The protein encoded by this gene belongs to the CDC2-like protein kinase (CLK) family. This protein kinase can interact with and phosphorylate the serine- and arginine-rich (SR) proteins, which are known to play an important role in the formation of spliceosomes, and thus may be involved in the regulation of alternative splicing. Studies in the Israeli sand rat Psammomys obesus... See more...

Aliases for CLK4 Gene

Aliases for CLK4 Gene

  • CDC Like Kinase 4 2 3 5
  • Dual Specificity Protein Kinase CLK4 3 4
  • CDC-Like Kinase 4 2 4
  • EC 2.7.12.1 4 51
  • Protein Serine Threonine Kinase Clk4 3
  • CLK4 5

External Ids for CLK4 Gene

Previous GeneCards Identifiers for CLK4 Gene

  • GC05M178182
  • GC05M178917
  • GC05M178098
  • GC05M178143
  • GC05M177962
  • GC05M172756
  • GC05M178029

Summaries for CLK4 Gene

Entrez Gene Summary for CLK4 Gene

  • The protein encoded by this gene belongs to the CDC2-like protein kinase (CLK) family. This protein kinase can interact with and phosphorylate the serine- and arginine-rich (SR) proteins, which are known to play an important role in the formation of spliceosomes, and thus may be involved in the regulation of alternative splicing. Studies in the Israeli sand rat Psammomys obesus suggested that the ubiquitin-like 5 (UBL5/BEACON), a highly conserved ubiquitin-like protein, may interact with and regulate the activity of this kinase. Multiple alternatively spliced transcript variants have been observed, but the full-length natures of which have not yet been determined. [provided by RefSeq, Jul 2008]

GeneCards Summary for CLK4 Gene

CLK4 (CDC Like Kinase 4) is a Protein Coding gene. Diseases associated with CLK4 include Cone-Rod Dystrophy 6 and Fanconi Anemia, Complementation Group A. Among its related pathways are Legionellosis and 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 CLK1.

UniProtKB/Swiss-Prot Summary for CLK4 Gene

  • Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates SRSF1 and SRSF3. Required for the regulation of alternative splicing of MAPT/TAU. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CLK4 Gene

Genomics for CLK4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for CLK4 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 CLK4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CLK4

Top Transcription factor binding sites by QIAGEN in the CLK4 gene promoter:
  • AML1a
  • c-Myc
  • FOXI1
  • FOXO4
  • GATA-1
  • HFH-3
  • Nkx2-5
  • TBP
  • TFIID

Genomic Locations for CLK4 Gene

Genomic Locations for CLK4 Gene
chr5:178,602,664-178,630,615
(GRCh38/hg38)
Size:
27,952 bases
Orientation:
Minus strand
chr5:178,029,665-178,057,616
(GRCh37/hg19)
Size:
27,952 bases
Orientation:
Minus strand

Genomic View for CLK4 Gene

Genes around CLK4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CLK4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CLK4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CLK4 Gene

Proteins for CLK4 Gene

  • Protein details for CLK4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9HAZ1-CLK4_HUMAN
    Recommended name:
    Dual specificity protein kinase CLK4
    Protein Accession:
    Q9HAZ1

    Protein attributes for CLK4 Gene

    Size:
    481 amino acids
    Molecular mass:
    57492 Da
    Quaternary structure:
    • Interacts with UBL5.

    Three dimensional structures from OCA and Proteopedia for CLK4 Gene

neXtProt entry for CLK4 Gene

Selected DME Specific Peptides for CLK4 Gene

Q9HAZ1:
  • VSTRHYRAPEVIL
  • LTHTDLKPENILFV
  • EHLAMMER

Post-translational modifications for CLK4 Gene

Other Protein References for CLK4 Gene

Antibody Products

  • Abcam antibodies for CLK4
  • Santa Cruz Biotechnology (SCBT) Antibodies for CLK4

Domains & Families for CLK4 Gene

Gene Families for CLK4 Gene

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

Protein Domains for CLK4 Gene

Suggested Antigen Peptide Sequences for CLK4 Gene

GenScript: Design optimal peptide antigens:
  • CDC-like kinase 4 (B9EG64_HUMAN)
  • CDC-like kinase 4 (CLK4_HUMAN)
  • cDNA FLJ51841, highly similar to Dual specificity protein kinase CLK4 (EC 2.7.12.1) (Q4G0Z5_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9HAZ1

UniProtKB/Swiss-Prot:

CLK4_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 CLK4: view

Function for CLK4 Gene

Molecular function for CLK4 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 and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates SRSF1 and SRSF3. Required for the regulation of alternative splicing of MAPT/TAU. 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:
TG003 inhibits its kinase activity and affects the regulation of alternative splicing mediated by phosphorylation of SR proteins.

