KCC1A_HUMAN
ID KCC1A_HUMAN Reviewed; 370 AA.
AC Q14012; Q3KPF6;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 209.
DE RecName: Full=Calcium/calmodulin-dependent protein kinase type 1;
DE EC=2.7.11.17;
DE AltName: Full=CaM kinase I;
DE Short=CaM-KI;
DE AltName: Full=CaM kinase I alpha;
DE Short=CaMKI-alpha;
GN Name=CAMK1;
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], PHOSPHORYLATION AT THR-177, MUTAGENESIS OF
RP LYS-49 AND THR-177, AND ACTIVITY REGULATION.
RX PubMed=7641687; DOI=10.1002/j.1460-2075.1995.tb00037.x;
RA Haribabu B., Hook S.S., Selbert M.A., Goldstein E.G., Tomhave E.D.,
RA Edelman A.M., Snyderman R., Means A.R.;
RT "Human calcium-calmodulin dependent protein kinase I: cDNA cloning, domain
RT structure and activation by phosphorylation at threonine-177 by calcium-
RT calmodulin dependent protein kinase I kinase.";
RL EMBO J. 14:3679-3686(1995).
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 PROTEIN SEQUENCE OF 1-9.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [4]
RP PHOSPHORYLATION BY CAMKK1.
RX PubMed=9662074; DOI=10.1007/bf02258368;
RA Hsu L.-S., Tsou A.-P., Chi C.-W., Lee C.-H., Chen J.-Y.;
RT "Cloning, expression and chromosomal localization of human Ca2+/calmodulin-
RT dependent protein kinase kinase.";
RL J. Biomed. Sci. 5:141-149(1998).
RN [5]
RP FUNCTION IN PHOSPHORYLATION OF HDAC5.
RX PubMed=11114197; DOI=10.1073/pnas.260501497;
RA McKinsey T.A., Zhang C.-L., Olson E.N.;
RT "Activation of the myocyte enhancer factor-2 transcription factor by
RT calcium/calmodulin-dependent protein kinase-stimulated binding of 14-3-3 to
RT histone deacetylase 5.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:14400-14405(2000).
RN [6]
RP PHOSPHORYLATION BY CAMKK2.
RX PubMed=11395482; DOI=10.1074/jbc.m011720200;
RA Hsu L.-S., Chen G.-D., Lee L.-S., Chi C.-W., Cheng J.-F., Chen J.-Y.;
RT "Human Ca2+/calmodulin-dependent protein kinase kinase beta gene encodes
RT multiple isoforms that display distinct kinase activity.";
RL J. Biol. Chem. 276:31113-31123(2001).
RN [7]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=12193581; DOI=10.1210/en.2001-211359;
RA Condon J.C., Pezzi V., Drummond B.M., Yin S., Rainey W.E.;
RT "Calmodulin-dependent kinase I regulates adrenal cell expression of
RT aldosterone synthase.";
RL Endocrinology 143:3651-3657(2002).
RN [8]
RP FUNCTION IN PHOSPHORYLATION OF EIF4G3.
RX PubMed=14507913; DOI=10.1074/jbc.m308781200;
RA Qin H., Raught B., Sonenberg N., Goldstein E.G., Edelman A.M.;
RT "Phosphorylation screening identifies translational initiation factor 4GII
RT as an intracellular target of Ca(2+)/calmodulin-dependent protein kinase
RT I.";
RL J. Biol. Chem. 278:48570-48579(2003).
RN [9]
RP FUNCTION IN CYCLIN-D1/CDK4 COMPLEX, AND MUTAGENESIS OF LYS-49.
RX PubMed=14754892; DOI=10.1074/jbc.m312543200;
RA Kahl C.R., Means A.R.;
RT "Regulation of cyclin D1/Cdk4 complexes by calcium/calmodulin-dependent
RT protein kinase I.";
RL J. Biol. Chem. 279:15411-15419(2004).
