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    Camkk2 calcium/calmodulin-dependent protein kinase kinase 2 [ Rattus norvegicus (Norway rat) ]

    Gene ID: 83506, updated on 2-Nov-2024

    Summary

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    Official Symbol
    Camkk2provided by RGD
    Official Full Name
    calcium/calmodulin-dependent protein kinase kinase 2provided by RGD
    Primary source
    RGD:620092
    See related
    EnsemblRapid:ENSRNOG00000001309 AllianceGenome:RGD:620092
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Rattus norvegicus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
    Summary
    Enables calcium/calmodulin-dependent protein kinase activity and calmodulin binding activity. Involved in activation of protein kinase activity. Predicted to be located in cytosol. Orthologous to human CAMKK2 (calcium/calmodulin dependent protein kinase kinase 2). [provided by Alliance of Genome Resources, Nov 2024]
    Expression
    Biased expression in Brain (RPKM 186.1), Lung (RPKM 49.0) and 9 other tissues See more
    Orthologs
    human mouse all
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    Genomic context

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    See Camkk2 in Genome Data Viewer
    Location:
    12q16
    Exon count:
    20
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCr8 (GCF_036323735.1) 12 NC_086030.1 (39451828..39505719)
    RS_2023_06 previous assembly mRatBN7.2 (GCF_015227675.2) 12 NC_051347.1 (33791023..33845000)
    106 previous assembly Rnor_6.0 (GCF_000001895.5) 12 NC_005111.4 (39253409..39302601)

    Chromosome 12 - NC_086030.1Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC120095970 Neighboring gene anaphase-promoting complex subunit 5 Neighboring gene U4 spliceosomal RNA Neighboring gene large ribosomal subunit protein uL30-like Neighboring gene uncharacterized LOC120095972 Neighboring gene purinergic receptor P2X 4 Neighboring gene ribosomal protein L32, pseudogene 11 Neighboring gene purinergic receptor P2X 7

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
    • Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
    • BioProject: PRJNA238328
    • Publication: PMID 24510058
    • Analysis date: Mon Jun 6 17:44:12 2016

    Bibliography

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    Related articles in PubMed

    1. CaMKK2 alleviates myocardial ischemia/reperfusion injury by inhibiting oxidative stress and inflammation via the action on the AMPK-AKT-GSK-3β/Nrf2 signaling cascade. Li C, et al. Inflamm Res, 2023 Jul. PMID 37338678
    2. Molecular cloning of Ca2+/calmodulin-dependent protein kinase kinase beta. Kitani T, et al. J Biochem, 1997 Jul. PMID 9276695
    3. Generation of autonomous activity of Ca(2+)/calmodulin-dependent protein kinase kinase β by autophosphorylation. Tokumitsu H, et al. Biochemistry, 2011 Sep 27. PMID 21859090
    4. Store-operated calcium entry-activated autophagy protects EPC proliferation via the CAMKK2-MTOR pathway in ox-LDL exposure. Yang J, et al. Autophagy, 2017 Jan 2. PMID 27791458, Free PMC Article
    5. CAMKK2, Regulated by Promoter Methylation, is a Prognostic Marker in Diffuse Gliomas. Liu DM, et al. CNS Neurosci Ther, 2016 Jun. PMID 27012733, Free PMC Article

    See all (22) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. CaMKK2 alleviates myocardial ischemia/reperfusion injury by inhibiting oxidative stress and inflammation via the action on the AMPK-AKT-GSK-3beta/Nrf2 signaling cascade.
      Title: CaMKK2 alleviates myocardial ischemia/reperfusion injury by inhibiting oxidative stress and inflammation via the action on the AMPK-AKT-GSK-3β/Nrf2 signaling cascade.
    2. the CAMKK2-MTOR pathway has a role in store-operated calcium entry-activated autophagy protection of endothelial progenitor cell proliferation in ox-LDL exposure
      Title: Store-operated calcium entry-activated autophagy protects EPC proliferation via the CAMKK2-MTOR pathway in ox-LDL exposure.
    3. Site-directed mutagenesis analysis revealed that Leu(358) in CaMKKbeta/Ile(322) in CaMKKalpha confer, at least in part, a distinct recognition of AMPK but not of CaMKIalpha.
      Title: Differential AMP-activated Protein Kinase (AMPK) Recognition Mechanism of Ca2+/Calmodulin-dependent Protein Kinase Kinase Isoforms.
    4. CaMKKalpha and CaMKKbeta are capable of phosphorylating and activating CaMKIV in living cells.
      Title: Analysis of Distinct Roles of CaMKK Isoforms Using STO-609-Resistant Mutants in Living Cells.
    5. Arsenic induced ventricular hypertrophy occurs via MEF2A/CAMKK2/CALM3/TNNI3 signaling.
      Title: The novel regulations of MEF2A, CAMKK2, CALM3, and TNNI3 in ventricular hypertrophy induced by arsenic exposure in rats.
    6. Data show that protein kinase A (PKA) regulates the alternative splicing of Ca(2)/calmodulin-dependent protein kinase kinase 2 (CaMKK2) to produce variants that differentially modulate neuronal differentiation.
      Title: Differential effects of PKA-controlled CaMKK2 variants on neuronal differentiation.
    7. phosphorylation of CaMKKbeta regulates its half-life.
      Title: Ca2+/Calmodulin-dependent protein kinase kinase beta is regulated by multisite phosphorylation.
    8. in contrast to the alpha isoform, CaMKKbeta exhibited increased autonomous activity, which was caused, at least in part, by autophosphorylation at Thr(482), resulting in partial disruption of the autoinhibitory mechanism
      Title: Generation of autonomous activity of Ca(2+)/calmodulin-dependent protein kinase kinase β by autophosphorylation.
    9. This study demonistrated that isoform-specific function for CaMKIIbeta that regulates ubiquitin signaling at the centrosome and thereby orchestrates dendrite patterning, with important implications for neuronal connectivity in the brain.
      Title: A CaMKIIβ signaling pathway at the centrosome regulates dendrite patterning in the brain.
    10. Overexpression of CaMKKbeta in mammalian cells increases AMPK activity, whereas pharmacological inhibition of CaMKK, or downregulation of CaMKKbeta using RNA interference, almost completely abolishes AMPK activation
      Title: Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells.
    Submit: New GeneRIF Correction

