Full text data of CSNK1A1
CSNK1A1
[Confidence: high (present in two of the MS resources)]
Casein kinase I isoform alpha; CKI-alpha; 2.7.11.1 (CK1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Casein kinase I isoform alpha; CKI-alpha; 2.7.11.1 (CK1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00183400
IPI00183400 Casein kinase I, alpha isoform Casein kinase I, alpha isoform membrane n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a n/a 1 n/a 1 n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00183400 Casein kinase I, alpha isoform Casein kinase I, alpha isoform membrane n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a n/a 1 n/a 1 n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
Comments
Isoform P48729-2 was detected.
Isoform P48729-2 was detected.
UniProt
P48729
ID KC1A_HUMAN Reviewed; 337 AA.
AC P48729; D3DQG0; D3DQG1; Q4JJA0; Q5U046; Q5U047; Q6FGA2; Q96HD2;
read moreAC Q9UDK3;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-MAY-2003, sequence version 2.
DT 22-JAN-2014, entry version 145.
DE RecName: Full=Casein kinase I isoform alpha;
DE Short=CKI-alpha;
DE EC=2.7.11.1;
DE AltName: Full=CK1;
GN Name=CSNK1A1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=8050587; DOI=10.1016/0014-5793(94)00679-2;
RA Tapia C., Featherstone T., Gomez C., Taillon-Miller P., Allende C.C.,
RA Allende J.E.;
RT "Cloning and chromosomal localization of the gene coding for human
RT protein kinase CK1.";
RL FEBS Lett. 349:307-312(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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
RT (CKI), a novel member of the CKI gene family.";
RL J. Biol. Chem. 270:14875-14883(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Lin L., Nong W., Zhou G., Ke R., Shen C., Zhong G., Zheng Z.,
RA Liang M., Huang B., Li H., Yang S.;
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 65-83; 111-152 AND 179-204, FUNCTION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=1409656; DOI=10.1073/pnas.89.20.9454;
RA Brockman J.L., Gross S.D., Sussman M.R., Anderson R.A.;
RT "Cell cycle-dependent localization of casein kinase I to mitotic
RT spindles.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:9454-9458(1992).
RN [9]
RP ROLE IN WNT SIGNALING.
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.,
RA Lin X., He X.;
RT "Control of beta-catenin phosphorylation/degradation by a dual-kinase
RT mechanism.";
RL Cell 108:837-847(2002).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [11]
RP FUNCTION, INTERACTION WITH TUT1, AND SUBCELLULAR LOCATION.
RX PubMed=18305108; DOI=10.1074/jbc.M800656200;
RA Gonzales M.L., Mellman D.L., Anderson R.A.;
RT "CKIalpha is associated with and phosphorylates star-PAP and is also
RT required for expression of select star-PAP target messenger RNAs.";
RL J. Biol. Chem. 283:12665-12673(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-156 (ISOFORM 2), AND
RP MASS SPECTROMETRY.
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
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [13]
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.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
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 [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2 AND LYS-8, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [16]
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.,
RA Buerckstuemmer T., 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 [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [18]
RP VARIANT [LARGE SCALE ANALYSIS] HIS-297.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., 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. It can phosphorylate a large number of proteins.
CC Participates in Wnt signaling. Phosphorylates CTNNB1 at 'Ser-45'.
CC May play a role in segregating chromosomes during mitosis.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- SUBUNIT: Monomer. Interacts with the Axin complex. Interacts with
CC TUT1, leading to TUT1 phosphorylation.
CC -!- INTERACTION:
CC Q00987:MDM2; NbExp=3; IntAct=EBI-1383726, EBI-389668;
CC O15151:MDM4; NbExp=2; IntAct=EBI-1383726, EBI-398437;
CC Q13546:RIPK1; NbExp=5; IntAct=EBI-1383726, EBI-358507;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome. Chromosome, centromere,
CC kinetochore. Nucleus speckle. Note=Localizes to the centrosome in
CC interphase cells, and to kinetochore fibers during mitosis.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P48729-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P48729-2; Sequence=VSP_035455;
CC Note=Contains a phosphoserine at position 156;
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CK1 Ser/Thr
CC protein kinase family. Casein kinase I subfamily.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org//Genes/CSNK1A1ID40168ch5q32.html";
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DR EMBL; X80693; CAA56710.1; -; mRNA.