RN [10]
RP FUNCTION, AND INTERACTION WITH MARK2.
RX PubMed=17442826; DOI=10.1523/jneurosci.0725-07.2007;
RA Uboha N.V., Flajolet M., Nairn A.C., Picciotto M.R.;
RT "A calcium- and calmodulin-dependent kinase Ialpha/microtubule affinity
RT regulating kinase 2 signaling cascade mediates calcium-dependent neurite
RT outgrowth.";
RL J. Neurosci. 27:4413-4423(2007).
RN [11]
RP FUNCTION IN HIPPOCAMPAL DENDRITITE GROWTH, AND TISSUE SPECIFICITY.
RX PubMed=17056143; DOI=10.1016/j.neures.2006.09.013;
RA Kamata A., Sakagami H., Tokumitsu H., Owada Y., Fukunaga K., Kondo H.;
RT "Spatiotemporal expression of four isoforms of Ca2+/calmodulin-dependent
RT protein kinase I in brain and its possible roles in hippocampal dendritic
RT growth.";
RL Neurosci. Res. 57:86-97(2007).
RN [12]
RP FUNCTION IN PHOSPHORYLATION OF ARHGEF7/BETAPIX, AND INTERACTION WITH
RP ARHGEF7/BETAPIX AND GIT1.
RX PubMed=18184567; DOI=10.1016/j.neuron.2007.11.016;
RA Saneyoshi T., Wayman G., Fortin D., Davare M., Hoshi N., Nozaki N.,
RA Natsume T., Soderling T.R.;
RT "Activity-dependent synaptogenesis: regulation by a CaM-kinase kinase/CaM-
RT kinase I/betaPIX signaling complex.";
RL Neuron 57:94-107(2008).
RN [13]
RP FUNCTION IN AXON ELONGATION.
RX PubMed=20181577; DOI=10.1523/jneurosci.5984-09.2010;
RA Neal A.P., Molina-Campos E., Marrero-Rosado B., Bradford A.B., Fox S.M.,
RA Kovalova N., Hannon H.E.;
RT "CaMKK-CaMKI signaling pathways differentially control axon and dendrite
RT elongation in cortical neurons.";
RL J. Neurosci. 30:2807-2809(2010).
RN [14]
RP REVIEW.
RX PubMed=11749376; DOI=10.1021/cr0002386;
RA Soderling T.R., Stull J.T.;
RT "Structure and regulation of calcium/calmodulin-dependent protein
RT kinases.";
RL Chem. Rev. 101:2341-2352(2001).
RN [15]
RP REVIEW ON FUNCTION IN NEURONAL PLASTICITY.
RX PubMed=18817731; DOI=10.1016/j.neuron.2008.08.021;
RA Wayman G.A., Lee Y.S., Tokumitsu H., Silva A.J., Silva A., Soderling T.R.;
RT "Calmodulin-kinases: modulators of neuronal development and plasticity.";
RL Neuron 59:914-931(2008).
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., 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 [17]
RP REVIEW ON INVOLVEMENT IN CELL CYCLE.
RX PubMed=21301225; DOI=10.4161/cc.10.4.14798;
RA Skelding K.A., Rostas J.A., Verrills N.M.;
RT "Controlling the cell cycle: the role of calcium/calmodulin-stimulated
RT protein kinases I and II.";
RL Cell Cycle 10:631-639(2011).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [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 [19]
RP UBIQUITINATION AT LYS-59.
RX PubMed=23707388; DOI=10.1016/j.cellsig.2013.05.012;
RA Mallampalli R.K., Kaercher L., Snavely C., Pulijala R., Chen B.B., Coon T.,
RA Zhao J., Agassandian M.;
RT "Fbxl12 triggers G1 arrest by mediating degradation of calmodulin kinase
RT I.";
RL Cell. Signal. 25:2047-2059(2013).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-363, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-315 IN COMPLEXES WITH ATP,
RP DOMAIN, AND ACTIVITY REGULATION.
