KC1E_MOUSE
ID KC1E_MOUSE Reviewed; 416 AA.
AC Q9JMK2; Q8R389;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 2.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Casein kinase I isoform epsilon;
DE Short=CKI-epsilon;
DE Short=CKIe;
DE EC=2.7.11.1 {ECO:0000269|PubMed:19414593};
GN Name=Csnk1e;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10640823; DOI=10.1159/000015403;
RA Kusuda J., Hirai M., Tanuma R., Hashimoto K.;
RT "cDNA cloning and chromosome mapping of the mouse casein kinase I epsilon
RT gene (Csnk1e).";
RL Cytogenet. Cell Genet. 87:99-101(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 FUNCTION AS PER1 KINASE, AND MUTAGENESIS OF LYS-38.
RX PubMed=10848614; DOI=10.1128/mcb.20.13.4888-4899.2000;
RA Vielhaber E., Eide E., Rivers A., Gao Z.-H., Virshup D.M.;
RT "Nuclear entry of the circadian regulator mPER1 is controlled by mammalian
RT casein kinase I epsilon.";
RL Mol. Cell. Biol. 20:4888-4899(2000).
RN [4]
RP IDENTIFICATION IN A COMPLEX WITH CLOCK; PER1; PER2; CRY1; CRY2; CSNK1D AND
RP CSNK1E.
RX PubMed=11779462; DOI=10.1016/s0092-8674(01)00610-9;
RA Lee C., Etchegaray J.-P., Cagampang F.R.A., Loudon A.S.I., Reppert S.M.;
RT "Posttranslational mechanisms regulate the mammalian circadian clock.";
RL Cell 107:855-867(2001).
RN [5]
RP INTERACTION WITH ANKRD6.
RX PubMed=12183362; DOI=10.1101/gad.230402;
RA Schwarz-Romond T., Asbrand C., Bakkers J., Kuehl M., Schaeffer H.J.,
RA Huelsken J., Behrens J., Hammerschmidt M., Birchmeier W.;
RT "The ankyrin repeat protein diversin recruits casein kinase Iepsilon to the
RT beta-catenin degradation complex and acts in both canonical Wnt and Wnt/JNK
RT signaling.";
RL Genes Dev. 16:2073-2084(2002).
RN [6]
RP FUNCTION AS PER PROTEINS KINASE.
RX PubMed=14701732; DOI=10.1128/mcb.24.2.584-594.2004;
RA Lee C., Weaver D.R., Reppert S.M.;
RT "Direct association between mouse PERIOD and CKIepsilon is critical for a
RT functioning circadian clock.";
RL Mol. Cell. Biol. 24:584-594(2004).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [8]
RP TISSUE SPECIFICITY, AND INDUCTION.
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 [9]
RP DISRUPTION PHENOTYPE, FUNCTION, AND MUTAGENESIS OF ARG-178.
RX PubMed=18400165; DOI=10.1016/j.neuron.2008.01.019;
RA Meng Q.J., Logunova L., Maywood E.S., Gallego M., Lebiecki J., Brown T.M.,
RA Sladek M., Semikhodskii A.S., Glossop N.R., Piggins H.D., Chesham J.E.,
RA Bechtold D.A., Yoo S.H., Takahashi J.S., Virshup D.M., Boot-Handford R.P.,
RA Hastings M.H., Loudon A.S.;
RT "Setting clock speed in mammals: the CK1 epsilon tau mutation in mice
RT accelerates circadian pacemakers by selectively destabilizing PERIOD
RT proteins.";
RL Neuron 58:78-88(2008).
RN [10]
RP FUNCTION IN CIRCADIAN CLOCK, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, AND
RP SUBCELLULAR LOCATION.
RX PubMed=19414593; DOI=10.1128/mcb.00338-09;
RA Etchegaray J.P., Machida K.K., Noton E., Constance C.M., Dallmann R.,
RA Di Napoli M.N., DeBruyne J.P., Lambert C.M., Yu E.A., Reppert S.M.,
RA Weaver D.R.;
RT "Casein kinase 1 delta regulates the pace of the mammalian circadian
RT clock.";
RL Mol. Cell. Biol. 29:3853-3866(2009).
RN [11]
RP FUNCTION IN CIRCADIAN CLOCK, AND DEPHOSPHORYLATION.
