P38A iso3 a proline-directed ser/thr MAP kinase, and one of four p38 kinases that play important roles in cellular responses to inflammatory cytokines, DNA damage, oxidative stress, and some GPCRs, leading to direct activation of transcription factors and of other downstream kinases including MSK1, MSK2, eEF2K, MAPKAPK2 and -5 (MK2, -5), and PRAK. MSK1 and -2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli. eEF2K is important for the elongation of mRNA during translation. MK2 & 5 control gene expression mostly at the post-transcriptional level. 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, which then cleaves the ectodomain of TGF-alpha family ligands, a process leading to the activation of EGFR signaling and cell proliferation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Examples include ATF1, ATF2, ATF6, ELK1, PTPRH, CHOPO, 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 phosphorylation of histone H3 on Ser10. Phosphorylates the ubiquitin ligase SIAH2, regulating its activity towards EGLN3. May also inhibit the lysosomal degradation pathway of autophagy by interfering with the intracellular trafficking of the transmembrane protein ATG9. Regulates the endocytosis of membrane receptors that depend on RAB5A. Regulates the clathrin-mediated internalization of EGFR induced by inflammatory cytokines and UV irradiation by phosphorylating the EGFR and RAB5A effectors. Required in mid-fetal development for the growth of embryo-derived blood vessels in the labyrinth layer of the placenta. Plays an essential role in developmental and stress-induced erythropoiesis, through regulation of EPO gene expression. Activated by cell stresses such as DNA damage, heat shock, osmotic shock, anisomycin and sodium arsenite, as well as pro-inflammatory stimuli such as LPS and IL-1. Phosphorylated by ZAP70 in an alternative activation pathway in response to TCR signaling in T-cells, a pathway is inhibited by GADD45A. Five alternatively spliced isoforms of the human protein have been reported. Isoform 3 (Mxi2) activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2. Isoform 4 (Exip) may play a role in the early onset of apoptosis Note: This description may include information from UniProtKB.
Protein type: EC; Kinase, protein; Protein kinase, CMGC; Protein kinase, Ser/Thr (non-receptor)
Chromosomal Location of mouse Ortholog: 17 A3.3|17 14.85 cM
Cellular Component:  cell; cytoplasm; cytosol; glutamatergic synapse; mitochondrion; nuclear speck; nucleus; spindle pole
Molecular Function:  ATP binding; enzyme binding; kinase activity; MAP kinase activity; mitogen-activated protein kinase p38 binding; NFAT protein binding; nucleotide binding; protein binding; protein C-terminus binding; protein kinase activity; protein phosphatase binding; protein serine/threonine kinase activity; transferase activity
Biological Process:  angiogenesis; apoptotic process; cartilage condensation; cell morphogenesis; cellular response to DNA damage stimulus; cellular response to ionizing radiation; cellular response to lipopolysaccharide; cellular response to lipoteichoic acid; cellular response to organic substance; cellular response to tumor necrosis factor; cellular response to vascular endothelial growth factor stimulus; cellular response to virus; chondrocyte differentiation; DNA damage checkpoint; fatty acid oxidation; glucose metabolic process; intracellular signal transduction; lipopolysaccharide-mediated signaling pathway; myoblast differentiation involved in skeletal muscle regeneration; negative regulation of canonical Wnt signaling pathway; osteoclast differentiation; p38MAPK cascade; peptidyl-serine phosphorylation; phosphorylation; placenta development; positive regulation of brown fat cell differentiation; positive regulation of cardiac muscle cell proliferation; positive regulation of cyclase activity; positive regulation of cytokine secretion involved in immune response; positive regulation of erythrocyte differentiation; positive regulation of gene expression; positive regulation of glucose import; positive regulation of interleukin-12 secretion; positive regulation of macrophage chemotaxis; positive regulation of metallopeptidase activity; positive regulation of myoblast differentiation; positive regulation of myoblast fusion; positive regulation of myotube differentiation; positive regulation of protein import into nucleus; positive regulation of reactive oxygen species metabolic process; positive regulation of transcription by RNA polymerase II; protein autophosphorylation; protein phosphorylation; regulation of cytokine production involved in inflammatory response; regulation of gene expression; regulation of ossification; regulation of synaptic membrane adhesion; regulation of transcription by RNA polymerase II; regulation of transcription, DNA-templated; response to lipopolysaccharide; response to muramyl dipeptide; response to muscle stretch; signal transduction in response to DNA damage; skeletal muscle tissue development; stress-activated MAPK cascade; stress-induced premature senescence; striated muscle cell differentiation; transmembrane receptor protein serine/threonine kinase signaling pathway; vascular endothelial growth factor receptor signaling pathway
Reference #:  P47811-3 (UniProtKB)
Alt. Names/Synonyms: Crk; Crk1; CSB; Csbp1; Csbp2; MAP kinase 14; MAP kinase p38 alpha; MAPK 14; Mapk14; Mitogen-activated protein kinase 14; Mitogen-activated protein kinase p38 alpha; MK14; Mxi; Mxi2; p38; p38 MAP kinase alpha; p38 MAPK; p38-; p38-alpha; P38A; P38A iso3; p38alpha; p38M; p38MAPK; PRKM14; PRKM15
Gene Symbols: Mapk14
Molecular weight: 41,487 Da
Basal Isoelectric point: 5.6  Predict pI for various phosphorylation states
CST Pathways:  Angiogenesis  |  B Cell Receptor Signaling  |  NF-kB Signaling  |  Phospholipase Signaling  |  Regulation of P38 MAPKs  |  T Cell Receptor Signaling  |  TGF-ß Signaling  |  Toll-Like Receptor Signaling  |  Translation: eIF4E and p70S6K
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P38A iso3

Protein Structure Not Found.

Cross-references to other databases:  Pfam  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene  |  Ensembl Protein