ID KC1A_HUMAN Reviewed; 337 AA. AC P48729; D3DQG0; D3DQG1; Q4JJA0; Q5U046; Q5U047; Q6FGA2; Q71TU5; Q96HD2; AC Q9UDK3; DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. DT 23-MAY-2003, sequence version 2. DT 27-MAR-2024, entry version 227. DE RecName: Full=Casein kinase I isoform alpha; DE Short=CKI-alpha; DE EC=2.7.11.1 {ECO:0000269|PubMed:11955436}; DE AltName: Full=CK1; GN Name=CSNK1A1; 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] (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 protein RT 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 (CKI), a RT novel member of the CKI gene family."; RL J. Biol. Chem. 270:14875-14883(1995). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RX PubMed=15498874; DOI=10.1073/pnas.0404089101; RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X., RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.; RT "Large-scale cDNA transfection screening for genes related to cancer RT development and progression."; RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., RA 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 [6] 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 vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RA Lin L., Nong W., Zhou G., Ke R., Shen C., Zhong G., Zheng Z., Liang M., RA Huang B., Li H., Yang S.; RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [10] 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [11] RP PROTEIN SEQUENCE OF 65-83; 111-152 AND 179-204, FUNCTION, AND SUBCELLULAR RP 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 [12] RP ROLE IN WNT SIGNALING, AND INTERACTION WITH AXIN COMPLEX. 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 [13] 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 phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [14] 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 [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-156 (ISOFORM 2), AND RP 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 [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 ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-8, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA 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 [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-321 (ISOFORM 3), AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(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 FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=22017875; DOI=10.1016/j.molcel.2011.08.030; RA Gao D., Inuzuka H., Tan M.K., Fukushima H., Locasale J.W., Liu P., Wan L., RA Zhai B., Chin Y.R., Shaik S., Lyssiotis C.A., Gygi S.P., Toker A., RA Cantley L.C., Asara J.M., Harper J.W., Wei W.; RT "mTOR drives its own activation via SCF(betaTrCP)-dependent degradation of RT the mTOR inhibitor DEPTOR."; RL Mol. Cell 44:290-303(2011). RN [22] RP FUNCTION, CATALYTIC ACTIVITY, AND PHOSPHORYLATION. RX PubMed=22017877; DOI=10.1016/j.molcel.2011.09.005; RA Duan S., Skaar J.R., Kuchay S., Toschi A., Kanarek N., Ben-Neriah Y., RA Pagano M.; RT "mTOR generates an auto-amplification loop by triggering the betaTrCP- and RT CK1alpha-dependent degradation of DEPTOR."; RL Mol. Cell 44:317-324(2011). RN [23] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. 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., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [24] RP FUNCTION, INTERACTION WITH FAM83H, AND SUBCELLULAR LOCATION. RX PubMed=23902688; DOI=10.1242/jcs.129684; RA Kuga T., Kume H., Kawasaki N., Sato M., Adachi J., Shiromizu T., RA Hoshino I., Nishimori T., Matsubara H., Tomonaga T.; RT "A novel mechanism of keratin cytoskeleton organization through casein RT kinase Ialpha and FAM83H in colorectal cancer."; RL J. Cell Sci. 126:4721-4731(2013). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=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 [26] RP INTERACTION WITH FAM83D. RX PubMed=31338967; DOI=10.15252/embr.201847495; RA Fulcher L.J., He Z., Mei L., Macartney T.J., Wood N.T., Prescott A.R., RA Whigham A.J., Varghese J., Gourlay R., Ball G., Clarke R., Campbell D.G., RA Maxwell C.A., Sapkota G.P.; RT "FAM83D directs protein kinase CK1alpha to the mitotic spindle for proper RT spindle positioning."; RL EMBO Rep. 20:e47495-e47495(2019). RN [27] 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., 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 (PubMed:18305108, PubMed:11955436, PubMed:1409656, CC PubMed:23902688). It can phosphorylate a large number of proteins CC (PubMed:18305108, PubMed:11955436, PubMed:1409656, PubMed:23902688). CC Participates in Wnt signaling (PubMed:11955436). Phosphorylates CTNNB1 CC at 'Ser-45' (PubMed:11955436). May phosphorylate PER1 and PER2 (By CC similarity). May play a role in segregating chromosomes during mitosis CC (PubMed:1409656). May play a role in keratin cytoskeleton disassembly CC and thereby, it may regulate epithelial cell migration CC (PubMed:23902688). Acts as a positive regulator of mTORC1 and mTORC2 CC signaling in response to nutrients by mediating phosphorylation of CC DEPTOR inhibitor (PubMed:22017875, PubMed:22017877). Acts as an CC inhibitor of NLRP3 inflammasome assembly by mediating phosphorylation CC of NLRP3 (By similarity). {ECO:0000250|UniProtKB:Q8BK63, CC ECO:0000269|PubMed:11955436, ECO:0000269|PubMed:1409656, CC ECO:0000269|PubMed:18305108, ECO:0000269|PubMed:22017875, CC ECO:0000269|PubMed:22017877, ECO:0000269|PubMed:23902688}. 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:11955436, ECO:0000269|PubMed:22017875, CC ECO:0000269|PubMed:22017877}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990; CC Evidence={ECO:0000269|PubMed:11955436, ECO:0000269|PubMed:22017875, CC ECO:0000269|PubMed:22017877}; 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 -!- SUBUNIT: Interacts with the Axin complex (PubMed:11955436). Interacts CC with TUT1, leading to TUT1 phosphorylation (PubMed:1409656). Interacts CC with FAM83H; recruits CSNK1A1 to keratin filaments (PubMed:23902688). CC Interacts with FAM83D (via N-terminus); in mitotic cells CC (PubMed:31338967). {ECO:0000269|PubMed:11955436, CC ECO:0000269|PubMed:1409656, ECO:0000269|PubMed:23902688, CC ECO:0000269|PubMed:31338967}. CC -!- INTERACTION: CC P48729; Q9BXL7: CARD11; NbExp=5; IntAct=EBI-1383726, EBI-7006141; CC P48729; Q96SW2: CRBN; NbExp=3; IntAct=EBI-1383726, EBI-2510250; CC P48729; Q5T0W9: FAM83B; NbExp=8; IntAct=EBI-1383726, EBI-2556565; CC P48729; Q9BQN1: FAM83C; NbExp=6; IntAct=EBI-1383726, EBI-1220251; CC P48729; Q9H4H8: FAM83D; NbExp=5; IntAct=EBI-1383726, EBI-2556127; CC P48729; Q2M2I3: FAM83E; NbExp=6; IntAct=EBI-1383726, EBI-21993639; CC P48729; Q8NEG4: FAM83F; NbExp=7; IntAct=EBI-1383726, EBI-1563144; CC P48729; A6ND36: FAM83G; NbExp=13; IntAct=EBI-1383726, EBI-1047240; CC P48729; Q6ZRV2: FAM83H; NbExp=11; IntAct=EBI-1383726, EBI-2556538; CC P48729; P08238: HSP90AB1; NbExp=2; IntAct=EBI-1383726, EBI-352572; CC P48729; Q9UDY8: MALT1; NbExp=7; IntAct=EBI-1383726, EBI-1047372; CC P48729; Q00987: MDM2; NbExp=3; IntAct=EBI-1383726, EBI-389668; CC P48729; O15151: MDM4; NbExp=2; IntAct=EBI-1383726, EBI-398437; CC P48729; Q13546: RIPK1; NbExp=5; IntAct=EBI-1383726, EBI-358507; CC P48729-1; Q9BXL7: CARD11; NbExp=5; IntAct=EBI-10106282, EBI-7006141; CC P48729-1; Q5S007: LRRK2; NbExp=2; IntAct=EBI-10106282, EBI-5323863; CC P48729-2; Q00987: MDM2; NbExp=3; IntAct=EBI-2040168, EBI-389668; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:1409656}. CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome CC {ECO:0000269|PubMed:1409656}. Chromosome, centromere, kinetochore CC {ECO:0000269|PubMed:1409656}. Nucleus speckle CC {ECO:0000303|PubMed:18305108}. Cytoplasm, cytoskeleton, cilium basal CC body {ECO:0000250|UniProtKB:Q8BK63}. Cytoplasm, cytoskeleton, spindle CC {ECO:0000250|UniProtKB:Q8BK63}. Note=Localizes to the centrosome in CC interphase cells, and to kinetochore fibers during mitosis. Also CC recruited to the keratin cytoskeleton (PubMed:23902688). CC {ECO:0000269|PubMed:1409656, ECO:0000269|PubMed:23902688}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P48729-1; Sequence=Displayed; CC Name=2; CC IsoId=P48729-2; Sequence=VSP_035455; CC Name=3; CC IsoId=P48729-3; Sequence=VSP_055131; CC -!