TISIDB

Summary
Symbol	MAPK1
Name	mitogen-activated protein kinase 1
Aliases	ERK2; p41mapk; MAPK2; PRKM2; PRKM1; ERK-2; ERT1; P42MAPK; p41; p42-MAPK; MAP kinase 1; MAP kinase 2; MAP kin ......
Chromosomal Location	22q11.2
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 [ TOP ]
Subcellular Location	Cytoplasm, cytoskeleton, spindle Nucleus. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm. Membrane, caveola Note=Associated with the spindle during prometaphase and metaphase (By similarity). PEA15-binding and phosphorylated DAPK1 promote its cytoplasmic retention. Phosphorylation at Ser- 246 and Ser-248 as well as autophosphorylation at Thr-190 promote nuclear localization.
Domain	PF00069 Protein kinase domain
Function	Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the 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. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Mediates phosphorylation of TPR in respons to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation. Phosphorylates CDK2AP2 (By similarity). ; FUNCTION: Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity.

> Gene Ontology [ TOP ]
Biological Process	GO:0000187 activation of MAPK activity GO:0000189 MAPK import into nucleus GO:0000723 telomere maintenance GO:0001503 ossification GO:0001701 in utero embryonic development GO:0001890 placenta development GO:0001892 embryonic placenta development GO:0002237 response to molecule of bacterial origin GO:0002429 immune response-activating cell surface receptor signaling pathway GO:0002431 Fc receptor mediated stimulatory signaling pathway GO:0002433 immune response-regulating cell surface receptor signaling pathway involved in phagocytosis GO:0002757 immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0002768 immune response-regulating cell surface receptor signaling pathway GO:0006206 pyrimidine nucleobase metabolic process GO:0006278 RNA-dependent DNA biosynthetic process GO:0006417 regulation of translation GO:0006606 protein import into nucleus GO:0006909 phagocytosis GO:0006913 nucleocytoplasmic transport GO:0007004 telomere maintenance via telomerase GO:0007030 Golgi organization GO:0007034 vacuolar transport GO:0007259 JAK-STAT cascade GO:0007409 axonogenesis GO:0007411 axon guidance GO:0007423 sensory organ development GO:0007507 heart development GO:0007596 blood coagulation GO:0007599 hemostasis GO:0008543 fibroblast growth factor receptor signaling pathway GO:0009112 nucleobase metabolic process GO:0009266 response to temperature stimulus GO:0009408 response to heat GO:0009636 response to toxic substance GO:0010001 glial cell differentiation GO:0010608 posttranscriptional regulation of gene expression GO:0010799 regulation of peptidyl-threonine phosphorylation GO:0010800 positive regulation of peptidyl-threonine phosphorylation GO:0010833 telomere maintenance via telomere lengthening GO:0014031 mesenchymal cell development GO:0014032 neural crest cell development GO:0014033 neural crest cell differentiation GO:0014065 phosphatidylinositol 3-kinase signaling GO:0014066 regulation of phosphatidylinositol 3-kinase signaling GO:0016197 endosomal transport GO:0016233 telomere capping GO:0016482 cytosolic transport GO:0017038 protein import GO:0018105 peptidyl-serine phosphorylation GO:0018107 peptidyl-threonine phosphorylation GO:0018209 peptidyl-serine modification GO:0018210 peptidyl-threonine modification GO:0019233 sensory perception of pain GO:0019858 cytosine metabolic process GO:0030168 platelet activation GO:0030278 regulation of ossification GO:0030323 respiratory tube development GO:0030324 lung development GO:0030335 positive regulation of cell migration GO:0030878 thyroid gland development GO:0030879 mammary gland development GO:0031098 stress-activated protein kinase signaling cascade GO:0031647 regulation of protein stability GO:0031663 lipopolysaccharide-mediated signaling pathway 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:0032386 regulation of intracellular transport GO:0032496 response to lipopolysaccharide GO:0032844 regulation of homeostatic process GO:0032846 positive regulation of homeostatic process GO:0032872 regulation of stress-activated MAPK cascade GO:0033044 regulation of chromosome organization GO:0033598 mammary gland epithelial cell proliferation GO:0033674 positive regulation of kinase activity GO:0034248 regulation of cellular amide metabolic process GO:0034250 positive regulation of cellular amide metabolic process GO:0034504 protein localization to nucleus GO:0034605 cellular response to heat GO:0035051 cardiocyte differentiation GO:0035270 endocrine system development GO:0038093 Fc receptor signaling pathway GO:0038094 Fc-gamma receptor signaling pathway GO:0038095 Fc-epsilon receptor signaling pathway GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis GO:0038127 ERBB signaling pathway GO:0040017 positive regulation of locomotion GO:0042063 gliogenesis GO:0042471 ear morphogenesis GO:0042473 outer ear morphogenesis GO:0043330 response to exogenous dsRNA 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:0043434 response to peptide hormone GO:0043583 ear development GO:0043627 response to estrogen GO:0044344 cellular response to fibroblast growth factor stimulus GO:0044744 protein targeting to nucleus GO:0045022 early endosome to late endosome