DUSP1

Summary

DUSP1 (dual specificity phosphatase 1, HGNC:3064) is a protein-coding gene on chromosome 5q35.1, encoding Dual specificity protein phosphatase 1 (P28562). Dual specificity phosphatase that dephosphorylates MAP kinase MAPK1/ERK2 on both ‘Thr-183’ and ‘Tyr-185’, regulating its activity during the meiotic cell cycle.

The protein encoded by this gene is a phosphatase with dual specificity for tyrosine and threonine. The encoded protein can dephosphorylate MAP kinase MAPK1/ERK2, which results in its involvement in several cellular processes. This protein appears to play an important role in the human cellular response to environmental stress as well as in the negative regulation of cellular proliferation. Finally, the encoded protein can make some solid tumors resistant to both chemotherapy and radiotherapy, making it a target for cancer therapy.

Source: NCBI Gene 1843 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 51 total
• Druggable target: yes
• MANE Select transcript: NM_004417

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3064
Approved symbol	DUSP1
Name	dual specificity phosphatase 1
Location	5q35.1
Locus type	gene with protein product
Status	Approved
Aliases	HVH1, CL100, MKP-1
Ensembl gene	ENSG00000120129
Ensembl biotype	protein_coding
OMIM	600714
Entrez	1843

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000239223, ENST00000868089, ENST00000868090, ENST00000868091, ENST00000868092

RefSeq mRNA: 1 — MANE Select: NM_004417 NM_004417

CCDS: CCDS4380

Canonical transcript exons

ENST00000239223 — 4 exons

Exon	Start	End
ENSE00000769464	172769575	172769794
ENSE00000769465	172770161	172770306
ENSE00000812856	172770586	172771195
ENSE00001876542	172768096	172769132

Expression profiles

Bgee: expression breadth ubiquitous, 302 present calls, max score 99.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 316.3458 / max 11281.8587, expressed in 1824 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
64894	311.0472	1824
64888	1.9737	641
64883	1.1902	436
64881	0.6120	255
64884	0.4573	192
64886	0.4391	203
64887	0.4294	186
64885	0.1121	46
64882	0.0847	40

Top tissues by expression

303 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
vena cava	UBERON:0004087	99.94	gold quality
nipple	UBERON:0002030	99.91	gold quality
urethra	UBERON:0000057	99.89	gold quality
upper leg skin	UBERON:0004262	99.89	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.89	gold quality
mucosa of urinary bladder	UBERON:0001259	99.88	gold quality
cardia of stomach	UBERON:0001162	99.87	gold quality
lower lobe of lung	UBERON:0008949	99.85	gold quality
saphenous vein	UBERON:0007318	99.84	gold quality
trachea	UBERON:0003126	99.82	gold quality
pharyngeal mucosa	UBERON:0000355	99.79	gold quality
penis	UBERON:0000989	99.79	gold quality
mucosa of stomach	UBERON:0001199	99.77	gold quality
cauda epididymis	UBERON:0004360	99.75	gold quality
seminal vesicle	UBERON:0000998	99.74	gold quality
pericardium	UBERON:0002407	99.74	gold quality
monocyte	CL:0000576	99.72	gold quality
mononuclear cell	CL:0000842	99.72	gold quality
skin of hip	UBERON:0001554	99.72	gold quality
adult organism	UBERON:0007023	99.72	gold quality
synovial joint	UBERON:0002217	99.71	gold quality
renal medulla	UBERON:0000362	99.70	gold quality
leukocyte	CL:0000738	99.68	gold quality
periodontal ligament	UBERON:0008266	99.68	gold quality
mammary duct	UBERON:0001765	99.66	gold quality
left uterine tube	UBERON:0001303	99.64	gold quality
trigeminal ganglion	UBERON:0001675	99.64	gold quality
parotid gland	UBERON:0001831	99.62	gold quality
gall bladder	UBERON:0002110	99.62	gold quality
popliteal artery	UBERON:0002250	99.59	gold quality

Single-cell (SCXA)

Detected in 40 experiment(s), a significant marker in 32.

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	12189.65
E-HCAD-11	yes	10613.80
E-GEOD-149689	yes	7303.29
E-GEOD-100618	yes	7028.96
E-GEOD-76312	yes	6068.33
E-MTAB-9841	yes	5594.29
E-GEOD-106540	yes	4183.30
E-MTAB-8221	yes	4161.46
E-GEOD-114530	yes	3475.80
E-GEOD-124472	yes	2681.30
E-GEOD-89232	yes	2476.39
E-MTAB-10287	yes	2474.31
E-CURD-79	yes	2092.55
E-MTAB-8530	yes	1735.84
E-MTAB-8498	yes	867.94

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ATF1, ATF2, ATM, BMAL1, CEBPB, CLOCK, CREB1, CREM, DMTF1, E2F1, HES1, IRF6, JUN, LHX8, MYC, MYOD1, NFKB1, NFKB, NFKBIA, NR3C1, NR4A2, PGR, PPARG, PTEN, RARA, RARG, RBPJ, RELA, STAT6, TBXT, TP53, TSC22D3, USF1, ZBTB7A

miRNA regulators (miRDB)

91 targeting DUSP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-568	99.98	69.86	2084
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-512-3P	99.97	67.35	1049

Literature-anchored findings (GeneRIF, showing 40)

