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Protein

Homeodomain-interacting protein kinase 1

Gene

HIPK1

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

Functioni

Serine/threonine-protein kinase involved in transcription regulation and TNF-mediated cellular apoptosis. Plays a role as a corepressor for homeodomain transcription factors. Phosphorylates DAXX and MYB. Phosphorylates DAXX in response to stress, and mediates its translocation from the nucleus to the cytoplasm. Inactivates MYB transcription factor activity by phosphorylation. Prevents MAP3K5-JNK activation in the absence of TNF. TNF triggers its translocation to the cytoplasm in response to stress stimuli, thus activating nuclear MAP3K5-JNK by derepression and promoting apoptosis. May be involved in anti-oxidative stress responses. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis. Promotes angiogenesis and to be involved in erythroid differentiation. May be involved in malignant squamous cell tumor formation.5 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei219ATPCurated1
Active sitei315Proton acceptorCurated1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi196 – 204ATPCurated9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processTranscription, Transcription regulation
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-2032785 YAP1- and WWTR1 (TAZ)-stimulated gene expression
R-HSA-5578768 Physiological factors
R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation
SignaLinkiQ86Z02

Names & Taxonomyi

Protein namesi
Recommended name:
Homeodomain-interacting protein kinase 1 (EC:2.7.11.1)
Alternative name(s):
Nuclear body-associated kinase 2
Gene namesi
Name:HIPK1
Synonyms:KIAA0630, MYAK, NBAK2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000163349.21
HGNCiHGNC:19006 HIPK1
MIMi608003 gene
neXtProtiNX_Q86Z02

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi25K → R: Reduced sumoylation and cytoplasmic subcellular location. Impaired sumoylation and cytoplasmic subcellular location; when associated with R-317; R-440; R-556 and R-1203. 1 Publication1
Mutagenesisi219K → A: Loss of kinase activity. 1 Publication1
Mutagenesisi315D → N: Loss of kinase activity and impaired MAP3K5-JNK inactivation. 1 Publication1
Mutagenesisi317K → R: Nuclear subcellular location. Impaired sumoylation and cytoplasmic subcellular location; when associated with R-25; R-440; R-556 and R-1203. 1 Publication1
Mutagenesisi440K → R: Nuclear subcellular location. Impaired sumoylation and cytoplasmic subcellular location; when associated with R-25; R-317; R-556 and R-1203. 1 Publication1
Mutagenesisi556K → R: Nuclear subcellular location. Impaired sumoylation and cytoplasmic subcellular location; when associated with R-25; R-317; R-440 and R-1203. 1 Publication1
Mutagenesisi1203K → R: Nuclear subcellular location. Impaired sumoylation and cytoplasmic subcellular location; when associated with R-25; R-317; R-440 and R-556. 1 Publication1

Organism-specific databases

DisGeNETi204851
OpenTargetsiENSG00000163349
PharmGKBiPA134897980

Chemistry databases

ChEMBLiCHEMBL5427
GuidetoPHARMACOLOGYi2033

Polymorphism and mutation databases

BioMutaiHIPK1
DMDMi34395641

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000859931 – 1210Homeodomain-interacting protein kinase 1Add BLAST1210

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki25Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate
Cross-linki25Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Cross-linki120Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki124Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei872PhosphoserineCombined sources1
Modified residuei967PhosphoserineCombined sources1
Cross-linki991Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei1200PhosphoserineCombined sources1
Cross-linki1203Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication

Post-translational modificationi

Autophosphorylated. Phosphorylated and activated by JNK1.1 Publication
Degraded by PARK7 at the protein level.
Sumoylated. When conjugated it is directed to nuclear speckles. SENP1-mediated desumoylation is mediated by TNF in response to stress stimuli, triggering transient translocation from nucleus to cytoplasm.2 Publications

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ86Z02
MaxQBiQ86Z02
PaxDbiQ86Z02
PeptideAtlasiQ86Z02
PRIDEiQ86Z02
ProteomicsDBi70492
70493 [Q86Z02-2]
70494 [Q86Z02-3]
70495 [Q86Z02-4]

PTM databases

iPTMnetiQ86Z02
PhosphoSitePlusiQ86Z02

Expressioni

Tissue specificityi

Ubiquitously expressed with highest levels in skeletal muscle and heart. Overexpressed in breast cancer cell lines. Isoform 2 is highly expressed in testis.2 Publications

Gene expression databases

BgeeiENSG00000163349 Expressed in 239 organ(s), highest expression level in oviduct epithelium
CleanExiHS_HIPK1
ExpressionAtlasiQ86Z02 baseline and differential
GenevisibleiQ86Z02 HS

Organism-specific databases

HPAiHPA016664

Interactioni

Subunit structurei

Interacts with Nkx1-2, Nkx2-5, MYB, PARK7, DAXX and p53/TP53. Part of a cytoplasmic complex made of HIPK1, DAB2IP and MAP3K5 in response to TNF. This complex formation promotes MAP3K5-JNK activation and subsequent apoptosis.5 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi128490, 17 interactors
ELMiQ86Z02
IntActiQ86Z02, 17 interactors
MINTiQ86Z02
STRINGi9606.ENSP00000358571

