The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with c... See more...

Aliases for DUSP4 Gene

Aliases for DUSP4 Gene

  • Dual Specificity Phosphatase 4 2 3 5
  • MAP Kinase Phosphatase 2 2 3 4
  • MKP-2 2 3 4
  • Mitogen-Activated Protein Kinase Phosphatase 2 3 4
  • Dual Specificity Protein Phosphatase HVH2 3 4
  • Dual Specificity Protein Phosphatase 4 3 4
  • VH1 Homologous Phosphatase 2 2 3
  • HVH2 2 3
  • MKP2 3 4
  • TYP 2 3
  • Serine/Threonine Specific Protein Phosphatase 3
  • EC 3.1.3.16 4
  • EC 3.1.3.48 4
  • DUSP4 5
  • VH2 4

External Ids for DUSP4 Gene

Previous GeneCards Identifiers for DUSP4 Gene

  • GC08M028766
  • GC08M029698
  • GC08M029014
  • GC08M029215
  • GC08M029249
  • GC08M027737
  • GC08M029190

Summaries for DUSP4 Gene

Entrez Gene Summary for DUSP4 Gene

  • The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene product inactivates ERK1, ERK2 and JNK, is expressed in a variety of tissues, and is localized in the nucleus. Two alternatively spliced transcript variants, encoding distinct isoforms, have been observed for this gene. In addition, multiple polyadenylation sites have been reported. [provided by RefSeq, Jul 2008]

GeneCards Summary for DUSP4 Gene

DUSP4 (Dual Specificity Phosphatase 4) is a Protein Coding gene. Diseases associated with DUSP4 include Echolalia and Ogden Syndrome. Among its related pathways are RET signaling and Nuclear Events (kinase and transcription factor activation). Gene Ontology (GO) annotations related to this gene include phosphatase activity and protein tyrosine/serine/threonine phosphatase activity. An important paralog of this gene is DUSP1.

UniProtKB/Swiss-Prot Summary for DUSP4 Gene

  • Regulates mitogenic signal transduction by dephosphorylating both Thr and Tyr residues on MAP kinases ERK1 and ERK2.

Gene Wiki entry for DUSP4 Gene

Additional gene information for DUSP4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for DUSP4 Gene

Genomics for DUSP4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for DUSP4 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 DUSP4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for DUSP4

Top Transcription factor binding sites by QIAGEN in the DUSP4 gene promoter:
  • Nkx3-1 v1
  • Nkx3-1 v2
  • p53

Genomic Locations for DUSP4 Gene

Genomic Locations for DUSP4 Gene
chr8:29,333,062-29,350,684
(GRCh38/hg38)
Size:
17,623 bases
Orientation:
Minus strand
chr8:29,190,579-29,208,267
(GRCh37/hg19)
Size:
17,689 bases
Orientation:
Minus strand

Genomic View for DUSP4 Gene

Genes around DUSP4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
DUSP4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for DUSP4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for DUSP4 Gene

Proteins for DUSP4 Gene

  • Protein details for DUSP4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q13115-DUS4_HUMAN
    Recommended name:
    Dual specificity protein phosphatase 4
    Protein Accession:
    Q13115
    Secondary Accessions:
    • B2RBU5
    • D3DSU4
    • G5E930
    • Q13524

    Protein attributes for DUSP4 Gene

    Size:
    394 amino acids
    Molecular mass:
    42953 Da
    Quaternary structure:
    • Hollow spherical complex composed of 24 subunits with pseudooctahedral symmetry, has a tetramer as the basic unit.
    Miscellaneous:
    • [Isoform 2]: Does not bind to JNK or ERK, and is more susceptible to proteosomal degradation.

    Three dimensional structures from OCA and Proteopedia for DUSP4 Gene

    Alternative splice isoforms for DUSP4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for DUSP4 Gene

Post-translational modifications for DUSP4 Gene

  • Phosphorylation in the C-terminus by ERK1/2 inhibits proteasomal degradation and stabilizes the protein.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for DUSP4 Gene

No data available for DME Specific Peptides for DUSP4 Gene

Domains & Families for DUSP4 Gene

Gene Families for DUSP4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Enzymes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for DUSP4 Gene

Suggested Antigen Peptide Sequences for DUSP4 Gene

GenScript: Design optimal peptide antigens:
  • Mitogen-activated protein kinase phosphatase 2 (DUS4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q13115

UniProtKB/Swiss-Prot:

DUS4_HUMAN :
  • Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.
Family:
  • Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.
genes like me logo Genes that share domains with DUSP4: view

