TISIDB

Summary
Symbol	DUSP6
Name	dual specificity phosphatase 6
Aliases	MKP-3; PYST1; HH19; MKP3; MAP kinase phosphatase 3; dual specificity protein phosphatase PYST1; mitogen-acti ......
Chromosomal Location	12q22-q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Cytoplasm
Domain	PF00782 Dual specificity phosphatase PF00581 Rhodanese-like domain
Function	Inactivates MAP kinases. Has a specificity for the ERK family (PubMed:9858808). Plays an important role in alleviating chronic postoperative pain. Necessary for the normal dephosphorylation of the long-lasting phosphorylated forms of spinal MAPK1/3 and MAP kinase p38 induced by peripheral surgery, which drives the resolution of acute postoperative allodynia (By similarity). Also important for dephosphorylation of MAPK1/3 in local wound tissue, which further contributes to resolution of acute pain (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0000187 activation of MAPK activity GO:0000188 inactivation of MAPK activity GO:0001704 formation of primary germ layer GO:0001706 endoderm formation GO:0001708 cell fate specification GO:0001711 endodermal cell fate commitment GO:0001714 endodermal cell fate specification GO:0001933 negative regulation of protein phosphorylation GO:0003002 regionalization GO:0006469 negative regulation of protein kinase activity GO:0006470 protein dephosphorylation GO:0007369 gastrulation GO:0007389 pattern specification process GO:0007492 endoderm development GO:0007507 heart development GO:0008543 fibroblast growth factor receptor signaling pathway GO:0009953 dorsal/ventral pattern formation GO:0010453 regulation of cell fate commitment GO:0010470 regulation of gastrulation GO:0016311 dephosphorylation GO:0032147 activation of protein kinase activity GO:0033673 negative regulation of kinase activity GO:0033674 positive regulation of kinase activity GO:0035265 organ growth GO:0035335 peptidyl-tyrosine dephosphorylation GO:0035987 endodermal cell differentiation GO:0040036 regulation of fibroblast growth factor receptor signaling pathway GO:0042326 negative regulation of phosphorylation GO:0042493 response to drug GO:0042659 regulation of cell fate specification GO:0042663 regulation of endodermal cell fate specification GO:0043405 regulation of MAP kinase activity GO:0043406 positive regulation of MAP kinase activity GO:0043407 negative regulation of MAP kinase activity GO:0043409 negative regulation of MAPK cascade GO:0043410 positive regulation of MAPK cascade GO:0044344 cellular response to fibroblast growth factor stimulus GO:0045165 cell fate commitment GO:0045860 positive regulation of protein kinase activity GO:0045995 regulation of embryonic development GO:0046620 regulation of organ growth GO:0048638 regulation of developmental growth GO:0051348 negative regulation of transferase activity GO:0051409 response to nitrosative stress GO:0060419 heart growth GO:0060420 regulation of heart growth GO:0060795 cell fate commitment involved in formation of primary germ layer GO:0070371 ERK1 and ERK2 cascade GO:0070372 regulation of ERK1 and ERK2 cascade GO:0070373 negative regulation of ERK1 and ERK2 cascade GO:0071774 response to fibroblast growth factor GO:0071900 regulation of protein serine/threonine kinase activity GO:0071901 negative regulation of protein serine/threonine kinase activity GO:0071902 positive regulation of protein serine/threonine kinase activity GO:0090287 regulation of cellular response to growth factor stimulus GO:1902532 negative regulation of intracellular signal transduction GO:1903224 regulation of endodermal cell differentiation
Molecular Function	GO:0004721 phosphoprotein phosphatase activity GO:0004725 protein tyrosine phosphatase activity GO:0008138 protein tyrosine/serine/threonine phosphatase activity GO:0016791 phosphatase activity GO:0017017 MAP kinase tyrosine/serine/threonine phosphatase activity GO:0033549 MAP kinase phosphatase activity GO:0042578 phosphoric ester hydrolase activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04010 MAPK signaling pathway
Reactome	R-HSA-170984: ARMS-mediated activation R-HSA-166054: Activated TLR4 signalling R-HSA-422475: Axon guidance R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-2172127: DAP12 interactions R-HSA-2424491: DAP12 signaling R-HSA-1266738: Developmental Biology R-HSA-186763: Downstream signal transduction R-HSA-198753: ERK/MAPK targets R-HSA-202670: ERKs are inactivated R-HSA-2871796: FCERI mediated MAPK activation R-HSA-2454202: Fc epsilon receptor (FCERI) signaling R-HSA-170968: Frs2-mediated activation R-HSA-179812: GRB2 events in EGFR signaling R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK R-HSA-2428924: IGF1R signaling cascade R-HSA-112399: IRS-mediated signalling R-HSA-2428928: IRS-related events triggered by IGF1R R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-74751: Insulin receptor signalling cascade R-HSA-912526: Interleukin receptor SHC signaling R-HSA-451927: Interleukin-2 signaling R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling R-HSA-450294: MAP kinase activation in TLR cascade R-HSA-5683057: MAPK family signaling cascades R-HSA-450282: MAPK targets/ Nuclear events mediated by MAP kinases R-HSA-5684996: MAPK1/MAPK3 signaling R-HSA-975871: MyD88 cascade initiated on plasma membrane R-HSA-975155: MyD88 dependent cascade initiated on endosome R-HSA-166166: MyD88-independent TLR3/TLR4 cascade R-HSA-166058: MyD88 R-HSA-375165: NCAM signaling for neurite out-growth R-HSA-187037: NGF signalling via TRKA from the plasma membrane R-HSA-5675221: Negative regulation of MAPK pathway R-HSA-198725: Nuclear Events (kinase and transcription factor activation) R-HSA-169893: Prolonged ERK activation events R-HSA-112409: RAF-independent MAPK1/3 activation R-HSA-5673001: RAF/MAP kinase cascade R-HSA-8853659: RET signaling R-HSA-180336: SHC1 events in EGFR signaling R-HSA-112412: SOS-mediated signalling R-HSA-162582: Signal Transduction R-HSA-177929: Signaling by EGFR R-HSA-372790: Signaling by GPCR R-HSA-74752: Signaling by Insulin receptor R-HSA-449147: Signaling by Interleukins R-HSA-2586552: Signaling by Leptin R-HSA-186797: Signaling by PDGF R-HSA-1433557: Signaling by SCF-KIT R-HSA-2404192: Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) R-HSA-194138: Signaling by VEGF R-HSA-166520: Signalling by NGF R-HSA-187687: Signalling to ERKs R-HSA-167044: Signalling to RAS R-HSA-187706: Signalling to p38 via RIT and RIN R-HSA-168180: TRAF6 Mediated Induction of proinflammatory cytokines R-HSA-975138: TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation R-HSA-937061: TRIF-mediated TLR3/TLR4 signaling R-HSA-168142: Toll Like Receptor 10 (TLR10) Cascade R-HSA-181438: Toll Like Receptor 2 (TLR2) Cascade R-HSA-168164: Toll Like Receptor 3 (TLR3) Cascade R-HSA-166016: Toll Like Receptor 4 (TLR4) Cascade R-HSA-168176: Toll Like Receptor 5 (TLR5) Cascade R-HSA-168181: Toll Like Receptor 7/8 (TLR7/8) Cascade R-HSA-168138: Toll Like Receptor 9 (TLR9) Cascade R-HSA-168179: Toll Like Receptor TLR1 R-HSA-168188: Toll Like Receptor TLR6 R-HSA-168898: Toll-Like Receptors Cascades R-HSA-4420097: VEGFA-VEGFR2 Pathway R-HSA-5218921: VEGFR2 mediated cell proliferation

