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
| Field | Value |
|---|---|
| HGNC ID | HGNC:3069 |
| Approved symbol | DUSP3 |
| Name | dual specificity phosphatase 3 |
| Location | 17q21.31 |
| Locus type | gene with protein product |
| Status | Approved |
| Ensembl gene | ENSG00000108861 |
| Ensembl biotype | protein_coding |
| OMIM | 600183 |
| Entrez | 1845 |
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
| Exon | Start | End |
|---|---|---|
| ENSE00000854206 | 43778800 | 43778977 |
| ENSE00001292277 | 43766125 | 43769814 |
| ENSE00003568193 | 43774712 | 43774938 |
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:
| Tissue | QTL | q-value | Slope | Lead variant |
|---|---|---|---|---|
| Whole Blood | eqtl | 1.9e-21 | +0.23 | 17:43773321:C:G |
| Muscle Skeletal | sqtl | 2.2e-12 | -1.05 | 17:43774624:T:C |
| Artery Tibial | sqtl | 2.1e-11 | +1.42 | 17:43774624:T:C |
| Cells Cultured fibroblasts | eqtl | 5.1e-09 | +0.31 | 17:43766891:G:C |
| Esophagus Mucosa | eqtl | 1.6e-07 | -0.15 | 17:43802259:C:T |
| Esophagus Gastroesophageal Junction | sqtl | 7.8e-06 | +1.43 | 17:43774624:T:C |
| Artery Aorta | sqtl | 9.5e-06 | +1.21 | 17:43774624:T:C |
| Muscle Skeletal | eqtl | 1.2e-05 | +0.13 | 17:43765224:A:G |
| Artery Coronary | sqtl | 1.9e-04 | +1.38 | 17:43774624:T:C |
| Esophagus Muscularis | sqtl | 4.4e-04 | +1.17 | 17:43776870:G:T |
| Colon Sigmoid | sqtl | 8.6e-04 | +1.28 | 17:43774624:T:C |
| Artery Tibial | eqtl | 1.0e-03 | -0.21 | 17:43835134:C:G |
| Thyroid | eqtl | 3.8e-03 | +0.12 | 17:43837458:C:T |
| Artery Aorta | eqtl | 7.2e-03 | +0.14 | 17:43814671:C:A |
| Pituitary | eqtl | 7.4e-03 | +0.22 | 17:43456911:C:T |
| Testis | sqtl | 1.0e-02 | +0.72 | 17:43720816:C:A |
| Skin Not Sun Exposed Suprapubic | eqtl | 1.0e-02 | -0.12 | 17:43768456:G:A |
| Brain Cerebellar Hemisphere | eqtl | 1.1e-02 | -0.33 | 17:43187992:G:A |
| Heart Atrial Appendage | sqtl | 1.2e-02 | -1.15 | 17:43776870:G:T |
| Nerve Tibial | eqtl | 1.2e-02 | +0.30 | 17:43952508:C:T |
FANTOM5 promoters
4 alternative TSS:
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 166277 | 44.6308 | 1812 |
| 166276 | 1.7228 | 1012 |
| 166272 | 0.4248 | 205 |
| 166273 | 0.3600 | 174 |
Top tissues by expression
showing 100 of 301 tissues by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| skeletal muscle tissue of rectus abdominis | UBERON:0004511 | 98.72 | gold quality |
| skeletal muscle tissue of biceps brachii | UBERON:0004502 | 98.62 | gold quality |
| biceps brachii | UBERON:0001507 | 98.34 | gold quality |
| saphenous vein | UBERON:0007318 | 98.28 | gold quality |
| vastus lateralis | UBERON:0001379 | 98.22 | gold quality |
| hindlimb stylopod muscle | UBERON:0004252 | 98.22 | gold quality |
| skeletal muscle tissue | UBERON:0001134 | 98.20 | gold quality |
| left ventricle myocardium | UBERON:0006566 | 98.20 | gold quality |
| quadriceps femoris | UBERON:0001377 | 98.10 | gold quality |
| cardiac ventricle | UBERON:0002082 | 98.08 | gold quality |
| heart left ventricle | UBERON:0002084 | 98.08 | gold quality |
| diaphragm | UBERON:0001103 | 97.97 | gold quality |
| gastrocnemius | UBERON:0001388 | 97.86 | gold quality |
| heart right ventricle | UBERON:0002080 | 97.83 | gold quality |
| muscle tissue | UBERON:0002385 | 97.79 | gold quality |
| muscle organ | UBERON:0001630 | 97.71 | gold quality |
| skeletal muscle organ | UBERON:0014892 | 97.71 | gold quality |
| apex of heart | UBERON:0002098 | 97.70 | gold quality |
| myocardium | UBERON:0002349 | 97.70 | gold quality |
| gluteal muscle | UBERON:0002000 | 97.66 | gold quality |
| body of tongue | UBERON:0011876 | 97.60 | gold quality |
| muscle of leg | UBERON:0001383 | 97.53 | gold quality |
| heart | UBERON:0000948 | 97.37 | gold quality |
| triceps brachii | UBERON:0001509 | 97.22 | gold quality |
| deltoid | UBERON:0001476 | 97.17 | gold quality |
| right coronary artery | UBERON:0001625 | 97.04 | gold quality |
| lateral nuclear group of thalamus | UBERON:0002736 | 96.93 | gold quality |
| cauda epididymis | UBERON:0004360 | 96.82 | gold quality |
| cardiac atrium | UBERON:0002081 | 96.77 | gold quality |
| right atrium auricular region | UBERON:0006631 | 96.72 | gold quality |
| type B pancreatic cell | CL:0000169 | 96.71 | gold quality |
| lower esophagus muscularis layer | UBERON:0035833 | 96.68 | gold quality |
| lower esophagus | UBERON:0013473 | 96.67 | gold quality |
| cardiac muscle of right atrium | UBERON:0003379 | 96.66 | gold quality |
| renal medulla | UBERON:0000362 | 96.63 | gold quality |
| orbitofrontal cortex | UBERON:0004167 | 96.56 | gold quality |
| prefrontal cortex | UBERON:0000451 | 96.19 | gold quality |
| coronary artery | UBERON:0001621 | 96.13 | gold quality |
| muscle layer of sigmoid colon | UBERON:0035805 | 96.11 | gold quality |
| dorsal root ganglion | UBERON:0000044 | 96.10 | gold quality |
| esophagogastric junction muscularis propria | UBERON:0035841 | 96.09 | gold quality |
| frontal pole | UBERON:0002795 | 96.06 | gold quality |
| left coronary artery | UBERON:0001626 | 95.98 | gold quality |
| artery | UBERON:0001637 | 95.95 | gold quality |
| popliteal artery | UBERON:0002250 | 95.92 | gold quality |
| tibial artery | UBERON:0007610 | 95.92 | gold quality |
| Brodmann (1909) area 9 | UBERON:0013540 | 95.88 | gold quality |
| cardia of stomach | UBERON:0001162 | 95.84 | gold quality |
| aorta | UBERON:0000947 | 95.81 | gold quality |
| vena cava | UBERON:0004087 | 95.80 | gold quality |
| urethra | UBERON:0000057 | 95.79 | gold quality |
| dorsolateral prefrontal cortex | UBERON:0009834 | 95.75 | gold quality |
| adult mammalian kidney | UBERON:0000082 | 95.74 | gold quality |
| tibialis anterior | UBERON:0001385 | 95.72 | gold quality |
| pylorus | UBERON:0001166 | 95.70 | gold quality |
| thoracic aorta | UBERON:0001515 | 95.66 | gold quality |
| Brodmann (1909) area 46 | UBERON:0006483 | 95.66 | gold quality |
| ascending aorta | UBERON:0001496 | 95.63 | gold quality |
| tongue | UBERON:0001723 | 95.56 | gold quality |
| frontal cortex | UBERON:0001870 | 95.56 | gold quality |
| substantia nigra pars compacta | UBERON:0001965 | 95.56 | gold quality |
| superficial temporal artery | UBERON:0001614 | 95.55 | gold quality |
| dorsal motor nucleus of vagus nerve | UBERON:0002870 | 95.54 | gold quality |
| lower lobe of lung | UBERON:0008949 | 95.46 | gold quality |
