UniProtKB - Q8VBY2 (KKCC1_MOUSE)
Protein
Calcium/calmodulin-dependent protein kinase kinase 1
Gene
Camkk1
Organism
Mus musculus (Mouse)
Status
Functioni
Calcium/calmodulin-dependent protein kinase that belongs to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Phosphorylates CAMK1, CAMK1D, CAMK1G and CAMK4. Involved in regulating cell apoptosis. Promotes cell survival by phosphorylating AKT1/PKB that inhibits pro-apoptotic BAD/Bcl2-antagonist of cell death.1 Publication
Catalytic activityi
Activity regulationi
Activated by Ca2+/calmodulin. Binding of calmodulin may relieve intrasteric autoinhibition. Partially inhibited upon phosphorylation by PRCAKA/PKA (By similarity). May be regulated through phosphorylation by CAMK1 and CAMK4.By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 157 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 275 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 134 – 142 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- calmodulin binding Source: MGI
- calmodulin-dependent protein kinase activity Source: MGI
- protein serine/threonine kinase activity Source: GO_Central
GO - Biological processi
- activation of protein kinase activity Source: MGI
- intracellular signal transduction Source: GO_Central
- positive regulation of protein kinase activity Source: MGI
Keywordsi
Molecular function | Calmodulin-binding, Kinase, Serine/threonine-protein kinase, Transferase |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-MMU-111932, CaMK IV-mediated phosphorylation of CREB R-MMU-442729, CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde R-MMU-9619229, Activation of RAC1 downstream of NMDARs |
Names & Taxonomyi
Protein namesi | Recommended name: Calcium/calmodulin-dependent protein kinase kinase 1 (EC:2.7.11.17)Short name: CaM-KK 1 Short name: CaM-kinase kinase 1 Short name: CaMKK 1 Alternative name(s): CaM-kinase IV kinase Calcium/calmodulin-dependent protein kinase kinase alpha Short name: CaM-KK alpha Short name: CaM-kinase kinase alpha Short name: CaMKK alpha |
Gene namesi | Name:Camkk1 Synonyms:Camkk |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1891766, Camkk1 |
Subcellular locationi
Cytosol
- cytosol Source: Reactome
Nucleus
- nucleoplasm Source: Reactome
Other locations
- cytoplasm Source: GO_Central
Keywords - Cellular componenti
Cytoplasm, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086142 | 1 – 505 | Calcium/calmodulin-dependent protein kinase kinase 1Add BLAST | 505 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 67 | PhosphoserineBy similarity | 1 | |
Modified residuei | 74 | PhosphoserineCombined sources | 1 | |
Modified residuei | 78 | Asymmetric dimethylarginineCombined sources | 1 | |
Modified residuei | 100 | PhosphoserineCombined sources | 1 | |
Modified residuei | 108 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 458 | PhosphoserineCombined sources | 1 | |
Modified residuei | 475 | PhosphoserineBy similarity | 1 | |
Modified residuei | 492 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Appears to be autophosphorylated in a Ca2+/calmodulin-dependent manner. Phosphorylated at multiple sites by PRCAKA/PKA. Phosphorylation of Ser-458 is blocked upon binding to Ca2+/calmodulin. In vitro, phosphorylated by CAMK1 and CAMK4 (By similarity).By similarity
Keywords - PTMi
Methylation, PhosphoproteinProteomic databases
EPDi | Q8VBY2 |
jPOSTi | Q8VBY2 |
MaxQBi | Q8VBY2 |
PaxDbi | Q8VBY2 |
PeptideAtlasi | Q8VBY2 |
PRIDEi | Q8VBY2 |
PTM databases
iPTMneti | Q8VBY2 |
PhosphoSitePlusi | Q8VBY2 |
Expressioni
Tissue specificityi
Widely expressed. Differentially expressed in various brain regions.1 Publication
Gene expression databases
Bgeei | ENSMUSG00000020785, Expressed in dentate gyrus of hippocampal formation granule cell and 223 other tissues |
ExpressionAtlasi | Q8VBY2, baseline and differential |
Genevisiblei | Q8VBY2, MM |
Interactioni
Subunit structurei
Interacts with CAMK4 and calmodulin.
By similarityGO - Molecular functioni
- calmodulin binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 207756, 6 interactors |
MINTi | Q8VBY2 |
STRINGi | 10090.ENSMUSP00000090613 |
Miscellaneous databases
RNActi | Q8VBY2, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 128 – 409 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 282 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 167 – 189 | RP domainAdd BLAST | 23 | |
Regioni | 435 – 440 | Autoinhibitory domainBy similarity | 6 | |
Regioni | 438 – 463 | Calmodulin-bindingBy similarityAdd BLAST | 26 |
Domaini
The autoinhibitory domain overlaps with the calmodulin binding region and may be involved in intrasteric autoinhibition.
