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Homeodomain-interacting protein kinase 2 (hHIPk2) (EC 2.7.11.1)

 HIPK2_HUMAN             Reviewed;        1198 AA.
Q9H2X6; Q75MR7; Q8WWI4; Q9H2Y1;
27-APR-2001, integrated into UniProtKB/Swiss-Prot.
06-JUN-2002, sequence version 2.
12-SEP-2018, entry version 185.
RecName: Full=Homeodomain-interacting protein kinase 2;
Short=hHIPk2;
EC=2.7.11.1;
Name=HIPK2;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE
SPECIFICITY, AND MUTAGENESIS OF LYS-228.
TISSUE=Liver, and Testis;
PubMed=11267674; DOI=10.1016/S0167-4781(00)00308-0;
Wang Y., Hofmann T.G., Runkel L., Haaf T., Schaller H., Debatin K.-M.,
Hug H.;
"Isolation and characterization of cDNAs for the protein kinase
HIPK2.";
Biochim. Biophys. Acta 1518:168-172(2001).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
TISSUE=Frontal cortex;
Stukart G.C., Dias-Neto E.;
"Sequencing of hHIPk2, a human homolog of mouse homeodomain
interacting protein kinase 2.";
Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=12853948; DOI=10.1038/nature01782;
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R.,
Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K.,
Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
Waterston R.H., Wilson R.K.;
"The DNA sequence of human chromosome 7.";
Nature 424:157-164(2003).
[4]
NUCLEOTIDE SEQUENCE [MRNA] OF 8-1198 (ISOFORM 2).
Pierantoni G.M., Benvenuto G., Chiariotti L., Fusco A.;
Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
[5]
INTERACTION WITH TRADD.
PubMed=11032752; DOI=10.1006/bbrc.2000.3700;
Li X., Wang Y., Debatin K.-M., Hug H.;
"The serine/threonine kinase HIPK2 interacts with TRADD, but not with
CD95 or TNF-R1 in 293T cells.";
Biochem. Biophys. Res. Commun. 277:513-517(2000).
[6]
TISSUE SPECIFICITY.
PubMed=11798164; DOI=10.1006/bbrc.2001.6310;
Pierantoni G.M., Bulfone A., Pentimalli F., Fedele M., Iuliano R.,
Santoro M., Chiariotti L., Ballabio A., Fusco A.;
"The homeodomain-interacting protein kinase 2 gene is expressed late
in embryogenesis and preferentially in retina, muscle, and neural
tissues.";
Biochem. Biophys. Res. Commun. 290:942-947(2002).
[7]
INTERACTION WITH RANBP9, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
LYS-228.
PubMed=12220523; DOI=10.1016/S0006-291X(02)02020-X;
Wang Y., Marion Schneider E., Li X., Duttenhoefer I., Debatin K.-M.,
Hug H.;
"HIPK2 associates with RanBPM.";
Biochem. Biophys. Res. Commun. 297:148-153(2002).
[8]
INTERACTION WITH TP73; TP53 AND TP63, MUTAGENESIS OF LYS-228, AND
FUNCTION.
PubMed=11925430; DOI=10.1074/jbc.M200153200;
Kim E.-J., Park J.-S., Um S.-J.;
"Identification and characterization of HIPK2 interacting with p73 and
modulating functions of the p53 family in vivo.";
J. Biol. Chem. 277:32020-32028(2002).
[9]
SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION, INTERACTION WITH TP53 AND
CREBBP, MUTAGENESIS OF LYS-228, FUNCTION, AND INDUCTION.
PubMed=11740489; DOI=10.1038/ncb715;
Hofmann T.G., Moeller A., Sirma H., Zentgraf H., Taya Y., Droege W.,
Will H., Schmitz M.L.;
"Regulation of p53 activity by its interaction with homeodomain-
interacting protein kinase-2.";
Nat. Cell Biol. 4:1-10(2002).
[10]
SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-228.
PubMed=12907596;
Moeller A., Sirma H., Hofmann T.G., Rueffer S., Klimczak E.,
Droege W., Will H., Schmitz M.L.;
"PML is required for homeodomain-interacting protein kinase 2 (HIPK2)-
mediated p53 phosphorylation and cell cycle arrest but is dispensable
for the formation of HIPK domains.";
Cancer Res. 63:4310-4314(2003).
[11]
FUNCTION, INTERACTION WITH DAXX, AND MUTAGENESIS OF LYS-228.
PubMed=14678985;
Hofmann T.G., Stollberg N., Schmitz M.L., Will H.;
"HIPK2 regulates transforming growth factor-beta-induced c-Jun NH(2)-
terminal kinase activation and apoptosis in human hepatoma cells.";
Cancer Res. 63:8271-8277(2003).
[12]
FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH P53DINP1.
PubMed=12851404; DOI=10.1074/jbc.M301979200;
Tomasini R., Samir A.A., Carrier A., Isnardon D., Cecchinelli B.,
Soddu S., Malissen B., Dagorn J.-C., Iovanna J.L., Dusetti N.J.;
"TP53INP1s and homeodomain-interacting protein kinase-2 (HIPK2) are
partners in regulating p53 activity.";
J. Biol. Chem. 278:37722-37729(2003).
[13]
FUNCTION, INTERACTION WITH SKI; SMAD1; SMAD2 AND SMAD3, AND
MUTAGENESIS OF LYS-228 AND 359-SER--TYR-361.
PubMed=12874272; DOI=10.1074/jbc.M307112200;
Harada J., Kokura K., Kanei-Ishii C., Nomura T., Khan M.M., Kim Y.,
Ishii S.;
"Requirement of the co-repressor homeodomain-interacting protein
kinase 2 for ski-mediated inhibition of bone morphogenetic protein-
induced transcriptional activation.";
J. Biol. Chem. 278:38998-39005(2003).
[14]
INTERACTION WITH SP100.
PubMed=14647468; DOI=10.1038/sj.onc.1207079;
Moeller A., Sirma H., Hofmann T.G., Staege H., Gresko E., Luedi K.S.,
Klimczak E., Droege W., Will H., Schmitz M.L.;
"Sp100 is important for the stimulatory effect of homeodomain-
interacting protein kinase-2 on p53-dependent gene expression.";
Oncogene 22:8731-8737(2003).
