Browse MAPK14

Summary
SymbolMAPK14
Namemitogen-activated protein kinase 14
Aliases PRKM14; Mxi2; PRKM15; p38 MAP kinase; CSPB1; CSBP1; CSBP2; EXIP; SAPK2A; p38ALPHA; CSAID-binding protein; Cs ......
Chromosomal Location6p21.3-p21.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm Nucleus
Domain PF00069 Protein kinase domain
Function

Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1. RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2. MAPK14 interacts also with casein kinase II, leading to its activation through autophosphorylation and further phosphorylation of TP53/p53. In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. In a similar way, MAPK14 phosphorylates the ubiquitin ligase SIAH2, regulating its activity towards EGLN3. MAPK14 may also inhibit the lysosomal degradation pathway of autophagy by interfering with the intracellular trafficking of the transmembrane protein ATG9. Another function of MAPK14 is to regulate the endocytosis of membrane receptors by different mechanisms that impinge on the small GTPase RAB5A. In addition, clathrin-mediated EGFR internalization induced by inflammatory cytokines and UV irradiation depends on MAPK14-mediated phosphorylation of EGFR itself as well as of RAB5A effectors. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Another p38 MAPK substrate is FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A. The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates CDC25B and CDC25C which is required for binding to 14-3-3 proteins and leads to initiation of a G2 delay after ultraviolet radiation. Phosphorylates TIAR following DNA damage, releasing TIAR from GADD45A mRNA and preventing mRNA degradation. The p38 MAPKs may also have kinase-independent roles, which are thought to be due to the binding to targets in the absence of phosphorylation. Protein O-Glc-N-acylation catalyzed by the OGT is regulated by MAPK14, and, although OGT does not seem to be phosphorylated by MAPK14, their interaction increases upon MAPK14 activation induced by glucose deprivation. This interaction may regulate OGT activity by recruiting it to specific targets such as neurofilament H, stimulating its O-Glc-N-acylation. Required in mid-fetal development for the growth of embryo-derived blood vessels in the labyrinth layer of the placenta. Also plays an essential role in developmental and stress-induced erythropoiesis, through regulation of EPO gene expression. Isoform MXI2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2. Isoform EXIP may play a role in the early onset of apoptosis. Phosphorylates S100A9 at 'Thr-113'. ; FUNCTION: (Microbial infection) Activated by phosphorylation by M.tuberculosis EsxA in T-cells leading to inhibition of IFN-gamma production; phosphorylation is apparent within 15 minute and is inhibited by kinase-specific inhibitors SB203580 and siRNA (PubMed:21586573).

> Gene Ontology
 
Biological Process GO:0000075 cell cycle checkpoint
GO:0000077 DNA damage checkpoint
GO:0000187 activation of MAPK activity
GO:0000768 syncytium formation by plasma membrane fusion
GO:0001501 skeletal system development
GO:0001502 cartilage condensation
GO:0001503 ossification
GO:0001525 angiogenesis
GO:0001819 positive regulation of cytokine production
GO:0001890 placenta development
GO:0002062 chondrocyte differentiation
GO:0002237 response to molecule of bacterial origin
GO:0002262 myeloid cell homeostasis
GO:0002521 leukocyte differentiation
GO:0002532 production of molecular mediator involved in inflammatory response
GO:0002534 cytokine production involved in inflammatory response
GO:0002573 myeloid leukocyte differentiation
GO:0005996 monosaccharide metabolic process
GO:0006006 glucose metabolic process
GO:0006606 protein import into nucleus
