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Aliases for CLK2 Gene

Aliases for CLK2 Gene

  • CDC Like Kinase 2 2 3 5
  • CDC-Like Kinase 2 2 4
  • EC 2.7.12.1 4 61

External Ids for CLK2 Gene

Previous GeneCards Identifiers for CLK2 Gene

  • GC01M153090
  • GC01M150973
  • GC01M152010
  • GC01M152449
  • GC01M152045
  • GC01M153499
  • GC01M155232
  • GC01M126594

Summaries for CLK2 Gene

Entrez Gene Summary for CLK2 Gene

  • 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]

GeneCards Summary for CLK2 Gene

CLK2 (CDC Like Kinase 2) is a Protein Coding gene. Among its related pathways are mRNA Splicing - Major Pathway. GO annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is CLK3.

UniProtKB/Swiss-Prot for CLK2 Gene

  • Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex. May be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing and can cause redistribution of SR proteins from speckles to a diffuse nucleoplasmic distribution. Acts as a suppressor of hepatic gluconeogenesis and glucose output by repressing PPARGC1A transcriptional activity on gluconeogenic genes via its phosphorylation. Phosphorylates PPP2R5B thereby stimulating the assembly of PP2A phosphatase with the PPP2R5B-AKT1 complex leading to dephosphorylation of AKT1. Phosphorylates: PTPN1, SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.

Tocris Summary for CLK2 Gene

  • CLKs (Cdc2-like kinase) are dual specificity protein kinases which are involved in gene splicing regulation. The CLK family has four family members: CLK1/STY, CLK2, CLK3 and CLK4. CLKs are useful targets for studying diseases attributed to gene mis-splicing events.

Gene Wiki entry for CLK2 Gene

No data available for CIViC summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CLK2 Gene

Genomics for CLK2 Gene

Regulatory Elements for CLK2 Gene

Enhancers for CLK2 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH01G154940 1.9 FANTOM5 Ensembl ENCODE dbSUPER 1.7 +335.5 335478 6.0 HDGF FOXA2 MLX WRNIP1 ARID4B DMAP1 YBX1 ZNF143 ZNF207 SP5 KCNN3 EFNA3 MSTO2P RUSC1 PMVK ADAR CLK2 RUSC1-AS1 GC01M154946 ENSG00000270361
GH01G154857 1.8 FANTOM5 Ensembl ENCODE dbSUPER 1.5 +417.7 417706 5.7 HDGF PKNOX1 WRNIP1 SIN3A ZNF766 GLIS2 GATA2 ELK1 ZNF143 ZNF207 KCNN3 ADAR PBXIP1 RUSC1 MUC1 FDPS PMVK RUSC1-AS1 CLK2 PIR50309
GH01G154998 1.9 FANTOM5 ENCODE dbSUPER 1.4 +274.0 274040 11.3 MLX CREB3L1 AGO1 ZFP64 YBX1 DMAP1 FEZF1 YY1 SLC30A9 ZNF416 KIAA0907 THBS3 ENSG00000271267 RUSC1-AS1 ZBTB7B EFNA4 ASH1L-AS1 DCST1 KRTCAP2 DPM3
GH01G155514 0.5 FANTOM5 ENCODE 3.3 -236.3 -236294 0.2 RUSC1 RUSC1-AS1 KRTCAP2 CLK2 SCAMP3 GBA GC01P155549 GC01P155434 GC01P155435 GC01P155433
GH01G155276 1 ENCODE 0.7 +0.7 680 2.2 PKNOX1 ATF1 ARID4B E2F7 SIN3A ZNF121 GLIS2 ZNF143 KLF7 KLF13 HCN3 GBA MUC1 CLK2
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around CLK2 on UCSC Golden Path with GeneCards custom track

Promoters for CLK2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000014055 791 1401 PKNOX1 ATF1 ARID4B E2F7 SIN3A ZNF121 GLIS2 ZNF143 KLF7 KLF13

Genomic Location for CLK2 Gene

Chromosome:
1
Start:
155,262,868 bp from pter
End:
155,278,491 bp from pter
Size:
15,624 bases
Orientation:
Minus strand

Genomic View for CLK2 Gene

Genes around CLK2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CLK2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CLK2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CLK2 Gene

Proteins for CLK2 Gene

  • Protein details for CLK2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P49760-CLK2_HUMAN
    Recommended name:
    Dual specificity protein kinase CLK2
    Protein Accession:
    P49760
    Secondary Accessions:
    • B1AVS9
    • B5MBX6
    • Q96CQ0

    Protein attributes for CLK2 Gene

    Size:
    499 amino acids
    Molecular mass:
    60090 Da
    Quaternary structure:
    • Interacts with RBMX. Interacts with AKT1 and UBL5.