| cingulate cortex | UBERON:0003027 | 95.43 | gold quality |
| olfactory bulb | UBERON:0002264 | 95.41 | gold quality |
| nipple | UBERON:0002030 | 95.39 | gold quality |
| smooth muscle tissue | UBERON:0001135 | 95.38 | gold quality |
| right frontal lobe | UBERON:0002810 | 95.37 | gold quality |
| anterior cingulate cortex | UBERON:0009835 | 95.36 | gold quality |
| inferior olivary complex | UBERON:0002127 | 95.34 | gold quality |
| pons | UBERON:0000988 | 95.20 | gold quality |
| right lobe of liver | UBERON:0001114 | 95.17 | gold quality |
| neocortex | UBERON:0001950 | 95.17 | gold quality |
| substantia nigra pars reticulata | UBERON:0001966 | 95.16 | gold quality |
| parietal lobe | UBERON:0001872 | 95.14 | gold quality |
| superior frontal gyrus | UBERON:0002661 | 95.10 | gold quality |
| Brodmann (1909) area 10 | UBERON:0013541 | 95.02 | gold quality |
| descending thoracic aorta | UBERON:0002345 | 94.92 | gold quality |
| cerebral cortex | UBERON:0000956 | 94.91 | gold quality |
| trigeminal ganglion | UBERON:0001675 | 94.91 | gold quality |
| islet of Langerhans | UBERON:0000006 | 94.88 | gold quality |
| pharyngeal mucosa | UBERON:0000355 | 94.88 | gold quality |
| amygdala | UBERON:0001876 | 94.87 | gold quality |
| liver | UBERON:0002107 | 94.85 | gold quality |
| temporal lobe | UBERON:0001871 | 94.80 | gold quality |
| entorhinal cortex | UBERON:0002728 | 94.77 | gold quality |
| lower esophagus mucosa | UBERON:0035834 | 94.77 | gold quality |
| dorsal plus ventral thalamus | UBERON:0001897 | 94.76 | gold quality |
| postcentral gyrus | UBERON:0002581 | 94.75 | gold quality |
| lateral globus pallidus | UBERON:0002476 | 94.68 | gold quality |
| sigmoid colon | UBERON:0001159 | 94.54 | gold quality |
| medulla oblongata | UBERON:0001896 | 94.50 | gold quality |
| superior vestibular nucleus | UBERON:0007227 | 94.39 | gold quality |
| jejunum | UBERON:0002115 | 94.35 | gold quality |
| telencephalon | UBERON:0001893 | 94.32 | gold quality |
| cerebellar vermis | UBERON:0004720 | 94.25 | gold quality |
| ventral tegmental area | UBERON:0002691 | 94.22 | gold quality |
| hypothalamus | UBERON:0001898 | 94.21 | gold quality |
| fundus of stomach | UBERON:0001160 | 94.17 | gold quality |
Single-cell (SCXA)
Detected in 1 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | no | 0.00 |
HPA expression
RNA tissue specificity: Tissue enhanced
showing 60 of 74 HPA tissues / cells by nTPM:
| Tissue / cell | Axis | nTPM |
|---|---|---|
| Skeletal muscle | tissue | 245.3 |
| Tongue | tissue | 199.4 |
| Corpus callosum | tissue | 151.8 |
| Spinal cord | tissue | 135.9 |
| Heart muscle | tissue | 130.0 |
| Cerebral cortex | tissue | 115.1 |
| Motor cortex | tissue | 115.1 |
| Somatosensory cortex | tissue | 111.6 |
| Midbrain | tissue | 108.9 |
| Occipital cortex | tissue | 107.3 |
| Medulla oblongata | tissue | 106.2 |
| Prefrontal cortex | tissue | 102.6 |
| Hippocampal formation | tissue | 98.9 |
| Entorhinal cortex | tissue | 97.8 |
| Temporal cortex | tissue | 93.5 |
| Insular cortex | tissue | 93.3 |
| Thalamus | tissue | 93.2 |
| Cingulate cortex | tissue | 93.2 |
| Retrosplenial cortex | tissue | 91.7 |
| Substantia nigra | tissue | 91.2 |
| Superior colliculi | tissue | 85.0 |
| Pons | tissue | 84.5 |
| Putamen | tissue | 76.1 |
| Postcentral gyrus | tissue | 72.5 |
| Seminal vesicle | tissue | 68.7 |
| Ventral pallidum | tissue | 65.4 |
| Locus coeruleus | tissue | 63.3 |
| Hippocampus | tissue | 61.1 |
| Amygdala | tissue | 59.6 |
| Liver | tissue | 59.6 |
| Smooth muscle | tissue | 58.8 |
| Periaqueductal gray | tissue | 56.2 |
| Hypothalamus | tissue | 55.9 |
| Septum | tissue | 55.0 |
| Kidney | tissue | 53.0 |
| Choroid plexus | tissue | 52.5 |
| Basal ganglia | tissue | 51.9 |
| Nucleus accumbens | tissue | 46.7 |
| Esophagus | tissue | 45.4 |
| Parathyroid gland | tissue | 44.2 |
| Prostate | tissue | 42.1 |
| Olfactory bulb | tissue | 40.0 |
| Urinary bladder | tissue | 37.3 |
| Lung | tissue | 34.0 |
| Adrenal gland | tissue | 33.7 |
| Adipose tissue | tissue | 33.6 |
| Vagina | tissue | 32.3 |
| Pancreas | tissue | 32.1 |
| Pituitary gland | tissue | 32.0 |
| Gallbladder | tissue | 31.3 |
| Cerebellum | tissue | 30.3 |
| Spleen | tissue | 29.7 |
| Endometrium 1 | tissue | 29.6 |
| Placenta | tissue | 29.5 |
| Epididymis | tissue | 29.4 |
| Retina | tissue | 28.5 |
| Colon | tissue | 28.2 |
| Thyroid gland | tissue | 26.2 |
| Duodenum | tissue | 26.2 |
| Small intestine | tissue | 25.8 |
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:
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-MIR-4668-3P | 100.00 | 68.74 | 2635 |
| HSA-MIR-5011-5P | 100.00 | 83.46 | 5820 |
| HSA-MIR-6758-5P | 100.00 | 66.21 | 1470 |
| HSA-MIR-6856-5P | 100.00 | 65.47 | 1298 |
| HSA-MIR-371B-5P | 99.99 | 75.34 | 4759 |
| HSA-MIR-373-5P | 99.98 | 75.36 | 4753 |
| HSA-MIR-616-5P | 99.98 | 75.58 | 4775 |
| HSA-MIR-3617-3P | 99.98 | 67.86 | 918 |
| HSA-MIR-4775 | 99.98 | 75.00 | 6394 |
| HSA-MIR-548AN | 99.97 | 70.91 | 2817 |
| HSA-MIR-3065-5P | 99.97 | 71.56 | 3281 |
| HSA-MIR-6888-3P | 99.97 | 65.95 | 1170 |
| HSA-MIR-6825-5P | 99.96 | 69.81 | 3431 |
| HSA-MIR-590-3P | 99.96 | 74.34 | 6478 |
| HSA-MIR-548AA | 99.96 | 70.64 | 3753 |
| HSA-MIR-548AP-3P | 99.96 | 70.64 | 3753 |
| HSA-MIR-548T-3P | 99.96 | 70.64 | 3753 |
| HSA-MIR-4725-3P | 99.96 | 69.53 | 2520 |
| HSA-MIR-6780B-5P | 99.96 | 69.60 | 2562 |
| HSA-MIR-23A-3P | 99.95 | 74.24 | 3163 |
| HSA-MIR-23B-3P | 99.95 | 74.24 | 3163 |
| HSA-MIR-23C | 99.95 | 73.92 | 3192 |
| HSA-MIR-141-3P | 99.94 | 72.79 | 2421 |
| HSA-MIR-200A-3P | 99.94 | 72.68 | 2420 |
| HSA-MIR-651-3P | 99.94 | 73.48 | 5177 |
| HSA-MIR-6721-5P | 99.93 | 68.92 | 2981 |
| HSA-MIR-515-5P | 99.92 | 69.82 | 2343 |
| HSA-MIR-519E-5P | 99.92 | 69.62 | 2358 |
| HSA-MIR-124-3P | 99.89 | 73.74 | 3043 |
| HSA-MIR-506-3P | 99.89 | 73.55 | 3057 |
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 level | 1 |
| decreased hemoglobin content | 1 |
| increased circulating glycerol level | 1 |
| decreased lean body mass | 1 |
| abnormal humerus morphology | 1 |
| decreased circulating creatinine level | 1 |
| decreased angiogenesis | 1 |
| decreased grip strength | 1 |
| decreased red blood cell distribution width | 1 |
| decreased bone mineral content | 1 |
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.