DR EMBL; L37042; AAC41760.1; -; mRNA.
DR EMBL; CR542206; CAG47002.1; -; mRNA.
DR EMBL; BT019829; AAV38632.1; -; mRNA.
DR EMBL; BT019830; AAV38633.1; -; mRNA.
DR EMBL; DQ082865; AAY84562.1; -; mRNA.
DR EMBL; CH471062; EAW61767.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW61769.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW61773.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW61776.1; -; Genomic_DNA.
DR EMBL; BC008717; AAH08717.1; -; mRNA.
DR PIR; A57011; A57011.
DR PIR; S46254; S46254.
DR RefSeq; NP_001020276.1; NM_001025105.2.
DR RefSeq; NP_001258670.1; NM_001271741.1.
DR RefSeq; NP_001258671.1; NM_001271742.1.
DR RefSeq; NP_001883.4; NM_001892.5.
DR UniGene; Hs.529862; -.
DR UniGene; Hs.712555; -.
DR ProteinModelPortal; P48729; -.
DR SMR; P48729; 17-302.
DR DIP; DIP-40367N; -.
DR IntAct; P48729; 39.
DR MINT; MINT-193806; -.
DR STRING; 9606.ENSP00000261798; -.
DR BindingDB; P48729; -.
DR ChEMBL; CHEMBL2111458; -.
DR GuidetoPHARMACOLOGY; 1995; -.
DR PhosphoSite; P48729; -.
DR DMDM; 31077177; -.
DR PaxDb; P48729; -.
DR PRIDE; P48729; -.
DR DNASU; 1452; -.
DR Ensembl; ENST00000377843; ENSP00000367074; ENSG00000113712.
DR Ensembl; ENST00000515768; ENSP00000421689; ENSG00000113712.
DR GeneID; 1452; -.
DR KEGG; hsa:1452; -.
DR UCSC; uc003lqx.2; human.
DR CTD; 1452; -.
DR GeneCards; GC05M148854; -.
DR HGNC; HGNC:2451; CSNK1A1.
DR HPA; CAB016680; -.
DR MIM; 600505; gene.
DR neXtProt; NX_P48729; -.
DR PharmGKB; PA26951; -.
DR eggNOG; COG0515; -.
DR HOVERGEN; HBG000176; -.
DR KO; K08957; -.
DR OMA; YKILHGG; -.
DR OrthoDB; EOG7CZK5W; -.
DR PhylomeDB; P48729; -.
DR BRENDA; 2.7.11.1; 2681.
DR Reactome; REACT_111102; Signal Transduction.
DR SignaLink; P48729; -.
DR ChiTaRS; CSNK1A1; human.
DR GeneWiki; Casein_kinase_1,_alpha_1; -.
DR GenomeRNAi; 1452; -.
DR NextBio; 5955; -.
DR PRO; PR:P48729; -.
DR ArrayExpress; P48729; -.
DR Bgee; P48729; -.
DR CleanEx; HS_CSNK1A1; -.
DR Genevestigator; P48729; -.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0000777; C:condensed chromosome kinetochore; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0007067; P:mitosis; IEA:UniProtKB-KW.
DR GO; GO:0016055; P:Wnt receptor signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR011009; Kinase-like_dom.
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 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 Acetylation; Alternative splicing; ATP-binding; Cell cycle;
KW Cell division; Centromere; Chromosome; Complete proteome; Cytoplasm;
KW Cytoskeleton; Direct protein sequencing; Kinase; Kinetochore; Mitosis;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Wnt signaling pathway.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 337 Casein kinase I isoform alpha.
FT /FTId=PRO_0000192822.
FT DOMAIN 17 285 Protein kinase.
FT NP_BIND 23 31 ATP (By similarity).
FT ACT_SITE 136 136 Proton acceptor (By similarity).
FT BINDING 46 46 ATP (By similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 8 8 N6-acetyllysine.
FT VAR_SEQ 152 152 K -> KCLESPVGKRKRSMTVSTSQDPSFSGLNQ (in
FT isoform 2).
FT /FTId=VSP_035455.
FT VARIANT 297 297 D -> H (in a breast pleomorphic lobular
FT carcinoma sample; somatic mutation).
FT /FTId=VAR_042073.
FT CONFLICT 45 45 V -> L (in Ref. 1; CAA56710).
