DUSP10

Summary

DUSP10 (dual specificity phosphatase 10, HGNC:3065) is a protein-coding gene on chromosome 1q41, encoding Dual specificity protein phosphatase 10 (Q9Y6W6). Protein phosphatase involved in the inactivation of MAP kinases.

Dual specificity protein phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the MAP kinase superfamily, which is associated with cellular proliferation and differentiation. Different members of this family of dual specificity phosphatases show distinct substrate specificities for MAP kinases, different tissue distribution and subcellular localization, and different modes of expression induction by extracellular stimuli. This gene product binds to and inactivates p38 and SAPK/JNK. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 11221 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 75 total
• Druggable target: yes
• MANE Select transcript: NM_007207

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3065
Approved symbol	DUSP10
Name	dual specificity phosphatase 10
Location	1q41
Locus type	gene with protein product
Status	Approved
Aliases	MKP-5, MKP5
Ensembl gene	ENSG00000143507
Ensembl biotype	protein_coding
OMIM	608867
Entrez	11221

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 3 nonsense_mediated_decay

ENST00000366899, ENST00000468085, ENST00000477026, ENST00000494642, ENST00000891851, ENST00000891852, ENST00000891853, ENST00000891854, ENST00000891855, ENST00000891856, ENST00000959625

RefSeq mRNA: 1 — MANE Select: NM_007207 NM_007207

CCDS: CCDS1528

Canonical transcript exons

ENST00000366899 — 4 exons

Exon	Start	End
ENSE00001285025	221701424	221702677
ENSE00001921320	221741981	221742089
ENSE00002307909	221738934	221739787
ENSE00003619064	221706095	221706466

Expression profiles

Bgee: expression breadth ubiquitous, 271 present calls, max score 94.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.2753 / max 1027.0341, expressed in 1766 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
17584	36.1040	1766
17583	0.1170	45
201957	0.0507	23
17578	0.0036	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.49	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.45	gold quality
biceps brachii	UBERON:0001507	92.97	gold quality
secondary oocyte	CL:0000655	91.14	gold quality
buccal mucosa cell	CL:0002336	90.67	gold quality
stromal cell of endometrium	CL:0002255	90.58	gold quality
right lobe of liver	UBERON:0001114	89.93	gold quality
oocyte	CL:0000023	89.69	gold quality
triceps brachii	UBERON:0001509	89.32	gold quality
liver	UBERON:0002107	89.02	gold quality
skeletal muscle tissue	UBERON:0001134	88.05	gold quality
vastus lateralis	UBERON:0001379	87.70	gold quality
quadriceps femoris	UBERON:0001377	86.92	gold quality
nasal cavity epithelium	UBERON:0005384	86.70	gold quality
pigmented layer of retina	UBERON:0001782	85.35	gold quality
muscle tissue	UBERON:0002385	85.28	gold quality
ventricular zone	UBERON:0003053	85.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.37	gold quality
gluteal muscle	UBERON:0002000	83.15	gold quality
muscle organ	UBERON:0001630	83.00	gold quality
body of pancreas	UBERON:0001150	82.30	gold quality
deltoid	UBERON:0001476	82.14	gold quality
nasal cavity mucosa	UBERON:0001826	81.92	gold quality
granulocyte	CL:0000094	81.79	gold quality
choroid plexus epithelium	UBERON:0003911	81.71	gold quality
monocyte	CL:0000576	81.69	gold quality
mononuclear cell	CL:0000842	81.62	gold quality
leukocyte	CL:0000738	81.50	gold quality
hindlimb stylopod muscle	UBERON:0004252	81.43	gold quality
epithelium of nasopharynx	UBERON:0001951	81.30	silver quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-7052	yes	530.38
E-CURD-46	yes	7.35
E-MTAB-9801	yes	6.28
E-MTAB-6678	yes	4.88
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF2

miRNA regulators (miRDB)

118 targeting DUSP10, 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-1252-5P	100.00	69.80	2774
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
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-5696	99.98	72.36	4487
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-3148	99.97	75.06	6478
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062

Literature-anchored findings (GeneRIF, showing 28)