GO:0006631 fatty acid metabolic process
GO:0006913 nucleocytoplasmic transport
GO:0006949 syncytium formation
GO:0007178 transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0007265 Ras protein signal transduction
GO:0007507 heart development
GO:0007517 muscle organ development
GO:0007519 skeletal muscle tissue development
GO:0007520 myoblast fusion
GO:0007568 aging
GO:0007569 cell aging
GO:0008643 carbohydrate transport
GO:0008645 hexose transport
GO:0009306 protein secretion
GO:0009314 response to radiation
GO:0009612 response to mechanical stimulus
GO:0009615 response to virus
GO:0010212 response to ionizing radiation
GO:0010608 posttranscriptional regulation of gene expression
GO:0010827 regulation of glucose transport
GO:0010828 positive regulation of glucose transport
GO:0010830 regulation of myotube differentiation
GO:0010831 positive regulation of myotube differentiation
GO:0014706 striated muscle tissue development
GO:0014835 myoblast differentiation involved in skeletal muscle regeneration
GO:0014855 striated muscle cell proliferation
GO:0014902 myotube differentiation
GO:0015749 monosaccharide transport
GO:0015758 glucose transport
GO:0016055 Wnt signaling pathway
GO:0016202 regulation of striated muscle tissue development
GO:0017038 protein import
GO:0018105 peptidyl-serine phosphorylation
GO:0018209 peptidyl-serine modification
GO:0019318 hexose metabolic process
GO:0019395 fatty acid oxidation
GO:0030099 myeloid cell differentiation
GO:0030111 regulation of Wnt signaling pathway
GO:0030178 negative regulation of Wnt signaling pathway
GO:0030218 erythrocyte differentiation
GO:0030258 lipid modification
GO:0030278 regulation of ossification
GO:0030316 osteoclast differentiation
GO:0031098 stress-activated protein kinase signaling cascade
GO:0031099 regeneration
GO:0031279 regulation of cyclase activity
GO:0031281 positive regulation of cyclase activity
GO:0031570 DNA integrity checkpoint
GO:0031663 lipopolysaccharide-mediated signaling pathway
GO:0032147 activation of protein kinase activity
GO:0032386 regulation of intracellular transport
GO:0032388 positive regulation of intracellular transport
GO:0032495 response to muramyl dipeptide
GO:0032496 response to lipopolysaccharide
GO:0032615 interleukin-12 production
GO:0032655 regulation of interleukin-12 production
GO:0032735 positive regulation of interleukin-12 production
GO:0032844 regulation of homeostatic process
GO:0032846 positive regulation of homeostatic process
GO:0033002 muscle cell proliferation
GO:0033157 regulation of intracellular protein transport
GO:0033674 positive regulation of kinase activity
GO:0034101 erythrocyte homeostasis
GO:0034440 lipid oxidation
GO:0034504 protein localization to nucleus
GO:0035265 organ growth
GO:0035924 cellular response to vascular endothelial growth factor stimulus
GO:0035994 response to muscle stretch
GO:0038066 p38MAPK cascade
GO:0042246 tissue regeneration
GO:0042306 regulation of protein import into nucleus
GO:0042307 positive regulation of protein import into nucleus
GO:0042692 muscle cell differentiation
GO:0042770 signal transduction in response to DNA damage
GO:0043403 skeletal muscle tissue regeneration
GO:0043405 regulation of MAP kinase activity
GO:0043406 positive regulation of MAP kinase activity
GO:0043410 positive regulation of MAPK cascade
GO:0043487 regulation of RNA stability
GO:0043488 regulation of mRNA stability
GO:0043489 RNA stabilization
GO:0044723 single-organism carbohydrate metabolic process
GO:0044744 protein targeting to nucleus
GO:0045444 fat cell differentiation
GO:0045445 myoblast differentiation
GO:0045598 regulation of fat cell differentiation
GO:0045600 positive regulation of fat cell differentiation
GO:0045637 regulation of myeloid cell differentiation
