HIPK1_HUMAN
ID HIPK1_HUMAN Reviewed; 1210 AA.
AC Q86Z02; A6NJ34; O75125; Q5SQL2; Q5SQL4; Q5SQL5; Q8IYD7; Q8NDN5; Q8NEB6;
AC Q8TBZ1;
DT 29-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Homeodomain-interacting protein kinase 1;
DE EC=2.7.11.1;
DE AltName: Full=Nuclear body-associated kinase 2;
GN Name=HIPK1; Synonyms=KIAA0630, MYAK, NBAK2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Miyata Y.;
RT "Molecular cloning of human HIPK1.";
RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3 AND 4).
RC TISSUE=Testis;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 318-1210 (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 720-1210 (ISOFORMS 1/3/4).
RC TISSUE=Brain;
RX PubMed=9734811; DOI=10.1093/dnares/5.3.169;
RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H.,
RA Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. X. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:169-176(1998).
RN [7]
RP FUNCTION, AND PHOSPHORYLATION BY JNK1.
RX PubMed=12968034; DOI=10.1074/jbc.m213201200;
RA Song J.J., Lee Y.J.;
RT "Role of the ASK1-SEK1-JNK1-HIPK1 signal in Daxx trafficking and ASK1
RT oligomerization.";
RL J. Biol. Chem. 278:47245-47252(2003).
RN [8]
RP TISSUE SPECIFICITY, AND INTERACTION WITH DAXX.
RX PubMed=12529400; DOI=10.1128/mcb.23.3.950-960.2003;
RA Ecsedy J.A., Michaelson J.S., Leder P.;
RT "Homeodomain-interacting protein kinase 1 modulates Daxx localization,
RT phosphorylation, and transcriptional activity.";
RL Mol. Cell. Biol. 23:950-960(2003).
RN [9]
RP INTERACTION WITH TP53, TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=12702766; DOI=10.1073/pnas.0530308100;
RA Kondo S., Lu Y., Debbas M., Lin A.W., Sarosi I., Itie A., Wakeham A.,
RA Tuan J., Saris C., Elliott G., Ma W., Benchimol S., Lowe S.W., Mak T.W.,
RA Thukral S.K.;
RT "Characterization of cells and gene-targeted mice deficient for the p53-
RT binding kinase homeodomain-interacting protein kinase 1 (HIPK1).";
RL Proc. Natl. Acad. Sci. U.S.A. 100:5431-5436(2003).
RN [10]
RP FUNCTION, INTERACTION WITH DAB2IP AND MAP3K5, SUBCELLULAR LOCATION,
RP SUMOYLATION AT LYS-25 AND LYS-1203, DESUMOYLATION MEDIATED BY TNF, AND
RP MUTAGENESIS OF LYS-25; ASP-315; LYS-317; LYS-440; LYS-556 AND LYS-1203.
RX PubMed=15701637; DOI=10.1074/jbc.m414262200;
RA Li X., Zhang R., Luo D., Park S.-J., Wang Q., Kim Y., Min W.;
RT "Tumor necrosis factor alpha-induced desumoylation and cytoplasmic
RT translocation of homeodomain-interacting protein kinase 1 are critical for
RT apoptosis signal-regulating kinase 1-JNK/p38 activation.";
RL J. Biol. Chem. 280:15061-15070(2005).
RN [11]
RP FUNCTION IN ANTI-OXIDATIVE STRESS, INTERACTION WITH PARK7, SUBCELLULAR
RP LOCATION, AND DEGRADATION BY PARK7.
RX PubMed=16390825; DOI=10.1080/10715760500456847;
RA Sekito A., Koide-Yoshida S., Niki T., Taira T., Iguchi-Ariga S.M.M.,
RA Ariga H.;
RT "DJ-1 interacts with HIPK1 and affects H2O2-induced cell death.";
RL Free Radic. Res. 40:155-165(2006).
RN [12]
RP DESUMOYLATION BY SENP1, AND SUBCELLULAR LOCATION.
