKS
1010 1020 1030 1040 1050
KSSSNVTSTS GHSSGSSSGA ITYRQQRPGP HFQQQQPLNL SQAQQHITTD
1060 1070 1080 1090 1100
RTGSHRRQQA YITPTMAQAP YSFPHNSPSH GTVHPHLAAA AAAAHLPTQP
1110 1120 1130 1140 1150
HLYTYTAPAA LGSTGTVAHL VASQGSARHT VQHTAYPASI VHQVPVSMGP
1160 1170 1180 1190
RVLPSPTIHP SQYPAQFAHQ TYISASPAST VYTGYPLSPA KVNQYPYI
Length:1,198
Mass (Da):130,966
Last modified:June 6, 2002 - v2
Checksum:i6022D5710E8D2D93
GO
Isoform 2 (identifier: Q9H2X6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     808-907: Missing.
     989-1018: VNTSHHSSSYKSKSSSNVTSTSGHSSGSSS → GNLGPGQGRNLSLESGFPAFLLLEMLLYGS
     1019-1198: Missing.

Show »
Length:918
Mass (Da):101,013
Checksum:iBA34005E15CFC5CD
GO
Isoform 3 (identifier: Q9H2X6-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     595-621: Missing.

Show »
Length:1,171
Mass (Da):128,158
Checksum:iC38A3241948C7D66
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti33I → V in AAG41236 (PubMed:11267674).Curated1
Sequence conflicti59L → P in AAG41236 (PubMed:11267674).Curated1
Sequence conflicti64T → S in AAG41236 (PubMed:11267674).Curated1
Sequence conflicti169S → F in AAG35710 (Ref. 4) Curated1
Sequence conflicti187V → S in AAG35710 (Ref. 4) Curated1
Sequence conflicti202L → S in AAG35710 (Ref. 4) Curated1
Sequence conflicti233H → R in AAG41236 (PubMed:11267674).Curated1
Sequence conflicti471N → I in AAL37371 (Ref. 2) Curated1
Sequence conflicti669P → S in AAG35710 (Ref. 4) Curated1
Sequence conflicti711T → N in AAG35710 (Ref. 4) Curated1
Sequence conflicti717 – 719PPA → SPT in AAG35710 (Ref. 4) Curated3
Sequence conflicti724T → D in AAG35710 (Ref. 4) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040547792R → Q.1 PublicationCorresponds to variant rs56132157dbSNPEnsembl.1
Natural variantiVAR_0405481027R → Q.1 PublicationCorresponds to variant rs35255718dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_004804595 – 621Missing in isoform 3. 1 PublicationAdd BLAST27
Alternative sequenceiVSP_004805808 – 907Missing in isoform 2. 1 PublicationAdd BLAST100
Alternative sequenceiVSP_004806989 – 1018VNTSH…SGSSS → GNLGPGQGRNLSLESGFPAF LLLEMLLYGS in isoform 2. 1 PublicationAdd BLAST30
Alternative sequenceiVSP_0048071019 – 1198Missing in isoform 2. 1 PublicationAdd BLAST180

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF208291 mRNA. Translation: AAG41236.1.
AF326592 mRNA. Translation: AAL37371.1.
AC005531 Genomic DNA. Translation: AAS00368.1.
AC073184 Genomic DNA. No translation available.
AC006021 Genomic DNA. No translation available.
AC141932 Genomic DNA. No translation available.
AF207702 mRNA. Translation: AAG35710.1.
CCDSiCCDS75666.1. [Q9H2X6-3]
CCDS75667.1. [Q9H2X6-1]
RefSeqiNP_001106710.1. NM_001113239.2. [Q9H2X6-3]
NP_073577.3. NM_022740.4. [Q9H2X6-1]
UniGeneiHs.731417.