transport GO:0045727 positive regulation of translation GO:0045860 positive regulation of protein kinase activity GO:0048015 phosphatidylinositol-mediated signaling GO:0048017 inositol lipid-mediated signaling GO:0048167 regulation of synaptic plasticity GO:0048308 organelle inheritance GO:0048313 Golgi inheritance GO:0048538 thymus development GO:0048562 embryonic organ morphogenesis GO:0048568 embryonic organ development GO:0048608 reproductive structure development GO:0048645 animal organ formation GO:0048667 cell morphogenesis involved in neuron differentiation GO:0048708 astrocyte differentiation GO:0048732 gland development GO:0048762 mesenchymal cell differentiation GO:0048863 stem cell differentiation GO:0048864 stem cell development GO:0050673 epithelial cell proliferation GO:0050804 modulation of synaptic transmission GO:0050806 positive regulation of synaptic transmission GO:0050817 coagulation GO:0050851 antigen receptor-mediated signaling pathway GO:0050852 T cell receptor signaling pathway GO:0050853 B cell receptor signaling pathway GO:0050878 regulation of body fluid levels GO:0051052 regulation of DNA metabolic process GO:0051054 positive regulation of DNA metabolic process GO:0051090 regulation of sequence-specific DNA binding transcription factor activity GO:0051169 nuclear transport GO:0051170 nuclear import GO:0051272 positive regulation of cellular component movement GO:0051403 stress-activated MAPK cascade GO:0051493 regulation of cytoskeleton organization GO:0051972 regulation of telomerase activity GO:0051973 positive regulation of telomerase activity GO:0060020 Bergmann glial cell differentiation GO:0060249 anatomical structure homeostasis GO:0060291 long-term synaptic potentiation GO:0060324 face development GO:0060396 growth hormone receptor signaling pathway GO:0060397 JAK-STAT cascade involved in growth hormone signaling pathway GO:0060416 response to growth hormone GO:0060425 lung morphogenesis GO:0060438 trachea development GO:0060439 trachea morphogenesis GO:0060440 trachea formation GO:0060485 mesenchyme development GO:0060541 respiratory system development GO:0060627 regulation of vesicle-mediated transport GO:0060674 placenta blood vessel development GO:0060711 labyrinthine layer development GO:0060716 labyrinthine layer blood vessel development GO:0061180 mammary gland epithelium development GO:0061307 cardiac neural crest cell differentiation involved in heart development GO:0061308 cardiac neural crest cell development involved in heart development 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:0070849 response to epidermal growth factor GO:0071216 cellular response to biotic stimulus GO:0071219 cellular response to molecule of bacterial origin GO:0071222 cellular response to lipopolysaccharide GO:0071375 cellular response to peptide hormone stimulus GO:0071378 cellular response to growth hormone stimulus GO:0071396 cellular response to lipid GO:0071417 cellular response to organonitrogen compound GO:0071774 response to fibroblast growth factor 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:0072527 pyrimidine-containing compound metabolic process GO:0072584 caveolin-mediated endocytosis GO:0090170 regulation of Golgi inheritance GO:0090596 sensory organ morphogenesis GO:0097011 cellular response to granulocyte macrophage colony-stimulating factor stimulus GO:0097012 response to granulocyte macrophage colony-stimulating factor GO:0097485 neuron projection guidance GO:0097696 STAT cascade GO:0098927 vesicle-mediated transport between endosomal compartments GO:1900034 regulation of cellular response to heat GO:1901652 response to peptide GO:1901653 cellular response to peptide GO:1902593 single-organism nuclear import GO:1903335 regulation of vacuolar transport GO:1903358 regulation of Golgi organization GO:1903649 regulation of cytoplasmic transport 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:2000147 positive regulation of cell motility GO:2000278 regulation of DNA biosynthetic process GO:2000573 positive regulation of DNA biosynthetic process GO:2000641 regulation of early endosome to late endosome transport GO:2001252 positive regulation of chromosome organization
Molecular Function	GO:0001784 phosphotyrosine binding GO:0004674 protein serine/threonine kinase activity GO:0004702 receptor signaling protein serine/threonine kinase activity GO:0004707 MAP kinase activity GO:0005057 receptor signaling protein activity GO:0008134 transcription factor binding GO:0008353 RNA polymerase II carboxy-terminal domain kinase activity GO:0019902 phosphatase binding GO:0031435 mitogen-activated protein kinase kinase kinase binding GO:0045309 protein phosphorylated amino acid binding GO:0051219 phosphoprotein binding
Cellular Component	GO:0005769 early endosome GO:0005770 late endosome GO:0005819 spindle GO:0005901 caveola GO:0005924 cell-substrate adherens junction GO:0005925 focal adhesion GO:0030055 cell-substrate junction GO:0030424 axon GO:0030425 dendrite GO:0031143 pseudopodium GO:0032838 cell projection cytoplasm GO:0032839 dendrite cytoplasm GO:0043025 neuronal cell body GO:0043204 perikaryon GO:0044297 cell body GO:0044853 plasma membrane raft GO:0045121 membrane raft GO:0072686 mitotic spindle GO:0098589 membrane region GO:0098857 membrane microdomain GO:0099568 cytoplasmic region