| Organism | UniProt | Identity | Method |
|---|---|---|---|
| Pongo abelii | Q5RD73 | 100.0% | Diamond |
| Bos taurus | Q2KJ36 | 99.2% | Diamond |
| Rattus norvegicus | Q63340 | 98.8% | Diamond |
| Mus musculus | Q91Z46 | 98.8% | Diamond |
| Pan troglodytes | P0C594 | 98.2% | Diamond |
| Xenopus laevis | Q4V7N3 | 97.8% | Diamond |
| Xenopus tropicalis | A4IHU7 | 92.3% | Diamond |
| Sus scrofa | P0C596 | 90.5% | Diamond |
| Takifugu rubripes | P0C599 | 89.0% | Diamond |
| Tetraodon nigroviridis | Q4RQD3 | 89.0% | Diamond |
| Monodelphis domestica | P0C593 | 86.4% | Diamond |
| Gasterosteus aculeatus | P0C5A0 | 82.9% | Diamond |
| Gallus gallus | P0C597 | 82.1% | Diamond |
| Anolis carolinensis | P0C598 | 81.9% | Diamond |
| Oryzias latipes | P0C5A1 | 80.9% | Diamond |
| Equus caballus | P0C592 | 78.5% | Diamond |
| Danio rerio | Q566R7 | 69.1% | Diamond |
| Callorhinchus milii | P0C5A2 | 68.5% | Diamond |
| Arabidopsis thaliana | Q9M8K7 | 64.0% | Diamond |
| Dictyostelium discoideum | Q55CS8 | 62.6% | Diamond |
| Saccharomyces cerevisiae S288C | P40479 | 52.7% | Diamond |
| Drosophila melanogaster | Q6NN85 | 50.9% | Diamond |
| Vaccinia virus WR | P07239 | 99.4% | Diamond |
| Vaccinia virus Copenhagen | P20495 | 99.4% | Diamond |
| Monkeypox virus | A0A7H0DN78 | 98.8% | Diamond |
| Orgyia pseudotsugata multiple nucleopolyhedrovirus | O10273 | 53.8% | Diamond |
| Betaentomopoxvirus amoorei | Q9EMX1 | 51.9% | Diamond |
| Invertebrate iridescent virus 6 | O55737 | 49.4% | 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).
| Symbol | Type | Entrez |
|---|---|---|
| LINC02594 | ncRNA | 105371786 |
| MEOX1 | protein-coding | 4222 |
| SOST | protein-coding | 50964 |
| CFAP97D1 | protein-coding | 284067 |
| MPP3 | protein-coding | 4356 |
| CD300LG | protein-coding | 146894 |
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 ID | Names | Canonical? |
|---|---|---|
| P51452-1 | 1 | yes |
| P51452-2 | 2 |
RefSeq proteins (1): NP_004081* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR000340 | Dual-sp_phosphatase_cat-dom | Domain |
| IPR000387 | Tyr_Pase_dom | Domain |
| IPR016130 | Tyr_Pase_AS | Active_site |
| IPR020405 | Atypical_DUSP_subfamA | Family |
| IPR020422 | TYR_PHOSPHATASE_DUAL_dom | Domain |
| IPR029021 | Prot-tyrosine_phosphatase-like | Homologous_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.
| Substrate | Km (mM) | Measurements |
|---|---|---|
| 4-NITROPHENYL PHOSPHATE | 0.0008–148 | 84 |
| 6,8-DIFLUORO-4-METHYLUMBELLIFERYL PHOSPHATE | 0.0039–0.862 | 27 |
| 6,8-DIFLUORO-4-METHYLUMBELLIFERYL PHOSPHATE | 0.023–0.862 | 22 |
| P-NITROPHENYL PHOSPHATE | 0.0024–10 | 20 |
| 4-NITROPHENYL PHOSPHATE | 0.0028–12.7 | 13 |
| DADEPYLIPQQG | 0.0003–0.1 | 12 |
| P-NITROPHENYL PHOSPHATE | 3–200 | 11 |
| PHOSPHOTYROSINE | 0.012–30 | 11 |
| LYSOZYME | 0.0003–0.012 | 5 |
| MYELIN BASIC PROTEIN | 0.0001–0.022 | 5 |
| RRAPTVA | 0.058–1.954 | 4 |
| ACETYL-DADEPY-NH2 | 0.0228–0.219 | 4 |
| ACETYL-DADEPYL-NH2 | 1.1–97.5 | 4 |
| PHOSPHOCASEIN | 0.0001–0.002 | 3 |
| PHOSPHOHISTONE | 0.0023–0.0723 | 3 |
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:
| PDB | Title | Method | Resolution (Å) |
|---|---|---|---|
| 8TK6 | HUMAN VH1-RELATED DUAL-SPECIFICITY PHOSPHATASE (VHR) in apo form | X-RAY DIFFRACTION | 1.65 |
| 8TK2 | HUMAN VH1-RELATED DUAL-SPECIFICITY PHOSPHATASE (VHR) complexed with … | X-RAY DIFFRACTION | 1.7 |
| 8TK4 | HUMAN VH1-RELATED DUAL-SPECIFICITY PHOSPHATASE (VHR) complexed with phosphate | X-RAY DIFFRACTION | 1.8 |
| 3F81 | Interaction of VHR with SA3 | X-RAY DIFFRACTION | 1.9 |
| 8TK5 | HUMAN VH1-RELATED DUAL-SPECIFICITY PHOSPHATASE (VHR) complexed with HEPES | X-RAY DIFFRACTION | 1.9 |
| 9DJ9 | HUMAN VH1-RELATED DUAL-SPECIFICITY PHOSPHATASE (VHR) in distinct apo form | X-RAY DIFFRACTION | 1.92 |
| 8TK3 | HUMAN VH1-RELATED DUAL-SPECIFICITY PHOSPHATASE (VHR) having oxidized catalytic cysteine … | X-RAY DIFFRACTION | 2 |
| 1VHR | HUMAN VH1-RELATED DUAL-SPECIFICITY PHOSPHATASE | X-RAY DIFFRACTION | 2.1 |
| 1J4X | HUMAN VH1-RELATED DUAL-SPECIFICITY PHOSPHATASE C124S MUTANT-PEPTIDE COMPLEX | X-RAY DIFFRACTION | 2.75 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-P51452-F1 | 96.10 | 0.93 |
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)
| Position | Role |
|---|---|
| 124 | phosphocysteine 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:
| ID | Pathway | Evidence |
|---|---|---|
| R-HSA-202670 | ERKs are inactivated | curated |
| R-HSA-1280215 | Cytokine Signaling in Immune system | — |
| R-HSA-198753 | ERK/MAPK targets | — |
| R-HSA-168256 | Immune System | — |
| R-HSA-168249 | Innate Immune System | — |
| R-HSA-448424 | Interleukin-17 signaling | — |
| R-HSA-450294 | MAP kinase activation | — |
| R-HSA-450282 | MAPK targets/ Nuclear events mediated by MAP kinases | — |
| R-HSA-975871 | MyD88 cascade initiated on plasma membrane | — |
| R-HSA-975155 | MyD88 dependent cascade initiated on endosome | — |
| R-HSA-166166 | MyD88-independent TLR4 cascade | — |