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04010 MAPK signaling pathway

Reactome

R-HSA-170984: ARMS-mediated activation
R-HSA-166054: Activated TLR4 signalling
R-HSA-422475: Axon guidance
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-2172127: DAP12 interactions
R-HSA-2424491: DAP12 signaling
R-HSA-1266738: Developmental Biology
R-HSA-186763: Downstream signal transduction
R-HSA-198753: ERK/MAPK targets
R-HSA-202670: ERKs are inactivated
R-HSA-2871796: FCERI mediated MAPK activation
R-HSA-2454202: Fc epsilon receptor (FCERI) signaling
R-HSA-170968: Frs2-mediated activation
R-HSA-179812: GRB2 events in EGFR signaling
R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK
R-HSA-2428924: IGF1R signaling cascade
R-HSA-112399: IRS-mediated signalling
R-HSA-2428928: IRS-related events triggered by IGF1R
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-74751: Insulin receptor signalling cascade
R-HSA-912526: Interleukin receptor SHC signaling
R-HSA-451927: Interleukin-2 signaling
R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling
R-HSA-450294: MAP kinase activation in TLR cascade
R-HSA-5683057: MAPK family signaling cascades
R-HSA-450282: MAPK targets/ Nuclear events mediated by MAP kinases
R-HSA-5684996: MAPK1/MAPK3 signaling
R-HSA-975871: MyD88 cascade initiated on plasma membrane
R-HSA-975155: MyD88 dependent cascade initiated on endosome
R-HSA-166166: MyD88-independent TLR3/TLR4 cascade
R-HSA-166058: MyD88
R-HSA-375165: NCAM signaling for neurite out-growth
R-HSA-187037: NGF signalling via TRKA from the plasma membrane
R-HSA-5675221: Negative regulation of MAPK pathway
R-HSA-198725: Nuclear Events (kinase and transcription factor activation)
R-HSA-169893: Prolonged ERK activation events
R-HSA-112409: RAF-independent MAPK1/3 activation
R-HSA-5673001: RAF/MAP kinase cascade
R-HSA-8853659: RET signaling
R-HSA-180336: SHC1 events in EGFR signaling
R-HSA-112412: SOS-mediated signalling
R-HSA-162582: Signal Transduction
R-HSA-177929: Signaling by EGFR
R-HSA-372790: Signaling by GPCR
R-HSA-74752: Signaling by Insulin receptor
R-HSA-449147: Signaling by Interleukins
R-HSA-2586552: Signaling by Leptin
R-HSA-186797: Signaling by PDGF
R-HSA-1433557: Signaling by SCF-KIT
R-HSA-2404192: Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
R-HSA-194138: Signaling by VEGF
R-HSA-166520: Signalling by NGF
R-HSA-187687: Signalling to ERKs
R-HSA-167044: Signalling to RAS
R-HSA-187706: Signalling to p38 via RIT and RIN
R-HSA-168180: TRAF6 Mediated Induction of proinflammatory cytokines
R-HSA-975138: TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-HSA-937061: TRIF-mediated TLR3/TLR4 signaling
R-HSA-168142: Toll Like Receptor 10 (TLR10) Cascade
R-HSA-181438: Toll Like Receptor 2 (TLR2) Cascade
R-HSA-168164: Toll Like Receptor 3 (TLR3) Cascade
R-HSA-166016: Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168176: Toll Like Receptor 5 (TLR5) Cascade
R-HSA-168181: Toll Like Receptor 7/8 (TLR7/8) Cascade
R-HSA-168138: Toll Like Receptor 9 (TLR9) Cascade
R-HSA-168179: Toll Like Receptor TLR1
R-HSA-168188: Toll Like Receptor TLR6
R-HSA-168898: Toll-Like Receptors Cascades
R-HSA-4420097: VEGFA-VEGFR2 Pathway
R-HSA-5218921: VEGFR2 mediated cell proliferation

