This gene encodes a protein belonging to the serine/threonine type protein kinase family. This protein is a nuclear dual-specificity kinase that regulates the intranuclear distribution of the serine/arginine-rich (SR) family of splicing factors. Two transcript variants encoding different isoforms have been found for this gene. Related pseudogenes are located on chromosomes 1 an... See more...

Aliases for CLK3 Gene

Aliases for CLK3 Gene

  • CDC Like Kinase 3 2 3 5
  • Dual Specificity Protein Kinase CLK3 3 4
  • CDC-Like Kinase 3 2 4
  • EC 2.7.12.1 4 50
  • PHCLK3/152 3
  • PHCLK3 3
  • CLK3 5

External Ids for CLK3 Gene

Previous GeneCards Identifiers for CLK3 Gene

  • GC15U990010
  • GC15P068014
  • GC15P072476
  • GC15P072616
  • GC15P072687
  • GC15P074900
  • GC15P051698

Summaries for CLK3 Gene

Entrez Gene Summary for CLK3 Gene

  • This gene encodes a protein belonging to the serine/threonine type protein kinase family. This protein is a nuclear dual-specificity kinase that regulates the intranuclear distribution of the serine/arginine-rich (SR) family of splicing factors. Two transcript variants encoding different isoforms have been found for this gene. Related pseudogenes are located on chromosomes 1 and 9. [provided by RefSeq, Jul 2008]

GeneCards Summary for CLK3 Gene

CLK3 (CDC Like Kinase 3) is a Protein Coding gene. Among its related pathways are Translational Control and mRNA Splicing - Major Pathway. Gene Ontology (GO) annotations related to this gene include protein kinase activity. An important paralog of this gene is CLK2.

UniProtKB/Swiss-Prot Summary for CLK3 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. Phosphorylates SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.

Tocris Summary for CLK3 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 CLK3 Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CLK3 Gene

Genomics for CLK3 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for CLK3 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CLK3 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CLK3

Top Transcription factor binding sites by QIAGEN in the CLK3 gene promoter:
  • E2F
  • E2F-1
  • E2F-2
  • E2F-3a
  • E2F-4
  • Nkx2-5

Genomic Locations for CLK3 Gene

Latest Assembly
chr15:74,598,500-74,645,414
(GRCh38/hg38)
Size:
46,915 bases
Orientation:
Plus strand

Previous Assembly
chr15:74,900,713-74,922,542
(GRCh37/hg19 by Entrez Gene)
Size:
21,830 bases
Orientation:
Plus strand

chr15:74,890,841-74,932,057
(GRCh37/hg19 by Ensembl)
Size:
41,217 bases
Orientation:
Plus strand

Genomic View for CLK3 Gene

Genes around CLK3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CLK3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CLK3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CLK3 Gene

Proteins for CLK3 Gene

  • Protein details for CLK3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P49761-CLK3_HUMAN
    Recommended name:
    Dual specificity protein kinase CLK3
    Protein Accession:
    P49761
    Secondary Accessions:
    • D3DW59
    • Q53Y48
    • Q9BRS3
    • Q9BUJ7

    Protein attributes for CLK3 Gene

    Size:
    638 amino acids
    Molecular mass:
    73515 Da
    Quaternary structure:
    No Data Available
    SequenceCaution:
    • Sequence=AAH02555.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAH19881.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
    Miscellaneous:
    • [Isoform 2]: Lacks the kinase domain. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

    Three dimensional structures from OCA and Proteopedia for CLK3 Gene

    Alternative splice isoforms for CLK3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CLK3 Gene

Selected DME Specific Peptides for CLK3 Gene

P49761:
  • DFGSATFDHEHH
  • PYRTRKHAHHCHKRRTRSCSSASSRSQQSSKRSSRSVEDD
  • MMEKILGP
  • GFTLFQTH
  • EAARLEINVL
  • LTHTDLKPENILFV
  • VALKIIRN
  • HRRRSRER
  • VRHMAYQLC
  • GDWLQERYEIV
  • TRKQKYFY

Post-translational modifications for CLK3 Gene

  • Autophosphorylates on all three types of residues.
  • Ubiquitination at Lys317
  • Modification sites at PhosphoSitePlus