GO:0045639 positive regulation of myeloid cell differentiation
GO:0045646 regulation of erythrocyte differentiation
GO:0045648 positive regulation of erythrocyte differentiation
GO:0045661 regulation of myoblast differentiation
GO:0045663 positive regulation of myoblast differentiation
GO:0045844 positive regulation of striated muscle tissue development
GO:0045860 positive regulation of protein kinase activity
GO:0045927 positive regulation of growth
GO:0046323 glucose import
GO:0046324 regulation of glucose import
GO:0046326 positive regulation of glucose import
GO:0046620 regulation of organ growth
GO:0046622 positive regulation of organ growth
GO:0046822 regulation of nucleocytoplasmic transport
GO:0046824 positive regulation of nucleocytoplasmic transport
GO:0048010 vascular endothelial growth factor receptor signaling pathway
GO:0048255 mRNA stabilization
GO:0048514 blood vessel morphogenesis
GO:0048608 reproductive structure development
GO:0048634 regulation of muscle organ development
GO:0048636 positive regulation of muscle organ development
GO:0048638 regulation of developmental growth
GO:0048639 positive regulation of developmental growth
GO:0048705 skeletal system morphogenesis
GO:0048738 cardiac muscle tissue development
GO:0048872 homeostasis of number of cells
GO:0050663 cytokine secretion
GO:0050707 regulation of cytokine secretion
GO:0050708 regulation of protein secretion
GO:0050714 positive regulation of protein secretion
GO:0050715 positive regulation of cytokine secretion
GO:0050727 regulation of inflammatory response
GO:0050873 brown fat cell differentiation
GO:0051047 positive regulation of secretion
GO:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0051146 striated muscle cell differentiation
GO:0051147 regulation of muscle cell differentiation
GO:0051149 positive regulation of muscle cell differentiation
GO:0051153 regulation of striated muscle cell differentiation
GO:0051155 positive regulation of striated muscle cell differentiation
GO:0051169 nuclear transport
GO:0051170 nuclear import
GO:0051216 cartilage development
GO:0051222 positive regulation of protein transport
GO:0051403 stress-activated MAPK cascade
GO:0055017 cardiac muscle tissue growth
GO:0055021 regulation of cardiac muscle tissue growth
GO:0055023 positive regulation of cardiac muscle tissue growth
GO:0055024 regulation of cardiac muscle tissue development
GO:0055025 positive regulation of cardiac muscle tissue development
GO:0060038 cardiac muscle cell proliferation
GO:0060043 regulation of cardiac muscle cell proliferation
GO:0060045 positive regulation of cardiac muscle cell proliferation
GO:0060070 canonical Wnt signaling pathway
GO:0060142 regulation of syncytium formation by plasma membrane fusion
GO:0060143 positive regulation of syncytium formation by plasma membrane fusion
GO:0060419 heart growth
GO:0060420 regulation of heart growth
GO:0060421 positive regulation of heart growth
GO:0060537 muscle tissue development
GO:0060538 skeletal muscle organ development
GO:0060828 regulation of canonical Wnt signaling pathway
GO:0061448 connective tissue development
GO:0061458 reproductive system development
GO:0070935 3'-UTR-mediated mRNA stabilization
GO:0071214 cellular response to abiotic stimulus
GO:0071216 cellular response to biotic stimulus
GO:0071219 cellular response to molecule of bacterial origin
GO:0071222 cellular response to lipopolysaccharide
GO:0071396 cellular response to lipid
GO:0071478 cellular response to radiation
GO:0071479 cellular response to ionizing radiation
GO:0071900 regulation of protein serine/threonine kinase activity
GO:0071902 positive regulation of protein serine/threonine kinase activity
GO:0072331 signal transduction by p53 class mediator
