TISIDB

Summary
Symbol	MAP4K2
Name	mitogen-activated protein kinase kinase kinase kinase 2
Aliases	BL44; RAB8IP; B lymphocyte serine/threonine protein kinase; MAPK/ERK kinase kinase kinase 2; MEK kinase kina ......
Chromosomal Location	11q13.1
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 Basolateral cell membrane Peripheral membrane protein Golgi apparatus membrane Peripheral membrane protein
Domain	PF00780 CNH domain PF00069 Protein kinase domain
Function	Serine/threonine-protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Acts as a MAPK kinase kinase kinase (MAP4K) and is an upstream activator of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway and to a lesser extent of the p38 MAPKs signaling pathway. Required for the efficient activation of JNKs by TRAF6-dependent stimuli, including pathogen-associated molecular patterns (PAMPs) such as polyinosine-polycytidine (poly(IC)), lipopolysaccharides (LPS), lipid A, peptidoglycan (PGN), or bacterial flagellin. To a lesser degree, IL-1 and engagement of CD40 also stimulate MAP4K2-mediated JNKs activation. The requirement for MAP4K2/GCK is most pronounced for LPS signaling, and extends to LPS stimulation of c-Jun phosphorylation and induction of IL-8. Enhances MAP3K1 oligomerization, which may relieve N-terminal mediated MAP3K1 autoinhibition and lead to activation following autophosphorylation. Mediates also the SAP/JNK signaling pathway and the p38 MAPKs signaling pathway through activation of the MAP3Ks MAP3K10/MLK2 and MAP3K11/MLK3. May play a role in the regulation of vesicle targeting or fusion. regulation of vesicle targeting or fusion.

> Gene Ontology [ TOP ]
Biological Process	GO:0000185 activation of MAPKKK activity GO:0000187 activation of MAPK activity GO:0006903 vesicle targeting GO:0007254 JNK cascade GO:0007257 activation of JUN kinase activity GO:0031098 stress-activated protein kinase signaling cascade GO:0032147 activation of protein kinase activity GO:0032872 regulation of stress-activated MAPK cascade GO:0032874 positive regulation of stress-activated MAPK cascade GO:0033674 positive regulation of kinase activity GO:0043405 regulation of MAP kinase activity GO:0043406 positive regulation of MAP kinase activity GO:0043410 positive regulation of MAPK cascade GO:0043506 regulation of JUN kinase activity GO:0043507 positive regulation of JUN kinase activity GO:0045860 positive regulation of protein kinase activity GO:0046328 regulation of JNK cascade GO:0046330 positive regulation of JNK cascade GO:0051403 stress-activated MAPK cascade GO:0051640 organelle localization GO:0051648 vesicle localization GO:0051650 establishment of vesicle localization GO:0051656 establishment of organelle localization GO:0070302 regulation of stress-activated protein kinase signaling cascade GO:0070304 positive regulation of stress-activated protein kinase signaling cascade 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:0005057 receptor signaling protein activity GO:0008349 MAP kinase kinase kinase kinase activity GO:0031435 mitogen-activated protein kinase kinase kinase binding
Cellular Component	GO:0016323 basolateral plasma membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04010 MAPK signaling pathway
Reactome	-

Summary
Symbol	MAP4K2
Name	mitogen-activated protein kinase kinase kinase kinase 2
Aliases	BL44; RAB8IP; B lymphocyte serine/threonine protein kinase; MAPK/ERK kinase kinase kinase 2; MEK kinase kina ......
Chromosomal Location	11q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between MAP4K2 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	MAP4K2
Name	mitogen-activated protein kinase kinase kinase kinase 2
Aliases	BL44; RAB8IP; B lymphocyte serine/threonine protein kinase; MAPK/ERK kinase kinase kinase 2; MEK kinase kina ......
Chromosomal Location	11q13.1
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 MAP4K2 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	Second most enriched score: 0.52	Sensitive to T cell-mediated killing
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	MAP4K2
Name	mitogen-activated protein kinase kinase kinase kinase 2
Aliases	BL44; RAB8IP; B lymphocyte serine/threonine protein kinase; MAPK/ERK kinase kinase kinase 2; MEK kinase kina ......
Chromosomal Location	11q13.1
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 MAP4K2 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	0.095	0.781
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.43	0.726
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.158	0.881
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.097	0.76
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.124	0.946
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.063	0.979
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.105	0.757
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.214	0.848
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.008	0.994
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.426	0.206
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	1.788	0.274
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.053	0.498

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of MAP4K2 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	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	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	0	0	1
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	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	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	0	7.7	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	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	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	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	MAP4K2
Name	mitogen-activated protein kinase kinase kinase kinase 2
Aliases	BL44; RAB8IP; B lymphocyte serine/threonine protein kinase; MAPK/ERK kinase kinase kinase 2; MEK kinase kina ......
Chromosomal Location	11q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of MAP4K2. 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	MAP4K2
Name	mitogen-activated protein kinase kinase kinase kinase 2
Aliases	BL44; RAB8IP; B lymphocyte serine/threonine protein kinase; MAPK/ERK kinase kinase kinase 2; MEK kinase kina ......
Chromosomal Location	11q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of MAP4K2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by MAP4K2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	MAP4K2
Name	mitogen-activated protein kinase kinase kinase kinase 2
Aliases	BL44; RAB8IP; B lymphocyte serine/threonine protein kinase; MAPK/ERK kinase kinase kinase 2; MEK kinase kina ......
Chromosomal Location	11q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of MAP4K2. 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	MAP4K2
Name	mitogen-activated protein kinase kinase kinase kinase 2
Aliases	BL44; RAB8IP; B lymphocyte serine/threonine protein kinase; MAPK/ERK kinase kinase kinase 2; MEK kinase kina ......
Chromosomal Location	11q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of MAP4K2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	MAP4K2
Name	mitogen-activated protein kinase kinase kinase kinase 2
Aliases	BL44; RAB8IP; B lymphocyte serine/threonine protein kinase; MAPK/ERK kinase kinase kinase 2; MEK kinase kina ......
Chromosomal Location	11q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between MAP4K2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	MAP4K2
Name	mitogen-activated protein kinase kinase kinase kinase 2
Aliases	BL44; RAB8IP; B lymphocyte serine/threonine protein kinase; MAPK/ERK kinase kinase kinase 2; MEK kinase kina ......
Chromosomal Location	11q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting MAP4K2 collected from DrugBank database.

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

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