Browse MAP2K7

Summary
SymbolMAP2K7
Namemitogen-activated protein kinase kinase 7
Aliases MKK7; Jnkk2; PRKMK7; MAPKK7; MEK; MEK 7; SAPKK-4; SAPKK4; JNK-activating kinase 2; MAP kinase kinase 7; MAPK ......
Chromosomal Location19p13.3-p13.2
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
 
Subcellular Location Nucleus. Cytoplasm
Domain PF00069 Protein kinase domain
Function

Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4/MKK4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The monophosphorylation of JNKs on the Thr residue is sufficient to increase JNK activity indicating that MAP2K7/MKK7 is important to trigger JNK activity, while the additional phosphorylation of the Tyr residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific role in JNK signal transduction pathway activated by proinflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis.

> Gene Ontology
 
Biological Process GO:0000187 activation of MAPK activity
GO:0000723 telomere maintenance
GO:0002764 immune response-regulating signaling pathway
GO:0002768 immune response-regulating cell surface receptor signaling pathway
GO:0006278 RNA-dependent DNA biosynthetic process
GO:0006970 response to osmotic stress
GO:0007004 telomere maintenance via telomerase
GO:0007254 JNK cascade
GO:0007257 activation of JUN kinase activity
GO:0009266 response to temperature stimulus
GO:0009314 response to radiation
GO:0009408 response to heat
GO:0009411 response to UV
GO:0009416 response to light stimulus
GO:0010833 telomere maintenance via telomere lengthening
GO:0016233 telomere capping
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018212 peptidyl-tyrosine modification
GO:0031098 stress-activated protein kinase signaling cascade
GO:0032147 activation of protein kinase activity
GO:0032200 telomere organization
GO:0032204 regulation of telomere maintenance
GO:0032206 positive regulation of telomere maintenance
GO:0032210 regulation of telomere maintenance via telomerase
GO:0032212 positive regulation of telomere maintenance via telomerase
GO:0032844 regulation of homeostatic process
GO:0032846 positive regulation of homeostatic process
GO:0032872 regulation of stress-activated MAPK cascade
GO:0032874 positive regulation of stress-activated MAPK cascade
GO:0033044 regulation of chromosome organization
GO:0033674 positive regulation of kinase activity
GO:0034612 response to tumor necrosis factor
GO:0035897 proteolysis in other organism
GO:0038093 Fc receptor signaling pathway
GO:0038095 Fc-epsilon receptor signaling pathway
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:0044033 multi-organism metabolic process
GO:0045860 positive regulation of protein kinase activity
GO:0046328 regulation of JNK cascade
GO:0046330 positive regulation of JNK cascade
GO:0051052 regulation of DNA metabolic process
GO:0051054 positive regulation of DNA metabolic process
GO:0051403 stress-activated MAPK cascade
GO:0051972 regulation of telomerase activity
GO:0051973 positive regulation of telomerase activity
GO:0060249 anatomical structure homeostasis
GO:0070302 regulation of stress-activated protein kinase signaling cascade
GO:0070304 positive regulation of stress-activated protein kinase signaling cascade
GO:0071897 DNA biosynthetic process
GO:0071900 regulation of protein serine/threonine kinase activity
GO:0071902 positive regulation of protein serine/threonine kinase activity
GO:1904353 regulation of telomere capping
GO:1904355 positive regulation of telomere capping
GO:1904356 regulation of telomere maintenance via telomere lengthening
GO:1904358 positive regulation of telomere maintenance via telomere lengthening
GO:2000278 regulation of DNA biosynthetic process
GO:2000573 positive regulation of DNA biosynthetic process
GO:2001252 positive regulation of chromosome organization
Molecular Function GO:0000287 magnesium ion binding
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
GO:0019902 phosphatase binding
GO:0019903 protein phosphatase binding
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa04010 MAPK signaling pathway
hsa04012 ErbB signaling pathway
hsa04141 Protein processing in endoplasmic reticulum
hsa04380 Osteoclast differentiation
hsa04530 Tight junction
hsa04620 Toll-like receptor signaling pathway
hsa04660 T cell receptor signaling pathway
hsa04664 Fc epsilon RI signaling pathway
hsa04668 TNF signaling pathway
hsa04722 Neurotrophin signaling pathway
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-2871796: FCERI mediated MAPK activation
R-HSA-2454202: Fc epsilon receptor (FCERI) signaling
R-HSA-168256: Immune System
R-HSA-5663205: Infectious disease
R-HSA-168249: Innate Immune System
R-HSA-450321: JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
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
Summary
SymbolMAP2K7
Namemitogen-activated protein kinase kinase 7
Aliases MKK7; Jnkk2; PRKMK7; MAPKK7; MEK; MEK 7; SAPKK-4; SAPKK4; JNK-activating kinase 2; MAP kinase kinase 7; MAPK ......
Chromosomal Location19p13.3-p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between MAP2K7 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
 