• Structural information provides an explanation of constitutive activity of MKP5 as well as the structural insight into substrate-induced activation occurred in other MKPs. (PMID:16806267)
• Mitogen-activated protein kinase phosphatase-5 (MKP5) mediates anti-inflammatory activities of phytochemicals curcumin, resveratrol and [6]-gingerol. (PMID:17151092)
• Catalytic domain of MKP5 is in an active conformation, and two loops in the active site have backbone shifts of up to 5 A. (PMID:17400920)
• 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)
• p38 MAP kinase down-regulates extracellular signal-regulated kinase via activation of MKP-3 in human monocytes exposed to asbestos to enhance TNF-alpha gene expression. (PMID:18314537)
• a function for ASC that is distinct from the inflammasome in modulating MAPK activity and chemokine expression and further identify DUSP10 as a novel ASC target. (PMID:21487011)
• DUSPs 10 and 16 are positive regulators of activation, apparently acting by modulating cross-talk between the p38 and ERK pathways. (PMID:22245064)
• A distinct interaction mode revealed by the crystal structure of the kinase p38alpha with the MAPK binding domain of the phosphatase MKP5. (PMID:22375048)
• MKP-5 interacts with ERK, retains it in the cytoplasm, suppresses its activation and downregulates ERK-dependent transcription. (PMID:22711061)
• Data indicate that the activities of phosphoprotein phosphatases MKP5 and MKP7 were determined in the system. (PMID:23233447)
• Certain mutations in DUSP10 correlate with the incidence of colorectal cancer(CRC). Thus, the function of the DUSP10 gene product may contribute toward CRC in the Han Chinese population. (PMID:23872954)
• Single nucleotide polymorphism in DUSP10 gene is associated with celiac disease. (PMID:23936387)
• Depletion of miR-181 family members by miRNA inhibitors enhanced the expression of MKP-5 and suppressed the phosphorylation of p38 MAPK after exposure to PAHs, which promotes cancer cell migration. (PMID:23993976)
• Data suggest that vitamin D receptor target genes (DUSP10; THBD, thrombomodulin; NRIP1, nuclear receptor interacting protein 1; TRAK1, trafficking protein kinesin binding 1) can be used as markers for individual’s response to vitamin D3 supplements. (PMID:24975273)
• Increased Dusp10 expression is associated with better survival rate in colorectal cancer patients. (PMID:25772234)
• In females, three SNPs were associated with decreased colorectal cancer risk: rs11118838, rs12724393, and rs908858. However, in males, only one SNP, rs908858, was associated with decreased colorectal cancer risk. (PMID:25973098)
• This study demonstrates that AGR2, which is overexpressed in a variety of human cancers and provides a poor prognosis, up-regulates DUSP10 which subsequently inhibits p38 MAPK and prevents p53 activation by phosphorylation. (PMID:26733232)
• High DUSP10 expression is associated with Metastasis of Hepatocellular Carcinoma. (PMID:28674078)
• Our findings uncover novel associations of progressive supranuclear palsy with SLCO1A2 (rs11568563) and DUSP10 (rs6687758) variants (PMID:29986742)
• Data found DUSP10 downregulated by rhinovirus (RV) infection. siRNA-mediated knockdown of DUSP10 identified a role for the protein in negatively regulating inflammatory cytokine production in response to IL-1beta alone and in combination with RV, without any effect on RV replication. This study identifies DUSP10 as an important regulator of airway inflammation in respiratory viral infection. (PMID:30333178)
• Study of genome-wide epigenetic changes in bronchial epithelial cells of asthmatic patients, following cells treatment with vitamin D3 and Poly (I:C)(a viral analogue) allows the identification of biologically plausible candidate genes for viral infections and asthma, such as DUSP10 and SLC44A1. (PMID:31122150)
• Gene overexpression and knockdown demonstrated that MKP-5 could alleviate glucolipotoxicity-induced apoptosis via the endoplasmic reticulum (ER) stress and mitochondrial apoptosis pathways owing to the altered regulation of caspase family members and ER stress-related molecules. MKP-5 is a main mediator for glucolipotoxicity-induced islet cell dysfunction and apoptosis, with JNK and P38 as critical downstream pathways. (PMID:31202710)
• High DUSP10 expression is associated with pulmonary fibrosis. (PMID:31483681)
• An allosteric site on MKP5 reveals a strategy for small-molecule inhibition. (PMID:32843541)
• SETD8 potentiates constitutive ERK1/2 activation via epigenetically silencing DUSP10 expression in pancreatic cancer. (PMID:33232789)
• De novo germline mutation in the dual specificity phosphatase 10 gene accelerates autoimmune diabetes. (PMID:34782469)
• MiRNA-363-3p/DUSP10/JNK axis mediates chemoresistance by enhancing DNA damage repair in diffuse large B-cell lymphoma. (PMID:35488020)
• DUSP10 is a novel immune-related biomarker connected with survival and cellular proliferation in lower-grade glioma. (PMID:37387540)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dusp10	ENSDARG00000052465
mus_musculus	Dusp10	ENSMUSG00000039384
rattus_norvegicus	Dusp10	ENSRNOG00000004003

