KC1E_HUMAN
ID KC1E_HUMAN Reviewed; 416 AA.
AC P49674;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 217.
DE RecName: Full=Casein kinase I isoform epsilon;
DE Short=CKI-epsilon;
DE Short=CKIe;
DE EC=2.7.11.1 {ECO:0000269|PubMed:29222110};
GN Name=CSNK1E;
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].
RC TISSUE=Placenta;
RX PubMed=7797465; DOI=10.1074/jbc.270.25.14875;
RA Fish K.J., Cegielska A., Getman M.E., Landes G.M., Virshup D.M.;
RT "Isolation and characterization of human casein kinase I epsilon (CKI), a
RT novel member of the CKI gene family.";
RL J. Biol. Chem. 270:14875-14883(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Ono K., Murata-Hori M., Hosoya H.;
RT "Casein kinase I epsilon from HeLa cell.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH SOCS3, INDUCTION, AND
RP FUNCTION.
RC TISSUE=Hematopoietic stem cell;
RX PubMed=15070676; DOI=10.1182/blood-2003-08-2768;
RA Okamura A., Iwata N., Nagata A., Tamekane A., Shimoyama M., Gomyo H.,
RA Yakushijin K., Urahama N., Hamaguchi M., Fukui C., Chihara K., Ito M.,
RA Matsui T.;
RT "Involvement of casein kinase Iepsilon in cytokine-induced granulocytic
RT differentiation.";
RL Blood 103:2997-3004(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [7]
RP INTERACTION WITH PER1.
RX PubMed=10790862; DOI=10.1097/00001756-200004070-00011;
RA Keesler G.A., Camacho F., Guo Y., Virshup D., Mondadori C., Yao Z.;
RT "Phosphorylation and destabilization of human period I clock protein by
RT human casein kinase I epsilon.";
RL NeuroReport 11:951-955(2000).
RN [8]
RP ROLE IN WNT SIGNALING.
RX PubMed=12556519; DOI=10.1074/jbc.m213265200;
RA Hino S., Michiue T., Asashima M., Kikuchi A.;
RT "Casein kinase I epsilon enhances the binding of Dvl-1 to Frat-1 and is
RT essential for Wnt-3a-induced accumulation of beta-catenin.";
RL J. Biol. Chem. 278:14066-14073(2003).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [10]
RP FUNCTION AS PER1 KINASE.
RX PubMed=15917222; DOI=10.1074/jbc.m502862200;
RA Shirogane T., Jin J., Ang X.L., Harper J.W.;
RT "SCFbeta-TRCP controls clock-dependent transcription via casein kinase 1-
RT dependent degradation of the mammalian period-1 (Per1) protein.";
RL J. Biol. Chem. 280:26863-26872(2005).
RN [11]
RP INTERACTION WITH DBNDD2.
RX PubMed=16618118; DOI=10.1021/bi052354e;
RA Yin H., Laguna K.A., Li G., Kuret J.;
RT "Dysbindin structural homologue CK1BP is an isoform-selective binding
RT partner of human casein kinase-1.";
RL Biochemistry 45:5297-5308(2006).
RN [12]
RP INTERACTION WITH LRP5 AND LRP6.
RX PubMed=16513652; DOI=10.1074/jbc.m510580200;
RA Swiatek W., Kang H., Garcia B.A., Shabanowitz J., Coombs G.S., Hunt D.F.,
RA Virshup D.M.;
RT "Negative regulation of LRP6 function by casein kinase I epsilon
RT phosphorylation.";
RL J. Biol. Chem. 281:12233-12241(2006).
RN [13]
RP FUNCTION, AUTOPHOSPHORYLATION, DEPHOSPHORYLATION BY PPP5C, AND ACTIVITY
RP REGULATION.
RX PubMed=16790549; DOI=10.1073/pnas.0604138103;
RA Partch C.L., Shields K.F., Thompson C.L., Selby C.P., Sancar A.;
RT "Posttranslational regulation of the mammalian circadian clock by
RT cryptochrome and protein phosphatase 5.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:10467-10472(2006).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-343; SER-354; THR-362 AND
RP SER-363, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-363, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-343 AND SER-354, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-389, 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 [19]
RP INTERACTION WITH SNAI1.