  Literatures describing the relation between MAP2K7 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
26515496Breast CarcinomaBiomarker of response to immunotherapyFurthermore, Ras/MAPK activation and MHC expression may be predictive biomarkers of response to immune checkpoint inhibitors.
26944201Colon CarcinomaInhibit immunity (T cell function), resistant to immunotherapyThus, despite the central importance of the MAP kinase pathway in some aspects of T cell function, MEK-targeted agents can be compatible with T-cell-dependent immunotherapy.
25787767MelanomaInhibit immunity (T cell function)Our findings support the testing of triple combination therapy of BRAF and MEK inhibitors with immunotherapy in patients with BRAF(V600E) mutant metastatic melanoma.
29650805melanomaInhibit immunityTranscriptomic and proteomic analysis revealed that combining BET and MEK inhibitors mitigates a MAPK and checkpoint inhibitor resistance transcriptional signature, downregulates the transcription factor TCF19, and induces apoptosis.
29843107MelanomaResistant to immunotherapyMEK inhibition may increase survival of NRAS-mutated melanoma patients treated with checkpoint blockade: Results of a retrospective multicentre analysis of 364 patients. Therapy with oral MEK inhibitors before or after checkpoint inhibitor therapy showed a trend toward a survival benefit in patients with NRAS mutant melanoma.
16801397MelanomaInhibit immunityHere, we demonstrate a novel role of the activated MAPK pathway in immune evasion by melanoma cells with the mutation of BRAF, which encodes a MAPKKs, (BRAF(V600E)). MEK inhibitor U0126 or RNA interference (RNAi) for BRAF(V600E) decreased production of the immunosuppressive soluble factors interleukin (IL)-10, VEGF, or IL-6 from melanoma cells to levels comparable to those after signal transducer and activator of transcription (STAT)3 inactivation
Summary
SymbolMAP2K7
Namemitogen-activated protein kinase kinase 7
Aliases MKK7; Jnkk2; PRKMK7; MAPKK7; MEK; MEK 7; SAPKK-4; SAPKK4; JNK-activating kinase 2; MAP kinase kinase 7; MAPK ......
Chromosomal Location19p13.3-p13.2
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
  Statistical results of MAP2K7 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/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolMAP2K7
Namemitogen-activated protein kinase kinase 7
Aliases MKK7; Jnkk2; PRKMK7; MAPKK7; MEK; MEK 7; SAPKK-4; SAPKK4; JNK-activating kinase 2; MAP kinase kinase 7; MAPK ......
Chromosomal Location19p13.3-p13.2
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
 
Points in the above scatter plot represent the expression difference of MAP2K7 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.1810.385
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.3360.858
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.0710.96
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.0050.984
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.1130.949
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.1320.954
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.1110.714
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.0640.961
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.140.926
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.2950.817
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.4270.815
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0420.501
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of MAP2K7 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) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
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)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
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
SymbolMAP2K7
Namemitogen-activated protein kinase kinase 7
Aliases MKK7; Jnkk2; PRKMK7; MAPKK7; MEK; MEK 7; SAPKK-4; SAPKK4; JNK-activating kinase 2; MAP kinase kinase 7; MAPK ......
Chromosomal Location19p13.3-p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of MAP2K7. 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
SymbolMAP2K7
Namemitogen-activated protein kinase kinase 7
Aliases MKK7; Jnkk2; PRKMK7; MAPKK7; MEK; MEK 7; SAPKK-4; SAPKK4; JNK-activating kinase 2; MAP kinase kinase 7; MAPK ......
Chromosomal Location19p13.3-p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of MAP2K7. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by MAP2K7.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolMAP2K7
Namemitogen-activated protein kinase kinase 7
Aliases MKK7; Jnkk2; PRKMK7; MAPKK7; MEK; MEK 7; SAPKK-4; SAPKK4; JNK-activating kinase 2; MAP kinase kinase 7; MAPK ......
Chromosomal Location19p13.3-p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of MAP2K7. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolMAP2K7
Namemitogen-activated protein kinase kinase 7
Aliases MKK7; Jnkk2; PRKMK7; MAPKK7; MEK; MEK 7; SAPKK-4; SAPKK4; JNK-activating kinase 2; MAP kinase kinase 7; MAPK ......
Chromosomal Location19p13.3-p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of MAP2K7 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolMAP2K7
Namemitogen-activated protein kinase kinase 7
Aliases MKK7; Jnkk2; PRKMK7; MAPKK7; MEK; MEK 7; SAPKK-4; SAPKK4; JNK-activating kinase 2; MAP kinase kinase 7; MAPK ......
Chromosomal Location19p13.3-p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between MAP2K7 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolMAP2K7
Namemitogen-activated protein kinase kinase 7
Aliases MKK7; Jnkk2; PRKMK7; MAPKK7; MEK; MEK 7; SAPKK-4; SAPKK4; JNK-activating kinase 2; MAP kinase kinase 7; MAPK ......
Chromosomal Location19p13.3-p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting MAP2K7 collected from DrugBank database.
> Drugs from DrugBank database
 

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