Q9ERH7 (HIPK3_MOUSE) 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
Nuclear body-associated kinase 3
Short name=Nbak3

Gene names

Name:	Hipk3
Synonyms:	Fist3

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1192 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.2 Ref.6 Ref.8
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	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. Ref.1 Ref.2 Ref.5 Ref.6 Ref.8
Subcellular location	Cytoplasm. Nucleus Ref.2 Ref.5.
Tissue specificity	Heart, skeletal muscle, spleen, testis and lung. Ref.2
Post-translational modification	Autophosphorylated, but autophosphorylation is not required for catalytic activity By similarity. Ref.7 May be sumoylated.
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
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 negative regulation of JUN kinase activity Inferred from mutant phenotype Ref.2. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity Ref.1. Source: UniProtKB peptidyl-serine phosphorylation Inferred from direct assay Ref.2. Source: UniProtKB peptidyl-threonine phosphorylation Inferred from direct assay Ref.2. Source: UniProtKB positive regulation of DNA binding Inferred from sequence or structural similarity Ref.1. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	PML body Inferred from direct assay Ref.2. Source: UniProtKB cytoplasm Inferred from direct assay Ref.2. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction Ref.2. Source: UniProtKB protein serine/threonine kinase activity Inferred from direct assay Ref.2. Source: UniProtKB transcription corepressor activity Inferred from sequence or structural similarity Ref.1. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Fas	P25446	3	EBI-524356,EBI-296206