RX PubMed=23028635; DOI=10.1371/journal.pone.0044828;
RA Zha M., Zhong C., Ou Y., Han L., Wang J., Ding J.;
RT "Crystal structures of human CaMKIalpha reveal insights into the regulation
RT mechanism of CaMKI.";
RL PLoS ONE 7:E44828-E44828(2012).
RN [22]
RP VARIANTS [LARGE SCALE ANALYSIS] SER-217 AND LYS-361.
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: Calcium/calmodulin-dependent protein kinase that operates in
CC the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium
CC influx, regulates transcription activators activity, cell cycle,
CC hormone production, cell differentiation, actin filament organization
CC and neurite outgrowth. Recognizes the substrate consensus sequence
CC [MVLIF]-x-R-x(2)-[ST]-x(3)-[MVLIF]. Regulates axonal extension and
CC growth cone motility in hippocampal and cerebellar nerve cells. Upon
CC NMDA receptor-mediated Ca(2+) elevation, promotes dendritic growth in
CC hippocampal neurons and is essential in synapses for full long-term
CC potentiation (LTP) and ERK2-dependent translational activation.
CC Downstream of NMDA receptors, promotes the formation of spines and
CC synapses in hippocampal neurons by phosphorylating ARHGEF7/BETAPIX on
CC 'Ser-694', which results in the enhancement of ARHGEF7 activity and
CC activation of RAC1. Promotes neuronal differentiation and neurite
CC outgrowth by activation and phosphorylation of MARK2 on 'Ser-91', 'Ser-
CC 92', 'Ser-93' and 'Ser-294'. Promotes nuclear export of HDAC5 and
CC binding to 14-3-3 by phosphorylation of 'Ser-259' and 'Ser-498' in the
CC regulation of muscle cell differentiation. Regulates NUMB-mediated
CC endocytosis by phosphorylation of NUMB on 'Ser-276' and 'Ser-295'.
CC Involved in the regulation of basal and estrogen-stimulated migration
CC of medulloblastoma cells through ARHGEF7/BETAPIX phosphorylation (By
CC similarity). Is required for proper activation of cyclin-D1/CDK4
CC complex during G1 progression in diploid fibroblasts. Plays a role in
CC K(+) and ANG2-mediated regulation of the aldosterone synthase (CYP11B2)
CC to produce aldosterone in the adrenal cortex. Phosphorylates
CC EIF4G3/eIF4GII. In vitro phosphorylates CREB1, ATF1, CFTR, MYL9 and
CC SYN1/synapsin I. {ECO:0000250, ECO:0000269|PubMed:11114197,
CC ECO:0000269|PubMed:12193581, ECO:0000269|PubMed:14507913,
CC ECO:0000269|PubMed:14754892, ECO:0000269|PubMed:17056143,
CC ECO:0000269|PubMed:17442826, ECO:0000269|PubMed:18184567,
CC ECO:0000269|PubMed:20181577}.
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=2.7.11.17;
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=2.7.11.17;
CC -!- ACTIVITY REGULATION: Activated by Ca(2+)/calmodulin. Binding of
CC calmodulin results in conformational change that relieves intrasteric
CC autoinhibition and allows phosphorylation of Thr-177 within the
CC activation loop by CaMKK1 or CaMKK2. Phosphorylation of Thr-177 results
CC in several fold increase in total activity. Unlike CaMK4, is unable to
CC exhibit autonomous activity after Ca(2+)/calmodulin activation.
CC {ECO:0000269|PubMed:23028635, ECO:0000269|PubMed:7641687}.
CC -!- SUBUNIT: Monomer. Interacts with XPO1 (By similarity). Interacts with
CC MARK2, ARHGEF7/BETAPIX and GIT1. {ECO:0000250,
CC ECO:0000269|PubMed:17442826, ECO:0000269|PubMed:18184567}.