> 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 hsa04261 Adrenergic signaling in cardiomyocytes hsa04270 Vascular smooth muscle contraction hsa04320 Dorso-ventral axis formation hsa04350 TGF-beta signaling pathway hsa04360 Axon guidance hsa04370 VEGF signaling pathway hsa04380 Osteoclast differentiation hsa04510 Focal adhesion hsa04520 Adherens junction hsa04540 Gap junction hsa04550 Signaling pathways regulating pluripotency of stem cells hsa04611 Platelet activation hsa04620 Toll-like receptor signaling pathway hsa04621 NOD-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 hsa04713 Circadian entrainment hsa04720 Long-term potentiation hsa04722 Neurotrophin signaling pathway hsa04723 Retrograde endocannabinoid signaling hsa04724 Glutamatergic synapse 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 hsa04960 Aldosterone-regulated sodium reabsorption
Reactome	R-HSA-170984: ARMS-mediated activation R-HSA-166054: Activated TLR4 signalling R-HSA-442755: Activation of NMDA receptor upon glutamate binding and postsynaptic events R-HSA-450341: Activation of the AP-1 family of transcription factors R-HSA-1280218: Adaptive Immune System R-HSA-879415: Advanced glycosylation endproduct receptor signaling R-HSA-422475: Axon guidance R-HSA-442742: CREB phosphorylation through the activation of Ras R-HSA-111996: Ca-dependent events R-HSA-1640170: Cell Cycle R-HSA-69278: Cell Cycle, Mitotic R-HSA-2559583: Cellular Senescence R-HSA-3371556: Cellular response to heat stress R-HSA-2262752: Cellular responses to stress 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-1168372: Downstream signaling events of B Cell Receptor (BCR) R-HSA-198753: ERK/MAPK targets R-HSA-202670: ERKs are inactivated R-HSA-2871796: FCERI mediated MAPK activation R-HSA-2454202: Fc epsilon receptor (FCERI) signaling R-HSA-2029480: Fcgamma receptor (FCGR) dependent phagocytosis R-HSA-170968: Frs2-mediated activation R-HSA-112040: G-protein mediated events R-HSA-180292: GAB1 signalosome R-HSA-179812: GRB2 events in EGFR signaling R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK R-HSA-162658: Golgi Cisternae Pericentriolar Stack Reorganization R-HSA-982772: Growth hormone receptor signaling R-HSA-109582: Hemostasis 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-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-68886: M Phase R-HSA-450294: MAP kinase activation in TLR cascade R-HSA-5674135: MAP2K and MAPK activation R-HSA-5683057: MAPK family signaling cascades R-HSA-450282: MAPK targets/ Nuclear events mediated by MAP kinases R-HSA-112411: MAPK1 (ERK2) activation R-HSA-5684996: MAPK1/MAPK3 signaling R-HSA-68875: Mitotic Prophase 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-5654726: Negative regulation of FGFR1 signaling R-HSA-5654727: Negative regulation of FGFR2 signaling R-HSA-5654732: Negative regulation of FGFR3 signaling R-HSA-5654733: Negative regulation of FGFR4 signaling R-HSA-5675221: Negative regulation of MAPK pathway R-HSA-199418: Negative regulation of the PI3K/AKT network R-HSA-112316: Neuronal System R-HSA-112314: Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell R-HSA-6798695: Neutrophil degranulation R-HSA-198725: Nuclear Events (kinase and transcription factor activation) R-HSA-2559585: Oncogene Induced Senescence R-HSA-6802957: Oncogenic MAPK signaling R-HSA-111885: Opioid Signalling R-HSA-2559580: Oxidative Stress Induced Senescence R-HSA-198203: PI3K/AKT activation R-HSA-6811558: PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-HSA-1257604: PIP3 activates AKT signaling R-HSA-112043: PLC beta mediated events R-HSA-6802955: Paradoxical activation of RAF signaling by kinase inactive BRAF R-HSA-76002: Platelet activation, signaling and aggregation R-HSA-438064: Post NMDA receptor activation events R-HSA-169893: Prolonged ERK activation events R-HSA-112409: RAF-independent MAPK1/3 activation R-HSA-5673001: RAF/MAP kinase cascade R-HSA-8853659: RET signaling R-HSA-195258: RHO GTPase Effectors R-HSA-5663213: RHO GTPases Activate WASPs and WAVEs R-HSA-444257: RSK activation R-HSA-437239: Recycling pathway of L1 R-HSA-3371453: Regulation of HSF1-mediated heat shock response R-HSA-2029482: Regulation of actin dynamics for phagocytic cup formation R-HSA-2730905: Role of LAT2/NTAL/LAB on calcium mobilization R-HSA-180336: SHC1 events in EGFR signaling R-HSA-112412: SOS-mediated signalling R-HSA-2559582: Senescence-Associated Secretory Phenotype (SASP) R-HSA-162582: Signal Transduction R-HSA-74749: Signal attenuation R-HSA-445144: Signal transduction by L1 R-HSA-6802952: Signaling by BRAF and RAF fusions R-HSA-177929: Signaling by EGFR R-HSA-190236: Signaling by FGFR R-HSA-5654736: Signaling by FGFR1 R-HSA-5654738: Signaling by FGFR2 R-HSA-5654741: Signaling by FGFR3 R-HSA-5654743: Signaling by FGFR4 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-194315: Signaling by Rho GTPases 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-983705: Signaling by the B Cell Receptor (BCR) 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-1295596: Spry regulation of FGF signaling 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-456926: Thrombin signalling through proteinase activated receptors (PARs) 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-112315: Transmission across Chemical Synapses R-HSA-4420097: VEGFA-VEGFR2 Pathway R-HSA-5218921: VEGFR2 mediated cell proliferation R-HSA-111995: phospho-PLA2 pathway

