TISIDB

Summary
Symbol	MAP2K1
Name	mitogen-activated protein kinase kinase 1
Aliases	MEK1; MAPKK1; PRKMK1; CFC3; MKK1; ERK activator kinase 1; MAPK/ERK kinase 1; MAPKK 1; MEK 1; protein kinase, ......
Chromosomal Location	15q22.1-q22.33
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, cytoskeleton, microtubule organizing center, centrosome Cytoplasm, cytoskeleton, microtubule organizing center, spindle pole body Cytoplasm Nucleus Membrane Peripheral membrane protein Note=Localizes at centrosomes during prometaphase, midzone during anaphase and midbody during telophase/cytokinesis (PubMed:14737111). Membrane localization is probably regulated by its interaction with KSR1 (PubMed:10409742).
Domain	PF00069 Protein kinase domain
Function	Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis.

> Gene Ontology [ TOP ]
Biological Process	GO:0000187 activation of MAPK activity GO:0001701 in utero embryonic development GO:0001890 placenta development GO:0001892 embryonic placenta development GO:0006417 regulation of translation GO:0007030 Golgi organization GO:0007034 vacuolar transport GO:0007050 cell cycle arrest GO:0007409 axonogenesis GO:0007507 heart development GO:0007568 aging GO:0007569 cell aging GO:0008544 epidermis development GO:0009913 epidermal cell differentiation GO:0010001 glial cell differentiation GO:0010608 posttranscriptional regulation of gene expression GO:0010720 positive regulation of cell development GO:0010769 regulation of cell morphogenesis involved in differentiation GO:0010770 positive regulation of cell morphogenesis involved in differentiation GO:0010975 regulation of neuron projection development GO:0010976 positive regulation of neuron projection development GO:0016197 endosomal transport GO:0016441 posttranscriptional gene silencing GO:0016458 gene silencing GO:0016482 cytosolic transport GO:0017148 negative regulation of translation GO:0018108 peptidyl-tyrosine phosphorylation GO:0018212 peptidyl-tyrosine modification GO:0021549 cerebellum development GO:0021575 hindbrain morphogenesis GO:0021587 cerebellum morphogenesis GO:0021695 cerebellar cortex development GO:0021696 cerebellar cortex morphogenesis GO:0021697 cerebellar cortex formation GO:0022037 metencephalon development GO:0022604 regulation of cell morphogenesis GO:0030216 keratinocyte differentiation GO:0030323 respiratory tube development GO:0030324 lung development GO:0030878 thyroid gland development GO:0030902 hindbrain development GO:0031047 gene silencing by RNA GO:0031050 dsRNA fragmentation GO:0031098 stress-activated protein kinase signaling cascade GO:0031099 regeneration GO:0031102 neuron projection regeneration GO:0031103 axon regeneration GO:0031346 positive regulation of cell projection organization 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:0035270 endocrine system development GO:0035897 proteolysis in other organism GO:0040029 regulation of gene expression, epigenetic GO:0042063 gliogenesis 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:0043588 skin development GO:0044033 multi-organism metabolic process GO:0045022 early endosome to late endosome transport GO:0045666 positive regulation of neuron differentiation GO:0045786 negative regulation of cell cycle GO:0045860 positive regulation of protein kinase activity GO:0048308 organelle inheritance GO:0048313 Golgi inheritance GO:0048538 thymus development GO:0048568 embryonic organ development GO:0048608 reproductive structure development GO:0048645 animal organ formation GO:0048667 cell morphogenesis involved in neuron differentiation GO:0048678 response to axon injury GO:0048679 regulation of axon regeneration GO:0048708 astrocyte differentiation GO:0048732 gland development GO:0050673 epithelial cell proliferation GO:0050769 positive regulation of neurogenesis GO:0050770 regulation of axonogenesis GO:0050772 positive regulation of axonogenesis GO:0051403 stress-activated MAPK cascade GO:0051962 positive regulation of nervous system development GO:0060020 Bergmann glial cell differentiation GO:0060147 regulation of posttranscriptional gene silencing GO:0060148 positive regulation of posttranscriptional gene silencing GO:0060324 face development GO:0060425 lung morphogenesis GO:0060428 lung epithelium development GO:0060438 trachea development GO:0060439 trachea morphogenesis GO:0060440 trachea formation GO:0060502 epithelial cell proliferation involved in lung morphogenesis GO:0060541 respiratory system development GO:0060627 regulation of vesicle-mediated transport GO:0060674 placenta blood vessel development GO:0060711 labyrinthine layer development GO:0060964 regulation of gene silencing by miRNA GO:0060966 regulation of gene silencing by RNA GO:0060968 regulation of gene silencing GO:0061458 reproductive system development GO:0061564 axon development 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:0070570 regulation of neuron projection regeneration 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:0090398 cellular senescence GO:0098927 vesicle-mediated transport between endosomal compartments GO:1903034 regulation of response to wounding 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:0004721 phosphoprotein phosphatase activity GO:0004725 protein tyrosine phosphatase activity GO:0004728 receptor signaling protein tyrosine phosphatase activity GO:0005057 receptor signaling protein activity GO:0008022 protein C-terminus binding GO:0008047 enzyme activator activity GO:0016791 phosphatase activity GO:0019207 kinase regulator activity GO:0019209 kinase activator activity GO:0019887 protein kinase regulator activity GO:0030295 protein kinase activator activity GO:0042578 phosphoric ester hydrolase activity GO:0043539 protein serine/threonine kinase activator activity GO:0047485 protein N-terminus binding
Cellular Component	GO:0000922 spindle pole GO:0005769 early endosome GO:0005770 late endosome GO:0005816 spindle pole body GO:0005819 spindle GO:0005924 cell-substrate adherens junction GO:0005925 focal adhesion GO:0030055 cell-substrate junction

