GENERAL INFORMATIONi
Gene namei MAPK14
Synonyms CSBP1, CSBP2, CSPB1, Mxi2, p38, PRKM14, PRKM15
Gene descriptioni Mitogen-activated protein kinase 14
Protein classi Cancer-related genes
Enzymes
Predicted locationi Intracellular
Protein evidence Evidence at protein level (all genes)
GENE INFORMATIONi
Chromosome 6
Cytoband p21.31
Chromosome location (bp) 36027782 - 36111236
Number of transcriptsi 5
Ensembl ENSG00000112062 (version 109)
Entrez gene 1432
HGNC HGNC:6876
UniProt Q16539 (UniProt - Evidence at protein level)
neXtProt NX_Q16539
GeneCards MAPK14
Antibodypedia MAPK14 antibodies


PROTEIN FUNCTION
Protein function (UniProt)i 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 1, 2. 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 3, 4. 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 5. MAPK14 interacts also with casein kinase II, leading to its activation through autophosphorylation and further phosphorylation of TP53/p53 6. 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 7. MAPK14 may also inhibit the lysosomal degradation pathway of autophagy by interfering with the intracellular trafficking of the transmembrane protein ATG9 8. 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 9. 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 10. 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 11, 12, 13. 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 14. Phosphorylates TIAR following DNA damage, releasing TIAR from GADD45A mRNA and preventing mRNA degradation 15. 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 16. 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' 17. Phosphorylates NLRP1 downstream of MAP3K20/ZAK in response to UV-B irradiation and ribosome collisions, promoting activation of the NLRP1 inflammasome and pyroptosis 18. show less
Molecular function (UniProt)i Kinase, Serine/threonine-protein kinase, Transferase
Biological process (UniProt)i Apoptosis, Stress response, Transcription, Transcription regulation
Ligand (UniProt)i ATP-binding, Nucleotide-binding
Gene summary (Entrez)i The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is activated by various environmental stresses and proinflammatory cytokines. The activation requires its phosphorylation by MAP kinase kinases (MKKs), or its autophosphorylation triggered by the interaction of MAP3K7IP1/TAB1 protein with this kinase. The substrates of this kinase include transcription regulator ATF2, MEF2C, and MAX, cell cycle regulator CDC25B, and tumor suppressor p53, which suggest the roles of this kinase in stress related transcription and cell cycle regulation, as well as in genotoxic stress response. Four alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008] show less
PROTEIN INFORMATIONi
Splice variant SwissProt TrEMBL Protein class Gene ontology Length & mass Signal peptide
(predicted)		 Transmembrane regions
(predicted)
MAPK14-201
ENSP00000229794
ENST00000229794
Q16539
[Direct mapping] Mitogen-activated protein kinase 14
Show all
A0A024RD15
[Target identity:100%; Query identity:100%] Mitogen-activated protein kinase 14
Show all
Enzymes
   ENZYME proteins
   Transferases
   Kinases
   CMGC Ser/Thr protein kinases
   MEMSAT-SVM predicted membrane proteins
   SPOCTOPUS predicted membrane proteins
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Cancer-related genes
   Candidate cancer biomarkers
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Kim et al 2014)
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000077 [DNA damage checkpoint signaling]
GO:0000165 [MAPK cascade]
GO:0000166 [nucleotide binding]
GO:0000902 [cell morphogenesis]
GO:0000922 [spindle pole]
GO:0001502 [cartilage condensation]
GO:0001525 [angiogenesis]
GO:0001649 [osteoblast differentiation]