- PTM: Phosphorylated by MTOR in response to mitogenic stimulation, CC leading to its activation. {ECO:0000269|PubMed:22017877}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CK1 Ser/Thr CC protein kinase family. Casein kinase I subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/40168/CSNK1A1"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X80693; CAA56710.1; -; mRNA. DR EMBL; L37042; AAC41760.1; -; mRNA. DR EMBL; AF218004; AAG17246.1; -; mRNA. DR EMBL; AK294942; BAG58018.1; -; 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; AC021078; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471062; EAW61767.1; -; Genomic_DNA. DR EMBL; CH471062; EAW61769.1; -; Genomic_DNA. DR EMBL; CH471062; EAW61773.1; -; Genomic_DNA. DR EMBL; CH471062; EAW61774.1; -; Genomic_DNA. DR EMBL; CH471062; EAW61776.1; -; Genomic_DNA. DR EMBL; BC008717; AAH08717.1; -; mRNA. DR CCDS; CCDS47303.1; -. [P48729-1] DR CCDS; CCDS47304.1; -. [P48729-2] DR CCDS; CCDS64291.1; -. [P48729-3] DR PIR; A57011; A57011. DR PIR; S46254; S46254. DR RefSeq; NP_001020276.1; NM_001025105.2. [P48729-2] DR RefSeq; NP_001258670.1; NM_001271741.1. [P48729-3] DR RefSeq; NP_001258671.1; NM_001271742.1. DR RefSeq; NP_001883.4; NM_001892.5. [P48729-1] DR PDB; 5FQD; X-ray; 2.45 A; C/F=1-337. DR PDB; 6GZD; X-ray; 2.28 A; A=1-337. DR PDB; 7WTT; EM; 3.10 A; a=1-337. DR PDBsum; 5FQD; -. DR PDBsum; 6GZD; -. DR PDBsum; 7WTT; -. DR AlphaFoldDB; P48729; -. DR EMDB; EMD-32800; -. DR SMR; P48729; -. DR BioGRID; 107836; 363. DR ComplexPortal; CPX-107; Beta-catenin destruction core complex, APC-AXIN1-GSK3A variant. DR ComplexPortal; CPX-109; Beta-catenin destruction core complex, APC-AXIN1-GSK3B variant. DR ComplexPortal; CPX-439; Beta-catenin destruction core complex, APC-AXIN2-GSK3B variant. DR ComplexPortal; CPX-440; Beta-catenin destruction core complex, APC2-AXIN2-GSK3B variant. DR ComplexPortal; CPX-441; Beta-catenin destruction core complex, APC-AXIN2-GSK3A variant. DR ComplexPortal; CPX-442; Beta-catenin destruction core complex, APC2-AXIN1-GSK3A variant. DR ComplexPortal; CPX-443; Beta-catenin destruction core complex, APC2-AXIN2-GSK3A variant. DR ComplexPortal; CPX-99; Beta-catenin destruction core complex, APC2-AXIN1-GSK3B variant. DR DIP; DIP-40367N; -. DR IntAct; P48729; 126. DR MINT; P48729; -. DR STRING; 9606.ENSP00000261798; -. DR BindingDB; P48729; -. DR ChEMBL; CHEMBL2793; -. DR DrugBank; DB12010; Fostamatinib. DR DrugCentral; P48729; -. DR GuidetoPHARMACOLOGY; 1995; -. DR GlyGen; P48729; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P48729; -. DR MetOSite; P48729; -. DR PhosphoSitePlus; P48729; -. DR SwissPalm; P48729; -. DR BioMuta; CSNK1A1; -. DR DMDM; 31077177; -. DR CPTAC; CPTAC-2840; -. DR CPTAC; CPTAC-3147; -. DR EPD; P48729; -. DR jPOST; P48729; -. DR MassIVE; P48729; -. DR MaxQB; P48729; -. DR PaxDb; 9606-ENSP00000421689; -. DR PeptideAtlas; P48729; -. DR ProteomicsDB; 55928; -. [P48729-1] DR ProteomicsDB; 55929; -. [P48729-2] DR ProteomicsDB; 68630; -. DR Pumba; P48729; -. DR TopDownProteomics; P48729-1; -. [P48729-1] DR Antibodypedia; 27829; 742 antibodies from 39 providers. DR DNASU; 1452; -. DR Ensembl; ENST00000261798.10; ENSP00000261798.6; ENSG00000113712.19. [P48729-2] DR Ensembl; ENST00000377843.8; ENSP00000367074.2; ENSG00000113712.19. [P48729-1] DR Ensembl; ENST00000657001.1; ENSP00000499757.1; ENSG00000113712.19. [P48729-3] DR GeneID; 1452; -. DR