Domains & Families for CLK3 Gene

Gene Families for CLK3 Gene

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

Suggested Antigen Peptide Sequences for CLK3 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ38796 fis, clone LIVER2004514, highly similar to Dual specificity protein kinase CLK3 (EC 2.7.12.1) (B3KTV2_HUMAN)
  • CDC-like kinase 3 (CLK3_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P49761

UniProtKB/Swiss-Prot:

CLK3_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 CLK3: view

Function for CLK3 Gene

Molecular function for CLK3 Gene

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. Phosphorylates SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.12.1;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.12.1;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.12.1;.
UniProtKB/Swiss-Prot EnzymeRegulation:
Leucettine L41 inhibits its kinase activity and affects the regulation of alternative splicing mediated by phosphorylation of SR proteins.
GENATLAS Biochemistry:
CDC-like kinase 3,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

Enzyme Numbers (IUBMB) for CLK3 Gene

Phenotypes From GWAS Catalog for CLK3 Gene

Gene Ontology (GO) - Molecular Function for CLK3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0003723 RNA binding HDA 22658674
GO:0004672 protein kinase activity IEA --
GO:0004674 protein serine/threonine kinase activity TAS,ISS --
GO:0004712 protein serine/threonine/tyrosine kinase activity IEA --
genes like me logo Genes that share ontologies with CLK3: view
genes like me logo Genes that share phenotypes with CLK3: view

Animal Models for research

  • Taconic Biosciences Mouse Models for CLK3

miRNA for CLK3 Gene

miRTarBase miRNAs that target CLK3

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CLK3

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for CLK3 Gene

Localization for CLK3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CLK3 Gene

[Isoform 1]: Nucleus. Cytoplasm. Cytoplasmic vesicle, secretory vesicle, acrosome.
[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 CLK3 gene
Compartment Confidence
nucleus 5
cytoskeleton 4
cytosol 2
plasma membrane 1
extracellular 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (3)
  • Intermediate filaments (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CLK3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001669 acrosomal vesicle IEA --
GO:0005634 nucleus IEA,IDA 9637771
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IEA --
GO:0016020 membrane HDA 19946888
genes like me logo Genes that share ontologies with CLK3: view

Pathways & Interactions for CLK3 Gene

PathCards logo

SuperPathways for CLK3 Gene

genes like me logo Genes that share pathways with CLK3: view

Pathways by source for CLK3 Gene

1 BioSystems pathway for CLK3 Gene
1 Cell Signaling Technology pathway for CLK3 Gene

SIGNOR curated interactions for CLK3 Gene

Is inactivated by:

Gene Ontology (GO) - Biological Process for CLK3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006468 protein phosphorylation IEA,IDA 9637771
GO:0016310 phosphorylation IEA --
GO:0018108 peptidyl-tyrosine phosphorylation IEA --
GO:0043484 regulation of RNA splicing IDA 9637771
GO:0046777 protein autophosphorylation IEA --
genes like me logo Genes that share ontologies with CLK3: view

Drugs & Compounds for CLK3 Gene

(3) Drugs for CLK3 Gene - From: DrugBank

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
fostamatinib Approved, Investigational Pharma Target, inhibitor Kinase Inhibitors 0
ethyl 3-[(E)-2-amino-1-cyanoethenyl]-6,7-dichloro-1-methyl-1H-indole-2-carboxylate Experimental Pharma Target 0
K-00546 Experimental Pharma Target 0
genes like me logo Genes that share compounds with CLK3: view

Transcripts for CLK3 Gene

mRNA/cDNA for CLK3 Gene

3 REFSEQ mRNAs :
23 NCBI additional mRNA sequence :
27 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CLK3

Alternative Splicing Database (ASD) splice patterns (SP) for CLK3 Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3 ^ 4a · 4b · 4c · 4d ^ 5a · 5b ^ 6 ^ 7a · 7b · 7c · 7d ^ 8a · 8b ^ 9 ^ 10a · 10b ^ 11a · 11b · 11c ^ 12 ^ 13 ^
SP1: -
SP2:
SP3: - - -
SP4: - - - - -
SP5: - -
SP6: -
SP7: - - - -
SP8: - - -
SP9: - -
SP10: - - - - - -
SP11:
SP12: -
SP13: - - - - -
SP14: -

ExUns: 14a · 14b · 14c ^ 15a · 15b
SP1: - -
SP2: - -
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:
SP13:
SP14:

Relevant External Links for CLK3 Gene

GeneLoc Exon Structure for
CLK3

Expression for CLK3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CLK3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CLK3 Gene

This gene is overexpressed in Whole Blood (x4.2).