CC -!- INTERACTION:
CC Q14012; P54253: ATXN1; NbExp=12; IntAct=EBI-6380130, EBI-930964;
CC Q14012; Q8IU85: CAMK1D; NbExp=2; IntAct=EBI-6380130, EBI-3911453;
CC Q14012; P42858: HTT; NbExp=3; IntAct=EBI-6380130, EBI-466029;
CC Q14012; Q14005-2: IL16; NbExp=3; IntAct=EBI-6380130, EBI-17178971;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Note=Predominantly cytoplasmic. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in cells of the zona
CC glomerulosa of the adrenal cortex. {ECO:0000269|PubMed:12193581,
CC ECO:0000269|PubMed:17056143}.
CC -!- DOMAIN: The autoinhibitory domain overlaps with the calmodulin binding
CC region and interacts in the inactive folded state with the catalytic
CC domain as a pseudosubstrate. {ECO:0000269|PubMed:23028635}.
CC -!- PTM: Phosphorylated by CaMKK1 and CaMKK2 on Thr-177.
CC {ECO:0000269|PubMed:11395482, ECO:0000269|PubMed:7641687,
CC ECO:0000269|PubMed:9662074}.
CC -!- PTM: Polybiquitinated by the E3 ubiquitin-protein ligase complex
CC SCF(FBXL12), leading to proteasomal degradation.
CC {ECO:0000269|PubMed:23707388}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. CaMK subfamily. {ECO:0000305}.
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DR EMBL; L41816; AAA99458.1; -; mRNA.
DR EMBL; BC106754; AAI06755.1; -; mRNA.
DR EMBL; BC106755; AAI06756.1; -; mRNA.
DR CCDS; CCDS2582.1; -.
DR PIR; S57347; S57347.
DR RefSeq; NP_003647.1; NM_003656.4.
DR PDB; 4FG7; X-ray; 2.70 A; A=1-293.
DR PDB; 4FG8; X-ray; 2.20 A; A/B=1-315.
DR PDB; 4FG9; X-ray; 2.40 A; A/B=1-320.
DR PDB; 4FGB; X-ray; 2.60 A; A=1-320.
DR PDBsum; 4FG7; -.
DR PDBsum; 4FG8; -.
DR PDBsum; 4FG9; -.
DR PDBsum; 4FGB; -.
DR AlphaFoldDB; Q14012; -.
DR BMRB; Q14012; -.
DR SMR; Q14012; -.
DR BioGRID; 114106; 57.
DR DIP; DIP-41906N; -.
DR IntAct; Q14012; 45.
DR STRING; 9606.ENSP00000256460; -.
DR BindingDB; Q14012; -.
DR ChEMBL; CHEMBL2493; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q14012; -.
DR iPTMnet; Q14012; -.
DR PhosphoSitePlus; Q14012; -.
DR BioMuta; CAMK1; -.
DR DMDM; 3122301; -.
DR EPD; Q14012; -.
DR jPOST; Q14012; -.
DR MassIVE; Q14012; -.
DR MaxQB; Q14012; -.
DR PaxDb; Q14012; -.
DR PeptideAtlas; Q14012; -.
DR PRIDE; Q14012; -.
DR ProteomicsDB; 59795; -.
DR TopDownProteomics; Q14012; -.
DR Antibodypedia; 10278; 333 antibodies from 33 providers.
DR DNASU; 8536; -.
DR Ensembl; ENST00000256460.8; ENSP00000256460.3; ENSG00000134072.11.
DR GeneID; 8536; -.
DR KEGG; hsa:8536; -.
DR MANE-Select; ENST00000256460.8; ENSP00000256460.3; NM_003656.5; NP_003647.1.
DR UCSC; uc003bst.4; human.
DR CTD; 8536; -.
DR DisGeNET; 8536; -.
DR GeneCards; CAMK1; -.
