DUSP28

Summary

DUSP28 (dual specificity phosphatase 28, HGNC:33237) is a protein-coding gene on chromosome 2q37.3, encoding Dual specificity phosphatase 28 (Q4G0W2). Has phosphatase activity with the synthetic substrate 6,8-difluoro-4-methylumbelliferyl phosphate (in vitro).

Enables phosphatase activity. Involved in dephosphorylation.

Source: NCBI Gene 285193 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 14 total
• MANE Select transcript: NM_001370465

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33237
Approved symbol	DUSP28
Name	dual specificity phosphatase 28
Location	2q37.3
Locus type	gene with protein product
Status	Approved
Aliases	VHP, DUSP26
Ensembl gene	ENSG00000188542
Ensembl biotype	protein_coding
Entrez	285193

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000343217, ENST00000405954, ENST00000438823, ENST00000479788, ENST00000497221

RefSeq mRNA: 2 — MANE Select: NM_001370465 NM_001033575, NM_001370465

CCDS: CCDS33418

Canonical transcript exons

ENST00000405954 — 2 exons

Exon	Start	End
ENSE00001556723	240560357	240561077
ENSE00001564454	240561330	240565256

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 94.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.7385 / max 47.3532, expressed in 1672 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
26418	1.9321	823
26420	1.4327	990
26421	1.3737	808

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vastus lateralis	UBERON:0001379	94.06	gold quality
quadriceps femoris	UBERON:0001377	93.94	gold quality
biceps brachii	UBERON:0001507	92.15	gold quality
tibialis anterior	UBERON:0001385	92.10	silver quality
deltoid	UBERON:0001476	91.73	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.30	gold quality
left ventricle myocardium	UBERON:0006566	91.17	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.65	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.57	gold quality
skeletal muscle tissue	UBERON:0001134	90.25	gold quality
sperm	CL:0000019	88.67	gold quality
muscle tissue	UBERON:0002385	88.59	gold quality
cardiac muscle of right atrium	UBERON:0003379	87.86	silver quality
gastrocnemius	UBERON:0001388	87.07	gold quality
muscle of leg	UBERON:0001383	86.94	gold quality
ileal mucosa	UBERON:0000331	86.73	silver quality
endothelial cell	CL:0000115	86.65	silver quality
epithelial cell of pancreas	CL:0000083	84.97	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.95	gold quality
granulocyte	CL:0000094	84.66	gold quality
apex of heart	UBERON:0002098	84.22	gold quality
adult organism	UBERON:0007023	82.82	gold quality
right testis	UBERON:0004534	82.81	gold quality
heart left ventricle	UBERON:0002084	82.73	gold quality
cardiac ventricle	UBERON:0002082	82.61	gold quality
anterior cingulate cortex	UBERON:0009835	82.58	gold quality
myocardium	UBERON:0002349	82.26	silver quality
left testis	UBERON:0004533	82.04	gold quality
heart right ventricle	UBERON:0002080	81.79	gold quality
caudate nucleus	UBERON:0001873	81.53	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting DUSP28, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-154-5P	98.92	66.65	733
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-942-3P	98.81	69.04	876
HSA-MIR-655-5P	98.74	65.93	888
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-1301-3P	98.64	68.27	1071
HSA-MIR-5047	98.64	68.62	1035
HSA-MIR-7156-3P	98.25	67.66	859
HSA-MIR-3166	98.24	66.63	1223
HSA-MIR-124-5P	98.11	67.65	1095
HSA-MIR-12120	98.05	68.44	1768
HSA-MIR-12127	97.93	66.67	793
HSA-MIR-4681	89.50	61.59	122

Literature-anchored findings (GeneRIF, showing 7)