RX PubMed=20305697; DOI=10.1038/onc.2010.77;
RA Xu Y., Lee S.H., Kim H.S., Kim N.H., Piao S., Park S.H., Jung Y.S.,
RA Yook J.I., Park B.J., Ha N.C.;
RT "Role of CK1 in GSK3beta-mediated phosphorylation and degradation of
RT snail.";
RL Oncogene 29:3124-3133(2010).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-363, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-389; SER-405 AND SER-408, 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 [23]
RP FUNCTION, AND INTERACTION WITH DDX3X.
RX PubMed=23413191; DOI=10.1126/science.1231499;
RA Cruciat C.M., Dolde C., de Groot R.E., Ohkawara B., Reinhard C.,
RA Korswagen H.C., Niehrs C.;
RT "RNA helicase DDX3 is a regulatory subunit of casein kinase 1 in Wnt-beta-
RT catenin signaling.";
RL Science 339:1436-1441(2013).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [25]
RP INTERACTION WITH DDX3X, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-38.
RX PubMed=29222110; DOI=10.1242/jcs.207316;
RA Dolde C., Bischof J., Grueter S., Montada A., Halekotte J., Peifer C.,
RA Kalbacher H., Baumann U., Knippschild U., Suter B.;
RT "A CK1 FRET biosensor reveals that DDX3X is an essential activator of
RT CK1epsilon.";
RL J. Cell Sci. 131:0-0(2018).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.74 ANGSTROMS) OF 1-294 ALONE AND IN COMPLEX WITH
RP INHIBITOR, AND SUBUNIT.
RX PubMed=23106386; DOI=10.1021/jm301336n;
RA Long A.M., Zhao H., Huang X.;
RT "Structural basis for the potent and selective inhibition of casein kinase
RT 1 epsilon.";
RL J. Med. Chem. 55:10307-10311(2012).
RN [27]
RP VARIANTS [LARGE SCALE ANALYSIS] LEU-256 AND ARG-413.
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: Casein kinases are operationally defined by their
CC preferential utilization of acidic proteins such as caseins as
CC substrates. Can phosphorylate a large number of proteins. Participates
CC in Wnt signaling. Phosphorylates DVL1 and DVL2. Central component of
CC the circadian clock. In balance with PP1, determines the circadian
CC period length, through the regulation of the speed and rhythmicity of
CC PER1 and PER2 phosphorylation. Controls PER1 and PER2 nuclear transport
CC and degradation. Inhibits cytokine-induced granuloytic differentiation.
CC {ECO:0000269|PubMed:12556519, ECO:0000269|PubMed:15070676,
CC ECO:0000269|PubMed:15917222, ECO:0000269|PubMed:16790549,
CC ECO:0000269|PubMed:23413191}.
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; Evidence={ECO:0000269|PubMed:29222110};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609;
CC Evidence={ECO:0000269|PubMed:29222110};
CC -!- ACTIVITY REGULATION: Phosphorylation leads to a decrease of the
CC catalytic activity. {ECO:0000269|PubMed:16790549}.
CC -!- SUBUNIT: Monomer (PubMed:23106386). Component of the circadian core
CC oscillator, which includes the CRY proteins, CLOCK, or NPAS2,
CC ARTNL/BMAL1 or ARTNL2/BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER
CC proteins (By similarity). Interacts with PER1 (PubMed:10790862).
CC Interacts with ANKRD6 (By similarity). Interacts with DBNDD2
CC (PubMed:16618118). Interacts with LRP5 and LRP6 (PubMed:16513652).
CC Interacts with SOCS3 (PubMed:15070676). Interacts with SNAI1 (via zinc
CC fingers) (PubMed:20305697). Interacts with DDX3X; this interaction
CC greatly enhances CSNK1E affinity for ATP and DVL2 phosphorylation, but
CC inhibits DDX3X ATPase/helicase activity. In the presence of RNA, the
CC interaction is decreased (PubMed:23413191, PubMed:29222110).
CC {ECO:0000250|UniProtKB:Q9JMK2, ECO:0000269|PubMed:10790862,
CC ECO:0000269|PubMed:15070676, ECO:0000269|PubMed:16513652,
CC ECO:0000269|PubMed:16618118, ECO:0000269|PubMed:20305697,
CC ECO:0000269|PubMed:23106386, ECO:0000269|PubMed:23413191,
CC ECO:0000269|PubMed:29222110}.
