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DUSP3

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Summary

DUSP3 (dual specificity phosphatase 3, HGNC:3069) is a protein-coding gene on chromosome 17q21.31, encoding Dual specificity protein phosphatase 3 (P51452). Shows activity both for tyrosine-protein phosphate and serine-protein phosphate, but displays a strong preference toward phosphotyrosines.

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 maps in a region that contains the BRCA1 locus which confers susceptibility to breast and ovarian cancer. Although DUSP3 is expressed in both breast and ovarian tissues, mutation screening in breast cancer pedigrees and in sporadic tumors was negative, leading to the conclusion that this gene is not BRCA1.

Source: NCBI Gene 1845 — RefSeq curated summary.

At a glance

  • GWAS associations: 6
  • Clinical variants (ClinVar): 24 total
  • GTEx eGene: eQTL in 21 tissues, sQTL in 13 (q < 0.05)
  • Constraint (gnomAD): pLI 0.04 (LoF-tolerant), LOEUF 1.06 (unconstrained)
  • MANE Select transcript: NM_004090

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:3069
Approved symbolDUSP3
Namedual specificity phosphatase 3
Location17q21.31
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000108861
Ensembl biotypeprotein_coding
OMIM600183
Entrez1845

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000226004

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 3: 1, TSL 5: 2

ENST00000226004, ENST00000590342, ENST00000590753, ENST00000590935, ENST00000591618, ENST00000861136, ENST00000949183, ENST00000983223, ENST00001106969, ENST00001117433, ENST00001142215

RefSeq mRNA: 1 — MANE Select: NM_004090 NM_004090

CCDS: CCDS11469

Canonical transcript exons

ENST00000226004 — 3 exons

ExonStartEnd
ENSE000008542064377880043778977
ENSE000012922774376612543769814
ENSE000035681934377471243774938

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 98.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.1384 / max 297.3607, expressed in 1813 samples.

Highest expression (Bgee): skeletal muscle tissue of rectus abdominis, skeletal muscle tissue of biceps brachii, biceps brachii, saphenous vein, vastus lateralis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

DUSP3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 21 tissues and its splicing (sQTL) in 13 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 34 significant tissue × QTL associations:

TissueQTLq-valueSlopeLead variant
Whole Bloodeqtl1.9e-21+0.2317:43773321:C:G
Muscle Skeletalsqtl2.2e-12-1.0517:43774624:T:C
Artery Tibialsqtl2.1e-11+1.4217:43774624:T:C
Cells Cultured fibroblastseqtl5.1e-09+0.3117:43766891:G:C
Esophagus Mucosaeqtl1.6e-07-0.1517:43802259:C:T
Esophagus Gastroesophageal Junctionsqtl7.8e-06+1.4317:43774624:T:C
Artery Aortasqtl9.5e-06+1.2117:43774624:T:C
Muscle Skeletaleqtl1.2e-05+0.1317:43765224:A:G
Artery Coronarysqtl1.9e-04+1.3817:43774624:T:C
Esophagus Muscularissqtl4.4e-04+1.1717:43776870:G:T
Colon Sigmoidsqtl8.6e-04+1.2817:43774624:T:C
Artery Tibialeqtl1.0e-03-0.2117:43835134:C:G
Thyroideqtl3.8e-03+0.1217:43837458:C:T
Artery Aortaeqtl7.2e-03+0.1417:43814671:C:A
Pituitaryeqtl7.4e-03+0.2217:43456911:C:T
Testissqtl1.0e-02+0.7217:43720816:C:A
Skin Not Sun Exposed Suprapubiceqtl1.0e-02-0.1217:43768456:G:A
Brain Cerebellar Hemisphereeqtl1.1e-02-0.3317:43187992:G:A
Heart Atrial Appendagesqtl1.2e-02-1.1517:43776870:G:T
Nerve Tibialeqtl1.2e-02+0.3017:43952508:C:T

FANTOM5 promoters

4 alternative TSS:

Promoter IDTPM avgSamples expressed
16627744.63081812
1662761.72281012
1662720.4248205
1662730.3600174

Top tissues by expression

showing 100 of 301 tissues by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
skeletal muscle tissue of rectus abdominisUBERON:000451198.72gold quality
skeletal muscle tissue of biceps brachiiUBERON:000450298.62gold quality
biceps brachiiUBERON:000150798.34gold quality
saphenous veinUBERON:000731898.28gold quality
vastus lateralisUBERON:000137998.22gold quality
hindlimb stylopod muscleUBERON:000425298.22gold quality
skeletal muscle tissueUBERON:000113498.20gold quality
left ventricle myocardiumUBERON:000656698.20gold quality
quadriceps femorisUBERON:000137798.10gold quality
cardiac ventricleUBERON:000208298.08gold quality
heart left ventricleUBERON:000208498.08gold quality
diaphragmUBERON:000110397.97gold quality
gastrocnemiusUBERON:000138897.86gold quality
heart right ventricleUBERON:000208097.83gold quality
muscle tissueUBERON:000238597.79gold quality
muscle organUBERON:000163097.71gold quality
skeletal muscle organUBERON:001489297.71gold quality
apex of heartUBERON:000209897.70gold quality
myocardiumUBERON:000234997.70gold quality
gluteal muscleUBERON:000200097.66gold quality
body of tongueUBERON:001187697.60gold quality
muscle of legUBERON:000138397.53gold quality
heartUBERON:000094897.37gold quality
triceps brachiiUBERON:000150997.22gold quality
deltoidUBERON:000147697.17gold quality
right coronary arteryUBERON:000162597.04gold quality
lateral nuclear group of thalamusUBERON:000273696.93gold quality
cauda epididymisUBERON:000436096.82gold quality
cardiac atriumUBERON:000208196.77gold quality
right atrium auricular regionUBERON:000663196.72gold quality
type B pancreatic cellCL:000016996.71gold quality
lower esophagus muscularis layerUBERON:003583396.68gold quality
lower esophagusUBERON:001347396.67gold quality
cardiac muscle of right atriumUBERON:000337996.66gold quality
renal medullaUBERON:000036296.63gold quality
orbitofrontal cortexUBERON:000416796.56gold quality
prefrontal cortexUBERON:000045196.19gold quality
coronary arteryUBERON:000162196.13gold quality
muscle layer of sigmoid colonUBERON:003580596.11gold quality
dorsal root ganglionUBERON:000004496.10gold quality
esophagogastric junction muscularis propriaUBERON:003584196.09gold quality
frontal poleUBERON:000279596.06gold quality
left coronary arteryUBERON:000162695.98gold quality
arteryUBERON:000163795.95gold quality
popliteal arteryUBERON:000225095.92gold quality
tibial arteryUBERON:000761095.92gold quality
Brodmann (1909) area 9UBERON:001354095.88gold quality
cardia of stomachUBERON:000116295.84gold quality
aortaUBERON:000094795.81gold quality
vena cavaUBERON:000408795.80gold quality
urethraUBERON:000005795.79gold quality
dorsolateral prefrontal cortexUBERON:000983495.75gold quality
adult mammalian kidneyUBERON:000008295.74gold quality
tibialis anteriorUBERON:000138595.72gold quality
pylorusUBERON:000116695.70gold quality
thoracic aortaUBERON:000151595.66gold quality
Brodmann (1909) area 46UBERON:000648395.66gold quality
ascending aortaUBERON:000149695.63gold quality
tongueUBERON:000172395.56gold quality
frontal cortexUBERON:000187095.56gold quality
substantia nigra pars compactaUBERON:000196595.56gold quality
superficial temporal arteryUBERON:000161495.55gold quality
dorsal motor nucleus of vagus nerveUBERON:000287095.54gold quality
lower lobe of lungUBERON:000894995.46gold quality
cingulate cortexUBERON:000302795.43gold quality
olfactory bulbUBERON:000226495.41gold quality
nippleUBERON:000203095.39gold quality
smooth muscle tissueUBERON:000113595.38gold quality
right frontal lobeUBERON:000281095.37gold quality
anterior cingulate cortexUBERON:000983595.36gold quality
inferior olivary complexUBERON:000212795.34gold quality
ponsUBERON:000098895.20gold quality
right lobe of liverUBERON:000111495.17gold quality
neocortexUBERON:000195095.17gold quality
substantia nigra pars reticulataUBERON:000196695.16gold quality
parietal lobeUBERON:000187295.14gold quality
superior frontal gyrusUBERON:000266195.10gold quality
Brodmann (1909) area 10UBERON:001354195.02gold quality
descending thoracic aortaUBERON:000234594.92gold quality
cerebral cortexUBERON:000095694.91gold quality
trigeminal ganglionUBERON:000167594.91gold quality
islet of LangerhansUBERON:000000694.88gold quality
pharyngeal mucosaUBERON:000035594.88gold quality
amygdalaUBERON:000187694.87gold quality
liverUBERON:000210794.85gold quality
temporal lobeUBERON:000187194.80gold quality
entorhinal cortexUBERON:000272894.77gold quality
lower esophagus mucosaUBERON:003583494.77gold quality
dorsal plus ventral thalamusUBERON:000189794.76gold quality
postcentral gyrusUBERON:000258194.75gold quality
lateral globus pallidusUBERON:000247694.68gold quality
sigmoid colonUBERON:000115994.54gold quality
medulla oblongataUBERON:000189694.50gold quality
superior vestibular nucleusUBERON:000722794.39gold quality
jejunumUBERON:000211594.35gold quality
telencephalonUBERON:000189394.32gold quality
cerebellar vermisUBERON:000472094.25gold quality
ventral tegmental areaUBERON:000269194.22gold quality
hypothalamusUBERON:000189894.21gold quality
fundus of stomachUBERON:000116094.17gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3no0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 74 HPA tissues / cells by nTPM:

