KC1A_DROME
ID KC1A_DROME Reviewed; 337 AA.
AC P54367; A4V4D3; Q0KHT2; Q9VYK2;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=Casein kinase I isoform alpha;
DE Short=CKI-alpha;
DE Short=DmCK1;
DE EC=2.7.11.1;
GN Name=CkIalpha; Synonyms=CKI; ORFNames=CG2028;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Canton-S; TISSUE=Embryo;
RA Glover C.V.C., Kandala G.;
RL Submitted (APR-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ACTIVITY REGULATION, COFACTOR,
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND PHOSPHORYLATION.
RC STRAIN=Canton-S; TISSUE=Embryo;
RX PubMed=8832407; DOI=10.1242/jcs.109.7.1847;
RA Santos J.A., Logarinho E., Tapia C., Allende C.C., Allende J.E.,
RA Sunkel C.E.;
RT "The casein kinase 1 alpha gene of Drosophila melanogaster is
RT developmentally regulated and the kinase activity of the protein induced by
RT DNA damage.";
RL J. Cell Sci. 109:1847-1856(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [6]
RP FUNCTION.
RX PubMed=11955436; DOI=10.1016/s0092-8674(02)00685-2;
RA Liu C., Li Y., Semenov M., Han C., Baeg G.-H., Tan Y., Zhang Z., Lin X.,
RA He X.;
RT "Control of beta-catenin phosphorylation/degradation by a dual-kinase
RT mechanism.";
RL Cell 108:837-847(2002).
RN [7]
RP FUNCTION.
RX PubMed=11927557; DOI=10.1093/emboj/21.7.1733;
RA Yanagawa S., Matsuda Y., Lee J.S., Matsubayashi H., Sese S., Kadowaki T.,
RA Ishimoto A.;
RT "Casein kinase I phosphorylates the Armadillo protein and induces its
RT degradation in Drosophila.";
RL EMBO J. 21:1733-1742(2002).
RN [8]
RP FUNCTION.
RX PubMed=15616566; DOI=10.1038/nature03179;
RA Jia J., Tong C., Wang B., Luo L., Jiang J.;
RT "Hedgehog signalling activity of Smoothened requires phosphorylation by
RT protein kinase A and casein kinase I.";
RL Nature 432:1045-1050(2004).
RN [9]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH COS.
RX PubMed=15691767; DOI=10.1016/j.devcel.2005.01.001;
RA Zhang W., Zhao Y., Tong C., Wang G., Wang B., Jia J., Jiang J.;
RT "Hedgehog-regulated Costal2-kinase complexes control phosphorylation and
RT proteolytic processing of Cubitus interruptus.";
RL Dev. Cell 8:267-278(2005).
RN [10]
RP FUNCTION.
RX PubMed=16326393; DOI=10.1016/j.devcel.2005.10.006;
RA Jia J., Zhang L., Zhang Q., Tong C., Wang B., Hou F., Amanai K., Jiang J.;
RT "Phosphorylation by double-time/CKIepsilon and CKIalpha targets cubitus
RT interruptus for Slimb/beta-TRCP-mediated proteolytic processing.";
RL Dev. Cell 9:819-830(2005).
RN [11]
RP FUNCTION, AND MUTAGENESIS OF GLY-43.
RX PubMed=22095083; DOI=10.1534/genetics.111.133827;
RA Legent K., Steinhauer J., Richard M., Treisman J.E.;
RT "A screen for X-linked mutations affecting Drosophila photoreceptor
RT differentiation identifies Casein kinase 1alpha as an essential negative
RT regulator of wingless signaling.";
RL Genetics 190:601-616(2012).
RN [12]
RP FUNCTION.
RX PubMed=25723539; DOI=10.1371/journal.pgen.1005014;
RA Nguyen H.Q., Nye J., Buster D.W., Klebba J.E., Rogers G.C., Bosco G.;
RT "Drosophila casein kinase I alpha regulates homolog pairing and genome
RT organization by modulating condensin II subunit Cap-H2 levels.";
RL PLoS Genet. 11:E1005014-E1005014(2015).