> KEGG and Reactome Pathway [ TOP ]
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 hsa04062 Chemokine signaling pathway hsa04066 HIF-1 signaling pathway hsa04068 FoxO signaling pathway hsa04071 Sphingolipid signaling pathway hsa04114 Oocyte meiosis hsa04140 Regulation of autophagy hsa04150 mTOR signaling pathway hsa04151 PI3K-Akt signaling pathway hsa04210 Apoptosis hsa04270 Vascular smooth muscle contraction hsa04320 Dorso-ventral axis formation hsa04370 VEGF signaling pathway hsa04380 Osteoclast differentiation hsa04510 Focal adhesion 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 hsa04666 Fc gamma R-mediated phagocytosis hsa04668 TNF signaling pathway hsa04720 Long-term potentiation hsa04722 Neurotrophin signaling pathway hsa04725 Cholinergic synapse hsa04726 Serotonergic synapse hsa04730 Long-term depression hsa04810 Regulation of actin cytoskeleton hsa04910 Insulin signaling pathway hsa04912 GnRH signaling pathway hsa04914 Progesterone-mediated oocyte maturation 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-166054: Activated TLR4 signalling 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-446652: Interleukin-1 signaling R-HSA-451927: Interleukin-2 signaling R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling R-HSA-373760: L1CAM interactions R-HSA-450294: MAP kinase activation in TLR cascade R-HSA-5674135: MAP2K and MAPK activation R-HSA-5684264: MAP3K8 (TPL2)-dependent MAPK1/3 activation R-HSA-5683057: MAPK family signaling cascades R-HSA-5684996: MAPK1/MAPK3 signaling R-HSA-110056: MAPK3 (ERK1) activation 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-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-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 R-HSA-4420097: VEGFA-VEGFR2 Pathway R-HSA-5218921: VEGFR2 mediated cell proliferation

> KEGG and Reactome Pathway

[ TOP ]

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
hsa04062 Chemokine signaling pathway
hsa04066 HIF-1 signaling pathway
hsa04068 FoxO signaling pathway
hsa04071 Sphingolipid signaling pathway
hsa04114 Oocyte meiosis
hsa04140 Regulation of autophagy
hsa04150 mTOR signaling pathway
hsa04151 PI3K-Akt signaling pathway
hsa04210 Apoptosis
hsa04270 Vascular smooth muscle contraction
hsa04320 Dorso-ventral axis formation
hsa04370 VEGF signaling pathway
hsa04380 Osteoclast differentiation
hsa04510 Focal adhesion
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
hsa04666 Fc gamma R-mediated phagocytosis
hsa04668 TNF signaling pathway
hsa04720 Long-term potentiation
hsa04722 Neurotrophin signaling pathway
hsa04725 Cholinergic synapse
hsa04726 Serotonergic synapse
hsa04730 Long-term depression
hsa04810 Regulation of actin cytoskeleton
hsa04910 Insulin signaling pathway
hsa04912 GnRH signaling pathway
hsa04914 Progesterone-mediated oocyte maturation
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-166054: Activated TLR4 signalling
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-446652: Interleukin-1 signaling
R-HSA-451927: Interleukin-2 signaling
R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling
R-HSA-373760: L1CAM interactions
R-HSA-450294: MAP kinase activation in TLR cascade
R-HSA-5674135: MAP2K and MAPK activation
R-HSA-5684264: MAP3K8 (TPL2)-dependent MAPK1/3 activation
R-HSA-5683057: MAPK family signaling cascades
R-HSA-5684996: MAPK1/MAPK3 signaling
R-HSA-110056: MAPK3 (ERK1) activation
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-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-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
R-HSA-4420097: VEGFA-VEGFR2 Pathway
R-HSA-5218921: VEGFR2 mediated cell proliferation