    Three dimensional structures from OCA and Proteopedia for CLK2 Gene

    Alternative splice isoforms for CLK2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CLK2 Gene

Selected DME Specific Peptides for CLK2 Gene

P49760:
  • DFGSATFDHEHH
  • VSTRHYRAPEVIL
  • GFTLFQTH
  • EAARLEINVL
  • LTHTDLKPENILFV
  • GDWLQERYEIV
  • LFQTHDN
  • TRKQKYFY
  • EHLAMMER

Post-translational modifications for CLK2 Gene

  • Autophosphorylates on all three types of residues. Phosphorylation on Ser-34 and Thr-127 by AKT1 is induced by ionizing radiation or insulin. Phosphorylation plays a critical role in cell proliferation following low dose radiation and prevents cell death following high dose radiation. Phosphorylation at Thr-344 by PKB/AKT2 induces its kinase activity which is required for its stability. The phosphorylation status at Ser-142 influences its subnuclear localization; inhibition of phosphorylation at Ser-142 results in accumulation in the nuclear speckle.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for CLK2 Gene

Gene Families for CLK2 Gene

Protein Domains for CLK2 Gene

Graphical View of Domain Structure for InterPro Entry

P49760

UniProtKB/Swiss-Prot:

CLK2_HUMAN :
  • Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. Lammer subfamily.
Family:
  • Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. Lammer subfamily.
genes like me logo Genes that share domains with CLK2: view

Function for CLK2 Gene

Molecular function for CLK2 Gene

GENATLAS Biochemistry:
CDC-like kinase 2,with two alternatively spliced forms,one catalytically active and one inactive isoforms,interacting with and inducing the nuclear redistribution of SR proteins SFRS* (see symbols),widely expressed
UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a protein = ADP + a phosphoprotein.
UniProtKB/Swiss-Prot EnzymeRegulation:
5,6-dichloro-1-b-D-ribofuranosylbenzimidazole (DRB) inhibits autophosphorylation. TG003 inhibits its kinase activity and affects the regulation of alternative splicing mediated by phosphorylation of SR proteins (By similarity).
UniProtKB/Swiss-Prot Function:
Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex. May be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing and can cause redistribution of SR proteins from speckles to a diffuse nucleoplasmic distribution. Acts as a suppressor of hepatic gluconeogenesis and glucose output by repressing PPARGC1A transcriptional activity on gluconeogenic genes via its phosphorylation. Phosphorylates PPP2R5B thereby stimulating the assembly of PP2A phosphatase with the PPP2R5B-AKT1 complex leading to dephosphorylation of AKT1. Phosphorylates: PTPN1, SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.

Enzyme Numbers (IUBMB) for CLK2 Gene

Gene Ontology (GO) - Molecular Function for CLK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity IEA --
GO:0004674 protein serine/threonine kinase activity IDA,IEA 10480872
GO:0004712 protein serine/threonine/tyrosine kinase activity IEA --
GO:0004713 protein tyrosine kinase activity IEA --
GO:0005515 protein binding IPI 16189514
genes like me logo Genes that share ontologies with CLK2: view
genes like me logo Genes that share phenotypes with CLK2: view

Animal Model Products

  • Taconic Biosciences Mouse Models for CLK2

CRISPR Products

Inhibitory RNA Products

No data available for Human Phenotype Ontology , Animal Models , miRNA , Transcription Factor Targets and HOMER Transcription for CLK2 Gene

Localization for CLK2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CLK2 Gene