Tissue / cellAxisnTPM
Skeletal muscletissue245.3
Tonguetissue199.4
Corpus callosumtissue151.8
Spinal cordtissue135.9
Heart muscletissue130.0
Cerebral cortextissue115.1
Motor cortextissue115.1
Somatosensory cortextissue111.6
Midbraintissue108.9
Occipital cortextissue107.3
Medulla oblongatatissue106.2
Prefrontal cortextissue102.6
Hippocampal formationtissue98.9
Entorhinal cortextissue97.8
Temporal cortextissue93.5
Insular cortextissue93.3
Thalamustissue93.2
Cingulate cortextissue93.2
Retrosplenial cortextissue91.7
Substantia nigratissue91.2
Superior colliculitissue85.0
Ponstissue84.5
Putamentissue76.1
Postcentral gyrustissue72.5
Seminal vesicletissue68.7
Ventral pallidumtissue65.4
Locus coeruleustissue63.3
Hippocampustissue61.1
Amygdalatissue59.6
Livertissue59.6
Smooth muscletissue58.8
Periaqueductal graytissue56.2
Hypothalamustissue55.9
Septumtissue55.0
Kidneytissue53.0
Choroid plexustissue52.5
Basal gangliatissue51.9
Nucleus accumbenstissue46.7
Esophagustissue45.4
Parathyroid glandtissue44.2
Prostatetissue42.1
Olfactory bulbtissue40.0
Urinary bladdertissue37.3
Lungtissue34.0
Adrenal glandtissue33.7
Adipose tissuetissue33.6
Vaginatissue32.3
Pancreastissue32.1
Pituitary glandtissue32.0
Gallbladdertissue31.3
Cerebellumtissue30.3
Spleentissue29.7
Endometrium 1tissue29.6
Placentatissue29.5
Epididymistissue29.4
Retinatissue28.5
Colontissue28.2
Thyroid glandtissue26.2
Duodenumtissue26.2
Small intestinetissue25.8

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — White matter (151.8), Ventral spinal cord (135.9), Dorsal spinal cord (114.6), Dorsal hippocampus (98.9), Blood vessel (83.3).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting DUSP3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 167 miRNAs:

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4668-3P100.0068.742635
HSA-MIR-5011-5P100.0083.465820
HSA-MIR-6758-5P100.0066.211470
HSA-MIR-6856-5P100.0065.471298
HSA-MIR-371B-5P99.9975.344759
HSA-MIR-373-5P99.9875.364753
HSA-MIR-616-5P99.9875.584775
HSA-MIR-3617-3P99.9867.86918
HSA-MIR-477599.9875.006394
HSA-MIR-548AN99.9770.912817
HSA-MIR-3065-5P99.9771.563281
HSA-MIR-6888-3P99.9765.951170
HSA-MIR-6825-5P99.9669.813431
HSA-MIR-590-3P99.9674.346478
HSA-MIR-548AA99.9670.643753
HSA-MIR-548AP-3P99.9670.643753
HSA-MIR-548T-3P99.9670.643753
HSA-MIR-4725-3P99.9669.532520
HSA-MIR-6780B-5P99.9669.602562
HSA-MIR-23A-3P99.9574.243163
HSA-MIR-23B-3P99.9574.243163
HSA-MIR-23C99.9573.923192
HSA-MIR-141-3P99.9472.792421
HSA-MIR-200A-3P99.9472.682420
HSA-MIR-651-3P99.9473.485177
HSA-MIR-6721-5P99.9368.922981
HSA-MIR-515-5P99.9269.822343
HSA-MIR-519E-5P99.9269.622358
HSA-MIR-124-3P99.8973.743043
HSA-MIR-506-3P99.8973.553057

Functional genomics

gnomAD constraint: pLI 0.0402, LOEUF 1.06, missense Z 0.729 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000226004 — one region, missense o/e 0.83.

Literature-anchored findings (GeneRIF, showing 27)

