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 27-MAR-2024, entry version 181. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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. DR AlphaFoldDB; Q86Z02; -. DR SMR; Q86Z02; -. DR BioGRID; 128490; 27. DR ELM; Q86Z02; -. DR IntAct; Q86Z02; 23. DR MINT; Q86Z02; -. DR STRING; 9606.ENSP00000407442; -. DR BindingDB; Q86Z02; -. DR ChEMBL; CHEMBL5427; -. DR DrugCentral; Q86Z02; -. DR GuidetoPHARMACOLOGY; 2033; -. DR GlyCosmos; Q86Z02; 1 site, 1 glycan. DR GlyGen; Q86Z02; 6 sites, 1 O-linked glycan (6 sites). 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; 9606-ENSP00000358571; -. DR PeptideAtlas; Q86Z02; -. DR ProteomicsDB; 70492; -. [Q86Z02-1] DR ProteomicsDB; 70493; -. [Q86Z02-2] DR ProteomicsDB; 70494; -. [Q86Z02-3] DR ProteomicsDB; 70495; -. [Q86Z02-4] DR Pumba; Q86Z02; -. DR Antibodypedia; 20149; 386 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 AGR; HGNC:19006; -. 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; 3095114at2759; -. 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; 21 hits in 1190 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 213 other cell types or tissues. DR ExpressionAtlas; Q86Z02; baseline and differential. 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: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 CDD; cd14228; STKc_HIPK1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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 PANTHER; PTHR24058; DUAL SPECIFICITY PROTEIN KINASE; 1. DR PANTHER; PTHR24058:SF43; HOMEODOMAIN-INTERACTING PROTEIN KINASE 1; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; Q86Z02; HS. 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; FT R-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 FT MAP3K5-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 //