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FLASH GENE
Symbol CAMKK2 contributors: mct - updated : 08-03-2023
HGNC name calcium/calmodulin-dependent protein kinase kinase 2, beta
HGNC id 1470
DNA
TYPE functioning gene
STRUCTURE 60.62 kb     17 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Map cen - D12S366 - D12S86 - D12S349 - D12S321 - CAMKK2 - D12S342 - D12S340 - qter
Authors Gene Map (98)
RNA
TRANSCRIPTS type messenger
text several transcripts resulting from alternative polyadenylation and/or splicing of exons 14 and/or 16 (PMID: 11395482)
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
17 initiation site 5620 64.6 588 - 2008 18436530
also known as beta 1
17 polyA site 2981 58.8 533 - 2008 18436530
  • also known as beta 2
  • containing an alternate segment in the 3' coding region and differing in the 3' UTR compared to variant 1
  • 16 splicing 5577 59.5 541 - 2008 18436530
  • also known as beta 1del16
  • lacking a segment in the coding region which leads to a frameshift compared to variant 1
  • encoding the same protein than variant 7
  • 16 splicing 5491 59.8 545 - 2008 18436530
  • also known as beta 1del14
  • lacking an in-frame segment of the coding region compared to variant 1
  • 15 - 5448 54.7 498 - 2008 18436530
  • also known as beta 1del14del16
  • having multiple differences in the coding region compared to variant 1, one of which results in a translational frameshift
  • 16 splicing 4923 59.5 541 - 2008 18436530
  • differing in the 5' UTR and also lacking a segment in the coding region, which leads to a frameshift compared to variant 1
  • encoding the same protein than variant 2
  • 16 splicing 2852 54 490 - 2008 18436530
  • also known as beta 2del14
  • differing in the 3' UTR and having multiple coding region differences compared to variant 1
  • 16 - 4905 - 588 - 2008 18436530
    16 - 4523 - 556 - 2008 18436530
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineadrenal glandcortexzona glomerula highly Homo sapiens
     adrenal glandcortexzona fasciculata lowly Homo sapiens
    Lymphoid/Immunespleen    
     thymus    
    Nervousbrain   highly Homo sapiens
    Reproductivemale systemtestis   
     male systemprostate  highly
    Respiratoryrespiratory tractlarynx  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose    Homo sapiens
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    not specificadipocyte Homo sapiens
    cell lineage
    cell lines in human non small cell lung cancers
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a catalytic domain
  • a regulatory region composed of an autoinhibitory domain
  • a CaM binding domain
  • AAs 129-151 participate in the release of the autoinhibitory domain from its catalytic core, resulting in generation of autonomous activity
  • a flag-tagged protein
  • HOMOLOGY
    interspecies homolog to rattus Cmkkbeta
    Homologene
    FAMILY
  • protein kinase superfamily
  • Ser/Thr protein kinase family
  • Ca2+/calmodulin-dependent kinase (CaMK) family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • serine/threonine protein kinase, calcium/calmodulin dependent
  • acting upstream of AMP-activated protein kinase in mammalian cells
  • has potentially a male-specific function in hippocampal memory formation and we have identified male-restricted transcription occurring during hippocampal memory formation
  • regulates hypothalamic production of the orexigenic hormone NPY and contributes to the regulation of energy balance
  • with STK11, catalyzing activation of PRKAB1 by phosphorylation at Thr172
  • act as regulatory enzymes for downstream protein kinases in various Ca2+-dependent cellular processes
  • mediates potentially novel Ca2+-signaling pathway(s), which are independent of downstream protein kinases
  • isoform-specific function for CAMKK2 that regulates ubiquitin signaling at the centrosome and thereby orchestrates dendrite patterning, with important implications for neuronal connectivity in the brain
  • role for CAMKK2 in the restriction of granulocytic fate commitment and differentiation of myeloid progenitor cells
  • CAMKK2 and PRKAB1 function in a signaling pathway that participates in the regulation of adiposity
  • CaMKK2 plays a pivotal role in the calcium signaling cascade regulating adrenal aldosterone production
  • is a molecular rheostat for insulin action
  • plays a role in the calcium/calmodulin-dependent kinase cascade
  • role for CAMKK2 as a negative regulator of myoblast differentiation and proliferation
  • CAMKK2-mediated cell-type-specific differential regulation of mitochondrial function
  • CAMKK2 likely sustains cell proliferation in large part through effects on organelle integrity and membrane trafficking
  • involved in maintaining various physiological and cellular processes within the cell that regulate energy homeostasis and cell growth
  • role of CAMKK2 in Golgi-associated vesicle trafficking
  • regulates bone remodeling through its effects on osteoblasts and osteoclasts
  • novel CAMKK2-mediated paracrine mechanism of osteoclast regulation by female osteocytes
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • CAMKK2-PRKAB1 complex that can be specifically targeted by small molecule drugs to treat disease
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • activating CAMK1, CAMK4 when coexpressed in Jurkat T cells
  • PACSIN1 is a CAMKK substrate (first non-kinase substrate for CaMKK2)
  • CAMKK2 can form a complex with and activate PRKAB1
  • important AR-regulated gene in the context of Prostate cancer and as a critical regulator of macrophage activation
  • YWHAG directly interacts with the kinase domain of CAMKK2 and the region containing the inhibitory phosphorylation site Thr145 within the N-terminal extension
  • a novel role of GPR39 in enhancing tight junction assembly in intestinal epithelial cells (IECs) via phospholipase C-CAMKK2-AMPK pathways
  • GEMIN4 is a direct interactor, capable of binding CAMKK2 and COPI subunits
  • JMJD1C regulates CAMKK2-AMPK signaling to participate in cardiac hypertrophy
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in gastric cancer and leads to progression
    tumoral       gain of function
    in hepatocellular carcinoma (HCC) and negatively correlated with HCC patient survival
    Susceptibility to bipolar and psychiatric disorders
    Variant & Polymorphism SNP Single-Nucleotide Polymorphisms increasing the risk of bipolar and psychiatric disorders
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductive 
    novel therapeutic target for sex hormone-regulated cancers
    neuromuscularmyopathy 
    CAMKK2 could serve as a potential target to treat patients with muscle injury or myopathies
    cancerdigestivestomach
    CAMKK2 as a novel therapeutic target in gastric cancer
    cancerdigestiveliver
    CaMKK2 and CaMK4 may represent potential targets for hepatic cancer
    diabete  
    CaMKK2 may be an attractive therapeutic target for combatting comorbidities associated with perturbed insulin signaling
    ANIMAL & CELL MODELS
  • CaMKK2 null mice have increased adiposity and larger adipocytes than do wild-type mice, whereas energy balance is unchanged