Summary
Symbol	MAP2K1
Name	mitogen-activated protein kinase kinase 1
Aliases	MEK1; MAPKK1; PRKMK1; CFC3; MKK1; ERK activator kinase 1; MAPK/ERK kinase 1; MAPKK 1; MEK 1; protein kinase, ......
Chromosomal Location	15q22.1-q22.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between MAP2K1 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 ]

Literatures describing the relation between MAP2K1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
26707829	Melanoma	Resistant to immunotherapy	The greatest survival improvement was observed with the combination of BRAF plus MEK inhibitors as well as with Programmed-death-1 (PD1) blockers with or without cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) blockers, respectively, with these two treatment strategies showing similar survival outcomes.
26880715	Lung Carcinoma	Inhibit immunity (T cell function)	Overexpression of the mutant KRAS(G12V)gene in wild-type KRAS tumor cells led to regulatory T-cell (Treg) induction. We also demonstrate that mutant KRAS induces the secretion of IL10 and transforming growth factor-β1 (both required for Treg induction) by tumor cells through the activation of the MEK-ERK-AP1 pathway.
25294906	Thyroid Gland Papillary Carcinoma	Inhibit 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.
27656909	Melanoma; Breast Carcinoma	Inhibit immunity; immunotherapy target	The combinations of nanoscale MEK- and PI3K-targeting supramolecular therapeutics with checkpoint PDL1 and PD1 inhibitors exert enhanced antitumor outcome in melanoma and breast cancers in vivo, respectively.
18008004	Melanoma	Inhibit immunity (T cell function)	Employing 2 independent, genome-wide microarray analyses, we identified CD200 as a highly dynamic, downstream target of RAS/RAF/MEK/ERK activation in melanoma. CD200 protein was similarly overexpressed in human melanoma cell lines and primary tumors. Melanoma cell lines expressing endogenous CD200 repressed primary T cell activation by DCs, while knockdown of CD200 by shRNA abrogated this immunosuppressive effect.
17363736	Multiple Myeloma-IgG	Inhibit immunity (T cell function)	We observed that B7-H1 was expressed in most MM plasma cells, but not cells isolated from monoclonal gammopathy of undetermined significance or healthy donors. This expression was increased or induced by IFN-gamma and Toll-like receptor (TLR) ligands in isolated MM plasma cells. Blocking the MEK/ERK pathway inhibited IFN-gamma-mediated and TLR-mediated expression of B7-H1. Inhibition of the MyD88 and TRAF6 adaptor proteins of the TLR pathway blocked not only B7-H1 expression induced by TLR ligands but also that mediated by IFN-gamma. IFN-gamma-induced STAT1 activation, via MEK/ERK and MyD88/TRAF6, and inhibition of STAT1 reduced B7-H1 expression. MM plasma cells stimulated with IFN-gamma or TLR ligands inhibited cytotoxic T lymphocytes (CTLs) generation and this immunosuppressive effect was inhibited by preincubation with an anti-B7-H1 antibody, the UO126 MEK inhibitor, or by transfection of a dominant-negative mutant of MyD88.
23878189	chronic myelogenous leukemia	Inhibit immunity	Importantly, a recent study demonstrated that engagement of the MEK/Erk pathway is critical for IFNa-induced phosphodiesterase 4 (PDE4) activation and repression ofcAMP in Treg cells (78). This study provided evidence for a novel type I IFN-induced, Erk-mediated, function, involving inhibition of the suppressive effects of Tregs on CD4? T cells and NK cells
16917008	Multiple myeloma(IgA, IgD, IgE, IgM, IgG)	Promote immunity	These abnormalities may be attributed to elevated production of autocrine cytokines such as IL-6, activated p38 and STAT3, and inhibited MEK/ERK signaling pathways in the progenitor cells. Treatment with neutralizing IL-6-specific antibody and, more importantly, p38 inhibitor, or both, could correct these abnormalities. Treating patient-derived cells with these agents not only significantly increased cell yield but also produced MoDCs that were as functional as their normal counterparts.