Enzyme Numbers (IUBMB) for CLK4 Gene

Phenotypes From GWAS Catalog for CLK4 Gene

Gene Ontology (GO) - Molecular Function for CLK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0004672 protein kinase activity IEA --
GO:0004674 protein serine/threonine kinase activity IEA,ISS --
GO:0004712 protein serine/threonine/tyrosine kinase activity IEA --
GO:0004713 protein tyrosine kinase activity IEA --
genes like me logo Genes that share ontologies with CLK4: view
genes like me logo Genes that share phenotypes with CLK4: view

Animal Model Products

  • Taconic Biosciences Mouse Models for CLK4

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CLK4

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for CLK4 Gene

Localization for CLK4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CLK4 Gene

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 CLK4 gene
Compartment Confidence
nucleus 4
cytoskeleton 3
cytosol 2
plasma membrane 1
extracellular 1
mitochondrion 1
endoplasmic reticulum 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Actin filaments (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CLK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
genes like me logo Genes that share ontologies with CLK4: view

Pathways & Interactions for CLK4 Gene

PathCards logo

SuperPathways for CLK4 Gene

SuperPathway Contained pathways
1 Legionellosis
2 mRNA Splicing - Major Pathway
genes like me logo Genes that share pathways with CLK4: view

Pathways by source for CLK4 Gene

1 BioSystems pathway for CLK4 Gene
1 KEGG pathway for CLK4 Gene

SIGNOR curated interactions for CLK4 Gene

Inactivates:

Gene Ontology (GO) - Biological Process for CLK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006468 protein phosphorylation IEA --
GO:0016310 phosphorylation IEA --
GO:0018108 peptidyl-tyrosine phosphorylation IEA --
GO:0043484 regulation of RNA splicing IMP 19168442
GO:0046777 protein autophosphorylation IEA --
genes like me logo Genes that share ontologies with CLK4: view

Drugs & Compounds for CLK4 Gene

(4) Drugs for CLK4 Gene - From: DrugBank, ApexBio, and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
fostamatinib Approved, Investigational Pharma Target, inhibitor Kinase Inhibitors 0
ATP Investigational Nutra Agonist, Activator, Partial agonist, Antagonist, Full agonist, Gating inhibitor, Pore Blocker, Potentiation 0
KH CB19 Pharma inhibitor of CLK1 and CLK4, potent and selective 0
ML167 Pharma Clk4 inhibitor,highly selective 0

(2) Additional Compounds for CLK4 Gene - From: HMDB and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist 58-64-0
TG 003
719277-26-6

(1) Tocris Compounds for CLK4 Gene

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

(2) ApexBio Compounds for CLK4 Gene

Compound Action Cas Number
KH CB19 inhibitor of CLK1 and CLK4, potent and selective 1354037-26-5
ML167 Clk4 inhibitor,highly selective 1285702-20-6
genes like me logo Genes that share compounds with CLK4: view

Drug Products

Transcripts for CLK4 Gene

mRNA/cDNA for CLK4 Gene

1 REFSEQ mRNAs :
21 NCBI additional mRNA sequence :
15 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CLK4

Alternative Splicing Database (ASD) splice patterns (SP) for CLK4 Gene

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

ExUns: 13 ^ 14 ^ 15 ^ 16
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:

Relevant External Links for CLK4 Gene

GeneLoc Exon Structure for
CLK4

Expression for CLK4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CLK4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CLK4 Gene

This gene is overexpressed in Brain - Cerebellum (x6.4) and Brain - Cerebellar Hemisphere (x6.0).

Protein differential expression in normal tissues from HIPED for CLK4 Gene

This gene is overexpressed in Monocytes (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CLK4 Gene



Protein tissue co-expression partners for CLK4 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CLK4

SOURCE GeneReport for Unigene cluster for CLK4 Gene:

Hs.406557

mRNA Expression by UniProt/SwissProt for CLK4 Gene:

Q9HAZ1-CLK4_HUMAN
Tissue specificity: Expressed in liver, kidney, heart, muscle, brain and endothelial cells.

