TISIDB

Summary
Symbol	MAP3K1
Name	mitogen-activated protein kinase kinase kinase 1, E3 ubiquitin protein ligase
Aliases	MEKK; MAPKKK1; MEKK1; mitogen-activated protein kinase kinase kinase 1; MEKK 1; SRXY6; MAP/ERK kinase kinase ......
Chromosomal Location	5q11.2
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	Component of a protein kinase signal transduction cascade (PubMed:9808624). Activates the ERK and JNK kinase pathways by phosphorylation of MAP2K1 and MAP2K4 (PubMed:9808624). May phosphorylate the MAPK8/JNK1 kinase (PubMed:17761173). Activates CHUK and IKBKB, the central protein kinases of the NF-kappa-B pathway (PubMed:9808624).

> Gene Ontology [ TOP ]
Biological Process	GO:0000186 activation of MAPKK activity GO:0002218 activation of innate immune response GO:0002221 pattern recognition receptor signaling pathway GO:0002224 toll-like receptor signaling pathway GO:0002755 MyD88-dependent toll-like receptor signaling pathway GO:0002757 immune response-activating signal transduction GO:0002758 innate immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0002768 immune response-regulating cell surface receptor signaling pathway GO:0009612 response to mechanical stimulus GO:0031349 positive regulation of defense response GO:0032147 activation of protein kinase activity GO:0033674 positive regulation of kinase activity GO:0038093 Fc receptor signaling pathway GO:0038095 Fc-epsilon receptor signaling pathway GO:0043405 regulation of MAP kinase activity GO:0043410 positive regulation of MAPK cascade GO:0045088 regulation of innate immune response GO:0045089 positive regulation of innate immune response GO:0045860 positive regulation of protein kinase activity GO:0071214 cellular response to abiotic stimulus GO:0071260 cellular response to mechanical stimulus GO:0071496 cellular response to external stimulus GO:0071900 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:0004709 MAP kinase kinase kinase activity GO:0005057 receptor signaling protein activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04010 MAPK signaling pathway hsa04120 Ubiquitin mediated proteolysis hsa04530 Tight junction hsa04622 RIG-I-like receptor signaling pathway hsa04722 Neurotrophin signaling pathway hsa04912 GnRH signaling pathway
Reactome	R-HSA-166054: Activated TLR4 signalling R-HSA-2871796: FCERI mediated MAPK activation R-HSA-2454202: Fc epsilon receptor (FCERI) signaling R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-975871: MyD88 cascade initiated on plasma membrane R-HSA-975155: MyD88 dependent cascade initiated on endosome R-HSA-166058: MyD88 R-HSA-168928: RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways R-HSA-933542: TRAF6 mediated NF-kB activation R-HSA-975138: TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation R-HSA-168142: Toll Like Receptor 10 (TLR10) Cascade R-HSA-181438: Toll Like Receptor 2 (TLR2) 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

> KEGG and Reactome Pathway

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KEGG

hsa04010 MAPK signaling pathway
hsa04120 Ubiquitin mediated proteolysis
hsa04530 Tight junction
hsa04622 RIG-I-like receptor signaling pathway
hsa04722 Neurotrophin signaling pathway
hsa04912 GnRH signaling pathway

Reactome

R-HSA-166054: Activated TLR4 signalling
R-HSA-2871796: FCERI mediated MAPK activation
R-HSA-2454202: Fc epsilon receptor (FCERI) signaling
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-975871: MyD88 cascade initiated on plasma membrane
R-HSA-975155: MyD88 dependent cascade initiated on endosome
R-HSA-166058: MyD88
R-HSA-168928: RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
R-HSA-933542: TRAF6 mediated NF-kB activation
R-HSA-975138: TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-HSA-168142: Toll Like Receptor 10 (TLR10) Cascade
R-HSA-181438: Toll Like Receptor 2 (TLR2) 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

