(data stored in ACNUC26462 zone)

SWISSPROT: 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   11-DEC-2019, entry version 196.
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   -!- 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}.
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   SMR; Q14012; -.
DR   BioGrid; 114106; 37.
DR   DIP; DIP-41906N; -.
DR   IntAct; Q14012; 19.
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   DNASU; 8536; -.
DR   Ensembl; ENST00000256460; ENSP00000256460; ENSG00000134072.
DR   GeneID; 8536; -.
DR   KEGG; hsa:8536; -.
DR   UCSC; uc003bst.4; human.
DR   CTD; 8536; -.
DR   DisGeNET; 8536; -.
DR   EuPathDB; HostDB:ENSG00000134072.10; -.
DR   GeneCards; CAMK1; -.
DR   HGNC; HGNC:1459; CAMK1.
DR   HPA; CAB031904; -.
DR   HPA; HPA051409; -.
DR   MIM; 604998; gene.
DR   neXtProt; NX_Q14012; -.
DR   OpenTargets; ENSG00000134072; -.
DR   PharmGKB; PA26048; -.
DR   eggNOG; KOG0032; Eukaryota.
DR   eggNOG; ENOG410XRMJ; LUCA.
DR   GeneTree; ENSGT00940000156378; -.
DR   HOGENOM; HOG000233016; -.
DR   InParanoid; Q14012; -.
DR   KO; K08794; -.
DR   OMA; QVQPCRY; -.
DR   OrthoDB; 330091at2759; -.
DR   PhylomeDB; Q14012; -.
DR   TreeFam; TF314166; -.
DR   BRENDA; 2.7.11.17; 2681.
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   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 172 organ(s), highest expression level in left adrenal gland.
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:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR   GO; GO:0032091; P:negative regulation of protein binding; IDA:UniProtKB.
DR   GO; GO:0006913; P:nucleocytoplasmic transport; IEA:Ensembl.
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;
DR   PRODOM; Q14012.
DR   SWISS-2DPAGE; Q14012.
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; Polymorphism;
KW   Reference proteome; Serine/threonine-protein kinase; Transferase;
KW   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   NP_BIND         26..34
FT                   /note="ATP"
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         49
FT                   /note="ATP"
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:0000244|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:0000244|PDB:4FG8"
FT   STRAND          20..29
FT                   /evidence="ECO:0000244|PDB:4FG8"
FT   STRAND          32..39
FT                   /evidence="ECO:0000244|PDB:4FG8"
FT   TURN            40..42
FT                   /evidence="ECO:0000244|PDB:4FG8"
FT   STRAND          45..52
FT                   /evidence="ECO:0000244|PDB:4FG8"
FT   HELIX           66..70
FT                   /evidence="ECO:0000244|PDB:4FG8"
FT   STRAND          81..86
FT                   /evidence="ECO:0000244|PDB:4FG8"
FT   STRAND          88..95
FT                   /evidence="ECO:0000244|PDB:4FG8"
FT   STRAND          100..102
FT                   /evidence="ECO:0000244|PDB:4FG9"
FT   HELIX           103..109
FT                   /evidence="ECO:0000244|PDB:4FG8"
FT   HELIX           115..134
FT                   /evidence="ECO:0000244|PDB:4FG8"
FT   HELIX           144..146
FT                   /evidence="ECO:0000244|PDB:4FG8"
FT   STRAND          147..152
FT                   /evidence="ECO:0000244|PDB:4FG8"
FT   STRAND          158..160
FT                   /evidence="ECO:0000244|PDB:4FG8"
FT   HELIX           166..168
FT                   /evidence="ECO:0000244|PDB:4FGB"
FT   HELIX           173..178
FT                   /evidence="ECO:0000244|PDB:4FG8"
FT   TURN            182..184
FT                   /evidence="ECO:0000244|PDB:4FG8"
FT   HELIX           187..190
FT                   /evidence="ECO:0000244|PDB:4FG8"
FT   HELIX           198..213
FT                   /evidence="ECO:0000244|PDB:4FG8"
FT   HELIX           223..232
FT                   /evidence="ECO:0000244|PDB:4FG8"
FT   TURN            239..244
FT                   /evidence="ECO:0000244|PDB:4FG8"
FT   HELIX           247..256
FT                   /evidence="ECO:0000244|PDB:4FG8"
FT   TURN            261..263
FT                   /evidence="ECO:0000244|PDB:4FG8"
FT   HELIX           267..272
FT                   /evidence="ECO:0000244|PDB:4FG8"
FT   HELIX           274..277
FT                   /evidence="ECO:0000244|PDB:4FG8"
FT   HELIX           287..297
FT                   /evidence="ECO:0000244|PDB:4FG8"
FT   HELIX           301..311
FT                   /evidence="ECO:0000244|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
//

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