FT CONFLICT 74 74 P -> T (in Ref. 4; AAV38633).
FT CONFLICT 122 122 S -> A (in Ref. 8; AA sequence).
FT CONFLICT 129 129 T -> TK (in Ref. 8; AA sequence).
FT CONFLICT 231 231 Q -> K (in Ref. 7; AAH08717).
FT CONFLICT 250 250 K -> E (in Ref. 5; AAY84562).
FT CONFLICT 330 330 T -> S (in Ref. 1; CAA56710 and 4;
FT AAV38632/AAV38633).
SQ SEQUENCE 337 AA; 38915 MW; 1B2085AE33CAFAC2 CRC64;
MASSSGSKAE FIVGGKYKLV RKIGSGSFGD IYLAINITNG EEVAVKLESQ KARHPQLLYE
SKLYKILQGG VGIPHIRWYG QEKDYNVLVM DLLGPSLEDL FNFCSRRFTM KTVLMLADQM
ISRIEYVHTK NFIHRDIKPD NFLMGIGRHC NKLFLIDFGL AKKYRDNRTR QHIPYREDKN
LTGTARYASI NAHLGIEQSR RDDMESLGYV LMYFNRTSLP WQGLKAATKK QKYEKISEKK
MSTPVEVLCK GFPAEFAMYL NYCRGLRFEE APDYMYLRQL FRILFRTLNH QYDYTFDWTM
LKQKAAQQAA SSSGQGQQAQ TPTGKQTDKT KSNMKGF
//
ID KC1A_HUMAN Reviewed; 337 AA.
AC P48729; D3DQG0; D3DQG1; Q4JJA0; Q5U046; Q5U047; Q6FGA2; Q96HD2;
read moreAC Q9UDK3;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-MAY-2003, sequence version 2.
DT 22-JAN-2014, entry version 145.
DE RecName: Full=Casein kinase I isoform alpha;
DE Short=CKI-alpha;
DE EC=2.7.11.1;
DE AltName: Full=CK1;
GN Name=CSNK1A1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=8050587; DOI=10.1016/0014-5793(94)00679-2;
RA Tapia C., Featherstone T., Gomez C., Taillon-Miller P., Allende C.C.,
RA Allende J.E.;
RT "Cloning and chromosomal localization of the gene coding for human
RT protein kinase CK1.";
RL FEBS Lett. 349:307-312(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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
RT (CKI), a novel member of the CKI gene family.";
RL J. Biol. Chem. 270:14875-14883(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Lin L., Nong W., Zhou G., Ke R., Shen C., Zhong G., Zheng Z.,
RA Liang M., Huang B., Li H., Yang S.;
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 65-83; 111-152 AND 179-204, FUNCTION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=1409656; DOI=10.1073/pnas.89.20.9454;
RA Brockman J.L., Gross S.D., Sussman M.R., Anderson R.A.;
RT "Cell cycle-dependent localization of casein kinase I to mitotic
RT spindles.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:9454-9458(1992).
RN [9]
RP ROLE IN WNT SIGNALING.
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.,
RA Lin X., He X.;
RT "Control of beta-catenin phosphorylation/degradation by a dual-kinase
RT mechanism.";
RL Cell 108:837-847(2002).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [11]
RP FUNCTION, INTERACTION WITH TUT1, AND SUBCELLULAR LOCATION.
RX PubMed=18305108; DOI=10.1074/jbc.M800656200;
RA Gonzales M.L., Mellman D.L., Anderson R.A.;
RT "CKIalpha is associated with and phosphorylates star-PAP and is also
RT required for expression of select star-PAP target messenger RNAs.";
RL J. Biol. Chem. 283:12665-12673(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-156 (ISOFORM 2), AND
RP MASS SPECTROMETRY.
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
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [13]
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.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
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 [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2 AND LYS-8, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [16]
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.,
RA Buerckstuemmer T., 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 [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [18]
RP VARIANT [LARGE SCALE ANALYSIS] HIS-297.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., 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. It can phosphorylate a large number of proteins.
CC Participates in Wnt signaling. Phosphorylates CTNNB1 at 'Ser-45'.
CC May play a role in segregating chromosomes during mitosis.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- SUBUNIT: Monomer. Interacts with the Axin complex. Interacts with
CC TUT1, leading to TUT1 phosphorylation.