• CL100 down regulation is associated with advanced stages of epithelial ovarian neoplasms (PMID:12080474)
• glucocorticoids synergistically enhance NTHi-induced TLR2 expression via specific up-regulation of the MAPK phosphatase-1 (MKP-1) that, in turn, leads to dephosphorylation and inactivation of p38 MAPK (PMID:12356755)
• Data suggest that mitogen-activated protein kinase phosphatase 1 (MKP-1) participates in a negative-feedback loop which regulates p38 function and that dexamethasone may inhibit proinflammatory gene expression in part by inducing MKP-1 expression. (PMID:12391149)
• Expression of MKP-1 may be associated with shorter progression-free survival times (PMID:12432554)
• role of activation on cAMP-dependent protein kinase enhancement of CYP17 transcription (PMID:12506119)
• our data suggest that deletion of the hv3005 and the 3-30.3 genes may predispose individual SLE patients to the development of lupus nephritis (PMID:12765304)
• MKP1 is a transcriptional target of p53 involved in cell cycle regulation (PMID:12890671)
• Cardiopulmonary bypass reduces ERK1/2 and p38 activity in peripheral tissue, potentially by MKP-1. (PMID:12947325)
• requirement of MAPK phosphatase-1 induction and therefore, inhibition of p38 MAPK in the ANP-mediated inhibition of TNF-alpha-induced expression of MCP-1 (PMID:12960255)
• Jak2 is required for Ang II-induced ERK2 inactivation via induction of MKP-1 gene expression. (PMID:14551204)
• Here we found that hypoxia induces MKP-1 expression in human hepatoma cells HepG2 in a time-dependent manner. (PMID:14680833)
• the molecular mechanisms underlying the survival function of NGF in CESS B cell line predominantly consist in maintaining elevated levels of MKP-1 protein, which controls p38 MAPK activation. (PMID:14724291)
• The expression of MKP-1 in gastric cancer cell line was elevated under hypoxia, which could downregulate the hypoxia-inducible factor 1 trans-activition activity thereby repressing the expression of downstream target vascular endothelial growth factor. (PMID:15059515)
• CL100/MKP-1 has a role in progression of non-small cell lung cancer (PMID:15173070)
• Prevalent MKP-1 expression in renal cell carcinoma contributes to cancer cell survival by attenuating an apoptosis inducing signal cascade via JNK. (PMID:15247770)
• expression of the CL-100 phosphatase and its subsequent regulation of ERK activity play a key regulatory role in the thrombin signaling pathway (PMID:15339908)
• MKP-1 induction may be antiapoptotic om breast epithelial cells and a breast cancer cell line. (PMID:15448190)
• Rat ANP induces MKP-1 via endothelial Rac1 and Nox/Nox2. (PMID:15569826)
• Glucocorticoid receptor-induced MPK-1 expression inhibits paclitaxel-associated MAPK activation and contributes to breast cancer cell survival (PMID:15590693)
• MKP-1 is an important mediator of endotoxin tolerance via p38 regulation (PMID:15614136)
• preheating accelerates MAP kinase inactivation after a second heat shock, which is related to a HSP70-mediated increase in p-MKP-1 (PMID:15677475)
• DNA damage in transcribed genes induces apoptosis via the JNK pathway and MKP-1. (PMID:16044158)
• Hypoxia-induced MKP-1 protects overactivation of hypoxia-inducible factor 1 activation through inhibiting ERK kinase activity. (PMID:16081065)
• A molecular target of macrophage migration inhibitory factor - glucocorticoid crosstalk. (PMID:16224818)
• MKP-1 proteolysis can be achieved via ERK and SCF(Skp2) cooperation, thereby sustaining ERK activation (PMID:16286470)
• data suggest that MKP-1, a negative regulator of ERK1/2, plays a proapoptotic role in oxidative stress-induced cell death in neuroblastoma SH-SY5Y cell line (PMID:16289033)
• The MKP-1 expression in HCC (hepatocellular carcinoma) was an independent prognostic factor for outcome in HCC patients. (PMID:16293973)
• Anandamide-induced rapid MKP-1 expression switches off MAPK signal transduction in microglial cells activated by stimulation of pattern recognition receptors. (PMID:16387640)
• MKP-1 is required for cisplatin resistance in tumor cells. (PMID:16951204)
• DUSP1 is a central regulator of innate immunity, and its expression can profoundly affect the outcome of inflammatory challenges.[review] (PMID:17073741)
• These results suggest the existence of an ERK1/2-driven negative feed-back regulation of ERK5 signaling in epidermal growth factor-stimulated HK-2 cells, which is mediated by MKP-3, DUSP5 and/or MKP-1. (PMID:17131384)
• In human mesangial cells, connective tissue growth factor induces the rapid transcriptional activation and synthesis of MKP-1 (MAPK phosphatase-1), a dual specificity phosphatase that dephosphorylates p38 MAPK. (PMID:17489738)
• E2F-1 is a transcriptional activator of DUSP1 and DUSP1 is a link between E2F-1 and MAP kinases (PMID:17638884)
• The transcription factor ATF2, which is phosphorylated and activated by JNK, is a critical mediator for inducible expression of DUSP1 and DUSP10 in this signaling pathway. (PMID:17681939)
• Data suggest that JNK activation and decreased expression of MKP-1 may play important roles in progression of urothelial carcinoma. (PMID:17690186)
• Regulation of ERK by MKP-1 provides a novel mechanism for control of osteoblast proliferation by glucocorticoids (PMID:17761948)
• Ethanol-induced oxidative stress enhanced the tyrosine phosphorylation of PKCdelta, which in turn caused the proteasomal degradation of MKP-1, leading to sustained JNK activation and increased apoptosis in VL-17A cells. (PMID:17848570)
• Distinct MAPK signaling pathways for thrombin versus VEGF induction of MKP-1 in endothelial cells. MKP-1 induction important in VEGF-stimulated endothelial cell migration. (PMID:18003751)
• MKP-1 plays a critical role in ERK-mediated cisplatin resistance in ovarian carcinoma cells. (PMID:18089824)
• in patients with rheumatic heart disease and heart failure MKP-1 activity was depressed in class IV patients compared to those in classes II and III (PMID:18095520)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dusp1	ENSDARG00000100515
mus_musculus	Dusp1	ENSMUSG00000024190
rattus_norvegicus	Dusp1	ENSRNOG00000069024