Function for DUSP4 Gene

Molecular function for DUSP4 Gene

UniProtKB/Swiss-Prot Function:
Regulates mitogenic signal transduction by dephosphorylating both Thr and Tyr residues on MAP kinases ERK1 and ERK2.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] + phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620; EC=3.1.3.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU10044, ECO:0000269|PubMed:7535768};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] + phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474, ChEBI:CHEBI:83421; EC=3.1.3.16; Evidence={ECO:0000269|PubMed:7535768};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] + phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474, ChEBI:CHEBI:61977; EC=3.1.3.16; Evidence={ECO:0000269|PubMed:7535768};.
GENATLAS Biochemistry:
dual specificity (tyr/thr) phosphatase 4,vaccinia virus phosphatase VH1-like 2,expressed in placenta,pancreas,involved in signal transduction

Enzyme Numbers (IUBMB) for DUSP4 Gene

Phenotypes From GWAS Catalog for DUSP4 Gene

Gene Ontology (GO) - Molecular Function for DUSP4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004721 phosphoprotein phosphatase activity IEA,IBA 21873635
GO:0004725 protein tyrosine phosphatase activity IDA 7535768
GO:0005515 protein binding IPI 16038800
GO:0008138 protein tyrosine/serine/threonine phosphatase activity IBA --
GO:0008330 protein tyrosine/threonine phosphatase activity IDA 7535768
genes like me logo Genes that share ontologies with DUSP4: view
genes like me logo Genes that share phenotypes with DUSP4: view

Animal Models for DUSP4 Gene

MGI Knock Outs for DUSP4:

Animal Model Products

  • Taconic Biosciences Mouse Models for DUSP4

CRISPR Products

miRNA for DUSP4 Gene

miRTarBase miRNAs that target DUSP4

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for DUSP4

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for DUSP4 Gene

Localization for DUSP4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for DUSP4 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 DUSP4 gene
Compartment Confidence
nucleus 5
cytosol 4
plasma membrane 2
extracellular 2
cytoskeleton 2
mitochondrion 2
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for DUSP4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IBA,IDA 7535768
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IBA 21873635
genes like me logo Genes that share ontologies with DUSP4: view

Pathways & Interactions for DUSP4 Gene

PathCards logo

SuperPathways for DUSP4 Gene

SuperPathway Contained pathways
1 RET signaling
2 Activated TLR4 signalling
3 Nuclear Events (kinase and transcription factor activation)
4 MAPK signaling pathway
5 Developmental Biology
genes like me logo Genes that share pathways with DUSP4: view

Pathways by source for DUSP4 Gene

2 GeneGo (Thomson Reuters) pathways for DUSP4 Gene
  • Development EGFR signaling pathway
  • Signal transduction_Erk Interactions- Inhibition of Erk
1 Qiagen pathway for DUSP4 Gene
  • JNK Pathway
1 Cell Signaling Technology pathway for DUSP4 Gene

SIGNOR curated interactions for DUSP4 Gene

Inactivates:

Gene Ontology (GO) - Biological Process for DUSP4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000188 inactivation of MAPK activity IBA,IDA 7535768
GO:0001706 endoderm formation IBA 21873635
GO:0006470 protein dephosphorylation IEA,IBA 21873635
GO:0016311 dephosphorylation IDA 24531476
GO:0035335 peptidyl-tyrosine dephosphorylation IDA 7535768
genes like me logo Genes that share ontologies with DUSP4: view

Drugs & Compounds for DUSP4 Gene

(6) Drugs for DUSP4 Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Phosphoric acid Approved Pharma 0
Water Approved Pharma 0
Calcium Nutra 6556

(3) Additional Compounds for DUSP4 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Phosphate
  • [po(OH)3]
  • Acide phosphorique
  • Acidum phosphoricum
  • H3PO4
  • Orthophosphoric acid
14066-19-4, 14265-44-2
genes like me logo Genes that share compounds with DUSP4: view

Transcripts for DUSP4 Gene

mRNA/cDNA for DUSP4 Gene

2 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
2 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 DUSP4

Alternative Splicing Database (ASD) splice patterns (SP) for DUSP4 Gene

No ASD Table

Relevant External Links for DUSP4 Gene

GeneLoc Exon Structure for
DUSP4

Expression for DUSP4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for DUSP4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for DUSP4 Gene

This gene is overexpressed in Stomach (x5.3) and Breast - Mammary Tissue (x4.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for DUSP4 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for DUSP4

SOURCE GeneReport for Unigene cluster for DUSP4 Gene:

