MAPK14 report

I. Expression across cell types

II. Expression across tissues

III. Associated gene sets

GO_0006366Biological processtranscription by RNA polymerase II
GO_0032495Biological processresponse to muramyl dipeptide
GO_0002062Biological processchondrocyte differentiation
GO_0006935Biological processchemotaxis
GO_0002862Biological processnegative regulation of inflammatory response to antigenic stimulus
GO_0002021Biological processresponse to dietary excess
GO_0090090Biological processnegative regulation of canonical Wnt signaling pathway
GO_0030168Biological processplatelet activation
GO_0010831Biological processpositive regulation of myotube differentiation
GO_1900015Biological processregulation of cytokine production involved in inflammatory response
GO_2000379Biological processpositive regulation of reactive oxygen species metabolic process
GO_0000902Biological processcell morphogenesis
GO_0038066Biological processp38MAPK cascade
GO_0035924Biological processcellular response to vascular endothelial growth factor stimulus
GO_0006006Biological processglucose metabolic process
GO_0007166Biological processcell surface receptor signaling pathway
GO_0035331Biological processnegative regulation of hippo signaling
GO_0001525Biological processangiogenesis
GO_0007178Biological processcell surface receptor protein serine/threonine kinase signaling pathway
GO_0007519Biological processskeletal muscle tissue development
GO_0006357Biological processregulation of transcription by RNA polymerase II
GO_0001649Biological processosteoblast differentiation
GO_0007165Biological processsignal transduction
GO_0010628Biological processpositive regulation of gene expression
GO_0042307Biological processpositive regulation of protein import into nucleus
GO_0051149Biological processpositive regulation of muscle cell differentiation
GO_0045663Biological processpositive regulation of myoblast differentiation
GO_0051403Biological processstress-activated MAPK cascade
GO_0071223Biological processcellular response to lipoteichoic acid
GO_0045648Biological processpositive regulation of erythrocyte differentiation
GO_0071222Biological processcellular response to lipopolysaccharide
GO_0031098Biological processstress-activated protein kinase signaling cascade
GO_0060348Biological processbone development
GO_0071479Biological processcellular response to ionizing radiation
GO_0042770Biological processsignal transduction in response to DNA damage
GO_0000077Biological processDNA damage checkpoint signaling
GO_0030316Biological processosteoclast differentiation
GO_0043536Biological processpositive regulation of blood vessel endothelial cell migration
GO_0060045Biological processpositive regulation of cardiac muscle cell proliferation
GO_0099179Biological processregulation of synaptic membrane adhesion
GO_0051146Biological processstriated muscle cell differentiation
GO_0071493Biological processcellular response to UV-B
GO_0048010Biological processvascular endothelial growth factor receptor signaling pathway
GO_0001502Biological processcartilage condensation
GO_0045944Biological processpositive regulation of transcription by RNA polymerase II
GO_0031663Biological processlipopolysaccharide-mediated signaling pathway
GO_0018105Biological processpeptidyl-serine phosphorylation
GO_0035994Biological processresponse to muscle stretch
GO_0046326Biological processpositive regulation of glucose import
GO_0019395Biological processfatty acid oxidation
GO_0032735Biological processpositive regulation of interleukin-12 production
GO_0032868Biological processresponse to insulin
GO_0090400Biological processstress-induced premature senescence
GO_0001890Biological processplacenta development
GO_1901741Biological processpositive regulation of myoblast fusion
GO_0098586Biological processcellular response to virus
GO_0071356Biological processcellular response to tumor necrosis factor
GO_0035556Biological processintracellular signal transduction
GO_0090336Biological processpositive regulation of brown fat cell differentiation
GO_0070935Biological process3'-UTR-mediated mRNA stabilization
GO_0006915Biological processapoptotic process
GO_0090398Biological processcellular senescence
GO_0048863Biological processstem cell differentiation
GO_0031281Biological processpositive regulation of cyclase activity
GO_0046323Biological processglucose import
GO_0030278Biological processregulation of ossification
GO_0098978Cellular componentglutamatergic synapse
GO_1904813Cellular componentficolin-1-rich granule lumen
GO_0005634Cellular componentnucleus
GO_0005576Cellular componentextracellular region
GO_0000922Cellular componentspindle pole
GO_0005654Cellular componentnucleoplasm
GO_0005739Cellular componentmitochondrion
GO_0034774Cellular componentsecretory granule lumen
GO_0005737Cellular componentcytoplasm
GO_0016607Cellular componentnuclear speck
GO_0005829Cellular componentcytosol
GO_0004708Molecular functionMAP kinase kinase activity
GO_0005524Molecular functionATP binding
GO_0004707Molecular functionMAP kinase activity
GO_0106310Molecular functionprotein serine kinase activity
GO_0051525Molecular functionNFAT protein binding
GO_0019899Molecular functionenzyme binding
GO_0048273Molecular functionmitogen-activated protein kinase p38 binding
GO_0004674Molecular functionprotein serine/threonine kinase activity
GO_0005515Molecular functionprotein binding
GO_0019903Molecular functionprotein phosphatase binding

IV. Literature review

[source]
Gene nameMAPK14
Protein nameMitogen-activated protein kinase 14 (EC 2.7.11.24) (Mitogen-activated protein kinase p38 alpha)
mitogen-activated protein kinase (EC 2.7.11.24)
Mitogen-activated protein kinase 14 (MAP kinase 14) (MAPK 14) (EC 2.7.11.24) (Cytokine suppressive anti-inflammatory drug-binding protein) (CSAID-binding protein) (CSBP) (MAP kinase MXI2) (MAX-interacting protein 2) (Mitogen-activated protein kinase p38 alpha) (MAP kinase p38 alpha) (Stress-activated protein kinase 2a) (SAPK2a)
SynonymsCSPB1
hCG_1818055
SAPK2A
CSBP1
MXI2
CSBP2
CSBP
DescriptionFUNCTION: 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 pro-inflammatory 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' . Phosphorylates NLRP1 downstream of MAP3K20/ZAK in response to UV-B irradiation and ribosome collisions, promoting activation of the NLRP1 inflammasome and pyroptosis . .; 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 minutes and is inhibited by kinase-specific inhibitors SB203580 and siRNA . .

AccessionsENST00000468133.5
ENST00000310795.8 [Q16539-4]
ENST00000229794.9 [Q16539-1]
ENST00000474429.5
ENST00000472333.1
Q16539
B5TY33
B4E0K5
ENST00000491957.5
E7EX54
L7RSM2
ENST00000229795.8 [Q16539-2]
H7C4E2