GO:0072593 reactive oxygen species metabolic process
GO:0072610 interleukin-12 secretion
GO:0090090 negative regulation of canonical Wnt signaling pathway
GO:0090316 positive regulation of intracellular protein transport
GO:0090335 regulation of brown fat cell differentiation
GO:0090336 positive regulation of brown fat cell differentiation
GO:0090398 cellular senescence
GO:0090400 stress-induced premature senescence
GO:0098586 cellular response to virus
GO:0098743 cell aggregation
GO:0198738 cell-cell signaling by wnt
GO:1900015 regulation of cytokine production involved in inflammatory response
GO:1900180 regulation of protein localization to nucleus
GO:1900182 positive regulation of protein localization to nucleus
GO:1901652 response to peptide
GO:1901739 regulation of myoblast fusion
GO:1901741 positive regulation of myoblast fusion
GO:1901796 regulation of signal transduction by p53 class mediator
GO:1901861 regulation of muscle tissue development
GO:1901863 positive regulation of muscle tissue development
GO:1902593 single-organism nuclear import
GO:1903532 positive regulation of secretion by cell
GO:1903533 regulation of protein targeting
GO:1903706 regulation of hemopoiesis
GO:1903708 positive regulation of hemopoiesis
GO:1903829 positive regulation of cellular protein localization
GO:1904589 regulation of protein import
GO:1904591 positive regulation of protein import
GO:1904951 positive regulation of establishment of protein localization
GO:2000377 regulation of reactive oxygen species metabolic process
GO:2000379 positive regulation of reactive oxygen species metabolic process
GO:2001182 regulation of interleukin-12 secretion
GO:2001184 positive regulation of interleukin-12 secretion
Molecular Function GO:0004674 protein serine/threonine kinase activity
GO:0004702 receptor signaling protein serine/threonine kinase activity
GO:0004707 MAP kinase activity
GO:0004708 MAP kinase kinase activity
GO:0004712 protein serine/threonine/tyrosine kinase activity
GO:0005057 receptor signaling protein activity
GO:0008134 transcription factor binding
GO:0019902 phosphatase binding
GO:0019903 protein phosphatase binding
GO:0051525 NFAT protein binding
Cellular Component GO:0000922 spindle pole
GO:0005819 spindle
> KEGG and Reactome Pathway
 
KEGG hsa04010 MAPK signaling pathway
hsa04015 Rap1 signaling pathway
hsa04068 FoxO signaling pathway
hsa04071 Sphingolipid signaling pathway
hsa04261 Adrenergic signaling in cardiomyocytes
hsa04370 VEGF signaling pathway
hsa04380 Osteoclast differentiation
hsa04550 Signaling pathways regulating pluripotency of stem cells
hsa04611 Platelet activation
hsa04620 Toll-like receptor signaling pathway
hsa04621 NOD-like receptor signaling pathway
hsa04622 RIG-I-like receptor signaling pathway
hsa04660 T cell receptor signaling pathway
hsa04664 Fc epsilon RI signaling pathway
hsa04668 TNF signaling pathway
hsa04670 Leukocyte transendothelial migration
hsa04722 Neurotrophin signaling pathway
hsa04723 Retrograde endocannabinoid signaling
hsa04728 Dopaminergic synapse
hsa04750 Inflammatory mediator regulation of TRP channels
hsa04912 GnRH signaling pathway
hsa04914 Progesterone-mediated oocyte maturation
hsa04917 Prolactin signaling pathway
Reactome R-HSA-418592: ADP signalling through P2Y purinoceptor 1
R-HSA-166054: Activated TLR4 signalling
R-HSA-2151209: Activation of PPARGC1A (PGC-1alpha) by phosphorylation
R-HSA-450341: Activation of the AP-1 family of transcription factors
R-HSA-375170: CDO in myogenesis
R-HSA-1500931: Cell-Cell communication
R-HSA-2559583: Cellular Senescence
R-HSA-2262752: Cellular responses to stress
R-HSA-376172: DSCAM interactions
R-HSA-1266738: Developmental Biology
R-HSA-198753: ERK/MAPK targets
R-HSA-74160: Gene Expression
R-HSA-212436: Generic Transcription Pathway