| R-HSA-166058 | MyD88:MAL(TIRAP) cascade initiated on plasma membrane | — |
| R-HSA-198725 | Nuclear Events (kinase and transcription factor activation) | — |
| R-HSA-162582 | Signal Transduction | — |
| R-HSA-449147 | Signaling by Interleukins | — |
| R-HSA-187037 | Signaling by NTRK1 (TRKA) | — |
| R-HSA-166520 | Signaling by NTRKs | — |
| R-HSA-9006934 | Signaling by Receptor Tyrosine Kinases | — |
| R-HSA-975138 | TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation | — |
| R-HSA-937061 | TRIF (TICAM1)-mediated TLR4 signaling | — |
| R-HSA-168142 | Toll Like Receptor 10 (TLR10) Cascade | — |
| R-HSA-181438 | Toll Like Receptor 2 (TLR2) Cascade | — |
| R-HSA-168164 | Toll Like Receptor 3 (TLR3) Cascade | — |
| R-HSA-166016 | Toll Like Receptor 4 (TLR4) Cascade | — |
| R-HSA-168176 | Toll Like Receptor 5 (TLR5) Cascade | — |
| R-HSA-168181 | Toll Like Receptor 7/8 (TLR7/8) Cascade | — |
| R-HSA-168138 | Toll Like Receptor 9 (TLR9) Cascade | — |
| R-HSA-168179 | Toll Like Receptor TLR1:TLR2 Cascade | — |
| R-HSA-168188 | Toll Like Receptor TLR6:TLR2 Cascade | — |
| R-HSA-168898 | Toll-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:
| Category | Pathways |
|---|---|
| Toll-like Receptor Cascades | 7 |
| Immune System | 2 |
| Toll Like Receptor 4 (TLR4) Cascade | 2 |
| Toll Like Receptor 2 (TLR2) Cascade | 2 |
| ERK/MAPK targets | 1 |
| Toll Like Receptor TLR1:TLR2 Cascade | 1 |
| Toll Like Receptor TLR6:TLR2 Cascade | 1 |
| Signaling by Receptor Tyrosine Kinases | 1 |
| Innate Immune System | 1 |
| Signaling by NTRKs | 1 |
| Signaling by NTRK1 (TRKA) | 1 |
GO top-level categories
showing 60 of 63 GO namespaces:
| Category | Terms |
|---|---|
| phosphoprotein phosphatase activity | 4 |
| cellular anatomical structure | 4 |
| negative regulation of MAPK cascade | 2 |
| phosphate-containing compound metabolic process | 1 |
| cell migration | 1 |
| regulation of cell migration | 1 |
| negative regulation of cell motility | 1 |
| protein dephosphorylation | 1 |
| epidermal growth factor receptor signaling pathway | 1 |
| regulation of epidermal growth factor receptor signaling pathway | 1 |
| negative regulation of ERBB signaling pathway | 1 |
| MAPK cascade | 1 |
| regulation of MAPK cascade | 1 |
| negative regulation of intracellular signal transduction | 1 |
| mitotic cell cycle | 1 |
| regulation of mitotic cell cycle | 1 |
| positive regulation of cell cycle | 1 |
| JNK cascade | 1 |
| regulation of JNK cascade | 1 |
| T cell receptor signaling pathway | 1 |
| regulation of T cell receptor signaling pathway | 1 |
| negative regulation of antigen receptor-mediated signaling pathway | 1 |
| T cell activation | 1 |
| regulation of T cell activation | 1 |
| negative regulation of lymphocyte activation | 1 |
| negative regulation of leukocyte cell-cell adhesion | 1 |
| chemotaxis | 1 |
| negative regulation of response to external stimulus | 1 |
| negative regulation of locomotion | 1 |
| regulation of chemotaxis | 1 |
| regulation of cell-matrix adhesion | 1 |
| focal adhesion assembly | 1 |
| regulation of cell-substrate junction assembly | 1 |
| ERK1 and ERK2 cascade | 1 |
| regulation of ERK1 and ERK2 cascade | 1 |
| response to epidermal growth factor | 1 |
| cellular response to growth factor stimulus | 1 |
| focal adhesion disassembly | 1 |
| regulation of focal adhesion disassembly | 1 |
| positive regulation of cell-substrate junction organization | 1 |
| dephosphorylation | 1 |
| protein modification process | 1 |
| signal transduction | 1 |
| regulation of signal transduction | 1 |
| negative regulation of cell communication | 1 |
| negative regulation of signaling | 1 |
| negative regulation of response to stimulus | 1 |
| protein binding | 1 |
| phosphoric ester hydrolase activity | 1 |
| kinase binding | 1 |
| protein tyrosine kinase inhibitor activity | 1 |
| signaling receptor binding | 1 |
| protein tyrosine kinase binding | 1 |
| protein kinase binding | 1 |
| phosphatase activity | 1 |
| catalytic activity, acting on a protein | 1 |
| binding | 1 |
| catalytic activity | 1 |
| plasma membrane | 1 |
| intracellular membrane-bounded organelle | 1 |
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:
Protein interactions and networks
STRING
showing 16 of 1,219 interactions by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| DUSP3 | PTS | Q03393 | 675 |
| DUSP3 | PTPN1 | P18031 | 659 |
| DUSP3 | EPM2A | O95278 | 625 |
| DUSP3 | PTPN7 | P35236 | 610 |
| DUSP3 | DUSP23 | Q9BVJ7 | 609 |
| DUSP3 | PTPRA | P18433 | 571 |
| DUSP3 | VRK3 | Q8IV63 | 569 |
| DUSP3 | ZAP70 | P43403 | 561 |
| DUSP3 | GBP5 | Q96PP8 | 550 |
| DUSP3 | KDM2A | Q9Y2K7 | 522 |
| DUSP3 | PTPN2 | P17706 | 509 |
| DUSP3 | MAPK1 | P28482 | 496 |
| DUSP3 | NFATC2 | Q13469 | 486 |
| DUSP3 | ACP1 | P24666 | 484 |
| DUSP3 | LHFPL2 | Q6ZUX7 | 470 |
| DUSP3 | CDC14A | Q9UNH5 | 470 |
IntAct
Human interaction partners of DUSP3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).
