KKCC1_MOUSE
ID KKCC1_MOUSE Reviewed; 505 AA.
AC Q8VBY2; Q9R054;
DT 07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Calcium/calmodulin-dependent protein kinase kinase 1;
DE Short=CaM-KK 1;
DE Short=CaM-kinase kinase 1;
DE Short=CaMKK 1;
DE EC=2.7.11.17;
DE AltName: Full=CaM-kinase IV kinase;
DE AltName: Full=Calcium/calmodulin-dependent protein kinase kinase alpha;
DE Short=CaM-KK alpha;
DE Short=CaM-kinase kinase alpha;
DE Short=CaMKK alpha;
GN Name=Camkk1; Synonyms=Camkk;
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 [MRNA].
RX PubMed=10560916; DOI=10.1016/s0301-472x(99)00108-3;
RA Lawson N.D., Zain M., Zibello T., Picciotto M.R., Nairn A.C., Berliner N.;
RT "Modulation of a calcium/calmodulin-dependent protein kinase cascade by
RT retinoic acid during neutrophil maturation.";
RL Exp. Hematol. 27:1682-1690(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/SvJ;
RX PubMed=17015467; DOI=10.1128/mcb.01452-06;
RA Blaeser F., Sanders M.J., Truong N., Ko S., Wu L.J., Wozniak D.F.,
RA Fanselow M.S., Zhuo M., Chatila T.A.;
RT "Long-term memory deficits in Pavlovian fear conditioning in
RT Ca2+/calmodulin kinase kinase alpha-deficient mice.";
RL Mol. Cell. Biol. 26:9105-9115(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Salivary gland;
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 [4]
RP PROTEIN SEQUENCE OF 114-129 AND 440-451, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=12654522; DOI=10.1016/s0169-328x(02)00698-8;
RA Vinet J., Carra S., Blom J.M.C., Harvey M., Brunello N., Barden N.,
RA Tascedda F.;
RT "Cloning of mouse Ca2+/calmodulin-dependent protein kinase kinase beta
RT (CaMKKbeta) and characterization of CaMKKbeta and CaMKKalpha distribution
RT in the adult mouse brain.";
RL Brain Res. Mol. Brain Res. 111:216-221(2003).
RN [6]
RP FUNCTION IN PHOSPHORYLATION OF CAMK1G.
RX PubMed=12637513; DOI=10.1074/jbc.m300578200;
RA Takemoto-Kimura S., Terai H., Takamoto M., Ohmae S., Kikumura S., Segi E.,
RA Arakawa Y., Furuyashiki T., Narumiya S., Bito H.;
RT "Molecular cloning and characterization of CLICK-III/CaMKIgamma, a novel
RT membrane-anchored neuronal Ca2+/calmodulin-dependent protein kinase
RT (CaMK).";
RL J. Biol. Chem. 278:18597-18605(2003).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain cortex;
RX PubMed=17114649; DOI=10.1074/mcp.m600046-mcp200;
RA Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F.,
RA Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B.,
RA Panse C., Schlapbach R., Mansuy I.M.;
RT "Qualitative and quantitative analyses of protein phosphorylation in naive
RT and stimulated mouse synaptosomal preparations.";
RL Mol. Cell. Proteomics 6:283-293(2007).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-74; SER-100; SER-458 AND
RP SER-492, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Lung;
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).
RN [9]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-78, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- FUNCTION: Calcium/calmodulin-dependent protein kinase that belongs to a
CC proposed calcium-triggered signaling cascade involved in a number of
CC cellular processes. Phosphorylates CAMK1, CAMK1D, CAMK1G and CAMK4.
CC Involved in regulating cell apoptosis. Promotes cell survival by
CC phosphorylating AKT1/PKB that inhibits pro-apoptotic BAD/Bcl2-
CC antagonist of cell death. {ECO:0000269|PubMed:12637513}.
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 may relieve intrasteric autoinhibition. Partially inhibited
CC upon phosphorylation by PRCAKA/PKA (By similarity). May be regulated
CC through phosphorylation by CAMK1 and CAMK4. {ECO:0000250}.
CC -!- SUBUNIT: Interacts with CAMK4 and calmodulin. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Differentially expressed in
CC various brain regions. {ECO:0000269|PubMed:12654522}.
CC -!- DOMAIN: The autoinhibitory domain overlaps with the calmodulin binding
CC region and may be involved in intrasteric autoinhibition.
CC -!- DOMAIN: The RP domain (arginine/proline-rich) is involved in the
CC recognition of CAMKI and CAMK4 as substrates. {ECO:0000250}.
CC -!- PTM: Appears to be autophosphorylated in a Ca(2+)/calmodulin-dependent
CC manner. Phosphorylated at multiple sites by PRCAKA/PKA. Phosphorylation
CC of Ser-458 is blocked upon binding to Ca(2+)/calmodulin. In vitro,
CC phosphorylated by CAMK1 and CAMK4 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; AF117384; AAF08348.1; -; mRNA.
DR EMBL; AF461706; AAL67849.1; -; Genomic_DNA.
DR EMBL; AF461702; AAL67849.1; JOINED; Genomic_DNA.
DR EMBL; AF461703; AAL67849.1; JOINED; Genomic_DNA.
DR EMBL; AF461705; AAL67849.1; JOINED; Genomic_DNA.
