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Q9H422 (HIPK3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:HIPK3
Synonyms:DYRK6, FIST3, PKY
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1215 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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). Ref.7 Ref.8

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Subunit structure

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. Ref.6 Ref.8

Subcellular location

Cytoplasm. Nucleus Ref.2.

Tissue specificity

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. Ref.1 Ref.2 Ref.5

Post-translational modification

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

May be sumoylated By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. HIPK subfamily.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processApoptosis
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

mRNA transcription

Inferred from direct assay Ref.8. Source: UniProtKB

negative regulation of JUN kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of apoptotic process

Inferred from mutant phenotype Ref.7. Source: UniProtKB

peptidyl-serine phosphorylation

Inferred from sequence or structural similarity Ref.2. Source: UniProtKB

peptidyl-threonine phosphorylation

Inferred from sequence or structural similarity Ref.2. Source: UniProtKB

protein phosphorylation

Inferred from direct assay Ref.7. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentPML body

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay. Source: HPA

nucleus

Inferred from direct assay. Source: HPA

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein kinase activity

Inferred from direct assay Ref.7. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from sequence or structural similarity Ref.2. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9H422-1)

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.
Isoform 2 (identifier: Q9H422-2)

Also known as: FIST;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12151215Homeodomain-interacting protein kinase 3
PRO_0000085998

Regions

Domain197 – 525329Protein kinase
Nucleotide binding203 – 2119ATP By similarity
Region767 – 944178Interaction with AR By similarity
Region796 – 89196Interaction with FAS By similarity
Region855 – 1011157Required for localization to nuclear speckles By similarity
Region866 – 91853SUMO interaction motifs (SIM); required for nuclear localization and kinase activity By similarity
Region870 – 88011Interaction with UBL1 Probable
Compositional bias910 – 96253Ser-rich

Sites

Active site3221Proton acceptor By similarity
Binding site2261ATP By similarity

Amino acid modifications

Modified residue3591Phosphotyrosine By similarity
Cross-link27Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Cross-link1208Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Natural variations

Alternative sequence770 – 79021Missing in isoform 2.
VSP_013140
Natural variant1421Q → R. Ref.9
Corresponds to variant rs34193811 [ dbSNP | Ensembl ].
VAR_040549
Natural variant1701G → E. Ref.9
Corresponds to variant rs34698015 [ dbSNP | Ensembl ].
VAR_040550
Natural variant1911C → R. Ref.9
Corresponds to variant rs35689361 [ dbSNP | Ensembl ].
VAR_040551
Natural variant4741V → I.
Corresponds to variant rs266472 [ dbSNP | Ensembl ].
VAR_051627
Natural variant5001S → N. Ref.9
Corresponds to variant rs11032229 [ dbSNP | Ensembl ].
VAR_040552
Natural variant7291P → L. Ref.9
Corresponds to variant rs55807239 [ dbSNP | Ensembl ].
VAR_040553

Experimental info

Mutagenesis2261K → R: Loss of kinase activity and impaired activation of SF1. Ref.8
Sequence conflict691N → K in AAG25990. Ref.2
Sequence conflict1111A → V in AAC64294. Ref.1
Sequence conflict11481Q → K in AAG25990. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (HIPK3) [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: E952D04786955721

FASTA1,215133,743
        10         20         30         40         50         60 
MASQVLVYPP YVYQTQSSAF CSVKKLKVEP SSCVFQERNY PRTYVNGRNF GNSHPPTKGS 

        70         80         90        100        110        120 
AFQTKIPFNR PRGHNFSLQT SAVVLKNTAG ATKVIAAQAQ QAHVQAPQIG AWRNRLHFLE 

       130        140        150        160        170        180 
GPQRCGLKRK SEELDNHSSA MQIVDELSIL PAMLQTNMGN PVTVVTATTG SKQNCTTGEG 

       190        200        210        220        230        240 
DYQLVQHEVL CSMKNTYEVL DFLGRGTFGQ VVKCWKRGTN EIVAIKILKN HPSYARQGQI 