RX PubMed=21930935; DOI=10.1073/pnas.1107178108;
RA Lee H.M., Chen R., Kim H., Etchegaray J.P., Weaver D.R., Lee C.;
RT "The period of the circadian oscillator is primarily determined by the
RT balance between casein kinase 1 and protein phosphatase 1.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:16451-16456(2011).
RN [12]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-382, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
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. Central component of the
CC circadian clock. In balance with PP1, determines the circadian period
CC length, through the regulation of the speed and rhythmicity of PER1 and
CC PER2 phosphorylation. Controls PER1 and PER2 nuclear transport and
CC degradation. Inhibits cytokine-induced granuloytic differentiation.
CC {ECO:0000269|PubMed:10848614, ECO:0000269|PubMed:14701732,
CC ECO:0000269|PubMed:18400165, ECO:0000269|PubMed:19414593,
CC ECO:0000269|PubMed:21930935}.
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 Evidence={ECO:0000269|PubMed:19414593};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC Evidence={ECO:0000269|PubMed:19414593};
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:19414593};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609;
CC Evidence={ECO:0000269|PubMed:19414593};
CC -!- ACTIVITY REGULATION: Phosphorylation leads to a decrease in the
CC catalytic activity. {ECO:0000250}.
CC -!- SUBUNIT: Monomer (By similarity). 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 (PubMed:11779462). Interacts with ANKRD6 (PubMed:12183362).
CC Interacts with PER1 (By similarity). Interacts with DBNDD2, LRP5, LRP6
CC and SOCS3 (By similarity). Interacts with SNAI1 (via zinc fingers) (By
CC similarity). Interacts with DDX3X; this interaction greatly enhances
CC CSNK1E affinity for ATP and DVL2 phosphorylation, but inhibits DDX3X
CC ATPase/helicase activity. In the presence of RNA, the interaction is
CC decreased (By similarity). {ECO:0000250|UniProtKB:P49674,
CC ECO:0000269|PubMed:11779462, ECO:0000269|PubMed:12183362}.
CC -!- INTERACTION:
CC Q9JMK2; O08785: Clock; NbExp=2; IntAct=EBI-771709, EBI-79859;
CC Q9JMK2; O35973: Per1; NbExp=2; IntAct=EBI-771709, EBI-1266764;
CC Q9JMK2; O54943: Per2; NbExp=4; IntAct=EBI-771709, EBI-1266779;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus
CC {ECO:0000269|PubMed:19414593}.
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 {ECO:0000269|PubMed:16790549}.
CC -!- INDUCTION: Down-regulated during granulocytic differentiation. Does not
CC show circadian oscillations. {ECO:0000269|PubMed:16790549}.
CC -!- PTM: Autophosphorylated. Partially dephosphorylated by PPP5C. May be
CC dephosphorylated by PP1.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Has no apparent effect on
CC circadian oscillation of protein levels. Mice exhibit a small but
CC significant increase in circadian period length.
CC {ECO:0000269|PubMed:18400165, ECO:0000269|PubMed:19414593}.
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; AB028736; BAA88107.2; -; mRNA.
DR EMBL; BC026127; AAH26127.1; -; mRNA.
DR CCDS; CCDS27640.1; -.
DR PIR; S47616; S47616.
DR RefSeq; NP_001276827.1; NM_001289898.1.
DR RefSeq; NP_038795.3; NM_013767.6.
DR RefSeq; XP_017172146.1; XM_017316657.1.
DR RefSeq; XP_017172147.1; XM_017316658.1.
DR RefSeq; XP_017172148.1; XM_017316659.1.
DR AlphaFoldDB; Q9JMK2; -.
DR SMR; Q9JMK2; -.
DR BioGRID; 205180; 51.
DR DIP; DIP-32410N; -.
DR IntAct; Q9JMK2; 57.
DR MINT; Q9JMK2; -.
DR STRING; 10090.ENSMUSP00000113975; -.
DR iPTMnet; Q9JMK2; -.
DR PhosphoSitePlus; Q9JMK2; -.
DR EPD; Q9JMK2; -.
DR jPOST; Q9JMK2; -.
DR MaxQB; Q9JMK2; -.
DR PaxDb; Q9JMK2; -.
DR PeptideAtlas; Q9JMK2; -.
DR PRIDE; Q9JMK2; -.
DR ProteomicsDB; 269448; -.
DR DNASU; 27373; -.
DR Ensembl; ENSMUST00000117786; ENSMUSP00000113341; ENSMUSG00000022433.