CC -!- INTERACTION:
CC Q00987:MDM2; NbExp=3; IntAct=EBI-1383726, EBI-389668;
CC O15151:MDM4; NbExp=2; IntAct=EBI-1383726, EBI-398437;
CC Q13546:RIPK1; NbExp=5; IntAct=EBI-1383726, EBI-358507;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome. Chromosome, centromere,
CC kinetochore. Nucleus speckle. Note=Localizes to the centrosome in
CC interphase cells, and to kinetochore fibers during mitosis.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P48729-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P48729-2; Sequence=VSP_035455;
CC Note=Contains a phosphoserine at position 156;
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CK1 Ser/Thr
CC protein kinase family. Casein kinase I subfamily.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org//Genes/CSNK1A1ID40168ch5q32.html";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X80693; CAA56710.1; -; mRNA.
DR EMBL; L37042; AAC41760.1; -; mRNA.
DR EMBL; CR542206; CAG47002.1; -; mRNA.
DR EMBL; BT019829; AAV38632.1; -; mRNA.
DR EMBL; BT019830; AAV38633.1; -; mRNA.
DR EMBL; DQ082865; AAY84562.1; -; mRNA.
DR EMBL; CH471062; EAW61767.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW61769.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW61773.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW61776.1; -; Genomic_DNA.
DR EMBL; BC008717; AAH08717.1; -; mRNA.
DR PIR; A57011; A57011.
DR PIR; S46254; S46254.
DR RefSeq; NP_001020276.1; NM_001025105.2.
DR RefSeq; NP_001258670.1; NM_001271741.1.
DR RefSeq; NP_001258671.1; NM_001271742.1.
DR RefSeq; NP_001883.4; NM_001892.5.
DR UniGene; Hs.529862; -.
DR UniGene; Hs.712555; -.
DR ProteinModelPortal; P48729; -.
DR SMR; P48729; 17-302.
DR DIP; DIP-40367N; -.
DR IntAct; P48729; 39.
DR MINT; MINT-193806; -.
DR STRING; 9606.ENSP00000261798; -.
DR BindingDB; P48729; -.
DR ChEMBL; CHEMBL2111458; -.
DR GuidetoPHARMACOLOGY; 1995; -.
DR PhosphoSite; P48729; -.
DR DMDM; 31077177; -.
DR PaxDb; P48729; -.
DR PRIDE; P48729; -.
DR DNASU; 1452; -.
DR Ensembl; ENST00000377843; ENSP00000367074; ENSG00000113712.
DR Ensembl; ENST00000515768; ENSP00000421689; ENSG00000113712.
DR GeneID; 1452; -.
DR KEGG; hsa:1452; -.
DR UCSC; uc003lqx.2; human.
DR CTD; 1452; -.
DR GeneCards; GC05M148854; -.
DR HGNC; HGNC:2451; CSNK1A1.
DR HPA; CAB016680; -.
DR MIM; 600505; gene.
DR neXtProt; NX_P48729; -.
DR PharmGKB; PA26951; -.
DR eggNOG; COG0515; -.
DR HOVERGEN; HBG000176; -.
DR KO; K08957; -.
DR OMA; YKILHGG; -.
DR OrthoDB; EOG7CZK5W; -.
DR PhylomeDB; P48729; -.
DR BRENDA; 2.7.11.1; 2681.
DR Reactome; REACT_111102; Signal Transduction.
DR SignaLink; P48729; -.
DR ChiTaRS; CSNK1A1; human.
DR GeneWiki; Casein_kinase_1,_alpha_1; -.
DR GenomeRNAi; 1452; -.
DR NextBio; 5955; -.
DR PRO; PR:P48729; -.
DR ArrayExpress; P48729; -.
DR Bgee; P48729; -.
DR CleanEx; HS_CSNK1A1; -.
DR Genevestigator; P48729; -.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0000777; C:condensed chromosome kinetochore; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0007067; P:mitosis; IEA:UniProtKB-KW.
DR GO; GO:0016055; P:Wnt receptor signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR011009; Kinase-like_dom.
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 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 Acetylation; Alternative splicing; ATP-binding; Cell cycle;
KW Cell division; Centromere; Chromosome; Complete proteome; Cytoplasm;
KW Cytoskeleton; Direct protein sequencing; Kinase; Kinetochore; Mitosis;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Wnt signaling pathway.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 337 Casein kinase I isoform alpha.
