DUSP10 (dual specificity phosphatase 10)

2010-05-01 Larisa Nonn Affiliation

Department of Pathology, University of Illinois at Chicago, 840 S. Wood St., Room 130 CSN, MC 847, Chicago, IL 60612, USA

Identity

HGNC

DUSP10

LOCATION

1q41

LOCUSID

11221

ALIAS

MKP-5,MKP5

FUSION GENES

Show Gene Fusions

DNA/RNA

DUSP10 mRNA transcript variants.

Description

The DUSP10 gene consists of 5 exons and 4 introns spanning 40 kb.

Transcription

There are three mRNA transcript variants for DUSP10 and two protein isoforms. Variant 1 is the full length protein, isoform a. Variants 2 and 3 have different 5 mRNA transcripts, but the same start site in exon 3 and are missing the N-terminus. Variants 2 and 3 only contain the C-terminal catalytic domain and code for isoform b.
The ATG site is on Exon 2.
DUSP10 Variant 1 (isoform a), NM_007207.3.
DUSP10 Variant 2 (isoform b), NM_144728.1.
DUSP10 Variant 3 (isoform b), NM_144729.1.

Proteins

Note

Dual specificity protein phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the MAPK superfamily (MAPK/ERK, SAPK/JNK, p38), which is associated with cellular proliferation and differentiation. Different members of this family of dual specificity phosphatases show distinct substrate specificities for MAPKs, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli.
DUSP10 gene product binds to and inactivates p38 and SAPK/JNK, but not MAPK/ERK.

Description

DUSP10 gene is translated into two different protein products. Transcript variant 1 codes for the full-length DUSP10 isoform a (NP_009138.1) of 482 amino acids and a molecular weight of 52 kDa. Transcript variants 2 and 3 encode for a shorter protein, DUSP10 isoform b (NP_653329.1), that is 140 amino acids in length.

Expression

DUSP10 mRNA is widely expressed in liver, skeletal muscle, retina, macrophages, colon, fetal heart, spleen, infant brain, pregnant uterus, prostate epithelium and ovarian tumors.
DUSP10 mRNA is inducible by oxidative stress via JNK and ATF activation.

Localisation

DUSP10 is present in both the cytoplasm and nucleus of the cell.

Function

DUSP10 is a MAP kinase phosphatase with substrate specificy for jun N-terminal kinase (JNK) and p38.

Homology

The DUSP10 gene is conserved in chimpanzee, dog, cow, mouse, rat, chicken and zebrafish.

Mutations

Note

There are no characterized mutations in DUSP10.

Implicated in

Entity name

Prostate cancer

Note

To date, DUSP10 levels or mutation have not been associated with any disease. However, DUSP10 mRNA levels were lower in prostate cell lines derived from malignant tumor than from cells derived from normal prostate tissue (Nonn et al., 2006). Additionally, DUSP10 mRNA levels are inducible in prostate cells by treatment with 1,25-dihydoxyvitamin D, curcumin, reseveratrol and gingerol (Nonn et al., 2006; Nonn et al., 2007).

Article Bibliography

Pubmed ID	Last Year	Title	Authors
16806267	2006	Crystal structure of the catalytic domain of human MAP kinase phosphatase 5: structural insight into constitutively active phosphatase.	Jeong DG et al
11060451	2000	Expression and comparative chromosomal mapping of MKP-5 genes DUSP10/Dusp10.	Masuda K et al
17151092	2007	Chemopreventive anti-inflammatory activities of curcumin and other phytochemicals mediated by MAP kinase phosphatase-5 in prostate cells.	Nonn L et al
16618780	2006	Inhibition of p38 by vitamin D reduces interleukin-6 production in normal prostate cells via mitogen-activated protein kinase phosphatase 5: implications for prostate cancer prevention by vitamin D.	Nonn L et al
10391943	1999	Molecular cloning and characterization of a novel dual specificity phosphatase, MKP-5.	Tanoue T et al
17681939	2007	Several dual specificity phosphatases coordinate to control the magnitude and duration of JNK activation in signaling response to oxidative stress.	Teng CH et al
10597297	1999	MKP5, a new member of the MAP kinase phosphatase family, which selectively dephosphorylates stress-activated kinases.	Theodosiou A et al
15306813	2004	Regulation of innate and adaptive immune responses by MAP kinase phosphatase 5.	Zhang Y et al

Other Information

Locus ID:

NCBI: 11221
MIM: 608867
HGNC: 3065
Ensembl: ENSG00000143507

Variants:

dbSNP: 11221
ClinVar: 11221
TCGA: ENSG00000143507
COSMIC: DUSP10

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000143507	ENST00000366899	Q9Y6W6
ENSG00000143507	ENST00000468085	A0A0B4J2F5
ENSG00000143507	ENST00000477026	A0A0B4J2F5
ENSG00000143507	ENST00000494642	A0A0B4J2F5

