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Protein

Homeodomain-interacting protein kinase 1

Gene

Hipk1

Organism
Mus musculus (Mouse)
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.4 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

  • ATP binding Source: UniProtKB-KW
  • protein kinase activity Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB-KW
  • transcription corepressor activity Source: UniProtKB

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-MMU-6804756 Regulation of TP53 Activity through Phosphorylation

Names & Taxonomyi

Protein namesi
Recommended name:
Homeodomain-interacting protein kinase 1 (EC:2.7.11.1)
Alternative name(s):
Nuclear body-associated kinase 2
Protein kinase Myak
Gene namesi
Name:Hipk1
Synonyms:Kiaa0630, Myak, Nbak2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1314873 Hipk1

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

Disruption phenotypei

Small eyes with deficient lens, abnormal retinal lamination, and thickened retinas.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi219K → A: Abolishes enzymatic activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000859941 – 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); alternateBy similarity
Cross-linki25Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Cross-linki120Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki124Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei872PhosphoserineBy similarity1
Cross-linki991Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei1200PhosphoserineBy similarity1
Cross-linki1203Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

Post-translational modificationi

Phosphorylated and activated by JNK1 (By similarity). Autophosphorylated.By similarity
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.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiO88904
PaxDbiO88904
PRIDEiO88904

PTM databases

iPTMnetiO88904
PhosphoSitePlusiO88904

Expressioni

Tissue specificityi

Ubiquitously expressed, with high levels in reproductive tissues. Expressed in the epithelial layer of mammary gland, uterus and epididymis, in the corpus luteum, and in post-meiotic round spermatids.2 Publications

Developmental stagei

Highest at E12, where it is expressed primarily in the central nervous system. Highly induced during primary fetal liver erythropoiesis. Expressed in the inner retina during late embryogenesis, predominantly in cytoplasm.3 Publications

Gene expression databases

BgeeiENSMUSG00000008730 Expressed in 274 organ(s), highest expression level in blood
CleanExiMM_HIPK1
ExpressionAtlasiO88904 baseline and differential
GenevisibleiO88904 MM

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.3 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi200306, 2 interactors
IntActiO88904, 5 interactors
MINTiO88904
STRINGi10090.ENSMUSP00000029438

Structurei

3D structure databases

ProteinModelPortaliO88904
SMRiO88904
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
HOGENOMiHOG000231785
HOVERGENiHBG051908
InParanoidiO88904
KOiK08826
OMAiTDWRNAH
OrthoDBiEOG091G0UMX
PhylomeDBiO88904
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 (3+)i

Sequence statusi: Complete.

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

This entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: O88904-1) [UniParc]FASTAAdd to basket
Also known as: 2b, Myak-L

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
ATQGQASSSH QVANFNLPAY DQGLLLPAPA VEHIVVTAAD SSGSAATATF
110 120 130 140 150
QSSQTLTHRS NVSLLEPYQK CGLKRKSEEV ESNGSVQIIE 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 SHLLDFPHSS 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 AWQQLPGVAL HNSVQPAAVI PEAMGSSQQL ADWRNAHSHG
810 820 830 840 850
NQYSTIMQQP SLLTNHVTLA TAQPLNVGVA HVVRQQQSSS LPSKKNKQSA
860 870 880 890 900
PVSSKSSLEV LPSQVYSLVG SSPLRTTSSY NSLVPVQDQH QPIIIPDTPS
910 920 930 940 950
PPVSVITIRS DTDEEEDNKY KPNSSSLKAR SNVISYVTVN DSPDSDSSLS
960 970 980 990 1000
SPHPTDTLSA LRGNSGTLLE GPGRPAADGI GTRTIIVPPL KTQLGDCTVA
1010 1020 1030 1040 1050
TQASGLLSSK TKPVASVSGQ SSGCCITPTG YRAQRGGASA VQPLNLSQNQ
1060 1070 1080 1090 1100
QSSSASTSQE RSSNPAPRRQ QAFVAPLSQA PYAFQHGSPL HSTGHPHLAP
1110 1120 1130 1140 1150
APAHLPSQPH LYTYAAPTSA AALGSTSSIA HLFSPQGSSR HAAAYTTHPS
1160 1170 1180 1190 1200
TLVHQVPVSV GPSLLTSASV APAQYQHQFA TQSYIGSSRG STIYTGYPLS
1210
PTKISQYSYL
Length:1,210
Mass (Da):130,723
Last modified:March 15, 2005 - v2
Checksum:i26D264B883220640
GO
Isoform 2 (identifier: O88904-2) [UniParc]FASTAAdd to basket
Also known as: 2a

The sequence of this isoform differs from the canonical sequence as follows:
     702-746: Missing.