Paralogs (31): DUSP13B (ENSG00000079393), DUSP12 (ENSG00000081721), SSH1 (ENSG00000084112), DUSP3 (ENSG00000108861), PTPMT1 (ENSG00000110536), DUSP16 (ENSG00000111266), EPM2A (ENSG00000112425), DUSP22 (ENSG00000112679), 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)

Protein

Protein identifiers

Dual specificity protein phosphatase 1 — P28562 (reviewed: P28562)

Alternative names: Dual specificity protein phosphatase hVH1, Mitogen-activated protein kinase phosphatase 1, Protein-tyrosine phosphatase CL100

All UniProt accessions (1): P28562

UniProt curated annotations — full annotation on UniProt →

Function. Dual specificity phosphatase that dephosphorylates MAP kinase MAPK1/ERK2 on both ‘Thr-183’ and ‘Tyr-185’, regulating its activity during the meiotic cell cycle.

Subcellular location. Nucleus.

Tissue specificity. Expressed at high levels in the lung, liver placenta and pancreas. Moderate levels seen in the heart and skeletal muscle. Lower levels found in the brain and kidney.

Post-translational modifications. Phosphorylation at Ser-359 and Ser-364 by MAPK1/ERK2 and MAPK3/ERK1 reduces its rate of degradation. ‘Lys-48’-linked polyubiquitinated by NEURL3, leading to proteasomal degradation.

Induction. By oxidative stress and heat shock.

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

RefSeq proteins (1): NP_004408* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000340	Dual-sp_phosphatase_cat-dom	Domain
IPR000387	Tyr_Pase_dom	Domain
IPR001763	Rhodanese-like_dom	Domain
IPR003595	Tyr_Pase_cat	Domain
IPR008343	MKP	Family
IPR016130	Tyr_Pase_AS	Active_site
IPR020422	TYR_PHOSPHATASE_DUAL_dom	Domain
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR036873	Rhodanese-like_dom_sf	Homologous_superfamily

Pfam: PF00581, 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)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
6,8-DIFLUORO-4-METHYLUMBELLIFERYL PHOSPHATE	0.023–0.862	22
4-NITROPHENYL PHOSPHATE	0.0028–12.7	13
P-NITROPHENYL PHOSPHATE	3–200	11
RRAPTVA	0.058–1.954	4
PHOSPHOCASEIN	0.0001–0.002	3
PHOSPHOHISTONE	0.0023–0.0723	3
PHOSPHORYLATED MYOSIN LIGHT CHAIN PEPTIDE	0.01–0.11	3
PHOSPHOSERINE-MYELIN BASIC PROTEIN	0.0004–0.022	3
DLDVPIPGRFDRRVSVAAE	0.0006–0.0138	2
DLDVPIPGRFDRRVY(P)VAAE	0.0025–0.023	2
PHOSPHORYLASE A	0.004–0.021	2
RRA(PT)VA	0.0536–0.308	2
80S-RIBOSOME	0.0027	1
AAAPTVA	0.206	1
AGPALSPVPPV	0.357	1

Catalyzed reactions (Rhea), 3 shown:

• 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): strand 7, helix 7, domain 2, modified residue 2, sequence variant 2, chain 1, turn 1, active site 1, mutagenesis site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6D66	X-RAY DIFFRACTION	2.23
6D65	X-RAY DIFFRACTION	2.35
6APX	X-RAY DIFFRACTION	2.49
6D67	X-RAY DIFFRACTION	2.55

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28562-F1	80.09	0.53

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): 258 (phosphocysteine intermediate)

Post-translational modifications (2): 359, 364

Mutagenesis-validated functional residues (1):

Position	Phenotype
258	loss of phosphatase activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-112409	RAF-independent MAPK1/3 activation
R-HSA-5675221	Negative regulation of MAPK pathway

MSigDB gene sets: 746 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GSE45365_NK_CELL_VS_CD8_TCELL_DN, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE45365_NK_CELL_VS_BCELL_UP, ATF_B, BIOCARTA_TNFR2_PATHWAY, GGGACCA_MIR133A_MIR133B, GOBP_CHROMOSOME_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_CELL_CYCLE_CHECKPOINT, FREAC2_01

GO Biological Process (31): endoderm formation (GO:0001706), negative regulation of cell adhesion (GO:0007162), signal transduction (GO:0007165), negative regulation of cell population proliferation (GO:0008285), response to light stimulus (GO:0009416), response to estradiol (GO:0032355), response to retinoic acid (GO:0032526), cellular response to hormone stimulus (GO:0032870), response to testosterone (GO:0033574), intracellular signal transduction (GO:0035556), peptidyl-threonine dephosphorylation (GO:0035970), response to hydrogen peroxide (GO:0042542), positive regulation of apoptotic process (GO:0043065), negative regulation of apoptotic process (GO:0043066), negative regulation of MAPK cascade (GO:0043409), response to glucocorticoid (GO:0051384), negative regulation of meiotic cell cycle (GO:0051447), response to cAMP (GO:0051591), response to calcium ion (GO:0051592), peptidyl-serine dephosphorylation (GO:0070262), negative regulation of ERK1 and ERK2 cascade (GO:0070373), negative regulation of monocyte chemotaxis (GO:0090027), regulation of mitotic cell cycle spindle assembly checkpoint (GO:0090266), negative regulation of p38MAPK cascade (GO:1903753), cellular response to chemokine (GO:1990869), negative regulation of DNA biosynthetic process (GO:2000279), protein dephosphorylation (GO:0006470), dephosphorylation (GO:0016311), peptidyl-tyrosine dephosphorylation (GO:0035335), negative regulation of MAP kinase activity (GO:0043407), ERK1 and ERK2 cascade (GO:0070371)