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by RGD

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables calcium ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables calcium ion binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables calcium ion binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables calcium/calmodulin-dependent protein kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables calcium/calmodulin-dependent protein kinase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables calmodulin binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein kinase activator activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables protein kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein kinase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables protein serine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein serine/threonine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in CAMKK-AMPK signaling cascade IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in CAMKK-AMPK signaling cascade IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in CAMKK-AMPK signaling cascade ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in activation of protein kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of protein phosphorylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of protein phosphorylation ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in protein autophosphorylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein autophosphorylation ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in protein autophosphorylation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in protein phosphorylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein phosphorylation ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in protein phosphorylation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in protein phosphorylation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytosol IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cytosol ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in neuron projection IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    calcium/calmodulin-dependent protein kinase kinase 2
    Names
    Ca+/Calmodulin-dependent protein kinase kinase beta (CaM-kinase kinase beta)
    CaM-kinase kinase beta
    caM-KK 2
    caM-KK beta
    caM-kinase kinase 2
    caMKK 2
    caMKK beta
    calcium/calmodulin-dependent protein kinase 2 beta
    calcium/calmodulin-dependent protein kinase kinase 2, beta
    calcium/calmodulin-dependent protein kinase kinase beta
    NP_001382590.1
    NP_112628.2
    XP_038945738.1
    XP_038945739.1
    XP_038945740.1
    XP_038945741.1
    XP_038945742.1
    XP_038945743.1
    XP_038945744.1
    XP_038945745.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001395661.1 → NP_001382590.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform 2

      Status: VALIDATED

      Source sequence(s)
      JAXUCZ010000012
      Conserved Domains (1) summary
      cl21453
      Location:161 → 208
      PKc_like; Protein Kinases, catalytic domain

    2. NM_031338.3 → NP_112628.2  calcium/calmodulin-dependent protein kinase kinase 2 isoform 1

      Status: VALIDATED

      Source sequence(s)
      JAXUCZ010000012
      UniProtKB/Swiss-Prot
      O88831
      Related
      ENSRNOP00000093619.2, ENSRNOT00000109897.2
      Conserved Domains (1) summary
      cd14199
      Location:161 → 446
      STKc_CaMKK2; Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2

    RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCr8

    Genomic

    1. NC_086030.1 Reference GRCr8

      Range
      39451828..39505719
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_039089814.2 → XP_038945742.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X5

      UniProtKB/Swiss-Prot
      O88831
      Related
      ENSRNOP00000001774.8, ENSRNOT00000001774.8
      Conserved Domains (1) summary
      cd14199
      Location:161 → 446
      STKc_CaMKK2; Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2

    2. XM_039089816.2 → XP_038945744.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X7

      UniProtKB/Swiss-Prot
      O88831
      Conserved Domains (1) summary
      cl21453
      Location:161 → 441
      PKc_like; Protein Kinases, catalytic domain

    3. XM_039089812.2 → XP_038945740.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X3

      UniProtKB/Swiss-Prot
      O88831
      UniProtKB/TrEMBL
      A0A8I6GKR3
      Conserved Domains (1) summary
      cd14199
      Location:161 → 446
      STKc_CaMKK2; Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2

    4. XM_039089813.2 → XP_038945741.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X4

      UniProtKB/Swiss-Prot
      O88831
      UniProtKB/TrEMBL
      A0A8I5ZSP8
      Related
      ENSRNOP00000081396.1, ENSRNOT00000097411.2
      Conserved Domains (1) summary
      cd14199
      Location:161 → 446
      STKc_CaMKK2; Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2

    5. XM_039089811.2 → XP_038945739.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X2

      UniProtKB/Swiss-Prot
      O88831
      UniProtKB/TrEMBL
      F1LPT4
      Related
      ENSRNOP00000099222.1, ENSRNOT00000172213.1
      Conserved Domains (1) summary
      cl21453
      Location:161 → 441
      PKc_like; Protein Kinases, catalytic domain

    6. XM_039089815.2 → XP_038945743.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X6

      UniProtKB/Swiss-Prot
      O88831
      Conserved Domains (1) summary
      cl21453
      Location:161 → 441
      PKc_like; Protein Kinases, catalytic domain

    7. XM_039089810.2 → XP_038945738.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X1

      UniProtKB/Swiss-Prot
      O88831
      Conserved Domains (1) summary
      cd14199
      Location:161 → 446
      STKc_CaMKK2; Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2

    8. XM_039089817.2 → XP_038945745.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X8

      UniProtKB/TrEMBL
      A6J176
      Conserved Domains (1) summary
      cl21453
      Location:1 → 255
      PKc_like; Protein Kinases, catalytic domain
    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O88831.1 GenPept UniProtKB/Swiss-Prot:O88831

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