DR EMBL; AF461704; AAL67849.1; JOINED; Genomic_DNA.
DR EMBL; BC017529; AAH17529.1; -; mRNA.
DR CCDS; CCDS24993.1; -.
DR RefSeq; NP_061371.2; NM_018883.2.
DR RefSeq; XP_006533823.1; XM_006533760.3.
DR RefSeq; XP_006533824.1; XM_006533761.3.
DR AlphaFoldDB; Q8VBY2; -.
DR SMR; Q8VBY2; -.
DR BioGRID; 207756; 6.
DR MINT; Q8VBY2; -.
DR STRING; 10090.ENSMUSP00000090613; -.
DR iPTMnet; Q8VBY2; -.
DR PhosphoSitePlus; Q8VBY2; -.
DR EPD; Q8VBY2; -.
DR jPOST; Q8VBY2; -.
DR MaxQB; Q8VBY2; -.
DR PaxDb; Q8VBY2; -.
DR PeptideAtlas; Q8VBY2; -.
DR PRIDE; Q8VBY2; -.
DR ProteomicsDB; 264760; -.
DR Antibodypedia; 3968; 216 antibodies from 33 providers.
DR DNASU; 55984; -.
DR Ensembl; ENSMUST00000092937; ENSMUSP00000090613; ENSMUSG00000020785.
DR GeneID; 55984; -.
DR KEGG; mmu:55984; -.
DR UCSC; uc007jzt.1; mouse.
DR CTD; 84254; -.
DR MGI; MGI:1891766; Camkk1.
DR VEuPathDB; HostDB:ENSMUSG00000020785; -.
DR eggNOG; KOG0585; Eukaryota.
DR GeneTree; ENSGT00940000154890; -.
DR InParanoid; Q8VBY2; -.
DR OMA; MACGPCM; -.
DR OrthoDB; 1044255at2759; -.
DR PhylomeDB; Q8VBY2; -.
DR TreeFam; TF313013; -.
DR Reactome; R-MMU-111932; CaMK IV-mediated phosphorylation of CREB.
DR Reactome; R-MMU-442729; CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde.
DR Reactome; R-MMU-9619229; Activation of RAC1 downstream of NMDARs.
DR BioGRID-ORCS; 55984; 1 hit in 74 CRISPR screens.
DR PRO; PR:Q8VBY2; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q8VBY2; protein.
DR Bgee; ENSMUSG00000020785; Expressed in dentate gyrus of hippocampal formation granule cell and 174 other tissues.
DR ExpressionAtlas; Q8VBY2; baseline and differential.
DR Genevisible; Q8VBY2; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005516; F:calmodulin binding; ISO:MGI.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; ISS:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0032147; P:activation of protein kinase activity; ISO:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
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 ATP-binding; Calmodulin-binding; Cytoplasm; Direct protein sequencing;
KW Kinase; Methylation; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..505
FT /note="Calcium/calmodulin-dependent protein kinase kinase
FT 1"
FT /id="PRO_0000086142"
FT DOMAIN 128..409
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 28..66
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 84..105
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 167..189
FT /note="RP domain"
FT REGION 435..440
FT /note="Autoinhibitory domain"
FT /evidence="ECO:0000250"
FT REGION 438..463
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250"
FT REGION 460..505
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 275
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 134..142
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 157
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 67
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N5S9"
FT MOD_RES 74
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 78
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 100
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 108
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P97756"
FT MOD_RES 458
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 475
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97756"
FT MOD_RES 492
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 99..100
FT /note="IS -> MC (in Ref. 1; AAF08348)"
FT /evidence="ECO:0000305"
FT CONFLICT 198..199
FT /note="QE -> HD (in Ref. 1; AAF08348)"
FT /evidence="ECO:0000305"
FT CONFLICT 382
FT /note="L -> S (in Ref. 1; AAF08348)"
FT /evidence="ECO:0000305"
FT CONFLICT 417
FT /note="L -> I (in Ref. 1; AAF08348)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 505 AA; 55838 MW; 179915A25628F9C4 CRC64;
MESGPAVCCQ DPRAELVDRV AAINVAHLEE ADEGPEPARN GVDPPPRARA ASVIPGSASR
PTPVRPSLSA RKFSLQERPA GSCLGAQVGP YSTGPASHIS PRSWRRPTIE SHRVAISDTE
DCVQLNQYKL QSEIGKGAYG VVRLAYNESE DRHYAMKVLS KKKLLKQYGF PRRPPPRGSQ
ATQGGPAKQL LPLERVYQEI AILKKLDHVN VVKLIEVLDD PAEDNLYLVF DLLRKGPVME
VPCDKPFPEE QARLYLRDII LGLEYLHCQK IVHRDIKPSN LLLGDDGHVK IADFGVSNQF
EGNDAQLSST AGTPAFMAPE AISDSGQSFS GKALDVWATG VTLYCFVYGK CPFIDDYILT
LHRKIKNEAV VFPEEPEVSE DLKDLILRML DKNPETRIGV SDIKLHPWVT KHGEEPLPSE
EEHCSVVEVT EEEVKNSVRL IPSWTTVILV KSMLRKRSFG NPFEPQARRE ERSMSAPGSL
LMKEGCGEGC KSPELPGVQE DEAAS