11 partners by confidence:
| Partner | Interaction type | MIscore | Records |
|---|---|---|---|
| MEOX1 | physical association | 0.560 | 3 |
| ERLIN1 | association | 0.530 | 5 |
| MAPK1 | dephosphorylation reaction | 0.440 | 1 |
| MAPK3 | dephosphorylation reaction | 0.440 | 1 |
| TUFM | physical association | 0.400 | 1 |
| BNIP3L | physical association | 0.370 | 1 |
| CASK | physical association | 0.370 | 1 |
| NEUROD1 | physical association | 0.370 | 1 |
| POU3F1 | association | 0.350 | 1 |
| HLA-B | physical association | 0.000 | 1 |
| MCC | physical association | 0.000 | 1 |
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:
| A | Effect | B | Mechanism |
|---|---|---|---|
| DUSP3 | “down-regulates activity” | MAPK3 | dephosphorylation |
| TYK2 | up-regulates | DUSP3 | phosphorylation |
| DUSP3 | “down-regulates activity” | EGFR | dephosphorylation |
| DUSP3 | “down-regulates activity” | ERBB2 | dephosphorylation |
| DUSP3 | “down-regulates activity” | NPM1 | dephosphorylation |
| DUSP3 | “down-regulates activity” | PTK2 | dephosphorylation |
| DUSP3 | “down-regulates activity” | STAT3 | dephosphorylation |
| ZAP70 | up-regulates | DUSP3 | phosphorylation |
| DUSP3 | “down-regulates activity” | MAPK1 | dephosphorylation |
| DUSP3 | “down-regulates activity” | Gbeta | dephosphorylation |
| DUSP3 | “down-regulates activity” | ERK1/2 | dephosphorylation |
| VRK3 | “up-regulates activity” | DUSP3 | binding |
| SYK | “up-regulates activity” | DUSP3 | phosphorylation |
| ZAP70 | “up-regulates activity” | DUSP3 | phosphorylation |
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):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 20 |
| Likely benign | 1 |
| Benign | 0 |
SpliceAI
Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 26 predictions of 268):
| Position(s) | Effect | Δscore | Sites |
|---|---|---|---|
| 17:43769624 | donor_gain | 1.0000 | |
| 17:43774710–43774711 | donor_loss | 1.0000 | 5 |
| 17:43774939–43774940 | acceptor_loss | 1.0000 | 5 |
| 17:43769815–43769816 | acceptor_loss | 0.9900 | 6 |
| 17:43774710 | donor_loss | 0.9900 | |
| 17:43774939 | acceptor_loss | 0.9900 | |
| 17:43778798–43778799 | donor_loss | 0.9900 | 4 |
| 17:43778811 | donor_gain | 0.9900 | |
| 17:43769628 | donor_gain | 0.9700 | |
| 17:43778309 | donor_gain | 0.9700 |
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:
| Residue | Likely-pathogenic substitutions | Mean am_pathogenicity | Max am_pathogenicity |
|---|---|---|---|
| M140 | 9 | 0.819 | 0.988 |
| D92 | 8 | 0.998 | 1.000 |
| S129 | 8 | 0.985 | 0.997 |
| F166 | 8 | 0.981 | 0.999 |
| H123 | 8 | 0.959 | 0.992 |
| N61 | 8 | 0.957 | 0.997 |
| F102 | 8 | 0.933 | 0.986 |
| N163 | 8 | 0.931 | 0.990 |
| H58 | 8 | 0.852 | 0.990 |
| H70 | 8 | 0.820 | 0.936 |
| F108 | 7 | 0.977 | 0.996 |
| C124 | 7 | 0.972 | 0.997 |
| F96 | 7 | 0.942 | 0.997 |
| M69 | 7 | 0.881 | 0.965 |
| E126 | 7 | 0.844 | 0.916 |
| F77 | 7 | 0.832 | 0.962 |
| F68 | 7 | 0.805 | 0.939 |
| D164 | 7 | 0.723 | 0.821 |
| G127 | 6 | 0.995 | 0.998 |
| R130 | 6 | 0.992 | 0.998 |
HPA cancer prognostics
RNA cancer specificity: Low cancer specificity
Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.
3 prognostic cancer types:
| Cancer | Prognostic | p-value |
|---|---|---|
| Kidney Renal Clear Cell Carcinoma (TCGA) | favorable | 2.24e-05 |
| Ovary Serous Cystadenocarcinoma (validation) | unfavorable | 0.00046 |
| Head and Neck Squamous Cell Carcinoma (TCGA) | unfavorable | 0.000882 |
Disease associations
OMIM: gene MIM:600183 | disease phenotypes:
GWAS associations
6 associations:
| Study | Trait | p-value |
|---|---|---|
| GCST011348_20 | High density lipoprotein cholesterol levels | 2e-41 |
| GCST006423_13 | Fracture | 3e-25 |
| GCST002899_34 | HDL cholesterol | 1e-14 |
| GCST002897_5 | Triglycerides | 8e-13 |
| GCST003660_1 | HDL cholesterol | 1e-11 |
| GCST009391_1166 | Metabolite levels | 8e-6 |
EFO canonical traits (from GWAS)
3 canonical traits:
| EFO ID | Trait name |
|---|---|
| EFO:0004530 | triglyceride measurement |
| EFO:0004612 | high density lipoprotein cholesterol measurement |
| EFO:0010370 | lysophosphatidylethanolamine 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.