Summary
Symbol	DUSP6
Name	dual specificity phosphatase 6
Aliases	MKP-3; PYST1; HH19; MKP3; MAP kinase phosphatase 3; dual specificity protein phosphatase PYST1; mitogen-acti ......
Chromosomal Location	12q22-q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between DUSP6 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining [ TOP ]
There is no record.

Summary
Symbol	DUSP6
Name	dual specificity phosphatase 6
Aliases	MKP-3; PYST1; HH19; MKP3; MAP kinase phosphatase 3; dual specificity protein phosphatase PYST1; mitogen-acti ......
Chromosomal Location	12q22-q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

[ TOP ]

Statistical results of DUSP6 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	logFC: 2.83; FDR: 0.000150	Sensitive to T cell-mediated killing
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	DUSP6
Name	dual specificity phosphatase 6
Aliases	MKP-3; PYST1; HH19; MKP3; MAP kinase phosphatase 3; dual specificity protein phosphatase PYST1; mitogen-acti ......
Chromosomal Location	12q22-q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the expression difference of DUSP6 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.12	0.814
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.103	0.973
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.119	0.954
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.199	0.66
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.659	0.754
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.382	0.886
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.298	0.613
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.774	0.718
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.301	0.895
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.848	0.544
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	1.528	0.469
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.526	0.000323

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of DUSP6 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	7.4	0	7.4	0.0709
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	7.4	0	7.4	0.096
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	5.9	-1.1	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	9.1	-1.4	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	3.7	-1.1	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	7.7	-7.7	0.371
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	DUSP6
Name	dual specificity phosphatase 6
Aliases	MKP-3; PYST1; HH19; MKP3; MAP kinase phosphatase 3; dual specificity protein phosphatase PYST1; mitogen-acti ......
Chromosomal Location	12q22-q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of DUSP6. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	DUSP6
Name	dual specificity phosphatase 6
Aliases	MKP-3; PYST1; HH19; MKP3; MAP kinase phosphatase 3; dual specificity protein phosphatase PYST1; mitogen-acti ......
Chromosomal Location	12q22-q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of DUSP6. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by DUSP6. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	DUSP6
Name	dual specificity phosphatase 6
Aliases	MKP-3; PYST1; HH19; MKP3; MAP kinase phosphatase 3; dual specificity protein phosphatase PYST1; mitogen-acti ......
Chromosomal Location	12q22-q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of DUSP6. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	DUSP6
Name	dual specificity phosphatase 6
Aliases	MKP-3; PYST1; HH19; MKP3; MAP kinase phosphatase 3; dual specificity protein phosphatase PYST1; mitogen-acti ......
Chromosomal Location	12q22-q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of DUSP6 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	DUSP6
Name	dual specificity phosphatase 6
Aliases	MKP-3; PYST1; HH19; MKP3; MAP kinase phosphatase 3; dual specificity protein phosphatase PYST1; mitogen-acti ......
Chromosomal Location	12q22-q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between DUSP6 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	DUSP6
Name	dual specificity phosphatase 6
Aliases	MKP-3; PYST1; HH19; MKP3; MAP kinase phosphatase 3; dual specificity protein phosphatase PYST1; mitogen-acti ......
Chromosomal Location	12q22-q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting DUSP6 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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