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    CLK2 CDC like kinase 2 [ Homo sapiens (human) ]

    Gene ID: 1196, updated on 2-Nov-2024

    Summary

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    Official Symbol
    CLK2provided by HGNC
    Official Full Name
    CDC like kinase 2provided by HGNC
    Primary source
    HGNC:HGNC:2069
    See related
    Ensembl:ENSG00000176444 MIM:602989; AllianceGenome:HGNC:2069
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Summary
    This gene encodes a dual specificity protein kinase that phosphorylates serine/threonine and tyrosine-containing substrates. Activity of this protein regulates serine- and arginine-rich (SR) proteins of the spliceosomal complex, thereby influencing alternative transcript splicing. Chromosomal translocations have been characterized between this locus and the PAFAH1B3 (platelet-activating factor acetylhydrolase 1b, catalytic subunit 3 (29kDa)) gene on chromosome 19, resulting in the production of a fusion protein. Note that this gene is distinct from the TELO2 gene (GeneID:9894), which shares the CLK2 alias, but encodes a protein that is involved in telomere length regulation. There is a pseudogene for this gene on chromosome 7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]
    Expression
    Ubiquitous expression in spleen (RPKM 18.0), lymph node (RPKM 16.4) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See CLK2 in Genome Data Viewer
    Location:
    1q22
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (155262868..155273504, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (154401428..154412064, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (155232659..155243295, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:155219706-155220308 Neighboring gene endosomal transmembrane epsin interactor 3 Neighboring gene secretory carrier membrane protein 3 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:155243888-155244388 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:155254443-155254943 Neighboring gene hyperpolarization activated cyclic nucleotide gated potassium channel 3 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:155263898-155264430 Neighboring gene pyruvate kinase L/R Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:155275791-155276290 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1812 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1813 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1814 Neighboring gene farnesyl diphosphate synthase Neighboring gene RUSC1 antisense RNA 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Cdc2-like kinase 2 is a key regulator of the cell cycle via FOXO3a/p27 in glioblastoma. Park SY, et al. Oncotarget, 2016 May 3. PMID 27050366, Free PMC Article
    2. CLK2 Is an Oncogenic Kinase and Splicing Regulator in Breast Cancer. Yoshida T, et al. Cancer Res, 2015 Apr 1. PMID 25670169
    3. Homozygosity mapping of a gene responsible for gelatinous drop-like corneal dystrophy to chromosome 1p. Tsujikawa M, et al. Am J Hum Genet, 1998 Oct. PMID 9758629, Free PMC Article
    4. CDC Like Kinase 2 plays an oncogenic role in colorectal cancer via modulating the Wnt/β-catenin signaling. Zhou HB, et al. Neoplasma, 2022 May. PMID 35293765
    5. CLK2 promotes occurrence and development of non-small cell lung cancer. Liu B, et al. J BUON, 2021 Jan-Feb. PMID 33721432

    See all (71) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. CDC Like Kinase 2 plays an oncogenic role in colorectal cancer via modulating the Wnt/beta-catenin signaling.
      Title: CDC Like Kinase 2 plays an oncogenic role in colorectal cancer via modulating the Wnt/β-catenin signaling.
    2. CLK2 promotes occurrence and development of non-small cell lung cancer.
      Title: CLK2 promotes occurrence and development of non-small cell lung cancer.
    3. These findings suggest that CLK2 plays a critical role in controlling the cell cycle and survival of glioblastoma
      Title: Cdc2-like kinase 2 is a key regulator of the cell cycle via FOXO3a/p27 in glioblastoma.
    4. Clk1, Clk2 and Clk4 prevent chromatin breakage by regulating the Aurora B-dependent abscission checkpoint.
      Title: Clks 1, 2 and 4 prevent chromatin breakage by regulating the Aurora B-dependent abscission checkpoint.
    5. Loss of CLK2 in luminal breast cancer cells leads to the upregulation of epithelial-to-mesenchymal transition (EMT)-related genes and a switch to mesenchymal splice variants of several genes.
      Title: CLK2 Is an Oncogenic Kinase and Splicing Regulator in Breast Cancer.
    6. 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.
    7. CLK1 Increases While CLK2 Decreases HIV-1 Gene Expression.
      Title: Differential effect of CLK SR Kinases on HIV-1 gene expression: potential novel targets for therapy.
    8. AKT activation controls cell survival to ionizing radiation by phosphorylating CLK2, revealing an important regulatory mechanism required for promoting cell survival.
      Title: Phosphorylation of CLK2 at serine 34 and threonine 127 by AKT controls cell survival after ionizing radiation.
    9. Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing of tissue factor in human endothelial cells.
      Title: Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing of tissue factor in human endothelial cells.
    Submit: New GeneRIF Correction

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    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

    Clone Names

    • MGC61500

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    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
    		  
    enables protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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
    		  
    Process Evidence Code Pubs
    involved_in negative regulation of gluconeogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in protein autophosphorylation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of RNA splicing IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of RNA splicing IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to ionizing radiation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in nuclear body IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nuclear speck IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    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 