DR HGNC; HGNC:1459; CAMK1.
DR HPA; ENSG00000134072; Tissue enhanced (adrenal).
DR MIM; 604998; gene.
DR neXtProt; NX_Q14012; -.
DR OpenTargets; ENSG00000134072; -.
DR PharmGKB; PA26048; -.
DR VEuPathDB; HostDB:ENSG00000134072; -.
DR eggNOG; KOG0032; Eukaryota.
DR GeneTree; ENSGT00940000156378; -.
DR HOGENOM; CLU_000288_63_0_1; -.
DR InParanoid; Q14012; -.
DR OMA; RPKVQPC; -.
DR OrthoDB; 330091at2759; -.
DR PhylomeDB; Q14012; -.
DR TreeFam; TF314166; -.
DR BRENDA; 2.7.11.17; 2681.
DR PathwayCommons; Q14012; -.
DR Reactome; R-HSA-9617324; Negative regulation of NMDA receptor-mediated neuronal transmission.
DR Reactome; R-HSA-9619229; Activation of RAC1 downstream of NMDARs.
DR SignaLink; Q14012; -.
DR SIGNOR; Q14012; -.
DR BioGRID-ORCS; 8536; 13 hits in 1112 CRISPR screens.
DR ChiTaRS; CAMK1; human.
DR GeneWiki; CAMK1; -.
DR GenomeRNAi; 8536; -.
DR Pharos; Q14012; Tchem.
DR PRO; PR:Q14012; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q14012; protein.
DR Bgee; ENSG00000134072; Expressed in right adrenal gland cortex and 129 other tissues.
DR ExpressionAtlas; Q14012; baseline and differential.
DR Genevisible; Q14012; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005516; F:calmodulin binding; IBA:GO_Central.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0032091; P:negative regulation of protein binding; IDA:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0006913; P:nucleocytoplasmic transport; IEA:Ensembl.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0060999; P:positive regulation of dendritic spine development; IMP:UniProtKB.
DR GO; GO:0051149; P:positive regulation of muscle cell differentiation; IMP:BHF-UCL.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IDA:UniProtKB.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IMP:UniProtKB.
DR GO; GO:1901985; P:positive regulation of protein acetylation; IMP:UniProtKB.
DR GO; GO:0046827; P:positive regulation of protein export from nucleus; IDA:UniProtKB.
DR GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0051835; P:positive regulation of synapse structural plasticity; IMP:UniProtKB.
DR GO; GO:0060143; P:positive regulation of syncytium formation by plasma membrane fusion; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0051147; P:regulation of muscle cell differentiation; IDA:UniProtKB.
DR GO; GO:0043393; P:regulation of protein binding; IDA:UniProtKB.
DR GO; GO:0032880; P:regulation of protein localization; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Allosteric enzyme; ATP-binding; Calmodulin-binding;
KW Cell cycle; Cytoplasm; Developmental protein; Differentiation;
KW Direct protein sequencing; Isopeptide bond; Kinase; Neurogenesis;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT CHAIN 1..370
FT /note="Calcium/calmodulin-dependent protein kinase type 1"
FT /id="PRO_0000086076"
FT DOMAIN 20..276
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 276..316
FT /note="Autoinhibitory domain"
FT REGION 296..317
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250"
FT MOTIF 315..321
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT ACT_SITE 141
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 BINDING 49
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT MOD_RES 177
FT /note="Phosphothreonine; by CaMKK1 and CaMKK2"
FT /evidence="ECO:0000269|PubMed:7641687"
FT MOD_RES 363
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT CROSSLNK 59
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000305|PubMed:23707388"
FT VARIANT 217
FT /note="P -> S (in a metastatic melanoma sample; somatic
FT mutation; dbSNP:rs907102077)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040596"
FT VARIANT 361
FT /note="E -> K (in dbSNP:rs56033923)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040597"
FT MUTAGEN 49
FT /note="K->A: Catalytically inactive form; prevents CDK4
FT activation."
