TISIDB

Summary
Symbol	MAP2K3
Name	mitogen-activated protein kinase kinase 3
Aliases	MEK3; MKK3; MAPKK3; MAPK/ERK kinase 3; MAP kinase kinase 3; dual specificity mitogen activated protein kinas ......
Chromosomal Location	17q11.2
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	-
Domain	PF00069 Protein kinase domain
Function	Dual specificity kinase. Is activated by cytokines and environmental stress in vivo. Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinase p38. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14.

> Gene Ontology [ TOP ]
Biological Process	GO:0000187 activation of MAPK activity GO:0018108 peptidyl-tyrosine phosphorylation GO:0018212 peptidyl-tyrosine modification GO:0032147 activation of protein kinase activity GO:0033674 positive regulation of kinase activity GO:0035897 proteolysis in other organism GO:0043405 regulation of MAP kinase activity GO:0043406 positive regulation of MAP kinase activity GO:0043410 positive regulation of MAPK cascade GO:0044033 multi-organism metabolic process GO:0045860 positive regulation of protein kinase activity GO:0071900 regulation of protein serine/threonine kinase activity GO:0071902 positive regulation of protein serine/threonine kinase activity
Molecular Function	GO:0004674 protein serine/threonine kinase activity GO:0004702 receptor signaling protein serine/threonine kinase activity GO:0004708 MAP kinase kinase activity GO:0004712 protein serine/threonine/tyrosine kinase activity GO:0004713 protein tyrosine kinase activity GO:0005057 receptor signaling protein activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04010 MAPK signaling pathway hsa04015 Rap1 signaling pathway hsa04620 Toll-like receptor signaling pathway hsa04664 Fc epsilon RI signaling pathway hsa04668 TNF signaling pathway hsa04750 Inflammatory mediator regulation of TRP channels hsa04912 GnRH signaling pathway
Reactome	R-HSA-166054: Activated TLR4 signalling R-HSA-2559583: Cellular Senescence R-HSA-2262752: Cellular responses to stress R-HSA-1643685: Disease R-HSA-168256: Immune System R-HSA-5663205: Infectious disease R-HSA-168249: Innate Immune System R-HSA-450294: MAP kinase activation in TLR cascade 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-2559580: Oxidative Stress Induced Senescence 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-5339562: Uptake and actions of bacterial toxins R-HSA-5210891: Uptake and function of anthrax toxins R-HSA-450302: activated TAK1 mediates p38 MAPK activation

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04010 MAPK signaling pathway
hsa04015 Rap1 signaling pathway
hsa04620 Toll-like receptor signaling pathway
hsa04664 Fc epsilon RI signaling pathway
hsa04668 TNF signaling pathway
hsa04750 Inflammatory mediator regulation of TRP channels
hsa04912 GnRH signaling pathway

Reactome

R-HSA-166054: Activated TLR4 signalling
R-HSA-2559583: Cellular Senescence
R-HSA-2262752: Cellular responses to stress
R-HSA-1643685: Disease
R-HSA-168256: Immune System
R-HSA-5663205: Infectious disease
R-HSA-168249: Innate Immune System
R-HSA-450294: MAP kinase activation in TLR cascade
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-2559580: Oxidative Stress Induced Senescence
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-5339562: Uptake and actions of bacterial toxins
R-HSA-5210891: Uptake and function of anthrax toxins
R-HSA-450302: activated TAK1 mediates p38 MAPK activation

Summary
Symbol	MAP2K3
Name	mitogen-activated protein kinase kinase 3
Aliases	MEK3; MKK3; MAPKK3; MAPK/ERK kinase 3; MAP kinase kinase 3; dual specificity mitogen activated protein kinas ......
Chromosomal Location	17q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between MAP2K3 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	MAP2K3
Name	mitogen-activated protein kinase kinase 3
Aliases	MEK3; MKK3; MAPKK3; MAPK/ERK kinase 3; MAP kinase kinase 3; dual specificity mitogen activated protein kinas ......
Chromosomal Location	17q11.2
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 MAP2K3 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	NA/NS	NA/NS
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	STARS Score: 3.56; FDR: 0.048	Resistant to T cell-mediated killing
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	MAP2K3
Name	mitogen-activated protein kinase kinase 3
Aliases	MEK3; MKK3; MAPKK3; MAPK/ERK kinase 3; MAP kinase kinase 3; dual specificity mitogen activated protein kinas ......
Chromosomal Location	17q11.2
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 MAP2K3 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	0.191	0.532
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.024	0.992
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.356	0.821
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.037	0.917
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.303	0.88
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.469	0.857
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.078	0.838
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.179	0.9
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.034	0.984
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.556	0.725
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	0.768	0.743
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.109	0.158

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of MAP2K3 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	5.9	-5.9	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	33.3	-33.3	0.231
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	2.7	-2.7	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.4	-3.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	5.9	-5.9	0.447
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	16.7	-16.7	0.429
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	11.1	-11.1	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	7.7	-7.7	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	8.3	-8.3	1

Summary
Symbol	MAP2K3
Name	mitogen-activated protein kinase kinase 3
Aliases	MEK3; MKK3; MAPKK3; MAPK/ERK kinase 3; MAP kinase kinase 3; dual specificity mitogen activated protein kinas ......
Chromosomal Location	17q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of MAP2K3. 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	MAP2K3
Name	mitogen-activated protein kinase kinase 3
Aliases	MEK3; MKK3; MAPKK3; MAPK/ERK kinase 3; MAP kinase kinase 3; dual specificity mitogen activated protein kinas ......
Chromosomal Location	17q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of MAP2K3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by MAP2K3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	MAP2K3
Name	mitogen-activated protein kinase kinase 3
Aliases	MEK3; MKK3; MAPKK3; MAPK/ERK kinase 3; MAP kinase kinase 3; dual specificity mitogen activated protein kinas ......
Chromosomal Location	17q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of MAP2K3. 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	MAP2K3
Name	mitogen-activated protein kinase kinase 3
Aliases	MEK3; MKK3; MAPKK3; MAPK/ERK kinase 3; MAP kinase kinase 3; dual specificity mitogen activated protein kinas ......
Chromosomal Location	17q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of MAP2K3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	MAP2K3
Name	mitogen-activated protein kinase kinase 3
Aliases	MEK3; MKK3; MAPKK3; MAPK/ERK kinase 3; MAP kinase kinase 3; dual specificity mitogen activated protein kinas ......
Chromosomal Location	17q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between MAP2K3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	MAP2K3
Name	mitogen-activated protein kinase kinase 3
Aliases	MEK3; MKK3; MAPKK3; MAPK/ERK kinase 3; MAP kinase kinase 3; dual specificity mitogen activated protein kinas ......
Chromosomal Location	17q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting MAP2K3 collected from DrugBank database.

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

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