| Ligand | Measure | Value |
|---|---|---|
| 5-(tosylmethyl)-2-furoic acid | IC50 | 23 nM |
| 3,4-Dihydroxycinnamate, XVII | IC50 | 24 nM |
| 4-(phenylmethyl)-N-(4-sulfamoylphenyl)piperazine-1-carboxamide | KI | 50 nM |
| SMR000278513 | IC50 | 57.2 nM |
| 4-chloranyl-N-(3,4-dihydro-2H-thiochromen-4-yl)-3-sulfamoyl-benzamide | IC50 | 121 nM |
| MLS000621468 | KI | 125 nM |
| N-[3-[(2-methoxyphenyl)sulfamoyl]-4-(1-pyrrolidinyl)phenyl]-3-methyl-2-thiophenecarboxamide | IC50 | 163 nM |
| (7Z)-3-bromo-7-[(2-chlorophenyl)methylidene]-[1,3]thiazolo[4,5]imidazo[1,2-b]pyridin-8-one | IC50 | 181 nM |
| (2E)-3-{3-[dihydroxy(oxo)–stibanyl]phenyl}prop-2-enoic acid | IC50 | 200 nM |
| 4-amino-3-(4-methylphenyl)-5-[(4-methyl-1-piperazinyl)carbonyl]-1,3-thiazole-2(3H)-thione | IC50 | 250 nM |
| cid_9512029 | IC50 | 313 nM |
| 1-(2,6-dichlorophenyl)-3-(2-phenylethyl)thiourea | IC50 | 342 nM |
| cid_3578672 | IC50 | 342 nM |
| 1-[[1-(1-phenylethyl)-3-pyrrolidinyl]methyl]-3-(2,4,6-trimethylphenyl)thiourea | IC50 | 343 nM |
| 2-(5-((3-(4-(2-chlorobenzyloxy)phenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl)ethanesulfonic acid | IC50 | 470 nM |
| cid_67062 | IC50 | 485 nM |
| 1-[2,3-bis(2-furanyl)-6-quinoxalinyl]-3-(2-methoxyethyl)urea | IC50 | 492 nM |
| MLS000409155 | IC50 | 498 nM |
| SMR000311544 | IC50 | 500 nM |
| cid_3823393 | IC50 | 520 nM |
| cid_2162931 | IC50 | 567 nM |
| 3-methyl-7-(3-phenylpropyl)-8-[2-(1-piperidinyl)ethylthio]purine-2,6-dione | IC50 | 570 nM |
| MLS-0437609.0002 | IC50 | 682 nM |
| MLS000584539 | IC50 | 696 nM |
| MLS000050448 | IC50 | 716 nM |
| (4-bromophenyl)-[4-(phenylmethyl)-1-piperazinyl]methanethione | IC50 | 719 nM |
| 1-(3-chloro-4-methoxyphenyl)-3-[2-(4-methyl-1-piperidinyl)ethyl]thiourea | IC50 | 720 nM |
| MLS-0109562.0001 | IC50 | 727 nM |
| cid_6161440 | IC50 | 730 nM |
| 3-[[5-(acetyloxymethyl)-3-[(2,4-dimethoxyphenyl)carbamoyl]-8-methylpyrano[2,3-c]pyridin-2-ylidene]amino]benzoic acid | IC50 | 737 nM |
| N’-(5-chloro-2-methoxyphenyl)-N-[(1-methyl-1H-indol-3-yl)methyl]-N-(3-morpholin-4-ylpropyl)thiourea | IC50 | 754 nM |
| CHEMBL2316908 | IC50 | 800 nM |
| SMR000624920 | IC50 | 804 nM |
| 2-((Z)-4-oxo-5-((E)-3-phenylallylidene)-2-thioxothiazolidin-3-yl)ethane-sulfonic acid | KI | 809 nM |
| SMR000143195 | IC50 | 810 nM |
| 6-[(5Z)-5-(1-methyl-2-oxo-3-indolylidene)-4-oxo-2-sulfanylidene-3-thiazolidinyl]hexanoic acid | IC50 | 836 nM |
| SMR001268769 | IC50 | 927 nM |
| MLS000679877 | IC50 | 937 nM |
| SMR000198085 | IC50 | 942 nM |
| (5-methyl-2-thiophenyl)-[4-(phenylmethyl)-1-piperazinyl]methanethione | IC50 | 997 nM |
| MLS001008494 | IC50 | 1030 nM |
| N’-(4-chloro-2-methoxyphenyl)-N-[(1-methyl-1H-indol-3-yl)methyl]-N-(3-morpholin-4-ylpropyl)thiourea | IC50 | 1030 nM |
| MLS001196239 | IC50 | 1030 nM |
| 1-(3-propan-2-yloxypropyl)-3-(4-sulfamoylphenyl)thiourea | IC50 | 1080 nM |
| 6-Chloro-7-(2-morpholin-4-yl-ethylamino)-phthalazine-5,8-dione | IC50 | 1100 nM |
| 1-(3-chloro-4-methoxyphenyl)-3-[3-(1-pyrrolidinyl)propyl]thiourea | IC50 | 1120 nM |
| 1-[(4-bromophenyl)carbonothioyl]-4-methylpiperazine | IC50 | 1140 nM |
| 1-[(E)-(1,3-dimethylpyrazol-4-yl)methylideneamino]-3-phenyl-thiourea | IC50 | 1220 nM |
| MLS-0091940.0001 | IC50 | 1230 nM |
| 2,3,4,5-tetrahydroxy-6-benzo[7]annulenone | IC50 | 1230 nM |
ChEMBL bioactivities
458 potent at pChembl≥5 of 686 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 7.75 | IC50 | 18 | nM | CHEMBL565795 |
| 7.19 | IC50 | 65 | nM | CHEMBL1460470 |
| 7.15 | IC50 | 71 | nM | CHEMBL567069 |
| 7.13 | IC50 | 74 | nM | CHEMBL584481 |
| 7.11 | IC50 | 78 | nM | CHEMBL565810 |
| 7.08 | IC50 | 82.8 | nM | CHEMBL1460470 |
| 6.92 | IC50 | 121 | nM | CHEMBL1460470 |
| 6.90 | IC50 | 127 | nM | CHEMBL1608642 |
| 6.84 | IC50 | 143 | nM | CHEMBL1322542 |
| 6.79 | IC50 | 163 | nM | CHEMBL1463248 |
| 6.74 | IC50 | 181 | nM | CHEMBL1448629 |
| 6.67 | IC50 | 216 | nM | CHEMBL1385949 |
| 6.66 | IC50 | 220 | nM | CHEMBL1705741 |
| 6.66 | IC50 | 218 | nM | CHEMBL1445488 |
| 6.65 | IC50 | 226 | nM | CHEMBL1393151 |
| 6.60 | IC50 | 250 | nM | CHEMBL1605172 |
| 6.58 | IC50 | 260 | nM | CHEMBL1304193 |
| 6.57 | IC50 | 271 | nM | CHEMBL1385949 |
| 6.57 | IC50 | 270 | nM | CHEMBL565371 |
| 6.51 | IC50 | 312 | nM | CHEMBL1421970 |
| 6.51 | IC50 | 308 | nM | CHEMBL1371869 |
| 6.48 | IC50 | 331 | nM | CHEMBL1608642 |
| 6.47 | IC50 | 341 | nM | CHEMBL1410244 |
| 6.47 | IC50 | 339 | nM | CHEMBL1426299 |
| 6.47 | IC50 | 342 | nM | CHEMBL1331149 |
| 6.47 | IC50 | 342 | nM | CHEMBL1408579 |
| 6.46 | IC50 | 343 | nM | CHEMBL1381413 |
| 6.46 | IC50 | 343 | nM | CHEMBL1353918 |
| 6.46 | IC50 | 345 | nM | CHEMBL1603381 |
| 6.46 | IC50 | 347 | nM | CHEMBL1408579 |
| 6.45 | IC50 | 353 | nM | CHEMBL1370165 |
| 6.44 | IC50 | 366 | nM | CHEMBL1608642 |
| 6.43 | IC50 | 370 | nM | CHEMBL1608642 |
| 6.42 | IC50 | 382 | nM | CHEMBL1445488 |
| 6.41 | IC50 | 386 | nM | CHEMBL1504939 |
| 6.40 | IC50 | 402 | nM | CHEMBL1605172 |
| 6.39 | IC50 | 408 | nM | CHEMBL1727679 |
| 6.32 | IC50 | 480 | nM | CHEMBL1536896 |
| 6.32 | IC50 | 480 | nM | CHEMBL1732016 |
| 6.31 | IC50 | 485 | nM | CHEMBL1271266 |
| 6.31 | IC50 | 492 | nM | CHEMBL1501132 |
| 6.30 | IC50 | 500 | nM | CHEMBL1540065 |
| 6.30 | IC50 | 498 | nM | CHEMBL1421470 |
| 6.29 | IC50 | 509 | nM | CHEMBL1461216 |
| 6.28 | IC50 | 530 | nM | CHEMBL1304193 |
| 6.26 | IC50 | 549 | nM | CHEMBL1445488 |
| 6.26 | IC50 | 544 | nM | CHEMBL1724282 |
| 6.25 | IC50 | 567 | nM | CHEMBL1540317 |
| 6.24 | IC50 | 570 | nM | CHEMBL1569991 |
| 6.17 | IC50 | 680 | nM | CHEMBL1608654 |
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.
