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Protein

Homeodomain-interacting protein kinase 3

Gene

Hipk3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Serine/threonine-protein kinase involved in transcription regulation, apoptosis and steroidogenic gene expression. Phosphorylates JUN and RUNX2. Seems to negatively regulate apoptosis by promoting FADD phosphorylation. Enhances androgen receptor-mediated transcription. May act as a transcriptional corepressor for NK homeodomain transcription factors. The phosphorylation of NR5A1 activates SF1 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation. In osteoblasts, supports transcription activation: phosphorylates RUNX2 that synergizes with SPEN/MINT to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE).3 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei226 – 2261ATPPROSITE-ProRule annotation
Active sitei322 – 3221Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi203 – 2119ATPPROSITE-ProRule annotation

GO - Molecular functioni

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

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • mRNA transcription Source: MGI
  • negative regulation of apoptotic process Source: MGI
  • negative regulation of JUN kinase activity Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • peptidyl-serine phosphorylation Source: UniProtKB
  • peptidyl-threonine phosphorylation Source: UniProtKB
  • positive regulation of DNA binding Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Transcription, Transcription regulation

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Homeodomain-interacting protein kinase 3 (EC:2.7.11.1)
Alternative name(s):
Androgen receptor-interacting nuclear protein kinase
Short name:
ANPK
Fas-interacting serine/threonine-protein kinase
Short name:
FIST
Nuclear body-associated kinase 3
Short name:
Nbak3
Gene namesi
Name:Hipk3
Synonyms:Fist3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1314882. Hipk3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nucleus Source: UniProtKB
  • PML body Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi226 – 2261K → R: Loss of kinase activity and impaired activation of SF1. 2 Publications
Mutagenesisi226 – 2261K → S: Impairs catalytic activity. 2 Publications
Mutagenesisi322 – 3221D → N: Impairs catalytic activity and abolishes interaction with DAXX. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11921192Homeodomain-interacting protein kinase 3PRO_0000085999Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki27 – 27Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei359 – 3591PhosphotyrosineCombined sources
Cross-linki1185 – 1185Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

Post-translational modificationi

Autophosphorylated, but autophosphorylation is not required for catalytic activity.By similarity
May be sumoylated.

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9ERH7.
PRIDEiQ9ERH7.

PTM databases

iPTMnetiQ9ERH7.
PhosphoSiteiQ9ERH7.

Expressioni

Tissue specificityi

Heart, skeletal muscle, spleen, testis and lung.1 Publication

Gene expression databases

BgeeiENSMUSG00000027177.
CleanExiMM_HIPK3.
ExpressionAtlasiQ9ERH7. baseline and differential.
GenevisibleiQ9ERH7. MM.

Interactioni

Subunit structurei

Interacts with UBL1/SUMO-1 (By similarity). Interacts with and stabilizes ligand-bound androgen receptor (AR). Interacts with Nkx1-2. Interacts with FAS and DAXX. Probably part of a complex consisting of HIPK3, FAS and FADD. Binds to NR5A1/SF1, SPEN/MINT and RUNX2.By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
FasP254463EBI-524356,EBI-296206

Protein-protein interaction databases

BioGridi200308. 1 interaction.
IntActiQ9ERH7. 3 interactions.
STRINGi10090.ENSMUSP00000028600.