[15]
DESUMOYLATION.
PubMed=16253240; DOI=10.1016/j.febslet.2005.10.010;
Kim Y.H., Sung K.S., Lee S.-J., Kim Y.-O., Choi C.Y., Kim Y.;
"Desumoylation of homeodomain-interacting protein kinase 2 (HIPK2)
through the cytoplasmic-nuclear shuttling of the SUMO-specific
protease SENP1.";
FEBS Lett. 579:6272-6278(2005).
[16]
CLEAVAGE BY CASP6 AT ASP-923 AND ASP-984.
PubMed=16601678; DOI=10.1038/sj.emboj.7601077;
Gresko E., Roscic A., Ritterhoff S., Vichalkovski A., del Sal G.,
Schmitz M.L.;
"Autoregulatory control of the p53 response by caspase-mediated
processing of HIPK2.";
EMBO J. 25:1883-1894(2006).
[17]
INTERACTION WITH CBX4, SUMOYLATION AT LYS-32, AND FUNCTION.
PubMed=17018294; DOI=10.1016/j.molcel.2006.08.004;
Roscic A., Moeller A., Calzado M.A., Renner F., Wimmer V.C.,
Gresko E., Luedi K.S., Schmitz M.L.;
"Phosphorylation-dependent control of Pc2 SUMO E3 ligase activity by
its substrate protein HIPK2.";
Mol. Cell 24:77-89(2006).
[18]
FUNCTION AS HMGA1 KINASE.
PubMed=17960875; DOI=10.1021/pr700571d;
Zhang Q., Wang Y.;
"Homeodomain-interacting protein kinase-2 (HIPK2) phosphorylates
HMGA1a at Ser-35, Thr-52, and Thr-77 and modulates its DNA binding
affinity.";
J. Proteome Res. 6:4711-4719(2007).
[19]
FUNCTION AS RUNX1 AND EP300 KINASE, AND MUTAGENESIS OF LYS-228.
PubMed=18695000; DOI=10.1182/blood-2008-01-134122;
Wee H.-J., Voon D.C.-C., Bae S.-C., Ito Y.;
"PEBP2-beta/CBF-beta-dependent phosphorylation of RUNX1 and p300 by
HIPK2: implications for leukemogenesis.";
Blood 112:3777-3787(2008).
[20]
INTERACTION WITH WSB1, AND UBIQUITINATION BY WSB1.
PubMed=18093972; DOI=10.1074/jbc.M708873200;
Choi D.W., Seo Y.-M., Kim E.-A., Sung K.S., Ahn J.W., Park S.-J.,
Lee S.-R., Choi C.Y.;
"Ubiquitination and degradation of homeodomain-interacting protein
kinase 2 by WD40 repeat/SOCS box protein WSB-1.";
J. Biol. Chem. 283:4682-4689(2008).
[21]
FUNCTION, AND UBIQUITINATION BY FBXO3.
PubMed=18809579; DOI=10.1128/MCB.00897-08;
Shima Y., Shima T., Chiba T., Irimura T., Pandolfi P.P.,
Kitabayashi I.;
"PML activates transcription by protecting HIPK2 and p300 from
SCFFbx3-mediated degradation.";
Mol. Cell. Biol. 28:7126-7138(2008).
[22]
INDUCTION BY DNA DAMAGE, INTERACTION WITH SIAH1, AND UBIQUITINATION BY
SIAH1.
PubMed=18536714; DOI=10.1038/ncb1743;
Winter M., Sombroek D., Dauth I., Moehlenbrink J., Scheuermann K.,
Crone J., Hofmann T.G.;
"Control of HIPK2 stability by ubiquitin ligase Siah-1 and checkpoint
kinases ATM and ATR.";
Nat. Cell Biol. 10:812-824(2008).
[23]
FUNCTION AS HIF1A TRANSCRIPTION REGULATOR AND ANGIOGENESIS PROMOTER.
PubMed=19046997; DOI=10.1016/j.bbamcr.2008.10.013;
Nardinocchi L., Puca R., Guidolin D., Belloni A.S., Bossi G.,
Michiels C., Sacchi A., Onisto M., D'Orazi G.;
"Transcriptional regulation of hypoxia-inducible factor 1alpha by
HIPK2 suggests a novel mechanism to restrain tumor growth.";
Biochim. Biophys. Acta 1793:368-377(2009).
[24]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
Mann M., Daub H.;
"Large-scale proteomics analysis of the human kinome.";
Mol. Cell. Proteomics 8:1751-1764(2009).
[25]
FUNCTION AS PML KINASE, INTERACTION WITH PML, AND MUTAGENESIS OF
LYS-228.
PubMed=19015637; DOI=10.1038/onc.2008.420;
Gresko E., Ritterhoff S., Sevilla-Perez J., Roscic A., Froebius K.,
Kotevic I., Vichalkovski A., Hess D., Hemmings B.A., Schmitz M.L.;
"PML tumor suppressor is regulated by HIPK2-mediated phosphorylation
in response to DNA damage.";
Oncogene 28:698-708(2009).
[26]
FUNCTION AS ZBTB4 KINASE, AND INTERACTION WITH ZBTB4.
PubMed=19448668; DOI=10.1038/onc.2009.109;
Yamada D., Perez-Torrado R., Filion G., Caly M., Jammart B.,
Devignot V., Sasai N., Ravassard P., Mallet J., Sastre-Garau X.,
Schmitz M.L., Defossez P.A.;
"The human protein kinase HIPK2 phosphorylates and downregulates the
methyl-binding transcription factor ZBTB4.";
Oncogene 28:2535-2544(2009).
[27]
INDUCTION BY ZINC DURING HYPOXIA.
PubMed=19714248; DOI=10.1371/journal.pone.0006819;
Nardinocchi L., Puca R., Sacchi A., Rechavi G., Givol D., D'Orazi G.;
"Targeting hypoxia in cancer cells by restoring homeodomain
interacting protein-kinase 2 and p53 activity and suppressing HIF-
1alpha.";
PLoS ONE 4:E6819-E6819(2009).
[28]
FUNCTION AS PDX1 KINASE.
