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Browse MAP2K2

Summary
SymbolMAP2K2
Namemitogen-activated protein kinase kinase 2
Aliases MEK2; PRKMK2; CFC4; MAPKK2; MKK2; ERK activator kinase 2; MAP kinase kinase 2; MAPK/ERK kinase 2; mitogen-ac ......
Chromosomal Location19p13.3
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 Membrane Peripheral membrane protein Note=Membrane localization is probably regulated by its interaction with KSR1.
Domain PF00069 Protein kinase domain
Function

Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases (By similarity).

> Gene Ontology
 
Biological Process GO:0000187 activation of MAPK activity
GO:0006417 regulation of translation
GO:0007030 Golgi organization
GO:0007034 vacuolar transport
GO:0010608 posttranscriptional regulation of gene expression
GO:0016197 endosomal transport
GO:0016441 posttranscriptional gene silencing
GO:0016458 gene silencing
GO:0016482 cytosolic transport
GO:0017148 negative regulation of translation
GO:0018105 peptidyl-serine phosphorylation
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018209 peptidyl-serine modification
GO:0018212 peptidyl-tyrosine modification
GO:0031047 gene silencing by RNA
GO:0031050 dsRNA fragmentation
GO:0031098 stress-activated protein kinase signaling cascade
GO:0032147 activation of protein kinase activity
GO:0032386 regulation of intracellular transport
GO:0032872 regulation of stress-activated MAPK cascade
GO:0033674 positive regulation of kinase activity
GO:0034248 regulation of cellular amide metabolic process
GO:0034249 negative regulation of cellular amide metabolic process
GO:0035194 posttranscriptional gene silencing by RNA
GO:0035195 gene silencing by miRNA
GO:0035196 production of miRNAs involved in gene silencing by miRNA
GO:0035897 proteolysis in other organism
GO:0036289 peptidyl-serine autophosphorylation
GO:0040029 regulation of gene expression, epigenetic
GO:0043331 response to dsRNA
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:0045022 early endosome to late endosome transport
GO:0045860 positive regulation of protein kinase activity
GO:0046777 protein autophosphorylation
GO:0048308 organelle inheritance
GO:0048313 Golgi inheritance
GO:0051403 stress-activated MAPK cascade
GO:0060147 regulation of posttranscriptional gene silencing
GO:0060148 positive regulation of posttranscriptional gene silencing
GO:0060627 regulation of vesicle-mediated transport
GO:0060964 regulation of gene silencing by miRNA
GO:0060966 regulation of gene silencing by RNA
GO:0060968 regulation of gene silencing
GO:0070302 regulation of stress-activated protein kinase signaling cascade
GO:0070371 ERK1 and ERK2 cascade
GO:0070372 regulation of ERK1 and ERK2 cascade
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0070918 production of small RNA involved in gene silencing by RNA
GO:0070920 regulation of production of small RNA involved in gene silencing by RNA
GO:0071359 cellular response to dsRNA
GO:0071407 cellular response to organic cyclic compound
GO:0071900 regulation of protein serine/threonine kinase activity
GO:0071902 positive regulation of protein serine/threonine kinase activity
GO:0090170 regulation of Golgi inheritance
GO:0098927 vesicle-mediated transport between endosomal compartments
GO:1903335 regulation of vacuolar transport
GO:1903358 regulation of Golgi organization
GO:1903649 regulation of cytoplasmic transport
GO:1903798 regulation of production of miRNAs involved in gene silencing by miRNA
GO:1903800 positive regulation of production of miRNAs involved in gene silencing by miRNA
GO:2000637 positive regulation of gene silencing by miRNA
GO:2000641 regulation of early endosome to late endosome transport
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
GO:0008047 enzyme activator activity
GO:0019207 kinase regulator activity
GO:0019209 kinase activator activity
GO:0019887 protein kinase regulator activity
GO:0030165 PDZ domain binding
GO:0030295 protein kinase activator activity
GO:0043539 protein serine/threonine kinase activator activity
GO:0097110 scaffold protein binding
Cellular Component GO:0005769 early endosome
GO:0005770 late endosome
GO:0005777 peroxisome
GO:0005778 peroxisomal membrane
GO:0005874 microtubule
GO:0005924 cell-substrate adherens junction
GO:0005925 focal adhesion
GO:0009898 cytoplasmic side of plasma membrane
GO:0030055 cell-substrate junction
GO:0031903 microbody membrane
GO:0042579 microbody
GO:0044438 microbody part
GO:0044439 peroxisomal part
GO:0098552 side of membrane
GO:0098562 cytoplasmic side of membrane
> KEGG and Reactome Pathway
 
