Q9H422 (HIPK3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	HIPK3
Synonyms:	DYRK6, FIST3, PKY

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1215 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Apoptosis Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic 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 regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	PML body Inferred from electronic annotation. Source: Compara cytoplasm Inferred from direct assay. Source: HPA nucleus Inferred from direct assay. Source: HPA
Molecular_function	ATP binding Non-traceable author statement. 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1215	1215	Homeodomain-interacting protein kinase 3		PRO_0000085998
Regions
	Domain	197 – 525	329	Protein kinase
	Nucleotide binding	203 – 211	9	ATP By similarity
	Region	767 – 944	178	Interaction with AR By similarity
	Region	796 – 891	96	Interaction with FAS By similarity
	Region	855 – 1011	157	Required for localization to nuclear speckles By similarity
	Region	866 – 918	53	SUMO interaction motifs (SIM); required for nuclear localization and kinase activity By similarity
	Region	870 – 880	11	Interaction with UBL1 Probable
	Compositional bias	910 – 962	53	Ser-rich
Sites
	Active site	322	1	Proton acceptor By similarity
	Binding site	226	1	ATP By similarity
Amino acid modifications
	Modified residue	359	1	Phosphotyrosine By similarity
	Cross-link	27		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
	Cross-link	1208		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Natural variations
	Alternative sequence	770 – 790	21	Missing in isoform 2.		VSP_013140
	Natural variant	142	1	Q → R. Ref.9 Corresponds to variant rs34193811 [ dbSNP | Ensembl ].		VAR_040549
	Natural variant	170	1	G → E. Ref.9 Corresponds to variant rs34698015 [ dbSNP | Ensembl ].		VAR_040550
	Natural variant	191	1	C → R. Ref.9 Corresponds to variant rs35689361 [ dbSNP | Ensembl ].		VAR_040551
	Natural variant	474	1	V → I. Corresponds to variant rs266472 [ dbSNP | Ensembl ].		VAR_051627
	Natural variant	500	1	S → N. Ref.9 Corresponds to variant rs11032229 [ dbSNP | Ensembl ].		VAR_040552
	Natural variant	729	1	P → L. Ref.9 Corresponds to variant rs55807239 [ dbSNP | Ensembl ].		VAR_040553
Experimental info
	Mutagenesis	226	1	K → R: Loss of kinase activity and impaired activation of SF1. Ref.8
	Sequence conflict	69	1	N → K in AAG25990. Ref.2
	Sequence conflict	111	1	A → V in AAC64294. Ref.1
	Sequence conflict	1148	1	Q → K in AAG25990. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (HIPK3) [UniParc]. Last modified March 1, 2001. Version 1. Checksum: E952D04786955721	FASTA	1,215	133,743
	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
	Isoform 2 (FIST) [UniParc]. Checksum: 9F7C34FB1110F10B	FASTA	1,194	131,256
	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 KKNKQCQNRS NSLQNTNIPH 790 800 810 820 830 840 SAFISPKIIN GKDVEEVSCI ETQDNQNSEG EARNCCETSI RQDSDSSVSD KQRQTIIIAD 850 860 870 880 890 900 SPSPAVSVIT ISSDTDEEET SQRHSLRECK GSLDCEACQS TLNIDRMCSL SSPDSTLSTS 910 920 930 940 950 960 SSGQSSPSPC KRPNSMSDEE QESSCDTVDG SPTSDSSGHD SPFAESTFVE DTHENTELVS 970 980 990 1000 1010 1020 SADTETKPAV CSVVVPPVEL ENGLNADEHM ANTDSICQPL IKGRSAPGRL NQPSAVGTRQ 1030 1040 1050 1060 1070 1080 QKLTSAFQQQ HLNFSQVQHF GSGHQEWNGN FGHRRQQAYI PTSVTSNPFT LSHGSPNHTA 1090 1100 1110 1120 1130 1140 VHAHLAGNTH LGGQPTLLPY PSSATLSSAA PVAHLLASPC TSRPMLQHPT YNISHPSGIV 1150 1160 1170 1180 1190 HQVPVGLNPR LLPSPTIHQT QYKPIFPPHS YIAASPAYTG FPLSPTKLSQ YPYM

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
IPI	IPI00099522. IPI00554546.
RefSeq	NP_001041665.1. NM_001048200.1. NP_005725.3. NM_005734.3.
UniGene	Hs.201918.
3D structure databases
ProteinModelPortal	Q9H422.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9H422. 6 interactions.
MINT	MINT-1183373.
STRING	9606.ENSP00000304226.
PTM databases
PhosphoSite	Q9H422.
Polymorphism databases
DMDM	61213741.
Proteomic databases
PaxDb	Q9H422.
PRIDE	Q9H422.
Protocols and materials databases
DNASU	10114.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000303296; ENSP00000304226; ENSG00000110422. ENST00000379016; ENSP00000368301; ENSG00000110422. ENST00000456517; ENSP00000398241; ENSG00000110422. ENST00000525975; ENSP00000431710; ENSG00000110422.
GeneID	10114.
KEGG	hsa:10114.
UCSC	uc001mul.1. human. uc001mum.1. human.
Organism-specific databases
CTD	10114.
GeneCards	GC11P033235.
HGNC	HGNC:4915. HIPK3.
HPA	HPA028069.
MIM	604424. gene.
neXtProt	NX_Q9H422.
PharmGKB	PA29292.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000231785.
HOVERGEN	HBG051908.
InParanoid	Q9H422.
KO	K08826.
OMA	NISHPSG.
OrthoDB	EOG4F1X2F.
PhylomeDB	Q9H422.
Gene expression databases
ArrayExpress	Q9H422.
Bgee	Q9H422.
CleanEx	HS_HIPK3.
Genevestigator	Q9H422.
GermOnline	ENSG00000110422. Homo sapiens.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q9H422.
ChEMBL	CHEMBL4577.
ChiTaRS	HIPK3. human.
GenomeRNAi	10114.
NextBio	38263.
SOURCE	Search...

Entry information

Entry name

HIPK3_HUMAN

Accession

Primary (citable) accession number: Q9H422
Secondary accession number(s): O14632 , Q2PBG4, Q2PBG5, Q92632, Q9HAS2

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 109 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.