KEGG; hsa:1452; -. DR MANE-Select; ENST00000377843.8; ENSP00000367074.2; NM_001892.6; NP_001883.4. DR UCSC; uc003lqw.3; human. [P48729-1] DR AGR; HGNC:2451; -. DR CTD; 1452; -. DR DisGeNET; 1452; -. DR GeneCards; CSNK1A1; -. DR HGNC; HGNC:2451; CSNK1A1. DR HPA; ENSG00000113712; Low tissue specificity. DR MIM; 600505; gene. DR neXtProt; NX_P48729; -. DR OpenTargets; ENSG00000113712; -. DR PharmGKB; PA26951; -. DR VEuPathDB; HostDB:ENSG00000113712; -. DR eggNOG; KOG1163; Eukaryota. DR GeneTree; ENSGT00940000153700; -. DR HOGENOM; CLU_019279_2_7_1; -. DR InParanoid; P48729; -. DR OMA; PAEFPMY; -. DR OrthoDB; 1534388at2759; -. DR PhylomeDB; P48729; -. DR TreeFam; TF354246; -. DR BRENDA; 2.7.11.1; 2681. DR PathwayCommons; P48729; -. DR Reactome; R-HSA-195253; Degradation of beta-catenin by the destruction complex. DR Reactome; R-HSA-196299; Beta-catenin phosphorylation cascade. DR Reactome; R-HSA-4641262; Disassembly of the destruction complex and recruitment of AXIN to the membrane. DR Reactome; R-HSA-5339716; Signaling by GSK3beta mutants. DR Reactome; R-HSA-5358747; CTNNB1 S33 mutants aren't phosphorylated. DR Reactome; R-HSA-5358749; CTNNB1 S37 mutants aren't phosphorylated. DR Reactome; R-HSA-5358751; CTNNB1 S45 mutants aren't phosphorylated. DR Reactome; R-HSA-5358752; CTNNB1 T41 mutants aren't phosphorylated. DR Reactome; R-HSA-5467337; APC truncation mutants have impaired AXIN binding. DR Reactome; R-HSA-5467340; AXIN missense mutants destabilize the destruction complex. DR Reactome; R-HSA-5467348; Truncations of AMER1 destabilize the destruction complex. DR Reactome; R-HSA-5610783; Degradation of GLI2 by the proteasome. DR Reactome; R-HSA-5610785; GLI3 is processed to GLI3R by the proteasome. DR Reactome; R-HSA-5635838; Activation of SMO. DR Reactome; R-HSA-9694631; Maturation of nucleoprotein. DR SignaLink; P48729; -. DR SIGNOR; P48729; -. DR BioGRID-ORCS; 1452; 660 hits in 1215 CRISPR screens. DR ChiTaRS; CSNK1A1; human. DR GeneWiki; Casein_kinase_1,_alpha_1; -. DR GenomeRNAi; 1452; -. DR Pharos; P48729; Tchem. DR PRO; PR:P48729; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; P48729; Protein. DR Bgee; ENSG00000113712; Expressed in stromal cell of endometrium and 201 other cell types or tissues. DR ExpressionAtlas; P48729; baseline and differential. DR GO; GO:0030877; C:beta-catenin destruction complex; IDA:ParkinsonsUK-UCL. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0036064; C:ciliary basal body; ISS:UniProtKB. DR GO; GO:0005929; C:cilium; TAS:Reactome. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0000776; C:kinetochore; IEA:UniProtKB-KW. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0005819; C:spindle; ISS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004672; F:protein kinase activity; ISS:UniProtKB. 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:0007049; P:cell cycle; IEA:UniProtKB-KW. 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:0031670; P:cellular response to nutrient; IDA:UniProt. DR GO; GO:0007030; P:Golgi organization; IMP:ParkinsonsUK-UCL. DR GO; GO:0045104; P:intermediate filament cytoskeleton organization; IMP:UniProtKB. DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:WormBase. DR GO; GO:1900226; P:negative regulation of NLRP3 inflammasome complex assembly; ISS:UniProtKB. DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IMP:ParkinsonsUK-UCL. DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:FlyBase. DR GO; GO:0035025; P:positive regulation of Rho protein signal transduction; IDA:ParkinsonsUK-UCL. DR GO; GO:1904263; P:positive regulation of TORC1 signaling; IDA:UniProtKB. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; NAS:ComplexPortal. DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB. DR GO; GO:0007165; P:signal transduction; IBA:GO_Central. DR GO; GO:0019082; P:viral protein processing; TAS:Reactome. DR GO; GO:0016055; P:Wnt signaling pathway; TAS:Reactome. DR CDD; cd14128; STKc_CK1_alpha; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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 PANTHER; PTHR11909:SF20; CASEIN KINASE I ISOFORM ALPHA; 1. DR PANTHER; PTHR11909; CASEIN KINASE-RELATED; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; P48729; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Cell cycle; KW Cell division; Cell projection; Centromere; Chromosome; Cytoplasm; KW Cytoskeleton; Direct protein sequencing; Kinase; Kinetochore; Mitosis; KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; KW Serine/threonine-protein kinase; Transferase; Wnt signaling pathway. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:22814378" FT CHAIN 2..337 FT /note="Casein kinase I isoform alpha" FT /id="PRO_0000192822" FT DOMAIN 17..285 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 309..337 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 136 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 23..31 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 46 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:22814378" FT MOD_RES 4 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 8 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT VAR_SEQ 152 FT /note="K -> KCLESPVGKRKRSMTVSTSQDPSFSGLNQ (in isoform 2)" FT /evidence="ECO:0000303|Ref.7" FT /id="VSP_035455" FT VAR_SEQ 324..335 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15498874" FT /id="VSP_055131" FT VARIANT 297 FT /note="D -> H (in a breast pleomorphic lobular carcinoma FT sample; somatic mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042073" FT CONFLICT 45 FT /note="V -> L (in Ref. 1; CAA56710)" FT /evidence="ECO:0000305" FT CONFLICT 74 FT /note="P -> T (in Ref. 6; AAV38633)" FT /evidence="ECO:0000305" FT CONFLICT 122 FT /note="S -> A (in Ref. 11; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 129 FT /note="T -> TK (in Ref. 11; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 231 FT /note="Q -> K (in Ref. 10; AAH08717)" FT /evidence="ECO:0000305" FT CONFLICT 250 FT /note="K -> E (in Ref. 7; AAY84562)" FT /evidence="ECO:0000305" FT CONFLICT 330 FT /note="T -> S (in Ref. 1; CAA56710 and 6; FT AAV38632/AAV38633)" FT /evidence="ECO:0000305" FT TURN 14..16 FT /evidence="ECO:0007829|PDB:6GZD" FT STRAND 17..25 FT /evidence="ECO:0007829|PDB:6GZD" FT STRAND 27..36 FT /evidence="ECO:0007829|PDB:6GZD" FT TURN 37..39 FT /evidence="ECO:0007829|PDB:6GZD" FT STRAND 42..50 FT /evidence="ECO:0007829|PDB:6GZD" FT HELIX 57..67 FT /evidence="ECO:0007829|PDB:6GZD" FT STRAND 76..82 FT /evidence="ECO:0007829|PDB:6GZD" FT STRAND 85..91 FT /evidence="ECO:0007829|PDB:6GZD" FT HELIX 97..103 FT /evidence="ECO:0007829|PDB:6GZD" FT HELIX 110..129 FT /evidence="ECO:0007829|PDB:6GZD" FT HELIX 139..141 FT /evidence="ECO:0007829|PDB:6GZD" FT STRAND 142..144 FT /evidence="ECO:0007829|PDB:6GZD" FT HELIX 147..149 FT /evidence="ECO:0007829|PDB:6GZD" FT STRAND 153..155 FT /evidence="ECO:0007829|PDB:6GZD" FT HELIX 158..160 FT /evidence="ECO:0007829|PDB:7WTT" FT TURN 167..169 FT /evidence="ECO:0007829|PDB:6GZD" FT TURN 185..187 FT /evidence="ECO:0007829|PDB:6GZD" FT HELIX 190..193 FT /evidence="ECO:0007829|PDB:6GZD" FT HELIX 200..216 FT /evidence="ECO:0007829|PDB:6GZD" FT TURN 220..223 FT /evidence="ECO:0007829|PDB:6GZD" FT HELIX 229..242 FT /evidence="ECO:0007829|PDB:6GZD" FT HELIX 245..248 FT /evidence="ECO:0007829|PDB:6GZD" FT TURN 249..251 FT /evidence="ECO:0007829|PDB:6GZD" FT HELIX 254..265 FT /evidence="ECO:0007829|PDB:6GZD" FT HELIX 274..287 FT /evidence="ECO:0007829|PDB:6GZD" FT HELIX 297..304 FT /evidence="ECO:0007829|PDB:6GZD" FT MOD_RES P48729-2:156 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976" FT MOD_RES P48729-3:321 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:20068231" 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 //