  • VHR, a Vaccinia virus VH1-related dual-specific protein phosphatase, is phosphorylated at Y138 by ZAP-70. (PMID:12447358)
  • VHR is required for cell-cycle progression as it modulates MAP kinase activation in a cell-cycle phase-dependent manner. (PMID:16604064)
  • deregulated expression of BRCA1-IRIS is likely to reduce dependence on normal physiological growth stimuli (PMID:17278098)
  • Small dual-specificity phosphatase VHR selectively dephosphorylates tyrosine-phosphorylated interferon-alpha- and beta-activated transcription factor STAT5, leading to the subsequent inhibition of STAT5 function. (PMID:17785772)
  • Results highlight the importance of a high intracellular Zn(2+) content and the VHR/ZAP-70/ERK1,2-associated pathways in the modulation of LNCaP prostate cancer cell growth. (PMID:18311544)
  • VHR can be considered as a new marker for cancer progression in cervix carcinoma and potential new target for anticancer therapy (PMID:18505570)
  • VHR has a direct role in the inhibition of JNK-dependent apoptosis in LNCaP cells and may therefore have a role in prostate cancer progression. (PMID:19010898)
  • VHR expression enhances the signaling of ErbB receptors and may be involved in NSCLC pathogenesis. (PMID:21262974)
  • Enteric commensal bacteria induce extracellular signal-regulated kinase pathway signaling via formyl peptide receptor-dependent redox modulation of dual specific phosphatase 3 (PMID:21921027)
  • Proteins containing the class II motifs are efficient VHR substrates in vitro, suggesting that VHR may act on a novel class of yet unidentified Tyr(P) proteins in vivo. (PMID:23322772)
  • we report the first successful site-specific incorporation of sulfotyrisine into VHR through the use of expanding genetic code (PMID:23918168)
  • DUSP3 interacting partners are nucleolar proteins involved in processes related to DNA repair and senescence. (PMID:24245651)
  • VHR can dimerize inside cells, and that VHR catalytic activity is reduced upon dimerization. (PMID:24798147)
  • DUSP3 is a pro-angiogenic atypical dual-specificity phosphatase. (PMID:24886454)
  • Data suggest levels of gene expression of both DUSP3 (dual specificity phosphatase 3) and PSME3 (proteasome activator subunit 3) are associated with susceptibility to Staphylococcus aureus infection/sepsis in humans and in mouse disease model. (PMID:24901344)
  • Our results demonstrate that DUSP3 plays a key and nonredundant role as a regulator of innate immune responses (PMID:25876765)
  • In the phosphatase-silenced cells, the normal bipolar spindle structure was restored by chemical inhibition of Erk1/2 and ectopic overexpression of Dusp3. We propose that at M phase Dusp3 keeps Erk1/2 activity in check to facilitate normal mitosis. (PMID:27423135)
  • Nuclear HSP70 leads to enhancement of vaccinia H1-related phosphatase (VHR) activity via protein-protein interaction rather than its molecular chaperone activity, thereby suppressing excessive ERK activation. Downregulation of either VRK3 or HSP70 rendered cells vulnerable to glutamate-induced apoptosis. (PMID:27941812)
  • The loss of DUSP3 activity markedly increases gamma radiation-induced DNA strand breaks, suggesting a potential novel role for DUSP3 in DNA repair. (PMID:28389334)
  • In PTP1B and VHR, two new allosteric clusters were identified in each enzyme. (PMID:28625849)
  • Data indicated that regulating non-receptor tyrosine kinase FAK and cell migration is a newly revealed function of VHR/DUSP3. (PMID:28759036)
  • Study demonstrated that miR-1915-3p might promote the proliferation and metastasis of breast cancer by repression of DUSP3 and serum miR-1915-3p and miR-455-3p could serve as diagnostic and predictive biomarkers for breast cancer. (PMID:30048472)
  • Allosteric Impact of the Variable Insert Loop in Vaccinia H1-Related (VHR) Phosphatase. (PMID:32348128)
  • DUSP3 maintains genomic stability and cell proliferation by modulating NER pathway and cell cycle regulatory proteins. (PMID:32380926)
  • Regulation of signal transducer and activator of transcription 3 activation by dual-specificity phosphatase 3. (PMID:32475380)
  • The role of dual-specificity phosphatase 3 in melanocytic oncogenesis. (PMID:35899430)
  • DUSP3 modulates IRES-dependent translation of mRNAs through dephosphorylation of the HNRNPC protein in cells under genotoxic stimulus. (PMID:38538536)

Cross-species orthologs

0 orthologs

Paralogs (31): DUSP13B (ENSG00000079393), DUSP12 (ENSG00000081721), SSH1 (ENSG00000084112), PTPMT1 (ENSG00000110536), DUSP16 (ENSG00000111266), EPM2A (ENSG00000112425), DUSP22 (ENSG00000112679), DUSP1 (ENSG00000120129), DUSP4 (ENSG00000120875), STYXL1 (ENSG00000127952), DUSP9 (ENSG00000130829), DUSP26 (ENSG00000133878), DUSP5 (ENSG00000138166), DUSP6 (ENSG00000139318), SSH2 (ENSG00000141298), DUSP10 (ENSG00000143507), DUSP15 (ENSG00000149599), DUSP2 (ENSG00000158050), KASH5 (ENSG00000161609), DUSP19 (ENSG00000162999), DUSP7 (ENSG00000164086), DUSP18 (ENSG00000167065), SSH3 (ENSG00000172830), DUSP8 (ENSG00000184545), DUSP28 (ENSG00000188542), DUSP29 (ENSG00000188716), DUSP21 (ENSG00000189037), STYX (ENSG00000198252), STYXL2 (ENSG00000198842), DUSP14 (ENSG00000276023), DUSP13A (ENSG00000293543)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1919599) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 10 distinct phenotype terms.

Mouse phenotype (MP)Records
increased circulating insulin level1
decreased hemoglobin content1
increased circulating glycerol level1
decreased lean body mass1
abnormal humerus morphology1
decreased circulating creatinine level1
decreased angiogenesis1
decreased grip strength1
decreased red blood cell distribution width1
decreased bone mineral content1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

OrganismUniProtIdentityMethod
Pongo abeliiQ5RD73100.0%Diamond
Bos taurusQ2KJ3699.2%Diamond
Rattus norvegicusQ6334098.8%Diamond
Mus musculusQ91Z4698.8%Diamond
Pan troglodytesP0C59498.2%Diamond
Xenopus laevisQ4V7N397.8%Diamond
Xenopus tropicalisA4IHU792.3%Diamond
Sus scrofaP0C59690.5%Diamond
Takifugu rubripesP0C59989.0%Diamond
Tetraodon nigroviridisQ4RQD389.0%Diamond
Monodelphis domesticaP0C59386.4%Diamond
Gasterosteus aculeatusP0C5A082.9%Diamond
Gallus gallusP0C59782.1%Diamond
Anolis carolinensisP0C59881.9%Diamond
Oryzias latipesP0C5A180.9%Diamond
Equus caballusP0C59278.5%Diamond
Danio rerioQ566R769.1%Diamond
Callorhinchus miliiP0C5A268.5%Diamond
Arabidopsis thalianaQ9M8K764.0%Diamond
Dictyostelium discoideumQ55CS862.6%Diamond
Saccharomyces cerevisiae S288CP4047952.7%Diamond
Drosophila melanogasterQ6NN8550.9%Diamond
Vaccinia virus WRP0723999.4%Diamond
Vaccinia virus CopenhagenP2049599.4%Diamond
Monkeypox virusA0A7H0DN7898.8%Diamond
Orgyia pseudotsugata multiple nucleopolyhedrovirusO1027353.8%Diamond
Betaentomopoxvirus amooreiQ9EMX151.9%Diamond
Invertebrate iridescent virus 6O5573749.4%Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

SymbolTypeEntrez
LINC02594ncRNA105371786
MEOX1protein-coding4222
SOSTprotein-coding50964
CFAP97D1protein-coding284067
MPP3protein-coding4356
CD300LGprotein-coding146894

Protein

Protein identifiers

Dual specificity protein phosphatase 3 — P51452 (reviewed: P51452)

Alternative names: Dual specificity protein phosphatase VHR, Vaccinia H1-related phosphatase

All UniProt accessions (4): P51452, K7ELG5, K7EPK5, K7ES89

UniProt curated annotations — full annotation on UniProt →

Function. Shows activity both for tyrosine-protein phosphate and serine-protein phosphate, but displays a strong preference toward phosphotyrosines. Specifically dephosphorylates and inactivates ERK1 and ERK2.

Subunit / interactions. Microtubule inner protein component of sperm flagellar doublet microtubules. Interacts with VRK3; this interaction activates DUSP3 phosphatase activity.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Flagellum axoneme.

Similarity. Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.