> 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
hsa04261 Adrenergic signaling in cardiomyocytes
hsa04270 Vascular smooth muscle contraction
hsa04320 Dorso-ventral axis formation
hsa04350 TGF-beta signaling pathway
hsa04360 Axon guidance
hsa04370 VEGF signaling pathway
hsa04380 Osteoclast differentiation
hsa04510 Focal adhesion
hsa04520 Adherens junction
hsa04540 Gap junction
hsa04550 Signaling pathways regulating pluripotency of stem cells
hsa04611 Platelet activation
hsa04620 Toll-like receptor signaling pathway
hsa04621 NOD-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
hsa04713 Circadian entrainment
hsa04720 Long-term potentiation
hsa04722 Neurotrophin signaling pathway
hsa04723 Retrograde endocannabinoid signaling
hsa04724 Glutamatergic synapse
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
hsa04960 Aldosterone-regulated sodium reabsorption

Reactome

R-HSA-170984: ARMS-mediated activation
R-HSA-166054: Activated TLR4 signalling
R-HSA-442755: Activation of NMDA receptor upon glutamate binding and postsynaptic events
R-HSA-450341: Activation of the AP-1 family of transcription factors
R-HSA-1280218: Adaptive Immune System
R-HSA-879415: Advanced glycosylation endproduct receptor signaling
R-HSA-422475: Axon guidance
R-HSA-442742: CREB phosphorylation through the activation of Ras
R-HSA-111996: Ca-dependent events
R-HSA-1640170: Cell Cycle
R-HSA-69278: Cell Cycle, Mitotic
R-HSA-2559583: Cellular Senescence
R-HSA-3371556: Cellular response to heat stress
R-HSA-2262752: Cellular responses to stress
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-1168372: Downstream signaling events of B Cell Receptor (BCR)
R-HSA-198753: ERK/MAPK targets
R-HSA-202670: ERKs are inactivated
R-HSA-2871796: FCERI mediated MAPK activation
R-HSA-2454202: Fc epsilon receptor (FCERI) signaling
R-HSA-2029480: Fcgamma receptor (FCGR) dependent phagocytosis
R-HSA-170968: Frs2-mediated activation
R-HSA-112040: G-protein mediated events
R-HSA-180292: GAB1 signalosome
R-HSA-179812: GRB2 events in EGFR signaling
R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK
R-HSA-162658: Golgi Cisternae Pericentriolar Stack Reorganization
R-HSA-982772: Growth hormone receptor signaling
R-HSA-109582: Hemostasis
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-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-68886: M Phase
R-HSA-450294: MAP kinase activation in TLR cascade
R-HSA-5674135: MAP2K and MAPK activation
R-HSA-5683057: MAPK family signaling cascades
R-HSA-450282: MAPK targets/ Nuclear events mediated by MAP kinases
R-HSA-112411: MAPK1 (ERK2) activation
R-HSA-5684996: MAPK1/MAPK3 signaling
R-HSA-68875: Mitotic Prophase
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-5654726: Negative regulation of FGFR1 signaling
R-HSA-5654727: Negative regulation of FGFR2 signaling
R-HSA-5654732: Negative regulation of FGFR3 signaling
R-HSA-5654733: Negative regulation of FGFR4 signaling
R-HSA-5675221: Negative regulation of MAPK pathway
R-HSA-199418: Negative regulation of the PI3K/AKT network
R-HSA-112316: Neuronal System
R-HSA-112314: Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell
R-HSA-6798695: Neutrophil degranulation
R-HSA-198725: Nuclear Events (kinase and transcription factor activation)
R-HSA-2559585: Oncogene Induced Senescence
R-HSA-6802957: Oncogenic MAPK signaling
R-HSA-111885: Opioid Signalling
R-HSA-2559580: Oxidative Stress Induced Senescence
R-HSA-198203: PI3K/AKT activation
R-HSA-6811558: PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-1257604: PIP3 activates AKT signaling
R-HSA-112043: PLC beta mediated events
R-HSA-6802955: Paradoxical activation of RAF signaling by kinase inactive BRAF
R-HSA-76002: Platelet activation, signaling and aggregation
R-HSA-438064: Post NMDA receptor activation events
R-HSA-169893: Prolonged ERK activation events
R-HSA-112409: RAF-independent MAPK1/3 activation
R-HSA-5673001: RAF/MAP kinase cascade
R-HSA-8853659: RET signaling
R-HSA-195258: RHO GTPase Effectors
R-HSA-5663213: RHO GTPases Activate WASPs and WAVEs
R-HSA-444257: RSK activation
R-HSA-437239: Recycling pathway of L1
R-HSA-3371453: Regulation of HSF1-mediated heat shock response
R-HSA-2029482: Regulation of actin dynamics for phagocytic cup formation
R-HSA-2730905: Role of LAT2/NTAL/LAB on calcium mobilization
R-HSA-180336: SHC1 events in EGFR signaling
R-HSA-112412: SOS-mediated signalling
R-HSA-2559582: Senescence-Associated Secretory Phenotype (SASP)
R-HSA-162582: Signal Transduction
R-HSA-74749: Signal attenuation
R-HSA-445144: Signal transduction by L1
R-HSA-6802952: Signaling by BRAF and RAF fusions
R-HSA-177929: Signaling by EGFR
R-HSA-190236: Signaling by FGFR
R-HSA-5654736: Signaling by FGFR1
R-HSA-5654738: Signaling by FGFR2
R-HSA-5654741: Signaling by FGFR3
R-HSA-5654743: Signaling by FGFR4
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-194315: Signaling by Rho GTPases
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-983705: Signaling by the B Cell Receptor (BCR)
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-1295596: Spry regulation of FGF signaling
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-456926: Thrombin signalling through proteinase activated receptors (PARs)
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-112315: Transmission across Chemical Synapses
R-HSA-4420097: VEGFA-VEGFR2 Pathway
R-HSA-5218921: VEGFR2 mediated cell proliferation
R-HSA-111995: phospho-PLA2 pathway

