HIPK4_HUMAN
ID HIPK4_HUMAN Reviewed; 616 AA.
AC Q8NE63; A8K863; Q96M54;
DT 04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Homeodomain-interacting protein kinase 4;
DE EC=2.7.11.1;
GN Name=HIPK4;
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 [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
RP VARIANTS [LARGE SCALE ANALYSIS] THR-106; MET-171; MET-381; THR-386;
RP ARG-406; SER-421 AND CYS-481.
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: Protein kinase that phosphorylates human TP53 at Ser-9, and
CC thus induces TP53 repression of BIRC5 promoter (By similarity). May act
CC as a corepressor of transcription factors (Potential). {ECO:0000250,
CC ECO:0000305}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- INTERACTION:
CC Q8NE63; Q92624: APPBP2; NbExp=3; IntAct=EBI-6381114, EBI-743771;
CC Q8NE63; P08238: HSP90AB1; NbExp=2; IntAct=EBI-6381114, EBI-352572;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- PTM: Autophosphorylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. HIPK subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB71458.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={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; AK057380; BAB71458.1; ALT_SEQ; mRNA.
DR EMBL; AK292228; BAF84917.1; -; mRNA.
DR EMBL; BC034501; AAH34501.1; -; mRNA.
DR CCDS; CCDS12555.1; -.
DR RefSeq; NP_653286.2; NM_144685.4.
DR AlphaFoldDB; Q8NE63; -.
DR SMR; Q8NE63; -.
DR BioGRID; 127086; 29.
DR IntAct; Q8NE63; 32.
DR STRING; 9606.ENSP00000291823; -.
DR BindingDB; Q8NE63; -.
DR ChEMBL; CHEMBL1075167; -.
DR DrugCentral; Q8NE63; -.
DR iPTMnet; Q8NE63; -.
DR PhosphoSitePlus; Q8NE63; -.
DR BioMuta; HIPK4; -.
DR DMDM; 74762559; -.
DR jPOST; Q8NE63; -.
DR MassIVE; Q8NE63; -.
DR PaxDb; Q8NE63; -.
DR PeptideAtlas; Q8NE63; -.
DR PRIDE; Q8NE63; -.
DR Antibodypedia; 16956; 297 antibodies from 28 providers.
DR DNASU; 147746; -.
DR Ensembl; ENST00000291823.3; ENSP00000291823.1; ENSG00000160396.9.
DR GeneID; 147746; -.
DR KEGG; hsa:147746; -.
DR MANE-Select; ENST00000291823.3; ENSP00000291823.1; NM_144685.5; NP_653286.2.
DR UCSC; uc002onp.3; human.
DR CTD; 147746; -.
DR DisGeNET; 147746; -.
DR GeneCards; HIPK4; -.
DR HGNC; HGNC:19007; HIPK4.
DR HPA; ENSG00000160396; Group enriched (brain, testis).
DR MIM; 611712; gene.
DR neXtProt; NX_Q8NE63; -.
DR OpenTargets; ENSG00000160396; -.
DR PharmGKB; PA134883524; -.
DR VEuPathDB; HostDB:ENSG00000160396; -.
DR eggNOG; KOG0667; Eukaryota.
DR GeneTree; ENSGT00940000161512; -.
DR HOGENOM; CLU_000288_5_14_1; -.
DR InParanoid; Q8NE63; -.
DR OMA; DWTLEGI; -.
DR OrthoDB; 59821at2759; -.
DR PhylomeDB; Q8NE63; -.
DR TreeFam; TF105417; -.
DR PathwayCommons; Q8NE63; -.
DR SignaLink; Q8NE63; -.
DR BioGRID-ORCS; 147746; 9 hits in 1104 CRISPR screens.
DR ChiTaRS; HIPK4; human.
DR GenomeRNAi; 147746; -.
DR Pharos; Q8NE63; Tchem.
DR PRO; PR:Q8NE63; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q8NE63; protein.
DR Bgee; ENSG00000160396; Expressed in left testis and 94 other tissues.
DR ExpressionAtlas; Q8NE63; baseline and differential.
DR Genevisible; Q8NE63; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; 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:0016572; P:histone phosphorylation; 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:0046777; P:protein autophosphorylation; IEA:Ensembl.
DR GO; GO:1901796; P:regulation of signal transduction by p53 class mediator; IEA:Ensembl.
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 ATP-binding; Cytoplasm; Kinase; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..616
FT /note="Homeodomain-interacting protein kinase 4"
FT /id="PRO_0000232401"
FT DOMAIN 11..347
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 486..616
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 495..509
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 547..561
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 136
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 17..25
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 40
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 511
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3V016"
FT VARIANT 106
FT /note="A -> T (in dbSNP:rs34434715)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040554"
FT VARIANT 171
FT /note="V -> M (in dbSNP:rs55964225)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040555"
FT VARIANT 302
FT /note="R -> Q (in dbSNP:rs11670988)"
FT /id="VAR_030578"
FT VARIANT 381
FT /note="T -> M (in dbSNP:rs55760165)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040556"
FT VARIANT 386
FT /note="A -> T (in dbSNP:rs56365273)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040557"
FT VARIANT 406
FT /note="S -> R (in dbSNP:rs56094851)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040558"
FT VARIANT 421
FT /note="G -> S (in dbSNP:rs56117722)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040559"
FT VARIANT 481
FT /note="R -> C (in dbSNP:rs55801979)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040560"
FT CONFLICT 374
FT /note="Q -> R (in Ref. 1; BAB71458)"
FT /evidence="ECO:0000305"
FT CONFLICT 445
FT /note="T -> A (in Ref. 1; BAB71458)"
FT /evidence="ECO:0000305"
FT CONFLICT 581
FT /note="E -> G (in Ref. 1; BAF84917)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 616 AA; 69425 MW; 02429E8F2070C6C0 CRC64;
MSTIQSETDC YDIIEVLGKG TFGEVAKGWR RSTGEMVAIK ILKNDAYRNR IIKNELKLLH
CMRGLDPEEA HVIRFLEFFH DALKFYLVFE LLEQNLFEFQ KENNFAPLPA RHIRTVTLQV
LTALARLKEL AIIHADLKPE NIMLVDQTRC PFRVKVIDFG SASIFSEVRY VKEPYIQSRF
YRAPEILLGL PFCEKVDVWS LGCVMAELHL GWPLYPGNNE YDQVRYICET QGLPKPHLLH
AACKAHHFFK RNPHPDAANP WQLKSSADYL AETKVRPLER RKYMLKSLDQ IETVNGGSVA
SRLTFPDREA LAEHADLKSM VELIKRMLTW ESHERISPSA ALRHPFVSMQ QLRSAHETTH
YYQLSLRSYR LSLQVEGKPP TPVVAAEDGT PYYCLAEEKE AAGMGSVAGS SPFFREEKAP
GMQRAIDQLD DLSLQEAGHG LWGETCTNAV SDMMVPLKAA ITGHHVPDSG PEPILAFYSS
RLAGRHKARK PPAGSKSDSN FSNLIRLSQV SPEDDRPCRG SSWEEGEHLG ASAEPLAILQ
RDEDGPNIDN MTMEAERPDP ELFDPSSCPG EWLSEPDCTL ESVRGPRAQG LPPRRSHQHG
PPRGATSFLQ HVTGHH