PubMed=20637728; DOI=10.1016/j.bbrc.2010.07.035;
An R., da Silva Xavier G., Semplici F., Vakhshouri S., Hao H.X.,
Rutter J., Pagano M.A., Meggio F., Pinna L.A., Rutter G.A.;
"Pancreatic and duodenal homeobox 1 (PDX1) phosphorylation at serine-
269 is HIPK2-dependent and affects PDX1 subnuclear localization.";
Biochem. Biophys. Res. Commun. 399:155-161(2010).
[29]
FUNCTION AS CTNNB1 KINASE.
PubMed=20307497; DOI=10.1016/j.bbrc.2010.03.099;
Kim E.-A., Kim J.E., Sung K.S., Choi D.W., Lee B.J., Choi C.Y.;
"Homeodomain-interacting protein kinase 2 (HIPK2) targets beta-catenin
for phosphorylation and proteasomal degradation.";
Biochem. Biophys. Res. Commun. 394:966-971(2010).
[30]
FUNCTION AS ATF1 KINASE, AND INTERACTION WITH ATF1.
PubMed=20980392; DOI=10.1242/jcs.073627;
Hailemariam K., Iwasaki K., Huang B.W., Sakamoto K., Tsuji Y.;
"Transcriptional regulation of ferritin and antioxidant genes by HIPK2
under genotoxic stress.";
J. Cell Sci. 123:3863-3871(2010).
[31]
FUNCTION AS CREB1 KINASE, AND INTERACTION WITH CREB1.
PubMed=20573984; DOI=10.1091/mbc.E10-01-0015;
Sakamoto K., Huang B.-W., Iwasaki K., Hailemariam K.,
Ninomiya-Tsuji J., Tsuji Y.;
"Regulation of genotoxic stress response by homeodomain-interacting
protein kinase 2 through phosphorylation of cyclic AMP response
element-binding protein at serine 271.";
Mol. Biol. Cell 21:2966-2974(2010).
[32]
SUBCELLULAR LOCATION, SUMOYLATION, NUCLEAR LOCALIZATION SIGNALS,
MUTAGENESIS OF LYS-803; LYS-805; ARG-833; LYS-835; 885-VAL--SER-892
AND 893-ASP--GLU-899, AND INTERACTION WITH CBX4.
PubMed=21145359; DOI=10.1016/j.bbamcr.2010.11.022;
de la Vega L., Froebius K., Moreno R., Calzado M.A., Geng H.,
Schmitz M.L.;
"Control of nuclear HIPK2 localization and function by a SUMO
interaction motif.";
Biochim. Biophys. Acta 1813:283-297(2011).
[33]
SUBCELLULAR LOCATION, SUMOYLATION, FUNCTION, AND MUTAGENESIS OF
885-VAL--ILE-888 AND 892-SER--ASP-895.
PubMed=21192925; DOI=10.1016/j.yexcr.2010.12.016;
Sung K.S., Lee Y.A., Kim E.T., Lee S.R., Ahn J.H., Choi C.Y.;
"Role of the SUMO-interacting motif in HIPK2 targeting to the PML
nuclear bodies and regulation of p53.";
Exp. Cell Res. 317:1060-1070(2011).
[34]
REVIEW ON DNA DAMAGE SIGNALING, INDUCTION BY GENOTOXIC AGENTS, AND
STABILIZATION BY DNA DAMAGE.
PubMed=18974774; DOI=10.1038/cdd.2008.154;
Sombroek D., Hofmann T.G.;
"How cells switch HIPK2 on and off.";
Cell Death Differ. 16:187-194(2009).
[35]
REVIEW.
PubMed=19788416; DOI=10.1111/j.1742-4658.2009.07331.x;
Bitomsky N., Hofmann T.G.;
"Apoptosis and autophagy: Regulation of apoptosis by DNA damage
signalling - roles of p53, p73 and HIPK2.";
FEBS J. 276:6074-6083(2009).
[36]
REVIEW AS HYPOXIA AND TP53 REGULATOR.
PubMed=20234185; DOI=10.4161/cc.9.7.11125;
Nardinocchi L., Puca R., Givol D., D'Orazi G.;
"HIPK2-a therapeutical target to be (re)activated for tumor
suppression: role in p53 activation and HIF-1? inhibition.";
Cell Cycle 9:1270-1275(2010).
[37]
REVIEW AS TP53 REGULATOR, AND INDUCTION BY GENOTOXIC AGENTS AND
HYPOXIA.
PubMed=20514025; DOI=10.1038/onc.2010.183;
Puca R., Nardinocchi L., Givol D., D'Orazi G.;
"Regulation of p53 activity by HIPK2: molecular mechanisms and
therapeutical implications in human cancer cells.";
Oncogene 29:4378-4387(2010).
[38]
FUNCTION.
PubMed=22825850; DOI=10.1074/jbc.M112.390120;
Pelisch F., Pozzi B., Risso G., Munoz M.J., Srebrow A.;
"DNA damage-induced heterogeneous nuclear ribonucleoprotein K
SUMOylation regulates p53 transcriptional activation.";
J. Biol. Chem. 287:30789-30799(2012).
[39]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Liver;
PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
Wang L., Ye M., Zou H.;
"An enzyme assisted RP-RPLC approach for in-depth analysis of human
liver phosphoproteome.";
J. Proteomics 96:253-262(2014).
[40]
SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-32; LYS-953 AND LYS-973, AND
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=28112733; DOI=10.1038/nsmb.3366;
Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
Nielsen M.L.;
"Site-specific mapping of the human SUMO proteome reveals co-
modification with phosphorylation.";
Nat. Struct. Mol. Biol. 24:325-336(2017).
[41]
VARIANTS [LARGE SCALE ANALYSIS] GLN-792 AND GLN-1027.
PubMed=17344846; DOI=10.1038/nature05610;
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.;
"Patterns of somatic mutation in human cancer genomes.";
Nature 446:153-158(2007).