GO:0001890 [placenta development]
GO:0002021 [response to dietary excess]
GO:0002062 [chondrocyte differentiation]
GO:0002862 [negative regulation of inflammatory response to antigenic stimulus]
GO:0004672 [protein kinase activity]
GO:0004674 [protein serine/threonine kinase activity]
GO:0004707 [MAP kinase activity]
GO:0004708 [MAP kinase kinase activity]
GO:0005515 [protein binding]
GO:0005524 [ATP binding]
GO:0005576 [extracellular region]
GO:0005634 [nucleus]
GO:0005654 [nucleoplasm]
GO:0005737 [cytoplasm]
GO:0005739 [mitochondrion]
GO:0005829 [cytosol]
GO:0006006 [glucose metabolic process]
GO:0006355 [regulation of DNA-templated transcription]
GO:0006357 [regulation of transcription by RNA polymerase II]
GO:0006366 [transcription by RNA polymerase II]
GO:0006468 [protein phosphorylation]
GO:0006915 [apoptotic process]
GO:0006935 [chemotaxis]
GO:0006974 [cellular response to DNA damage stimulus]
GO:0007165 [signal transduction]
GO:0007166 [cell surface receptor signaling pathway]
GO:0007178 [transmembrane receptor protein serine/threonine kinase signaling pathway]
GO:0007519 [skeletal muscle tissue development]
GO:0010628 [positive regulation of gene expression]
GO:0010831 [positive regulation of myotube differentiation]
GO:0016301 [kinase activity]
GO:0016310 [phosphorylation]
GO:0016607 [nuclear speck]
GO:0016740 [transferase activity]
GO:0018105 [peptidyl-serine phosphorylation]
GO:0019211 [phosphatase activator activity]
GO:0019395 [fatty acid oxidation]
GO:0019899 [enzyme binding]
GO:0019903 [protein phosphatase binding]
GO:0030168 [platelet activation]
GO:0030278 [regulation of ossification]
GO:0030316 [osteoclast differentiation]
GO:0031281 [positive regulation of cyclase activity]
GO:0031663 [lipopolysaccharide-mediated signaling pathway]
GO:0032495 [response to muramyl dipeptide]
GO:0032496 [response to lipopolysaccharide]
GO:0032735 [positive regulation of interleukin-12 production]
GO:0032868 [response to insulin]
GO:0034774 [secretory granule lumen]
GO:0035331 [negative regulation of hippo signaling]
GO:0035556 [intracellular signal transduction]
GO:0035924 [cellular response to vascular endothelial growth factor stimulus]
GO:0035994 [response to muscle stretch]
GO:0038066 [p38MAPK cascade]
GO:0042307 [positive regulation of protein import into nucleus]
GO:0042770 [signal transduction in response to DNA damage]
GO:0045648 [positive regulation of erythrocyte differentiation]
GO:0045663 [positive regulation of myoblast differentiation]
GO:0045944 [positive regulation of transcription by RNA polymerase II]
GO:0046323 [glucose import]
GO:0046326 [positive regulation of glucose import]
GO:0048010 [vascular endothelial growth factor receptor signaling pathway]
GO:0048273 [mitogen-activated protein kinase p38 binding]
GO:0048863 [stem cell differentiation]
GO:0051146 [striated muscle cell differentiation]
GO:0051149 [positive regulation of muscle cell differentiation]
GO:0051403 [stress-activated MAPK cascade]
GO:0051525 [NFAT protein binding]
GO:0060045 [positive regulation of cardiac muscle cell proliferation]
GO:0060348 [bone development]
GO:0070935 [3'-UTR-mediated mRNA stabilization]
GO:0071222 [cellular response to lipopolysaccharide]
GO:0071223 [cellular response to lipoteichoic acid]
GO:0071356 [cellular response to tumor necrosis factor]
GO:0071479 [cellular response to ionizing radiation]
GO:0071493 [cellular response to UV-B]
GO:0090090 [negative regulation of canonical Wnt signaling pathway]
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:0098978 [glutamatergic synapse]
GO:0099179 [regulation of synaptic membrane adhesion]
GO:0106310 [protein serine kinase activity]
GO:0140537 [transcription regulator activator activity]