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1192	1192	Homeodomain-interacting protein kinase 3		PRO_0000085999
Regions
	Domain	197 – 525	329	Protein kinase
	Nucleotide binding	203 – 211	9	ATP By similarity
	Region	767 – 921	155	Interaction with AR By similarity
	Region	775 – 868	94	Interaction with FAS
	Region	832 – 988	157	Required for localization to nuclear speckles By similarity
	Region	843 – 895	53	SUMO interaction motifs (SIM); required for nuclear localization and kinase activity By similarity
	Region	847 – 857	11	Interaction with UBL1 By similarity
	Compositional bias	887 – 939	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 Ref.7
	Modified residue	785	1	Phosphoserine By similarity
	Cross-link	27		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
	Cross-link	1185		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Experimental info
	Mutagenesis	226	1	K → R: Loss of kinase activity and impaired activation of SF1. Ref.2 Ref.6
	Mutagenesis	226	1	K → S: Impairs catalytic activity. Ref.2 Ref.6
	Mutagenesis	322	1	D → N: Impairs catalytic activity and abolishes interaction with DAXX. Ref.2
	Sequence conflict	65	1	K → N in AAC63012. Ref.1
	Sequence conflict	405	1	Y → H in AAC63012. Ref.1
	Sequence conflict	813	1	G → R in AAC63012. Ref.1
	Sequence conflict	813	1	G → R in AAG25989. Ref.2
	Sequence conflict	813	1	G → R in AAD52570. Ref.3
	Sequence conflict	985	1	D → G in AAC63012. Ref.1
	Sequence conflict	985	1	D → G in AAD52570. Ref.3
	Sequence conflict	1084	1	A → D in AAC63012. Ref.1
	Sequence conflict	1186	1	L → V in AAC63012. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9ERH7 [UniParc]. Last modified July 27, 2011. Version 3. Checksum: D153322BAFB5F3F9	FASTA	1,192	130,081
	10 20 30 40 50 60 MASQVLVYPP YVYQTQSSAF CSVKKLKVEP SGCVFQERTY PQIHVNGRNF GNSHPSTKGS 70 80 90 100 110 120 AFQTKIPFTK PRGHSFSLQA GAIVVKDTAG ATKVLAAQAQ QAGVEAPRAV VWRNRLHFLE 130 140 150 160 170 180 GPQRCGLKRK SEELENHSGA MQIVDELSIL PAMLQTNMGN PVTVVTATTG SKQNCTSGEG 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 PVLQQVATAL KKLKSLGLIH ADLKPENIML VDPVRQPYRV KVIDFGSASH VSKTVCSTYL 370 380 390 400 410 420 QSRYYRAPEI ILGLPFCEAI DMWSLGCVIA ELFLGWPLYP GALEYDQIRY ISQTQGLPGE 430 440 450 460 470 480 QLLNVGTKST RFFCRETDMS HSGWRLKTLE EHEAETGMKS KEARKYIFNS LDDIVHVNTV 490 500 510 520 530 540 MDLEGGDLLA EKADRREFVN LLKKMLLIDA DLRITPIETL NHPFVNMKHL LDFPHSNHVK 550 560 570 580 590 600 SCFHIMDICK SPSSCETNNH SKMSLLRPVA SNGTAALAAN FTKVGTLRSQ ALTTSAHSVV 610 620 630 640 650 660 HHGIPLQAGT AQFGCGDAFH QTLIICPPAI QGIPAAHGKP TSYSIRVDNT VPLVTQAPAV 670 680 690 700 710 720 QPLQIRPGVL SQQTWSGRTQ QMLIPAWQQV TPMAPAAATL TSEGMAGSQR LGDWGKMIPH 730 740 750 760 770 780 SNHYNSVMPP PLLTNQITLS APQPISVGIA HVVWPQPATT KKNKLCQNRS NSLQNTNIPH 790 800 810 820 830 840 SAFISPKIIS GKEVEEVSCV DTQDNHTSEG EAGTCREASV RQDSSVSDKQ RQTIIIADSP 850 860 870 880 890 900 SPAVSVITIS SDSDDEETSP RPSLRECKGS LDCEACQSTL NIDRMCSLSS PDSTLSTSSS 910 920 930 940 950 960 GQSSPSPCKR PNSMSDDEQE SGCETVDGSP TSDSSGHDSP FAENSFVEDA HQNTELGTCA 970 980 990 1000 1010 1020 GPEAKPAVGT AVEPPVGRES GLSVDEHMAN TDSTCQPLRK GQPAPGKLHQ PPALGARQQK 1030 1040 1050 1060 1070 1080 PAAAFPQQHL NLSQVQHFGT GHQEWNGNFG HRRQQAYIPT SVTSNPFTLS HGSPNHTAVH 1090 1100 1110 1120 1130 1140 AHLAGSTHLG GQPTLLPYPS SASLSSAAPV AHLLASPCTS RPMLQHPTYN ISHPSGIVHQ 1150 1160 1170 1180 1190 VPVGINPRLL PSPTIHQTQY KPIFPPHSYI AASPAYTGFP LSPTKLSQYP YM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Homeodomain-interacting protein kinases, a novel family of co-repressors for homeodomain transcription factors." Kim Y.H., Choi C.Y., Lee S.-J., Conti M.A., Kim Y. J. Biol. Chem. 273:25875-25879(1998) [PubMed: 9748262] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH NKX1-2. Strain: BALB/c.
[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: 11034606] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH FAS AND DAXX, IDENTIFICATION IN A COMPLEX WITH FAS AND FADD, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF LYS-226 AND ASP-322. Strain: CD-1. Tissue: Testis.
[3]	"Protein kinases associated with PML/CBP nuclear bodies and filamentous threads regulate transcription and inhibit cell growth." Sather S.L., Johnson N.L., Johnson G.L. Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed: 19468303] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6.
[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: 9725910] [Abstract] Cited for: INTERACTION WITH AR, SUBCELLULAR LOCATION.
[6]	"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: 17210646] [Abstract] Cited for: FUNCTION AS KINASE AND IN CAMP SIGNALING PATHWAY, INTERACTION WITH NR5A1/SF1, MUTAGENESIS OF LYS-226.
[7]	"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain." Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P. J. Proteome Res. 7:311-318(2008) [PubMed: 18034455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-359, MASS SPECTROMETRY. Tissue: Brain.
[8]	"Runx2 trans-activation mediated by the MSX2-interacting nuclear target requires homeodomain interacting protein kinase-3." Sierra O.L., Towler D.A. Mol. Endocrinol. 24:1478-1497(2010) [PubMed: 20484411] [Abstract] Cited for: FUNCTION AS RUNX2 KINASE, INTERACTION WITH RUNX2 AND SPEN/MINT.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF077660 mRNA. Translation: AAC63012.1. AF305238 mRNA. Translation: AAG25989.1. AF170305 mRNA. Translation: AAD52570.1. AL844591 Genomic DNA. Translation: CAM23687.1.
IPI	IPI00319076.
PIR	T17089.
RefSeq	NP_034564.2. NM_010434.2.
UniGene	Mm.257925.
3D structure databases
ProteinModelPortal	Q9ERH7.
SMR	Q9ERH7. Positions 171-526.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9ERH7. 3 interactions.
STRING	Q9ERH7.
PTM databases
PhosphoSite	Q9ERH7.
Proteomic databases
PRIDE	Q9ERH7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000028600; ENSMUSP00000028600; ENSMUSG00000027177. ENSMUST00000111124; ENSMUSP00000106753; ENSMUSG00000027177.
GeneID	15259.
KEGG	mmu:15259.
NMPDR	fig|10090.3.peg.6491.
Organism-specific databases
CTD	10114.
MGI	MGI:1314882. Hipk3.
Phylogenomic databases
eggNOG	roNOG11331.
GeneTree	ENSGT00550000074148.
HOVERGEN	HBG051908.
OrthoDB	EOG4F1X2F.
PhylomeDB	Q9ERH7.
Gene expression databases
ArrayExpress	Q9ERH7.
Bgee	Q9ERH7.
CleanEx	MM_HIPK3.
Genevestigator	Q9ERH7.
GermOnline	ENSMUSG00000027177. Mus musculus.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. IPR002290. Ser/Thr_kinase_dom. [Graphical view]
KO	K08826.
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
NextBio	287881.
SOURCE	Search...

Entry information

Entry name

HIPK3_MOUSE

Accession

Primary (citable) accession number: Q9ERH7
Secondary accession number(s): A2AQH2, O88906, Q9QZR2

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	July 27, 2011
Last modified:	December 14, 2011
This is version 90 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program