FT /FTId=PRO_0000192822.
FT DOMAIN 17 285 Protein kinase.
FT NP_BIND 23 31 ATP (By similarity).
FT ACT_SITE 136 136 Proton acceptor (By similarity).
FT BINDING 46 46 ATP (By similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 8 8 N6-acetyllysine.
FT VAR_SEQ 152 152 K -> KCLESPVGKRKRSMTVSTSQDPSFSGLNQ (in
FT isoform 2).
FT /FTId=VSP_035455.
FT VARIANT 297 297 D -> H (in a breast pleomorphic lobular
FT carcinoma sample; somatic mutation).
FT /FTId=VAR_042073.
FT CONFLICT 45 45 V -> L (in Ref. 1; CAA56710).
FT CONFLICT 74 74 P -> T (in Ref. 4; AAV38633).
FT CONFLICT 122 122 S -> A (in Ref. 8; AA sequence).
FT CONFLICT 129 129 T -> TK (in Ref. 8; AA sequence).
FT CONFLICT 231 231 Q -> K (in Ref. 7; AAH08717).
FT CONFLICT 250 250 K -> E (in Ref. 5; AAY84562).
FT CONFLICT 330 330 T -> S (in Ref. 1; CAA56710 and 4;
FT AAV38632/AAV38633).
SQ SEQUENCE 337 AA; 38915 MW; 1B2085AE33CAFAC2 CRC64;
MASSSGSKAE FIVGGKYKLV RKIGSGSFGD IYLAINITNG EEVAVKLESQ KARHPQLLYE
SKLYKILQGG VGIPHIRWYG QEKDYNVLVM DLLGPSLEDL FNFCSRRFTM KTVLMLADQM
ISRIEYVHTK NFIHRDIKPD NFLMGIGRHC NKLFLIDFGL AKKYRDNRTR QHIPYREDKN
LTGTARYASI NAHLGIEQSR RDDMESLGYV LMYFNRTSLP WQGLKAATKK QKYEKISEKK
MSTPVEVLCK GFPAEFAMYL NYCRGLRFEE APDYMYLRQL FRILFRTLNH QYDYTFDWTM
LKQKAAQQAA SSSGQGQQAQ TPTGKQTDKT KSNMKGF
//
MIM
600505
*RECORD*
*FIELD* NO
600505
*FIELD* TI
*600505 CASEIN KINASE I, ALPHA-1; CSNK1A1
;;CK1
*FIELD* TX
CLONING
Tapia et al. (1994) isolated a cDNA encoding human casein kinase I from
read morea fetal brain library using PCR primers based on the bovine sequence.
The cDNA was sequenced and shown to have a predicted amino acid sequence
identical to the bovine protein except that it contains 12 additional
amino acids at the carboxyl end.
GENE FUNCTION
Jia et al. (2004) showed that protein kinase A (PKA; see 188830) and
casein kinase I (CKI) regulate Smo (601500) cell surface accumulation
and activity in response to hedgehog (Hh; see 600725). Blocking PKA or
CKI activity in the Drosophila wing disc prevented Hh-induced Smo
accumulation and attenuated pathway activity, whereas increasing PKA
activity promoted Smo accumulation and pathway activation. Jia et al.
(2004) showed that PKA and CKI phosphorylate Smo at several sites, and
that phosphorylation-deficient forms of Smo fail to accumulate on the
cell surface and are unable to transduce the Hh signal. Conversely,
phosphorylation-mimicking Smo variants showed constitutive cell surface
expression and signaling activity. Furthermore, Jia et al. (2004) found
that the levels of Smo cell surface expression and activity correlated
with its levels of phosphorylation. Jia et al. (2004) concluded that Hh
induces progressive Smo phosphorylation by PKA and CKI, leading to
elevation of Smo cell surface levels and signaling activity.
Bidere et al. (2009) conducted parallel screens involving a mass
spectrometry analysis of CARMA1 (607210) binding partners and an RNA
interference screen for growth inhibition of the CBM-dependent
'activated B cell-like' (ABC) subtype of diffuse large B-cell lymphoma
(DLBCL; see 605027). Bidere et al. (2009) reported that both screens
identified CK1-alpha as a bifunctional regulator of NF-kappa-B (164011).