GO:1900015 [regulation of cytokine production involved in inflammatory response]
GO:1901741 [positive regulation of myoblast fusion]
GO:1904813 [ficolin-1-rich granule lumen]
GO:2000379 [positive regulation of reactive oxygen species metabolic process]
Show all
 360 aa
41.3 kDa 		No 0
MAPK14-202
ENSP00000229795
ENST00000229795
Q16539
[Direct mapping] Mitogen-activated protein kinase 14
Show all
L7RSM2
[Target identity:100%; Query identity:100%] Mitogen-activated protein kinase 14
Show all
Enzymes
   ENZYME proteins
   Transferases
   Kinases
   CMGC Ser/Thr protein kinases
   MEMSAT-SVM predicted membrane proteins
   SPOCTOPUS predicted membrane proteins
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Cancer-related genes
   Candidate cancer biomarkers
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Kim et al 2014)
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000166 [nucleotide binding]
GO:0002862 [negative regulation of inflammatory response to antigenic stimulus]
GO:0004672 [protein kinase activity]
GO:0004674 [protein serine/threonine kinase activity]
GO:0004707 [MAP kinase activity]
GO:0004708 [MAP kinase kinase activity]
GO:0005515 [protein binding]
GO:0005524 [ATP binding]
GO:0005576 [extracellular region]
GO:0005634 [nucleus]
GO:0005654 [nucleoplasm]
GO:0005737 [cytoplasm]
GO:0005829 [cytosol]
GO:0006357 [regulation of transcription by RNA polymerase II]
GO:0006468 [protein phosphorylation]
GO:0006915 [apoptotic process]
GO:0006935 [chemotaxis]
GO:0007165 [signal transduction]
GO:0007166 [cell surface receptor signaling pathway]
GO:0010628 [positive regulation of gene expression]
GO:0010831 [positive regulation of myotube differentiation]
GO:0016301 [kinase activity]
GO:0016310 [phosphorylation]
GO:0016607 [nuclear speck]
GO:0016740 [transferase activity]
GO:0018105 [peptidyl-serine phosphorylation]
GO:0019899 [enzyme binding]
GO:0019903 [protein phosphatase binding]
GO:0030168 [platelet activation]
GO:0030316 [osteoclast differentiation]
GO:0031281 [positive regulation of cyclase activity]
GO:0032735 [positive regulation of interleukin-12 production]
GO:0034774 [secretory granule lumen]
GO:0035331 [negative regulation of hippo signaling]
GO:0035556 [intracellular signal transduction]
GO:0035924 [cellular response to vascular endothelial growth factor stimulus]
GO:0038066 [p38MAPK cascade]
GO:0042770 [signal transduction in response to DNA damage]
GO:0045648 [positive regulation of erythrocyte differentiation]
GO:0045663 [positive regulation of myoblast differentiation]
GO:0048010 [vascular endothelial growth factor receptor signaling pathway]
GO:0048273 [mitogen-activated protein kinase p38 binding]
GO:0051149 [positive regulation of muscle cell differentiation]
GO:0051403 [stress-activated MAPK cascade]
GO:0051525 [NFAT protein binding]
GO:0070935 [3'-UTR-mediated mRNA stabilization]
GO:0071222 [cellular response to lipopolysaccharide]
GO:0071223 [cellular response to lipoteichoic acid]
GO:0071479 [cellular response to ionizing radiation]
GO:0071493 [cellular response to UV-B]
GO:0090398 [cellular senescence]
GO:0090400 [stress-induced premature senescence]
GO:0098586 [cellular response to virus]
GO:0106310 [protein serine kinase activity]
GO:1900015 [regulation of cytokine production involved in inflammatory response]
GO:1901741 [positive regulation of myoblast fusion]
GO:1904813 [ficolin-1-rich granule lumen]
GO:2000379 [positive regulation of reactive oxygen species metabolic process]
Show all
 360 aa
41.5 kDa 		No 0
MAPK14-203
ENSP00000308669
ENST00000310795
Q16539
[Direct mapping] Mitogen-activated protein kinase 14
Show all
Enzymes
   ENZYME proteins
   Transferases
   Kinases
   CMGC Ser/Thr protein kinases
   MEMSAT-SVM predicted membrane proteins
   SPOCTOPUS predicted membrane proteins