Summary
Symbol	MAPK1
Name	mitogen-activated protein kinase 1
Aliases	ERK2; p41mapk; MAPK2; PRKM2; PRKM1; ERK-2; ERT1; P42MAPK; p41; p42-MAPK; MAP kinase 1; MAP kinase 2; MAP kin ......
Chromosomal Location	22q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between MAPK1 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 MAPK1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
28218497	Lymphoma	Inhibit immunity (T cell function)	Suppression of ERK by a chemical inhibitor or genetic silencing of ERK2 expression prevents drug-induced PD-L1 expression.
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.
26364607	Gastric Carcinoma	Promote immunity (NK cell function)	In contrast, another cell line AGS expressing low levels of HLA-I with activated NKp30/MAPK/IL-12 (interleukin-12) or IL-2 (interleukin-2) pathway was susceptible to NK lysis. Treatment of tumor bearing mice with systemic administration of IL-12 in combination with intratumor injection of anti-HLA-I antibody significantly increased NK cell recruitment into xenograft tumors, which became sensitive to NK killing, resulting in reduced tumor progression.
25658629	Non-Small Cell Lung Carcinoma	Inhibit immunity (T cell function)	EGFR activation upregulated PD-L1 through p-ERK1/2/p-c-Jun but not through p-AKT/p-S6 pathway. PD-L1 mediated by EGFR activation could induce the apoptosis of T cells through PD-L1/PD-1 axis in tumor cells and peripheral blood mononuclear cells coculture system.
25589622	E7+ tumor TC-1	Inhibit immunity (T cell function)	Gain of HIF-1α under normoxia in cancer mediates immune adaptation through the AKT/ERK and VEGFA axes. We found that tumor cells gain HIF-1α in the course of immune selection under normoxia and that HIF-1α renders tumor cells resistant to lysis by tumor-specific cytotoxic T lymphocytes (CTL) in culture and in mice.
25273090	Colon Carcinoma	Inhibit immunity (T cell function)	Tumor-derived osteopontin suppresses antitumor immunity by promoting extramedullary myelopoiesis. In this study, we found that osteopontin expressed by tumor cells enhances extramedullary myelopoiesis in a CD44-dependent manner through the Erk1/2-MAPK pathway.
25261236	Breast Carcinoma	Inhibit immunity	In this study, we show that DCs isolated from patients with metastatic or locally advanced breast cancer express high levels of the adiponectin receptors AdipoR1 and AdipoR2, which are sufficient to blunt antitumor immunity. AdipoR1 stimulated IL10 production by activating the AMPK and MAPKp38 pathways, whereas AdipoR2 modified inflammatory processes by activating the COX-2 and PPARγ pathways.
27364554	Melanoma; Lung carcinoma	Promote immunity (T cell function)	Here we show that activin A triggers SMAD2 and ERK1/2 pathways in dendritic cells (DC) expressing type I and II activin receptors, and upregulates production of the TNFα family cytokines BAFF (TALL-1, TNFSF13B) and APRIL (TALL-2, TNFSF13A), which is blocked by SMAD2 and ERK1/2 inhibitors, respectively. BAFF and APRIL derived from activin A-treated DCs upregulate proliferation and survival of T cells expressing the corresponding receptors, BAFF-R and TACI.
19299748	Plasma cell myeloma	Promote immunity	We next demonstrated that p38 MAPK pathway controlled both IFN-alpha secretion and IFN-alpha-mediated cell death. Moreover, cell death also involved activation of ERK1/2 pathway.