Chemistry databases

BindingDBiQ86Z02

Structurei

3D structure databases

ProteinModelPortaliQ86Z02
SMRiQ86Z02
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini190 – 518Protein kinasePROSITE-ProRule annotationAdd BLAST329

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni885 – 1093Interaction with TP531 PublicationAdd BLAST209
Regioni891 – 998Required for localization to nuclear specklesBy similarityAdd BLAST108
Regioni902 – 926SUMO interaction motifs (SIM); required for nuclear localization and kinase activityBy similarityAdd BLAST25

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi844 – 847Nuclear localization signal 1 (NLS1)By similarity4

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0667 Eukaryota
ENOG410XPET LUCA
GeneTreeiENSGT00760000119032
HOVERGENiHBG051908
InParanoidiQ86Z02
KOiK08826
OMAiTDWRNAH
OrthoDBiEOG091G0UMX
PhylomeDBiQ86Z02
TreeFamiTF105417

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 5 potential isoforms that are computationally mapped.iShow all

Isoform 1 (identifier: Q86Z02-1) [UniParc]FASTAAdd to basket
Also known as: HIPK1-alpha

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
MASQLQVFSP PSVSSSAFCS AKKLKIEPSG WDVSGQSSND KYYTHSKTLP
60 70 80 90 100
ATQGQANSSH QVANFNIPAY DQGLLLPAPA VEHIVVTAAD SSGSAATSTF
110 120 130 140 150
QSSQTLTHRS NVSLLEPYQK CGLKRKSEEV DSNGSVQIIE EHPPLMLQNR
160 170 180 190 200
TVVGAAATTT TVTTKSSSSS GEGDYQLVQH EILCSMTNSY EVLEFLGRGT
210 220 230 240 250
FGQVAKCWKR STKEIVAIKI LKNHPSYARQ GQIEVSILSR LSSENADEYN
260 270 280 290 300
FVRSYECFQH KNHTCLVFEM LEQNLYDFLK QNKFSPLPLK YIRPILQQVA
310 320 330 340 350
TALMKLKSLG LIHADLKPEN IMLVDPVRQP YRVKVIDFGS ASHVSKAVCS
360 370 380 390 400
TYLQSRYYRA PEIILGLPFC EAIDMWSLGC VIAELFLGWP LYPGASEYDQ
410 420 430 440 450
IRYISQTQGL PAEYLLSAGT KTTRFFNRDP NLGYPLWRLK TPEEHELETG
460 470 480 490 500
IKSKEARKYI FNCLDDMAQV NMSTDLEGTD MLAEKADRRE YIDLLKKMLT
510 520 530 540 550
IDADKRITPL KTLNHQFVTM THLLDFPHSN HVKSCFQNME ICKRRVHMYD
560 570 580 590 600
TVSQIKSPFT THVAPNTSTN LTMSFSNQLN TVHNQASVLA SSSTAAAATL
610 620 630 640 650
SLANSDVSLL NYQSALYPSS AAPVPGVAQQ GVSLQPGTTQ ICTQTDPFQQ
660 670 680 690 700
TFIVCPPAFQ TGLQATTKHS GFPVRMDNAV PIVPQAPAAQ PLQIQSGVLT
710 720 730 740 750
QGSCTPLMVA TLHPQVATIT PQYAVPFTLS CAAGRPALVE QTAAVLQAWP
760 770 780 790 800
GGTQQILLPS TWQQLPGVAL HNSVQPTAMI PEAMGSGQQL ADWRNAHSHG
810 820 830 840 850
NQYSTIMQQP SLLTNHVTLA TAQPLNVGVA HVVRQQQSSS LPSKKNKQSA
860 870 880 890 900
PVSSKSSLDV LPSQVYSLVG SSPLRTTSSY NSLVPVQDQH QPIIIPDTPS
910 920 930 940 950
PPVSVITIRS DTDEEEDNKY KPSSSGLKPR SNVISYVTVN DSPDSDSSLS
960 970 980 990 1000
SPYSTDTLSA LRGNSGSVLE GPGRVVADGT GTRTIIVPPL KTQLGDCTVA
1010 1020 1030 1040 1050
TQASGLLSNK TKPVASVSGQ SSGCCITPTG YRAQRGGTSA AQPLNLSQNQ
1060 1070 1080 1090 1100
QSSAAPTSQE RSSNPAPRRQ QAFVAPLSQA PYTFQHGSPL HSTGHPHLAP
1110 1120 1130 1140 1150
APAHLPSQAH LYTYAAPTSA AALGSTSSIA HLFSPQGSSR HAAAYTTHPS
1160 1170 1180 1190 1200
TLVHQVPVSV GPSLLTSASV APAQYQHQFA TQSYIGSSRG STIYTGYPLS
1210
PTKISQYSYL
Length:1,210
Mass (Da):130,843
Last modified:June 1, 2003 - v1
Checksum:iDB0BBFA6DF152909
GO
Isoform 2 (identifier: Q86Z02-2) [UniParc]FASTAAdd to basket
Also known as: HIPK1-beta

The sequence of this isoform differs from the canonical sequence as follows:
     1049-1075: NQQSSAAPTSQERSSNPAPRRQQAFVA → VSAMGYCLLFGPCTVVTFWRTLLLAGC
     1076-1210: Missing.

