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Protein

Homeodomain-interacting protein kinase 3

Gene

HIPK3

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, 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).2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei226ATPPROSITE-ProRule annotation1
Active sitei322Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi203 – 211ATPPROSITE-ProRule annotation9

GO - Molecular functioni

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

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • mRNA transcription Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of JUN kinase activity Source: UniProtKB
  • peptidyl-serine phosphorylation Source: UniProtKB
  • peptidyl-threonine phosphorylation Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB-KW
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

Enzyme and pathway databases

BioCyciZFISH:HS03308-MONOMER.
SignaLinkiQ9H422.
SIGNORiQ9H422.

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
Homolog of protein kinase YAK1
Gene namesi
Name:HIPK3
Synonyms:DYRK6, FIST3, PKY
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:4915. HIPK3.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi226K → R: Loss of kinase activity and impaired activation of SF1. 1 Publication1

Organism-specific databases

DisGeNETi10114.
OpenTargetsiENSG00000110422.
PharmGKBiPA29292.

Chemistry databases

ChEMBLiCHEMBL4577.
GuidetoPHARMACOLOGYi2035.

Polymorphism and mutation databases

DMDMi61213741.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000859981 – 1215Homeodomain-interacting protein kinase 3Add BLAST1215

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki27Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei359PhosphotyrosineBy similarity1
Cross-linki1208Glycyl 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.By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9H422.
MaxQBiQ9H422.
PaxDbiQ9H422.
PeptideAtlasiQ9H422.
PRIDEiQ9H422.

PTM databases

iPTMnetiQ9H422.
PhosphoSitePlusiQ9H422.

Expressioni

Tissue specificityi

Overexpressed in multidrug resistant cells. Highly expressed in heart and skeletal muscle, and at lower levels in placenta, pancreas, brain, spleen, prostate, thymus, testis, small intestine, colon and leukocytes. Not found in liver and lung.3 Publications

Gene expression databases

BgeeiENSG00000110422.
CleanExiHS_HIPK3.
ExpressionAtlasiQ9H422. baseline and differential.
GenevisibleiQ9H422. HS.

Organism-specific databases

HPAiHPA028069.

Interactioni

Subunit structurei

Interacts with Nkx1-2. Interacts with FAS and DAXX. Probably part of a complex consisting of HIPK3, FAS and FADD. Interacts with and stabilizes ligand-bound androgen receptor (AR) (By similarity). Interacts with UBL1/SUMO-1. Binds to NR5A1/SF1, SPEN/MINT and RUNX2.By similarity2 Publications

Protein-protein interaction databases

BioGridi115420. 30 interactors.
IntActiQ9H422. 22 interactors.
MINTiMINT-1183373.
STRINGi9606.ENSP00000304226.

Chemistry databases

BindingDBiQ9H422.

Structurei

3D structure databases

ProteinModelPortaliQ9H422.
SMRiQ9H422.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini197 – 525Protein kinasePROSITE-ProRule annotationAdd BLAST329

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni767 – 944Interaction with ARBy similarityAdd BLAST178
Regioni796 – 891Interaction with FASBy similarityAdd BLAST96
Regioni855 – 1011Required for localization to nuclear specklesBy similarityAdd BLAST157
Regioni866 – 918SUMO interaction motifs (SIM); required for nuclear localization and kinase activityBy similarityAdd BLAST53
Regioni870 – 880Interaction with UBL1CuratedAdd BLAST11

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi910 – 962Ser-richAdd BLAST53

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0667. Eukaryota.
ENOG410XPET. LUCA.
GeneTreeiENSGT00760000119032.
HOGENOMiHOG000231785.
HOVERGENiHBG051908.
InParanoidiQ9H422.
KOiK08826.
OMAiPAMLQTN.
OrthoDBiEOG091G0UMX.
PhylomeDBiQ9H422.
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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9H422-1) [UniParc]FASTAAdd to basket
Also known as: HIPK3