RX PubMed=18219322; DOI=10.1038/sj.cdd.4402303;
RA Li X., Luo Y., Yu L., Lin Y., Luo D., Zhang H., He Y., Kim Y.-O., Kim Y.,
RA Tang S., Min W.;
RT "SENP1 mediates TNF-induced desumoylation and cytoplasmic translocation of
RT HIPK1 to enhance ASK1-dependent apoptosis.";
RL Cell Death Differ. 15:739-750(2008).
RN [13]
RP FUNCTION AS MYB KINASE, INTERACTION WITH MYB, MUTAGENESIS OF LYS-219, AND
RP SUBCELLULAR LOCATION.
RX PubMed=19646965; DOI=10.1016/j.bbrc.2009.07.139;
RA Matre V., Nordgaard O., Alm-Kristiansen A.H., Ledsaak M., Gabrielsen O.S.;
RT "HIPK1 interacts with c-Myb and modulates its activity through
RT phosphorylation.";
RL Biochem. Biophys. Res. Commun. 388:150-154(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-872, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-967 AND SER-1200, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [16]
RP FUNCTION.
RX PubMed=24559171; DOI=10.1021/bi500013w;
RA Mooney S.M., Qiu R., Kim J.J., Sacho E.J., Rajagopalan K., Johng D.,
RA Shiraishi T., Kulkarni P., Weninger K.R.;
RT "Cancer/testis antigen PAGE4, a regulator of c-Jun transactivation, is
RT phosphorylated by homeodomain-interacting protein kinase 1, a component of
RT the stress-response pathway.";
RL Biochemistry 53:1670-1679(2014).
RN [17]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-25, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [18]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-25, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033;
RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V.,
RA Vertegaal A.C.;
RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage.";
RL Cell Rep. 10:1778-1791(2015).
RN [19]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-25; LYS-120; LYS-124 AND LYS-991,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [20]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=28289210; DOI=10.1073/pnas.1700082114;
RA Kulkarni P., Jolly M.K., Jia D., Mooney S.M., Bhargava A., Kagohara L.T.,
RA Chen Y., Hao P., He Y., Veltri R.W., Grishaev A., Weninger K., Levine H.,
RA Orban J.;
RT "Phosphorylation-induced conformational dynamics in an intrinsically
RT disordered protein and potential role in phenotypic heterogeneity.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:E2644-E2653(2017).
RN [21]
RP VARIANTS [LARGE SCALE ANALYSIS] CYS-310 AND VAL-1165.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Serine/threonine-protein kinase involved in transcription
CC regulation and TNF-mediated cellular apoptosis. Plays a role as a
CC corepressor for homeodomain transcription factors. Phosphorylates DAXX
CC and MYB. Phosphorylates DAXX in response to stress, and mediates its
CC translocation from the nucleus to the cytoplasm. Inactivates MYB
CC transcription factor activity by phosphorylation. Prevents MAP3K5-JNK
CC activation in the absence of TNF. TNF triggers its translocation to the
CC cytoplasm in response to stress stimuli, thus activating nuclear
CC MAP3K5-JNK by derepression and promoting apoptosis. May be involved in
CC anti-oxidative stress responses. Involved in the regulation of eye
CC size, lens formation and retinal lamination during late embryogenesis.
CC Promotes angiogenesis and to be involved in erythroid differentiation.
CC May be involved in malignant squamous cell tumor formation.
CC Phosphorylates PAGE4 at 'Thr-51' which is critical for the ability of
CC PAGE4 to potentiate the transcriptional activator activity of JUN
CC (PubMed:24559171). {ECO:0000269|PubMed:12702766,
CC ECO:0000269|PubMed:12968034, ECO:0000269|PubMed:15701637,
CC ECO:0000269|PubMed:16390825, ECO:0000269|PubMed:19646965,
CC ECO:0000269|PubMed:24559171}.
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 Nkx1-2, Nkx2-5, MYB, PARK7, DAXX and p53/TP53.
CC Part of a cytoplasmic complex made of HIPK1, DAB2IP and MAP3K5 in
CC response to TNF. This complex formation promotes MAP3K5-JNK activation
CC and subsequent apoptosis. {ECO:0000269|PubMed:12529400,
CC ECO:0000269|PubMed:12702766, ECO:0000269|PubMed:15701637,
CC ECO:0000269|PubMed:16390825, ECO:0000269|PubMed:19646965}.