FT /evidence="ECO:0000269|PubMed:14754892,
FT ECO:0000269|PubMed:7641687"
FT MUTAGEN 177
FT /note="T->A: Loss of activation by CaMKK1."
FT /evidence="ECO:0000269|PubMed:7641687"
FT MUTAGEN 177
FT /note="T->D: Partial activation in absence of CaMKK1."
FT /evidence="ECO:0000269|PubMed:7641687"
FT HELIX 16..18
FT /evidence="ECO:0007829|PDB:4FG8"
FT STRAND 20..29
FT /evidence="ECO:0007829|PDB:4FG8"
FT STRAND 32..39
FT /evidence="ECO:0007829|PDB:4FG8"
FT TURN 40..42
FT /evidence="ECO:0007829|PDB:4FG8"
FT STRAND 45..52
FT /evidence="ECO:0007829|PDB:4FG8"
FT HELIX 66..70
FT /evidence="ECO:0007829|PDB:4FG8"
FT STRAND 81..86
FT /evidence="ECO:0007829|PDB:4FG8"
FT STRAND 88..95
FT /evidence="ECO:0007829|PDB:4FG8"
FT STRAND 100..102
FT /evidence="ECO:0007829|PDB:4FG9"
FT HELIX 103..109
FT /evidence="ECO:0007829|PDB:4FG8"
FT HELIX 115..134
FT /evidence="ECO:0007829|PDB:4FG8"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:4FG8"
FT STRAND 147..152
FT /evidence="ECO:0007829|PDB:4FG8"
FT STRAND 158..160
FT /evidence="ECO:0007829|PDB:4FG8"
FT HELIX 166..168
FT /evidence="ECO:0007829|PDB:4FGB"
FT HELIX 173..178
FT /evidence="ECO:0007829|PDB:4FG8"
FT TURN 182..184
FT /evidence="ECO:0007829|PDB:4FG8"
FT HELIX 187..190
FT /evidence="ECO:0007829|PDB:4FG8"
FT HELIX 198..213
FT /evidence="ECO:0007829|PDB:4FG8"
FT HELIX 223..232
FT /evidence="ECO:0007829|PDB:4FG8"
FT TURN 239..244
FT /evidence="ECO:0007829|PDB:4FG8"
FT HELIX 247..256
FT /evidence="ECO:0007829|PDB:4FG8"
FT TURN 261..263
FT /evidence="ECO:0007829|PDB:4FG8"
FT HELIX 267..272
FT /evidence="ECO:0007829|PDB:4FG8"
FT HELIX 274..277
FT /evidence="ECO:0007829|PDB:4FG8"
FT HELIX 287..297
FT /evidence="ECO:0007829|PDB:4FG8"
FT HELIX 301..311
FT /evidence="ECO:0007829|PDB:4FG9"
SQ SEQUENCE 370 AA; 41337 MW; 57FA20ECE00FA76C CRC64;
MLGAVEGPRW KQAEDIRDIY DFRDVLGTGA FSEVILAEDK RTQKLVAIKC IAKEALEGKE
GSMENEIAVL HKIKHPNIVA LDDIYESGGH LYLIMQLVSG GELFDRIVEK GFYTERDASR
LIFQVLDAVK YLHDLGIVHR DLKPENLLYY SLDEDSKIMI SDFGLSKMED PGSVLSTACG
TPGYVAPEVL AQKPYSKAVD CWSIGVIAYI LLCGYPPFYD ENDAKLFEQI LKAEYEFDSP
YWDDISDSAK DFIRHLMEKD PEKRFTCEQA LQHPWIAGDT ALDKNIHQSV SEQIKKNFAK
SKWKQAFNAT AVVRHMRKLQ LGTSQEGQGQ TASHGELLTP VAGGPAAGCC CRDCCVEPGT
ELSPTLPHQL