Isoforms (2)

UniProt IDNamesCanonical?
P51452-11yes
P51452-22

RefSeq proteins (1): NP_004081* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000340Dual-sp_phosphatase_cat-domDomain
IPR000387Tyr_Pase_domDomain
IPR016130Tyr_Pase_ASActive_site
IPR020405Atypical_DUSP_subfamAFamily
IPR020422TYR_PHOSPHATASE_DUAL_domDomain
IPR029021Prot-tyrosine_phosphatase-likeHomologous_superfamily

Pfam: PF00782

Enzyme classification (BRENDA)

  • EC 3.1.3.16 — protein-serine/threonine phosphatase (BRENDA: 92 organisms, 641 substrates, 468 inhibitors, 127 Km, 67 kcat entries)
  • EC 3.1.3.48 — protein-tyrosine-phosphatase (BRENDA: 59 organisms, 501 substrates, 1326 inhibitors, 270 Km, 165 kcat entries)

Substrate kinetics (BRENDA)

129 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

SubstrateKm (mM)Measurements
4-NITROPHENYL PHOSPHATE0.0008–14884
6,8-DIFLUORO-4-METHYLUMBELLIFERYL PHOSPHATE0.0039–0.86227
6,8-DIFLUORO-4-METHYLUMBELLIFERYL PHOSPHATE0.023–0.86222
P-NITROPHENYL PHOSPHATE0.0024–1020
4-NITROPHENYL PHOSPHATE0.0028–12.713
DADEPYLIPQQG0.0003–0.112
P-NITROPHENYL PHOSPHATE3–20011
PHOSPHOTYROSINE0.012–3011
LYSOZYME0.0003–0.0125
MYELIN BASIC PROTEIN0.0001–0.0225
RRAPTVA0.058–1.9544
ACETYL-DADEPY-NH20.0228–0.2194
ACETYL-DADEPYL-NH21.1–97.54
PHOSPHOCASEIN0.0001–0.0023
PHOSPHOHISTONE0.0023–0.07233

Catalyzed reactions (Rhea)

  • O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate (RHEA:10684)
  • O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate (RHEA:20629)
  • O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate (RHEA:47004)

UniProt features (24 total): helix 10, strand 8, turn 2, chain 1, domain 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

9 structures by resolution:

PDBTitleMethodResolution (Å)
8TK6HUMAN VH1-RELATED DUAL-SPECIFICITY PHOSPHATASE (VHR) in apo formX-RAY DIFFRACTION1.65
8TK2HUMAN VH1-RELATED DUAL-SPECIFICITY PHOSPHATASE (VHR) complexed with …X-RAY DIFFRACTION1.7
8TK4HUMAN VH1-RELATED DUAL-SPECIFICITY PHOSPHATASE (VHR) complexed with phosphateX-RAY DIFFRACTION1.8
3F81Interaction of VHR with SA3X-RAY DIFFRACTION1.9
8TK5HUMAN VH1-RELATED DUAL-SPECIFICITY PHOSPHATASE (VHR) complexed with HEPESX-RAY DIFFRACTION1.9
9DJ9HUMAN VH1-RELATED DUAL-SPECIFICITY PHOSPHATASE (VHR) in distinct apo formX-RAY DIFFRACTION1.92
8TK3HUMAN VH1-RELATED DUAL-SPECIFICITY PHOSPHATASE (VHR) having oxidized catalytic cysteine …X-RAY DIFFRACTION2
1VHRHUMAN VH1-RELATED DUAL-SPECIFICITY PHOSPHATASEX-RAY DIFFRACTION2.1
1J4XHUMAN VH1-RELATED DUAL-SPECIFICITY PHOSPHATASE C124S MUTANT-PEPTIDE COMPLEXX-RAY DIFFRACTION2.75

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P51452-F196.100.93

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Predicted intracellular proteins, Plasma proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytosol

Antibody reliability (HPA): IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1)

PositionRole
124phosphocysteine intermediate

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 30; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

30 pathways:

IDPathwayEvidence
R-HSA-202670ERKs are inactivatedcurated
R-HSA-1280215Cytokine Signaling in Immune system—
R-HSA-198753ERK/MAPK targets—
R-HSA-168256Immune System—
R-HSA-168249Innate Immune System—
R-HSA-448424Interleukin-17 signaling—
R-HSA-450294MAP kinase activation—
R-HSA-450282MAPK targets/ Nuclear events mediated by MAP kinases—
R-HSA-975871MyD88 cascade initiated on plasma membrane—
R-HSA-975155MyD88 dependent cascade initiated on endosome—
R-HSA-166166MyD88-independent TLR4 cascade—
R-HSA-166058MyD88:MAL(TIRAP) cascade initiated on plasma membrane—
R-HSA-198725Nuclear Events (kinase and transcription factor activation)—
R-HSA-162582Signal Transduction—
R-HSA-449147Signaling by Interleukins—
R-HSA-187037Signaling by NTRK1 (TRKA)—
R-HSA-166520Signaling by NTRKs—
R-HSA-9006934Signaling by Receptor Tyrosine Kinases—
R-HSA-975138TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation—
R-HSA-937061TRIF (TICAM1)-mediated TLR4 signaling—
R-HSA-168142Toll Like Receptor 10 (TLR10) Cascade—
R-HSA-181438Toll Like Receptor 2 (TLR2) Cascade—
R-HSA-168164Toll Like Receptor 3 (TLR3) Cascade—
R-HSA-166016Toll Like Receptor 4 (TLR4) Cascade—
R-HSA-168176Toll Like Receptor 5 (TLR5) Cascade—
R-HSA-168181Toll Like Receptor 7/8 (TLR7/8) Cascade—
R-HSA-168138Toll Like Receptor 9 (TLR9) Cascade—
R-HSA-168179Toll Like Receptor TLR1:TLR2 Cascade—
R-HSA-168188Toll Like Receptor TLR6:TLR2 Cascade—
R-HSA-168898Toll-like Receptor Cascades—

MSigDB gene sets: 344 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GOBP_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GOBP_FOCAL_ADHESION_ASSEMBLY, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP

GO Biological Process (16): dephosphorylation (GO:0016311), negative regulation of cell migration (GO:0030336), peptidyl-tyrosine dephosphorylation (GO:0035335), negative regulation of epidermal growth factor receptor signaling pathway (GO:0042059), negative regulation of MAPK cascade (GO:0043409), positive regulation of mitotic cell cycle (GO:0045931), negative regulation of JNK cascade (GO:0046329), negative regulation of T cell receptor signaling pathway (GO:0050860), negative regulation of T cell activation (GO:0050868), negative regulation of chemotaxis (GO:0050922), regulation of focal adhesion assembly (GO:0051893), negative regulation of ERK1 and ERK2 cascade (GO:0070373), cellular response to epidermal growth factor stimulus (GO:0071364), positive regulation of focal adhesion disassembly (GO:0120183), protein dephosphorylation (GO:0006470), negative regulation of signal transduction (GO:0009968)

GO Molecular Function (13): protein serine/threonine phosphatase activity (GO:0004722), protein tyrosine phosphatase activity (GO:0004725), cytoskeletal protein binding (GO:0008092), protein tyrosine/serine/threonine phosphatase activity (GO:0008138), phosphatase activity (GO:0016791), protein kinase binding (GO:0019901), receptor signaling protein tyrosine kinase inhibitor activity (GO:0030294), receptor tyrosine kinase binding (GO:0030971), MAP kinase phosphatase activity (GO:0033549), protein tyrosine kinase binding (GO:1990782), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (5): immunological synapse (GO:0001772), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

11 top-level categories:

