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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 56

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. Gene Ontology (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

Additional gene information 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

GeneHancer (GH) Regulatory Elements for CLK2 Gene

Promoters and enhancers for CLK2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH01I155272 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 550.4 +5.1 5072 2.3 HDGF PKNOX1 SMAD1 MLX ARNT ARID4B SIN3A DMAP1 YY1 POLR2B CLK2 GBA PYGO2 PKLR LOC101928120 FDPS RUSC1 RUSC1-AS1 MIR555 MSTO2P
GH01I155276 Promoter/Enhancer 2 EPDnew Ensembl ENCODE 570 +0.7 680 2.2 PKNOX1 ATF1 ARID4B SIN3A GLIS2 E2F8 ZNF143 KLF7 ATF7 SP3 HCN3 CLK2 GBA GON4L KHDC4 SHC1 YY1AP1 THBS3 ENSG00000271267 FLAD1
GH01I155242 Promoter/Enhancer 2.4 EPDnew Ensembl ENCODE dbSUPER 216.7 +34.2 34249 2.9 FEZF1 YBX1 IRF4 YY1 ZNF213 E2F8 ZNF416 ZNF143 ZNF548 SP3 GBA KHDC4 GON4L CLK2 ENSG00000271267 MSTO1 MSTO2P RUSC1-AS1 THBS3 SHC1
GH01I154998 Promoter/Enhancer 2.7 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 91.4 +274.0 274040 11.3 CLOCK MLX YBX1 DMAP1 YY1 ZNF213 E2F8 ZNF416 ZNF143 SP3 ZBTB7B GON4L CLK2 UBAP2L KHDC4 ENSG00000271267 RUSC1-AS1 MSTO1 THBS3 MSTO2P
GH01I156111 Promoter/Enhancer 2.7 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 65.5 -842.9 -842898 19.4 CLOCK MLX ZFP64 FEZF1 DMAP1 IRF4 YY1 SLC30A9 ZNF213 E2F8 LMNA GON4L CLK2 RRNAD1 KHDC4 LOC246784 MSTO1 MSTO2P PRCC ISG20L2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around CLK2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the CLK2 gene promoter:

Genomic Locations for CLK2 Gene

Genomic Locations for CLK2 Gene
chr1:155,262,868-155,278,491
(GRCh38/hg38)
Size:
15,624 bases
Orientation:
Minus strand
chr1:155,232,659-155,248,282
(GRCh37/hg19)

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.

Domains & Families for CLK2 Gene

Gene Families for CLK2 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

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

Phenotypes From GWAS Catalog 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 IEA,IDA 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

Clone Products

  • Addgene plasmids for CLK2

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

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (4)
  • Nuclear bodies (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CLK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA,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
ATP Investigational Nutra Agonist 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:

Clone Products

  • Addgene plasmids for CLK2

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

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 33 34
  • 99.93 (n)
cow
(Bos Taurus)
Mammalia CLK2 33 34
  • 93.91 (n)
dog
(Canis familiaris)
Mammalia CLK2 33 34
  • 93.31 (n)
mouse
(Mus musculus)
Mammalia Clk2 33 16 34
  • 92.57 (n)
rat
(Rattus norvegicus)
Mammalia Clk2 33
  • 91.63 (n)
oppossum
(Monodelphis domestica)
Mammalia CLK2 34
  • 91 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 34
  • 61 (a)
ManyToMany
chicken
(Gallus gallus)
Aves CLK2 33 34
  • 75.35 (n)
lizard
(Anolis carolinensis)
Reptilia CLK2 34
  • 80 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia clk2 33
  • 72.51 (n)
African clawed frog
(Xenopus laevis)
Amphibia clk2-prov 33
zebrafish
(Danio rerio)
Actinopterygii clk2b 34
  • 71 (a)
OneToMany
clk2a 33 34
  • 67 (n)
wufb20c02 33
fruit fly
(Drosophila melanogaster)
Insecta Doa 33 34
  • 64.71 (n)
worm
(Caenorhabditis elegans)
Secernentea tag-172 33 34
  • 58.81 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes KNS1 34
  • 21 (a)
OneToMany
thale cress
(Arabidopsis thaliana)
eudicotyledons FC2 33
  • 54.34 (n)
Alicante grape
(Vitis vinifera)
eudicotyledons Vvi.1597 33
rice
(Oryza sativa)
Liliopsida Os.35712 33
sea squirt
(Ciona savignyi)
Ascidiacea CSA.719 34
  • 57 (a)
OneToMany
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.12198 33
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

Sequence variations from dbSNP and Humsavar for CLK2 Gene

SNP ID Clin Chr 01 pos Variation AA Info Type
rs1000140263 -- 155,273,618(-) G/A upstream_transcript_variant
rs1000575136 -- 155,265,140(-) A/G intron_variant
rs1001205723 -- 155,271,898(-) C/T intron_variant
rs1001352514 -- 155,269,676(-) G/A/C 5_prime_UTR_variant, coding_sequence_variant, missense_variant, non_coding_transcript_variant
rs1001385232 -- 155,269,957(-) C/T intron_variant

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

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

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)

Additional Variant Information 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 for CLK2 Gene

Disorders for CLK2 Gene

Additional Disease Information for 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 … Scheit KH (Journal of molecular biology 1994) 2 3 4 22 58
  2. Phosphorylation of CLK2 at serine 34 and threonine 127 by AKT controls cell survival after ionizing radiation. (PMID: 20682768) Nam SY … Jin YW (The Journal of biological chemistry 2010) 3 4 58
  3. Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing of tissue factor in human endothelial cells. (PMID: 19168442) Eisenreich A … Rauch U (Circulation research 2009) 3 4 58
  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 (The Journal of biological chemistry 2009) 3 4 58
  5. HCLK2 is essential for the mammalian S-phase checkpoint and impacts on Chk1 stability. (PMID: 17384638) Collis SJ … Boulton SJ (Nature cell biology 2007) 3 22 58

Products for CLK2 Gene

Sources for CLK2 Gene