19278954	Leukemia	Promote immunity	This combination activated phospho-ZAP70 and phospho-ERK1/2 signaling in TCRVgamma9(+) cells and strongly enhanced their ADCC activity.
28536100	Mesothelioma	Inhibit immunity	We show that M-CSFR inhibition using the CSF-1R kinase inhibitor PLX3397 (pexidartinib) effectively reduced numbers of tumor-associated macrophages (TAMs) . TAM depletion could potentially reactivate antitumor immunity.
28533272	Melanoma; Renal Cell Carcinoma; Squamous Cell Carcinoma; Glioblastoma; Mastocytoma; Hepatocellular Carcinoma	Promote immunity (T cell function)	PD-1:28 engineering reinstated Th1 function in tumor-infiltrating lymphocytes that had been functionally disabled in the human renal cell carcinoma environment without unleashing undesired Th2 cytokines or IL10. Involved mechanisms may be correlated to restoration of ERK and AKT signaling pathways.
18025475	Actinic (Solar) Keratosis; Skin Basal Cell Carcinoma; Squamous Cell Carcinoma	Inhibit immunity (T cell function)	Here we demonstrate that human keratinocyte-derived skin tumors may evade T cell-mediated antitumor immune responses by down-regulating the expression of CCL27 through the activation of epidermal growth factor receptor (EGFR)-Ras-MAPK-signaling pathways. Compared with healthy skin, CCL27 mRNA and protein expression was progressively lost in transformed keratinocytes of actinic keratoses and basal and squamous cell carcinomas.
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.
21441454	Melanoma	Inhibit immunity	Interaction of LAG-3 with MHC II expressed on melanoma cells upregulates both MAPK/Erk and PI3K/Akt pathways, albeit with different kinetics. Inhibition studies using specific inhibitors of both pathways provided evidence of their involvement in the LAG-3-induced protection from apoptosis.
23878189	chronic myelogenous leukemia	Promote immunity(T/NK cell function)	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
21796616	Melanoma	Promote immunity	The production of multiple cytokines (IFNgamma, TNFalpha, IL-2) and upregulation of LAMP-1 (CD107a) by tumor (Melan-A/MART-1) specific T-cells was comparable to virus (EBV-BMLF1) specific CD8 T-cells. Furthermore, phosphorylation of STAT1, STAT5 and ERK1/2, and expression of CD3 zeta chain were similar in tumor- and virus-specific T-cells, demonstrating functional signaling pathways.
16951314	PAN-Cancer	Promote immunity	Experiments with ERK-1/2 inhibitors demonstrated that bryostatin-1 induction of IFN- gamma and T-bet was ERK-dependent and IL-12-independent. Similar results were obtained from both normal donors and cancer patients. In summary, our results suggest that bryostatin-1-induced IFN-gamma expression is T-bet independent. They also suggest for the first time that IFN- gamma and T-bet can be induced in human DC through an ERK-dependent pathway. Bryostatin-1-induced IFN- gamma may play a crucial role in the initiation of the immune response, before specific recognition by T cells that could be beneficial in the treatment of cancer.
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.
16801397	Melanoma	Inhibit immunity	Here, 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
Symbol	MAPK1
Name	mitogen-activated protein kinase 1
Aliases	ERK2; p41mapk; MAPK2; PRKM2; PRKM1; ERK-2; ERT1; P42MAPK; p41; p42-MAPK; MAP kinase 1; MAP kinase 2; MAP kin ......
Chromosomal Location	22q11.2
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