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
MAPK signaling pathway	KEGG	ko04010
MAPK signaling pathway	KEGG	hsa04010
Immune System	REACTOME	R-HSA-168256
Innate Immune System	REACTOME	R-HSA-168249
DAP12 interactions	REACTOME	R-HSA-2172127
DAP12 signaling	REACTOME	R-HSA-2424491
RAF/MAP kinase cascade	REACTOME	R-HSA-5673001
Negative regulation of MAPK pathway	REACTOME	R-HSA-5675221
Fc epsilon receptor (FCERI) signaling	REACTOME	R-HSA-2454202
FCERI mediated MAPK activation	REACTOME	R-HSA-2871796
Cytokine Signaling in Immune system	REACTOME	R-HSA-1280215
Signaling by Interleukins	REACTOME	R-HSA-449147
Interleukin-2 signaling	REACTOME	R-HSA-451927
Interleukin receptor SHC signaling	REACTOME	R-HSA-912526
Interleukin-3, 5 and GM-CSF signaling	REACTOME	R-HSA-512988
Signal Transduction	REACTOME	R-HSA-162582
Signaling by EGFR	REACTOME	R-HSA-177929
GRB2 events in EGFR signaling	REACTOME	R-HSA-179812
SHC1 events in EGFR signaling	REACTOME	R-HSA-180336
Signaling by Insulin receptor	REACTOME	R-HSA-74752
Insulin receptor signalling cascade	REACTOME	R-HSA-74751
IRS-mediated signalling	REACTOME	R-HSA-112399
SOS-mediated signalling	REACTOME	R-HSA-112412
Signalling by NGF	REACTOME	R-HSA-166520
NGF signalling via TRKA from the plasma membrane	REACTOME	R-HSA-187037
Signalling to ERKs	REACTOME	R-HSA-187687
Signalling to RAS	REACTOME	R-HSA-167044
Signalling to p38 via RIT and RIN	REACTOME	R-HSA-187706
Prolonged ERK activation events	REACTOME	R-HSA-169893
Frs2-mediated activation	REACTOME	R-HSA-170968
ARMS-mediated activation	REACTOME	R-HSA-170984
Signaling by PDGF	REACTOME	R-HSA-186797
Downstream signal transduction	REACTOME	R-HSA-186763
Signaling by VEGF	REACTOME	R-HSA-194138
VEGFA-VEGFR2 Pathway	REACTOME	R-HSA-4420097
VEGFR2 mediated cell proliferation	REACTOME	R-HSA-5218921
Signaling by SCF-KIT	REACTOME	R-HSA-1433557
MAPK family signaling cascades	REACTOME	R-HSA-5683057
MAPK1/MAPK3 signaling	REACTOME	R-HSA-5684996
RAF-independent MAPK1/3 activation	REACTOME	R-HSA-112409
Signaling by GPCR	REACTOME	R-HSA-372790
Gastrin-CREB signalling pathway via PKC and MAPK	REACTOME	R-HSA-881907
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)	REACTOME	R-HSA-2404192
IGF1R signaling cascade	REACTOME	R-HSA-2428924
IRS-related events triggered by IGF1R	REACTOME	R-HSA-2428928
Signaling by Leptin	REACTOME	R-HSA-2586552
Developmental Biology	REACTOME	R-HSA-1266738
Axon guidance	REACTOME	R-HSA-422475
NCAM signaling for neurite out-growth	REACTOME	R-HSA-375165
RET signaling	REACTOME	R-HSA-8853659

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
37387540	2023	DUSP10 is a novel immune-related biomarker connected with survival and cellular proliferation in lower-grade glioma.	0
37387540	2023	DUSP10 is a novel immune-related biomarker connected with survival and cellular proliferation in lower-grade glioma.	0
35488020	2022	MiRNA-363-3p/DUSP10/JNK axis mediates chemoresistance by enhancing DNA damage repair in diffuse large B-cell lymphoma.	8
35488020	2022	MiRNA-363-3p/DUSP10/JNK axis mediates chemoresistance by enhancing DNA damage repair in diffuse large B-cell lymphoma.	8
33232789	2021	SETD8 potentiates constitutive ERK1/2 activation via epigenetically silencing DUSP10 expression in pancreatic cancer.	11
34782469	2021	De novo germline mutation in the dual specificity phosphatase 10 gene accelerates autoimmune diabetes.	3
33232789	2021	SETD8 potentiates constitutive ERK1/2 activation via epigenetically silencing DUSP10 expression in pancreatic cancer.	11
34782469	2021	De novo germline mutation in the dual specificity phosphatase 10 gene accelerates autoimmune diabetes.	3
32843541	2020	An allosteric site on MKP5 reveals a strategy for small-molecule inhibition.	9
32843541	2020	An allosteric site on MKP5 reveals a strategy for small-molecule inhibition.	9
30333178	2019	DUSP10 Negatively Regulates the Inflammatory Response to Rhinovirus through Interleukin-1β Signaling.	15
31122150	2019	Epigenome-wide effects of vitamin D on asthma bronchial epithelial cells.	2
31202710	2019	The protective role of the MKP-5-JNK/P38 pathway in glucolipotoxicity-induced islet β-cell dysfunction and apoptosis.	7
31483681	2019	Role of dual-specificity protein phosphatase DUSP10/MKP-5 in pulmonary fibrosis.	19
30333178	2019	DUSP10 Negatively Regulates the Inflammatory Response to Rhinovirus through Interleukin-1β Signaling.	15

Citation

Larisa Nonn

DUSP10 (dual specificity phosphatase 10)

Atlas Genet Cytogenet Oncol Haematol. 2010-05-01

Online version: http://atlasgeneticsoncology.org/gene/49913