CC -!- INTERACTION:
CC P49674; P25054: APC; NbExp=8; IntAct=EBI-749343, EBI-727707;
CC P49674; O15169: AXIN1; NbExp=5; IntAct=EBI-749343, EBI-710484;
CC P49674; O14640: DVL1; NbExp=6; IntAct=EBI-749343, EBI-723489;
CC P49674; O14641: DVL2; NbExp=4; IntAct=EBI-749343, EBI-740850;
CC P49674; Q92997: DVL3; NbExp=9; IntAct=EBI-749343, EBI-739789;
CC P49674; Q9BQ89: FAM110A; NbExp=3; IntAct=EBI-749343, EBI-1752811;
CC P49674; Q1W6H9: FAM110C; NbExp=3; IntAct=EBI-749343, EBI-3942563;
CC P49674; Q86UY5: FAM83A; NbExp=4; IntAct=EBI-749343, EBI-1384254;
CC P49674; P08238: HSP90AB1; NbExp=2; IntAct=EBI-749343, EBI-352572;
CC P49674; P23508: MCC; NbExp=4; IntAct=EBI-749343, EBI-307531;
CC P49674; Q00987: MDM2; NbExp=3; IntAct=EBI-749343, EBI-389668;
CC P49674; Q16625: OCLN; NbExp=8; IntAct=EBI-749343, EBI-2903088;
CC P49674; O15055: PER2; NbExp=6; IntAct=EBI-749343, EBI-1054296;
CC P49674; O75382: TRIM3; NbExp=3; IntAct=EBI-749343, EBI-2129889;
CC P49674; Q5T7W0: ZNF618; NbExp=5; IntAct=EBI-749343, EBI-6255994;
CC P49674; O70239: Axin1; Xeno; NbExp=7; IntAct=EBI-749343, EBI-6857773;
CC P49674; Q60838: Dvl2; Xeno; NbExp=3; IntAct=EBI-749343, EBI-641940;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in all tissues examined, including brain,
CC heart, lung, liver, pancreas, kidney, placenta and skeletal muscle.
CC Expressed in monocytes and lymphocytes but not in granulocytes.
CC -!- INDUCTION: Down-regulated during granulocytic differentiation.
CC {ECO:0000269|PubMed:15070676}.
CC -!- PTM: Autophosphorylated. Partially dephosphorylated by PPP5C. May be
CC dephosphorylated by PP1.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CK1 Ser/Thr
CC protein kinase family. Casein kinase I subfamily. {ECO:0000305}.
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DR EMBL; L37043; AAC41761.1; -; mRNA.
DR EMBL; AB024597; BAA92345.1; -; mRNA.
DR EMBL; AB091043; BAC10902.1; -; mRNA.
DR EMBL; CR456429; CAG30315.1; -; mRNA.
DR EMBL; AL020993; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC006490; AAH06490.1; -; mRNA.
DR CCDS; CCDS13970.1; -.
DR PIR; I61744; I61744.
DR RefSeq; NP_001276841.1; NM_001289912.1.
DR RefSeq; NP_001885.1; NM_001894.4.
DR RefSeq; NP_689407.1; NM_152221.2.
DR PDB; 4HNI; X-ray; 2.74 A; A/B=1-294.
DR PDB; 4HOK; X-ray; 2.77 A; A/C/E/G/I/K/M/O/Q/S/U/W=1-294.
DR PDBsum; 4HNI; -.
DR PDBsum; 4HOK; -.
DR AlphaFoldDB; P49674; -.
DR SMR; P49674; -.
DR BioGRID; 107838; 280.
DR BioGRID; 3196631; 5.
DR DIP; DIP-38050N; -.
DR IntAct; P49674; 155.
DR MINT; P49674; -.
DR STRING; 9606.ENSP00000380044; -.
DR BindingDB; P49674; -.
DR ChEMBL; CHEMBL4937; -.
DR DrugBank; DB06195; Seliciclib.
DR DrugBank; DB14989; Umbralisib.
DR DrugCentral; P49674; -.
DR GuidetoPHARMACOLOGY; 1998; -.
DR iPTMnet; P49674; -.
DR PhosphoSitePlus; P49674; -.
DR BioMuta; CSNK1E; -.
DR DMDM; 1346369; -.
DR EPD; P49674; -.
DR jPOST; P49674; -.
DR MassIVE; P49674; -.
DR PaxDb; P49674; -.
DR PeptideAtlas; P49674; -.