CK1-alpha dynamically associates with the CBM complex on T cell receptor
engagement to participate in cytokine production and lymphocyte
proliferation. However, CK1-alpha kinase activity has a contrasting role
by subsequently promoting the phosphorylation and inactivation of
CARMA1. CK1-alpha has thus a dual 'gating' function which first promotes
and then terminates receptor-induced NF-kappa-B. ABC DLBCL cells
required CK1-alpha for constitutive NF-kappa-B activity, indicating that
CK1-alpha functions as a conditionally essential malignancy gene.
Elyada et al. (2011) showed that casein kinase I-alpha, a component of
the beta-catenin (116806) destruction complex, is a critical regulator
of the Wnt signaling (see 164820) pathway. Inducing the ablation of
Csnk1a1 in the gut triggers massive Wnt activation, surprisingly without
causing tumorigenesis. CKI-alpha-deficient epithelium shows many of the
features of human colorectal tumors in addition to Wnt activation, in
particular the induction of the DNA damage response and cellular
senescence, both of which are thought to provide a barrier against
malignant transformation. The epithelial DNA damage response in mice is
accompanied by substantial activation of p53 (191170), suggesting that
the p53 pathway may counteract the protumorigenic effects of Wnt
hyperactivation. Notably, the transition from benign adenomas to
invasive colorectal cancer in humans is typically linked to p53
inactivation, underscoring the importance of p53 as a safeguard against
malignant progression; however, the mechanism of p53-mediated tumor
suppression is unknown. Elyada et al. (2011) showed that the maintenance
of intestinal homeostasis in CKI-alpha-deficient gut requires
p53-mediated growth control, because the combined ablation of Csnk1a1
and either p53 or its target gene p21 (116899) triggered high-grade
dysplasia with extensive proliferation. Unexpectedly, these ablations
also induced nonproliferating cells to invade the villous lamina propria
rapidly, producing invasive carcinomas throughout the small bowel.
Furthermore, in p53-deficient gut, loss of heterozygosity of the gene
encoding CKI-alpha caused a highly invasive carcinoma, indicating that
CKI-alpha caused a highly invasive carcinoma, indicating that CKI-alpha
functions as a tumor suppressor when p53 is inactivated. Elyada et al.
(2011) identified a set of genes (the p53-suppressed invasiveness
signature, PSIS) that is activated by the loss of both p53 and CKI-alpha
and which probably accounts for the brisk induction of invasiveness.
PSIS transcription and tumor invasion were suppressed by p21,
independently of cell cycle control. Restraining tissue invasion through
suppressing PSIS expression is thus a novel tumor suppressor function of
wildtype p53. PROX1 (601546), IFITM2 (605578), and IFITM3 (605579) are
all PSIS genes.
MAPPING
Tapia et al. (1994) identified YAC genomic clones containing the human
gene and used them to map CKI to chromosome 13q13. Fish et al. (1995)
mapped the CSNK1A1 gene to chromosome 13q13.1-q14.1 by FISH. However,
Gross (2011) mapped the CSNK1A1 gene to chromosome 5q32 based on an
alignment of the CSNK1A1 sequence (GenBank GENBANK BC008717) with the
genomic sequence (GRCh37).
*FIELD* RF
1. Bidere, N.; Ngo, V. N.; Lee, J.; Collins, C.; Zheng, L.; Wan, F.;
Davis, R. E.; Lenz, G.; Anderson, D. E.; Arnoult, D.; Vazquez, A.;
Sakai, K.; Zhang, J.; Meng, Z.; Veenstra, T. D.; Staudt, L. M.; Lenardo,
M. J.: Casein kinase 1-alpha governs antigen-receptor-induced NF-kappa-B
activation and human lymphoma cell survival. Nature 458: 92-96,
2009.
2. Elyada, E.; Pribluda, A.; Goldstein, R. E.; Morgenstern, Y.; Brachya,
G.; Cojocaru, G.; Snir-Alkalay, I.; Burstain, I.; Haffner-Krausz,
R.; Jung, S.; Wiener, Z.; Alitalo, K.; Oren, M.; Pikarsky, E.; Ben-Neriah,
Y.: CKI-alpha ablation highlights a critical role for p53 in invasiveness
control. Nature 470: 409-413, 2011.
3. Fish, K. J.; Cegielska, A.; Getman, M. E.; Landes, G. M.; Virshup,
D. M.: Isolation and characterization of human casein kinase I-epsilon
(CKI), a novel member of the CKI gene family. J. Biol. Chem. 270:
14875-14883, 1995.