KEGG hsa04010 MAPK signaling pathway
hsa04012 ErbB signaling pathway
hsa04014 Ras signaling pathway
hsa04015 Rap1 signaling pathway
hsa04022 cGMP-PKG signaling pathway
hsa04024 cAMP signaling pathway
hsa04066 HIF-1 signaling pathway
hsa04068 FoxO signaling pathway
hsa04071 Sphingolipid signaling pathway
hsa04140 Regulation of autophagy
hsa04150 mTOR signaling pathway
hsa04151 PI3K-Akt signaling pathway
hsa04210 Apoptosis
hsa04270 Vascular smooth muscle contraction
hsa04370 VEGF signaling pathway
hsa04540 Gap junction
hsa04550 Signaling pathways regulating pluripotency of stem cells
hsa04620 Toll-like receptor signaling pathway
hsa04650 Natural killer cell mediated cytotoxicity
hsa04660 T cell receptor signaling pathway
hsa04662 B cell receptor signaling pathway
hsa04664 Fc epsilon RI signaling pathway
hsa04720 Long-term potentiation
hsa04722 Neurotrophin signaling pathway
hsa04730 Long-term depression
hsa04810 Regulation of actin cytoskeleton
hsa04910 Insulin signaling pathway
hsa04912 GnRH signaling pathway
hsa04915 Estrogen signaling pathway
hsa04916 Melanogenesis
hsa04917 Prolactin signaling pathway
hsa04919 Thyroid hormone signaling pathway
hsa04921 Oxytocin signaling pathway
Reactome R-HSA-170984: ARMS-mediated activation
R-HSA-422475: Axon guidance
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-2172127: DAP12 interactions
R-HSA-2424491: DAP12 signaling
R-HSA-1266738: Developmental Biology
R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-186763: Downstream signal transduction
R-HSA-2871796: FCERI mediated MAPK activation
R-HSA-2454202: Fc epsilon receptor (FCERI) signaling
R-HSA-170968: Frs2-mediated activation
R-HSA-179812: GRB2 events in EGFR signaling
R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK
R-HSA-2428924: IGF1R signaling cascade
R-HSA-112399: IRS-mediated signalling
R-HSA-2428928: IRS-related events triggered by IGF1R
R-HSA-168256: Immune System
R-HSA-5663205: Infectious disease
R-HSA-168249: Innate Immune System
R-HSA-74751: Insulin receptor signalling cascade
R-HSA-912526: Interleukin receptor SHC signaling
R-HSA-451927: Interleukin-2 signaling
R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling
R-HSA-373760: L1CAM interactions
R-HSA-5674135: MAP2K and MAPK activation
R-HSA-5683057: MAPK family signaling cascades
R-HSA-112411: MAPK1 (ERK2) activation
R-HSA-5684996: MAPK1/MAPK3 signaling
R-HSA-375165: NCAM signaling for neurite out-growth
R-HSA-187037: NGF signalling via TRKA from the plasma membrane
R-HSA-5674499: Negative feedback regulation of MAPK pathway
R-HSA-5675221: Negative regulation of MAPK pathway
R-HSA-6802957: Oncogenic MAPK signaling
R-HSA-6802955: Paradoxical activation of RAF signaling by kinase inactive BRAF
R-HSA-169893: Prolonged ERK activation events
R-HSA-5673000: RAF activation
R-HSA-112409: RAF-independent MAPK1/3 activation
R-HSA-5673001: RAF/MAP kinase cascade
R-HSA-8853659: RET signaling
R-HSA-180336: SHC1 events in EGFR signaling
R-HSA-112412: SOS-mediated signalling
R-HSA-162582: Signal Transduction
R-HSA-445144: Signal transduction by L1
R-HSA-6802952: Signaling by BRAF and RAF fusions
R-HSA-177929: Signaling by EGFR
R-HSA-372790: Signaling by GPCR
R-HSA-74752: Signaling by Insulin receptor
R-HSA-449147: Signaling by Interleukins
R-HSA-2586552: Signaling by Leptin
R-HSA-186797: Signaling by PDGF
R-HSA-6802949: Signaling by RAS mutants
R-HSA-1433557: Signaling by SCF-KIT
R-HSA-2404192: Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
R-HSA-194138: Signaling by VEGF
R-HSA-6802948: Signaling by high-kinase activity BRAF mutants
R-HSA-6802946: Signaling by moderate kinase activity BRAF mutants
R-HSA-166520: Signalling by NGF
R-HSA-187687: Signalling to ERKs
R-HSA-167044: Signalling to RAS
R-HSA-187706: Signalling to p38 via RIT and RIN
R-HSA-5339562: Uptake and actions of bacterial toxins
R-HSA-5210891: Uptake and function of anthrax toxins
R-HSA-4420097: VEGFA-VEGFR2 Pathway
R-HSA-5218921: VEGFR2 mediated cell proliferation
Summary
SymbolMAP2K2
Namemitogen-activated protein kinase kinase 2
Aliases MEK2; PRKMK2; CFC4; MAPKK2; MKK2; ERK activator kinase 2; MAP kinase kinase 2; MAPK/ERK kinase 2; mitogen-ac ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between MAP2K2 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 MAP2K2 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