Summary
Symbol	MAP2K1
Name	mitogen-activated protein kinase kinase 1
Aliases	MEK1; MAPKK1; PRKMK1; CFC3; MKK1; ERK activator kinase 1; MAPK/ERK kinase 1; MAPKK 1; MEK 1; protein kinase, ......
Chromosomal Location	15q22.1-q22.33
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 MAP2K1 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	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	MAP2K1
Name	mitogen-activated protein kinase kinase 1
Aliases	MEK1; MAPKK1; PRKMK1; CFC3; MKK1; ERK activator kinase 1; MAPK/ERK kinase 1; MAPKK 1; MEK 1; protein kinase, ......
Chromosomal Location	15q22.1-q22.33
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 MAP2K1 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	0.085	0.69
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.272	0.903
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.043	0.977
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.254	0.451
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.169	0.924
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.365	0.875
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.035	0.932
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.135	0.934
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.015	0.993
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.28	0.846
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	0.916	0.672
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.047	0.409

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of MAP2K1 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	18.5	1.4	17.1	0.00519
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	18.5	1.7	16.8	0.0108
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	5.9	-1.1	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	9.1	-1.4	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	6.2	4.9	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	25	0	25	0.364
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	10.5	0	10.5	0.135
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	0	9.1	0.519
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	12.5	0	12.5	0.485
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	MAP2K1
Name	mitogen-activated protein kinase kinase 1
Aliases	MEK1; MAPKK1; PRKMK1; CFC3; MKK1; ERK activator kinase 1; MAPK/ERK kinase 1; MAPKK 1; MEK 1; protein kinase, ......
Chromosomal Location	15q22.1-q22.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of MAP2K1. 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	MAP2K1
Name	mitogen-activated protein kinase kinase 1
Aliases	MEK1; MAPKK1; PRKMK1; CFC3; MKK1; ERK activator kinase 1; MAPK/ERK kinase 1; MAPKK 1; MEK 1; protein kinase, ......
Chromosomal Location	15q22.1-q22.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of MAP2K1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by MAP2K1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	MAP2K1
Name	mitogen-activated protein kinase kinase 1
Aliases	MEK1; MAPKK1; PRKMK1; CFC3; MKK1; ERK activator kinase 1; MAPK/ERK kinase 1; MAPKK 1; MEK 1; protein kinase, ......
Chromosomal Location	15q22.1-q22.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of MAP2K1. 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	MAP2K1
Name	mitogen-activated protein kinase kinase 1
Aliases	MEK1; MAPKK1; PRKMK1; CFC3; MKK1; ERK activator kinase 1; MAPK/ERK kinase 1; MAPKK 1; MEK 1; protein kinase, ......
Chromosomal Location	15q22.1-q22.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of MAP2K1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	MAP2K1
Name	mitogen-activated protein kinase kinase 1
Aliases	MEK1; MAPKK1; PRKMK1; CFC3; MKK1; ERK activator kinase 1; MAPK/ERK kinase 1; MAPKK 1; MEK 1; protein kinase, ......
Chromosomal Location	15q22.1-q22.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between MAP2K1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	MAP2K1
Name	mitogen-activated protein kinase kinase 1
Aliases	MEK1; MAPKK1; PRKMK1; CFC3; MKK1; ERK activator kinase 1; MAPK/ERK kinase 1; MAPKK 1; MEK 1; protein kinase, ......
Chromosomal Location	15q22.1-q22.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting MAP2K1 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting MAP2K1.

ID	Name	Drug Type	Targets	#Targets
DB02152	K-252a	Small Molecule	MAP2K1, MET	2
DB03115	5-Bromo-N-(2,3-Dihydroxypropoxy)-3,4-Difluoro-2-[(2-Fluoro-4-Iodophenyl)Amino]Benzamide	Small Molecule	MAP2K1	1
DB05239	Cobimetinib	Small Molecule	MAP2K1	1
DB06616	Bosutinib	Small Molecule	ABL1, BCR, CAMK2G, CDK2, HCK, LYN, MAP2K1, MAP2K2, MAP3K2, SRC	10
DB06892	(5S)-4,5-difluoro-6-[(2-fluoro-4-iodophenyl)imino]-N-(2-hydroxyethoxy)cyclohexa-1,3-diene-1-carboxamide	Small Molecule	MAP2K1	1
DB07046	2-[(2-chloro-4-iodophenyl)amino]-N-{[(2R)-2,3-dihydroxypropyl]oxy}-3,4-difluorobenzamide	Small Molecule	MAP2K1	1
DB07101	PD-0325901	Small Molecule	MAP2K1	1
DB08130	N-(5-{3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}-1,3,4-oxadiazol-2-yl)ethane-1,2-diamine	Small Molecule	MAP2K1	1
DB08208	2-[(4-ETHYNYL-2-FLUOROPHENYL)AMINO]-3,4-DIFLUORO-N-(2-HYDROXYETHOXY)BENZAMIDE	Small Molecule	MAP2K1	1
DB08911	Trametinib	Small Molecule	MAP2K1, MAP2K2	2

Browse MAP2K1