4. Gross, M. B.: Personal Communication. Baltimore, Md. 2/9/2011.
5. Jia, J.; Tong, C.; Wang, B.; Luo, L.; Jiang, J.: Hedgehog signalling
activity of Smoothened requires phosphorylation by protein kinase
A and casein kinase I. Nature 432: 1045-1050, 2004.
6. Tapia, C.; Featherstone, T.; Gomez, C.; Taillon-Miller, P.; Allende,
C. C.; Allende, J. E.: Cloning and chromosomal localization of the
gene coding for human protein kinase CK1. FEBS Lett. 349: 307-312,
1994.
*FIELD* CN
Ada Hamosh - updated: 6/29/2011
Matthew B. Gross - updated: 2/9/2011
Ada Hamosh - updated: 4/2/2009
Ada Hamosh - updated: 3/3/2005
Patricia A. Hartz - updated: 9/9/2004
*FIELD* CD
Alan F. Scott: 4/24/1995
*FIELD* ED
carol: 07/06/2011
alopez: 7/5/2011
terry: 6/29/2011
mgross: 2/9/2011
alopez: 4/3/2009
terry: 4/2/2009
alopez: 3/4/2005
terry: 3/3/2005
mgross: 9/9/2004
psherman: 10/22/1999
dkim: 6/30/1998
mark: 5/13/1996
joanna: 12/6/1995
mark: 4/25/1995
mark: 4/24/1995
*RECORD*
*FIELD* NO
600505
*FIELD* TI
*600505 CASEIN KINASE I, ALPHA-1; CSNK1A1
;;CK1
*FIELD* TX
CLONING
Tapia et al. (1994) isolated a cDNA encoding human casein kinase I from
read morea fetal brain library using PCR primers based on the bovine sequence.
The cDNA was sequenced and shown to have a predicted amino acid sequence
identical to the bovine protein except that it contains 12 additional
amino acids at the carboxyl end.
GENE FUNCTION
Jia et al. (2004) showed that protein kinase A (PKA; see 188830) and
casein kinase I (CKI) regulate Smo (601500) cell surface accumulation
and activity in response to hedgehog (Hh; see 600725). Blocking PKA or
CKI activity in the Drosophila wing disc prevented Hh-induced Smo
accumulation and attenuated pathway activity, whereas increasing PKA
activity promoted Smo accumulation and pathway activation. Jia et al.
(2004) showed that PKA and CKI phosphorylate Smo at several sites, and
that phosphorylation-deficient forms of Smo fail to accumulate on the
cell surface and are unable to transduce the Hh signal. Conversely,
phosphorylation-mimicking Smo variants showed constitutive cell surface
expression and signaling activity. Furthermore, Jia et al. (2004) found
that the levels of Smo cell surface expression and activity correlated
with its levels of phosphorylation. Jia et al. (2004) concluded that Hh
induces progressive Smo phosphorylation by PKA and CKI, leading to
elevation of Smo cell surface levels and signaling activity.
Bidere et al. (2009) conducted parallel screens involving a mass
spectrometry analysis of CARMA1 (607210) binding partners and an RNA
interference screen for growth inhibition of the CBM-dependent
'activated B cell-like' (ABC) subtype of diffuse large B-cell lymphoma
(DLBCL; see 605027). Bidere et al. (2009) reported that both screens
identified CK1-alpha as a bifunctional regulator of NF-kappa-B (164011).
CK1-alpha dynamically associates with the CBM complex on T cell receptor
engagement to participate in cytokine production and lymphocyte
proliferation. However, CK1-alpha kinase activity has a contrasting role
by subsequently promoting the phosphorylation and inactivation of
CARMA1. CK1-alpha has thus a dual 'gating' function which first promotes
and then terminates receptor-induced NF-kappa-B. ABC DLBCL cells
required CK1-alpha for constitutive NF-kappa-B activity, indicating that
CK1-alpha functions as a conditionally essential malignancy gene.
