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    CLK1 CDC like kinase 1 [ Homo sapiens (human) ]

    Gene ID: 1195, updated on 27-Nov-2024

    Summary

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    Official Symbol
    CLK1provided by HGNC
    Official Full Name
    CDC like kinase 1provided by HGNC
    Primary source
    HGNC:HGNC:2068
    See related
    Ensembl:ENSG00000013441 MIM:601951; AllianceGenome:HGNC:2068
    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
    Also known as
    CLK; STY; CLK/STY
    Summary
    This gene encodes a member of the CDC2-like (or LAMMER) family of dual specificity protein kinases. In the nucleus, the encoded protein phosphorylates serine/arginine-rich proteins involved in pre-mRNA processing, releasing them into the nucleoplasm. The choice of splice sites during pre-mRNA processing may be regulated by the concentration of transacting factors, including serine/arginine rich proteins. Therefore, the encoded protein may play an indirect role in governing splice site selection. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]
    Expression
    Ubiquitous expression in bone marrow (RPKM 96.5), lymph node (RPKM 51.9) and 25 other tissues See more
    Orthologs
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    Genomic context

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    See CLK1 in Genome Data Viewer
    Location:
    2q33.1
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (200853009..200864658, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (201336455..201348106, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (201717732..201729381, complement)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene BICD cargo adaptor 1 pseudogene 1 Neighboring gene Sharpr-MPRA regulatory region 5577 Neighboring gene RNA, 5S ribosomal pseudogene 115 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16963 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16964 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16965 Neighboring gene peptidylprolyl isomerase like 3 Neighboring gene RNA, U6 small nuclear 312, pseudogene Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr2:201753436-201754635 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16968 Neighboring gene NGG1 interacting factor 3 like 1 Neighboring gene RNA, U6 small nuclear 762, pseudogene

    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
    • 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. Molecular cloning of a novel human cdc2/CDC28-like protein kinase. Johnson KW, et al. J Biol Chem, 1991 Feb 25. PMID 1704889
    2. Autoregulation of the human splice factor kinase CLK1 through exon skipping and intron retention. Uzor S, et al. Gene, 2018 Sep 5. PMID 29802995
    3. Clk1-regulated aerobic glycolysis is involved in glioma chemoresistance. Zhang L, et al. J Neurochem, 2017 Aug. PMID 28581641
    4. CLK-dependent exon recognition and conjoined gene formation revealed with a novel small molecule inhibitor. Funnell T, et al. Nat Commun, 2017 Feb 23. PMID 28232751, Free PMC Article
    5. Phosphoproteomic analysis identifies CLK1 as a novel therapeutic target in gastric cancer. Babu N, et al. Gastric Cancer, 2020 Sep. PMID 32333232

    See all (72) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Functions of SRPK, CLK and DYRK kinases in stem cells, development, and human developmental disorders.
      Title: Functions of SRPK, CLK and DYRK kinases in stem cells, development, and human developmental disorders.
    2. CLK1 reorganizes the splicing factor U1-70K for early spliceosomal protein assembly.
      Title: CLK1 reorganizes the splicing factor U1-70K for early spliceosomal protein assembly.
    3. Phosphoproteomic analysis identifies CLK1 as a novel therapeutic target in gastric cancer.
      Title: Phosphoproteomic analysis identifies CLK1 as a novel therapeutic target in gastric cancer.
    4. A conserved sequence motif bridges two protein kinases for enhanced phosphorylation and nuclear function of a splicing factor.
      Title: A conserved sequence motif bridges two protein kinases for enhanced phosphorylation and nuclear function of a splicing factor.
    5. LncRNA-dependent nuclear stress bodies promote intron retention through SR protein phosphorylation.
      Title: LncRNA-dependent nuclear stress bodies promote intron retention through SR protein phosphorylation.
    6. found that CLK1 amplifies its presence in the nucleus by forming a stable complex with the Ser-Arg protein substrate
      Title: Disordered protein interactions for an ordered cellular transition: Cdc2-like kinase 1 is transported to the nucleus via its Ser-Arg protein substrate.
    7. We now show that the ability of SRPK1 to mobilize SRSF1 from speckles to the nucleoplasm is dependent on active CLK1. Diffusion from speckles is promoted by the formation of an SRPK1-CLK1 complex that facilitates dissociation of SRSF1 from CLK1 and enhances the phosphorylation of several serine-proline dipeptides in this SR protein
      Title: Mobilization of a splicing factor through a nuclear kinase-kinase complex.
    8. Data suggest that CLK1 activity in both transformed and normal cells is carefully regulated via CLK1 alternative splicing through both exon 4 skipping and intron 4 retention. CLK1 autoregulates by favoring the expression of truncated isoforms, CLK1T1 and CLKT2 in environmental stress.
      Title: Autoregulation of the human splice factor kinase CLK1 through exon skipping and intron retention.
    9. These results thus reveal a large program of CLK1-regulated periodic alternative splicing intimately associated with cell cycle control.
      Title: An extensive program of periodic alternative splicing linked to cell cycle progression.
    10. Global CLK-dependent exon recognition and conjoined gene formation revealed with a novel small molecule inhibitor has been described.
      Title: CLK-dependent exon recognition and conjoined gene formation revealed with a novel small molecule inhibitor.
    Submit: New GeneRIF Correction See all GeneRIFs (23)

    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)

    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 GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H2AXY142 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H3Y41 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables non-membrane spanning protein tyrosine kinase activity TAS
    Traceable Author Statement
    more info
    		  
    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 chromatin remodeling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of RNA splicing IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of RNA splicing IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    dual specificity protein kinase CLK1
    Names
    CDC28/CDC2-like kinase
    protein tyrosine kinase STY
    NP_001155879.1
    NP_004062.2

    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_001162407.1 → NP_001155879.1  dual specificity protein kinase CLK1 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate splice site and upstream start codon, compared to variant 1. The resulting isoform (2) has a longer N-terminus, compared to isoform 1.
      Source sequence(s)
      AI251890, AK294295
      Consensus CDS
      CCDS54427.1
      UniProtKB/TrEMBL
      B7ZA12
      Related
      ENSP00000394734.2, ENST00000434813.3
      Conserved Domains (2) summary
      smart00220
      Location:203 → 519
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd14213
      Location:190 → 519
      PKc_CLK1_4; Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases 1 and 4

    2. NM_004071.4 → NP_004062.2  dual specificity protein kinase CLK1 isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the shorter isoform (1).
      Source sequence(s)
      AI251890, BC031549, DA225472
      Consensus CDS
      CCDS2331.1
      UniProtKB/Swiss-Prot
      B4DFW7, P49759, Q0P694, Q8N5V8
      UniProtKB/TrEMBL
      B7ZA12
      Related
      ENSP00000326830.4, ENST00000321356.9
      Conserved Domains (1) summary
      cd14213
      Location:148 → 477
      PKc_CLK1_4; Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases 1 and 4

    RNA

    1. NR_027855.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an alternate exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AI251890, BC028149, DA225472
      Related
      ENST00000432425.5

    2. NR_027856.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) retains several introns, compared to variant 1. The transcript is sufficiently abundant to represent as a RefSeq record; however, the variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AI251890, BC028573, DA225472, DB164846
      Related
      ENST00000473565.5

    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_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      200853009..200864658 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      201336455..201348106 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001024646.1: Suppressed sequence

      Description
      NM_001024646.1: 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
    P49759.2 GenPept UniProtKB/Swiss-Prot:P49759

    Gene LinkOut

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