DUSP10 (dual specificity phosphatase 10)

2010-05-01   Larisa Nonn 

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

Identity

HGNC
LOCATION
1q41
LOCUSID
ALIAS
MKP-5,MKP5
FUSION GENES

DNA/RNA

Atlas Image
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).

Bibliography

Pubmed IDLast YearTitleAuthors
168062672006Crystal structure of the catalytic domain of human MAP kinase phosphatase 5: structural insight into constitutively active phosphatase.Jeong DG et al
110604512000Expression and comparative chromosomal mapping of MKP-5 genes DUSP10/Dusp10.Masuda K et al
171510922007Chemopreventive anti-inflammatory activities of curcumin and other phytochemicals mediated by MAP kinase phosphatase-5 in prostate cells.Nonn L et al
166187802006Inhibition 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
103919431999Molecular cloning and characterization of a novel dual specificity phosphatase, MKP-5.Tanoue T et al
176819392007Several dual specificity phosphatases coordinate to control the magnitude and duration of JNK activation in signaling response to oxidative stress.Teng CH et al
105972971999MKP5, a new member of the MAP kinase phosphatase family, which selectively dephosphorylates stress-activated kinases.Theodosiou A et al
153068132004Regulation 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 IDTranscript IDUniprot
ENSG00000143507ENST00000366899Q9Y6W6
ENSG00000143507ENST00000468085A0A0B4J2F5
ENSG00000143507ENST00000477026A0A0B4J2F5
ENSG00000143507ENST00000494642A0A0B4J2F5

Expression (GTEx)

0
10
20
30
40
50
60
70

Pathways

PathwaySourceExternal ID
MAPK signaling pathwayKEGGko04010
MAPK signaling pathwayKEGGhsa04010
Immune SystemREACTOMER-HSA-168256
Innate Immune SystemREACTOMER-HSA-168249
DAP12 interactionsREACTOMER-HSA-2172127
DAP12 signalingREACTOMER-HSA-2424491
RAF/MAP kinase cascadeREACTOMER-HSA-5673001
Negative regulation of MAPK pathwayREACTOMER-HSA-5675221
Fc epsilon receptor (FCERI) signalingREACTOMER-HSA-2454202
FCERI mediated MAPK activationREACTOMER-HSA-2871796
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Signaling by InterleukinsREACTOMER-HSA-449147
Interleukin-2 signalingREACTOMER-HSA-451927
Interleukin receptor SHC signalingREACTOMER-HSA-912526
Interleukin-3, 5 and GM-CSF signalingREACTOMER-HSA-512988
Signal TransductionREACTOMER-HSA-162582
Signaling by EGFRREACTOMER-HSA-177929
GRB2 events in EGFR signalingREACTOMER-HSA-179812
SHC1 events in EGFR signalingREACTOMER-HSA-180336
Signaling by Insulin receptorREACTOMER-HSA-74752
Insulin receptor signalling cascadeREACTOMER-HSA-74751
IRS-mediated signallingREACTOMER-HSA-112399
SOS-mediated signallingREACTOMER-HSA-112412
Signalling by NGFREACTOMER-HSA-166520
NGF signalling via TRKA from the plasma membraneREACTOMER-HSA-187037
Signalling to ERKsREACTOMER-HSA-187687
Signalling to RASREACTOMER-HSA-167044
Signalling to p38 via RIT and RINREACTOMER-HSA-187706
Prolonged ERK activation eventsREACTOMER-HSA-169893
Frs2-mediated activationREACTOMER-HSA-170968
ARMS-mediated activationREACTOMER-HSA-170984
Signaling by PDGFREACTOMER-HSA-186797
Downstream signal transductionREACTOMER-HSA-186763
Signaling by VEGFREACTOMER-HSA-194138
VEGFA-VEGFR2 PathwayREACTOMER-HSA-4420097
VEGFR2 mediated cell proliferationREACTOMER-HSA-5218921
Signaling by SCF-KITREACTOMER-HSA-1433557
MAPK family signaling cascadesREACTOMER-HSA-5683057
MAPK1/MAPK3 signalingREACTOMER-HSA-5684996
RAF-independent MAPK1/3 activationREACTOMER-HSA-112409
Signaling by GPCRREACTOMER-HSA-372790
Gastrin-CREB signalling pathway via PKC and MAPKREACTOMER-HSA-881907
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)REACTOMER-HSA-2404192
IGF1R signaling cascadeREACTOMER-HSA-2428924
IRS-related events triggered by IGF1RREACTOMER-HSA-2428928
Signaling by LeptinREACTOMER-HSA-2586552
Developmental BiologyREACTOMER-HSA-1266738
Axon guidanceREACTOMER-HSA-422475
NCAM signaling for neurite out-growthREACTOMER-HSA-375165
RET signalingREACTOMER-HSA-8853659

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
171510922007Chemopreventive anti-inflammatory activities of curcumin and other phytochemicals mediated by MAP kinase phosphatase-5 in prostate cells.41
214870112011The NLR adaptor ASC/PYCARD regulates DUSP10, mitogen-activated protein kinase (MAPK), and chemokine induction independent of the inflammasome.34
223750482011A distinct interaction mode revealed by the crystal structure of the kinase p38α with the MAPK binding domain of the phosphatase MKP5.23
176819392007Several dual specificity phosphatases coordinate to control the magnitude and duration of JNK activation in signaling response to oxidative stress.22
239363872013A possible mechanism behind autoimmune disorders discovered by genome-wide linkage and association analysis in celiac disease.18
168062672006Crystal structure of the catalytic domain of human MAP kinase phosphatase 5: structural insight into constitutively active phosphatase.15
239939762013Polycyclic aromatic hydrocarbon (PAH)-mediated upregulation of hepatic microRNA-181 family promotes cancer cell migration by targeting MAPK phosphatase-5, regulating the activation of p38 MAPK.15
267332322016AGR2 oncoprotein inhibits p38 MAPK and p53 activation through a DUSP10-mediated regulatory pathway.15

Citation

Larisa Nonn

DUSP10 (dual specificity phosphatase 10)

Atlas Genet Cytogenet Oncol Haematol. 2010-05-01

Online version: http://atlasgeneticsoncology.org/gene/49913/dusp10