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. Negative
CC regulator of wg signaling (PubMed:22095083). Phosphorylates arm
CC directly or indirectly and stimulates its degradation which prevents
CC inappropriate wg signaling (PubMed:11955436, PubMed:11927557,
CC PubMed:22095083). Phosphorylates smo which promotes its accumulation at
CC the cell surface and its signaling activity in response to hh
CC (PubMed:15616566). Together with dco, regulates proteolytic processing
CC of ci by phosphorylating it which promotes its binding to slmb, the F-
CC box recognition component of the SCF(slmb) E3 ubiquitin-protein ligase
CC required for ci processing (PubMed:16326393). Inhibits condensin II
CC interphase activity by promoting degradation of the Cap-H2 regulatory
CC subunit and limiting the levels of chromatin-bound Cap-H2 which
CC regulates interphase chromosome organization (PubMed:25723539).
CC {ECO:0000269|PubMed:11927557, ECO:0000269|PubMed:11955436,
CC ECO:0000269|PubMed:15616566, ECO:0000269|PubMed:16326393,
CC ECO:0000269|PubMed:22095083, ECO:0000269|PubMed:25723539,
CC ECO:0000269|PubMed:8832407}.
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 -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:8832407};
CC -!- ACTIVITY REGULATION: Activity increases following DNA damage.
CC {ECO:0000269|PubMed:8832407}.
CC -!- SUBUNIT: Interacts with cos. {ECO:0000269|PubMed:15691767}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15691767,
CC ECO:0000269|PubMed:8832407}. Nucleus {ECO:0000269|PubMed:15691767,
CC ECO:0000269|PubMed:8832407}. Note=Levels in the nucleus are
CC significantly increased after DNA damage. {ECO:0000269|PubMed:8832407}.
CC -!- DEVELOPMENTAL STAGE: Expressed during early embryogenesis and in adult
CC females (at protein level). {ECO:0000269|PubMed:8832407}.
CC -!- PTM: Phosphorylated. The dephosphorylated kinase is active in the
CC cytoplasm while the active kinase in the nucleus is phosphorylated.
CC {ECO:0000269|PubMed:8832407}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CK1 Ser/Thr
CC protein kinase family. Casein kinase I subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA64358.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U55848; AAB16904.1; -; mRNA.
DR EMBL; X94695; CAA64358.1; ALT_INIT; mRNA.
DR EMBL; AE014298; AAF48192.1; -; Genomic_DNA.
DR EMBL; AE014298; AAN09313.1; -; Genomic_DNA.
DR EMBL; AY069346; AAL39491.1; -; mRNA.
DR RefSeq; NP_001162737.1; NM_001169266.3.
DR RefSeq; NP_001285163.1; NM_001298234.1.
DR RefSeq; NP_001285164.1; NM_001298235.1.
DR RefSeq; NP_511140.1; NM_078585.6.
DR RefSeq; NP_727631.1; NM_167331.4.
DR RefSeq; NP_727632.1; NM_167332.3.
DR AlphaFoldDB; P54367; -.
DR SMR; P54367; -.
DR BioGRID; 58615; 12.
DR DIP; DIP-22041N; -.
DR IntAct; P54367; 2.
DR STRING; 7227.FBpp0073513; -.
DR PaxDb; P54367; -.
DR PRIDE; P54367; -.
DR EnsemblMetazoa; FBtr0073680; FBpp0073513; FBgn0015024.
DR EnsemblMetazoa; FBtr0073682; FBpp0073515; FBgn0015024.
DR EnsemblMetazoa; FBtr0300380; FBpp0289609; FBgn0015024.
DR EnsemblMetazoa; FBtr0340408; FBpp0309354; FBgn0015024.
DR EnsemblMetazoa; FBtr0345162; FBpp0311372; FBgn0015024.
DR EnsemblMetazoa; FBtr0345163; FBpp0311373; FBgn0015024.
DR GeneID; 32221; -.
DR KEGG; dme:Dmel_CG2028; -.
DR UCSC; CG2028-RC; d. melanogaster.
DR CTD; 32221; -.
DR FlyBase; FBgn0015024; CkIalpha.
DR VEuPathDB; VectorBase:FBgn0015024; -.
DR eggNOG; KOG1163; Eukaryota.
