KCC1A_MOUSE
ID KCC1A_MOUSE Reviewed; 374 AA.
AC Q91YS8;
DT 10-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 170.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
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 [2]
RP FUNCTION IN ACTIVATION OF MAPK1/ERK2.
RX PubMed=15150258; DOI=10.1074/jbc.m401501200;
RA Schmitt J.M., Wayman G.A., Nozaki N., Soderling T.R.;
RT "Calcium activation of ERK mediated by calmodulin kinase I.";
RL J. Biol. Chem. 279:24064-24072(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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-673', 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. Is
CC required for proper activation of cyclin-D1/CDK4 complex during G1
CC progression in diploid fibroblasts. Plays a role in K(+) and ANG2-
CC mediated regulation of the aldosterone synthase (CYP11B2) to produce
CC aldosterone in the adrenal cortex. Phosphorylates EIF4G3/eIF4GII. In
CC vitro phosphorylates CREB1, ATF1, CFTR, MYL9 and SYN1/synapsin I (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:15150258}.
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 (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Monomer. Interacts with XPO1 (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q91YS8; P29351: Ptpn6; NbExp=3; IntAct=EBI-911352, EBI-2620699;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Note=Predominantly cytoplasmic. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
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:0000250}.
CC -!- PTM: Phosphorylated by CaMKK1 and CaMKK2 on Thr-177.
CC -!- PTM: Polybiquitinated by the E3 ubiquitin-protein ligase complex
CC SCF(FBXL12), leading to proteasomal degradation. {ECO:0000250}.
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; BC014825; AAH14825.1; -; mRNA.
DR CCDS; CCDS20415.1; -.
DR RefSeq; NP_598687.1; NM_133926.2.
DR AlphaFoldDB; Q91YS8; -.
DR BMRB; Q91YS8; -.
DR SMR; Q91YS8; -.
DR BioGRID; 206419; 19.
DR DIP; DIP-37754N; -.
DR IntAct; Q91YS8; 2.
DR STRING; 10090.ENSMUSP00000032409; -.
DR iPTMnet; Q91YS8; -.
DR PhosphoSitePlus; Q91YS8; -.
DR jPOST; Q91YS8; -.
DR MaxQB; Q91YS8; -.
DR PaxDb; Q91YS8; -.
DR PRIDE; Q91YS8; -.
DR ProteomicsDB; 301757; -.
DR Antibodypedia; 10278; 333 antibodies from 33 providers.
DR DNASU; 52163; -.
DR Ensembl; ENSMUST00000032409; ENSMUSP00000032409; ENSMUSG00000030272.
DR GeneID; 52163; -.
DR KEGG; mmu:52163; -.
DR UCSC; uc009dfk.1; mouse.
DR CTD; 8536; -.
DR MGI; MGI:1098535; Camk1.
DR VEuPathDB; HostDB:ENSMUSG00000030272; -.
DR eggNOG; KOG0032; Eukaryota.
DR GeneTree; ENSGT00940000156378; -.
DR InParanoid; Q91YS8; -.
DR OMA; RPKVQPC; -.
DR OrthoDB; 330091at2759; -.
DR PhylomeDB; Q91YS8; -.
DR TreeFam; TF314166; -.
DR Reactome; R-MMU-9619229; Activation of RAC1 downstream of NMDARs.
DR BioGRID-ORCS; 52163; 4 hits in 76 CRISPR screens.
DR ChiTaRS; Camk1; mouse.
DR PRO; PR:Q91YS8; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q91YS8; protein.
DR Bgee; ENSMUSG00000030272; Expressed in superior frontal gyrus and 249 other tissues.
DR ExpressionAtlas; Q91YS8; baseline and differential.
DR Genevisible; Q91YS8; MM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0014069; C:postsynaptic density; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0006913; P:nucleocytoplasmic transport; IDA:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0060999; P:positive regulation of dendritic spine development; ISS:UniProtKB.
DR GO; GO:0051149; P:positive regulation of muscle cell differentiation; ISO:MGI.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:1901985; P:positive regulation of protein acetylation; ISO:MGI.
DR GO; GO:0046827; P:positive regulation of protein export from nucleus; IDA:MGI.
DR GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0051835; P:positive regulation of synapse structural plasticity; ISS:UniProtKB.
DR GO; GO:0060143; P:positive regulation of syncytium formation by plasma membrane fusion; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
DR GO; GO:0051147; P:regulation of muscle cell differentiation; ISS:UniProtKB.
DR GO; GO:0043393; P:regulation of protein binding; ISS:UniProtKB.
DR GO; GO:0032880; P:regulation of protein localization; ISS:UniProtKB.
DR GO; GO:0050807; P:regulation of synapse organization; ISO:MGI.
DR GO; GO:0007165; P:signal transduction; IDA:MGI.
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 Allosteric enzyme; ATP-binding; Calmodulin-binding; Cell cycle; Cytoplasm;
KW Developmental protein; Differentiation; Isopeptide bond; Kinase;
KW Neurogenesis; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Ubl conjugation.
FT CHAIN 1..374
FT /note="Calcium/calmodulin-dependent protein kinase type 1"
FT /id="PRO_0000086077"
FT DOMAIN 20..276
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 276..316
FT /note="Autoinhibitory domain"
FT /evidence="ECO:0000250"
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 /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 49
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 177
FT /note="Phosphothreonine; by CaMKK1 and CaMKK2"
FT /evidence="ECO:0000250|UniProtKB:Q14012"
FT CROSSLNK 59
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q14012"
SQ SEQUENCE 374 AA; 41624 MW; 37889CDA717D3AB2 CRC64;
MPGAVEGPRW KQAEDIRDIY DFRDVLGTGA FSEVILAEDK RTQKLVAIKC IAKKALEGKE
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 TGSHGELLTP TAGGPAAGCC CRDCCVEPGS
ELPPAPPPSS RAMD