-!- FUNCTION: Serine/threonine-protein kinase involved in
transcription regulation, p53/TP53-mediated cellular apoptosis and
regulation of the cell cycle. Acts as a corepressor of several
transcription factors, including SMAD1 and POU4F1/Brn3a and
probably NK homeodomain transcription factors. Phosphorylates
PDX1, ATF1, PML, p53/TP53, CREB1, CTBP1, CBX4, RUNX1, EP300,
CTNNB1, HMGA1 and ZBTB4. Inhibits cell growth and promotes
apoptosis through the activation of p53/TP53 both at the
transcription level and at the protein level (by phosphorylation
and indirect acetylation). The phosphorylation of p53/TP53 may be
mediated by a p53/TP53-HIPK2-AXIN1 complex. Involved in the
response to hypoxia by acting as a transcriptional co-suppressor
of HIF1A. Mediates transcriptional activation of TP73. In response
to TGFB, cooperates with DAXX to activate JNK. Negative regulator
through phosphorylation and subsequent proteasomal degradation of
CTNNB1 and the antiapoptotic factor CTBP1. In the Wnt/beta-catenin
signaling pathway acts as an intermediate kinase between
MAP3K7/TAK1 and NLK to promote the proteasomal degradation of MYB.
Phosphorylates CBX4 upon DNA damage and promotes its E3 SUMO-
protein ligase activity. Activates CREB1 and ATF1 transcription
factors by phosphorylation in response to genotoxic stress. In
response to DNA damage, stabilizes PML by phosphorylation. PML,
HIPK2 and FBXO3 may act synergically to activate p53/TP53-
dependent transactivation. Promotes angiogenesis, and is involved
in erythroid differentiation, especially during fetal liver
erythropoiesis. Phosphorylation of RUNX1 and EP300 stimulates
EP300 transcription regulation activity. Triggers ZBTB4 protein
degradation in response to DNA damage. Modulates HMGA1 DNA-binding
affinity. In response to high glucose, triggers phosphorylation-
mediated subnuclear localization shifting of PDX1. Involved in the
regulation of eye size, lens formation and retinal lamination
during late embryogenesis. {ECO:0000269|PubMed:11740489,
ECO:0000269|PubMed:11925430, ECO:0000269|PubMed:12851404,
ECO:0000269|PubMed:12874272, ECO:0000269|PubMed:14678985,
ECO:0000269|PubMed:17018294, ECO:0000269|PubMed:17960875,
ECO:0000269|PubMed:18695000, ECO:0000269|PubMed:18809579,
ECO:0000269|PubMed:19015637, ECO:0000269|PubMed:19046997,
ECO:0000269|PubMed:19448668, ECO:0000269|PubMed:20307497,
ECO:0000269|PubMed:20573984, ECO:0000269|PubMed:20637728,
ECO:0000269|PubMed:20980392, ECO:0000269|PubMed:21192925,
ECO:0000269|PubMed:22825850}.
-!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
-!- SUBUNIT: Interacts with CREB1, SIAH1, WSB1, CBX4, TRADD, p53/TP53,
TP73, TP63, CREBBP, DAXX, P53DINP1, SKI, SMAD1, SMAD2 and SMAD3,
but not SMAD4. Interacts with ATF1, PML, RUNX1, EP300, NKX1-2,
NKX2-5, SPN/CD43, UBE2I, HMGA1, CTBP1, AXIN1, NLK, MYB, POU4F1,
POU4F2, POU4F3, UBE2I, UBL1 and ZBTB4. Probably part of a complex
consisting of p53/TP53, HIPK2 and AXIN1. Interacts with SP100;
positively regulates TP53-dependent transcription.
{ECO:0000269|PubMed:11032752, ECO:0000269|PubMed:11740489,
ECO:0000269|PubMed:11925430, ECO:0000269|PubMed:12220523,
ECO:0000269|PubMed:12851404, ECO:0000269|PubMed:12874272,
ECO:0000269|PubMed:14647468, ECO:0000269|PubMed:14678985,
ECO:0000269|PubMed:17018294, ECO:0000269|PubMed:18093972,
ECO:0000269|PubMed:18536714, ECO:0000269|PubMed:19015637,
ECO:0000269|PubMed:19448668, ECO:0000269|PubMed:20573984,
ECO:0000269|PubMed:20980392, ECO:0000269|PubMed:21145359}.
-!- INTERACTION:
P61962:DCAF7; NbExp=10; IntAct=EBI-348345, EBI-359808;
Q09472:EP300; NbExp=4; IntAct=EBI-348345, EBI-447295;
P51608:MECP2; NbExp=2; IntAct=EBI-348345, EBI-1189067;
Q01196:RUNX1; NbExp=4; IntAct=EBI-348345, EBI-925904;
-!- SUBCELLULAR LOCATION: Nucleus, PML body. Cytoplasm.
Note=Concentrated in PML/POD/ND10 nuclear bodies. Small amounts
are cytoplasmic.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=3;
Comment=Experimental confirmation may be lacking for some
isoforms.;
Name=1;
IsoId=Q9H2X6-1; Sequence=Displayed;
Name=2;
IsoId=Q9H2X6-2; Sequence=VSP_004805, VSP_004806, VSP_004807;
Name=3;
IsoId=Q9H2X6-3; Sequence=VSP_004804;
-!- TISSUE SPECIFICITY: Highly expressed in heart, muscle and kidney.
Weakly expressed in a ubiquitous way. Down-regulated in several
thyroid and breast tumors. {ECO:0000269|PubMed:11267674,
ECO:0000269|PubMed:11798164}.
-!- INDUCTION: Unstable in unstressed cells but stabilized upon DNA
damage. Induced by UV irradiation and other genotoxic agents
(adriamycin ADR, cisplatin CDDP, etoposide, IR, roscovitin), thus
triggering p53/TP53 apoptotic response. Consistutively negatively
regulated by SIAH1 and WSB1 through proteasomal degradation. This
negative regulation is impaired upon genotoxic stress. Repressed
upon hypoxia (often associated with tumors), through MDM2- (an E3
ubiquitin ligases) mediated proteasomal degradation, thus
inactivating p53/TP53 apoptotic response. This hypoxia repression
is reversed by zinc. The stabilization mediated by DNA damage
requires the damage checkpoint kinases ATM and ATR.
{ECO:0000269|PubMed:11740489, ECO:0000269|PubMed:18536714,
ECO:0000269|PubMed:18974774, ECO:0000269|PubMed:19714248,
ECO:0000269|PubMed:20514025}.
-!- PTM: Autophosphorylation at Tyr-361 in the activation loop
activates the kinase and promotes nuclear localization.
{ECO:0000250}.