DR GeneTree; ENSGT00940000153700; -.
DR HOGENOM; CLU_019279_2_7_1; -.
DR InParanoid; P54367; -.
DR OMA; PAEFPMY; -.
DR OrthoDB; 1097975at2759; -.
DR PhylomeDB; P54367; -.
DR BRENDA; 2.7.11.1; 1994.
DR Reactome; R-DME-195253; Degradation of beta-catenin by the destruction complex.
DR Reactome; R-DME-196299; Beta-catenin phosphorylation cascade.
DR Reactome; R-DME-209155; Phosphorylation of AXN and APC.
DR Reactome; R-DME-209159; Assembly of the CI containing complexes.
DR Reactome; R-DME-209190; Phosphorylation of CI.
DR Reactome; R-DME-209214; Phosphorylation of SMO.
DR Reactome; R-DME-209360; Ubiquitination and proteolysis of phosphorylated CI.
DR Reactome; R-DME-209396; Phosphorylation of ARM.
DR Reactome; R-DME-209413; Assembly of the 'destruction complex'.
DR Reactome; R-DME-209440; Recruitment of the 'destruction complex' to the receptor complex, the degradation of AXN and release of ARM.
DR Reactome; R-DME-209461; Ubiquitination and degradation of phosphorylated ARM.
DR Reactome; R-DME-432553; Phosphorylation of PER and TIM.
DR Reactome; R-DME-5610785; GLI3 is processed to GLI3R by the proteasome.
DR Reactome; R-DME-5635838; Activation of SMO.
DR SignaLink; P54367; -.
DR BioGRID-ORCS; 32221; 1 hit in 3 CRISPR screens.
DR GenomeRNAi; 32221; -.
DR PRO; PR:P54367; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0015024; Expressed in wing disc and 26 other tissues.
DR ExpressionAtlas; P54367; baseline and differential.
DR Genevisible; P54367; DM.
DR GO; GO:0030877; C:beta-catenin destruction complex; ISS:ParkinsonsUK-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
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; IDA:FlyBase.
DR GO; GO:0000902; P:cell morphogenesis; IMP:FlyBase.
DR GO; GO:0006281; P:DNA repair; IDA:FlyBase.
DR GO; GO:0042593; P:glucose homeostasis; IMP:FlyBase.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:FlyBase.
DR GO; GO:0035331; P:negative regulation of hippo signaling; IMP:FlyBase.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; IMP:FlyBase.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:1901800; P:positive regulation of proteasomal protein catabolic process; IMP:FlyBase.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:FlyBase.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IMP:FlyBase.
DR GO; GO:0006468; P:protein phosphorylation; IDA:FlyBase.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
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; Magnesium; Nucleotide-binding; Nucleus;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Wnt signaling pathway.
FT CHAIN 1..337
FT /note="Casein kinase I isoform alpha"
FT /id="PRO_0000192848"
FT DOMAIN 20..288
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 139
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 26..34
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 49
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MUTAGEN 43
FT /note="G->D: In 8B12; death primarily during embryogenesis
FT and early larval stages with no obvious cuticle patterning
FT defects."
FT /evidence="ECO:0000269|PubMed:22095083"
FT CONFLICT 331..337
FT /note="GKPLIAD -> ASP (in Ref. 2; CAA64358)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 337 AA; 39535 MW; 495144945093E69D CRC64;
MDKMRILKES RPEIIVGGKY RVIRKIGSGS FGDIYLGMSI QSGEEVAIKM ESAHARHPQL
LYEAKLYRIL SGGVGFPRIR HHGKEKNFNT LVMDLLGPSL EDLFNFCTRH FTIKTVLMLV
DQMIGRLEYI HLKCFIHRDI KPDNFLMGIG RHCNKLFLID FGLAKKFRDP HTRHHIVYRE
DKNLTGTARY ASINAHLGIE QSRRDDMESL GYVMMYFNRG VLPWQGMKAN TKQQKYEKIS
EKKMSTPIEV LCKGSPAEFS MYLNYCRSLR FEEQPDYMYL RQLFRILFRT LNHQYDYIYD
WTMLKQKTHQ GQPNPAILLE QLDKDKEKQN GKPLIAD