Elyada et al. (2011) showed that casein kinase I-alpha, a component of
the beta-catenin (116806) destruction complex, is a critical regulator
of the Wnt signaling (see 164820) pathway. Inducing the ablation of
Csnk1a1 in the gut triggers massive Wnt activation, surprisingly without
causing tumorigenesis. CKI-alpha-deficient epithelium shows many of the
features of human colorectal tumors in addition to Wnt activation, in
particular the induction of the DNA damage response and cellular
senescence, both of which are thought to provide a barrier against
malignant transformation. The epithelial DNA damage response in mice is
accompanied by substantial activation of p53 (191170), suggesting that
the p53 pathway may counteract the protumorigenic effects of Wnt
hyperactivation. Notably, the transition from benign adenomas to
invasive colorectal cancer in humans is typically linked to p53
inactivation, underscoring the importance of p53 as a safeguard against
malignant progression; however, the mechanism of p53-mediated tumor
suppression is unknown. Elyada et al. (2011) showed that the maintenance
of intestinal homeostasis in CKI-alpha-deficient gut requires
p53-mediated growth control, because the combined ablation of Csnk1a1
and either p53 or its target gene p21 (116899) triggered high-grade
dysplasia with extensive proliferation. Unexpectedly, these ablations
also induced nonproliferating cells to invade the villous lamina propria
rapidly, producing invasive carcinomas throughout the small bowel.
Furthermore, in p53-deficient gut, loss of heterozygosity of the gene
encoding CKI-alpha caused a highly invasive carcinoma, indicating that
CKI-alpha caused a highly invasive carcinoma, indicating that CKI-alpha
functions as a tumor suppressor when p53 is inactivated. Elyada et al.
(2011) identified a set of genes (the p53-suppressed invasiveness
signature, PSIS) that is activated by the loss of both p53 and CKI-alpha
and which probably accounts for the brisk induction of invasiveness.
PSIS transcription and tumor invasion were suppressed by p21,
independently of cell cycle control. Restraining tissue invasion through
suppressing PSIS expression is thus a novel tumor suppressor function of
wildtype p53. PROX1 (601546), IFITM2 (605578), and IFITM3 (605579) are
all PSIS genes.
MAPPING
Tapia et al. (1994) identified YAC genomic clones containing the human
gene and used them to map CKI to chromosome 13q13. Fish et al. (1995)
mapped the CSNK1A1 gene to chromosome 13q13.1-q14.1 by FISH. However,
Gross (2011) mapped the CSNK1A1 gene to chromosome 5q32 based on an
alignment of the CSNK1A1 sequence (GenBank GENBANK BC008717) with the
genomic sequence (GRCh37).
*FIELD* RF
1. Bidere, N.; Ngo, V. N.; Lee, J.; Collins, C.; Zheng, L.; Wan, F.;
Davis, R. E.; Lenz, G.; Anderson, D. E.; Arnoult, D.; Vazquez, A.;
Sakai, K.; Zhang, J.; Meng, Z.; Veenstra, T. D.; Staudt, L. M.; Lenardo,
M. J.: Casein kinase 1-alpha governs antigen-receptor-induced NF-kappa-B
activation and human lymphoma cell survival. Nature 458: 92-96,
2009.
2. Elyada, E.; Pribluda, A.; Goldstein, R. E.; Morgenstern, Y.; Brachya,
G.; Cojocaru, G.; Snir-Alkalay, I.; Burstain, I.; Haffner-Krausz,
R.; Jung, S.; Wiener, Z.; Alitalo, K.; Oren, M.; Pikarsky, E.; Ben-Neriah,
Y.: CKI-alpha ablation highlights a critical role for p53 in invasiveness
control. Nature 470: 409-413, 2011.
3. Fish, K. J.; Cegielska, A.; Getman, M. E.; Landes, G. M.; Virshup,
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*FIELD* CN
Ada Hamosh - updated: 6/29/2011
Matthew B. Gross - updated: 2/9/2011
Ada Hamosh - updated: 4/2/2009
Ada Hamosh - updated: 3/3/2005
Patricia A. Hartz - updated: 9/9/2004
*FIELD* CD
Alan F. Scott: 4/24/1995
*FIELD* ED
carol: 07/06/2011
alopez: 7/5/2011
terry: 6/29/2011
mgross: 2/9/2011
alopez: 4/3/2009
terry: 4/2/2009
alopez: 3/4/2005
terry: 3/3/2005
mgross: 9/9/2004
psherman: 10/22/1999
dkim: 6/30/1998
mark: 5/13/1996
joanna: 12/6/1995
mark: 4/25/1995
mark: 4/24/1995