Paralogs (31): DUSP13B (ENSG00000079393), DUSP12 (ENSG00000081721), SSH1 (ENSG00000084112), DUSP3 (ENSG00000108861), PTPMT1 (ENSG00000110536), DUSP16 (ENSG00000111266), EPM2A (ENSG00000112425), DUSP22 (ENSG00000112679), DUSP1 (ENSG00000120129), DUSP4 (ENSG00000120875), STYXL1 (ENSG00000127952), DUSP9 (ENSG00000130829), DUSP26 (ENSG00000133878), DUSP5 (ENSG00000138166), DUSP6 (ENSG00000139318), SSH2 (ENSG00000141298), 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 10 — Q9Y6W6 (reviewed: Q9Y6W6)

Alternative names: Mitogen-activated protein kinase phosphatase 5

All UniProt accessions (2): Q9Y6W6, A0A0B4J2F5

UniProt curated annotations — full annotation on UniProt →

Function. Protein phosphatase involved in the inactivation of MAP kinases. Has a specificity for the MAPK11/MAPK12/MAPK13/MAPK14 subfamily. It preferably dephosphorylates p38.

Subunit / interactions. Monomer. Interacts with MAPK14.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed in keratinocytes (at protein level). Detected in brain.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y6W6-1	1	yes
Q9Y6W6-2	2

RefSeq proteins (1): NP_009138* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000340	Dual-sp_phosphatase_cat-dom	Domain
IPR000387	Tyr_Pase_dom	Domain
IPR001763	Rhodanese-like_dom	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)
• 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), 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 (41 total): helix 18, strand 14, domain 2, mutagenesis site 2, chain 1, turn 1, region of interest 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

23 structures.

PDB	Method	Resolution (Å)
1ZZW	X-RAY DIFFRACTION	1.6
7UMV	X-RAY DIFFRACTION	1.8
7Y4B	X-RAY DIFFRACTION	1.86
7Y4C	X-RAY DIFFRACTION	1.87
7Y4E	X-RAY DIFFRACTION	1.93
9NYM	X-RAY DIFFRACTION	2
7Y4D	X-RAY DIFFRACTION	2.18
2OUC	X-RAY DIFFRACTION	2.2
7U4O	X-RAY DIFFRACTION	2.3
9O8W	X-RAY DIFFRACTION	2.39
9BPN	X-RAY DIFFRACTION	2.4
9NSB	X-RAY DIFFRACTION	2.5
7UMU	X-RAY DIFFRACTION	2.51
6MC1	X-RAY DIFFRACTION	2.7
7UN4	X-RAY DIFFRACTION	2.7
3TG1	X-RAY DIFFRACTION	2.71
2OUD	X-RAY DIFFRACTION	2.8
9BU4	X-RAY DIFFRACTION	2.9
9Q7X	X-RAY DIFFRACTION	2.95
7UN0	X-RAY DIFFRACTION	3
9OK9	X-RAY DIFFRACTION	3
7U4R	X-RAY DIFFRACTION	3.14
9Y55	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6W6-F1	70.95	0.38

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): 408 (phosphocysteine intermediate)

Mutagenesis-validated functional residues (2):

Position	Phenotype
180–181	reduced enzyme activity with mapk14.
203–204	strongly reduced affinity for mapk14. almost abolishes enzyme activity with mapk14.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-112409	RAF-independent MAPK1/3 activation
R-HSA-5675221	Negative regulation of MAPK pathway
R-HSA-9652817	Signaling by MAPK mutants