    General protein information

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    Preferred Names
    dual specificity protein kinase CLK2
    Names
    CLK kinase
    NP_001281267.1
    NP_001281268.1
    NP_001350633.1
    NP_003984.2
    XP_011507445.1
    XP_047300365.1
    XP_047300370.1
    XP_047300373.1
    XP_047300378.1
    XP_054185445.1
    XP_054185446.1
    XP_054185447.1
    XP_054185448.1
    XP_054185449.1
    XP_054190193.1
    XP_054190194.1
    XP_054190195.1
    XP_054190196.1
    XP_054190197.1

    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_001294338.2 → NP_001281267.1  dual specificity protein kinase CLK2 isoform 1

      See identical proteins and their annotated locations for NP_001281267.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AL713999, BC014067, BC053603, HY049688
      Consensus CDS
      CCDS72939.1
      UniProtKB/Swiss-Prot
      B1AVS9, B5MBX6, P49760, Q96CQ0
      UniProtKB/TrEMBL
      A8K7I0
      Related
      ENSP00000357345.4, ENST00000368361.9
      Conserved Domains (1) summary
      cd14215
      Location:150 → 479
      PKc_CLK2; Catalytic domain of the Dual-specificity protein kinase, CDC-like kinase 2

    2. NM_001294339.2 → NP_001281268.1  dual specificity protein kinase CLK2 isoform 3

      See identical proteins and their annotated locations for NP_001281268.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an exon in the 5' region and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (3) has a shorter N-terminus than isoform 1.
      Source sequence(s)
      AU136826, BC014067, HY049688, L29216
      UniProtKB/TrEMBL
      B7Z8N6, E7EQU3, Q9BRG8
      Related
      ENST00000476983.5
      Conserved Domains (1) summary
      cl21453
      Location:1 → 251
      PKc_like; Protein Kinases, catalytic domain

    3. NM_001363704.2 → NP_001350633.1  dual specificity protein kinase CLK2 isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) uses multiple alternate in-frame splice sites, compared to variant 1. The encoded isoform (4) is shorter than isoform 1.
      Source sequence(s)
      AL713999
      Consensus CDS
      CCDS86020.1
      UniProtKB/TrEMBL
      B1AVT0
      Related
      ENSP00000347759.4, ENST00000355560.4
      Conserved Domains (1) summary
      cd14215
      Location:148 → 477
      PKc_CLK2; Catalytic domain of the Dual-specificity protein kinase, CDC-like kinase 2

    4. NM_003993.4 → NP_003984.2  dual specificity protein kinase CLK2 isoform 2

      See identical proteins and their annotated locations for NP_003984.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
      Source sequence(s)
      AU136826, BC014067, HY049688
      Consensus CDS
      CCDS1107.1
      UniProtKB/Swiss-Prot
      P49760
      Related
      ENSP00000354856.5, ENST00000361168.9
      Conserved Domains (1) summary
      cd14215
      Location:149 → 478
      PKc_CLK2; Catalytic domain of the Dual-specificity protein kinase, CDC-like kinase 2

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      155262868..155273504 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011509143.2 → XP_011507445.1  dual specificity protein kinase CLK2 isoform X1

      See identical proteins and their annotated locations for XP_011507445.1

      Conserved Domains (1) summary
      cd14215
      Location:149 → 478
      PKc_CLK2; Catalytic domain of the Dual-specificity protein kinase, CDC-like kinase 2

    2. XM_047444422.1 → XP_047300378.1  dual specificity protein kinase CLK2 isoform X5

    3. XM_047444414.1 → XP_047300370.1  dual specificity protein kinase CLK2 isoform X3

    4. XM_047444409.1 → XP_047300365.1  dual specificity protein kinase CLK2 isoform X2

    5. XM_047444417.1 → XP_047300373.1  dual specificity protein kinase CLK2 isoform X4

    Reference GRCh38.p14 ALT_REF_LOCI_1

    Genomic

    1. NW_003315906.1 Reference GRCh38.p14 ALT_REF_LOCI_1

      Range
      67891..78527 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054329470.1 → XP_054185445.1  dual specificity protein kinase CLK2 isoform X1

    2. XM_054329474.1 → XP_054185449.1  dual specificity protein kinase CLK2 isoform X5

    3. XM_054329472.1 → XP_054185447.1  dual specificity protein kinase CLK2 isoform X3

    4. XM_054329471.1 → XP_054185446.1  dual specificity protein kinase CLK2 isoform X2

    5. XM_054329473.1 → XP_054185448.1  dual specificity protein kinase CLK2 isoform X4

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      154401428..154412064 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054334218.1 → XP_054190193.1  dual specificity protein kinase CLK2 isoform X1

    2. XM_054334222.1 → XP_054190197.1  dual specificity protein kinase CLK2 isoform X5

    3. XM_054334220.1 → XP_054190195.1  dual specificity protein kinase CLK2 isoform X3

    4. XM_054334219.1 → XP_054190194.1  dual specificity protein kinase CLK2 isoform X2

    5. XM_054334221.1 → XP_054190196.1  dual specificity protein kinase CLK2 isoform X4

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001291.2: Suppressed sequence

      Description
      NM_001291.2: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P49760.1 GenPept UniProtKB/Swiss-Prot:P49760

    Gene LinkOut

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

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