CC -!- INTERACTION:
CC Q86Z02; Q13643: FHL3; NbExp=4; IntAct=EBI-692891, EBI-741101;
CC Q86Z02; P04637: TP53; NbExp=2; IntAct=EBI-692891, EBI-366083;
CC Q86Z02-4; Q13643: FHL3; NbExp=3; IntAct=EBI-12025238, EBI-741101;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15701637,
CC ECO:0000269|PubMed:16390825, ECO:0000269|PubMed:18219322,
CC ECO:0000269|PubMed:19646965, ECO:0000269|PubMed:28289210}. Cytoplasm
CC {ECO:0000269|PubMed:15701637, ECO:0000269|PubMed:18219322,
CC ECO:0000269|PubMed:19646965, ECO:0000269|PubMed:28289210}. Nucleus
CC speckle {ECO:0000269|PubMed:16390825}. Note=Predominantly nuclear.
CC Translocates from nucleus to cytoplasm in response to stress stimuli
CC via SENP1-mediated desumoylation. {ECO:0000269|PubMed:15701637,
CC ECO:0000269|PubMed:18219322}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=HIPK1-alpha;
CC IsoId=Q86Z02-1; Sequence=Displayed;
CC Name=2; Synonyms=HIPK1-beta;
CC IsoId=Q86Z02-2; Sequence=VSP_013130, VSP_013131;
CC Name=3;
CC IsoId=Q86Z02-3; Sequence=VSP_013128;
CC Name=4;
CC IsoId=Q86Z02-4; Sequence=VSP_013127, VSP_013129;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with highest levels in
CC skeletal muscle and heart. Overexpressed in breast cancer cell lines.
CC Isoform 2 is highly expressed in testis. Expressed in both androgen-
CC dependent and androgen-independent prostate cancer cells
CC (PubMed:28289210). {ECO:0000269|PubMed:12529400,
CC ECO:0000269|PubMed:12702766, ECO:0000269|PubMed:28289210}.
CC -!- PTM: Autophosphorylated. Phosphorylated and activated by JNK1.
CC {ECO:0000269|PubMed:12968034}.
CC -!- PTM: Degraded by PARK7 at the protein level.
CC -!- PTM: Sumoylated. When conjugated it is directed to nuclear speckles.
CC SENP1-mediated desumoylation is mediated by TNF in response to stress
CC stimuli, triggering transient translocation from nucleus to cytoplasm.
CC {ECO:0000269|PubMed:15701637, ECO:0000269|PubMed:18219322}.
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; AB089957; BAC57075.1; -; mRNA.
DR EMBL; AL731797; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL137856; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471122; EAW56590.1; -; Genomic_DNA.
DR EMBL; BC028408; AAH28408.1; -; mRNA.
DR EMBL; BC033012; AAH33012.1; -; mRNA.
DR EMBL; BC036057; AAH36057.1; -; mRNA.
DR EMBL; AL833829; CAD38689.1; -; mRNA.
DR EMBL; AB014530; BAA31605.1; -; mRNA.
DR CCDS; CCDS41370.1; -. [Q86Z02-3]
DR CCDS; CCDS867.1; -. [Q86Z02-1]
DR CCDS; CCDS868.1; -. [Q86Z02-2]
DR CCDS; CCDS869.1; -. [Q86Z02-4]
DR RefSeq; NP_689909.2; NM_152696.3. [Q86Z02-2]
DR RefSeq; NP_852003.1; NM_181358.2. [Q86Z02-4]
DR RefSeq; NP_938009.1; NM_198268.2. [Q86Z02-1]
DR RefSeq; NP_938010.1; NM_198269.2. [Q86Z02-3]
DR RefSeq; XP_005270669.1; XM_005270612.4.
DR RefSeq; XP_005270670.1; XM_005270613.4. [Q86Z02-1]
DR AlphaFoldDB; Q86Z02; -.
DR SMR; Q86Z02; -.
DR BioGRID; 128490; 23.