CategoryPathways
Toll-like Receptor Cascades7
Immune System2
Toll Like Receptor 4 (TLR4) Cascade2
Toll Like Receptor 2 (TLR2) Cascade2
ERK/MAPK targets1
Toll Like Receptor TLR1:TLR2 Cascade1
Toll Like Receptor TLR6:TLR2 Cascade1
Signaling by Receptor Tyrosine Kinases1
Innate Immune System1
Signaling by NTRKs1
Signaling by NTRK1 (TRKA)1

GO top-level categories

showing 60 of 63 GO namespaces:

CategoryTerms
phosphoprotein phosphatase activity4
cellular anatomical structure4
negative regulation of MAPK cascade2
phosphate-containing compound metabolic process1
cell migration1
regulation of cell migration1
negative regulation of cell motility1
protein dephosphorylation1
epidermal growth factor receptor signaling pathway1
regulation of epidermal growth factor receptor signaling pathway1
negative regulation of ERBB signaling pathway1
MAPK cascade1
regulation of MAPK cascade1
negative regulation of intracellular signal transduction1
mitotic cell cycle1
regulation of mitotic cell cycle1
positive regulation of cell cycle1
JNK cascade1
regulation of JNK cascade1
T cell receptor signaling pathway1
regulation of T cell receptor signaling pathway1
negative regulation of antigen receptor-mediated signaling pathway1
T cell activation1
regulation of T cell activation1
negative regulation of lymphocyte activation1
negative regulation of leukocyte cell-cell adhesion1
chemotaxis1
negative regulation of response to external stimulus1
negative regulation of locomotion1
regulation of chemotaxis1
regulation of cell-matrix adhesion1
focal adhesion assembly1
regulation of cell-substrate junction assembly1
ERK1 and ERK2 cascade1
regulation of ERK1 and ERK2 cascade1
response to epidermal growth factor1
cellular response to growth factor stimulus1
focal adhesion disassembly1
regulation of focal adhesion disassembly1
positive regulation of cell-substrate junction organization1
dephosphorylation1
protein modification process1
signal transduction1
regulation of signal transduction1
negative regulation of cell communication1
negative regulation of signaling1
negative regulation of response to stimulus1
protein binding1
phosphoric ester hydrolase activity1
kinase binding1
protein tyrosine kinase inhibitor activity1
signaling receptor binding1
protein tyrosine kinase binding1
protein kinase binding1
phosphatase activity1
catalytic activity, acting on a protein1
binding1
catalytic activity1
plasma membrane1
intracellular membrane-bounded organelle1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 25 of 34 annotations. The rest are phylogenetic / computational / electronic (IEA).

25 experimentally-supported GO terms:

GO termNSEvidence
cellular response to epidermal growth factor stimulusBPmutant phenotype
dephosphorylationBPdirect assay
negative regulation of ERK1 and ERK2 cascadeBPdirect assay
negative regulation of JNK cascadeBPdirect assay
negative regulation of MAPK cascadeBPmutant phenotype
negative regulation of T cell activationBPdirect assay
negative regulation of T cell receptor signaling pathwayBPdirect assay
negative regulation of cell migrationBPmutant phenotype
negative regulation of chemotaxisBPmutant phenotype
peptidyl-tyrosine dephosphorylationBPdirect assay
positive regulation of focal adhesion disassemblyBPmutant phenotype
positive regulation of mitotic cell cycleBPmutant phenotype
regulation of focal adhesion assemblyBPmutant phenotype
cytosolCCdirect assay
immunological synapseCCdirect assay
nucleoplasmCCdirect assay
nucleusCCdirect assay
MAP kinase phosphatase activityMFmutant phenotype
cytoskeletal protein bindingMFphysical interaction
phosphatase activityMFdirect assay
protein kinase bindingMFdirect assay
protein tyrosine kinase bindingMFphysical interaction
protein tyrosine phosphatase activityMFdirect assay
protein tyrosine/serine/threonine phosphatase activityMFdirect assay
receptor tyrosine kinase bindingMFphysical interaction

Protein interactions and networks

STRING

showing 16 of 1,219 interactions by confidence (×1000):

Protein AProtein BPartner UniProtScore
DUSP3PTSQ03393675
DUSP3PTPN1P18031659
DUSP3EPM2AO95278625
DUSP3PTPN7P35236610
DUSP3DUSP23Q9BVJ7609
DUSP3PTPRAP18433571
DUSP3VRK3Q8IV63569
DUSP3ZAP70P43403561
DUSP3GBP5Q96PP8550
DUSP3KDM2AQ9Y2K7522
DUSP3PTPN2P17706509
DUSP3MAPK1P28482496
DUSP3NFATC2Q13469486
DUSP3ACP1P24666484
DUSP3LHFPL2Q6ZUX7470
DUSP3CDC14AQ9UNH5470

IntAct

Human interaction partners of DUSP3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

11 partners by confidence:

PartnerInteraction typeMIscoreRecords
MEOX1physical association0.5603
ERLIN1association0.5305
MAPK1dephosphorylation reaction0.4401
MAPK3dephosphorylation reaction0.4401
TUFMphysical association0.4001
BNIP3Lphysical association0.3701
CASKphysical association0.3701
NEUROD1physical association0.3701
POU3F1association0.3501
HLA-Bphysical association0.0001
MCCphysical association0.0001

BioGRID (91 interactions; top human partners by supporting records): AGO2 (Affinity Capture-RNA; 2 records), ARL6IP6 (Affinity Capture-MS; 2 records), C16orf71 (Affinity Capture-MS; 2 records), ERLIN1 (Affinity Capture-MS; 2 records), ERLIN2 (Affinity Capture-MS; 2 records), MAPK1 (Biochemical Activity; 2 records), MAPK3 (Biochemical Activity; 2 records), APP (Reconstituted Complex), ARF5 (Affinity Capture-MS), BAD (Proximity Label-MS), BNIP3L (Two-hybrid), C15orf57 (Affinity Capture-MS), C6orf120 (Affinity Capture-MS), CALCOCO2 (Proximity Label-MS), CARTPT (Affinity Capture-MS)

SIGNOR signaling

showing 14 of 16 signaling interactions:

AEffectBMechanism
DUSP3“down-regulates activity”MAPK3dephosphorylation
TYK2up-regulatesDUSP3phosphorylation
DUSP3“down-regulates activity”EGFRdephosphorylation
DUSP3“down-regulates activity”ERBB2dephosphorylation
DUSP3“down-regulates activity”NPM1dephosphorylation
DUSP3“down-regulates activity”PTK2dephosphorylation
DUSP3“down-regulates activity”STAT3dephosphorylation
ZAP70up-regulatesDUSP3phosphorylation
DUSP3“down-regulates activity”MAPK1dephosphorylation
DUSP3“down-regulates activity”Gbetadephosphorylation
DUSP3“down-regulates activity”ERK1/2dephosphorylation
VRK3“up-regulates activity”DUSP3binding
SYK“up-regulates activity”DUSP3phosphorylation
ZAP70“up-regulates activity”DUSP3phosphorylation

Disease & clinical

Genetic variants

Variant evidence for DUSP3: 24 ClinVar records (0 pathogenic / likely pathogenic); 6 GWAS associations.