MSigDB gene sets: 469 (showing top): GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_REGULATION_OF_RESPIRATORY_BURST, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, BROWNE_HCMV_INFECTION_6HR_DN, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_NEGATIVE_REGULATION_OF_OLIGODENDROCYTE_DIFFERENTIATION, GOBP_REGULATION_OF_STRESS_ACTIVATED_PROTEIN_KINASE_SIGNALING_CASCADE, GOBP_INFLAMMATORY_RESPONSE, FISCHER_G1_S_CELL_CYCLE, GOBP_NEGATIVE_REGULATION_OF_GLIOGENESIS, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH

GO Biological Process (23): regulation of adaptive immune response (GO:0002819), signal transduction (GO:0007165), negative regulation of epithelial cell migration (GO:0010633), dephosphorylation (GO:0016311), negative regulation of cell migration (GO:0030336), response to lipopolysaccharide (GO:0032496), negative regulation of stress-activated MAPK cascade (GO:0032873), positive regulation of regulatory T cell differentiation (GO:0045591), negative regulation of JNK cascade (GO:0046329), oligodendrocyte differentiation (GO:0048709), negative regulation of oligodendrocyte differentiation (GO:0048715), negative regulation of epithelial cell proliferation (GO:0050680), stress-activated MAPK cascade (GO:0051403), negative regulation of respiratory burst involved in inflammatory response (GO:0060266), negative regulation of ERK1 and ERK2 cascade (GO:0070373), regulation of brown fat cell differentiation (GO:0090335), negative regulation of p38MAPK cascade (GO:1903753), negative regulation of epithelium regeneration (GO:1905042), regulation of immune system process (GO:0002682), protein dephosphorylation (GO:0006470), regulation of innate immune response (GO:0045088), regulation of multicellular organismal process (GO:0051239), regulation of cell development (GO:0060284)

GO Molecular Function (12): protein serine/threonine phosphatase activity (GO:0004722), protein tyrosine/threonine phosphatase activity (GO:0008330), JUN kinase binding (GO:0008432), phosphatase activity (GO:0016791), MAP kinase tyrosine/serine/threonine phosphatase activity (GO:0017017), MAP kinase phosphatase activity (GO:0033549), MAP kinase tyrosine phosphatase activity (GO:0033550), mitogen-activated protein kinase p38 binding (GO:0048273), phosphoprotein phosphatase activity (GO:0004721), protein tyrosine phosphatase activity (GO:0004725), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-3 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of MAPK cascade	4
phosphoprotein phosphatase activity	4
cellular anatomical structure	3
negative regulation of multicellular organismal process	2
MAP kinase phosphatase activity	2
adaptive immune response	1
regulation of immune response	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
epithelial cell migration	1
regulation of epithelial cell migration	1
negative regulation of cell migration	1
phosphate-containing compound metabolic process	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
regulation of stress-activated MAPK cascade	1
stress-activated MAPK cascade	1
negative regulation of stress-activated protein kinase signaling cascade	1
regulatory T cell differentiation	1
positive regulation of T cell differentiation	1
regulation of regulatory T cell differentiation	1
JNK cascade	1
regulation of JNK cascade	1
central nervous system development	1
glial cell differentiation	1
negative regulation of glial cell differentiation	1
oligodendrocyte differentiation	1
regulation of oligodendrocyte differentiation	1
negative regulation of cell population proliferation	1
epithelial cell proliferation	1
regulation of epithelial cell proliferation	1
MAPK cascade	1
stress-activated protein kinase signaling cascade	1

Protein interactions and networks

STRING

1688 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DUSP10	JKAMP	Q9P055	868
DUSP10	MAPK14	Q16539	850
DUSP10	MAPK8	P45983	792
DUSP10	MAPK11	Q15759	558
DUSP10	DUSP8	Q13202	550
DUSP10	MAP3K5	Q99683	528
DUSP10	DUSP9	Q99956	513
DUSP10	MYC	P01106	503
DUSP10	JUN	P05412	503
DUSP10	MAPK12	P53778	494
DUSP10	DUSP7	Q16829	484
DUSP10	MAPK13	O15264	480
DUSP10	HNRNPC	P07910	469
DUSP10	DUSP6	Q16828	464
DUSP10	PTPN7	P35236	461