R-HSA-109582: Hemostasis
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-450604: KSRP (KHSRP) binds and destabilizes mRNA
R-HSA-450294: MAP kinase activation in TLR cascade
R-HSA-450282: MAPK targets/ Nuclear events mediated by MAP kinases
R-HSA-1592230: Mitochondrial biogenesis
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-525793: Myogenesis
R-HSA-187037: NGF signalling via TRKA from the plasma membrane
R-HSA-168638: NOD1/2 Signaling Pathway
R-HSA-6798695: Neutrophil degranulation
R-HSA-198725: Nuclear Events (kinase and transcription factor activation)
R-HSA-168643: Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
R-HSA-1852241: Organelle biogenesis and maintenance
R-HSA-2559580: Oxidative Stress Induced Senescence
R-HSA-76002: Platelet activation, signaling and aggregation
R-HSA-418346: Platelet homeostasis
R-HSA-432142: Platelet sensitization by LDL
R-HSA-5633007: Regulation of TP53 Activity
R-HSA-6804756: Regulation of TP53 Activity through Phosphorylation
R-HSA-450531: Regulation of mRNA stability by proteins that bind AU-rich elements
R-HSA-162582: Signal Transduction
R-HSA-392518: Signal amplification
R-HSA-194138: Signaling by VEGF
R-HSA-166520: Signalling by NGF
R-HSA-187687: Signalling to ERKs
R-HSA-167044: Signalling to RAS
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-3700989: Transcriptional Regulation by TP53
R-HSA-4420097: VEGFA-VEGFR2 Pathway
R-HSA-450302: activated TAK1 mediates p38 MAPK activation
R-HSA-171007: p38MAPK events
Summary
SymbolMAPK14
Namemitogen-activated protein kinase 14
Aliases PRKM14; Mxi2; PRKM15; p38 MAP kinase; CSPB1; CSBP1; CSBP2; EXIP; SAPK2A; p38ALPHA; CSAID-binding protein; Cs ......
Chromosomal Location6p21.3-p21.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between MAPK14 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 MAPK14 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
19688743MelanomaPromote immunity (T cell function)Gadd45b, a signaling molecule highly up-regulated during Th1 type responses, is studied for its role in limiting tumor growth. Mouse B16 melanoma cells implanted into Gadd45b(-/-) mice grew faster than those in WT or Gadd45b(+/-) littermate controls. The defect of Gadd45b(-/-) mice in tumor immunosurveillance was attributed to the reduced expression of IFN-gamma, granzyme B, and CCR5 in Gadd45b(-/-) CD8(+) T cells at the tumor site. Activation of p38 MAP kinase, but not ERK or JNK, by either TCR-stimuli or IL-12 and IL-18 is diminished in Gadd45b(-/-) CD8(+) T cells, resulting in reduced production of IFN-gamma.
21321117Chronic myelogenous leukemiaPromote immunity (NK cell function)Overexpression of IL-32alpha increases natural killer cell-mediated killing through up-regulation of Fas and UL16-binding protein 2 (ULBP2) expression in human chronic myeloid leukemia cells. T IL-32α-induced Fas and ULBP2 expression are regulated p38 MAPK.
24324467MelanomaInhibit immunityOur lab has additionally identified p38-MAPK as an important signaling element in human DC suppression, and recently validated it as such in ex vivo cultures of single-cell suspensions from melanoma metastases.
16917008Multiple myeloma(IgA, IgD, IgE, IgM, IgG)Inhibit immunityThese 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
SymbolMAPK14
Namemitogen-activated protein kinase 14
Aliases PRKM14; Mxi2; PRKM15; p38 MAP kinase; CSPB1; CSBP1; CSBP2; EXIP; SAPK2A; p38ALPHA; CSAID-binding protein; Cs ......
Chromosomal Location6p21.3-p21.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of MAPK14 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolMAPK14
Namemitogen-activated protein kinase 14
Aliases PRKM14; Mxi2; PRKM15; p38 MAP kinase; CSPB1; CSBP1; CSBP2; EXIP; SAPK2A; p38ALPHA; CSAID-binding protein; Cs ......
