Mitogen-activated protein kinase 11
| Name | Mitogen-activated protein kinase 11 |
|---|---|
| Synonyms | 2.7.11.24 MAP kinase 11 MAP kinase p38 beta Mitogen-activated protein kinase p38 beta p38-2 p38b PRKM11 SAPK2 SAPK2B Stress-activated protein kinase 2b |
| Gene Name | MAPK11 |
| Organism | Human |
| Amino acid sequence | >lcl|BSEQ0006615|Mitogen-activated protein kinase 11 MSGPRAGFYRQELNKTVWEVPQRLQGLRPVGSGAYGSVCSAYDARLRQKVAVKKLSRPFQ SLIHARRTYRELRLLKHLKHENVIGLLDVFTPATSIEDFSEVYLVTTLMGADLNNIVKCQ ALSDEHVQFLVYQLLRGLKYIHSAGIIHRDLKPSNVAVNEDCELRILDFGLARQADEEMT GYVATRWYRAPEIMLNWMHYNQTVDIWSVGCIMAELLQGKALFPGSDYIDQLKRIMEVVG TPSPEVLAKISSEHARTYIQSLPPMPQKDLSSIFRGANPLAIDLLGRMLVLDSDQRVSAA EALAHAYFSQYHDPEDEPEAEPYDESVEAKERTLEEWKELTYQEVLSFKPPEPPKPPGSL EIEQ |
| Number of residues | 364 |
| Molecular Weight | 41356.875 |
| Theoretical pI | 5.64 |
| GO Classification |
Functions
ATP binding protein serine/threonine kinase activity MAP kinase activity Processes
response to stress cellular response to virus organelle organization toll-like receptor 10 signaling pathway gene expression positive regulation of interleukin-12 secretion mitochondrion organization toll-like receptor 2 signaling pathway negative regulation of cardiac muscle cell proliferation toll-like receptor 3 signaling pathway transcription, DNA-templated toll-like receptor 4 signaling pathway innate immune response activation of MAPK activity toll-like receptor 5 signaling pathway muscle cell differentiation positive regulation of gene expression toll-like receptor 9 signaling pathway positive regulation of muscle cell differentiation regulation of mRNA stability signal transduction toll-like receptor signaling pathway neurotrophin TRK receptor signaling pathway MyD88-dependent toll-like receptor signaling pathway toll-like receptor TLR1 Ras protein signal transduction MyD88-independent toll-like receptor signaling pathway toll-like receptor TLR6 vascular endothelial growth factor receptor signaling pathway regulation of sequence-specific DNA binding transcription factor activity TRIF-dependent toll-like receptor signaling pathway intracellular signal transduction stress-activated MAPK cascade Components
cytosol nucleoplasm |
| General Function | Protein serine/threonine kinase activity |
| Specific Function | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK11 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. MAPK11 functions are mostly redundant with those of MAPK14. 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. 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. 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. Additional examples of p38 MAPK substrates are the 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. |
| Transmembrane Regions | |
| GenBank Protein ID | |
| UniProtKB ID | Q15759 |
| UniProtKB Entry Name | MK11_HUMAN |
| Cellular Location | Cytoplasm |
| Gene sequence | >lcl|BSEQ0017085|Mitogen-activated protein kinase 11 (MAPK11) ATGTCGGGCCCTCGCGCCGGCTTCTACCGGCAGGAGCTGAACAAGACCGTGTGGGAGGTG CCGCAGCGGCTGCAGGGGCTGCGCCCGGTGGGCTCCGGCGCCTACGGCTCCGTCTGTTCG GCCTACGACGCCCGGCTGCGCCAGAAGGTGGCGGTGAAGAAGCTGTCGCGCCCCTTCCAG TCGCTGATCCACGCGCGCAGAACGTACCGGGAGCTGCGGCTGCTCAAGCACCTGAAGCAC GAGAACGTCATCGGGCTTCTGGACGTCTTCACGCCGGCCACGTCCATCGAGGACTTCAGC GAAGTGTACTTGGTGACCACCCTGATGGGCGCCGACCTGAACAACATCGTCAAGTGCCAG GCGCTGAGCGACGAGCACGTTCAATTCCTGGTTTACCAGCTGCTGCGCGGGCTGAAGTAC ATCCACTCGGCCGGGATCATCCACCGGGACCTGAAGCCCAGCAACGTGGCTGTGAACGAG GACTGTGAGCTCAGGATCCTGGATTTCGGGCTGGCGCGCCAGGCGGACGAGGAGATGACC GGCTATGTGGCCACGCGCTGGTACCGGGCACCTGAGATCATGCTCAACTGGATGCATTAC AACCAAACAGTGGATATCTGGTCCGTGGGCTGCATCATGGCTGAGCTGCTCCAGGGCAAG GCCCTCTTCCCGGGAAGCGACTACATTGACCAGCTGAAGCGCATCATGGAAGTGGTGGGC ACACCCAGCCCTGAGGTTCTGGCAAAAATCTCCTCAGAACACGCCCGGACATATATCCAG TCCCTGCCCCCCATGCCCCAGAAGGACCTGAGCAGCATCTTCCGTGGAGCCAACCCCCTG GCCATAGACCTCCTTGGAAGGATGCTGGTGCTGGACAGTGACCAGAGGGTCAGTGCAGCT GAGGCACTGGCCCACGCCTACTTCAGCCAGTACCACGACCCCGAGGATGAGCCAGAGGCC GAGCCATATGATGAGAGCGTTGAGGCCAAGGAGCGCACGCTGGAGGAGTGGAAGGAGCTC ACTTACCAGGAAGTCCTCAGCTTCAAGCCCCCAGAGCCACCGAAGCCACCTGGCAGCCTG GAGATTGAGCAGTGA |
| GenBank Gene ID | U53442 |
| GeneCard ID | None |
| GenAtlas ID | MAPK11 |
| HGNC ID | HGNC:6873 |
| Chromosome Location | 22 |
| Locus | 22q13.33 |
| References |
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Related FRC
| FRCD ID | Name | Exact Mass | Structure |
|---|---|---|---|
Cadmium |
112.414 |