IntAct

176 interactions, top by confidence:

A	B	Type	Score
MAPK9	DUSP10	psi-mi:“MI:0915”(physical association)	0.760
DUSP10	MAPK9	psi-mi:“MI:0203”(dephosphorylation reaction)	0.760
DUSP10	CASK	psi-mi:“MI:0914”(association)	0.590
DUSP10	CASK	psi-mi:“MI:0407”(direct interaction)	0.590
FNDC3B	DUSP10	psi-mi:“MI:0915”(physical association)	0.560
HOXA1	DUSP10	psi-mi:“MI:0915”(physical association)	0.560
KRTAP3-2	DUSP10	psi-mi:“MI:0915”(physical association)	0.560
MAPK8	DUSP10	psi-mi:“MI:0915”(physical association)	0.560
CRYAA	DUSP10	psi-mi:“MI:0915”(physical association)	0.560
DYNC1H1	DUSP10	psi-mi:“MI:0915”(physical association)	0.560
DUSP10	ATN1	psi-mi:“MI:0915”(physical association)	0.560
DUSP10		psi-mi:“MI:0915”(physical association)	0.560
DUSP10	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	DUSP10	psi-mi:“MI:0915”(physical association)	0.560
DUSP10	GSN	psi-mi:“MI:0915”(physical association)	0.560
DUSP10	HRAS	psi-mi:“MI:0915”(physical association)	0.560
DUSP10	BACE2	psi-mi:“MI:0915”(physical association)	0.560
DUSP10	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (88): MAPK14 (Two-hybrid), MAPK8 (Two-hybrid), CASK (Affinity Capture-MS), MAPK9 (Affinity Capture-MS), OTUD4 (Affinity Capture-MS), ACTBL2 (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), EFHD1 (Affinity Capture-MS), ACTB (Affinity Capture-MS), DUSP10 (Affinity Capture-MS), DUSP10 (Two-hybrid), DUSP10 (Two-hybrid), DUSP10 (Two-hybrid), DUSP10 (Two-hybrid), DUSP10 (Reconstituted Complex)

ESM2 similar proteins: A0JPH7, A1A5Q0, B0R034, E1BTG2, E1C065, E1C760, F1MUG2, F7AEX0, G3XA57, O60308, P30306, P48966, Q02225, Q0IID7, Q0VBD2, Q14B46, Q28E45, Q28FA8, Q3UHZ5, Q4KM37, Q5EAW4, Q5FWH3, Q5JTW2, Q5RHY1, Q5XGX5, Q60949, Q6GQN0, Q6INA9, Q6NTY8, Q6NU40, Q6P5Q4, Q7L590, Q80U87, Q8BN58, Q8BXR9, Q8BZN6, Q8C5W4, Q8GT06, Q8K3X6, Q8N8V4

Diamond homologs: A0A0R4IVA4, A4D256, A6N3Q4, O60729, O75365, P81299, Q00684, Q0IID7, Q4CUJ8, Q54DU9, Q54Y32, Q59NH8, Q5B323, Q5R7J8, Q63739, Q6GQT0, Q6NKR2, Q6PFY9, Q78EG7, Q86BN8, Q86IL4, Q93096, Q9D658, Q9ESS0, Q9P7H1, Q9TSM6, Q9UNH5, Q9Y6W6, B4F7B7, F1QWM2, O09112, O54838, O55737, O77334, O95147, P0C594, P0C597, P0C599, P0C5A0, P0C5A1