| Compound | Assay | Type | Value | Unit |
|---|---|---|---|---|
| 2-[(5Z)-5-[[3-[4-[(4-chlorophenyl)methoxy]phenyl]-1-phenylpyrazol-4-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid | 443928: Inhibition of recombinant vaccina H1-related phosphatase | ic50 | 0.0180 | uM |
| 2-[(5Z)-5-[[3-[4-[(2-chlorophenyl)methoxy]phenyl]-1-phenylpyrazol-4-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid | 443928: Inhibition of recombinant vaccina H1-related phosphatase | ic50 | 0.0710 | uM |
| 2-[(5Z)-5-[[3-[4-[(2-fluorophenyl)methoxy]phenyl]-1-phenylpyrazol-4-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid | 443928: Inhibition of recombinant vaccina H1-related phosphatase | ic50 | 0.0740 | uM |
| 2-[(5Z)-4-oxo-5-[[1-phenyl-3-(4-phenylmethoxyphenyl)pyrazol-4-yl]methylidene]-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid | 443928: Inhibition of recombinant vaccina H1-related phosphatase | ic50 | 0.0780 | uM |
| 2-[(5Z)-4-oxo-5-[[1-phenyl-3-(4-piperidin-1-ylsulfonylphenyl)pyrazol-4-yl]methylidene]-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid | 443928: Inhibition of recombinant vaccina H1-related phosphatase | ic50 | 0.2700 | uM |
| (4-hydroxy-3-methoxyphenyl)-piperidin-1-ylmethanethione | 1206872: Inhibition of recombinant VHR (unknown origin) using OMFP as substrate after 1 hr by fluorescence assay | ic50 | 0.3700 | uM |
| 6-hydroxy-3-[2-(4-phenoxyphenyl)ethynyl]-2-phenyl-1-benzofuran-5-carboxylic acid | 725032: Inhibition of VHR (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis | ic50 | 0.8000 | uM |
| 2-[(5Z)-5-[(E)-3-phenylprop-2-enylidene]-2-sulfanylidene-1,3,4-thiadiazolidin-3-yl]ethanesulfonic acid | 443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studies | ki | 0.8090 | uM |
| 6-chloro-7-(2-morpholin-4-ylethylamino)phthalazine-5,8-dione | 217196: Inhibitory Activity against Recombinant Human VHR | ic50 | 1.1000 | uM |
| 4-[N-[(3-chlorophenyl)methyl]-C-pentadecylcarbonimidoyl]-3-hydroxy-2-(hydroxymethyl)-2H-furan-5-one | 673781: Inhibition of VHR | ic50 | 1.4300 | uM |
| 3-hydroxy-2-(hydroxymethyl)-4-[N-[(3-methylphenyl)methyl]-C-pentadecylcarbonimidoyl]-2H-furan-5-one | 1139714: Inhibition of Vaccinia H1-related phosphatase (unknown origin) by fluorescence emission assay | ic50 | 1.6000 | uM |
| (E)-N-[4-(1,3-benzoxazol-2-yl)phenyl]-3-[5-(2-nitrophenyl)furan-2-yl]prop-2-enamide | 443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studies | ki | 1.7600 | uM |
| 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-carboxylate | 593417: Inhibition of VHR | ic50 | 1.8000 | uM |
| 2-[(5Z)-5-[[3-(4-chlorophenyl)-1-phenylpyrazol-4-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid | 443928: Inhibition of recombinant vaccina H1-related phosphatase | ic50 | 1.8000 | uM |
| 2-[(5Z)-5-[[3-(4-methoxyphenyl)-1-phenylpyrazol-4-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid | 443928: Inhibition of recombinant vaccina H1-related phosphatase | ic50 | 1.8000 | uM |
| (5Z)-5-[[5-(4-nitrophenyl)furan-2-yl]methylidene]-4-sulfanylidene-1,3-thiazolidin-2-one | 443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studies | ki | 1.8600 | uM |
| 6-hydroxy-2-phenyl-3-[2-[3-(trifluoromethyl)phenyl]ethynyl]-1-benzofuran-5-carboxylic acid | 725032: Inhibition of VHR (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis | ic50 | 1.9000 | uM |
| 2-[(5Z)-4-oxo-5-[(E)-3-phenylprop-2-enylidene]-2-sulfanylidene-1,3-thiazolidin-3-yl]-3-phenylpropanoic acid | 443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studies | ki | 2.0100 | uM |
| 2-[4-(2,5-dimethylpyrrol-1-yl)phenyl]sulfanylacetic acid | 443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studies | ki | 2.0900 | uM |
| 6-hydroxy-2-phenyl-3-[2-[4-(trifluoromethoxy)phenyl]ethynyl]-1-benzofuran-5-carboxylic acid | 725032: Inhibition of VHR (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis | ic50 | 2.1000 | uM |
| 2-[(5Z)-5-[[3-(4-morpholin-4-ylsulfonylphenyl)-1-phenylpyrazol-4-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid | 443928: Inhibition of recombinant vaccina H1-related phosphatase | ic50 | 2.4000 | uM |
| ethyl 5-(4-bromophenyl)-4,6-dioxo-2H-pyrrolo[3,4-c]pyrazole-3-carboxylate | 443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studies | ki | 2.6400 | uM |
| 3-hydroxy-2-(hydroxymethyl)-4-[N-[(4-methylphenyl)methyl]-C-pentadecylcarbonimidoyl]-2H-furan-5-one | 673781: Inhibition of VHR | ic50 | 2.6800 | uM |
| N-(4-methoxy-1,3-benzothiazol-2-yl)-5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-amine | 1206872: Inhibition of recombinant VHR (unknown origin) using OMFP as substrate after 1 hr by fluorescence assay | ic50 | 2.6800 | uM |
| 1-dibenzofuran-3-yl-3-naphthalen-1-ylthiourea | 443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studies | ki | 2.9400 | uM |
| 1,4-dimethoxyanthracene-9,10-dione | 443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studies | ki | 3.0700 | uM |
| 2-[(5Z)-5-[[3-(4-methylphenyl)-1-phenylpyrazol-4-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid | 443928: Inhibition of recombinant vaccina H1-related phosphatase | ic50 | 3.1000 | uM |
| 2-[(5Z)-5-[[5-(3-chlorophenyl)furan-2-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid | 443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studies | ki | 3.1300 | uM |
| (5Z)-5-[[5-(2-bromo-4,5-dimethylphenyl)furan-2-yl]methylidene]-2-sulfanylideneimidazolidin-4-one | 443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studies | ki | 3.1900 | uM |
| 6-hydroxy-3-iodo-1-methyl-2-[3-[[2-oxo-2-(4-thiophen-3-ylanilino)acetyl]amino]phenyl]indole-5-carboxylic acid | 1182551: Inhibition of VHR (unknown origin) | ic50 | 3.2000 | uM |
| 1-(3-chlorophenyl)-6-hydroxy-5-[(E)-pyrrol-2-ylidenemethyl]-2-sulfanylidenepyrimidin-4-one | 443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studies | ki | 3.4900 | uM |
| 4-[N-[(4-chlorophenyl)methyl]-C-pentadecylcarbonimidoyl]-3-hydroxy-2-(hydroxymethyl)-2H-furan-5-one | 673781: Inhibition of VHR | ic50 | 3.6300 | uM |
| N-(4-fluoro-1,3-benzothiazol-2-yl)-5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-amine | 1206872: Inhibition of recombinant VHR (unknown origin) using OMFP as substrate after 1 hr by fluorescence assay | ic50 | 3.7000 | uM |
