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NameMitogen-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 NameMAPK11
OrganismHuman
Amino acid sequence
>lcl|BSEQ0006615|Mitogen-activated protein kinase 11
MSGPRAGFYRQELNKTVWEVPQRLQGLRPVGSGAYGSVCSAYDARLRQKVAVKKLSRPFQ
SLIHARRTYRELRLLKHLKHENVIGLLDVFTPATSIEDFSEVYLVTTLMGADLNNIVKCQ
ALSDEHVQFLVYQLLRGLKYIHSAGIIHRDLKPSNVAVNEDCELRILDFGLARQADEEMT
GYVATRWYRAPEIMLNWMHYNQTVDIWSVGCIMAELLQGKALFPGSDYIDQLKRIMEVVG
TPSPEVLAKISSEHARTYIQSLPPMPQKDLSSIFRGANPLAIDLLGRMLVLDSDQRVSAA
EALAHAYFSQYHDPEDEPEAEPYDESVEAKERTLEEWKELTYQEVLSFKPPEPPKPPGSL
EIEQ
Number of residues364
Molecular Weight41356.875
Theoretical pI5.64
GO Classification
Functions
  • protein serine/threonine kinase activity
  • MAP kinase activity
  • ATP binding
Processes
  • toll-like receptor TLR6
  • transcription, DNA-templated
  • TRIF-dependent toll-like receptor signaling pathway
  • activation of MAPK activity
  • cellular response to virus
  • positive regulation of gene expression
  • response to stress
  • gene expression
  • positive regulation of interleukin-12 secretion
  • regulation of mRNA stability
  • MyD88-dependent toll-like receptor signaling pathway
  • MyD88-independent toll-like receptor signaling pathway
  • innate immune response
  • regulation of sequence-specific DNA binding transcription factor activity
  • muscle cell differentiation
  • stress-activated MAPK cascade
  • positive regulation of muscle cell differentiation
  • toll-like receptor 10 signaling pathway
  • neurotrophin TRK receptor signaling pathway
  • toll-like receptor 2 signaling pathway
  • Ras protein signal transduction
  • toll-like receptor 3 signaling pathway
  • vascular endothelial growth factor receptor signaling pathway
  • toll-like receptor 4 signaling pathway
  • intracellular signal transduction
  • toll-like receptor 5 signaling pathway
  • organelle organization
  • toll-like receptor 9 signaling pathway
  • mitochondrion organization
  • signal transduction
  • toll-like receptor signaling pathway
  • negative regulation of cardiac muscle cell proliferation
  • toll-like receptor TLR1
Components
  • cytosol
  • nucleoplasm
General FunctionProtein serine/threonine kinase activity
Specific FunctionSerine/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.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDQ15759
UniProtKB Entry NameMK11_HUMAN
Cellular LocationCytoplasm
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 IDU53442
GeneCard IDNot Available
GenAtlas IDMAPK11
HGNC IDHGNC:6873
Chromosome Location22
Locus22q13.33
References
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