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
MASQVLVYPP YVYQTQSSAF CSVKKLKVEP SSCVFQERNY PRTYVNGRNF
60 70 80 90 100
GNSHPPTKGS AFQTKIPFNR PRGHNFSLQT SAVVLKNTAG ATKVIAAQAQ
110 120 130 140 150
QAHVQAPQIG AWRNRLHFLE GPQRCGLKRK SEELDNHSSA MQIVDELSIL
160 170 180 190 200
PAMLQTNMGN PVTVVTATTG SKQNCTTGEG 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
PILQQVATAL KKLKSLGLIH ADLKPENIML VDPVRQPYRV KVIDFGSASH
360 370 380 390 400
VSKTVCSTYL QSRYYRAPEI ILGLPFCEAI DMWSLGCVIA ELFLGWPLYP
410 420 430 440 450
GALEYDQIRY ISQTQGLPGE QLLNVGTKST RFFCKETDMS HSGWRLKTLE
460 470 480 490 500
EHEAETGMKS KEARKYIFNS LDDVAHVNTV MDLEGSDLLA EKADRREFVS
510 520 530 540 550
LLKKMLLIDA DLRITPAETL NHPFVNMKHL LDFPHSNHVK SCFHIMDICK
560 570 580 590 600
SHLNSCDTNN HNKTSLLRPV ASSSTATLTA NFTKIGTLRS QALTTSAHSV
610 620 630 640 650
VHHGIPLQAG TAQFGCGDAF QQTLIICPPA IQGIPATHGK PTSYSIRVDN
660 670 680 690 700
TVPLVTQAPA VQPLQIRPGV LSQTWSGRTQ QMLVPAWQQV TPLAPATTTL
710 720 730 740 750
TSESVAGSHR LGDWGKMISC SNHYNSVMPQ PLLTNQITLS APQPVSVGIA
760 770 780 790 800
HVVWPQPATT KKNKQCQNRG ILVKLMEWEP GREEINAFSW SNSLQNTNIP
810 820 830 840 850
HSAFISPKII NGKDVEEVSC IETQDNQNSE GEARNCCETS IRQDSDSSVS
860 870 880 890 900
DKQRQTIIIA DSPSPAVSVI TISSDTDEEE TSQRHSLREC KGSLDCEACQ
910 920 930 940 950
STLNIDRMCS LSSPDSTLST SSSGQSSPSP CKRPNSMSDE EQESSCDTVD
960 970 980 990 1000
GSPTSDSSGH DSPFAESTFV EDTHENTELV SSADTETKPA VCSVVVPPVE
1010 1020 1030 1040 1050
LENGLNADEH MANTDSICQP LIKGRSAPGR LNQPSAVGTR QQKLTSAFQQ
1060 1070 1080 1090 1100
QHLNFSQVQH FGSGHQEWNG NFGHRRQQAY IPTSVTSNPF TLSHGSPNHT
1110 1120 1130 1140 1150
AVHAHLAGNT HLGGQPTLLP YPSSATLSSA APVAHLLASP CTSRPMLQHP
1160 1170 1180 1190 1200
TYNISHPSGI VHQVPVGLNP RLLPSPTIHQ TQYKPIFPPH SYIAASPAYT
1210
GFPLSPTKLS QYPYM
Length:1,215
Mass (Da):133,743
Last modified:March 1, 2001 - v1
Checksum:iE952D04786955721
GO
Isoform 2 (identifier: Q9H422-2) [UniParc]FASTAAdd to basket
Also known as: FIST

The sequence of this isoform differs from the canonical sequence as follows:
     770-790: Missing.

Show »
Length:1,194
Mass (Da):131,256
Checksum:i9F7C34FB1110F10B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti69N → K in AAG25990 (PubMed:11034606).Curated1
Sequence conflicti111A → V in AAC64294 (PubMed:9373137).Curated1
Sequence conflicti1148Q → K in AAG25990 (PubMed:11034606).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040549142Q → R.1 PublicationCorresponds to variant rs34193811dbSNPEnsembl.1
Natural variantiVAR_040550170G → E.1 PublicationCorresponds to variant rs34698015dbSNPEnsembl.1
Natural variantiVAR_040551191C → R.1 PublicationCorresponds to variant rs35689361dbSNPEnsembl.1
Natural variantiVAR_051627474V → I.Corresponds to variant rs266472dbSNPEnsembl.1
Natural variantiVAR_040552500S → N.1 PublicationCorresponds to variant rs11032229dbSNPEnsembl.1
Natural variantiVAR_040553729P → L.1 PublicationCorresponds to variant rs55807239dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_013140770 – 790Missing in isoform 2. 1 PublicationAdd BLAST21

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF004849 mRNA. Translation: AAC64294.1.
AF305239 mRNA. Translation: AAG25990.1.
AL122015 Genomic DNA. Translation: CAC13164.1.
AL122015 Genomic DNA. Translation: CAJ55828.1.
Y09306 mRNA. Translation: CAA70489.1. Different termination.
CCDSiCCDS41634.1. [Q9H422-2]
CCDS7884.1. [Q9H422-1]
RefSeqiNP_001041665.1. NM_001048200.2. [Q9H422-2]
NP_001265092.1. NM_001278163.1. [Q9H422-2]
NP_005725.3. NM_005734.4. [Q9H422-1]
XP_005252786.1. XM_005252729.2. [Q9H422-1]
XP_016872565.1. XM_017017076.1. [Q9H422-1]
XP_016872566.1. XM_017017077.1. [Q9H422-2]
UniGeneiHs.201918.
Hs.709696.

