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

Gene ID: 83506, updated on 2-May-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
Ensembl: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 calmodulin binding activity and calmodulin-dependent protein kinase 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, Apr 2022]
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
  • 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. 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
  2. Molecular cloning of Ca2+/calmodulin-dependent protein kinase kinase beta. Kitani T, et al. J Biochem, 1997 Jul. PMID 9276695
  3. 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
  4. 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
  5. Analysis of Distinct Roles of CaMKK Isoforms Using STO-609-Resistant Mutants in Living Cells. Fujiwara Y, et al. Biochemistry, 2015 Jun 30. PMID 26050738

See all (21) 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 calmodulin binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables calmodulin-dependent protein kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables calmodulin-dependent protein kinase activity TAS
Traceable Author Statement
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 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 phosphorylation IBA
Inferred from Biological aspect of Ancestor
more info
  
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
    ENSRNOP00000085154.1, ENSRNOT00000117141.1
    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
    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
    Related
    ENSRNOP00000093619.1
    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
    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
    ENSRNOP00000001774.7
    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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