ClinVar

24 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance20
Likely benign1
Benign0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 26 predictions of 268):

Position(s)EffectΔscoreSites
17:43769624donor_gain1.0000
17:43774710–43774711donor_loss1.00005
17:43774939–43774940acceptor_loss1.00005
17:43769815–43769816acceptor_loss0.99006
17:43774710donor_loss0.9900
17:43774939acceptor_loss0.9900
17:43778798–43778799donor_loss0.99004
17:43778811donor_gain0.9900
17:43769628donor_gain0.9700
17:43778309donor_gain0.9700

AlphaMissense

540 missense substitutions predicted likely pathogenic (of 1,224 scored), across 133 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

ResidueLikely-pathogenic substitutionsMean am_pathogenicityMax am_pathogenicity
M14090.8190.988
D9280.9981.000
S12980.9850.997
F16680.9810.999
H12380.9590.992
N6180.9570.997
F10280.9330.986
N16380.9310.990
H5880.8520.990
H7080.8200.936
F10870.9770.996
C12470.9720.997
F9670.9420.997
M6970.8810.965
E12670.8440.916
F7770.8320.962
F6870.8050.939
D16470.7230.821
G12760.9950.998
R13060.9920.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

CancerPrognosticp-value
Kidney Renal Clear Cell Carcinoma (TCGA)favorable2.24e-05
Ovary Serous Cystadenocarcinoma (validation)unfavorable0.00046
Head and Neck Squamous Cell Carcinoma (TCGA)unfavorable0.000882

Disease associations

OMIM: gene MIM:600183 | disease phenotypes:

GWAS associations

6 associations:

StudyTraitp-value
GCST011348_20High density lipoprotein cholesterol levels2e-41
GCST006423_13Fracture3e-25
GCST002899_34HDL cholesterol1e-14
GCST002897_5Triglycerides8e-13
GCST003660_1HDL cholesterol1e-11
GCST009391_1166Metabolite levels8e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO IDTrait name
EFO:0004530triglyceride measurement
EFO:0004612high density lipoprotein cholesterol measurement
EFO:0010370lysophosphatidylethanolamine 20:4 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2635 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

493 measured of 700 human assays (722 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValue
5-(tosylmethyl)-2-furoic acidIC5023 nM
3,4-Dihydroxycinnamate, XVIIIC5024 nM
4-(phenylmethyl)-N-(4-sulfamoylphenyl)piperazine-1-carboxamideKI50 nM
SMR000278513IC5057.2 nM
4-chloranyl-N-(3,4-dihydro-2H-thiochromen-4-yl)-3-sulfamoyl-benzamideIC50121 nM
MLS000621468KI125 nM
N-[3-[(2-methoxyphenyl)sulfamoyl]-4-(1-pyrrolidinyl)phenyl]-3-methyl-2-thiophenecarboxamideIC50163 nM
(7Z)-3-bromo-7-[(2-chlorophenyl)methylidene]-[1,3]thiazolo[4,5]imidazo[1,2-b]pyridin-8-oneIC50181 nM
(2E)-3-{3-[dihydroxy(oxo)–stibanyl]phenyl}prop-2-enoic acidIC50200 nM
4-amino-3-(4-methylphenyl)-5-[(4-methyl-1-piperazinyl)carbonyl]-1,3-thiazole-2(3H)-thioneIC50250 nM
cid_9512029IC50313 nM
1-(2,6-dichlorophenyl)-3-(2-phenylethyl)thioureaIC50342 nM
cid_3578672IC50342 nM
1-[[1-(1-phenylethyl)-3-pyrrolidinyl]methyl]-3-(2,4,6-trimethylphenyl)thioureaIC50343 nM
2-(5-((3-(4-(2-chlorobenzyloxy)phenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl)ethanesulfonic acidIC50470 nM
cid_67062IC50485 nM
1-[2,3-bis(2-furanyl)-6-quinoxalinyl]-3-(2-methoxyethyl)ureaIC50492 nM
MLS000409155IC50498 nM
SMR000311544IC50500 nM
cid_3823393IC50520 nM
cid_2162931IC50567 nM
3-methyl-7-(3-phenylpropyl)-8-[2-(1-piperidinyl)ethylthio]purine-2,6-dioneIC50570 nM
MLS-0437609.0002IC50682 nM
MLS000584539IC50696 nM
MLS000050448IC50716 nM
(4-bromophenyl)-[4-(phenylmethyl)-1-piperazinyl]methanethioneIC50719 nM
1-(3-chloro-4-methoxyphenyl)-3-[2-(4-methyl-1-piperidinyl)ethyl]thioureaIC50720 nM
MLS-0109562.0001IC50727 nM
cid_6161440IC50730 nM
3-[[5-(acetyloxymethyl)-3-[(2,4-dimethoxyphenyl)carbamoyl]-8-methylpyrano[2,3-c]pyridin-2-ylidene]amino]benzoic acidIC50737 nM
N’-(5-chloro-2-methoxyphenyl)-N-[(1-methyl-1H-indol-3-yl)methyl]-N-(3-morpholin-4-ylpropyl)thioureaIC50754 nM
CHEMBL2316908IC50800 nM
SMR000624920IC50804 nM
2-((Z)-4-oxo-5-((E)-3-phenylallylidene)-2-thioxothiazolidin-3-yl)ethane-sulfonic acidKI809 nM
SMR000143195IC50810 nM
6-[(5Z)-5-(1-methyl-2-oxo-3-indolylidene)-4-oxo-2-sulfanylidene-3-thiazolidinyl]hexanoic acidIC50836 nM
SMR001268769IC50927 nM
MLS000679877IC50937 nM
SMR000198085IC50942 nM
(5-methyl-2-thiophenyl)-[4-(phenylmethyl)-1-piperazinyl]methanethioneIC50997 nM
MLS001008494IC501030 nM
N’-(4-chloro-2-methoxyphenyl)-N-[(1-methyl-1H-indol-3-yl)methyl]-N-(3-morpholin-4-ylpropyl)thioureaIC501030 nM
MLS001196239IC501030 nM
1-(3-propan-2-yloxypropyl)-3-(4-sulfamoylphenyl)thioureaIC501080 nM
6-Chloro-7-(2-morpholin-4-yl-ethylamino)-phthalazine-5,8-dioneIC501100 nM
1-(3-chloro-4-methoxyphenyl)-3-[3-(1-pyrrolidinyl)propyl]thioureaIC501120 nM
1-[(4-bromophenyl)carbonothioyl]-4-methylpiperazineIC501140 nM
1-[(E)-(1,3-dimethylpyrazol-4-yl)methylideneamino]-3-phenyl-thioureaIC501220 nM
MLS-0091940.0001IC501230 nM
2,3,4,5-tetrahydroxy-6-benzo[7]annulenoneIC501230 nM