Genome annotation databases

EnsembliENST00000303296; ENSP00000304226; ENSG00000110422. [Q9H422-1]
ENST00000379016; ENSP00000368301; ENSG00000110422. [Q9H422-2]
ENST00000456517; ENSP00000398241; ENSG00000110422. [Q9H422-2]
ENST00000525975; ENSP00000431710; ENSG00000110422. [Q9H422-2]
GeneIDi10114.
KEGGihsa:10114.
UCSCiuc001mul.3. human. [Q9H422-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF004849 mRNA. Translation: AAC64294.1.
AF305239 mRNA. Translation: AAG25990.1.
AL122015 Genomic DNA. Translation: CAC13164.1.
AL122015 Genomic DNA. Translation: CAJ55828.1.
Y09306 mRNA. Translation: CAA70489.1. Different termination.
CCDSiCCDS41634.1. [Q9H422-2]
CCDS7884.1. [Q9H422-1]
RefSeqiNP_001041665.1. NM_001048200.2. [Q9H422-2]
NP_001265092.1. NM_001278163.1. [Q9H422-2]
NP_005725.3. NM_005734.4. [Q9H422-1]
XP_005252786.1. XM_005252729.2. [Q9H422-1]
XP_016872565.1. XM_017017076.1. [Q9H422-1]
XP_016872566.1. XM_017017077.1. [Q9H422-2]
UniGeneiHs.201918.
Hs.709696.

3D structure databases

ProteinModelPortaliQ9H422.
SMRiQ9H422.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115420. 30 interactors.
IntActiQ9H422. 22 interactors.
MINTiMINT-1183373.
STRINGi9606.ENSP00000304226.

Chemistry databases

BindingDBiQ9H422.
ChEMBLiCHEMBL4577.
GuidetoPHARMACOLOGYi2035.

PTM databases

iPTMnetiQ9H422.
PhosphoSitePlusiQ9H422.

Polymorphism and mutation databases

DMDMi61213741.

Proteomic databases

EPDiQ9H422.
MaxQBiQ9H422.
PaxDbiQ9H422.
PeptideAtlasiQ9H422.
PRIDEiQ9H422.

Protocols and materials databases

DNASUi10114.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000303296; ENSP00000304226; ENSG00000110422. [Q9H422-1]
ENST00000379016; ENSP00000368301; ENSG00000110422. [Q9H422-2]
ENST00000456517; ENSP00000398241; ENSG00000110422. [Q9H422-2]
ENST00000525975; ENSP00000431710; ENSG00000110422. [Q9H422-2]
GeneIDi10114.
KEGGihsa:10114.
UCSCiuc001mul.3. human. [Q9H422-1]

Organism-specific databases

CTDi10114.
DisGeNETi10114.
GeneCardsiHIPK3.
HGNCiHGNC:4915. HIPK3.
HPAiHPA028069.
MIMi604424. gene.
neXtProtiNX_Q9H422.
OpenTargetsiENSG00000110422.
PharmGKBiPA29292.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0667. Eukaryota.
ENOG410XPET. LUCA.
GeneTreeiENSGT00760000119032.
HOGENOMiHOG000231785.
HOVERGENiHBG051908.
InParanoidiQ9H422.
KOiK08826.
OMAiPAMLQTN.
OrthoDBiEOG091G0UMX.
PhylomeDBiQ9H422.
TreeFamiTF105417.

Enzyme and pathway databases

BioCyciZFISH:HS03308-MONOMER.
SignaLinkiQ9H422.
SIGNORiQ9H422.

Miscellaneous databases

ChiTaRSiHIPK3. human.
GeneWikiiHIPK3.
GenomeRNAii10114.
PROiQ9H422.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000110422.
CleanExiHS_HIPK3.
ExpressionAtlasiQ9H422. baseline and differential.
GenevisibleiQ9H422. 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. 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_HUMAN
AccessioniPrimary (citable) accession number: Q9H422
Secondary accession number(s): O14632
, Q2PBG4, Q2PBG5, Q92632, Q9HAS2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: March 1, 2001
Last modified: November 2, 2016
This is version 141 of the entry and version 1 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: 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.