GO Molecular Function (9): phosphoprotein phosphatase activity (GO:0004721), protein serine/threonine phosphatase activity (GO:0004722), protein tyrosine phosphatase activity (GO:0004725), protein tyrosine/serine/threonine phosphatase activity (GO:0008138), MAP kinase tyrosine/serine/threonine phosphatase activity (GO:0017017), growth factor binding (GO:0019838), mitogen-activated protein kinase binding (GO:0051019), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
MAPK1/MAPK3 signaling	1
RAF/MAP kinase cascade	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to lipid	3
response to oxygen-containing compound	3
phosphoprotein phosphatase activity	3
negative regulation of cellular process	2
intracellular anatomical structure	2
protein dephosphorylation	2
apoptotic process	2
regulation of apoptotic process	2
formation of primary germ layer	1
endoderm development	1
cell adhesion	1
regulation of cell adhesion	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell population proliferation	1
regulation of cell population proliferation	1
response to radiation	1
response to hormone	1
cellular response to chemical stimulus	1
cellular response to endogenous stimulus	1
response to ketone	1
signal transduction	1
response to reactive oxygen species	1
positive regulation of programmed cell death	1
negative regulation of programmed cell death	1
MAPK cascade	1
regulation of MAPK cascade	1
negative regulation of intracellular signal transduction	1
response to corticosteroid	1
negative regulation of cell cycle	1
meiotic cell cycle	1
regulation of meiotic cell cycle	1
negative regulation of reproductive process	1
response to purine-containing compound	1
response to organophosphorus	1
response to metal ion	1
phosphatase activity	1

Protein interactions and networks

STRING

3454 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DUSP1	MAPK14	Q16539	902
DUSP1	MAPK8	P45983	874
DUSP1	MAPK3	P27361	828
DUSP1	JUN	P05412	825
DUSP1	MAPK1	P28482	818
DUSP1	FOS	P01100	796
DUSP1	ATF3	P18847	740
DUSP1	IL6	P05231	717
DUSP1	CALM1	P02593	710
DUSP1	ZFP36	P26651	707
DUSP1	FOSB	P53539	702
DUSP1	HDAC1	Q13547	696
DUSP1	NR4A1	P22736	686
DUSP1	MAPK11	Q15759	674
DUSP1	MAP2K1	Q02750	670

IntAct

24 interactions, top by confidence:

A	B	Type	Score
DUSP1	MAPK14	psi-mi:“MI:0915”(physical association)	0.770
DUSP1	MAPK14	psi-mi:“MI:2364”(proximity)	0.770
DUSP1	MAPK14	psi-mi:“MI:0203”(dephosphorylation reaction)	0.770
MAPK3	DUSP1	psi-mi:“MI:2364”(proximity)	0.710
DUSP1	MAPK3	psi-mi:“MI:0217”(phosphorylation reaction)	0.710
MAPK3	DUSP1	psi-mi:“MI:0203”(dephosphorylation reaction)	0.710
DUSP1	SKP2	psi-mi:“MI:0915”(physical association)	0.580
DUSP1	MAPK1	psi-mi:“MI:0915”(physical association)	0.540
MAPK1	DUSP1	psi-mi:“MI:0915”(physical association)	0.540
MAPK1	DUSP1	psi-mi:“MI:0217”(phosphorylation reaction)	0.540
UBB	DUSP1	psi-mi:“MI:0220”(ubiquitination reaction)	0.540
DUSP1	UBB	psi-mi:“MI:0915”(physical association)	0.540
Mapk8	DUSP1	psi-mi:“MI:0203”(dephosphorylation reaction)	0.440
HSPB2	DUSP1	psi-mi:“MI:0915”(physical association)	0.370
DUSP1	AATK	psi-mi:“MI:0915”(physical association)	0.370
DUSP1	ROR2	psi-mi:“MI:0915”(physical association)	0.370
POLR1H	DUSP1	psi-mi:“MI:0915”(physical association)	0.370
DUSP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
DUSP1	HSPB1	psi-mi:“MI:0914”(association)	0.350
DUSP1	CKS1B	psi-mi:“MI:0914”(association)	0.350
MAPK12	DUSP1	psi-mi:“MI:2364”(proximity)	0.270
DUSP1		psi-mi:“MI:0915”(physical association)	0.000
MAPK14	DUSP1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (132): DUSP1 (Two-hybrid), DUSP1 (Co-localization), DUSP1 (Co-localization), DUSP1 (Co-localization), MAPK14 (Affinity Capture-MS), DUSP1 (Affinity Capture-MS), MAPK14 (Affinity Capture-MS), SNX17 (Affinity Capture-MS), ABHD14B (Affinity Capture-MS), COPZ1 (Affinity Capture-MS), ICMT (Affinity Capture-MS), DUSP3 (Affinity Capture-MS), COX4I1 (Affinity Capture-MS), SRM (Affinity Capture-MS), PARK7 (Affinity Capture-MS)

ESM2 similar proteins: A1L1G1, A2XUN8, B2RYJ8, D3ZAA9, F1MH07, O08764, O95382, P28562, P28563, P47823, P51432, P54760, P58404, P70218, P70268, Q01970, Q0P5E6, Q12851, Q13144, Q13424, Q13425, Q14168, Q28626, Q4ACU6, Q5R8E2, Q5ZLR4, Q61161, Q61234, Q61235, Q63433, Q64623, Q68G30, Q6P9Q4, Q7TQI7, Q7XK25, Q7ZVR8, Q8CHW4, Q8K0G8, Q8N961, Q8R0H9

Diamond homologs: A0A7H0DN78, P07239, P0C597, P0C598, P0C5A0, P0C5A1, P0DOQ5, P0DOQ6, P20495, P28191, P28562, P28563, P29074, P51452, P80994, Q05923, Q13115, Q16690, Q16828, Q2KJ36, Q4RQD3, Q54R42, Q54T76, Q5RD73, Q62767, Q64346, Q64623, Q6B8I0, Q6B8I1, Q84JU4, Q85297, Q8BFV3, Q90W58, Q91790, Q99956, Q9D0T2, Q9DBB1, Q9J592, Q9M8K7, Q9PW71

SIGNOR signaling

32 interactions.