ChEMBL bioactivities

458 potent at pChembl≥5 of 686 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
7.75IC5018nMCHEMBL565795
7.19IC5065nMCHEMBL1460470
7.15IC5071nMCHEMBL567069
7.13IC5074nMCHEMBL584481
7.11IC5078nMCHEMBL565810
7.08IC5082.8nMCHEMBL1460470
6.92IC50121nMCHEMBL1460470
6.90IC50127nMCHEMBL1608642
6.84IC50143nMCHEMBL1322542
6.79IC50163nMCHEMBL1463248
6.74IC50181nMCHEMBL1448629
6.67IC50216nMCHEMBL1385949
6.66IC50220nMCHEMBL1705741
6.66IC50218nMCHEMBL1445488
6.65IC50226nMCHEMBL1393151
6.60IC50250nMCHEMBL1605172
6.58IC50260nMCHEMBL1304193
6.57IC50271nMCHEMBL1385949
6.57IC50270nMCHEMBL565371
6.51IC50312nMCHEMBL1421970
6.51IC50308nMCHEMBL1371869
6.48IC50331nMCHEMBL1608642
6.47IC50341nMCHEMBL1410244
6.47IC50339nMCHEMBL1426299
6.47IC50342nMCHEMBL1331149
6.47IC50342nMCHEMBL1408579
6.46IC50343nMCHEMBL1381413
6.46IC50343nMCHEMBL1353918
6.46IC50345nMCHEMBL1603381
6.46IC50347nMCHEMBL1408579
6.45IC50353nMCHEMBL1370165
6.44IC50366nMCHEMBL1608642
6.43IC50370nMCHEMBL1608642
6.42IC50382nMCHEMBL1445488
6.41IC50386nMCHEMBL1504939
6.40IC50402nMCHEMBL1605172
6.39IC50408nMCHEMBL1727679
6.32IC50480nMCHEMBL1536896
6.32IC50480nMCHEMBL1732016
6.31IC50485nMCHEMBL1271266
6.31IC50492nMCHEMBL1501132
6.30IC50500nMCHEMBL1540065
6.30IC50498nMCHEMBL1421470
6.29IC50509nMCHEMBL1461216
6.28IC50530nMCHEMBL1304193
6.26IC50549nMCHEMBL1445488
6.26IC50544nMCHEMBL1724282
6.25IC50567nMCHEMBL1540317
6.24IC50570nMCHEMBL1569991
6.17IC50680nMCHEMBL1608654

PubChem BioAssay actives

88 with measured affinity, of 476 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
2-[(5Z)-5-[[3-[4-[(4-chlorophenyl)methoxy]phenyl]-1-phenylpyrazol-4-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid443928: Inhibition of recombinant vaccina H1-related phosphataseic500.0180uM
2-[(5Z)-5-[[3-[4-[(2-chlorophenyl)methoxy]phenyl]-1-phenylpyrazol-4-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid443928: Inhibition of recombinant vaccina H1-related phosphataseic500.0710uM
2-[(5Z)-5-[[3-[4-[(2-fluorophenyl)methoxy]phenyl]-1-phenylpyrazol-4-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid443928: Inhibition of recombinant vaccina H1-related phosphataseic500.0740uM
2-[(5Z)-4-oxo-5-[[1-phenyl-3-(4-phenylmethoxyphenyl)pyrazol-4-yl]methylidene]-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid443928: Inhibition of recombinant vaccina H1-related phosphataseic500.0780uM
2-[(5Z)-4-oxo-5-[[1-phenyl-3-(4-piperidin-1-ylsulfonylphenyl)pyrazol-4-yl]methylidene]-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid443928: Inhibition of recombinant vaccina H1-related phosphataseic500.2700uM
(4-hydroxy-3-methoxyphenyl)-piperidin-1-ylmethanethione1206872: Inhibition of recombinant VHR (unknown origin) using OMFP as substrate after 1 hr by fluorescence assayic500.3700uM
6-hydroxy-3-[2-(4-phenoxyphenyl)ethynyl]-2-phenyl-1-benzofuran-5-carboxylic acid725032: Inhibition of VHR (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysisic500.8000uM
2-[(5Z)-5-[(E)-3-phenylprop-2-enylidene]-2-sulfanylidene-1,3,4-thiadiazolidin-3-yl]ethanesulfonic acid443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studieski0.8090uM
6-chloro-7-(2-morpholin-4-ylethylamino)phthalazine-5,8-dione217196: Inhibitory Activity against Recombinant Human VHRic501.1000uM
4-[N-[(3-chlorophenyl)methyl]-C-pentadecylcarbonimidoyl]-3-hydroxy-2-(hydroxymethyl)-2H-furan-5-one673781: Inhibition of VHRic501.4300uM
3-hydroxy-2-(hydroxymethyl)-4-[N-[(3-methylphenyl)methyl]-C-pentadecylcarbonimidoyl]-2H-furan-5-one1139714: Inhibition of Vaccinia H1-related phosphatase (unknown origin) by fluorescence emission assayic501.6000uM
(E)-N-[4-(1,3-benzoxazol-2-yl)phenyl]-3-[5-(2-nitrophenyl)furan-2-yl]prop-2-enamide443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studieski1.7600uM
2-[(3S)-1-[[(2R)-4-hexadecanoyl-3-hydroxy-5-oxo-2H-furan-2-yl]methoxy]-2-methyl-1-oxopentan-3-yl]oxyethyl (2R)-3-hydroxy-2-(hydroxymethyl)-5-oxo-2H-furan-4-carboxylate593417: Inhibition of VHRic501.8000uM
2-[(5Z)-5-[[3-(4-chlorophenyl)-1-phenylpyrazol-4-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid443928: Inhibition of recombinant vaccina H1-related phosphataseic501.8000uM
2-[(5Z)-5-[[3-(4-methoxyphenyl)-1-phenylpyrazol-4-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid443928: Inhibition of recombinant vaccina H1-related phosphataseic501.8000uM
(5Z)-5-[[5-(4-nitrophenyl)furan-2-yl]methylidene]-4-sulfanylidene-1,3-thiazolidin-2-one443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studieski1.8600uM
6-hydroxy-2-phenyl-3-[2-[3-(trifluoromethyl)phenyl]ethynyl]-1-benzofuran-5-carboxylic acid725032: Inhibition of VHR (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysisic501.9000uM
2-[(5Z)-4-oxo-5-[(E)-3-phenylprop-2-enylidene]-2-sulfanylidene-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studieski2.0100uM
2-[4-(2,5-dimethylpyrrol-1-yl)phenyl]sulfanylacetic acid443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studieski2.0900uM
6-hydroxy-2-phenyl-3-[2-[4-(trifluoromethoxy)phenyl]ethynyl]-1-benzofuran-5-carboxylic acid725032: Inhibition of VHR (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysisic502.1000uM
2-[(5Z)-5-[[3-(4-morpholin-4-ylsulfonylphenyl)-1-phenylpyrazol-4-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid443928: Inhibition of recombinant vaccina H1-related phosphataseic502.4000uM
ethyl 5-(4-bromophenyl)-4,6-dioxo-2H-pyrrolo[3,4-c]pyrazole-3-carboxylate443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studieski2.6400uM
3-hydroxy-2-(hydroxymethyl)-4-[N-[(4-methylphenyl)methyl]-C-pentadecylcarbonimidoyl]-2H-furan-5-one673781: Inhibition of VHRic502.6800uM
N-(4-methoxy-1,3-benzothiazol-2-yl)-5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-amine1206872: Inhibition of recombinant VHR (unknown origin) using OMFP as substrate after 1 hr by fluorescence assayic502.6800uM
1-dibenzofuran-3-yl-3-naphthalen-1-ylthiourea443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studieski2.9400uM
1,4-dimethoxyanthracene-9,10-dione443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studieski3.0700uM
2-[(5Z)-5-[[3-(4-methylphenyl)-1-phenylpyrazol-4-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid443928: Inhibition of recombinant vaccina H1-related phosphataseic503.1000uM
2-[(5Z)-5-[[5-(3-chlorophenyl)furan-2-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studieski3.1300uM
(5Z)-5-[[5-(2-bromo-4,5-dimethylphenyl)furan-2-yl]methylidene]-2-sulfanylideneimidazolidin-4-one443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studieski3.1900uM
6-hydroxy-3-iodo-1-methyl-2-[3-[[2-oxo-2-(4-thiophen-3-ylanilino)acetyl]amino]phenyl]indole-5-carboxylic acid1182551: Inhibition of VHR (unknown origin)ic503.2000uM
1-(3-chlorophenyl)-6-hydroxy-5-[(E)-pyrrol-2-ylidenemethyl]-2-sulfanylidenepyrimidin-4-one443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studieski3.4900uM
4-[N-[(4-chlorophenyl)methyl]-C-pentadecylcarbonimidoyl]-3-hydroxy-2-(hydroxymethyl)-2H-furan-5-one673781: Inhibition of VHRic503.6300uM
N-(4-fluoro-1,3-benzothiazol-2-yl)-5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-amine1206872: Inhibition of recombinant VHR (unknown origin) using OMFP as substrate after 1 hr by fluorescence assayic503.7000uM
4-[5-[(E)-(2-amino-3,7-dicyano-4,6-dimethylcyclopenta[b]pyridin-5-ylidene)methyl]furan-2-yl]-2-chlorobenzoic acid443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studieski3.8700uM
3-[2-(2,4-difluorophenyl)ethynyl]-6-hydroxy-2-phenyl-1-benzofuran-5-carboxylic acid725032: Inhibition of VHR (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysisic503.9000uM
6-chloro-7-(2-morpholin-4-ylethylamino)quinoline-5,8-dione217196: Inhibitory Activity against Recombinant Human VHRic504.0000uM
[3-[3-[(3S)-3-(methylcarbamoyl)-7-(sulfoamino)-3,4-dihydro-1H-isoquinolin-2-yl]-3-oxopropyl]phenyl]sulfamic acid262288: Inhibition of VHRic504.0000uM
(3-benzoylphenyl) 2-[(2R)-4-hexadecanoyl-3-hydroxy-5-oxo-2H-furan-2-yl]acetate217197: Inhibitory activity against vaccinia VH1-related phosphatase (VHR)ic504.0000uM
3-[2-(3-fluorophenyl)ethynyl]-6-hydroxy-2-phenyl-1-benzofuran-5-carboxylic acid725032: Inhibition of VHR (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysisic504.1000uM
2-[4-[(Z)-[5-(4-chlorophenyl)-6-ethoxycarbonyl-7-methyl-3-oxo-5H-[1,3]thiazolo[3,2-a]pyrimidin-2-ylidene]methyl]phenoxy]acetic acid569642: Inhibition of recombinant VHR expressed in Escherichia coliic504.2000uM
(5E)-5-[(5-iodofuran-2-yl)methylidene]-1-(4-methoxyphenyl)-2-sulfanylidene-1,3-diazinane-4,6-dione443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studieski4.4400uM
4-[C-[4-[4-[(4-chlorophenyl)methoxy]phenyl]butyl]-N-[(3-methylphenyl)methyl]carbonimidoyl]-3-hydroxy-2-(hydroxymethyl)-2H-furan-5-one1139709: Inhibition of Vaccinia H1-related phosphatase (unknown origin) by fluorescence emission assay in presence of 0.001% NP-40ic504.6000uM
(4-benzoylphenyl) 2-[(2R)-4-hexadecanoyl-3-hydroxy-5-oxo-2H-furan-2-yl]acetate217197: Inhibitory activity against vaccinia VH1-related phosphatase (VHR)ic504.6000uM
4-[N-[(3-fluorophenyl)methyl]-C-pentadecylcarbonimidoyl]-3-hydroxy-2-(hydroxymethyl)-2H-furan-5-one673781: Inhibition of VHRic504.6900uM
[4-[3-(trifluoromethyl)diazirin-3-yl]phenyl] 2-[(2R)-4-hexadecanoyl-3-hydroxy-5-oxo-2H-furan-2-yl]acetate217197: Inhibitory activity against vaccinia VH1-related phosphatase (VHR)ic504.7000uM
(2Z)-2-[1-[5-(1H-pyrrol-2-yl)furan-2-yl]ethylidene]pyrrole1799614: Phosphatase Inhibition Assay from Article 10.1002/cbic.200400135: “The core structures of roseophilin and the prodigiosin alkaloids define a new class of protein tyrosine phosphatase inhibitors.”ic504.9000uM
6-hydroxy-2-phenyl-3-(2-phenylethynyl)-1-benzofuran-5-carboxylic acid725032: Inhibition of VHR (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysisic505.0000uM
methyl 5-amino-6-(7-amino-6-methoxy-5,8-dioxoquinolin-2-yl)-4-(2-hydroxy-3,4-dimethoxyphenyl)-3-methylpyridine-2-carboxylate217196: Inhibitory Activity against Recombinant Human VHRic505.1000uM
4-[N-[[3-(dimethylamino)phenyl]methyl]-C-pentadecylcarbonimidoyl]-3-hydroxy-2-(hydroxymethyl)-2H-furan-5-one673781: Inhibition of VHRic505.1300uM
4-[N-[[2-(dimethylamino)phenyl]methyl]-C-pentadecylcarbonimidoyl]-3-hydroxy-2-(hydroxymethyl)-2H-furan-5-one673781: Inhibition of VHRic505.1900uM

