HIPK4_MOUSE
ID HIPK4_MOUSE Reviewed; 616 AA.
AC Q3V016; A8R3X8; B9EJV5;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 2.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Homeodomain-interacting protein kinase 4;
DE EC=2.7.11.1;
GN Name=Hipk4; Synonyms=Gm162;
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] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AUTOPHOSPHORYLATION, AND MUTAGENESIS OF LYS-40.
RX PubMed=18022393; DOI=10.1016/j.febslet.2007.11.022;
RA Arai S., Matsushita A., Du K., Yagi K., Okazaki Y., Kurokawa R.;
RT "Novel homeodomain-interacting protein kinase family member, HIPK4,
RT phosphorylates human p53 at serine 9.";
RL FEBS Lett. 581:5649-5657(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Ovary, and Uterus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-512, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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).
CC -!- FUNCTION: Protein kinase that phosphorylates murine TP53 at Ser-9, and
CC thus induces TP53 repression of BIRC5 promoter. May act as a
CC corepressor of transcription factors (Potential). {ECO:0000305}.
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 -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18022393}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q3V016-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3V016-2; Sequence=VSP_023035;
CC -!- TISSUE SPECIFICITY: Expressed at moderate levels in lung and white
CC adipose tissues and weakly in brain and liver.
CC {ECO:0000269|PubMed:18022393}.
CC -!- PTM: Autophosphorylated.
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; AB354583; BAF93448.1; -; mRNA.
DR EMBL; AK133498; BAE21689.1; -; mRNA.
DR EMBL; AC158304; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC147572; AAI47573.1; -; mRNA.
DR EMBL; BC147577; AAI47578.1; -; mRNA.
DR CCDS; CCDS21024.2; -. [Q3V016-1]
DR RefSeq; NP_001028487.2; NM_001033315.2. [Q3V016-1]
DR RefSeq; XP_011248824.1; XM_011250522.2. [Q3V016-2]
DR AlphaFoldDB; Q3V016; -.
DR SMR; Q3V016; -.
DR STRING; 10090.ENSMUSP00000103990; -.
DR iPTMnet; Q3V016; -.
DR PhosphoSitePlus; Q3V016; -.
DR PaxDb; Q3V016; -.
DR PeptideAtlas; Q3V016; -.
DR PRIDE; Q3V016; -.
DR ProteomicsDB; 273171; -. [Q3V016-1]
DR ProteomicsDB; 273172; -. [Q3V016-2]
DR Antibodypedia; 16956; 297 antibodies from 28 providers.
DR DNASU; 233020; -.
DR Ensembl; ENSMUST00000037134; ENSMUSP00000043175; ENSMUSG00000040424. [Q3V016-2]
DR Ensembl; ENSMUST00000108353; ENSMUSP00000103990; ENSMUSG00000040424. [Q3V016-1]
DR GeneID; 233020; -.
DR KEGG; mmu:233020; -.
DR UCSC; uc009fwl.2; mouse. [Q3V016-1]
DR CTD; 147746; -.
DR MGI; MGI:2685008; Hipk4.
DR VEuPathDB; HostDB:ENSMUSG00000040424; -.
DR eggNOG; KOG0667; Eukaryota.
DR GeneTree; ENSGT00940000161512; -.
DR HOGENOM; CLU_000288_5_14_1; -.
DR InParanoid; Q3V016; -.
DR OMA; DWTLEGI; -.
DR OrthoDB; 59821at2759; -.
DR PhylomeDB; Q3V016; -.
DR TreeFam; TF105417; -.
DR BioGRID-ORCS; 233020; 2 hits in 75 CRISPR screens.
DR PRO; PR:Q3V016; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q3V016; protein.
DR Bgee; ENSMUSG00000040424; Expressed in spermatid and 49 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0035173; F:histone kinase activity; IDA:MGI.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0016570; P:histone modification; IDA:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:MGI.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IBA:GO_Central.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
DR GO; GO:1901796; P:regulation of signal transduction by p53 class mediator; IDA:MGI.
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 Alternative splicing; ATP-binding; Cytoplasm; Kinase; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..616
FT /note="Homeodomain-interacting protein kinase 4"
FT /id="PRO_0000277604"
FT DOMAIN 11..347
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 487..616
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 496..510
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 545..559
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 136
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 17..25
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 40
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 512
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..204
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_023035"
FT MUTAGEN 40
FT /note="K->S: Loss of activity."
FT /evidence="ECO:0000269|PubMed:18022393"
FT CONFLICT 381
FT /note="P -> T (in Ref. 1; BAF93448 and 2; BAE21689)"
FT /evidence="ECO:0000305"
FT CONFLICT 499
FT /note="D -> N (in Ref. 1; BAF93448 and 2; BAE21689)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 616 AA; 69279 MW; 741CC756379D25C8 CRC64;
MATIQSETDC YDIIEVLGKG TFGEVAKGWR RSTGEMVAIK ILKNDAYRSR IIKNELKLLR
CVRGLDPDEA HVIRFLEFFH DALKFYLVFE LLEQNLFEFQ KENNFAPLPA RHIRTVTLQV
LRALARLKEL AIIHADLKPE NIMLVDQTRC PFRVKVIDFG SASIFSEVRY VKEPYIQSRF
YRAPEILLGL PFCEKVDVWS LGCVMAELHL GWPLYPGNNE YDQVRYICET QGLPKPHLLH
AARKAHHFFK RNPHPDATNP WQLKSSADYL AETKVRPLER RKYMLKSLDQ IETVNGGGAV
SRLSFPDREA LAEHADLKSM VELIKRMLTW ESHERISPSA ALRHPFVSMQ QLRSAHEATR
YYQLSLRGCR LSLQVDGKPP PPVIASAEDG PPYYRLAEEE ETAGLGGVTG SGSFFREDKA
PGMQRAIDQL DDLSLQEARR GLWSDTRADM VSDMLVPLKV ASTSHRVPDS GPEPILAFYG
SRLTGRHKAR KAPAGSKSDS NFSNLIRLSQ ASPEDAGPCR GSGWEEGEGR TTSTEPSVIP
QREGDGPGIK DRPMDAERPG PELFDPSSCP GEWLSEPEWT LEGIRGSRAQ GLPAHHPHPH
GPPRTTSFLQ HVGGHH