Genome annotation databases

EnsembliENST00000406875; ENSP00000385571; ENSG00000064393. [Q9H2X6-1]
ENST00000428878; ENSP00000413724; ENSG00000064393. [Q9H2X6-3]
GeneIDi28996.
KEGGihsa:28996.
UCSCiuc003vvd.5. human. [Q9H2X6-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF208291 mRNA. Translation: AAG41236.1.
AF326592 mRNA. Translation: AAL37371.1.
AC005531 Genomic DNA. Translation: AAS00368.1.
AC073184 Genomic DNA. No translation available.
AC006021 Genomic DNA. No translation available.
AC141932 Genomic DNA. No translation available.
AF207702 mRNA. Translation: AAG35710.1.
CCDSiCCDS75666.1. [Q9H2X6-3]
CCDS75667.1. [Q9H2X6-1]
RefSeqiNP_001106710.1. NM_001113239.2. [Q9H2X6-3]
NP_073577.3. NM_022740.4. [Q9H2X6-1]
UniGeneiHs.731417.

3D structure databases

ProteinModelPortaliQ9H2X6.
SMRiQ9H2X6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118815. 60 interactors.
DIPiDIP-31716N.
IntActiQ9H2X6. 19 interactors.
MINTiMINT-234689.
STRINGi9606.ENSP00000385571.

Chemistry databases

BindingDBiQ9H2X6.
ChEMBLiCHEMBL4576.
GuidetoPHARMACOLOGYi2034.

PTM databases

iPTMnetiQ9H2X6.
PhosphoSitePlusiQ9H2X6.

Polymorphism and mutation databases

BioMutaiHIPK2.
DMDMi21431782.

Proteomic databases

MaxQBiQ9H2X6.
PaxDbiQ9H2X6.
PeptideAtlasiQ9H2X6.
PRIDEiQ9H2X6.
TopDownProteomicsiQ9H2X6-2. [Q9H2X6-2]

Protocols and materials databases

DNASUi28996.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000406875; ENSP00000385571; ENSG00000064393. [Q9H2X6-1]
ENST00000428878; ENSP00000413724; ENSG00000064393. [Q9H2X6-3]
GeneIDi28996.
KEGGihsa:28996.
UCSCiuc003vvd.5. human. [Q9H2X6-1]

Organism-specific databases

CTDi28996.
DisGeNETi28996.
GeneCardsiHIPK2.
HGNCiHGNC:14402. HIPK2.
HPAiHPA007611.
MIMi606868. gene.
neXtProtiNX_Q9H2X6.
OpenTargetsiENSG00000064393.
PharmGKBiPA29291.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0667. Eukaryota.
ENOG410XPET. LUCA.
GeneTreeiENSGT00760000119032.
HOGENOMiHOG000231785.
HOVERGENiHBG051908.
InParanoidiQ9H2X6.
KOiK08826.
OMAiMIQNNAS.
OrthoDBiEOG091G0UMX.
PhylomeDBiQ9H2X6.
TreeFamiTF105417.

Enzyme and pathway databases

BioCyciZFISH:HS00803-MONOMER.
BRENDAi2.7.11.1. 2681.
ReactomeiR-HSA-2032785. YAP1- and WWTR1 (TAZ)-stimulated gene expression.
R-HSA-5578768. Physiological factors.
R-HSA-6804756. Regulation of TP53 Activity through Phosphorylation.
SignaLinkiQ9H2X6.
SIGNORiQ9H2X6.

Miscellaneous databases

ChiTaRSiHIPK2. human.
GeneWikiiHIPK2.
GenomeRNAii28996.
PMAP-CutDBQ9H2X6.
PROiQ9H2X6.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000064393.
CleanExiHS_HIPK2.
ExpressionAtlasiQ9H2X6. baseline and differential.
GenevisibleiQ9H2X6. HS.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
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]
ProtoNetiSearch...

Entry informationi

Entry nameiHIPK2_HUMAN
AccessioniPrimary (citable) accession number: Q9H2X6
Secondary accession number(s): Q75MR7, Q8WWI4, Q9H2Y1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: June 6, 2002
Last modified: November 2, 2016
This is version 169 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

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).1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.