       250        260        270        280        290        300 
EVSILARLST ENADEYNFVR AYECFQHRNH TCLVFEMLEQ NLYDFLKQNK FSPLPLKVIR 

       310        320        330        340        350        360 
PILQQVATAL KKLKSLGLIH ADLKPENIML VDPVRQPYRV KVIDFGSASH VSKTVCSTYL 

       370        380        390        400        410        420 
QSRYYRAPEI ILGLPFCEAI DMWSLGCVIA ELFLGWPLYP GALEYDQIRY ISQTQGLPGE 

       430        440        450        460        470        480 
QLLNVGTKST RFFCKETDMS HSGWRLKTLE EHEAETGMKS KEARKYIFNS LDDVAHVNTV 

       490        500        510        520        530        540 
MDLEGSDLLA EKADRREFVS LLKKMLLIDA DLRITPAETL NHPFVNMKHL LDFPHSNHVK 

       550        560        570        580        590        600 
SCFHIMDICK SHLNSCDTNN HNKTSLLRPV ASSSTATLTA NFTKIGTLRS QALTTSAHSV 

       610        620        630        640        650        660 
VHHGIPLQAG TAQFGCGDAF QQTLIICPPA IQGIPATHGK PTSYSIRVDN TVPLVTQAPA 

       670        680        690        700        710        720 
VQPLQIRPGV LSQTWSGRTQ QMLVPAWQQV TPLAPATTTL TSESVAGSHR LGDWGKMISC 

       730        740        750        760        770        780 
SNHYNSVMPQ PLLTNQITLS APQPVSVGIA HVVWPQPATT KKNKQCQNRG ILVKLMEWEP 

       790        800        810        820        830        840 
GREEINAFSW SNSLQNTNIP HSAFISPKII NGKDVEEVSC IETQDNQNSE GEARNCCETS 

       850        860        870        880        890        900 
IRQDSDSSVS DKQRQTIIIA DSPSPAVSVI TISSDTDEEE TSQRHSLREC KGSLDCEACQ 

       910        920        930        940        950        960 
STLNIDRMCS LSSPDSTLST SSSGQSSPSP CKRPNSMSDE EQESSCDTVD GSPTSDSSGH 

       970        980        990       1000       1010       1020 
DSPFAESTFV EDTHENTELV SSADTETKPA VCSVVVPPVE LENGLNADEH MANTDSICQP 

      1030       1040       1050       1060       1070       1080 
LIKGRSAPGR LNQPSAVGTR QQKLTSAFQQ QHLNFSQVQH FGSGHQEWNG NFGHRRQQAY 

      1090       1100       1110       1120       1130       1140 
IPTSVTSNPF TLSHGSPNHT AVHAHLAGNT HLGGQPTLLP YPSSATLSSA APVAHLLASP 

      1150       1160       1170       1180       1190       1200 
CTSRPMLQHP TYNISHPSGI VHQVPVGLNP RLLPSPTIHQ TQYKPIFPPH SYIAASPAYT 

      1210 
GFPLSPTKLS QYPYM 

« Hide

Isoform 2 (FIST) [UniParc].

Checksum: 9F7C34FB1110F10B
Show »