DR Ensembl; ENSMUST00000120859; ENSMUSP00000113975; ENSMUSG00000022433.
DR GeneID; 27373; -.
DR KEGG; mmu:27373; -.
DR UCSC; uc007wtl.2; mouse.
DR CTD; 1454; -.
DR MGI; MGI:1351660; Csnk1e.
DR VEuPathDB; HostDB:ENSMUSG00000022433; -.
DR eggNOG; KOG1164; Eukaryota.
DR GeneTree; ENSGT00940000153536; -.
DR HOGENOM; CLU_019279_2_2_1; -.
DR InParanoid; Q9JMK2; -.
DR OrthoDB; 1097975at2759; -.
DR PhylomeDB; Q9JMK2; -.
DR TreeFam; TF300544; -.
DR BRENDA; 2.7.11.1; 3474.
DR Reactome; R-MMU-201688; WNT mediated activation of DVL.
DR Reactome; R-MMU-2565942; Regulation of PLK1 Activity at G2/M Transition.
DR Reactome; R-MMU-380259; Loss of Nlp from mitotic centrosomes.
DR Reactome; R-MMU-380270; Recruitment of mitotic centrosome proteins and complexes.
DR Reactome; R-MMU-380284; Loss of proteins required for interphase microtubule organization from the centrosome.
DR Reactome; R-MMU-380320; Recruitment of NuMA to mitotic centrosomes.
DR Reactome; R-MMU-5620912; Anchoring of the basal body to the plasma membrane.
DR Reactome; R-MMU-6791226; Major pathway of rRNA processing in the nucleolus and cytosol.
DR Reactome; R-MMU-8854518; AURKA Activation by TPX2.
DR BioGRID-ORCS; 27373; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Csnk1e; mouse.
DR PRO; PR:Q9JMK2; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q9JMK2; protein.
DR Bgee; ENSMUSG00000022433; Expressed in embryonic brain and 275 other tissues.
DR ExpressionAtlas; Q9JMK2; baseline and differential.
DR Genevisible; Q9JMK2; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
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; IDA:UniProtKB.
DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl.
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; IMP:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; TAS:MGI.
DR GO; GO:0006897; P:endocytosis; IBA:GO_Central.
DR GO; GO:0032091; P:negative regulation of protein binding; IEA:Ensembl.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IGI:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
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; IGI:MGI.
DR GO; GO:2000052; P:positive regulation of non-canonical Wnt signaling pathway; IGI:ParkinsonsUK-UCL.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; IGI:ParkinsonsUK-UCL.
DR GO; GO:0008104; P:protein localization; IDA:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB.
DR GO; GO:0032880; P:regulation of protein localization; IMP: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 ATP-binding; Biological rhythms; Cytoplasm; Kinase; Methylation;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Wnt signaling pathway.
FT CHAIN 1..416
FT /note="Casein kinase I isoform epsilon"
FT /id="PRO_0000192838"
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 350..366
FT /note="Polar 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:0000250|UniProtKB:P49674"
FT MOD_RES 354
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49674"
FT MOD_RES 362
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P49674"
FT MOD_RES 363
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49674"
FT MOD_RES 382
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 389
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49674"
FT MOD_RES 405
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49674"
FT MOD_RES 408
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49674"
FT MUTAGEN 38
FT /note="K->A: Decreases PER1 phosphorylation."
FT /evidence="ECO:0000269|PubMed:10848614"
FT MUTAGEN 38
FT /note="K->R: Increases PER1 nuclear import."
FT /evidence="ECO:0000269|PubMed:10848614"
FT MUTAGEN 178
FT /note="R->C: Shortens circadian rhythm. Accelerates PER2
FT degradation."
FT /evidence="ECO:0000269|PubMed:18400165"
FT CONFLICT 28
FT /note="N -> D (in Ref. 1; BAA88107)"
FT /evidence="ECO:0000305"
FT CONFLICT 310
FT /note="E -> G (in Ref. 1; BAA88107)"
FT /evidence="ECO:0000305"
FT CONFLICT 379
FT /note="R -> G (in Ref. 1; BAA88107)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 416 AA; 47322 MW; 38CC5299BB9040D7 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 TPASRIQQTG
NTSPRAISRA DRERKVSMRL HRGAPANVSS SDLTGRQEVS RLAASQTSVP FDHLGK