Structurei

3D structure databases

ProteinModelPortaliQ9ERH7.
SMRiQ9ERH7. Positions 195-524.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini197 – 525329Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni767 – 921155Interaction with ARBy similarityAdd
BLAST
Regioni775 – 86894Interaction with FASAdd
BLAST
Regioni832 – 988157Required for localization to nuclear specklesBy similarityAdd
BLAST
Regioni843 – 89553SUMO interaction motifs (SIM); required for nuclear localization and kinase activityBy similarityAdd
BLAST
Regioni847 – 85711Interaction with UBL1By similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi887 – 93953Ser-richAdd
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0667. Eukaryota.
ENOG410XPET. LUCA.
GeneTreeiENSGT00760000119032.
HOGENOMiHOG000231785.
HOVERGENiHBG051908.
InParanoidiQ9ERH7.
KOiK08826.
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. 2 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9ERH7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASQVLVYPP YVYQTQSSAF CSVKKLKVEP SGCVFQERTY PQIHVNGRNF
60 70 80 90 100
GNSHPSTKGS AFQTKIPFTK PRGHSFSLQA GAIVVKDTAG ATKVLAAQAQ
110 120 130 140 150
QAGVEAPRAV VWRNRLHFLE GPQRCGLKRK SEELENHSGA MQIVDELSIL
160 170 180 190 200
PAMLQTNMGN PVTVVTATTG SKQNCTSGEG DYQLVQHEVL CSMKNTYEVL
210 220 230 240 250
DFLGRGTFGQ VVKCWKRGTN EIVAIKILKN HPSYARQGQI EVSILARLST
260 270 280 290 300
ENADEYNFVR AYECFQHRNH TCLVFEMLEQ NLYDFLKQNK FSPLPLKVIR
310 320 330 340 350
PVLQQVATAL KKLKSLGLIH ADLKPENIML VDPVRQPYRV KVIDFGSASH
360 370 380 390 400
VSKTVCSTYL QSRYYRAPEI ILGLPFCEAI DMWSLGCVIA ELFLGWPLYP
410 420 430 440 450
GALEYDQIRY ISQTQGLPGE QLLNVGTKST RFFCRETDMS HSGWRLKTLE
460 470 480 490 500
EHEAETGMKS KEARKYIFNS LDDIVHVNTV MDLEGGDLLA EKADRREFVN
510 520 530 540 550
LLKKMLLIDA DLRITPIETL NHPFVNMKHL LDFPHSNHVK SCFHIMDICK
560 570 580 590 600
SPSSCETNNH SKMSLLRPVA SNGTAALAAN FTKVGTLRSQ ALTTSAHSVV
610 620 630 640 650
HHGIPLQAGT AQFGCGDAFH QTLIICPPAI QGIPAAHGKP TSYSIRVDNT
660 670 680 690 700
VPLVTQAPAV QPLQIRPGVL SQQTWSGRTQ QMLIPAWQQV TPMAPAAATL
710 720 730 740 750
TSEGMAGSQR LGDWGKMIPH SNHYNSVMPP PLLTNQITLS APQPISVGIA
760 770 780 790 800
HVVWPQPATT KKNKLCQNRS NSLQNTNIPH SAFISPKIIS GKEVEEVSCV
810 820 830 840 850
DTQDNHTSEG EAGTCREASV RQDSSVSDKQ RQTIIIADSP SPAVSVITIS
860 870 880 890 900
SDSDDEETSP RPSLRECKGS LDCEACQSTL NIDRMCSLSS PDSTLSTSSS
910 920 930 940 950
GQSSPSPCKR PNSMSDDEQE SGCETVDGSP TSDSSGHDSP FAENSFVEDA
960 970 980 990 1000
HQNTELGTCA GPEAKPAVGT AVEPPVGRES GLSVDEHMAN TDSTCQPLRK
1010 1020 1030 1040 1050
GQPAPGKLHQ PPALGARQQK PAAAFPQQHL NLSQVQHFGT GHQEWNGNFG
1060 1070 1080 1090 1100
HRRQQAYIPT SVTSNPFTLS HGSPNHTAVH AHLAGSTHLG GQPTLLPYPS
1110 1120 1130 1140 1150
SASLSSAAPV AHLLASPCTS RPMLQHPTYN ISHPSGIVHQ VPVGINPRLL
1160 1170 1180 1190
PSPTIHQTQY KPIFPPHSYI AASPAYTGFP LSPTKLSQYP YM
Length:1,192
Mass (Da):130,081
Last modified:July 27, 2011 - v3
Checksum:iD153322BAFB5F3F9
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti65 – 651K → N in AAC63012 (PubMed:9748262).Curated
Sequence conflicti405 – 4051Y → H in AAC63012 (PubMed:9748262).Curated
Sequence conflicti813 – 8131G → R in AAC63012 (PubMed:9748262).Curated
Sequence conflicti813 – 8131G → R in AAG25989 (PubMed:11034606).Curated
Sequence conflicti813 – 8131G → R in AAD52570 (Ref. 3) Curated
Sequence conflicti985 – 9851D → G in AAC63012 (PubMed:9748262).Curated
Sequence conflicti985 – 9851D → G in AAD52570 (Ref. 3) Curated
Sequence conflicti1084 – 10841A → D in AAC63012 (PubMed:9748262).Curated
Sequence conflicti1186 – 11861L → V in AAC63012 (PubMed:9748262).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF077660 mRNA. Translation: AAC63012.1.
AF305238 mRNA. Translation: AAG25989.1.
AF170305 mRNA. Translation: AAD52570.1.
AL844591 Genomic DNA. Translation: CAM23687.1.
CCDSiCCDS16489.1.
PIRiT17089.
RefSeqiNP_034564.2. NM_010434.2.
UniGeneiMm.257925.

Genome annotation databases

EnsembliENSMUST00000028600; ENSMUSP00000028600; ENSMUSG00000027177.
ENSMUST00000111124; ENSMUSP00000106753; ENSMUSG00000027177.
GeneIDi15259.
KEGGimmu:15259.
UCSCiuc008lju.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF077660 mRNA. Translation: AAC63012.1.
AF305238 mRNA. Translation: AAG25989.1.
AF170305 mRNA. Translation: AAD52570.1.
AL844591 Genomic DNA. Translation: CAM23687.1.
CCDSiCCDS16489.1.
PIRiT17089.
RefSeqiNP_034564.2. NM_010434.2.
UniGeneiMm.257925.

3D structure databases

ProteinModelPortaliQ9ERH7.
SMRiQ9ERH7. Positions 195-524.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200308. 1 interaction.
IntActiQ9ERH7. 3 interactions.
STRINGi10090.ENSMUSP00000028600.

PTM databases

iPTMnetiQ9ERH7.
PhosphoSiteiQ9ERH7.

Proteomic databases

PaxDbiQ9ERH7.
PRIDEiQ9ERH7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000028600; ENSMUSP00000028600; ENSMUSG00000027177.
ENSMUST00000111124; ENSMUSP00000106753; ENSMUSG00000027177.
GeneIDi15259.
KEGGimmu:15259.
UCSCiuc008lju.2. mouse.

Organism-specific databases

CTDi10114.
MGIiMGI:1314882. Hipk3.

Phylogenomic databases

eggNOGiKOG0667. Eukaryota.
ENOG410XPET. LUCA.
GeneTreeiENSGT00760000119032.
HOGENOMiHOG000231785.
HOVERGENiHBG051908.
InParanoidiQ9ERH7.
KOiK08826.
TreeFamiTF105417.

Miscellaneous databases

ChiTaRSiHipk3. mouse.
PROiQ9ERH7.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000027177.
CleanExiMM_HIPK3.
ExpressionAtlasiQ9ERH7. baseline and differential.
GenevisibleiQ9ERH7. MM.

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. 2 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHIPK3_MOUSE
AccessioniPrimary (citable) accession number: Q9ERH7
Secondary accession number(s): A2AQH2, O88906, Q9QZR2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: July 27, 2011
Last modified: September 7, 2016
This is version 126 of the entry and version 3 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

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.