25294906Thyroid Gland Papillary CarcinomaInhibit immunity (infiltration)Treatment of PTC cell lines with the MEK1/2 inhibitor selumetinib or IFN increased HLA-ABC expression. Both MHC class I and β2-microglobulin expression was reduced or absent in 76% of PTC specimens and was associated with reduced tumor-infiltrating immune cells, including effector (CD3(+), CD8(+), CD16(+)) and suppressor (FoxP3(+)) populations.
Summary
SymbolMAP2K2
Namemitogen-activated protein kinase kinase 2
Aliases MEK2; PRKMK2; CFC4; MAPKK2; MKK2; ERK activator kinase 2; MAP kinase kinase 2; MAPK/ERK kinase 2; mitogen-ac ......
Chromosomal Location19p13.3
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 MAP2K2 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 NA/NS NA/NS
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 Total # shRNA with >= 4-fold: 1 Resistant to T-cell proliferation
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolMAP2K2
Namemitogen-activated protein kinase kinase 2
Aliases MEK2; PRKMK2; CFC4; MAPKK2; MKK2; ERK activator kinase 2; MAP kinase kinase 2; MAPK/ERK kinase 2; mitogen-ac ......
Chromosomal Location19p13.3
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 MAP2K2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.0240.944
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.1770.952
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.0840.97
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.2570.485
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.3090.887
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.1940.946
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.1680.672
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.3410.841
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.0110.996
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.1430.94
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.3540.901
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.0210.7
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of MAP2K2 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) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 414250250.222
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.703.70.27
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.703.70.314
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) 91611.16.24.91
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 592011.18.91
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
SymbolMAP2K2
Namemitogen-activated protein kinase kinase 2
Aliases MEK2; PRKMK2; CFC4; MAPKK2; MKK2; ERK activator kinase 2; MAP kinase kinase 2; MAPK/ERK kinase 2; mitogen-ac ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of MAP2K2. 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
SymbolMAP2K2
Namemitogen-activated protein kinase kinase 2
Aliases MEK2; PRKMK2; CFC4; MAPKK2; MKK2; ERK activator kinase 2; MAP kinase kinase 2; MAPK/ERK kinase 2; mitogen-ac ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of MAP2K2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by MAP2K2.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolMAP2K2
Namemitogen-activated protein kinase kinase 2
Aliases MEK2; PRKMK2; CFC4; MAPKK2; MKK2; ERK activator kinase 2; MAP kinase kinase 2; MAPK/ERK kinase 2; mitogen-ac ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of MAP2K2. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolMAP2K2
Namemitogen-activated protein kinase kinase 2
Aliases MEK2; PRKMK2; CFC4; MAPKK2; MKK2; ERK activator kinase 2; MAP kinase kinase 2; MAPK/ERK kinase 2; mitogen-ac ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of MAP2K2 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolMAP2K2
Namemitogen-activated protein kinase kinase 2
Aliases MEK2; PRKMK2; CFC4; MAPKK2; MKK2; ERK activator kinase 2; MAP kinase kinase 2; MAPK/ERK kinase 2; mitogen-ac ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between MAP2K2 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolMAP2K2
Namemitogen-activated protein kinase kinase 2
Aliases MEK2; PRKMK2; CFC4; MAPKK2; MKK2; ERK activator kinase 2; MAP kinase kinase 2; MAPK/ERK kinase 2; mitogen-ac ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting MAP2K2 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting MAP2K2.
ID Name Drug Type Targets #Targets
DB06616BosutinibSmall MoleculeABL1, BCR, CAMK2G, CDK2, HCK, LYN, MAP2K1, MAP2K2, MAP3K2, SRC10
DB08911TrametinibSmall MoleculeMAP2K1, MAP2K22