| 4-[5-[(E)-(2-amino-3,7-dicyano-4,6-dimethylcyclopenta[b]pyridin-5-ylidene)methyl]furan-2-yl]-2-chlorobenzoic acid | 443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studies | ki | 3.8700 | uM |
| 3-[2-(2,4-difluorophenyl)ethynyl]-6-hydroxy-2-phenyl-1-benzofuran-5-carboxylic acid | 725032: Inhibition of VHR (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis | ic50 | 3.9000 | uM |
| 6-chloro-7-(2-morpholin-4-ylethylamino)quinoline-5,8-dione | 217196: Inhibitory Activity against Recombinant Human VHR | ic50 | 4.0000 | uM |
| [3-[3-[(3S)-3-(methylcarbamoyl)-7-(sulfoamino)-3,4-dihydro-1H-isoquinolin-2-yl]-3-oxopropyl]phenyl]sulfamic acid | 262288: Inhibition of VHR | ic50 | 4.0000 | uM |
| (3-benzoylphenyl) 2-[(2R)-4-hexadecanoyl-3-hydroxy-5-oxo-2H-furan-2-yl]acetate | 217197: Inhibitory activity against vaccinia VH1-related phosphatase (VHR) | ic50 | 4.0000 | uM |
| 3-[2-(3-fluorophenyl)ethynyl]-6-hydroxy-2-phenyl-1-benzofuran-5-carboxylic acid | 725032: Inhibition of VHR (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis | ic50 | 4.1000 | uM |
| 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 acid | 569642: Inhibition of recombinant VHR expressed in Escherichia coli | ic50 | 4.2000 | uM |
| (5E)-5-[(5-iodofuran-2-yl)methylidene]-1-(4-methoxyphenyl)-2-sulfanylidene-1,3-diazinane-4,6-dione | 443921: Inhibition of recombinant vaccina H1-related phosphatase expressed in Escherichia coli by Michaelis-Menten kinetic studies | ki | 4.4400 | uM |
| 4-[C-[4-[4-[(4-chlorophenyl)methoxy]phenyl]butyl]-N-[(3-methylphenyl)methyl]carbonimidoyl]-3-hydroxy-2-(hydroxymethyl)-2H-furan-5-one | 1139709: Inhibition of Vaccinia H1-related phosphatase (unknown origin) by fluorescence emission assay in presence of 0.001% NP-40 | ic50 | 4.6000 | uM |
| (4-benzoylphenyl) 2-[(2R)-4-hexadecanoyl-3-hydroxy-5-oxo-2H-furan-2-yl]acetate | 217197: Inhibitory activity against vaccinia VH1-related phosphatase (VHR) | ic50 | 4.6000 | uM |
| 4-[N-[(3-fluorophenyl)methyl]-C-pentadecylcarbonimidoyl]-3-hydroxy-2-(hydroxymethyl)-2H-furan-5-one | 673781: Inhibition of VHR | ic50 | 4.6900 | uM |
| [4-[3-(trifluoromethyl)diazirin-3-yl]phenyl] 2-[(2R)-4-hexadecanoyl-3-hydroxy-5-oxo-2H-furan-2-yl]acetate | 217197: Inhibitory activity against vaccinia VH1-related phosphatase (VHR) | ic50 | 4.7000 | uM |
| (2Z)-2-[1-[5-(1H-pyrrol-2-yl)furan-2-yl]ethylidene]pyrrole | 1799614: 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.” | ic50 | 4.9000 | uM |
| 6-hydroxy-2-phenyl-3-(2-phenylethynyl)-1-benzofuran-5-carboxylic acid | 725032: Inhibition of VHR (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis | ic50 | 5.0000 | uM |
| methyl 5-amino-6-(7-amino-6-methoxy-5,8-dioxoquinolin-2-yl)-4-(2-hydroxy-3,4-dimethoxyphenyl)-3-methylpyridine-2-carboxylate | 217196: Inhibitory Activity against Recombinant Human VHR | ic50 | 5.1000 | uM |
| 4-[N-[[3-(dimethylamino)phenyl]methyl]-C-pentadecylcarbonimidoyl]-3-hydroxy-2-(hydroxymethyl)-2H-furan-5-one | 673781: Inhibition of VHR | ic50 | 5.1300 | uM |
| 4-[N-[[2-(dimethylamino)phenyl]methyl]-C-pentadecylcarbonimidoyl]-3-hydroxy-2-(hydroxymethyl)-2H-furan-5-one | 673781: Inhibition of VHR | ic50 | 5.1900 | uM |
CTD chemical–gene interactions
50 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Valproic Acid | affects expression, decreases expression, decreases methylation, increases expression | 6 |
| Benzo(a)pyrene | affects methylation, increases expression | 3 |
| Nickel | increases expression | 2 |
| Phenylmercuric Acetate | affects cotreatment, increases expression | 2 |
| Smoke | increases abundance, decreases expression | 2 |
| methylmercuric chloride | increases expression | 1 |
| bisphenol A | increases expression | 1 |
| sodium arsenite | increases expression | 1 |
| beta-methylcholine | affects expression | 1 |
| CGP 52608 | affects binding, increases reaction | 1 |
| deguelin | increases expression | 1 |
| 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide | increases expression, affects cotreatment | 1 |
| nutlin 3 | increases expression | 1 |
| ICG 001 | decreases expression | 1 |
| dorsomorphin | affects cotreatment, increases expression | 1 |
| jinfukang | increases expression | 1 |
| bis-N,N-dimethylamino-2-(N-methylpyrrolyl)methyl cyclopentadienyl titanium (IV) | increases expression | 1 |
| Gefitinib | affects response to substance | 1 |
| Sorafenib | affects cotreatment, increases expression | 1 |
| Resveratrol | decreases expression | 1 |
| Temozolomide | decreases expression | 1 |
| Decitabine | affects expression | 1 |
| Sunitinib | decreases expression | 1 |
| Air Pollutants | decreases expression, increases abundance | 1 |
| Arsenic | increases methylation | 1 |
| Cadmium | increases expression | 1 |
| Chelating Agents | increases expression, affects binding | 1 |
| Cisplatin | affects expression | 1 |
| Coal | decreases expression, increases abundance | 1 |
| Copper | affects binding, increases expression | 1 |
ChEMBL screening assays
101 unique, capped per target: 95 binding, 5 functional, 1 admet
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL1034380 | Binding | Inhibition of VHR expressed in Escherichia coli BL21(DE9) | Bitungolides A-F, new polyketides from the Indonesian sponge Theonella cf. swinhoei. — *J Nat Prod* |
| CHEMBL1738089 | Functional | PUBCHEM_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 |
| CHEMBL4626312 | ADMET | Inhibition of VHR (unknown origin) expressed in Escherichia coli BL21 using p-nitrophenyl phosphate as substrate measured after 30 mins by UV-vis spectrophotometric method | Highly 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):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_D7P2 | Ubigene A-549 DUSP3 KO | Cancer cell line | Male |
| CVCL_D8KH | Ubigene HCT 116 DUSP3 KO | Cancer cell line | Male |
| CVCL_D9DT | Ubigene HEK293 DUSP3 KO | Transformed cell line | Female |
| CVCL_E0C4 | Ubigene HeLa DUSP3 KO | Cancer cell line | Female |
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.
Related Atlas pages
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): bone fracture