FASTA1,194131,256

References

« Hide 'large scale' references
[1]"Identification and sequence of human PKY, a putative kinase with increased expression in multidrug-resistant cells, with homology to yeast protein kinase Yak1."
Begley D.A., Berkenpas M.B., Sampson K.E., Abraham I.
Gene 200:35-43(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[2]"FIST/HIPK3: a Fas/FADD-interacting serine/threonine kinase that induces FADD phosphorylation and inhibits Fas-mediated Jun NH2-terminal kinase activation."
Rochat-Steiner V., Becker K., Micheau O., Schneider P., Burns K., Tschopp J.
J. Exp. Med. 192:1165-1174(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[3]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Becker W., Joost H.G.
Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-295 (ISOFORMS 1/2).
[5]"Activation of androgen receptor function by a novel nuclear protein kinase."
Moilanen A.-M., Karvonen U., Poukka H., Jaenne O.A., Palvimo J.J.
Mol. Biol. Cell 9:2527-2543(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[6]"Covalent modification of p73alpha by SUMO-1. Two-hybrid screening with p73 identifies novel SUMO-1-interacting proteins and a SUMO-1 interaction motif."
Minty A., Dumont X., Kaghad M., Caput D.
J. Biol. Chem. 275:36316-36323(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UBL1.
[7]"JNK regulates HIPK3 expression and promotes resistance to Fas-mediated apoptosis in DU 145 prostate carcinoma cells."
Curtin J.F., Cotter T.G.
J. Biol. Chem. 279:17090-17100(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"Cyclic AMP stimulates SF-1-dependent CYP11A1 expression through homeodomain-interacting protein kinase 3-mediated Jun N-terminal kinase and c-Jun phosphorylation."
Lan H.-C., Li H.-J., Lin G., Lai P.-Y., Chung B.-C.
Mol. Cell. Biol. 27:2027-2036(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS KINASE AND IN CAMP SIGNALING PATHWAY, INTERACTION WITH NR5A1/SF1, MUTAGENESIS OF LYS-226.
[9]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] ARG-142; GLU-170; ARG-191; ASN-500 AND LEU-729.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS41634.1. [Q9H422-2]
CCDS7884.1. [Q9H422-1]
RefSeqNP_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_006718183.1. XM_006718120.1. [Q9H422-1]
UniGeneHs.201918.
Hs.709696.

3D structure databases

ProteinModelPortalQ9H422.
SMRQ9H422. Positions 189-557.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115420. 32 interactions.
IntActQ9H422. 22 interactions.
MINTMINT-1183373.
STRING9606.ENSP00000304226.

Chemistry

BindingDBQ9H422.
ChEMBLCHEMBL4577.
GuidetoPHARMACOLOGY2035.

PTM databases

PhosphoSiteQ9H422.

Polymorphism databases

DMDM61213741.

Proteomic databases

PaxDbQ9H422.
PRIDEQ9H422.

Protocols and materials databases

DNASU10114.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000303296; ENSP00000304226; ENSG00000110422. [Q9H422-1]
ENST00000379016; ENSP00000368301; ENSG00000110422. [Q9H422-2]
ENST00000456517; ENSP00000398241; ENSG00000110422. [Q9H422-2]
ENST00000525975; ENSP00000431710; ENSG00000110422. [Q9H422-2]
GeneID10114.
KEGGhsa:10114.
UCSCuc001mul.2. human. [Q9H422-1]
uc001mum.2. human. [Q9H422-2]

Organism-specific databases

CTD10114.
GeneCardsGC11P033235.
HGNCHGNC:4915. HIPK3.
HPAHPA028069.
MIM604424. gene.
neXtProtNX_Q9H422.
PharmGKBPA29292.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000231785.
HOVERGENHBG051908.
InParanoidQ9H422.
KOK08826.
OMAPAMLQTN.
OrthoDBEOG7034GK.
PhylomeDBQ9H422.
TreeFamTF105417.

Enzyme and pathway databases

SignaLinkQ9H422.

Gene expression databases

ArrayExpressQ9H422.
BgeeQ9H422.
CleanExHS_HIPK3.
GenevestigatorQ9H422.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 2 hits.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSHIPK3. human.
GeneWikiHIPK3.
GenomeRNAi10114.
NextBio38263.
PROQ9H422.
SOURCESearch...

Entry information

Entry nameHIPK3_HUMAN
AccessionPrimary (citable) accession number: Q9H422
Secondary accession number(s): O14632 expand/collapse secondary AC list , Q2PBG4, Q2PBG5, Q92632, Q9HAS2
Entry history
Integrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: March 1, 2001
Last modified: July 9, 2014
This is version 123 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM