HIPK3_MOUSE
ID HIPK3_MOUSE Reviewed; 1192 AA.
AC Q9ERH7; A2AQH2; O88906; Q9QZR2;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Homeodomain-interacting protein kinase 3;
DE EC=2.7.11.1;
DE AltName: Full=Androgen receptor-interacting nuclear protein kinase;
DE Short=ANPK;
DE AltName: Full=Fas-interacting serine/threonine-protein kinase;
DE Short=FIST;
DE AltName: Full=Nuclear body-associated kinase 3;
DE Short=Nbak3;
GN Name=Hipk3; Synonyms=Fist3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH NKX1-2.
RC STRAIN=BALB/cJ;
RX PubMed=9748262; DOI=10.1074/jbc.273.40.25875;
RA Kim Y.H., Choi C.Y., Lee S.-J., Conti M.A., Kim Y.;
RT "Homeodomain-interacting protein kinases, a novel family of co-repressors
RT for homeodomain transcription factors.";
RL J. Biol. Chem. 273:25875-25879(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH FAS AND DAXX, IDENTIFICATION
RP IN A COMPLEX WITH FAS AND FADD, TISSUE SPECIFICITY, SUBCELLULAR LOCATION,
RP FUNCTION, AND MUTAGENESIS OF LYS-226 AND ASP-322.
RC STRAIN=CD-1; TISSUE=Testis;
RX PubMed=11034606; DOI=10.1084/jem.192.8.1165;
RA Rochat-Steiner V., Becker K., Micheau O., Schneider P., Burns K.,
RA Tschopp J.;
RT "FIST/HIPK3: a Fas/FADD-interacting serine/threonine kinase that induces
RT FADD phosphorylation and inhibits Fas-mediated Jun NH2-terminal kinase
RT activation.";
RL J. Exp. Med. 192:1165-1174(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Sather S.L., Johnson N.L., Johnson G.L.;
RT "Protein kinases associated with PML/CBP nuclear bodies and filamentous
RT threads regulate transcription and inhibit cell growth.";
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP INTERACTION WITH AR, AND SUBCELLULAR LOCATION.
RX PubMed=9725910; DOI=10.1091/mbc.9.9.2527;
RA Moilanen A.-M., Karvonen U., Poukka H., Jaenne O.A., Palvimo J.J.;
RT "Activation of androgen receptor function by a novel nuclear protein
RT kinase.";
RL Mol. Biol. Cell 9:2527-2543(1998).
RN [6]
RP FUNCTION AS KINASE AND IN CAMP SIGNALING PATHWAY, INTERACTION WITH
RP NR5A1/SF1, AND MUTAGENESIS OF LYS-226.
RX PubMed=17210646; DOI=10.1128/mcb.02253-06;
RA Lan H.-C., Li H.-J., Lin G., Lai P.-Y., Chung B.-C.;
RT "Cyclic AMP stimulates SF-1-dependent CYP11A1 expression through
RT homeodomain-interacting protein kinase 3-mediated Jun N-terminal kinase and
RT c-Jun phosphorylation.";
RL Mol. Cell. Biol. 27:2027-2036(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-359, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-359, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP FUNCTION AS RUNX2 KINASE, AND INTERACTION WITH RUNX2 AND SPEN/MINT.
RX PubMed=20484411; DOI=10.1210/me.2010-0029;
RA Sierra O.L., Towler D.A.;
RT "Runx2 trans-activation mediated by the MSX2-interacting nuclear target
RT requires homeodomain interacting protein kinase-3.";
RL Mol. Endocrinol. 24:1478-1497(2010).
CC -!- FUNCTION: Serine/threonine-protein kinase involved in transcription
CC regulation, apoptosis and steroidogenic gene expression. Phosphorylates
CC JUN and RUNX2. Seems to negatively regulate apoptosis by promoting FADD
CC phosphorylation. Enhances androgen receptor-mediated transcription. May
CC act as a transcriptional corepressor for NK homeodomain transcription
CC factors. The phosphorylation of NR5A1 activates SF1 leading to
CC increased steroidogenic gene expression upon cAMP signaling pathway
CC stimulation. In osteoblasts, supports transcription activation:
CC phosphorylates RUNX2 that synergizes with SPEN/MINT to enhance FGFR2-
CC mediated activation of the osteocalcin FGF-responsive element (OCFRE).
CC {ECO:0000269|PubMed:11034606, ECO:0000269|PubMed:17210646,
CC ECO:0000269|PubMed:20484411}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- SUBUNIT: Interacts with UBL1/SUMO-1 (By similarity). Interacts with and
CC stabilizes ligand-bound androgen receptor (AR). Interacts with Nkx1-2.
CC Interacts with FAS and DAXX. Probably part of a complex consisting of
CC HIPK3, FAS and FADD. Binds to NR5A1/SF1, SPEN/MINT and RUNX2.
CC {ECO:0000250, ECO:0000269|PubMed:11034606, ECO:0000269|PubMed:17210646,
CC ECO:0000269|PubMed:20484411, ECO:0000269|PubMed:9725910,
CC ECO:0000269|PubMed:9748262}.
CC -!- INTERACTION:
CC Q9ERH7; P25446: Fas; NbExp=3; IntAct=EBI-524356, EBI-296206;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- TISSUE SPECIFICITY: Heart, skeletal muscle, spleen, testis and lung.
CC {ECO:0000269|PubMed:11034606}.
CC -!- PTM: Autophosphorylated, but autophosphorylation is not required for
CC catalytic activity. {ECO:0000250}.
CC -!- PTM: May be sumoylated.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. HIPK subfamily. {ECO:0000305}.
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DR EMBL; AF077660; AAC63012.1; -; mRNA.
DR EMBL; AF305238; AAG25989.1; -; mRNA.
DR EMBL; AF170305; AAD52570.1; -; mRNA.
DR EMBL; AL844591; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS16489.1; -.
DR PIR; T17089; T17089.
DR RefSeq; NP_034564.2; NM_010434.2.
DR AlphaFoldDB; Q9ERH7; -.
DR SMR; Q9ERH7; -.
DR BioGRID; 200308; 1.
DR IntAct; Q9ERH7; 3.
DR STRING; 10090.ENSMUSP00000028600; -.
DR iPTMnet; Q9ERH7; -.
DR PhosphoSitePlus; Q9ERH7; -.
DR PaxDb; Q9ERH7; -.
DR PRIDE; Q9ERH7; -.
DR ProteomicsDB; 269753; -.
DR Antibodypedia; 25715; 213 antibodies from 29 providers.
DR DNASU; 15259; -.
DR Ensembl; ENSMUST00000028600; ENSMUSP00000028600; ENSMUSG00000027177.
DR Ensembl; ENSMUST00000111124; ENSMUSP00000106753; ENSMUSG00000027177.
DR GeneID; 15259; -.
DR KEGG; mmu:15259; -.
DR UCSC; uc008lju.2; mouse.
DR CTD; 10114; -.
DR MGI; MGI:1314882; Hipk3.
DR VEuPathDB; HostDB:ENSMUSG00000027177; -.
DR eggNOG; KOG0667; Eukaryota.
DR GeneTree; ENSGT00940000155960; -.
DR HOGENOM; CLU_003045_2_0_1; -.
DR InParanoid; Q9ERH7; -.
DR OMA; CQPLKKG; -.
DR OrthoDB; 59821at2759; -.
DR TreeFam; TF105417; -.
DR BioGRID-ORCS; 15259; 6 hits in 80 CRISPR screens.
DR ChiTaRS; Hipk3; mouse.
DR PRO; PR:Q9ERH7; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9ERH7; protein.
DR Bgee; ENSMUSG00000027177; Expressed in vastus lateralis and 245 other tissues.
DR ExpressionAtlas; Q9ERH7; baseline and differential.
DR Genevisible; Q9ERH7; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0016605; C:PML body; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0003714; F:transcription corepressor activity; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0009299; P:mRNA transcription; ISO:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0043508; P:negative regulation of JUN kinase activity; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:UniProtKB.
DR GO; GO:0043388; P:positive regulation of DNA binding; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Apoptosis; ATP-binding; Cytoplasm; Isopeptide bond; Kinase;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transcription; Transcription regulation;
KW Transferase; Ubl conjugation.
FT CHAIN 1..1192
FT /note="Homeodomain-interacting protein kinase 3"
FT /id="PRO_0000085999"
FT DOMAIN 197..525
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 767..921
FT /note="Interaction with AR"
FT /evidence="ECO:0000250"
FT REGION 775..868
FT /note="Interaction with FAS"
FT /evidence="ECO:0000269|PubMed:11034606"
FT REGION 799..829
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 832..988
FT /note="Required for localization to nuclear speckles"
FT /evidence="ECO:0000250"
FT REGION 843..895
FT /note="SUMO interaction motifs (SIM); required for nuclear
FT localization and kinase activity"
FT /evidence="ECO:0000250"
FT REGION 847..857
FT /note="Interaction with UBL1"
FT /evidence="ECO:0000250"
FT REGION 889..943
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 956..1023
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 889..912
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 924..943
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 322
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 203..211
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 226
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 359
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18034455,
FT ECO:0007744|PubMed:21183079"
FT CROSSLNK 27
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 27
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9H422"
FT CROSSLNK 1185
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT MUTAGEN 226
FT /note="K->R: Loss of kinase activity and impaired
FT activation of SF1."