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Cancer-related genes
   Candidate cancer biomarkers
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Kim et al 2014)
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000166 [nucleotide binding]
GO:0002862 [negative regulation of inflammatory response to antigenic stimulus]
GO:0004672 [protein kinase activity]
GO:0004674 [protein serine/threonine kinase activity]
GO:0004707 [MAP kinase activity]
GO:0004708 [MAP kinase kinase activity]
GO:0005515 [protein binding]
GO:0005524 [ATP binding]
GO:0005576 [extracellular region]
GO:0005634 [nucleus]
GO:0005654 [nucleoplasm]
GO:0005737 [cytoplasm]
GO:0005829 [cytosol]
GO:0006357 [regulation of transcription by RNA polymerase II]
GO:0006468 [protein phosphorylation]
GO:0006915 [apoptotic process]
GO:0006935 [chemotaxis]
GO:0007165 [signal transduction]
GO:0007166 [cell surface receptor signaling pathway]
GO:0010628 [positive regulation of gene expression]
GO:0010831 [positive regulation of myotube differentiation]
GO:0016301 [kinase activity]
GO:0016310 [phosphorylation]
GO:0016607 [nuclear speck]
GO:0016740 [transferase activity]
GO:0018105 [peptidyl-serine phosphorylation]
GO:0019899 [enzyme binding]
GO:0019903 [protein phosphatase binding]
GO:0030168 [platelet activation]
GO:0030316 [osteoclast differentiation]
GO:0031281 [positive regulation of cyclase activity]
GO:0032735 [positive regulation of interleukin-12 production]
GO:0034774 [secretory granule lumen]
GO:0035331 [negative regulation of hippo signaling]
GO:0035556 [intracellular signal transduction]
GO:0035924 [cellular response to vascular endothelial growth factor stimulus]
GO:0038066 [p38MAPK cascade]
GO:0042770 [signal transduction in response to DNA damage]
GO:0045648 [positive regulation of erythrocyte differentiation]
GO:0045663 [positive regulation of myoblast differentiation]
GO:0048010 [vascular endothelial growth factor receptor signaling pathway]
GO:0048273 [mitogen-activated protein kinase p38 binding]
GO:0051149 [positive regulation of muscle cell differentiation]
GO:0051403 [stress-activated MAPK cascade]
GO:0051525 [NFAT protein binding]
GO:0070935 [3'-UTR-mediated mRNA stabilization]
GO:0071222 [cellular response to lipopolysaccharide]
GO:0071223 [cellular response to lipoteichoic acid]
GO:0071479 [cellular response to ionizing radiation]
GO:0071493 [cellular response to UV-B]
GO:0090398 [cellular senescence]
GO:0090400 [stress-induced premature senescence]
GO:0098586 [cellular response to virus]
GO:0106310 [protein serine kinase activity]
GO:1900015 [regulation of cytokine production involved in inflammatory response]
GO:1901741 [positive regulation of myoblast fusion]
GO:1904813 [ficolin-1-rich granule lumen]
GO:2000379 [positive regulation of reactive oxygen species metabolic process]
Show all
 307 aa
35.5 kDa 		No 0
MAPK14-204
ENSP00000419837
ENST00000468133
B4E0K5
[Direct mapping] Mitogen-activated protein kinase
Show all
   MEMSAT-SVM predicted membrane proteins
   SPOCTOPUS predicted membrane proteins
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000165 [MAPK cascade]
GO:0004672 [protein kinase activity]
GO:0004707 [MAP kinase activity]
GO:0005524 [ATP binding]
GO:0005829 [cytosol]
GO:0006468 [protein phosphorylation]
GO:0016301 [kinase activity]
GO:0016310 [phosphorylation]
GO:0016607 [nuclear speck]
Show all
 283 aa
32.4 kDa 		No 0
MAPK14-205
ENSP00000419141
ENST00000472333
E7EX54
[Direct mapping] Mitogen-activated protein kinase 14
Show all
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0004672 [protein kinase activity]
GO:0005524 [ATP binding]
GO:0006468 [protein phosphorylation]
Show all
 132 aa
15.4 kDa 		No 0

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