Isoform 1: Nucleus. Nucleus speckle. Note=Inhibition of phosphorylation at Ser-142 results in accumulation in the nuclear speckle. {ECO:0000250}.
Isoform 2: Nucleus speckle. Note=Co-localizes with serine- and arginine-rich (SR) proteins in the nuclear speckles.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CLK2 gene
Compartment Confidence
nucleus 5
cytosol 2

Gene Ontology (GO) - Cellular Components for CLK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA 9637771
GO:0005654 nucleoplasm IDA --
GO:0016604 nuclear body IDA --
GO:0016607 nuclear speck IEA --
genes like me logo Genes that share ontologies with CLK2: view

Pathways & Interactions for CLK2 Gene

SuperPathway Contained pathways
1 mRNA Splicing - Major Pathway
genes like me logo Genes that share pathways with CLK2: view

Pathways by source for CLK2 Gene

1 BioSystems pathway for CLK2 Gene

SIGNOR curated interactions for CLK2 Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for CLK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006468 protein phosphorylation IEA,IDA 9637771
GO:0010033 response to organic substance IEA --
GO:0010212 response to ionizing radiation IMP 20682768
GO:0016310 phosphorylation IEA --
GO:0018108 peptidyl-tyrosine phosphorylation IEA --
genes like me logo Genes that share ontologies with CLK2: view

Drugs & Compounds for CLK2 Gene

(2) Drugs for CLK2 Gene - From: ApexBio and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Adenosine triphosphate Approved Nutra 0
TG003 Pharma Cdc2-like kinase (Clk) inhibitor 0

(2) Additional Compounds for CLK2 Gene - From: Tocris and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
TG 003
719277-26-6

(1) Tocris Compounds for CLK2 Gene

Compound Action Cas Number
TG 003 Potent inhibitor of Clk-family kinases; also inhibits DYRK1A/B 719277-26-6

(1) ApexBio Compounds for CLK2 Gene

Compound Action Cas Number
TG003 Cdc2-like kinase (Clk) inhibitor 300801-52-9
genes like me logo Genes that share compounds with CLK2: view

Drug Products

Transcripts for CLK2 Gene

Unigene Clusters for CLK2 Gene

CDC-like kinase 2:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Alternative Splicing Database (ASD) splice patterns (SP) for CLK2 Gene

ExUns: 1a · 1b · 1c · 1d · 1e · 1f ^ 2 ^ 3a · 3b ^ 4a · 4b · 4c ^ 5a · 5b ^ 6a · 6b ^ 7a · 7b ^ 8a · 8b ^ 9a · 9b ^ 10 ^ 11a · 11b ^ 12 ^
SP1: - - - - - -
SP2: - - - - - -
SP3: - - - - - - - -
SP4: - -
SP5: - - - -
SP6: - - - -
SP7: - - - - - - -
SP8:
SP9: - -
SP10: -
SP11:
SP12:
SP13:

ExUns: 13 ^ 14 ^ 15a · 15b
SP1: -
SP2: -
SP3: -
SP4: -
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:
SP13:

Relevant External Links for CLK2 Gene

GeneLoc Exon Structure for
CLK2
ECgene alternative splicing isoforms for
CLK2

Expression for CLK2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for CLK2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for CLK2 Gene



Protein tissue co-expression partners for CLK2 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of CLK2 Gene:

CLK2

SOURCE GeneReport for Unigene cluster for CLK2 Gene:

Hs.73986

mRNA Expression by UniProt/SwissProt for CLK2 Gene:

P49760-CLK2_HUMAN
Tissue specificity: Endothelial cells.

Evidence on tissue expression from TISSUES for CLK2 Gene

  • Lung(4.3)
  • Nervous system(2.9)
genes like me logo Genes that share expression patterns with CLK2: view

Primer Products

No data available for mRNA differential expression in normal tissues , Protein differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for CLK2 Gene