DR ELM; Q86Z02; -.
DR IntAct; Q86Z02; 19.
DR MINT; Q86Z02; -.
DR STRING; 9606.ENSP00000358571; -.
DR BindingDB; Q86Z02; -.
DR ChEMBL; CHEMBL5427; -.
DR DrugCentral; Q86Z02; -.
DR GuidetoPHARMACOLOGY; 2033; -.
DR GlyGen; Q86Z02; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q86Z02; -.
DR PhosphoSitePlus; Q86Z02; -.
DR BioMuta; HIPK1; -.
DR DMDM; 34395641; -.
DR EPD; Q86Z02; -.
DR jPOST; Q86Z02; -.
DR MassIVE; Q86Z02; -.
DR MaxQB; Q86Z02; -.
DR PaxDb; Q86Z02; -.
DR PeptideAtlas; Q86Z02; -.
DR PRIDE; Q86Z02; -.
DR ProteomicsDB; 70492; -. [Q86Z02-1]
DR ProteomicsDB; 70493; -. [Q86Z02-2]
DR ProteomicsDB; 70494; -. [Q86Z02-3]
DR ProteomicsDB; 70495; -. [Q86Z02-4]
DR Antibodypedia; 20149; 339 antibodies from 30 providers.
DR DNASU; 204851; -.
DR Ensembl; ENST00000340480.8; ENSP00000340956.4; ENSG00000163349.22. [Q86Z02-3]
DR Ensembl; ENST00000369553.5; ENSP00000358566.1; ENSG00000163349.22. [Q86Z02-4]
DR Ensembl; ENST00000369558.5; ENSP00000358571.1; ENSG00000163349.22. [Q86Z02-1]
DR Ensembl; ENST00000369559.8; ENSP00000358572.4; ENSG00000163349.22. [Q86Z02-2]
DR Ensembl; ENST00000426820.7; ENSP00000407442.3; ENSG00000163349.22. [Q86Z02-1]
DR GeneID; 204851; -.
DR KEGG; hsa:204851; -.
DR MANE-Select; ENST00000426820.7; ENSP00000407442.3; NM_198268.3; NP_938009.1.
DR UCSC; uc001eel.4; human. [Q86Z02-1]
DR CTD; 204851; -.
DR DisGeNET; 204851; -.
DR GeneCards; HIPK1; -.
DR HGNC; HGNC:19006; HIPK1.
DR HPA; ENSG00000163349; Tissue enhanced (bone).
DR MIM; 608003; gene.
DR neXtProt; NX_Q86Z02; -.
DR OpenTargets; ENSG00000163349; -.
DR PharmGKB; PA134897980; -.
DR VEuPathDB; HostDB:ENSG00000163349; -.
DR eggNOG; KOG0667; Eukaryota.
DR GeneTree; ENSGT00940000155356; -.
DR HOGENOM; CLU_003045_1_1_1; -.
DR InParanoid; Q86Z02; -.
DR OMA; SQERSNN; -.
DR OrthoDB; 59821at2759; -.
DR PhylomeDB; Q86Z02; -.
DR TreeFam; TF105417; -.
DR PathwayCommons; Q86Z02; -.
DR Reactome; R-HSA-2032785; YAP1- and WWTR1 (TAZ)-stimulated gene expression.
DR Reactome; R-HSA-5578768; Physiological factors.
DR Reactome; R-HSA-6804756; Regulation of TP53 Activity through Phosphorylation.
DR SignaLink; Q86Z02; -.
DR SIGNOR; Q86Z02; -.
DR BioGRID-ORCS; 204851; 20 hits in 1113 CRISPR screens.
DR ChiTaRS; HIPK1; human.
DR GeneWiki; HIPK1; -.
DR GenomeRNAi; 204851; -.
DR Pharos; Q86Z02; Tchem.
DR PRO; PR:Q86Z02; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q86Z02; protein.
DR Bgee; ENSG00000163349; Expressed in bronchial epithelial cell and 211 other tissues.
DR ExpressionAtlas; Q86Z02; baseline and differential.