-!- PTM: Sumoylated. When conjugated it is directed to nuclear
speckles. Desumoylated by SENP1 (By similarity). Sumoylation on
Lys-32 is promoted by the E3 SUMO-protein ligase CBX4.
{ECO:0000250, ECO:0000269|PubMed:16253240,
ECO:0000269|PubMed:17018294, ECO:0000269|PubMed:21145359,
ECO:0000269|PubMed:21192925}.
-!- PTM: Ubiquitinated by FBXO3, WSB1 and SIAH1, leading to rapid
proteasome-dependent degradation. The degradation mediated by
FBXO3, but not ubiquitination, is prevented in the presence of
PML. The degradation mediated by WSB1 and SIAH1 is reversibly
reduced upon DNA damage. {ECO:0000269|PubMed:18093972,
ECO:0000269|PubMed:18536714, ECO:0000269|PubMed:18809579}.
-!- PTM: Cleaved at Asp-923 and Asp-984 by CASP6 in a p53/TP53-
dependent manner. The cleaved form lacks the autoinhibitory C-
terminal domain (AID), resulting in a hyperactive kinase, which
potentiates p53/TP53 Ser-46 phosphorylation and subsequent
activation of the cell death machinery.
{ECO:0000269|PubMed:16601678}.
-!- MISCELLANEOUS: Interesting targets for cancer therapy. HIPK2
deregulation would end up in a multifactorial response leading to
tumor chemoresistance by affecting p53/TP53 activity on one hand
and to angiogenesis and cell proliferation by affecting HIF1A
activity on the other hand. May provide important insights in the
process of tumor progression, and may also serve as the crucial
point in the diagnostic and therapeutical aspects of cancer. Tumor
treatment may potential be improved by zinc supplementation in
combination with chemotherapy to address hypoxia
(PubMed:20514025). {ECO:0000305|PubMed:20514025}.
-!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC
Ser/Thr protein kinase family. HIPK subfamily. {ECO:0000305}.
-!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
and Haematology;
URL="http://atlasgeneticsoncology.org/Genes/HIPK2ID40824ch7q34.html";
-----------------------------------------------------------------------
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Distributed under the Creative Commons Attribution (CC BY 4.0) License
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EMBL; AF208291; AAG41236.1; -; mRNA.
EMBL; AF326592; AAL37371.1; -; mRNA.
EMBL; AC005531; AAS00368.1; -; Genomic_DNA.
EMBL; AC073184; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AC006021; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AC141932; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AF207702; AAG35710.1; -; mRNA.
CCDS; CCDS75666.1; -. [Q9H2X6-3]
CCDS; CCDS75667.1; -. [Q9H2X6-1]
RefSeq; NP_001106710.1; NM_001113239.2. [Q9H2X6-3]
RefSeq; NP_073577.3; NM_022740.4. [Q9H2X6-1]
UniGene; Hs.731417; -.
ProteinModelPortal; Q9H2X6; -.
SMR; Q9H2X6; -.
BioGrid; 118815; 65.
CORUM; Q9H2X6; -.
DIP; DIP-31716N; -.
ELM; Q9H2X6; -.
IntAct; Q9H2X6; 21.
MINT; Q9H2X6; -.
STRING; 9606.ENSP00000385571; -.
BindingDB; Q9H2X6; -.
ChEMBL; CHEMBL4576; -.
GuidetoPHARMACOLOGY; 2034; -.
iPTMnet; Q9H2X6; -.
PhosphoSitePlus; Q9H2X6; -.
BioMuta; HIPK2; -.
DMDM; 21431782; -.
MaxQB; Q9H2X6; -.
PaxDb; Q9H2X6; -.
PeptideAtlas; Q9H2X6; -.
PRIDE; Q9H2X6; -.
ProteomicsDB; 80628; -.
ProteomicsDB; 80629; -. [Q9H2X6-2]
ProteomicsDB; 80630; -. [Q9H2X6-3]
TopDownProteomics; Q9H2X6-2; -. [Q9H2X6-2]
DNASU; 28996; -.
Ensembl; ENST00000406875; ENSP00000385571; ENSG00000064393. [Q9H2X6-1]
Ensembl; ENST00000428878; ENSP00000413724; ENSG00000064393. [Q9H2X6-3]
GeneID; 28996; -.
KEGG; hsa:28996; -.
UCSC; uc003vvd.5; human. [Q9H2X6-1]
CTD; 28996; -.
DisGeNET; 28996; -.
EuPathDB; HostDB:ENSG00000064393.15; -.
GeneCards; HIPK2; -.
HGNC; HGNC:14402; HIPK2.
HPA; HPA007611; -.
MIM; 606868; gene.
neXtProt; NX_Q9H2X6; -.
OpenTargets; ENSG00000064393; -.
PharmGKB; PA29291; -.
eggNOG; KOG0667; Eukaryota.
eggNOG; ENOG410XPET; LUCA.
GeneTree; ENSGT00760000119032; -.
HOGENOM; HOG000231785; -.
HOVERGEN; HBG051908; -.
InParanoid; Q9H2X6; -.
KO; K08826; -.
OMA; KVNQYPY; -.
OrthoDB; EOG091G0UMX; -.
PhylomeDB; Q9H2X6; -.
TreeFam; TF105417; -.
BRENDA; 2.7.11.1; 2681.
Reactome; R-HSA-2032785; YAP1- and WWTR1 (TAZ)-stimulated gene expression.
Reactome; R-HSA-3899300; SUMOylation of transcription cofactors.
Reactome; R-HSA-5578768; Physiological factors.
Reactome; R-HSA-6804756; Regulation of TP53 Activity through Phosphorylation.
Reactome; R-HSA-8939243; RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known.
SignaLink; Q9H2X6; -.
SIGNOR; Q9H2X6; -.
ChiTaRS; HIPK2; human.
GeneWiki; HIPK2; -.
GenomeRNAi; 28996; -.
PMAP-CutDB; Q9H2X6; -.
PRO; PR:Q9H2X6; -.
Proteomes; UP000005640; Chromosome 7.
Bgee; ENSG00000064393; Expressed in 239 organ(s), highest expression level in inferior vagus X ganglion.
CleanEx; HS_HIPK2; -.
ExpressionAtlas; Q9H2X6; baseline and differential.
Genevisible; Q9H2X6; HS.
GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
GO; GO:0016604; C:nuclear body; IDA:UniProtKB.
GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
GO; GO:0005634; C:nucleus; IDA:UniProtKB.
GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
GO; GO:0090575; C:RNA polymerase II transcription factor complex; ISS:BHF-UCL.
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
GO; GO:0004674; F:protein serine/threonine kinase activity; EXP:Reactome.
GO; GO:0001102; F:RNA polymerase II activating transcription factor binding; ISS:BHF-UCL.
GO; GO:0046332; F:SMAD binding; IPI:UniProtKB.
GO; GO:0003713; F:transcription coactivator activity; IEA:Ensembl.
GO; GO:0003714; F:transcription corepressor activity; IDA:UniProtKB.
GO; GO:0046790; F:virion binding; IPI:UniProtKB.
GO; GO:0007628; P:adult walking behavior; IEA:Ensembl.
GO; GO:0009952; P:anterior/posterior pattern specification; IEA:Ensembl.
GO; GO:0071456; P:cellular response to hypoxia; TAS:UniProtKB.
GO; GO:0006978; P:DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; IDA:BHF-UCL.
GO; GO:0048596; P:embryonic camera-type eye morphogenesis; IEA:Ensembl.
GO; GO:0060059; P:embryonic retina morphogenesis in camera-type eye; IEA:Ensembl.
GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB.
GO; GO:0001654; P:eye development; ISS:UniProtKB.
GO; GO:0097193; P:intrinsic apoptotic signaling pathway; NAS:UniProtKB.
GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; TAS:UniProtKB.
GO; GO:0061072; P:iris morphogenesis; IEA:Ensembl.
GO; GO:0060235; P:lens induction in camera-type eye; IEA:Ensembl.
GO; GO:0019048; P:modulation by virus of host morphology or physiology; NAS:UniProtKB.
GO; GO:0030514; P:negative regulation of BMP signaling pathway; IMP:UniProtKB.
GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
GO; GO:2000059; P:negative regulation of ubiquitin-dependent protein catabolic process; IMP:FlyBase.
GO; GO:0030182; P:neuron differentiation; IEA:Ensembl.
GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:BHF-UCL.
GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISS:BHF-UCL.
GO; GO:0030578; P:PML body organization; TAS:UniProtKB.
GO; GO:0045766; P:positive regulation of angiogenesis; IDA:UniProtKB.
GO; GO:0008284; P:positive regulation of cell proliferation; IEA:Ensembl.
GO; GO:0043388; P:positive regulation of DNA binding; IEA:Ensembl.
GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISS:BHF-UCL.
GO; GO:0046330; P:positive regulation of JNK cascade; IMP:UniProtKB.
GO; GO:0032092; P:positive regulation of protein binding; ISS:BHF-UCL.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:BHF-UCL.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:BHF-UCL.
GO; GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; IMP:UniProtKB.
GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
GO; GO:0051726; P:regulation of cell cycle; TAS:UniProtKB.
GO; GO:1901796; P:regulation of signal transduction by p53 class mediator; TAS:Reactome.
GO; GO:0010842; P:retina layer formation; IEA:Ensembl.
GO; GO:0060395; P:SMAD protein signal transduction; IDA:UniProtKB.
GO; GO:0007224; P:smoothened signaling pathway; IEA:Ensembl.
GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IEA:Ensembl.
GO; GO:0050882; P:voluntary musculoskeletal movement; IEA:Ensembl.
InterPro; IPR011009; Kinase-like_dom_sf.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR017441; Protein_kinase_ATP_BS.
InterPro; IPR008271; Ser/Thr_kinase_AS.
Pfam; PF00069; Pkinase; 1.
SMART; SM00220; S_TKc; 1.
SUPFAM; SSF56112; SSF56112; 1.
PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
1: Evidence at protein level;
Alternative splicing; Apoptosis; ATP-binding; Complete proteome;
Cytoplasm; DNA damage; Isopeptide bond; Kinase; Nucleotide-binding;
Nucleus; Phosphoprotein; Polymorphism; Reference proteome;
Serine/threonine-protein kinase; Transcription;
Transcription regulation; Transferase; Ubl conjugation.
CHAIN 1 1198 Homeodomain-interacting protein kinase 2.
/FTId=PRO_0000085995.
DOMAIN 199 527 Protein kinase. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
NP_BIND 205 213 ATP. {ECO:0000305}.
REGION 97 230 Transcriptional corepression.
{ECO:0000250}.
REGION 189 520 Interaction with DAXX.
{ECO:0000269|PubMed:14678985}.
REGION 539 844 Interaction with SKI and SMAD1.
{ECO:0000269|PubMed:12874272}.
REGION 752 897 Interaction with POU4F1. {ECO:0000250}.
REGION 774 876 Interaction with CTBP1. {ECO:0000250}.
REGION 787 897 Interaction with HMGA1. {ECO:0000250}.
REGION 846 941 Interaction with TP53 and TP73.
{ECO:0000269|PubMed:11925430}.
REGION 873 980 Required for localization to nuclear
speckles. {ECO:0000250}.
REGION 873 907 Interaction with UBE2I. {ECO:0000250}.
REGION 884 908 SUMO interaction motifs (SIM); required
for nuclear localization and kinase
activity.
REGION 935 1049 Interaction with AXIN1. {ECO:0000250}.
REGION 984 1198 Autoinhibitory domain (AID).
MOTIF 802 805 Nuclear localization signal 1 (NLS1).
MOTIF 832 835 Nuclear localization signal 2 (NLS2).
COMPBIAS 1088 1094 Poly-Ala.
ACT_SITE 324 324 Proton acceptor. {ECO:0000305}.
BINDING 228 228 ATP. {ECO:0000305}.
SITE 923 924 Cleavage; by CASP6.
SITE 984 985 Cleavage; by CASP6.
MOD_RES 16 16 Phosphoserine.
{ECO:0000250|UniProtKB:Q9QZR5}.
MOD_RES 118 118 Phosphoserine.
{ECO:0000250|UniProtKB:Q9QZR5}.
MOD_RES 135 135 Phosphoserine.
{ECO:0000250|UniProtKB:Q9QZR5}.
MOD_RES 141 141 Phosphothreonine.
{ECO:0000250|UniProtKB:Q9QZR5}.