Chromosomal Location6p21.3-p21.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of MAPK14 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.2250.322
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.2920.882
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.1780.898
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.0070.978
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.0080.997
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.0330.988
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.0430.914
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.1340.942
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.2530.903
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.2470.859
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.8060.697
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.0650.23
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of MAPK14 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27730001
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27590001
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91622.2022.20.12
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59400400.11
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolMAPK14
Namemitogen-activated protein kinase 14
Aliases PRKM14; Mxi2; PRKM15; p38 MAP kinase; CSPB1; CSBP1; CSBP2; EXIP; SAPK2A; p38ALPHA; CSAID-binding protein; Cs ......
Chromosomal Location6p21.3-p21.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of MAPK14. 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
SymbolMAPK14
Namemitogen-activated protein kinase 14
Aliases PRKM14; Mxi2; PRKM15; p38 MAP kinase; CSPB1; CSBP1; CSBP2; EXIP; SAPK2A; p38ALPHA; CSAID-binding protein; Cs ......
Chromosomal Location6p21.3-p21.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of MAPK14. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by MAPK14.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolMAPK14
Namemitogen-activated protein kinase 14
Aliases PRKM14; Mxi2; PRKM15; p38 MAP kinase; CSPB1; CSBP1; CSBP2; EXIP; SAPK2A; p38ALPHA; CSAID-binding protein; Cs ......
Chromosomal Location6p21.3-p21.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of MAPK14. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolMAPK14
Namemitogen-activated protein kinase 14
Aliases PRKM14; Mxi2; PRKM15; p38 MAP kinase; CSPB1; CSBP1; CSBP2; EXIP; SAPK2A; p38ALPHA; CSAID-binding protein; Cs ......
Chromosomal Location6p21.3-p21.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of MAPK14 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolMAPK14
Namemitogen-activated protein kinase 14
Aliases PRKM14; Mxi2; PRKM15; p38 MAP kinase; CSPB1; CSBP1; CSBP2; EXIP; SAPK2A; p38ALPHA; CSAID-binding protein; Cs ......
Chromosomal Location6p21.3-p21.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between MAPK14 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolMAPK14