Orthologs for CLK2 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for CLK2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CLK2 34 35
  • 99.93 (n)
cow
(Bos Taurus)
Mammalia CLK2 34 35
  • 93.91 (n)
dog
(Canis familiaris)
Mammalia CLK2 34 35
  • 93.31 (n)
mouse
(Mus musculus)
Mammalia Clk2 34 16 35
  • 92.57 (n)
rat
(Rattus norvegicus)
Mammalia Clk2 34
  • 91.63 (n)
oppossum
(Monodelphis domestica)
Mammalia CLK2 35
  • 91 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 35
  • 61 (a)
ManyToMany
chicken
(Gallus gallus)
Aves CLK2 34 35
  • 75.35 (n)
lizard
(Anolis carolinensis)
Reptilia CLK2 35
  • 80 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia clk2 34
  • 72.51 (n)
African clawed frog
(Xenopus laevis)
Amphibia clk2-prov 34
zebrafish
(Danio rerio)
Actinopterygii clk2b 35
  • 71 (a)
OneToMany
clk2a 34 35
  • 67 (n)
wufb20c02 34
fruit fly
(Drosophila melanogaster)
Insecta Doa 34 35
  • 64.71 (n)
worm
(Caenorhabditis elegans)
Secernentea tag-172 34 35
  • 58.81 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes KNS1 35
  • 21 (a)
OneToMany
thale cress
(Arabidopsis thaliana)
eudicotyledons FC2 34
  • 54.34 (n)
Alicante grape
(Vitis vinifera)
eudicotyledons Vvi.1597 34
rice
(Oryza sativa)
Liliopsida Os.35712 34
sea squirt
(Ciona savignyi)
Ascidiacea CSA.719 35
  • 57 (a)
OneToMany
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.12198 34
Species where no ortholog for CLK2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for CLK2 Gene

ENSEMBL:
Gene Tree for CLK2 (if available)
TreeFam:
Gene Tree for CLK2 (if available)

Paralogs for CLK2 Gene

Paralogs for CLK2 Gene

(6) SIMAP similar genes for CLK2 Gene using alignment to 5 proteins:

Pseudogenes.org Pseudogenes for CLK2 Gene

genes like me logo Genes that share paralogs with CLK2: view

Variants for CLK2 Gene

Structural Variations from Database of Genomic Variants (DGV) for CLK2 Gene

Variant ID Type Subtype PubMed ID
dgv3n68 CNV loss 17160897
esv23319 CNV gain 19812545
esv2758971 CNV gain 17122850
esv3384525 CNV duplication 20981092
esv33869 CNV loss 17666407
nsv1011773 CNV gain 25217958
nsv1150773 CNV insertion 26484159
nsv3010 CNV insertion 18451855
nsv436027 CNV insertion 17901297
nsv831636 CNV loss 17160897
nsv90 CNV insertion 15895083

Variation tolerance for CLK2 Gene

Residual Variation Intolerance Score: 27.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.35; 26.65% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for CLK2 Gene

Human Gene Mutation Database (HGMD)
CLK2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CLK2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Sequence variations from dbSNP and Humsavar for CLK2 Gene

Disorders for CLK2 Gene

Relevant External Links for CLK2

Atlas of Genetics and Cytogenetics in Oncology and Haematology:
CLK2

No disorders were found for CLK2 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for CLK2 Gene

Publications for CLK2 Gene

  1. Characterization by cDNA cloning of two new human protein kinases. Evidence by sequence comparison of a new family of mammalian protein kinases. (PMID: 7990150) Hanes J.J. … Scheit K.H. (J. Mol. Biol. 1994) 2 3 4 22 64
  2. Phosphorylation of CLK2 at serine 34 and threonine 127 by AKT controls cell survival after ionizing radiation. (PMID: 20682768) Nam S.Y. … Jin Y.W. (J. Biol. Chem. 2010) 3 4 64
  3. Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing of tissue factor in human endothelial cells. (PMID: 19168442) Eisenreich A. … Rauch U. (Circ. Res. 2009) 3 4 64
  4. Heterogeneous nuclear ribonucleoprotein G regulates splice site selection by binding to CC(A/C)-rich regions in pre-mRNA. (PMID: 19282290) Heinrich B. … Stamm S. (J. Biol. Chem. 2009) 3 4 64
  5. HCLK2 is essential for the mammalian S-phase checkpoint and impacts on Chk1 stability. (PMID: 17384638) Collis S.J. … Boulton S.J. (Nat. Cell Biol. 2007) 3 22 64

Products for CLK2 Gene

  • Addgene plasmids for CLK2

Sources for CLK2 Gene

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