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
DUSP10	“down-regulates activity”	IRF3	dephosphorylation
DUSP10	down-regulates	MAPK14	dephosphorylation
DUSP10	down-regulates	MAPK8	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 100 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
Long-term potentiation	6	40.2×	1e-06
Ras activation upon Ca2+ influx through NMDA receptor	5	40.2×	1e-05
Unblocking of NMDA receptors, glutamate binding and activation	5	38.3×	1e-05
Negative regulation of NMDA receptor-mediated neuronal transmission	5	38.3×	1e-05
Assembly and cell surface presentation of NMDA receptors	8	28.6×	7e-08
Neurexins and neuroligins	10	27.7×	9e-10
Protein-protein interactions at synapses	5	18.7×	4e-04
Non-integrin membrane-ECM interactions	5	10.9×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	9	55.0×	3e-11
protein localization to synapse	6	48.4×	4e-07
receptor clustering	6	39.4×	1e-06
regulation of postsynaptic membrane neurotransmitter receptor levels	7	36.5×	2e-07
cell-cell adhesion	9	9.6×	5e-05
protein-containing complex assembly	6	7.2×	8e-03
chemical synaptic transmission	7	5.7×	8e-03
nervous system development	9	4.3×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1088 predictions. Top by Δscore:

Variant	Effect	Δscore
1:221706090:GTTAC:G	donor_loss	1.0000
1:221706091:TTA:T	donor_loss	1.0000
1:221706092:TACC:T	donor_loss	1.0000
1:221706093:A:T	donor_loss	1.0000
1:221706094:C:CA	donor_loss	1.0000
1:221706105:AAAAG:A	donor_gain	1.0000
1:221706122:A:AC	donor_gain	1.0000
1:221706123:C:CC	donor_gain	1.0000
1:221741979:A:AC	donor_gain	1.0000
1:221741980:C:CC	donor_gain	1.0000
1:221741980:CTT:C	donor_gain	1.0000
1:221702673:TTCCT:T	acceptor_gain	0.9900
1:221702676:CT:C	acceptor_gain	0.9900
1:221702678:C:CC	acceptor_gain	0.9900
1:221706093:A:AC	donor_gain	0.9900
1:221706094:C:CC	donor_gain	0.9900
1:221706105:A:AC	donor_gain	0.9900
1:221706115:T:TA	donor_gain	0.9900
1:221706125:G:GA	donor_gain	0.9900
1:221706465:ACC:A	acceptor_loss	0.9900
1:221706467:C:G	acceptor_loss	0.9900
1:221706468:T:C	acceptor_loss	0.9900
1:221739788:C:CC	acceptor_gain	0.9900
1:221741923:ACAAT:A	donor_gain	0.9900
1:221741924:CAATC:C	donor_gain	0.9900
1:221741979:ACTT:A	donor_gain	0.9900
1:221741980:CT:C	donor_gain	0.9900
1:221741980:CTTC:C	donor_gain	0.9900
1:221741982:T:TA	donor_gain	0.9900
1:221702674:TCCT:T	acceptor_gain	0.9800

AlphaMissense

3185 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:221702476:A:G	L462P	1.000
1:221702488:A:G	F458S	1.000
1:221702494:A:G	L456P	1.000
1:221702497:A:C	L455W	1.000
1:221702497:A:G	L455S	1.000
1:221702500:T:G	Q454P	1.000
1:221702508:G:C	F451L	1.000
1:221702508:G:T	F451L	1.000
1:221702509:A:C	F451C	1.000
1:221702509:A:G	F451S	1.000
1:221702510:A:C	F451V	1.000
1:221702510:A:G	F451L	1.000
1:221702510:A:T	F451I	1.000
1:221702517:G:C	N448K	1.000
1:221702517:G:T	N448K	1.000
1:221702521:G:C	P447R	1.000
1:221702521:G:T	P447Q	1.000
1:221702522:G:A	P447S	1.000
1:221702522:G:T	P447T	1.000
1:221702527:A:T	I445N	1.000
1:221702536:C:G	R442P	1.000
1:221702537:G:C	R442G	1.000
1:221702544:T:A	K439N	1.000
1:221702544:T:G	K439N	1.000
1:221702548:A:T	V438D	1.000
1:221702558:A:C	Y435D	1.000
1:221702560:G:T	A434D	1.000
1:221702561:C:G	A434P	1.000
1:221702599:G:T	A421D	1.000
1:221702611:G:A	T417I	1.000

dbSNP variants (sampled 300 via entrez): RS1000072721 (1:221701111 C>T), RS1000143619 (1:221725413 G>A), RS1000162568 (1:221712442 A>T), RS1000229541 (1:221721238 G>T), RS1000257611 (1:221719006 C>A), RS1000310260 (1:221714664 A>C), RS1000314172 (1:221725273 T>G), RS1000385868 (1:221730880 A>T), RS1000457046 (1:221709313 G>T), RS1000637126 (1:221732912 T>C,G), RS1000739255 (1:221727156 C>A), RS1000747452 (1:221706038 A>T), RS1000803486 (1:221712795 A>C), RS1000846326 (1:221710931 T>C), RS1000997676 (1:221729787 A>G)