CTD chemical–gene interactions

50 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
Valproic Acidaffects expression, decreases expression, decreases methylation, increases expression6
Benzo(a)pyreneaffects methylation, increases expression3
Nickelincreases expression2
Phenylmercuric Acetateaffects cotreatment, increases expression2
Smokeincreases abundance, decreases expression2
methylmercuric chlorideincreases expression1
bisphenol Aincreases expression1
sodium arseniteincreases expression1
beta-methylcholineaffects expression1
CGP 52608affects binding, increases reaction1
deguelinincreases expression1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideincreases expression, affects cotreatment1
nutlin 3increases expression1
ICG 001decreases expression1
dorsomorphinaffects cotreatment, increases expression1
jinfukangincreases expression1
bis-N,N-dimethylamino-2-(N-methylpyrrolyl)methyl cyclopentadienyl titanium (IV)increases expression1
Gefitinibaffects response to substance1
Sorafenibaffects cotreatment, increases expression1
Resveratroldecreases expression1
Temozolomidedecreases expression1
Decitabineaffects expression1
Sunitinibdecreases expression1
Air Pollutantsdecreases expression, increases abundance1
Arsenicincreases methylation1
Cadmiumincreases expression1
Chelating Agentsincreases expression, affects binding1
Cisplatinaffects expression1
Coaldecreases expression, increases abundance1
Copperaffects binding, increases expression1

ChEMBL screening assays

101 unique, capped per target: 95 binding, 5 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1034380BindingInhibition of VHR expressed in Escherichia coli BL21(DE9)Bitungolides A-F, new polyketides from the Indonesian sponge Theonella cf. swinhoei. — *J Nat Prod*
CHEMBL1738089FunctionalPUBCHEM_BIOASSAY: SAR VHR1 Fluorescent Assay for In Vitro dose response studies. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID1654, AID1661, AID1878, AID1992, AID2004, AID2070, AID2085]PubChem BioAssay data set
CHEMBL4626312ADMETInhibition of VHR (unknown origin) expressed in Escherichia coli BL21 using p-nitrophenyl phosphate as substrate measured after 30 mins by UV-vis spectrophotometric methodHighly Potent and Selective N-Aryl Oxamic Acid-Based Inhibitors for Mycobacterium tuberculosis Protein Tyrosine Phosphatase B. — *J Med Chem*

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_D7P2Ubigene A-549 DUSP3 KOCancer cell lineMale
CVCL_D8KHUbigene HCT 116 DUSP3 KOCancer cell lineMale
CVCL_D9DTUbigene HEK293 DUSP3 KOTransformed cell lineFemale
CVCL_E0C4Ubigene HeLa DUSP3 KOCancer cell lineFemale

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for DUSP3 across ~30M SureChEMBL compounds — explore on Sugi Predict.

  • Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): bone fracture