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    Clk2 CDC-like kinase 2 [ Mus musculus (house mouse) ]

    Gene ID: 12748, updated on 21-Apr-2024

    Summary

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    Official Symbol
    Clk2provided by MGI
    Official Full Name
    CDC-like kinase 2provided by MGI
    Primary source
    MGI:MGI:1098669
    See related
    Ensembl:ENSMUSG00000068917 AllianceGenome:MGI:1098669
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Summary
    Enables protein serine/threonine kinase activity and protein tyrosine kinase activity. Involved in negative regulation of gluconeogenesis and protein autophosphorylation. Acts upstream of or within peptidyl-tyrosine phosphorylation and response to retinoic acid. Located in nucleus. Is expressed in several structures, including brain; genitourinary system; liver; retina; and thyroid gland. Orthologous to human CLK2 (CDC like kinase 2). [provided by Alliance of Genome Resources, Apr 2022]
    Expression
    Ubiquitous expression in limb E14.5 (RPKM 37.3), CNS E11.5 (RPKM 31.9) and 28 other tissues See more
    Orthologs
    human all
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    Genomic context

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    Location:
    3 F1; 3 39.01 cM
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 3 NC_000069.7 (89072102..89084394)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 3 NC_000069.6 (89164795..89177087)

    Chromosome 3 - NC_000069.7Genomic Context describing neighboring genes Neighboring gene predicted gene, 29704 Neighboring gene STARR-seq mESC enhancer starr_08224 Neighboring gene pyruvate kinase liver and red blood cell Neighboring gene hyperpolarization-activated, cyclic nucleotide-gated K+ 3 Neighboring gene predicted gene, 45927 Neighboring gene STARR-positive B cell enhancer ABC_E2079 Neighboring gene secretory carrier membrane protein 3 Neighboring gene predicted gene 16069 Neighboring gene endosomal transmembrane epsin interactor 3 Neighboring gene CapStarr-seq enhancer MGSCv37_chr3:88994426-88994609 Neighboring gene STARR-positive B cell enhancer ABC_E275 Neighboring gene predicted gene, 23269

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Mouse ENCODE transcriptome data
    • Description: RNA profiling data sets generated by the Mouse ENCODE project.
    • BioProject: PRJNA66167
    • Publication: PMID 25409824
    • Analysis date: n/a

    Bibliography

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    Related articles in PubMed

    1. Exercise decreases CLK2 in the liver of obese mice and prevents hepatic fat accumulation. Muñoz VR, et al. J Cell Biochem, 2018 Jul. PMID 29575149
    2. Adipose Tissue CLK2 Promotes Energy Expenditure during High-Fat Diet Intermittent Fasting. Hatting M, et al. Cell Metab, 2017 Feb 7. PMID 28089567, Free PMC Article
    3. CLK2 inhibition ameliorates autistic features associated with SHANK3 deficiency. Bidinosti M, et al. Science, 2016 Mar 11. PMID 26847545
    4. Clk2 and B56β mediate insulin-regulated assembly of the PP2A phosphatase holoenzyme complex on Akt. Rodgers JT, et al. Mol Cell, 2011 Feb 18. PMID 21329884, Free PMC Article
    5. Stress-responsive maturation of Clk1/4 pre-mRNAs promotes phosphorylation of SR splicing factor. Ninomiya K, et al. J Cell Biol, 2011 Oct 3. PMID 21949414, Free PMC Article