Namemitogen-activated protein kinase 14
Aliases PRKM14; Mxi2; PRKM15; p38 MAP kinase; CSPB1; CSBP1; CSBP2; EXIP; SAPK2A; p38ALPHA; CSAID-binding protein; Cs ......
Chromosomal Location6p21.3-p21.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting MAPK14 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting MAPK14.
ID Name Drug Type Targets #Targets
DB01254DasatinibSmall MoleculeABL1, ABL2, BCR, BTK, CSK, EPHA2, EPHA5, EPHB4, FGR, FRK, FYN, HSP ......22
DB017614-[5-[2-(1-Phenyl-Ethylamino)-Pyrimidin-4-Yl]-1-Methyl-4-(3-Trifluoromethylphenyl)-1h-Imidazol-2-Yl]-PiperidineSmall MoleculeMAPK141
DB01807N-[(3z)-5-Tert-Butyl-2-Phenyl-1,2-Dihydro-3h-Pyrazol-3-Ylidene]-N'-(4-Chlorophenyl)UreaSmall MoleculeMAPK141
DB019481-(2,6-Dichlorophenyl)-5-(2,4-Difluorophenyl)-7-Piperidin-4-Yl-3,4-Dihydroquinolin-2(1h)-OneSmall MoleculeMAPK141
DB01953Inhibitor of P38 KinaseSmall MoleculeMAPK141
DB019886((S)-3-Benzylpiperazin-1-Yl)-3-(Naphthalen-2-Yl)-4-(Pyridin-4-Yl)PyrazineSmall MoleculeMAPK141
DB021953-(4-Fluorophenyl)-1-Hydroxy-2-(Pyridin-4-Yl)-1h-Pyrrolo[3,2-B]PyridineSmall MoleculeMAPK141
DB022771-(5-Tert-Butyl-2-Methyl-2h-Pyrazol-3-Yl)-3-(4-Chloro-Phenyl)-UreaSmall MoleculeMAPK141
DB023523-(Benzyloxy)Pyridin-2-AmineSmall MoleculeLTA4H, MAPK142
DB028731-(2,6-Dichlorophenyl)-5-(2,4-Difluorophenyl)-7-Piperazin-1-Yl-3,4-Dihydroquinazolin-2(1h)-OneSmall MoleculeMAPK141
DB029844-[3-Methylsulfanylanilino]-6,7-DimethoxyquinazolineSmall MoleculeMAPK141
DB030441-(5-Tert-Butyl-2-P-Tolyl-2h-Pyrazol-3-Yl)-3-[4-(2-Morpholin-4-Yl-Ethoxy)-Naphthalen-1-Yl]-UreaSmall MoleculeMAPK141
DB031102-ChlorophenolSmall MoleculeMAPK141
DB039804-(Fluorophenyl)-1-Cyclopropylmethyl-5-(2-Amino-4-Pyrimidinyl)ImidazoleSmall MoleculeMAPK141
DB04338SB220025Small MoleculeMAPK1, MAPK142
DB046324-(2-HYDROXYBENZYLAMINO)-N-(3-(4-FLUOROPHENOXY)PHENYL)PIPERIDINE-1-SULFONAMIDESmall MoleculeMAPK141
DB04797TriazolopyridineSmall MoleculeMAPK141
DB05157KC706Small MoleculeMAPK11, MAPK12, MAPK13, MAPK144
DB05412TalmapimodSmall MoleculeIL1B, MAPK14, MT-CO2, TNF4
DB05470VX-702Small MoleculeIL1B, IL6, MAPK14, TNF4
DB068821-[1-(3-aminophenyl)-3-tert-butyl-1H-pyrazol-5-yl]-3-naphthalen-1-ylureaSmall MoleculeMAPK14, SRC2
DB06940N-ethyl-4-{[5-(methoxycarbamoyl)-2-methylphenyl]amino}-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxamideSmall MoleculeMAPK141
DB06991N-[2-methyl-5-(methylcarbamoyl)phenyl]-2-{[(1R)-1-methylpropyl]amino}-1,3-thiazole-5-carboxamideSmall MoleculeMAPK141
DB07138NeflamapimodSmall MoleculeMAPK141
DB07307N-cyclopropyl-4-methyl-3-[1-(2-methylphenyl)phthalazin-6-yl]benzamideSmall MoleculeMAPK141
DB074594-PHENOXY-N-(PYRIDIN-2-YLMETHYL)BENZAMIDESmall MoleculeMAPK141
DB076074-[5-(3-IODO-PHENYL)-2-(4-METHANESULFINYL-PHENYL)-1H-IMIDAZOL-4-YL]-PYRIDINESmall MoleculeMAPK141