MOD_RES 252 252 Phosphothreonine.
{ECO:0000250|UniProtKB:Q9QZR5}.
MOD_RES 273 273 Phosphothreonine.
{ECO:0000250|UniProtKB:Q9QZR5}.
MOD_RES 361 361 Phosphotyrosine; by autocatalysis.
{ECO:0000250|UniProtKB:Q9QZR5}.
MOD_RES 441 441 Phosphoserine.
{ECO:0000250|UniProtKB:Q9QZR5}.
MOD_RES 482 482 Phosphothreonine.
{ECO:0000250|UniProtKB:Q9QZR5}.
MOD_RES 517 517 Phosphothreonine.
{ECO:0000250|UniProtKB:Q9QZR5}.
MOD_RES 566 566 Phosphothreonine.
{ECO:0000250|UniProtKB:Q9QZR5}.
MOD_RES 634 634 Phosphoserine.
{ECO:0000250|UniProtKB:Q9QZR5}.
MOD_RES 668 668 Phosphoserine.
{ECO:0000250|UniProtKB:Q9QZR5}.
MOD_RES 687 687 Phosphothreonine.
{ECO:0000250|UniProtKB:Q9QZR5}.
MOD_RES 815 815 Phosphoserine.
{ECO:0000250|UniProtKB:Q9QZR5}.
MOD_RES 827 827 Phosphoserine.
{ECO:0000250|UniProtKB:Q9QZR5}.
MOD_RES 934 934 Phosphoserine.
{ECO:0000250|UniProtKB:Q9QZR5}.
MOD_RES 992 992 Phosphoserine.
{ECO:0000250|UniProtKB:Q9QZR5}.
MOD_RES 1041 1041 Phosphoserine.
{ECO:0000250|UniProtKB:Q9QZR5}.
MOD_RES 1155 1155 Phosphoserine.
{ECO:0000250|UniProtKB:Q9QZR5}.
MOD_RES 1188 1188 Phosphoserine.
{ECO:0000250|UniProtKB:Q9QZR5}.
CROSSLNK 32 32 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO);
alternate. {ECO:0000269|PubMed:17018294}.
CROSSLNK 32 32 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO2);
alternate. {ECO:0000244|PubMed:28112733}.
CROSSLNK 953 953 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO2).
{ECO:0000244|PubMed:28112733}.
CROSSLNK 973 973 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO2).
{ECO:0000244|PubMed:28112733}.
CROSSLNK 1191 1191 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO).
{ECO:0000250}.
VAR_SEQ 595 621 Missing (in isoform 3).
{ECO:0000303|Ref.2}.
/FTId=VSP_004804.
VAR_SEQ 808 907 Missing (in isoform 2).
{ECO:0000303|Ref.4}.
/FTId=VSP_004805.
VAR_SEQ 989 1018 VNTSHHSSSYKSKSSSNVTSTSGHSSGSSS -> GNLGPGQ
GRNLSLESGFPAFLLLEMLLYGS (in isoform 2).
{ECO:0000303|Ref.4}.
/FTId=VSP_004806.
VAR_SEQ 1019 1198 Missing (in isoform 2).
{ECO:0000303|Ref.4}.
/FTId=VSP_004807.
VARIANT 792 792 R -> Q (in dbSNP:rs56132157).
{ECO:0000269|PubMed:17344846}.
/FTId=VAR_040547.
VARIANT 1027 1027 R -> Q (in dbSNP:rs35255718).
{ECO:0000269|PubMed:17344846}.
/FTId=VAR_040548.
MUTAGEN 228 228 K->A: Locates in the nucleoplasm, no
effect on interaction with RANBP9, but
loss of kinase activity toward PML, RUNX1
and EP300. {ECO:0000269|PubMed:11267674,
ECO:0000269|PubMed:11740489,
ECO:0000269|PubMed:11925430,
ECO:0000269|PubMed:12220523,
ECO:0000269|PubMed:12874272,
ECO:0000269|PubMed:12907596,
ECO:0000269|PubMed:14678985,
ECO:0000269|PubMed:18695000,
ECO:0000269|PubMed:19015637}.
MUTAGEN 228 228 K->R: Abolishes enzymatic activity, no
effect on interaction with TP53 and TP73
or on BMP-induced transcriptional
activation. Enhances BMP-induced
transcriptional activation; when
associated with 359-AAF-361.
{ECO:0000269|PubMed:11267674,
ECO:0000269|PubMed:11740489,
ECO:0000269|PubMed:11925430,
ECO:0000269|PubMed:12220523,
ECO:0000269|PubMed:12874272,
ECO:0000269|PubMed:12907596,
ECO:0000269|PubMed:14678985,
ECO:0000269|PubMed:18695000,
ECO:0000269|PubMed:19015637}.
MUTAGEN 359 361 STY->AAF: Enhances BMP-induced
transcriptional activation; when
associated with R-228.
{ECO:0000269|PubMed:12874272}.
MUTAGEN 803 803 K->A: Impaired nuclear localization; when
associated with A-805.
{ECO:0000269|PubMed:21145359}.
MUTAGEN 805 805 K->A: Impaired nuclear localization; when
associated with A-803.
{ECO:0000269|PubMed:21145359}.
MUTAGEN 833 833 R->A: Impaired nuclear localization.
{ECO:0000269|PubMed:21145359}.
MUTAGEN 835 835 K->E: Impaired nuclear localization.
{ECO:0000269|PubMed:21145359}.
MUTAGEN 885 892 VSVITISS->KFMHFHRM: Loss of SUMO and CBX4
interaction, and impaired nuclear and
PML-nuclear bodies localization.
{ECO:0000269|PubMed:21145359}.
MUTAGEN 885 888 VSVI->KSAK: Loss of SUMO interaction, and
impaired nuclear and PML-nuclear bodies
localization.
{ECO:0000269|PubMed:21192925}.
MUTAGEN 892 895 SDTD->ADTA: Loss of SUMO interaction, and
impaired nuclear and PML-nuclear bodies
localization.
{ECO:0000269|PubMed:21192925}.
MUTAGEN 893 899 DTDEEEE->NFNQQQQ: Loss of SUMO and CBX4
interaction, and impaired nuclear and
PML-nuclear bodies localization.