Disease associations

OMIM: gene MIM:608867 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST000843_1	Colorectal cancer	2.000000e-09
GCST000843_5	Colorectal cancer	1.000000e-09
GCST002454_1	Colorectal cancer	9.000000e-09
GCST002707_15	Serum thyroid-stimulating hormone levels	4.000000e-06
GCST002919_6	Colorectal cancer	5.000000e-06
GCST002938_4	Copper levels	4.000000e-07
GCST003151_3	White matter lesion progression	2.000000e-06
GCST003152_5	White matter lesion progression (adjusted for white matter lesion burden at baseline)	7.000000e-06
GCST003995_18	Tonsillectomy	7.000000e-11
GCST005014_34	Tonsillectomy	7.000000e-11
GCST005591_4	Colorectal cancer	2.000000e-08
GCST006418_1	Progressive supranuclear palsy	5.000000e-08
GCST006418_10	Progressive supranuclear palsy	5.000000e-08
GCST006481_13	Lung function (FEV1)	3.000000e-08
GCST006481_29	Lung function (FEV1)	7.000000e-06
GCST006483_16	Lung function (FVC)	1.000000e-09
GCST006483_17	Lung function (FVC)	1.000000e-08
GCST006483_46	Lung function (FVC)	1.000000e-08
GCST007856_46	Colorectal cancer or advanced adenoma	6.000000e-16
GCST008595_19	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	2.000000e-08
GCST012478_1	Cluster headache	2.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007746	white matter lesion progression measurement
EFO:0007924	tonsillectomy risk measurement
EFO:0004314	forced expiratory volume
EFO:0004312	vital capacity
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2396511 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
6-hydroxy-3-iodo-1-methyl-2-[3-[[2-oxo-2-(4-thiophen-3-ylanilino)acetyl]amino]phenyl]indole-5-carboxylic acid	IC50	2900 nM	US-9522881: Hydroxyindole carboxylic acid based inhibitors for oncogenic Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2)

ChEMBL bioactivities

10 potent at pChembl≥5 of 18 total, top 10 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.55	IC50	2800	nM	CHEMBL1575436
5.54	IC50	2900	nM	CHEMBL3319356
5.42	IC50	3800	nM	CHEMBL1575436
5.40	IC50	4000	nM	CHEMBL5418996
5.30	IC50	5000	nM	CHEMBL5393799
5.24	IC50	5700	nM	CHEMBL3426913
5.21	IC50	6200	nM	CHEMBL5420188
5.16	Ki	6900	nM	CHEMBL4077342
5.15	IC50	7100	nM	CHEMBL5427332
5.12	IC50	7500	nM	CHEMBL5396788