Show »
Length:1,165
Mass (Da):126,144
Checksum:iC082CA8CD6BB206C
GO
Isoform 3 (identifier: O88904-3) [UniParc]FASTAAdd to basket
Also known as: Myak-S

The sequence of this isoform differs from the canonical sequence as follows:
     661-719: TGLQATTKHS...ATLHPQVATI → KSEQAEGNEG...KAFWIPCEDG
     720-1209: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:720
Mass (Da):79,448
Checksum:iFEEEFF23976995DD
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0R4J1V6A0A0R4J1V6_MOUSE
Homeodomain-interacting protein kin...
Hipk1
719Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti732Missing in AAC63010 (PubMed:9748262).Curated1
Sequence conflicti921K → E in AAC63010 (PubMed:9748262).Curated1
Sequence conflicti953H → Y in BAC65615 (PubMed:12693553).Curated1
Sequence conflicti954P → S in AAC63010 (PubMed:9748262).Curated1
Sequence conflicti954P → S in BAC65615 (PubMed:12693553).Curated1
Sequence conflicti1134S → F in AAC63010 (PubMed:9748262).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_013132661 – 719TGLQA…QVATI → KSEQAEGNEGLGETESSPGG QESGSGVSQGETTGGAQEQI HNPWTTSNNKAFWIPCEDG in isoform 3. 1 PublicationAdd BLAST59
Alternative sequenceiVSP_013133702 – 746Missing in isoform 2. 1 PublicationAdd BLAST45
Alternative sequenceiVSP_013134720 – 1209Missing in isoform 3. 1 PublicationAdd BLAST490

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF077658 mRNA Translation: AAC63010.1
AF071070 mRNA Translation: AAD41592.1
AF071071 mRNA Translation: AAD41593.1
AF170303 mRNA Translation: AAD52568.1
AF170304 mRNA Translation: AAD52569.1
BC145697 mRNA Translation: AAI45698.1
BC145699 mRNA Translation: AAI45700.1
AK122333 mRNA Translation: BAC65615.1
CCDSiCCDS38576.1 [O88904-1]
CCDS79992.1 [O88904-2]
PIRiT14357
RefSeqiNP_001288233.1, NM_001301304.1 [O88904-1]
NP_001288235.1, NM_001301306.1 [O88904-2]
NP_034562.2, NM_010432.2 [O88904-1]
UniGeneiMm.20827

Genome annotation databases

EnsembliENSMUST00000029438; ENSMUSP00000029438; ENSMUSG00000008730 [O88904-1]
ENSMUST00000106845; ENSMUSP00000102458; ENSMUSG00000008730 [O88904-2]
ENSMUST00000118317; ENSMUSP00000113998; ENSMUSG00000008730 [O88904-1]
GeneIDi15257
KEGGimmu:15257
UCSCiuc008qtg.2 mouse [O88904-1]
uc012cve.1 mouse [O88904-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF077658 mRNA Translation: AAC63010.1
AF071070 mRNA Translation: AAD41592.1
AF071071 mRNA Translation: AAD41593.1
AF170303 mRNA Translation: AAD52568.1
AF170304 mRNA Translation: AAD52569.1
BC145697 mRNA Translation: AAI45698.1
BC145699 mRNA Translation: AAI45700.1
AK122333 mRNA Translation: BAC65615.1
CCDSiCCDS38576.1 [O88904-1]
CCDS79992.1 [O88904-2]
PIRiT14357
RefSeqiNP_001288233.1, NM_001301304.1 [O88904-1]
NP_001288235.1, NM_001301306.1 [O88904-2]
NP_034562.2, NM_010432.2 [O88904-1]
UniGeneiMm.20827

3D structure databases

ProteinModelPortaliO88904
SMRiO88904
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200306, 2 interactors
IntActiO88904, 5 interactors
MINTiO88904
STRINGi10090.ENSMUSP00000029438

PTM databases

iPTMnetiO88904
PhosphoSitePlusiO88904

Proteomic databases

MaxQBiO88904
PaxDbiO88904
PRIDEiO88904

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000029438; ENSMUSP00000029438; ENSMUSG00000008730 [O88904-1]
ENSMUST00000106845; ENSMUSP00000102458; ENSMUSG00000008730 [O88904-2]
ENSMUST00000118317; ENSMUSP00000113998; ENSMUSG00000008730 [O88904-1]
GeneIDi15257
KEGGimmu:15257
UCSCiuc008qtg.2 mouse [O88904-1]
uc012cve.1 mouse [O88904-2]

Organism-specific databases

CTDi204851
MGIiMGI:1314873 Hipk1
RougeiSearch...

Phylogenomic databases

eggNOGiKOG0667 Eukaryota
ENOG410XPET LUCA
GeneTreeiENSGT00760000119032
HOGENOMiHOG000231785
HOVERGENiHBG051908
InParanoidiO88904
KOiK08826
OMAiTDWRNAH
OrthoDBiEOG091G0UMX
PhylomeDBiO88904
TreeFamiTF105417

Enzyme and pathway databases

ReactomeiR-MMU-6804756 Regulation of TP53 Activity through Phosphorylation

Miscellaneous databases

PROiPR:O88904
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000008730 Expressed in 274 organ(s), highest expression level in blood
CleanExiMM_HIPK1
ExpressionAtlasiO88904 baseline and differential
GenevisibleiO88904 MM

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
ProtoNetiSearch...

Entry informationi

Entry nameiHIPK1_MOUSE
AccessioniPrimary (citable) accession number: O88904
Secondary accession number(s): A6H5Z7
, Q80TV5, Q9QUQ8, Q9QZR3, Q9WVN7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 29, 2003
Last sequence update: March 15, 2005
Last modified: November 7, 2018
This is version 166 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

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

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