    See all (34) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. CLK2 in GABAergic neurons is critical in regulating energy balance and anxiety-like behavior in a gender-specific fashion.
      Title: CLK2 in GABAergic neurons is critical in regulating energy balance and anxiety-like behavior in a gender-specific fashion.
    2. High CLK2 expression is associated with obesity.
      Title: Exercise decreases CLK2 in the liver of obese mice and prevents hepatic fat accumulation.
    3. CLK2 is a regulatory component of diet-induced thermogenesis in brown adipose tissue.
      Title: Adipose Tissue CLK2 Promotes Energy Expenditure during High-Fat Diet Intermittent Fasting.
    4. Liver-specific Clk2 knockout mice fed a high-fat diet exhibit increased fasting levels of blood ketone bodies, reduced respiratory exchange ratio, and increased gene expression of fatty acid oxidation and ketogenic pathways.
      Title: Cdc2-like kinase 2 suppresses hepatic fatty acid oxidation and ketogenesis through disruption of the PGC-1α and MED1 complex.
    5. LAMMER/Cdc2-like kinase, represented by Doa and its mammalian homolog CLK2, is a critical and conserved component in the regulatory program of the mitosis-to-meiosis switch
      Title: The highly conserved LAMMER/CLK2 protein kinases prevent germ cell overproliferation in Drosophila.
    6. Cdc2-like kinase 2 (Clk2) directly phosphorylates the SR domain on PGC-1alpha, resulting in repression of gluconeogenic gene expression and hepatic glucose output.
      Title: Cdc2-like kinase 2 is an insulin-regulated suppressor of hepatic gluconeogenesis.
    Submit: New GeneRIF Correction

    Variation

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    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)
    • Gene trapped (1) 
    • Targeted (1)  1 citation
    • Endonuclease-mediated (3) 

    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

    Readthrough Gm45927

    Readthrough gene: Gm45927, Included gene: Scamp3

    Homology

    Gene Ontology Provided by MGI

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables identical protein binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables nucleotide binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein serine/threonine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein serine/threonine kinase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables protein serine/threonine/tyrosine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein tyrosine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein tyrosine kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables transferase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in negative regulation of gluconeogenesis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in peptidyl-tyrosine phosphorylation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    acts_upstream_of_or_within peptidyl-tyrosine phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within phosphorylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within protein autophosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein autophosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein phosphorylation ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in regulation of RNA splicing IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of RNA splicing ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in response to ionizing radiation ISO
    Inferred from Sequence Orthology
    more info
    		  
    acts_upstream_of_or_within response to organic substance IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within response to retinoic acid IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in nuclear body ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in nucleoplasm ISO
    Inferred from Sequence Orthology
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus ISO
    Inferred from Sequence Orthology
    more info
    		  

    General protein information

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    Preferred Names
    dual specificity protein kinase CLK2
    NP_001156904.1
    NP_031738.2

    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_001163432.2 → NP_001156904.1  dual specificity protein kinase CLK2 isoform 2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1.
      Source sequence(s)
      AC161600, BY021174, BY247622, BY738871, CD740936, CN538691, DT924403
      Consensus CDS
      CCDS50958.1
      UniProtKB/TrEMBL
      E9Q5Y1, F8WHX0
      Related
      ENSMUSP00000088445.6, ENSMUST00000090927.12
      Conserved Domains (2) summary
      smart00220
      Location:161 → 477
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd14215
      Location:148 → 477
      PKc_CLK2; Catalytic domain of the Dual-specificity protein kinase, CDC-like kinase 2

    2. NM_007712.4 → NP_031738.2  dual specificity protein kinase CLK2 isoform 1

      See identical proteins and their annotated locations for NP_031738.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AC161600, BY021174, BY247622, BY738871, CD740936, CN538691, DT924403
      Consensus CDS
      CCDS17491.1
      UniProtKB/Swiss-Prot
      E9Q721, O35491
      UniProtKB/TrEMBL
      E9Q5Y1
      Related
      ENSMUSP00000113390.3, ENSMUST00000121212.9
      Conserved Domains (2) summary
      smart00220
      Location:162 → 478
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd14215
      Location:149 → 478
      PKc_CLK2; Catalytic domain of the Dual-specificity protein kinase, CDC-like kinase 2

    RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000069.7 Reference GRCm39 C57BL/6J

      Range
      89072102..89084394
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O35491.2 GenPept UniProtKB/Swiss-Prot:O35491

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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