DR Genevisible; Q86Z02; HS.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016605; C:PML body; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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:0034333; P:adherens junction assembly; IEA:Ensembl.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IEA:Ensembl.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0060216; P:definitive hemopoiesis; ISS:UniProtKB.
DR GO; GO:0048596; P:embryonic camera-type eye morphogenesis; IEA:Ensembl.
DR GO; GO:0060059; P:embryonic retina morphogenesis in camera-type eye; IEA:Ensembl.
DR GO; GO:0072577; P:endothelial cell apoptotic process; IDA:UniProtKB.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IDA:UniProtKB.
DR GO; GO:0001654; P:eye development; ISS:UniProtKB.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IBA:GO_Central.
DR GO; GO:0061072; P:iris morphogenesis; IEA:Ensembl.
DR GO; GO:0060235; P:lens induction in camera-type eye; IEA:Ensembl.
DR GO; GO:0030182; P:neuron differentiation; IEA:Ensembl.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IBA:GO_Central.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0010803; P:regulation of tumor necrosis factor-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0010842; P:retina layer formation; IEA:Ensembl.
DR GO; GO:0007224; P:smoothened signaling pathway; IBA:GO_Central.
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; 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..1210
FT /note="Homeodomain-interacting protein kinase 1"
FT /id="PRO_0000085993"
FT DOMAIN 190..518
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 835..856
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 885..1093
FT /note="Interaction with TP53"
FT /evidence="ECO:0000269|PubMed:12702766"
FT REGION 891..998
FT /note="Required for localization to nuclear speckles"
FT /evidence="ECO:0000250"
FT REGION 902..926
FT /note="SUMO interaction motifs (SIM); required for nuclear
FT localization and kinase activity"
FT /evidence="ECO:0000250"
FT REGION 909..974
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1046..1069
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1084..1103
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 844..847
FT /note="Nuclear localization signal 1 (NLS1)"
FT /evidence="ECO:0000250"
FT COMPBIAS 909..923
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 924..964
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 315
FT /note="Proton acceptor"
FT /evidence="ECO:0000305"
FT BINDING 196..204
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT BINDING 219
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT MOD_RES 872
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 967
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1200
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 25
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT CROSSLNK 25
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733"
FT CROSSLNK 120
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 124
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 991
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1203
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:15701637"
FT VAR_SEQ 1..394
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013127"
FT VAR_SEQ 1..374
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013128"
FT VAR_SEQ 395..399
FT /note="ASEYD -> MVLMF (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013129"
FT VAR_SEQ 1049..1075
FT /note="NQQSSAAPTSQERSSNPAPRRQQAFVA -> VSAMGYCLLFGPCTVVTFWRT
FT LLLAGC (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013130"
FT VAR_SEQ 1076..1210
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013131"
FT VARIANT 6
FT /note="Q -> R (in dbSNP:rs35324789)"
FT /id="VAR_051626"
FT VARIANT 310
FT /note="G -> C (in dbSNP:rs34335651)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040546"
FT VARIANT 1165
FT /note="L -> V"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_046047"
FT MUTAGEN 25
FT /note="K->R: Reduced sumoylation and cytoplasmic
FT subcellular location. Impaired sumoylation and cytoplasmic
FT subcellular location; when associated with R-317; R-440; R-
FT 556 and R-1203."
FT /evidence="ECO:0000269|PubMed:15701637"
FT MUTAGEN 219
FT /note="K->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:19646965"
FT MUTAGEN 315
FT /note="D->N: Loss of kinase activity and impaired MAP3K5-
FT JNK inactivation."
FT /evidence="ECO:0000269|PubMed:15701637"
FT MUTAGEN 317
FT /note="K->R: Nuclear subcellular location. Impaired
FT sumoylation and cytoplasmic subcellular location; when
FT associated with R-25; R-440; R-556 and R-1203."
FT /evidence="ECO:0000269|PubMed:15701637"
FT MUTAGEN 440
FT /note="K->R: Nuclear subcellular location. Impaired
FT sumoylation and cytoplasmic subcellular location; when
FT associated with R-25; R-317; R-556 and R-1203."