A	Effect	B	Mechanism
MAPK1	down-regulates	DUSP1	phosphorylation
MAPK3	down-regulates	DUSP1	phosphorylation
DUSP1	“down-regulates activity”	MAPK14	dephosphorylation
EP300	up-regulates	DUSP1	acetylation
PTEN	“up-regulates quantity by expression”	DUSP1	“transcriptional regulation”
DUSP1	down-regulates	Gbeta	dephosphorylation
DUSP1	down-regulates	ERK1/2	dephosphorylation
Gbeta	down-regulates	DUSP1	phosphorylation
ERK1/2	down-regulates	DUSP1	phosphorylation
PRKAA2	“down-regulates quantity by destabilization”	DUSP1	phosphorylation
DUSP1	“down-regulates activity”	JUN	dephosphorylation
DUSP1	“up-regulates activity”	RUNX2	dephosphorylation
DUSP1	down-regulates	MAPK9	dephosphorylation
DUSP1	down-regulates	MAPK8	dephosphorylation
DUSP1	down-regulates	MAPK1	dephosphorylation
DUSP1	down-regulates	MAPK3	dephosphorylation
MAPK1	up-regulates	DUSP1	phosphorylation
MAPK3	up-regulates	DUSP1	phosphorylation
MAPK14	“up-regulates activity”	DUSP1	binding
RBPJ	up-regulates	DUSP1	binding
NR3C1	“up-regulates quantity”	DUSP1
RBPJ/NOTCH	“up-regulates quantity”	DUSP1	“transcriptional regulation”
DUSP1	“down-regulates activity”	MAPK3	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 14 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of HSF1-mediated heat shock response	5	58.0×	3e-06
Cellular responses to stress	5	15.3×	2e-04
Cellular responses to stimuli	5	13.1×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
intracellular signal transduction	5	14.7×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

232 predictions. Top by Δscore:

Variant	Effect	Δscore
5:172769129:GAGT:G	acceptor_gain	1.0000
5:172769131:GT:G	acceptor_gain	1.0000
5:172769131:GTC:G	acceptor_loss	1.0000
5:172769132:TC:T	acceptor_loss	1.0000
5:172769133:C:CC	acceptor_gain	1.0000
5:172769133:C:CG	acceptor_loss	1.0000
5:172769570:TTTAC:T	donor_loss	1.0000
5:172769571:TTACC:T	donor_loss	1.0000
5:172769572:TAC:T	donor_loss	1.0000
5:172769573:A:AT	donor_loss	1.0000
5:172769574:C:A	donor_loss	1.0000
5:172769790:CCACC:C	acceptor_gain	1.0000
5:172769791:CACC:C	acceptor_gain	1.0000
5:172769791:CACCC:C	acceptor_gain	1.0000
5:172769792:ACCCT:A	acceptor_loss	1.0000
5:172769793:CC:C	acceptor_gain	1.0000
5:172769793:CCCT:C	acceptor_loss	1.0000
5:172769794:CC:C	acceptor_gain	1.0000
5:172769795:C:A	acceptor_loss	1.0000
5:172769795:C:CC	acceptor_gain	1.0000
5:172769795:C:T	acceptor_gain	1.0000
5:172769796:T:C	acceptor_loss	1.0000
5:172769804:A:T	acceptor_gain	1.0000
5:172770582:GTACC:G	donor_loss	1.0000
5:172770583:TACC:T	donor_loss	1.0000
5:172769128:GGAGT:G	acceptor_gain	0.9900
5:172769130:AGT:A	acceptor_gain	0.9900
5:172769142:C:T	acceptor_gain	0.9900
5:172769573:A:AC	donor_gain	0.9900
5:172769574:C:CC	donor_gain	0.9900

AlphaMissense

2391 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:172768940:T:A	E309V	1.000
5:172768942:A:C	F308L	1.000
5:172768942:A:T	F308L	1.000
5:172768943:A:C	F308C	1.000
5:172768943:A:G	F308S	1.000
5:172768944:A:G	F308L	1.000
5:172768949:A:G	L306P	1.000
5:172768952:A:C	L305R	1.000
5:172768952:A:G	L305P	1.000
5:172768952:A:T	L305Q	1.000
5:172768954:C:A	Q304H	1.000
5:172768954:C:G	Q304H	1.000
5:172768955:T:G	Q304P	1.000
5:172768958:C:T	G303D	1.000
5:172768959:C:G	G303R	1.000
5:172768960:C:A	M302I	1.000
5:172768960:C:G	M302I	1.000
5:172768960:C:T	M302I	1.000
5:172768961:A:G	M302T	1.000
5:172768963:G:C	F301L	1.000
5:172768963:G:T	F301L	1.000
5:172768964:A:C	F301C	1.000
5:172768964:A:G	F301S	1.000
5:172768965:A:C	F301V	1.000
5:172768965:A:G	F301L	1.000
5:172768965:A:T	F301I	1.000
5:172768970:A:G	F299S	1.000
5:172768972:G:C	N298K	1.000
5:172768972:G:T	N298K	1.000
5:172768973:T:A	N298I	1.000

