Browse MAP4K2

Summary
SymbolMAP4K2
Namemitogen-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 Location11q13.1
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
 
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
 
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
 
KEGG hsa04010 MAPK signaling pathway
Reactome -
Summary
SymbolMAP4K2
Namemitogen-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 Location11q13.1
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
 

There is no record.

Summary
SymbolMAP4K2
Namemitogen-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 Location11q13.1
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
  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
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NS NA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR Second most enriched score: 0.52 Sensitive to T cell-mediated killing
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolMAP4K2
Namemitogen-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 Location11q13.1
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
 
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 Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.0950.781
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.430.726
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.1580.881
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.0970.76
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.1240.946
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.0630.979
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.1050.757
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.2140.848
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.0080.994
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 481.4260.206
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.7880.274
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.0530.498
> Mutation difference between responders and non-responders
 
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 Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14177.107.10.452
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 103100101
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27730001
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27590001
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.804.81
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.707.71
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91606.2-6.21
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59011.1-11.11
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolMAP4K2
Namemitogen-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 Location11q13.1
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
 
Summary
SymbolMAP4K2
Namemitogen-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 Location11q13.1
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
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolMAP4K2
Namemitogen-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 Location11q13.1
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
 
> Receptor
 
Summary
SymbolMAP4K2
Namemitogen-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 Location11q13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of MAP4K2 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolMAP4K2
Namemitogen-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 Location11q13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between MAP4K2 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolMAP4K2
Namemitogen-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 Location11q13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting MAP4K2 collected from DrugBank database.
> Drugs from DrugBank database
 

There is no record.