Evidence on tissue expression from TISSUES for CLK4 Gene

  • Kidney(4.4)
  • Nervous system(3.9)
  • Skin(2.3)
  • Intestine(2.1)
  • Heart(2.1)
genes like me logo Genes that share expression patterns with CLK4: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for CLK4 Gene

Orthologs for CLK4 Gene

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

Orthologs for CLK4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia CLK4 30 31
  • 99.65 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia CLK4 30 31
  • 95.29 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 95 (a)
OneToMany
-- 31
  • 91 (a)
OneToMany
-- 31
  • 56 (a)
OneToMany
Dog
(Canis familiaris)
Mammalia CLK4 30 31
  • 94.39 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Clk4 30 17 31
  • 90.64 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia CLK4 31
  • 90 (a)
OneToOne
Chicken
(Gallus gallus)
Aves CLK4 30 31
  • 77.73 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia CLK4 31
  • 74 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.17441 30
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia Str.4557 30
Zebrafish
(Danio rerio)
Actinopterygii clk4a 30 31
  • 63.44 (n)
ManyToMany
clk4b 31
  • 59 (a)
ManyToMany
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.1122 30
Fruit Fly
(Drosophila melanogaster)
Insecta Doa 31 32
  • 12 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea tag-172 31
  • 23 (a)
OneToMany
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes KNS1 31
  • 23 (a)
OneToMany
Bread mold
(Neurospora crassa)
Ascomycetes NCU00230 30
  • 50.17 (n)
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.719 31
  • 47 (a)
OneToMany
Species where no ortholog for CLK4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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)
  • 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)
  • Rat (Rattus norvegicus)
  • 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)

Evolution for CLK4 Gene

ENSEMBL:
Gene Tree for CLK4 (if available)
TreeFam:
Gene Tree for CLK4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CLK4: view image

Paralogs for CLK4 Gene

(6) SIMAP similar genes for CLK4 Gene using alignment to 7 proteins:

  • CLK4_HUMAN
  • B7ZL31_HUMAN
  • B9EG64_HUMAN
  • E7ES88_HUMAN
  • E7EWJ6_HUMAN
  • Q4G0Z5_HUMAN
  • Q6P090_HUMAN
genes like me logo Genes that share paralogs with CLK4: view

Variants for CLK4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CLK4 Gene

SNP ID Clinical significance and condition Chr 05 pos Variation AA Info Type
778337 Benign: not provided 178,618,643(-) G/A SYNONYMOUS_VARIANT
rs35272416 - p.Leu352Phe
rs55746655 - p.Ile363Val

Additional dbSNP identifiers (rs#s) for CLK4 Gene

Structural Variations from Database of Genomic Variants (DGV) for CLK4 Gene

Variant ID Type Subtype PubMed ID
nsv1120062 OTHER inversion 24896259

Variation tolerance for CLK4 Gene

Residual Variation Intolerance Score: 50.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.12; 22.82% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CLK4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
CLK4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CLK4 Gene

Disorders for CLK4 Gene

MalaCards: The human disease database

(2) MalaCards diseases for CLK4 Gene - From: DISEASES

Disorder Aliases PubMed IDs
cone-rod dystrophy 6
  • retinitis pigmentosa 6
fanconi anemia, complementation group a
  • fanca
- elite association - COSMIC cancer census association via MalaCards
Search CLK4 in MalaCards View complete list of genes associated with diseases
genes like me logo Genes that share disorders with CLK4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CLK4 Gene

Publications for CLK4 Gene

  1. Molecular characterization of a cDNA encoding functional human CLK4 kinase and localization to chromosome 5q35 [correction of 4q35]. (PMID: 11170754) Schultz J … Wallasch C (Genomics 2001) 2 3 4
  2. 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
  3. Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. (PMID: 17081983) Olsen JV … Mann M (Cell 2006) 3 4
  4. Beacon interacts with cdc2/cdc28-like kinases. (PMID: 12705895) Kantham L … Collier G (Biochemical and biophysical research communications 2003) 3 4
  5. Structural analysis of UBL5, a novel ubiquitin-like modifier. (PMID: 12824502) McNally T … Reilly RM (Protein science : a publication of the Protein Society 2003) 3 4

Products for CLK4 Gene

Sources for CLK4 Gene