Summary
Symbol	MAP3K1
Name	mitogen-activated protein kinase kinase kinase 1, E3 ubiquitin protein ligase
Aliases	MEKK; MAPKKK1; MEKK1; mitogen-activated protein kinase kinase kinase 1; MEKK 1; SRXY6; MAP/ERK kinase kinase ......
Chromosomal Location	5q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between MAP3K1 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	MAP3K1
Name	mitogen-activated protein kinase kinase kinase 1, E3 ubiquitin protein ligase
Aliases	MEKK; MAPKKK1; MEKK1; mitogen-activated protein kinase kinase kinase 1; MEKK 1; SRXY6; MAP/ERK kinase kinase ......
Chromosomal Location	5q11.2
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

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Statistical results of MAP3K1 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	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	Total # shRNA with >= 4-fold: 1	Resistant to T-cell proliferation
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	MAP3K1
Name	mitogen-activated protein kinase kinase kinase 1, E3 ubiquitin protein ligase
Aliases	MEKK; MAPKKK1; MEKK1; mitogen-activated protein kinase kinase kinase 1; MEKK 1; SRXY6; MAP/ERK kinase kinase ......
Chromosomal Location	5q11.2
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

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Points in the above scatter plot represent the expression difference of MAP3K1 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	0.555	0.125
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.994	0.508
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.236	0.832
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.398	0.15
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.49	0.819
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.286	0.92
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.001	0.998
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.31	0.864
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.289	0.882
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.555	0.631
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	1.033	0.527
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.081	0.352

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of MAP3K1 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	0	5.5	-5.5	0.572
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	0	6.8	-6.8	0.304
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	9.5	0	9.5	0.492
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	25	0	25	0.473
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	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	7.9	3.7	4.2	0.636
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	13.6	7.7	5.9	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	9.1	0	9.1	0.458
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	20	0	20	0.294

Summary
Symbol	MAP3K1
Name	mitogen-activated protein kinase kinase kinase 1, E3 ubiquitin protein ligase
Aliases	MEKK; MAPKKK1; MEKK1; mitogen-activated protein kinase kinase kinase 1; MEKK 1; SRXY6; MAP/ERK kinase kinase ......
Chromosomal Location	5q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of MAP3K1. 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	MAP3K1
Name	mitogen-activated protein kinase kinase kinase 1, E3 ubiquitin protein ligase
Aliases	MEKK; MAPKKK1; MEKK1; mitogen-activated protein kinase kinase kinase 1; MEKK 1; SRXY6; MAP/ERK kinase kinase ......
Chromosomal Location	5q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of MAP3K1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by MAP3K1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	MAP3K1
Name	mitogen-activated protein kinase kinase kinase 1, E3 ubiquitin protein ligase
Aliases	MEKK; MAPKKK1; MEKK1; mitogen-activated protein kinase kinase kinase 1; MEKK 1; SRXY6; MAP/ERK kinase kinase ......
Chromosomal Location	5q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of MAP3K1. 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	MAP3K1
Name	mitogen-activated protein kinase kinase kinase 1, E3 ubiquitin protein ligase
Aliases	MEKK; MAPKKK1; MEKK1; mitogen-activated protein kinase kinase kinase 1; MEKK 1; SRXY6; MAP/ERK kinase kinase ......
Chromosomal Location	5q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of MAP3K1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	MAP3K1
Name	mitogen-activated protein kinase kinase kinase 1, E3 ubiquitin protein ligase
Aliases	MEKK; MAPKKK1; MEKK1; mitogen-activated protein kinase kinase kinase 1; MEKK 1; SRXY6; MAP/ERK kinase kinase ......
Chromosomal Location	5q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between MAP3K1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	MAP3K1
Name	mitogen-activated protein kinase kinase kinase 1, E3 ubiquitin protein ligase
Aliases	MEKK; MAPKKK1; MEKK1; mitogen-activated protein kinase kinase kinase 1; MEKK 1; SRXY6; MAP/ERK kinase kinase ......
Chromosomal Location	5q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting MAP3K1 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting MAP3K1.

ID	Name	Drug Type	Targets	#Targets
DB06061	AZD-8330	Small Molecule	MAP3K1	1

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