dbSNP variants (sampled 300 via entrez): RS1000222677 (5:172772183 C>T), RS1000517485 (5:172771375 C>G,T), RS1000685993 (5:172770999 G>A,T), RS1000823494 (5:172771213 G>A,C), RS1001351105 (5:172767879 T>G), RS1001680397 (5:172772491 C>T), RS1001968409 (5:172771586 C>G), RS1002020554 (5:172771414 G>A,T), RS1002356983 (5:172769469 G>A,C), RS1002522435 (5:172769031 C>T), RS1002985137 (5:172768694 T>C), RS1003411162 (5:172772476 G>C,T), RS1003984688 (5:172769425 A>C,G,T), RS1004943080 (5:172771245 G>A), RS1005296397 (5:172768869 T>C,G)

Disease associations

OMIM: gene MIM:600714 | disease phenotypes: MIM:236600

GenCC curated gene-disease

Mondo (1): congenital hydrocephalus (MONDO:0016349)

Orphanet (1): Congenital hydrocephalus (Orphanet:2185)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST002626_3	Vertical cup-disc ratio	8.000000e-09
GCST003043_99	Inflammatory bowel disease	2.000000e-07
GCST003045_44	Ulcerative colitis	2.000000e-06
GCST004075_36	Vertical cup-disc ratio	5.000000e-09
GCST004075_37	Vertical cup-disc ratio	1.000000e-08
GCST004137_16	Optic cup area	2.000000e-08
GCST004137_32	Optic cup area	2.000000e-08
GCST006627_20	Diastolic blood pressure	3.000000e-10
GCST007614_41	C-reactive protein levels	6.000000e-09
GCST007615_19	C-reactive protein levels	6.000000e-12
GCST008363_45	Offspring birth weight	4.000000e-13
GCST009391_1011	Metabolite levels	7.000000e-06
GCST009412_19	Vertical cup-disc ratio	7.000000e-09
GCST009723_64	Vertical cup-disc ratio (adjusted for vertical disc diameter)	3.000000e-08
GCST009724_1	Vertical cup-disc ratio (multi-trait analysis)	4.000000e-14

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0006939	cup-to-disc ratio measurement
EFO:0006336	diastolic blood pressure
EFO:0004458	C-reactive protein measurement
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0010359	lysophosphatidylcholine 18:0 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6026 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

Binding affinities (BindingDB)