[ TOP ]

Statistical results of MAPK1 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	MAPK1
Name	mitogen-activated protein kinase 1
Aliases	ERK2; p41mapk; MAPK2; PRKM2; PRKM1; ERK-2; ERT1; P42MAPK; p41; p42-MAPK; MAP kinase 1; MAP kinase 2; MAP kin ......
Chromosomal Location	22q11.2
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

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Points in the above scatter plot represent the expression difference of MAPK1 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	-0.079	0.726
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.073	0.975
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.19	0.909
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.161	0.609
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.272	0.878
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.714	0.766
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.068	0.878
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.118	0.956
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.017	0.994
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.149	0.906
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	0.699	0.714
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.075	0.162

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of MAPK1 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	3.7	0	3.7	0.27
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	3.7	0	3.7	0.314
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	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	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	12.5	-12.5	0.52
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	14.3	-14.3	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	MAPK1
Name	mitogen-activated protein kinase 1
Aliases	ERK2; p41mapk; MAPK2; PRKM2; PRKM1; ERK-2; ERT1; P42MAPK; p41; p42-MAPK; MAP kinase 1; MAP kinase 2; MAP kin ......
Chromosomal Location	22q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of MAPK1. 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	MAPK1
Name	mitogen-activated protein kinase 1
Aliases	ERK2; p41mapk; MAPK2; PRKM2; PRKM1; ERK-2; ERT1; P42MAPK; p41; p42-MAPK; MAP kinase 1; MAP kinase 2; MAP kin ......
Chromosomal Location	22q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of MAPK1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by MAPK1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	MAPK1
Name	mitogen-activated protein kinase 1
Aliases	ERK2; p41mapk; MAPK2; PRKM2; PRKM1; ERK-2; ERT1; P42MAPK; p41; p42-MAPK; MAP kinase 1; MAP kinase 2; MAP kin ......
Chromosomal Location	22q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of MAPK1. 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	MAPK1
Name	mitogen-activated protein kinase 1
Aliases	ERK2; p41mapk; MAPK2; PRKM2; PRKM1; ERK-2; ERT1; P42MAPK; p41; p42-MAPK; MAP kinase 1; MAP kinase 2; MAP kin ......
Chromosomal Location	22q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of MAPK1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	MAPK1
Name	mitogen-activated protein kinase 1
Aliases	ERK2; p41mapk; MAPK2; PRKM2; PRKM1; ERK-2; ERT1; P42MAPK; p41; p42-MAPK; MAP kinase 1; MAP kinase 2; MAP kin ......
Chromosomal Location	22q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between MAPK1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	MAPK1
Name	mitogen-activated protein kinase 1
Aliases	ERK2; p41mapk; MAPK2; PRKM2; PRKM1; ERK-2; ERT1; P42MAPK; p41; p42-MAPK; MAP kinase 1; MAP kinase 2; MAP kin ......
Chromosomal Location	22q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting MAPK1 collected from DrugBank database.