DB07811N-cyclopropyl-2',6-dimethyl-4'-(5-methyl-1,3,4-oxadiazol-2-yl)biphenyl-3-carboxamideSmall MoleculeMAPK141
DB078294-[3-(4-FLUOROPHENYL)-1H-PYRAZOL-4-YL]PYRIDINESmall MoleculeMAPK141
DB078324-{4-[(5-hydroxy-2-methylphenyl)amino]quinolin-7-yl}-1,3-thiazole-2-carbaldehydeSmall MoleculeMAPK141
DB07833N-(3-cyanophenyl)-2'-methyl-5'-(5-methyl-1,3,4-oxadiazol-2-yl)-4-biphenylcarboxamideSmall MoleculeMAPK141
DB07834N-(cyclopropylmethyl)-2'-methyl-5'-(5-methyl-1,3,4-oxadiazol-2-yl)biphenyl-4-carboxamideSmall MoleculeMAPK141
DB07835N~3~-cyclopropyl-N~4~'-(cyclopropylmethyl)-6-methylbiphenyl-3,4'-dicarboxamideSmall MoleculeMAPK141
DB07941PH-797804Small MoleculeMAPK141
DB079422-fluoro-4-[4-(4-fluorophenyl)-1H-pyrazol-3-yl]pyridineSmall MoleculeMAPK141
DB079432-{4-[5-(4-chlorophenyl)-4-pyrimidin-4-yl-1H-pyrazol-3-yl]piperidin-1-yl}-2-oxoethanolSmall MoleculeMAPK141
DB08064N-(3-TERT-BUTYL-1H-PYRAZOL-5-YL)-N'-{4-CHLORO-3-[(PYRIDIN-3-YLOXY)METHYL]PHENYL}UREASmall MoleculeMAPK141
DB08068N-[4-CHLORO-3-(PYRIDIN-3-YLOXYMETHYL)-PHENYL]-3-FLUORO-Small MoleculeMAPK141
DB080913-FLUORO-5-MORPHOLIN-4-YL-N-[3-(2-PYRIDIN-4-YLETHYL)-1H-INDOL-5-YL]BENZAMIDESmall MoleculeMAPK141
DB080923-fluoro-N-1H-indol-5-yl-5-morpholin-4-ylbenzamideSmall MoleculeMAPK141
DB080933-(1-NAPHTHYLMETHOXY)PYRIDIN-2-AMINESmall MoleculeMAPK141
DB080953-(2-CHLOROPHENYL)-1-(2-{[(1S)-2-HYDROXY-1,2-DIMETHYLPROPYL]AMINO}PYRIMIDIN-4-YL)-1-(4-METHOXYPHENYL)UREASmall MoleculeMAPK141
DB080968-(2-CHLOROPHENYLAMINO)-2-(2,6-DIFLUOROPHENYLAMINO)-9-ETHYL-9H-PURINE-1,7-DIIUMSmall MoleculeMAPK141
DB080972-(2,6-DIFLUOROPHENOXY)-N-(2-FLUOROPHENYL)-9-ISOPROPYL-9H-PURIN-8-AMINESmall MoleculeMAPK141
DB08242N,4-dimethyl-3-[(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)amino]benzamideSmall MoleculeMAPK141
DB08349N-cyclopropyl-3-{[1-(2,4-difluorophenyl)-7-methyl-6-oxo-6,7-dihydro-1H-pyrazolo[3,4-b]pyridin-4-yl]amino}-4-methylbenzamideSmall MoleculeMAPK141
DB08351N-cyclopropyl-4-methyl-3-{2-[(2-morpholin-4-ylethyl)amino]quinazolin-6-yl}benzamideSmall MoleculeMAPK141
DB083526-[4-(2-fluorophenyl)-1,3-oxazol-5-yl]-N-(1-methylethyl)-1,3-benzothiazol-2-amineSmall MoleculeMAPK141
DB083952-(ETHOXYMETHYL)-4-(4-FLUOROPHENYL)-3-[2-(2-HYDROXYPHENOXY)PYRIMIDIN-4-YL]ISOXAZOL-5(2H)-ONESmall MoleculeMAPK141
DB08423[5-AMINO-1-(4-FLUOROPHENYL)-1H-PYRAZOL-4-YL][3-(PIPERIDIN-4-YLOXY)PHENYL]METHANONESmall MoleculeMAPK141
DB08424[5-AMINO-1-(4-FLUOROPHENYL)-1H-PYRAZOL-4-YL](3-{[(2R)-2,3-DIHYDROXYPROPYL]OXY}PHENYL)METHANONESmall MoleculeMAPK141
DB085214-[5-(4-FLUORO-PHENYL)-2-(4-METHANESULFINYL-PHENYL)-3H-IMIDAZOL-4-YL]-PYRIDINESmall MoleculeMAPK1, MAPK142
DB085224-(4-FLUOROPHENYL)-1-CYCLOROPROPYLMETHYL-5-(4-PYRIDYL)-IMIDAZOLESmall MoleculeMAPK141
DB087303-FLUORO-5-MORPHOLIN-4-YL-N-[1-(2-PYRIDIN-4-YLETHYL)-1H-INDOL-6-YL]BENZAMIDESmall MoleculeMAPK141