DR PRIDE; P49674; -.
DR ProteomicsDB; 56045; -.
DR Antibodypedia; 4043; 504 antibodies from 38 providers.
DR DNASU; 1454; -.
DR Ensembl; ENST00000359867.7; ENSP00000352929.3; ENSG00000213923.13.
DR Ensembl; ENST00000396832.6; ENSP00000380044.1; ENSG00000213923.13.
DR Ensembl; ENST00000403904.5; ENSP00000384074.1; ENSG00000213923.13.
DR GeneID; 102800317; -.
DR GeneID; 1454; -.
DR KEGG; hsa:102800317; -.
DR KEGG; hsa:1454; -.
DR MANE-Select; ENST00000396832.6; ENSP00000380044.1; NM_152221.3; NP_689407.1.
DR CTD; 102800317; -.
DR CTD; 1454; -.
DR DisGeNET; 102800317; -.
DR DisGeNET; 1454; -.
DR GeneCards; CSNK1E; -.
DR HGNC; HGNC:2453; CSNK1E.
DR HPA; ENSG00000213923; Low tissue specificity.
DR MalaCards; CSNK1E; -.
DR MIM; 600863; gene.
DR neXtProt; NX_P49674; -.
DR OpenTargets; ENSG00000213923; -.
DR PharmGKB; PA26953; -.
DR VEuPathDB; HostDB:ENSG00000213923; -.
DR eggNOG; KOG1164; Eukaryota.
DR GeneTree; ENSGT00940000153536; -.
DR HOGENOM; CLU_019279_2_2_1; -.
DR InParanoid; P49674; -.
DR OMA; TMHKISG; -.
DR OrthoDB; 1097975at2759; -.
DR PhylomeDB; P49674; -.
DR TreeFam; TF300544; -.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; P49674; -.
DR Reactome; R-HSA-201688; WNT mediated activation of DVL.
DR Reactome; R-HSA-2565942; Regulation of PLK1 Activity at G2/M Transition.
DR Reactome; R-HSA-380259; Loss of Nlp from mitotic centrosomes.
DR Reactome; R-HSA-380270; Recruitment of mitotic centrosome proteins and complexes.
DR Reactome; R-HSA-380284; Loss of proteins required for interphase microtubule organization from the centrosome.
DR Reactome; R-HSA-380320; Recruitment of NuMA to mitotic centrosomes.
DR Reactome; R-HSA-400253; Circadian Clock.
DR Reactome; R-HSA-5620912; Anchoring of the basal body to the plasma membrane.
DR Reactome; R-HSA-6791226; Major pathway of rRNA processing in the nucleolus and cytosol.
DR Reactome; R-HSA-8854518; AURKA Activation by TPX2.
DR SABIO-RK; P49674; -.
DR SignaLink; P49674; -.
DR SIGNOR; P49674; -.
DR BioGRID-ORCS; 102800317; 1 hit in 78 CRISPR screens.
DR BioGRID-ORCS; 1454; 10 hits in 1107 CRISPR screens.
DR ChiTaRS; CSNK1E; human.
DR GeneWiki; CSNK1E; -.
DR Pharos; P49674; Tclin.
DR PRO; PR:P49674; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; P49674; protein.
DR Bgee; ENSG00000213923; Expressed in cortical plate and 197 other tissues.
DR ExpressionAtlas; P49674; baseline and differential.
DR Genevisible; P49674; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030426; C:growth cone; IEA:Ensembl.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:1990904; C:ribonucleoprotein complex; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IDA:WormBase.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:WormBase.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IEA:Ensembl.
DR GO; GO:0048512; P:circadian behavior; IEA:Ensembl.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; TAS:ProtInc.
DR GO; GO:0006897; P:endocytosis; IBA:GO_Central.
DR GO; GO:0032091; P:negative regulation of protein binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:ParkinsonsUK-UCL.
DR GO; GO:1902004; P:positive regulation of amyloid-beta formation; IEA:Ensembl.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IBA:GO_Central.
DR GO; GO:2000052; P:positive regulation of non-canonical Wnt signaling pathway; IC:ParkinsonsUK-UCL.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:1905426; P:positive regulation of Wnt-mediated midbrain dopaminergic neuron differentiation; NAS:ParkinsonsUK-UCL.
DR GO; GO:0008104; P:protein localization; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0032880; P:regulation of protein localization; IDA:ParkinsonsUK-UCL.