PubChem BioAssay actives

10 with measured affinity, of 55 total; 9 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
3,3-dimethyl-1-[(9-methylsulfanyl-5,6-dihydrothieno[3,4-h]quinazolin-2-yl)sulfanyl]butan-2-one	1979134: Inhibition of MKP5 catalytic domain (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as p38alpha MAPK phosphopeptide dephosphorylation using phosphopeptide as substrate incubated for 15 mins followed by substrate addition by malachite green dye based analysis	ic50	2.8000	uM
6-hydroxy-3-iodo-1-methyl-2-[3-[[2-oxo-2-(4-thiophen-3-ylanilino)acetyl]amino]phenyl]indole-5-carboxylic acid	1182550: Inhibition of MKP5 (unknown origin)	ic50	2.9000	uM
1-[(9-chloro-5,6-dihydrobenzo[h]quinazolin-2-yl)sulfanyl]-3,3-dimethylbutan-2-one	1979134: Inhibition of MKP5 catalytic domain (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as p38alpha MAPK phosphopeptide dephosphorylation using phosphopeptide as substrate incubated for 15 mins followed by substrate addition by malachite green dye based analysis	ic50	4.0000	uM
1-[(9-ethyl-5,6-dihydrothieno[2,3-h]quinazolin-2-yl)sulfanyl]-3,3-dimethylbutan-2-one	1979134: Inhibition of MKP5 catalytic domain (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as p38alpha MAPK phosphopeptide dephosphorylation using phosphopeptide as substrate incubated for 15 mins followed by substrate addition by malachite green dye based analysis	ic50	5.0000	uM
4-[1-(cyclohexylamino)-1-oxohexan-2-yl]oxy-2-hydroxy-5-[2-[2-(trifluoromethoxy)phenyl]ethynyl]benzoic acid	1206785: Inhibition of MKP5 (unknown origin) using pNPP as substrate at pH 7 at 25 degC by spectrophotometric analysis	ic50	5.7000	uM
1-(5,6-dihydrobenzo[h]quinazolin-2-ylsulfanyl)-3,3-dimethylbutan-2-one	1979134: Inhibition of MKP5 catalytic domain (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as p38alpha MAPK phosphopeptide dephosphorylation using phosphopeptide as substrate incubated for 15 mins followed by substrate addition by malachite green dye based analysis	ic50	6.2000	uM
[fluoro-[4-[2-fluoro-3-[(2,4,5-trichlorophenyl)methyl]phenyl]phenyl]-morpholin-4-ylsulfonylmethyl]phosphonic acid	1477074: Inhibition of MKP5 (unknown origin) using pNPP as substrate preincubated for 5 mins followed by substrate addition measured for 20 mins by spectrophotometric analysis	ki	6.9000	uM
1-(5,6-dihydrothieno[2,3-h]quinazolin-2-ylsulfanyl)-3,3-dimethylbutan-2-one	1979134: Inhibition of MKP5 catalytic domain (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as p38alpha MAPK phosphopeptide dephosphorylation using phosphopeptide as substrate incubated for 15 mins followed by substrate addition by malachite green dye based analysis	ic50	7.1000	uM
3,3-dimethyl-1-[(9-methyl-5,6-dihydrobenzo[h]quinazolin-2-yl)sulfanyl]butan-2-one	1979134: Inhibition of MKP5 catalytic domain (unknown origin) expressed in Escherichia coli BL21 (DE3) cells assessed as p38alpha MAPK phosphopeptide dephosphorylation using phosphopeptide as substrate incubated for 15 mins followed by substrate addition by malachite green dye based analysis	ic50	7.5000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, affects methylation, decreases expression, affects cotreatment	5
Valproic Acid	decreases methylation, increases expression	4
Estradiol	increases expression, decreases expression, affects cotreatment	3
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	3
Tretinoin	decreases expression, increases expression	3
entinostat	increases expression, affects cotreatment	2
Resveratrol	affects cotreatment, decreases expression, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Arsenic	affects cotreatment, decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Cadmium	increases expression	2
Cisplatin	affects expression, increases expression	2
Copper	affects expression, increases expression, affects binding	2
Curcumin	increases expression	2
Diethylhexyl Phthalate	increases expression, decreases methylation, increases abundance	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Silicon Dioxide	increases expression	2
Tobacco Smoke Pollution	increases expression	2
tert-Butylhydroperoxide	affects cotreatment, increases expression, decreases reaction	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
4-oxoretinoic acid	increases expression	1
methylmercuric chloride	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
gingerol	increases expression	1
methylselenic acid	increases expression	1
sodium arsenate	increases abundance, increases expression	1

ChEMBL screening assays

10 unique, capped per target: 9 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2399957	Binding	Inhibition of MKP5 (unknown origin) using DiFMUP as substrate at 5 uM relative to control	Rhodanine-based PRL-3 inhibitors blocked the migration and invasion of metastatic cancer cells. — Bioorg Med Chem Lett
CHEMBL4626305	ADMET	Inhibition of MKP5 (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_D7P0	Ubigene A-549 DUSP10 KO	Cancer cell line	Male
CVCL_D8KE	Ubigene HCT 116 DUSP10 KO	Cancer cell line	Male
CVCL_D9DR	Ubigene HEK293 DUSP10 KO	Transformed cell line	Female
CVCL_E0C1	Ubigene HeLa DUSP10 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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