{ECO:0000269|PubMed:21145359}.
CONFLICT 33 33 I -> V (in Ref. 1; AAG41236).
{ECO:0000305}.
CONFLICT 59 59 L -> P (in Ref. 1; AAG41236).
{ECO:0000305}.
CONFLICT 64 64 T -> S (in Ref. 1; AAG41236).
{ECO:0000305}.
CONFLICT 169 169 S -> F (in Ref. 4; AAG35710).
{ECO:0000305}.
CONFLICT 187 187 V -> S (in Ref. 4; AAG35710).
{ECO:0000305}.
CONFLICT 202 202 L -> S (in Ref. 4; AAG35710).
{ECO:0000305}.
CONFLICT 233 233 H -> R (in Ref. 1; AAG41236).
{ECO:0000305}.
CONFLICT 471 471 N -> I (in Ref. 2; AAL37371).
{ECO:0000305}.
CONFLICT 669 669 P -> S (in Ref. 4; AAG35710).
{ECO:0000305}.
CONFLICT 711 711 T -> N (in Ref. 4; AAG35710).
{ECO:0000305}.
CONFLICT 717 719 PPA -> SPT (in Ref. 4; AAG35710).
{ECO:0000305}.
CONFLICT 724 724 T -> D (in Ref. 4; AAG35710).
{ECO:0000305}.
SEQUENCE 1198 AA; 130966 MW; 6022D5710E8D2D93 CRC64;
MAPVYEGMAS HVQVFSPHTL QSSAFCSVKK LKIEPSSNWD MTGYGSHSKV YSQSKNIPLS
QPATTTVSTS LPVPNPSLPY EQTIVFPGST GHIVVTSASS TSVTGQVLGG PHNLMRRSTV
SLLDTYQKCG LKRKSEEIEN TSSVQIIEEH PPMIQNNASG ATVATATTST ATSKNSGSNS
EGDYQLVQHE VLCSMTNTYE VLEFLGRGTF GQVVKCWKRG TNEIVAIKIL KNHPSYARQG
QIEVSILARL STESADDYNF VRAYECFQHK NHTCLVFEML EQNLYDFLKQ NKFSPLPLKY
IRPVLQQVAT ALMKLKSLGL IHADLKPENI MLVDPSRQPY RVKVIDFGSA SHVSKAVCST
YLQSRYYRAP EIILGLPFCE AIDMWSLGCV IAELFLGWPL YPGASEYDQI RYISQTQGLP
AEYLLSAGTK TTRFFNRDTD SPYPLWRLKT PDDHEAETGI KSKEARKYIF NCLDDMAQVN
MTTDLEGSDM LVEKADRREF IDLLKKMLTI DADKRITPIE TLNHPFVTMT HLLDFPHSTH
VKSCFQNMEI CKRRVNMYDT VNQSKTPFIT HVAPSTSTNL TMTFNNQLTT VHNQAPSSTS
ATISLANPEV SILNYPSTLY QPSAASMAAV AQRSMPLQTG TAQICARPDP FQQALIVCPP
GFQGLQASPS KHAGYSVRME NAVPIVTQAP GAQPLQIQPG LLAQQAWPSG TQQILLPPAW
QQLTGVATHT SVQHATVIPE TMAGTQQLAD WRNTHAHGSH YNPIMQQPAL LTGHVTLPAA
QPLNVGVAHV MRQQPTSTTS SRKSKQHQSS VRNVSTCEVS SSQAISSPQR SKRVKENTPP
RCAMVHSSPA CSTSVTCGWG DVASSTTRER QRQTIVIPDT PSPTVSVITI SSDTDEEEEQ
KHAPTSTVSK QRKNVISCVT VHDSPYSDSS SNTSPYSVQQ RAGHNNANAF DTKGSLENHC
TGNPRTIIVP PLKTQASEVL VECDSLVPVN TSHHSSSYKS KSSSNVTSTS GHSSGSSSGA
ITYRQQRPGP HFQQQQPLNL SQAQQHITTD RTGSHRRQQA YITPTMAQAP YSFPHNSPSH
GTVHPHLAAA AAAAHLPTQP HLYTYTAPAA LGSTGTVAHL VASQGSARHT VQHTAYPASI
VHQVPVSMGP RVLPSPTIHP SQYPAQFAHQ TYISASPAST VYTGYPLSPA KVNQYPYI


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HIRIP3 HIPK4 Gene homeodomain interacting protein kinase 4
HIRA HIPK3 Gene homeodomain interacting protein kinase 3
E15027m Mouse ELISA Kit FOR Homeodomain-interacting protein kinase 2 96T
E1349m Human ELISA Kit FOR Homeodomain-interacting protein kinase 1 96T
HIPK3 HIPK1 Gene homeodomain interacting protein kinase 1
E1002Ge Human ELISA Kit FOR Homeodomain-interacting protein kinase 4 96T
HIPK4 HIPK2 Gene homeodomain interacting protein kinase 2
CSB-EL010369HU Human Homeodomain-interacting protein kinase 3(HIPK3) ELISA kit 96T
CSB-EL010370MO Mouse Homeodomain-interacting protein kinase 4(HIPK4) ELISA kit 96T
CSB-EL010369MO Mouse Homeodomain-interacting protein kinase 3(HIPK3) ELISA kit 96T
CSB-EL010368HU Human Homeodomain-interacting protein kinase 2(HIPK2) ELISA kit 96T
CSB-EL010368MO Mouse Homeodomain-interacting protein kinase 2(HIPK2) ELISA kit 96T
CSB-EL010367MO Mouse Homeodomain-interacting protein kinase 1(HIPK1) ELISA kit 96T
GWB-49DE8C Anti- HIPK2 (homeodomain interacting protein kinase 2) Antibody
CSB-EL010367HU Human Homeodomain-interacting protein kinase 1(HIPK1) ELISA kit 96T
CSB-EL010370RA Rat Homeodomain-interacting protein kinase 4(HIPK4) ELISA kit SpeciesRat 96T
CSB-EL010367RA Rat Homeodomain-interacting protein kinase 1(HIPK1) ELISA kit SpeciesRat 96T
CSB-EL010369RA Rat Homeodomain-interacting protein kinase 3(HIPK3) ELISA kit SpeciesRat 96T


 

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