58 measured of 170 human assays (177 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
4-[5-(3-carbomethoxy-5-keto-2-methyl-1,4-dihydroindeno[1,2-b]pyridin-4-yl)-2-furyl]benzoic acid	EC50	0.00174 nM
1-Ethyl-6-methyl-3-thiophen-2-yl-1H-pyrimido[5,4-e][1,2,4]triazine-5,7-dione	IC50	72.2 nM
1,8-bis(azanyl)-3,6-dipyrrolidin-1-yl-2,7-naphthyridine-4-carbonitrile	IC50	3170 nM
(5-oxidanidyl-4-thiophen-2-ylcarbonyl-1,2,5-oxadiazol-5-ium-3-yl)-thiophen-2-yl-methanone	IC50	3490 nM
MLS000080844	EC50	4050 nM
2-[(5-amino-1H-1,2,4-triazol-3-yl)sulfanyl]-N-[3-cyano-7,7-dimethyl-5-[(E)-2-(5-methylfuran-2-yl)ethenyl]-6H-1-benzothiophen-2-yl]acetamide	EC50	6380 nM
MLS000071484	IC50	6410 nM
MLS000082957	IC50	10400 nM
MLS000050867	IC50	11400 nM
Icosa‐5,8,11,14‐tetraynoic acid (D3)	IC50	12100 nM
3-amino-N-(5-propylsulfanyl-1,3,4-thiadiazol-2-yl)-6-thiophen-2-ylthieno[2,3-b]pyridine-2-carboxamide	IC50	12400 nM
(5Z)-5-(5-bromo-2-methoxybenzylidene)-2-(2-furyl)[1,3]thiazolo[3,2-b][1,2,4]triazol-6(5H)-one	IC50	12800 nM
2-(2-furanyl)-4-quinolinecarboxylic acid [2-[4-amino-1-methyl-2,6-dioxo-3-(phenylmethyl)-5-pyrimidinyl]-2-oxoethyl] ester	IC50	13400 nM
5-bromanyl-N-(3-cyano-1-phenyl-pyrrolo[3,2-b]quinoxalin-2-yl)furan-2-carboxamide	IC50	14000 nM
MLS000085603	IC50	14200 nM
MLS000106874	IC50	14300 nM
8-(cyclohexoxycarbonyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-4-carboxylic acid	IC50	14500 nM
2-(4-ethoxyphenyl)-5-[1-[(2-methylpropan-2-yl)oxy-oxomethyl]-4-piperidinyl]-6-pyrazolo[1,5-a]pyrimidinecarboxylic acid	IC50	15000 nM
8-carbethoxy-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-4-carboxylic acid	IC50	15800 nM
2-(2-furanyl)-4-quinolinecarboxylic acid [2-[4-amino-1-methyl-3-(2-methylpropyl)-2,6-dioxo-5-pyrimidinyl]-2-oxoethyl] ester	IC50	16800 nM
2-(2-furanyl)-4-quinolinecarboxylic acid [2-[6-amino-1-methyl-2,4-dioxo-3-(phenylmethyl)-5-pyrimidinyl]-2-oxoethyl] ester	IC50	16900 nM
MLS000079944	IC50	17000 nM
2-(7-Ethyl-1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylsulfanyl)-N-(6-methoxy-benzothiazol-2-yl)-acetamide	IC50	18200 nM
1,2-Dione-Based Compound, 8	IC50	18400 nM
3-hydroxy-2-phenyl-2,3-dihydro-1,5-benzothiazepin-4(5H)-one	IC50	20100 nM
2-(2-furanyl)-4-quinolinecarboxylic acid [2-(4-amino-1,3-dimethyl-2,6-dioxo-5-pyrimidinyl)-2-oxoethyl] ester	IC50	20600 nM
MLS000093276	IC50	22700 nM
(Z)-7-[(1R,2S)-2-[(E,3S)-3-hydroxyoct-1-enyl]-5-keto-cyclopent-3-en-1-yl]hept-5-enoic acid	IC50	23300 nM
MLS000054842	IC50	23500 nM
2-(2-furanyl)-4-quinolinecarboxylic acid [2-[6-amino-1-(cyclopropylmethyl)-3-methyl-2,4-dioxo-5-pyrimidinyl]-2-oxoethyl] ester	IC50	24600 nM
MLS000091355	IC50	24900 nM
5-chloranyl-3-[2-[4-(2,3-dimethylphenyl)piperazin-1-yl]-2-oxidanylidene-ethyl]-1H-indole-2-carboxylic acid	IC50	25800 nM
2-amino-1-(3-methoxypropyl)-N-(3-methylbutyl)-3-pyrrolo[3,2-b]quinoxalinecarboxamide	IC50	26200 nM
2-amino-N-butyl-1-(3-methoxypropyl)-3-pyrrolo[3,2-b]quinoxalinecarboxamide	IC50	26200 nM
2-(1,5-dimethyl-3-oxidanylidene-2-phenyl-pyrazol-4-yl)iminoindene-1,3-dione	IC50	26200 nM
2-(4-methoxyphenyl)-5-[1-[(2-methylpropan-2-yl)oxy-oxomethyl]-4-piperidinyl]-6-pyrazolo[1,5-a]pyrimidinecarboxylic acid	IC50	26900 nM
9-cis-retinoic acid (9cRA)	IC50	27100 nM
2-cyclopropyl-4-quinolinecarboxylic acid [2-[6-amino-1-methyl-2,4-dioxo-3-(phenylmethyl)-5-pyrimidinyl]-2-oxoethyl] ester	IC50	28900 nM
MLS000106837	IC50	30200 nM
6-chloranyl-N-[2-(cyclohexen-1-yl)ethyl]-5-methyl-7-oxidanylidene-1H-pyrazolo[1,5-a]pyrimidine-3-carboxamide	IC50	31100 nM
MLS000050353	EC50	33300 nM
MLS000094302	IC50	35900 nM
5-({4-[2-cyano-2-(4-fluorophenyl)vinyl]-2-ethoxyphenoxy}methyl)-2-furoic acid	IC50	36100 nM
2,3-bis(2-furanyl)-N-phenyl-6-quinoxalinecarboxamide	EC50	36500 nM
5-oxidanylidene-N3-(oxolan-2-ylmethyl)-N8-pentyl-1-sulfanylidene-4H-[1,3]thiazolo[3,4-a]quinazoline-3,8-dicarboxamide	IC50	36700 nM
MLS000081820	IC50	39000 nM
6,7-dimethyl-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-4-carboxylic acid	IC50	40400 nM
1-butyl-2-[2-(2,4-dimethoxyphenyl)-2-oxidanylidene-ethyl]sulfanyl-benzimidazole-5-sulfonamide	IC50	42100 nM
6-hydroxy-4-phenyl-3,4-dihydro-2H-1-benzopyran-2-one	IC50	44200 nM
MLS000095236	IC50	45800 nM

ChEMBL bioactivities

14 potent at pChembl≥5 of 25 total, top 14 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.34	IC50	460	nM	CHEMBL565795
6.33	IC50	470	nM	CHEMBL567069
6.28	IC50	520	nM	CHEMBL584481
6.11	IC50	780	nM	CHEMBL565810
5.57	IC50	2700	nM	CHEMBL4460074
5.55	IC50	2800	nM	CHEMBL565371
5.32	IC50	4800	nM	CHEMBL4458682
5.18	IC50	6600	nM	CHEMBL4579674
5.10	IC50	7900	nM	CHEMBL4519826
5.10	IC50	8000	nM	CHEMBL1334684
5.10	IC50	8000	nM	CHEMBL1334633
5.10	IC50	8000	nM	CHEMBL1447034
5.08	IC50	8300	nM	CHEMBL4462328
5.06	IC50	8700	nM	CHEMBL4542577