Show »
Length:1,075
Mass (Da):116,731
Checksum:iDC4EE791F0EEC369
GO
Isoform 3 (identifier: Q86Z02-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-374: Missing.

Show »
Length:836
Mass (Da):89,481
Checksum:iED30D5EDCA8D4918
GO
Isoform 4 (identifier: Q86Z02-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-394: Missing.
     395-399: ASEYD → MVLMF

Show »
Length:816
Mass (Da):87,302
Checksum:i97A2176C8995F038
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q5SQL3Q5SQL3_HUMAN
Homeodomain-interacting protein kin...
HIPK1
1,165Annotation score:
J3KP92J3KP92_HUMAN
Homeodomain-interacting protein kin...
HIPK1
1,176Annotation score:
D6RC95D6RC95_HUMAN
Homeodomain-interacting protein kin...
HIPK1
119Annotation score:
H3BLW0H3BLW0_HUMAN
Homeodomain-interacting protein kin...
HIPK1
491Annotation score:
D6RF28D6RF28_HUMAN
Homeodomain-interacting protein kin...
HIPK1
106Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti721P → Q in AAH33012 (PubMed:15489334).Curated1
Sequence conflicti747Missing in BAA31605 (PubMed:9734811).Curated1
Sequence conflicti799H → Y in CAD38689 (PubMed:17974005).Curated1
Sequence conflicti1054A → V in AAH36057 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0516266Q → R. Corresponds to variant dbSNP:rs35324789Ensembl.1
Natural variantiVAR_040546310G → C1 PublicationCorresponds to variant dbSNP:rs34335651Ensembl.1
Natural variantiVAR_0460471165L → V1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0131271 – 394Missing in isoform 4. 1 PublicationAdd BLAST394
Alternative sequenceiVSP_0131281 – 374Missing in isoform 3. 1 PublicationAdd BLAST374
Alternative sequenceiVSP_013129395 – 399ASEYD → MVLMF in isoform 4. 1 Publication5
Alternative sequenceiVSP_0131301049 – 1075NQQSS…QAFVA → VSAMGYCLLFGPCTVVTFWR TLLLAGC in isoform 2. 1 PublicationAdd BLAST27
Alternative sequenceiVSP_0131311076 – 1210Missing in isoform 2. 1 PublicationAdd BLAST135

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB089957 mRNA Translation: BAC57075.1
AL731797 Genomic DNA No translation available.
AL137856 Genomic DNA No translation available.
CH471122 Genomic DNA Translation: EAW56590.1
BC028408 mRNA Translation: AAH28408.1
BC033012 mRNA Translation: AAH33012.1
BC036057 mRNA Translation: AAH36057.1
AL833829 mRNA Translation: CAD38689.1
AB014530 mRNA Translation: BAA31605.1
CCDSiCCDS41370.1 [Q86Z02-3]
CCDS867.1 [Q86Z02-1]
CCDS868.1 [Q86Z02-2]
CCDS869.1 [Q86Z02-4]
RefSeqiNP_689909.2, NM_152696.3 [Q86Z02-2]
NP_852003.1, NM_181358.2 [Q86Z02-4]
NP_938009.1, NM_198268.2 [Q86Z02-1]
NP_938010.1, NM_198269.2 [Q86Z02-3]
XP_005270669.1, XM_005270612.4 [Q86Z02-1]
XP_005270670.1, XM_005270613.4 [Q86Z02-1]
UniGeneiHs.532363

Genome annotation databases

EnsembliENST00000340480; ENSP00000340956; ENSG00000163349 [Q86Z02-3]
ENST00000369553; ENSP00000358566; ENSG00000163349 [Q86Z02-4]
ENST00000369558; ENSP00000358571; ENSG00000163349 [Q86Z02-1]
ENST00000369559; ENSP00000358572; ENSG00000163349 [Q86Z02-2]
ENST00000426820; ENSP00000407442; ENSG00000163349 [Q86Z02-1]
GeneIDi204851
KEGGihsa:204851
UCSCiuc001eel.4 human [Q86Z02-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiHIPK1_HUMAN
AccessioniPrimary (citable) accession number: Q86Z02
Secondary accession number(s): A6NJ34
, O75125, Q5SQL2, Q5SQL4, Q5SQL5, Q8IYD7, Q8NDN5, Q8NEB6, Q8TBZ1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 29, 2003
Last sequence update: June 1, 2003
Last modified: September 12, 2018
This is version 148 of the entry and version 1 of the sequence. See 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

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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