FT /evidence="ECO:0000269|PubMed:15701637"
FT MUTAGEN 556
FT /note="K->R: Nuclear subcellular location. Impaired
FT sumoylation and cytoplasmic subcellular location; when
FT associated with R-25; R-317; R-440 and R-1203."
FT /evidence="ECO:0000269|PubMed:15701637"
FT MUTAGEN 1203
FT /note="K->R: Nuclear subcellular location. Impaired
FT sumoylation and cytoplasmic subcellular location; when
FT associated with R-25; R-317; R-440 and R-556."
FT /evidence="ECO:0000269|PubMed:15701637"
FT CONFLICT 721
FT /note="P -> Q (in Ref. 4; AAH33012)"
FT /evidence="ECO:0000305"
FT CONFLICT 747
FT /note="Missing (in Ref. 6; BAA31605)"
FT /evidence="ECO:0000305"
FT CONFLICT 799
FT /note="H -> Y (in Ref. 5; CAD38689)"
FT /evidence="ECO:0000305"
FT CONFLICT 1054
FT /note="A -> V (in Ref. 4; AAH36057)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1210 AA; 130843 MW; DB0BBFA6DF152909 CRC64;
MASQLQVFSP PSVSSSAFCS AKKLKIEPSG WDVSGQSSND KYYTHSKTLP ATQGQANSSH
QVANFNIPAY DQGLLLPAPA VEHIVVTAAD SSGSAATSTF QSSQTLTHRS NVSLLEPYQK
CGLKRKSEEV DSNGSVQIIE EHPPLMLQNR TVVGAAATTT TVTTKSSSSS GEGDYQLVQH
EILCSMTNSY EVLEFLGRGT FGQVAKCWKR STKEIVAIKI LKNHPSYARQ GQIEVSILSR
LSSENADEYN FVRSYECFQH KNHTCLVFEM LEQNLYDFLK QNKFSPLPLK YIRPILQQVA
TALMKLKSLG LIHADLKPEN IMLVDPVRQP YRVKVIDFGS ASHVSKAVCS TYLQSRYYRA
PEIILGLPFC EAIDMWSLGC VIAELFLGWP LYPGASEYDQ IRYISQTQGL PAEYLLSAGT
KTTRFFNRDP NLGYPLWRLK TPEEHELETG IKSKEARKYI FNCLDDMAQV NMSTDLEGTD
MLAEKADRRE YIDLLKKMLT IDADKRITPL KTLNHQFVTM THLLDFPHSN HVKSCFQNME
ICKRRVHMYD TVSQIKSPFT THVAPNTSTN LTMSFSNQLN TVHNQASVLA SSSTAAAATL
SLANSDVSLL NYQSALYPSS AAPVPGVAQQ GVSLQPGTTQ ICTQTDPFQQ TFIVCPPAFQ
TGLQATTKHS GFPVRMDNAV PIVPQAPAAQ PLQIQSGVLT QGSCTPLMVA TLHPQVATIT
PQYAVPFTLS CAAGRPALVE QTAAVLQAWP GGTQQILLPS TWQQLPGVAL HNSVQPTAMI
PEAMGSGQQL ADWRNAHSHG NQYSTIMQQP SLLTNHVTLA TAQPLNVGVA HVVRQQQSSS
LPSKKNKQSA PVSSKSSLDV LPSQVYSLVG SSPLRTTSSY NSLVPVQDQH QPIIIPDTPS
PPVSVITIRS DTDEEEDNKY KPSSSGLKPR SNVISYVTVN DSPDSDSSLS SPYSTDTLSA
LRGNSGSVLE GPGRVVADGT GTRTIIVPPL KTQLGDCTVA TQASGLLSNK TKPVASVSGQ
SSGCCITPTG YRAQRGGTSA AQPLNLSQNQ QSSAAPTSQE RSSNPAPRRQ QAFVAPLSQA
PYTFQHGSPL HSTGHPHLAP APAHLPSQAH LYTYAAPTSA AALGSTSSIA HLFSPQGSSR
HAAAYTTHPS TLVHQVPVSV GPSLLTSASV APAQYQHQFA TQSYIGSSRG STIYTGYPLS
PTKISQYSYL