DR GO; GO:0007165; P:signal transduction; 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 3D-structure; ATP-binding; Biological rhythms; Cytoplasm; Kinase;
KW Methylation; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..416
FT /note="Casein kinase I isoform epsilon"
FT /id="PRO_0000192837"
FT DOMAIN 9..277
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 301..416
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 301..320
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 387..407
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 128
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 15..23
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 38
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 343
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 354
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 362
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 363
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:21406692"
FT MOD_RES 382
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q9JMK2"
FT MOD_RES 389
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 405
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 408
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 256
FT /note="R -> L (in a lung adenocarcinoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042082"
FT VARIANT 413
FT /note="H -> R (in dbSNP:rs35665927)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042083"
FT MUTAGEN 38
FT /note="K->R: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:29222110"
FT TURN 6..8
FT /evidence="ECO:0007829|PDB:4HNI"
FT STRAND 14..16
FT /evidence="ECO:0007829|PDB:4HNI"
FT STRAND 22..28
FT /evidence="ECO:0007829|PDB:4HNI"
FT TURN 29..31
FT /evidence="ECO:0007829|PDB:4HNI"
FT STRAND 35..41
FT /evidence="ECO:0007829|PDB:4HNI"
FT HELIX 51..56
FT /evidence="ECO:0007829|PDB:4HNI"
FT TURN 57..61
FT /evidence="ECO:0007829|PDB:4HNI"
FT STRAND 68..74
FT /evidence="ECO:0007829|PDB:4HNI"
FT STRAND 77..83
FT /evidence="ECO:0007829|PDB:4HNI"
FT HELIX 89..95
FT /evidence="ECO:0007829|PDB:4HNI"
FT TURN 96..98
FT /evidence="ECO:0007829|PDB:4HNI"
FT HELIX 102..120
FT /evidence="ECO:0007829|PDB:4HNI"
FT TURN 121..123
FT /evidence="ECO:0007829|PDB:4HNI"
FT HELIX 131..133
FT /evidence="ECO:0007829|PDB:4HNI"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:4HNI"
FT HELIX 139..141
FT /evidence="ECO:0007829|PDB:4HNI"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:4HNI"
FT STRAND 154..157
FT /evidence="ECO:0007829|PDB:4HNI"
FT TURN 159..161
FT /evidence="ECO:0007829|PDB:4HNI"
FT HELIX 177..179
FT /evidence="ECO:0007829|PDB:4HNI"
FT HELIX 182..185
FT /evidence="ECO:0007829|PDB:4HNI"
FT HELIX 192..208
FT /evidence="ECO:0007829|PDB:4HNI"
FT TURN 212..215
FT /evidence="ECO:0007829|PDB:4HOK"
FT HELIX 221..234
FT /evidence="ECO:0007829|PDB:4HNI"
FT HELIX 237..240
FT /evidence="ECO:0007829|PDB:4HNI"
FT TURN 241..243
FT /evidence="ECO:0007829|PDB:4HNI"
FT HELIX 246..255
FT /evidence="ECO:0007829|PDB:4HNI"
FT HELIX 266..280
FT /evidence="ECO:0007829|PDB:4HNI"
FT HELIX 289..291
FT /evidence="ECO:0007829|PDB:4HNI"
SQ SEQUENCE 416 AA; 47315 MW; EE1B1698AE914324 CRC64;
MELRVGNKYR LGRKIGSGSF GDIYLGANIA SGEEVAIKLE CVKTKHPQLH IESKFYKMMQ
GGVGIPSIKW CGAEGDYNVM VMELLGPSLE DLFNFCSRKF SLKTVLLLAD QMISRIEYIH
SKNFIHRDVK PDNFLMGLGK KGNLVYIIDF GLAKKYRDAR THQHIPYREN KNLTGTARYA
SINTHLGIEQ SRRDDLESLG YVLMYFNLGS LPWQGLKAAT KRQKYERISE KKMSTPIEVL
CKGYPSEFST YLNFCRSLRF DDKPDYSYLR QLFRNLFHRQ GFSYDYVFDW NMLKFGAARN
PEDVDRERRE HEREERMGQL RGSATRALPP GPPTGATANR LRSAAEPVAS TPASRIQPAG
NTSPRAISRV DRERKVSMRL HRGAPANVSS SDLTGRQEVS RIPASQTSVP FDHLGK