PubChem BioAssay actives

14 with measured affinity, of 79 total; 14 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	443923: Inhibition of recombinant MKP1	ic50	0.4600	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	443923: Inhibition of recombinant MKP1	ic50	0.4700	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	443923: Inhibition of recombinant MKP1	ic50	0.5200	uM
2-[(5Z)-4-oxo-5-[[1-phenyl-3-(4-phenylmethoxyphenyl)pyrazol-4-yl]methylidene]-2-sulfanylidene-1,3-thiazolidin-3-yl]ethanesulfonic acid	443923: Inhibition of recombinant MKP1	ic50	0.7800	uM
4-bromo-N-[[3-(5-chloro-1,3-benzoxazol-2-yl)phenyl]carbamothioyl]benzamide	1544977: Inhibition of His-tagged DUSP1 catalytic domain (152 to 323 residues) (unknown origin) using DiFMUP as substrate incubated for 30 mins by spectrofluorometric analysis	ic50	2.7000	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	443923: Inhibition of recombinant MKP1	ic50	2.8000	uM
N-[[3-(1,3-benzoxazol-2-yl)phenyl]carbamothioyl]-4-bromobenzamide	1544977: Inhibition of His-tagged DUSP1 catalytic domain (152 to 323 residues) (unknown origin) using DiFMUP as substrate incubated for 30 mins by spectrofluorometric analysis	ic50	4.8000	uM
4-methyl-N-[[3-(5-methyl-1,3-benzoxazol-2-yl)phenyl]carbamothioyl]benzamide	1544977: Inhibition of His-tagged DUSP1 catalytic domain (152 to 323 residues) (unknown origin) using DiFMUP as substrate incubated for 30 mins by spectrofluorometric analysis	ic50	6.6000	uM
4-bromo-N-[[3-(5-methyl-1,3-benzoxazol-2-yl)phenyl]carbamothioyl]benzamide	1544977: Inhibition of His-tagged DUSP1 catalytic domain (152 to 323 residues) (unknown origin) using DiFMUP as substrate incubated for 30 mins by spectrofluorometric analysis	ic50	7.9000	uM
8-ethoxycarbonyl-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-4-carboxylic acid	2037694: Inhibition of 6His-tagged recombinant MKP1 (unknown origin) expressed in Escherichia coli BL21 (DE3) using OMFP as substrate incubated for 60 mins by HTS assay	ic50	8.0000	uM
8-cyclohexyloxycarbonyl-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-4-carboxylic acid	2037694: Inhibition of 6His-tagged recombinant MKP1 (unknown origin) expressed in Escherichia coli BL21 (DE3) using OMFP as substrate incubated for 60 mins by HTS assay	ic50	8.0000	uM
6,7-dimethyl-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-4-carboxylic acid	2037694: Inhibition of 6His-tagged recombinant MKP1 (unknown origin) expressed in Escherichia coli BL21 (DE3) using OMFP as substrate incubated for 60 mins by HTS assay	ic50	8.0000	uM
N-[[4-chloro-3-(5-methyl-1,3-benzoxazol-2-yl)phenyl]carbamothioyl]-4-methylbenzamide	1544977: Inhibition of His-tagged DUSP1 catalytic domain (152 to 323 residues) (unknown origin) using DiFMUP as substrate incubated for 30 mins by spectrofluorometric analysis	ic50	8.3000	uM
4-bromo-N-[[4-chloro-3-(5-methyl-1,3-benzoxazol-2-yl)phenyl]carbamothioyl]benzamide	1544977: Inhibition of His-tagged DUSP1 catalytic domain (152 to 323 residues) (unknown origin) using DiFMUP as substrate incubated for 30 mins by spectrofluorometric analysis	ic50	8.7000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	decreases expression, increases abundance, affects expression, increases reaction, increases expression	7
sodium arsenite	affects expression, decreases expression, increases abundance, increases expression, increases reaction	6
Cadmium	increases abundance, increases expression	6
monomethylarsonous acid	affects expression, decreases expression, increases expression	5
Air Pollutants	increases expression, affects expression, increases abundance, decreases expression	5
Benzo(a)pyrene	increases expression	5
Dexamethasone	decreases reaction, decreases expression, increases expression, affects cotreatment, increases reaction	5
Estradiol	decreases reaction, increases expression, decreases expression, affects cotreatment, affects expression	5
Oxygen	affects cotreatment, decreases expression, decreases reaction, increases expression	5
Valproic Acid	increases expression	5
trichostatin A	increases activity, decreases reaction, increases expression, increases chemical synthesis, increases phosphorylation (+1 more)	4
arsenite	decreases methylation, increases expression, increases abundance, affects binding, increases reaction	4
Hydrogen Peroxide	affects expression, increases expression	4
methylmercuric chloride	increases expression	3
bisphenol A	decreases expression, increases methylation	3
Cisplatin	decreases expression, increases reaction, increases expression	3
Silver	decreases expression, increases expression	3
Tetradecanoylphorbol Acetate	affects cotreatment, decreases reaction, increases expression	3
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	3
Asbestos, Crocidolite	affects response to substance, increases expression	3
Genistein	decreases expression, increases expression	3
2-methyl-4-isothiazolin-3-one	increases expression	2
4-phenylenediamine	increases expression	2
resorcinol	increases expression	2
perfluorooctane sulfonic acid	decreases expression, increases expression	2
Fluticasone	increases reaction, affects cotreatment, increases expression	2
Salmeterol Xinafoate	affects cotreatment, increases expression, increases reaction	2
Resveratrol	increases activity, affects cotreatment, decreases expression, decreases reaction	2
Arsenic	increases expression	2
Vehicle Emissions	affects expression, increases reaction, increases expression	2

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1047961	Binding	Inhibition of recombinant MKP1	Multidentate small-molecule inhibitors of vaccinia H1-related (VHR) phosphatase decrease proliferation of cervix cancer cells. — J Med Chem

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1W5	Abcam A-549 DUSP1 KO	Cancer cell line	Male
CVCL_D2AI	Abcam HCT 116 DUSP1 KO	Cancer cell line	Male
CVCL_D7NZ	Ubigene A-549 DUSP1 KO	Cancer cell line	Male
CVCL_D8KD	Ubigene HCT 116 DUSP1 KO	Cancer cell line	Male
CVCL_D9DQ	Ubigene HEK293 DUSP1 KO	Transformed cell line	Female
CVCL_E0C0	Ubigene HeLa DUSP1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

1 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT06664372	Not specified	NOT_YET_RECRUITING	Insertion of Frontal Ventricular Catheter of VP Shunt in Congenital Hydrocephalus Guided by Trans Fontanelle Ultrasound