Hs.417962

Evidence on tissue expression from TISSUES for DUSP4 Gene

  • Skin(4.8)
  • Nervous system(4)
  • Lung(3.3)
  • Blood(2.5)
  • Pancreas(2.2)
  • Stomach(2.1)
  • Intestine(2.1)
genes like me logo Genes that share expression patterns with DUSP4: view

No data available for Protein differential expression in normal tissues , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for DUSP4 Gene

Orthologs for DUSP4 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for DUSP4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia DUSP4 30 31
  • 99.07 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia DUSP4 31
  • 95 (a)
OneToOne
LOC482880 30
  • 92.64 (n)
Cow
(Bos Taurus)
Mammalia DUSP4 30 31
  • 92.13 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Dusp4 30
  • 89.68 (n)
Mouse
(Mus musculus)
Mammalia Dusp4 30 17 31
  • 89.26 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 79 (a)
OneToMany
-- 31
  • 77 (a)
OneToMany
Oppossum
(Monodelphis domestica)
Mammalia DUSP4 31
  • 76 (a)
OneToOne
Chicken
(Gallus gallus)
Aves DUSP4 30 31
  • 81.42 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia DUSP4 31
  • 75 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia dusp4 30
  • 73.89 (n)
Zebrafish
(Danio rerio)
Actinopterygii dusp4 30 31
  • 71.12 (n)
OneToOne
zgc55423 30
Thale Cress
(Arabidopsis thaliana)
eudicotyledons IBR5 30
  • 47.18 (n)
Rice
(Oryza sativa)
Liliopsida Os02g0720300 30
  • 43 (n)
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 33 (a)
OneToMany
Species where no ortholog for DUSP4 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)
  • Baker's yeast (Saccharomyces cerevisiae)
  • 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)
  • Fruit Fly (Drosophila melanogaster)
  • 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 Vase (Ciona intestinalis)
  • 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)
  • Worm (Caenorhabditis elegans)

Evolution for DUSP4 Gene

ENSEMBL:
Gene Tree for DUSP4 (if available)
TreeFam:
Gene Tree for DUSP4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for DUSP4: view image

Paralogs for DUSP4 Gene

(8) SIMAP similar genes for DUSP4 Gene using alignment to 1 proteins:

  • DUS4_HUMAN
genes like me logo Genes that share paralogs with DUSP4: view

Variants for DUSP4 Gene

Additional dbSNP identifiers (rs#s) for DUSP4 Gene

Structural Variations from Database of Genomic Variants (DGV) for DUSP4 Gene

Variant ID Type Subtype PubMed ID
nsv951122 CNV deletion 24416366

Variation tolerance for DUSP4 Gene

Residual Variation Intolerance Score: 73.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.90; 18.70% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for DUSP4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
DUSP4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for DUSP4 Gene

Disorders for DUSP4 Gene

MalaCards: The human disease database

(4) MalaCards diseases for DUSP4 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
echolalia
ogden syndrome
  • ogdns
lymphopenia
  • lymphocytopenia
pervasive developmental disorder
  • pervasive development disorder
- elite association - COSMIC cancer census association via MalaCards
Search DUSP4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for DUSP4

genes like me logo Genes that share disorders with DUSP4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for DUSP4 Gene

Publications for DUSP4 Gene

  1. Isolation and characterization of a novel dual specific phosphatase, HVH2, which selectively dephosphorylates the mitogen-activated protein kinase. (PMID: 7535768) Guan KL … Butch E (The Journal of biological chemistry 1995) 2 3 4 23
  2. Differential regulation of MAP kinase activation by a novel splice variant of human MAP kinase phosphatase-2. (PMID: 19843478) Cadalbert LC … Plevin R (Cellular signalling 2010) 3 4 23
  3. Crystal structure of the catalytic domain of human MKP-2 reveals a 24-mer assembly. (PMID: 19415758) Jeong DG … Kim SJ (Proteins 2009) 3 4 23
  4. Chromosomal localization of three human dual specificity phosphatase genes (DUSP4, DUSP6, and DUSP7). (PMID: 9205128) Smith A … Ashworth A (Genomics 1997) 2 3 23
  5. The mitogen-activated protein kinase phosphatases PAC1, MKP-1, and MKP-2 have unique substrate specificities and reduced activity in vivo toward the ERK2 sevenmaker mutation. (PMID: 8626452) Chu Y … Kelly K (The Journal of biological chemistry 1996) 3 4 23

Products for DUSP4 Gene

Sources for DUSP4 Gene