Protein differential expression in normal tissues from HIPED for CLK3 Gene

This gene is overexpressed in Plasma (36.5), Liver (16.1), and Heart (10.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CLK3 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CLK3

SOURCE GeneReport for Unigene cluster for CLK3 Gene:

Hs.584748

mRNA Expression by UniProt/SwissProt for CLK3 Gene:

P49761-CLK3_HUMAN
Tissue specificity: Endothelial cells.

Evidence on tissue expression from TISSUES for CLK3 Gene

  • Liver(4.5)
  • Nervous system(4.1)
  • Intestine(2.9)
  • Muscle(2.2)
  • Skin(2.2)
  • Bone marrow(2)
genes like me logo Genes that share expression patterns with CLK3: view

No data available for Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for CLK3 Gene

Orthologs for CLK3 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for CLK3 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia CLK3 29 30
  • 99.73 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia CLK3 29 30
  • 95.58 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia CLK3 29 30
  • 94.35 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Clk3 29
  • 92.93 (n)
Mouse
(Mus musculus)
Mammalia Clk3 29 16 30
  • 86.94 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia CLK3 30
  • 78 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia CLK3 30
  • 73 (a)
OneToOne
Chicken
(Gallus gallus)
Aves CLK3 29 30
  • 76.39 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia CLK3 30
  • 87 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia clk3 29
  • 72.68 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta Doa 30
  • 13 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea tag-172 30
  • 25 (a)
OneToMany
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes KNS1 30
  • 21 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.719 30
  • 50 (a)
OneToMany
Species where no ortholog for CLK3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • 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 (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Zebrafish (Danio rerio)

Evolution for CLK3 Gene

ENSEMBL:
Gene Tree for CLK3 (if available)
TreeFam:
Gene Tree for CLK3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CLK3: view image
Alliance of Genome Resources:
Additional Orthologs for CLK3

Paralogs for CLK3 Gene

(5) SIMAP similar genes for CLK3 Gene using alignment to 15 proteins:

  • CLK3_HUMAN
  • B3KTV2_HUMAN
  • G5E959_HUMAN
  • H3BNC8_HUMAN
  • H3BNQ5_HUMAN
  • H3BQG1_HUMAN
  • H3BQR7_HUMAN
  • H3BRE4_HUMAN
  • H3BRK0_HUMAN
  • H3BRT8_HUMAN
  • H3BRW2_HUMAN
  • H3BTW9_HUMAN
  • H3BUL5_HUMAN
  • H3BV35_HUMAN
  • H3BVF8_HUMAN

Pseudogenes.org Pseudogenes for CLK3 Gene

genes like me logo Genes that share paralogs with CLK3: view

Variants for CLK3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CLK3 Gene

SNP ID Clinical significance and condition Chr 15 pos Variation AA Info Type
rs910378995 -- p.Gln607Arg
rs920443187 -- p.Arg628Trp
VAR_040413 -- p.Arg486Cys

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for CLK3 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for CLK3 Gene

Variant ID Type Subtype PubMed ID
esv28499 CNV gain 19812545
nsv1121512 CNV deletion 24896259
nsv457204 CNV loss 19166990
nsv527730 CNV loss 19592680
nsv569991 CNV loss 21841781
nsv817698 CNV gain 17921354
nsv951994 CNV deletion 24416366

Variation tolerance for CLK3 Gene

Residual Variation Intolerance Score: 13.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.84; 86.95% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CLK3 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
CLK3
Leiden Open Variation Database (LOVD)
CLK3

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CLK3 Gene

Disorders for CLK3 Gene

Additional Disease Information for CLK3

No disorders were found for CLK3 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for CLK3 Gene

Publications for CLK3 Gene

  1. The Clk2 and Clk3 dual-specificity protein kinases regulate the intranuclear distribution of SR proteins and influence pre-mRNA splicing. (PMID: 9637771) Duncan PI … Bell JC (Experimental cell research 1998) 3 4 22
  2. 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
  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
  4. Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. (PMID: 17081983) Olsen JV … Mann M (Cell 2006) 3 4
  5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4

Products for CLK3 Gene

Sources for CLK3 Gene