FT /evidence="ECO:0000269|PubMed:11034606,
FT ECO:0000269|PubMed:17210646"
FT MUTAGEN 226
FT /note="K->S: Impairs catalytic activity."
FT /evidence="ECO:0000269|PubMed:11034606,
FT ECO:0000269|PubMed:17210646"
FT MUTAGEN 322
FT /note="D->N: Impairs catalytic activity and abolishes
FT interaction with DAXX."
FT /evidence="ECO:0000269|PubMed:11034606"
FT CONFLICT 65
FT /note="K -> N (in Ref. 1; AAC63012)"
FT /evidence="ECO:0000305"
FT CONFLICT 405
FT /note="Y -> H (in Ref. 1; AAC63012)"
FT /evidence="ECO:0000305"
FT CONFLICT 813
FT /note="G -> R (in Ref. 1; AAC63012, 2; AAG25989 and 3;
FT AAD52570)"
FT /evidence="ECO:0000305"
FT CONFLICT 985
FT /note="D -> G (in Ref. 1; AAC63012 and 3; AAD52570)"
FT /evidence="ECO:0000305"
FT CONFLICT 1084
FT /note="A -> D (in Ref. 1; AAC63012)"
FT /evidence="ECO:0000305"
FT CONFLICT 1186
FT /note="L -> V (in Ref. 1; AAC63012)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1192 AA; 130081 MW; D153322BAFB5F3F9 CRC64;
MASQVLVYPP YVYQTQSSAF CSVKKLKVEP SGCVFQERTY PQIHVNGRNF GNSHPSTKGS
AFQTKIPFTK PRGHSFSLQA GAIVVKDTAG ATKVLAAQAQ QAGVEAPRAV VWRNRLHFLE
GPQRCGLKRK SEELENHSGA MQIVDELSIL PAMLQTNMGN PVTVVTATTG SKQNCTSGEG
DYQLVQHEVL CSMKNTYEVL DFLGRGTFGQ VVKCWKRGTN EIVAIKILKN HPSYARQGQI
EVSILARLST ENADEYNFVR AYECFQHRNH TCLVFEMLEQ NLYDFLKQNK FSPLPLKVIR
PVLQQVATAL KKLKSLGLIH ADLKPENIML VDPVRQPYRV KVIDFGSASH VSKTVCSTYL
QSRYYRAPEI ILGLPFCEAI DMWSLGCVIA ELFLGWPLYP GALEYDQIRY ISQTQGLPGE
QLLNVGTKST RFFCRETDMS HSGWRLKTLE EHEAETGMKS KEARKYIFNS LDDIVHVNTV
MDLEGGDLLA EKADRREFVN LLKKMLLIDA DLRITPIETL NHPFVNMKHL LDFPHSNHVK
SCFHIMDICK SPSSCETNNH SKMSLLRPVA SNGTAALAAN FTKVGTLRSQ ALTTSAHSVV
HHGIPLQAGT AQFGCGDAFH QTLIICPPAI QGIPAAHGKP TSYSIRVDNT VPLVTQAPAV
QPLQIRPGVL SQQTWSGRTQ QMLIPAWQQV TPMAPAAATL TSEGMAGSQR LGDWGKMIPH
SNHYNSVMPP PLLTNQITLS APQPISVGIA HVVWPQPATT KKNKLCQNRS NSLQNTNIPH
SAFISPKIIS GKEVEEVSCV DTQDNHTSEG EAGTCREASV RQDSSVSDKQ RQTIIIADSP
SPAVSVITIS SDSDDEETSP RPSLRECKGS LDCEACQSTL NIDRMCSLSS PDSTLSTSSS
GQSSPSPCKR PNSMSDDEQE SGCETVDGSP TSDSSGHDSP FAENSFVEDA HQNTELGTCA
GPEAKPAVGT AVEPPVGRES GLSVDEHMAN TDSTCQPLRK GQPAPGKLHQ PPALGARQQK
PAAAFPQQHL NLSQVQHFGT GHQEWNGNFG HRRQQAYIPT SVTSNPFTLS HGSPNHTAVH
AHLAGSTHLG GQPTLLPYPS SASLSSAAPV AHLLASPCTS RPMLQHPTYN ISHPSGIVHQ
VPVGINPRLL PSPTIHQTQY KPIFPPHSYI AASPAYTGFP LSPTKLSQYP YM