• Taken together, these data demonstrate that DUSP28 plays a significant role in HCC progression and may be a feasible molecular target for anti-cancer therapy. (PMID:25230705)
• Collectively, these results indicate that DUSP28 plays a key role in drug resistance and migratory activity in human pancreatic cells, and suggest that targeting DUSP28 might have clinical relevance in eradicating malignant pancreatic cancers. (PMID:26212664)
• Results collectively indicate unique links between dual-specificity phosphatase 28 (DUSP28) and mucins MUC5B/MUC16 and their roles in pancreatic cancer. (PMID:27230679)
• These results establish novel insight into DUSP28 and PDGF-A related autonomous signaling pathway in pancreatic cancer. (PMID:28986588)
• Structural and biochemical analysis of atypically low dephosphorylating activity of human dual-specificity phosphatase 28 (PMID:29121083)
• DUSP28 significantly increased the migration, invasion, and viability of metastatic pancreatic cancer cells through the activation of CREB, AKT, and ERK1/2 signaling pathways. (PMID:30902562)
• DUSP28 promotes cell proliferation, migration, and invasion by Akt/beta-catenin/Slug axis in breast cancer. (PMID:36520087)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dusp28	ENSDARG00000059695
mus_musculus	Dusp28	ENSMUSG00000047067
rattus_norvegicus	Dusp28	ENSRNOG00000090537

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), DUSP10 (ENSG00000143507), DUSP15 (ENSG00000149599), DUSP2 (ENSG00000158050), KASH5 (ENSG00000161609), DUSP19 (ENSG00000162999), DUSP7 (ENSG00000164086), DUSP18 (ENSG00000167065), SSH3 (ENSG00000172830), DUSP8 (ENSG00000184545), DUSP29 (ENSG00000188716), DUSP21 (ENSG00000189037), STYX (ENSG00000198252), STYXL2 (ENSG00000198842), DUSP14 (ENSG00000276023), DUSP13A (ENSG00000293543)

Protein

Protein identifiers

Dual specificity phosphatase 28 — Q4G0W2 (reviewed: Q4G0W2)

All UniProt accessions (2): Q4G0W2, H7C234

UniProt curated annotations — full annotation on UniProt →

Function. Has phosphatase activity with the synthetic substrate 6,8-difluoro-4-methylumbelliferyl phosphate (in vitro). Has almost no detectable activity with phosphotyrosine, even less activity with phosphothreonine and displays complete lack of activity with phosphoserine. The poor activity with phosphotyrosine may be due to steric hindrance by bulky amino acid sidechains that obstruct access to the active site.

Subunit / interactions. Monomer.

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

RefSeq proteins (2): NP_001028747, NP_001357394* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000340	Dual-sp_phosphatase_cat-dom	Domain
IPR000387	Tyr_Pase_dom	Domain
IPR020422	TYR_PHOSPHATASE_DUAL_dom	Domain
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR052103	Dual_spec_Phospatases	Family

Pfam: PF00782

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 (20 total): strand 7, helix 6, mutagenesis site 4, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5Y15	X-RAY DIFFRACTION	2.1
5Y16	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4G0W2-F1	90.88	0.82

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): 103 (phosphocysteine intermediate)

Mutagenesis-validated functional residues (4):

Position	Phenotype
102	decreases the already low catalytic activity.
103	loss of catalytic activity.
105	increases activity with phosphotyrosine; when associated with v-107.
107	increases activity with phosphotyrosine; when associated with a-105.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 157 (showing top): GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, ZHAN_MULTIPLE_MYELOMA_PR_DN, CAGCTG_AP4_Q5, YY1_Q6, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, HEN1_01, GOBP_DEPHOSPHORYLATION, GOBP_PROTEIN_DEPHOSPHORYLATION, chr8p12, DOUGLAS_BMI1_TARGETS_UP, GCM_CALM1, GCM_MAP1B, GOBP_ERK1_AND_ERK2_CASCADE

GO Biological Process (2): dephosphorylation (GO:0016311), protein dephosphorylation (GO:0006470)