> Drugs from DrugBank database

[ TOP ]

Details on drugs targeting MAPK1.

ID	Name	Drug Type	Targets	#Targets
DB01064	Isoprenaline	Small Molecule	ADRB1, ADRB2, ADRB3, MAPK1, PIK3R1, PIK3R2, PIK3R3, SOD1	8
DB01169	Arsenic trioxide	Small Molecule	AKT1, CCND1, CDKN1A, HDAC1, IKBKB, JUN, MAPK1, MAPK3, PML, TXNRD1	10
DB02116	Olomoucine	Small Molecule	CDK1, CDK2, CDK5, MAPK1	4
DB02482	Phosphonothreonine	Small Molecule	AURKA, CDK7, MAPK1, MAPK12, PRKACA, PRKACB, PRKCQ, RHO, S100A11	9
DB02733	Purvalanol	Small Molecule	CDK2, CDK4, MAPK1, MAPK3, SRPK2	5
DB04338	SB220025	Small Molecule	MAPK1, MAPK14	2
DB06195	Seliciclib	Small Molecule	CDK1, CDK2, CDK7, CDK9, CSNK1E, MAPK1, MAPK3	7
DB06641	Perifosine	Small Molecule	AKT1, MAPK1, PRKCA	3
DB06877	N,N-DIMETHYL-4-(4-PHENYL-1H-PYRAZOL-3-YL)-1H-PYRROLE-2-CARBOXAMIDE	Small Molecule	MAPK1	1
DB07010	N-BENZYL-4-[4-(3-CHLOROPHENYL)-1H-PYRAZOL-3-YL]-1H-PYRROLE-2-CARBOXAMIDE	Small Molecule	MAPK1, MAPK10	2
DB07264	(S)-N-(1-(3-CHLORO-4-FLUOROPHENYL)-2-HYDROXYETHYL)-4-(4-(3-CHLOROPHENYL)-1H-PYRAZOL-3-YL)-1H-PYRROLE-2-CARBOXAMIDE	Small Molecule	MAPK1	1
DB07788	(3R,5Z,8S,9S,11E)-8,9,16-TRIHYDROXY-14-METHOXY-3-METHYL-3,4,9,10-TETRAHYDRO-1H-2-BENZOXACYCLOTETRADECINE-1,7(8H)-DIONE	Small Molecule	MAPK1	1
DB07794	5-(2-PHENYLPYRAZOLO[1,5-A]PYRIDIN-3-YL)-1H-PYRAZOLO[3,4-C]PYRIDAZIN-3-AMINE	Small Molecule	MAPK1	1
DB07905	(1aR,8S,13S,14S,15aR)-5,13,14-trihydroxy-3-methoxy-8-methyl-8,9,13,14,15,15a-hexahydro-6H-oxireno[k][2]benzoxacyclotetradecine-6,12(1aH)-dione	Small Molecule	MAPK1	1
DB08513	[4-({5-(AMINOCARBONYL)-4-[(3-METHYLPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)PHENYL]ACETIC ACID	Small Molecule	INSR, IRS1, MAPK1	3
DB08521	4-[5-(4-FLUORO-PHENYL)-2-(4-METHANESULFINYL-PHENYL)-3H-IMIDAZOL-4-YL]-PYRIDINE	Small Molecule	MAPK1, MAPK14	2
DB11120	Turpentine	Small Molecule	MAPK1	1
DB13930	Ulixertinib	Small Molecule	MAPK1, MAPK3	2

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