The RP domain (arginine/proline-rich) is involved in the recognition of CAMKI and CAMK4 as substrates.By similarity
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0585, Eukaryota |
GeneTreei | ENSGT00940000154890 |
InParanoidi | Q8VBY2 |
OrthoDBi | 1044255at2759 |
PhylomeDBi | Q8VBY2 |
TreeFami | TF313013 |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
Q8VBY2-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MESGPAVCCQ DPRAELVDRV AAINVAHLEE ADEGPEPARN GVDPPPRARA
60 70 80 90 100
ASVIPGSASR PTPVRPSLSA RKFSLQERPA GSCLGAQVGP YSTGPASHIS
110 120 130 140 150
PRSWRRPTIE SHRVAISDTE DCVQLNQYKL QSEIGKGAYG VVRLAYNESE
160 170 180 190 200
DRHYAMKVLS KKKLLKQYGF PRRPPPRGSQ ATQGGPAKQL LPLERVYQEI
210 220 230 240 250
AILKKLDHVN VVKLIEVLDD PAEDNLYLVF DLLRKGPVME VPCDKPFPEE
260 270 280 290 300
QARLYLRDII LGLEYLHCQK IVHRDIKPSN LLLGDDGHVK IADFGVSNQF
310 320 330 340 350
EGNDAQLSST AGTPAFMAPE AISDSGQSFS GKALDVWATG VTLYCFVYGK
360 370 380 390 400
CPFIDDYILT LHRKIKNEAV VFPEEPEVSE DLKDLILRML DKNPETRIGV
410 420 430 440 450
SDIKLHPWVT KHGEEPLPSE EEHCSVVEVT EEEVKNSVRL IPSWTTVILV
460 470 480 490 500
KSMLRKRSFG NPFEPQARRE ERSMSAPGSL LMKEGCGEGC KSPELPGVQE
DEAAS
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketB1AUD3 | B1AUD3_MOUSE | Calcium/calmodulin-dependent protei... | Camkk1 | 342 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 99 – 100 | IS → MC in AAF08348 (PubMed:10560916).Curated | 2 | |
Sequence conflicti | 198 – 199 | QE → HD in AAF08348 (PubMed:10560916).Curated | 2 | |
Sequence conflicti | 382 | L → S in AAF08348 (PubMed:10560916).Curated | 1 | |
Sequence conflicti | 417 | L → I in AAF08348 (PubMed:10560916).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF117384 mRNA Translation: AAF08348.1 AF461706 , AF461702, AF461703, AF461705, AF461704 Genomic DNA Translation: AAL67849.1 BC017529 mRNA Translation: AAH17529.1 |
CCDSi | CCDS24993.1 |
RefSeqi | NP_061371.2, NM_018883.2 XP_006533823.1, XM_006533760.3 XP_006533824.1, XM_006533761.3 |
Genome annotation databases
Ensembli | ENSMUST00000092937; ENSMUSP00000090613; ENSMUSG00000020785 |
GeneIDi | 55984 |
KEGGi | mmu:55984 |
UCSCi | uc007jzt.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF117384 mRNA Translation: AAF08348.1 AF461706 , AF461702, AF461703, AF461705, AF461704 Genomic DNA Translation: AAL67849.1 BC017529 mRNA Translation: AAH17529.1 |
CCDSi | CCDS24993.1 |
RefSeqi | NP_061371.2, NM_018883.2 XP_006533823.1, XM_006533760.3 XP_006533824.1, XM_006533761.3 |
3D structure databases
SMRi | Q8VBY2 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 207756, 6 interactors |
MINTi | Q8VBY2 |
STRINGi | 10090.ENSMUSP00000090613 |
PTM databases
iPTMneti | Q8VBY2 |
PhosphoSitePlusi | Q8VBY2 |
Proteomic databases
EPDi | Q8VBY2 |
jPOSTi | Q8VBY2 |
MaxQBi | Q8VBY2 |
PaxDbi | Q8VBY2 |
PeptideAtlasi | Q8VBY2 |
PRIDEi | Q8VBY2 |
Protocols and materials databases
Antibodypediai | 3968, 201 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000092937; ENSMUSP00000090613; ENSMUSG00000020785 |
GeneIDi | 55984 |
KEGGi | mmu:55984 |
UCSCi | uc007jzt.1, mouse |
Organism-specific databases
CTDi | 84254 |
MGIi | MGI:1891766, Camkk1 |
Phylogenomic databases
eggNOGi | KOG0585, Eukaryota |
GeneTreei | ENSGT00940000154890 |
InParanoidi | Q8VBY2 |
OrthoDBi | 1044255at2759 |
PhylomeDBi | Q8VBY2 |
TreeFami | TF313013 |
Enzyme and pathway databases
Reactomei | R-MMU-111932, CaMK IV-mediated phosphorylation of CREB R-MMU-442729, CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde R-MMU-9619229, Activation of RAC1 downstream of NMDARs |
Miscellaneous databases
BioGRID-ORCSi | 55984, 1 hit in 17 CRISPR screens |
PROi | PR:Q8VBY2 |
RNActi | Q8VBY2, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000020785, Expressed in dentate gyrus of hippocampal formation granule cell and 223 other tissues |
ExpressionAtlasi | Q8VBY2, baseline and differential |
Genevisiblei | Q8VBY2, MM |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | KKCC1_MOUSE | |
Accessioni | Q8VBY2Primary (citable) accession number: Q8VBY2 Secondary accession number(s): Q9R054 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 7, 2004 |
Last sequence update: | March 1, 2002 | |
Last modified: | December 2, 2020 | |
This is version 154 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Human and mouse protein kinases
Human and mouse protein kinases: classification and index