GO Molecular Function (5): protein serine/threonine phosphatase activity (GO:0004722), protein tyrosine phosphatase activity (GO:0004725), phosphatase activity (GO:0016791), phosphoprotein phosphatase activity (GO:0004721), hydrolase activity (GO:0016787)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphoprotein phosphatase activity	2
phosphate-containing compound metabolic process	1
dephosphorylation	1
protein modification process	1
phosphoric ester hydrolase activity	1
phosphatase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1

Protein interactions and networks

STRING

1118 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DUSP28	AK2	P54819	603
DUSP28	C1QTNF8	P60827	451
DUSP28	PMPCA	Q10713	446
DUSP28	ZC3H15	Q8WU90	441
DUSP28	METTL22	Q9BUU2	441
DUSP28	AFG3L2	Q9Y4W6	420
DUSP28	GAB2	Q9UQC2	402
DUSP28	MYCBPAP	Q8TBZ2	386
DUSP28	WDR33	Q9C0J8	385
DUSP28	ANXA1	P04083	383
DUSP28	DNAJC22	Q8N4W6	366
DUSP28	CEP162	Q5TB80	362
DUSP28	SLC9A8	Q9Y2E8	357
DUSP28	ERRFI1	Q9UJM3	354
DUSP28	LMBR1L	Q6UX01	348

IntAct

5 interactions, top by confidence:

A	B	Type	Score
DUSP28	UBR3	psi-mi:“MI:0915”(physical association)	0.400
JOSD2		psi-mi:“MI:0914”(association)	0.350
CIMAP3	EPHA2	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350

BioGRID (65): DUSP28 (Affinity Capture-MS), DUSP28 (Affinity Capture-MS), UBR3 (Affinity Capture-MS), DUSP28 (Affinity Capture-MS), DUSP28 (Affinity Capture-MS), DUSP28 (Affinity Capture-MS), DUSP28 (Affinity Capture-MS), C9orf64 (Affinity Capture-MS), PPIA (Affinity Capture-MS), DHPS (Affinity Capture-MS), EIF4A2 (Affinity Capture-MS), DUSP21 (Affinity Capture-MS), RAD50 (Affinity Capture-MS), AK6 (Affinity Capture-MS), DYM (Affinity Capture-MS)

ESM2 similar proteins: A0A0B4J1F4, A0A0G2JXN2, A4FV98, A6QPA3, C9J798, C9JJ37, D3YWP0, D3ZVU9, D4A2K4, O43374, O70277, O75382, O95294, P0C6S8, P22674, P57775, Q08DS0, Q0GA42, Q3U410, Q3UGX3, Q4G0W2, Q4V892, Q5SUV1, Q5XIU1, Q6GQU6, Q6IA17, Q6PF15, Q6TDP3, Q6TDP4, Q7TNM2, Q7Z4K8, Q86WI3, Q8CIW5, Q8IZ69, Q8K430, Q8N531, Q8N8L6, Q8NE01, Q8WXI3, Q969K4

Diamond homologs: B4F7B7, F1QWM2, O09112, O54838, O55737, O77334, O95147, P0C594, P0C597, P0C599, P0C5A0, P0C5A1, P0C5A2, P28562, P28563, P51452, Q02256, Q05922, Q05923, Q0IID7, Q10038, Q13115, Q13202, Q148W8, Q16690, Q16828, Q16829, Q17QJ3, Q17QM8, Q1LWL2, Q2KJ36, Q39491, Q4G0W2, Q4RQD3, Q4V7N3, Q54R42, Q54T76, Q54Y32, Q556Y8, Q55CS7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

368 predictions. Top by Δscore:

Variant	Effect	Δscore
2:240561429:G:GT	donor_gain	1.0000
2:240561073:TCCAG:T	donor_loss	0.9900
2:240561074:CCAGG:C	donor_loss	0.9900
2:240561075:CAG:C	donor_loss	0.9900
2:240561076:AG:A	donor_loss	0.9900
2:240561077:GGTG:G	donor_loss	0.9900
2:240561078:GT:G	donor_loss	0.9900
2:240561079:T:G	donor_loss	0.9900
2:240561389:G:GT	donor_gain	0.9900
2:240561392:G:GG	donor_gain	0.9900
2:240561492:G:GT	donor_gain	0.9900
2:240561399:G:GT	donor_gain	0.9800
2:240561389:GAA:G	donor_gain	0.9700
2:240561430:G:T	donor_gain	0.9700
2:240561496:G:GT	donor_gain	0.9700
2:240561065:G:GT	donor_gain	0.9600
2:240563673:GCT:G	acceptor_gain	0.9600
2:240563087:G:GT	donor_gain	0.9400
2:240561493:A:T	donor_gain	0.9300
2:240561431:A:T	donor_gain	0.9200
2:240561516:G:GT	donor_gain	0.9000
2:240561328:AGAT:A	acceptor_gain	0.8700
2:240561329:GATG:G	acceptor_gain	0.8700
2:240561853:GTA:G	acceptor_gain	0.8700
2:240563672:A:AG	acceptor_gain	0.8700
2:240563673:G:GG	acceptor_gain	0.8700
2:240561078:G:GG	donor_gain	0.8400
2:240561324:TTGCA:T	acceptor_loss	0.8400
2:240561325:TGCA:T	acceptor_loss	0.8400
2:240561326:GCAG:G	acceptor_loss	0.8400

AlphaMissense

1103 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:240560899:A:T	D72V	0.999
2:240561372:T:C	F146L	0.999
2:240561374:C:A	F146L	0.999
2:240561374:C:G	F146L	0.999
2:240561373:T:C	F146S	0.997
2:240560830:T:A	V49D	0.996
2:240560900:C:A	D72E	0.996
2:240560900:C:G	D72E	0.996
2:240560992:G:A	C103Y	0.996
2:240561001:G:A	G106D	0.996
2:240561001:G:T	G106V	0.996
2:240561006:A:C	S108R	0.996
2:240561007:G:T	S108I	0.996
2:240561008:C:A	S108R	0.996
2:240561008:C:G	S108R	0.996
2:240561009:C:A	R109S	0.996
2:240561026:C:G	C114W	0.995
2:240560898:G:C	D72H	0.994
2:240560899:A:C	D72A	0.994
2:240560993:C:G	C103W	0.994
2:240561385:T:A	L150H	0.994
2:240560899:A:G	D72G	0.993
2:240561022:T:A	V113D	0.993
2:240561360:C:T	P142S	0.993
2:240561373:T:G	F146C	0.993
2:240561385:T:C	L150P	0.993
2:240560898:G:T	D72Y	0.992
2:240560986:T:A	V101D	0.992
2:240561024:T:C	C114R	0.992
2:240561025:G:A	C114Y	0.992

dbSNP variants (sampled 300 via entrez): RS1000041789 (2:240564693 G>A), RS1000114587 (2:240564554 A>G), RS1000188497 (2:240564803 A>G), RS1000260964 (2:240560054 T>C), RS1000758029 (2:240560312 G>A), RS1000992931 (2:240560310 G>A), RS1001213276 (2:240559379 TCTG>T), RS1001277949 (2:240560398 G>A), RS1001667521 (2:240558864 G>A,C), RS1001717024 (2:240563622 C>T), RS1001726589 (2:240559026 A>G), RS1002013370 (2:240562610 C>T), RS1002153189 (2:240562307 C>G,T), RS1002198812 (2:240562544 C>G,T), RS1002840140 (2:240558214 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006585_671	Blood protein levels	8.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, decreases expression, affects expression	7
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Lead	increases expression	1
Methyl Methanesulfonate	increases expression	1
Phthalic Acids	increases methylation	1
Quercetin	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tretinoin	increases expression	1
Cadmium Chloride	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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