MAPK11
entrez
5600
canonical
uniprot
Q15759
canonical
ensembl
ENSG00000185386
resolver
ensp
ENSP00000333685
resolver
genesymbol
MAPK11
resolver
genesymbol_syn
PRKM11
resolver
genesymbol_syn
SAPK2
resolver
genesymbol_syn
SAPK2B
resolver
hgnc
HGNC:6873
resolver
uniprot
A8K730
resolver
uniprot
B0LPG1
resolver
uniprot
B7Z630
resolver
uniprot
E7ETQ1
resolver
uniprot
L7RT27
resolver
uniprot
O00284
resolver
uniprot
O15472
resolver
uniprot
Q2XNF2
resolver
uniprot_entry
MK11_HUMAN
resolver
uniprot_sec
A8K730
resolver
uniprot_sec
B0LPG1
resolver
uniprot_sec
B7Z630
resolver
uniprot_sec
E7ETQ1
resolver
uniprot_sec
L7RT27
resolver
uniprot_sec
O00284
resolver
uniprot_sec
O15472
resolver
uniprot_sec
Q2XNF2
resolver
activity_regulation
ACTIVITY REGULATION: Activated by phosphorylation on threonine and tyrosine by MAP2K3/MKK3, MAP2K4/MKK4 and MAP2K6/MKK6. MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK11 induced by environmental stress. HDAC3 interacts directly and selectively with MAPK11 to repress ATF2 transcriptional activity, and regulate TNF gene expression in LPS-stimulated cells. Inhibited by SB203580 and pyridinyl-imidazole related compounds. {ECO:0000269|PubMed:11359773, ECO:0000269|PubMed:15356147, ECO:0000269|PubMed:9218798, ECO:0000269|PubMed:9430721}.
uniprot
proteins
amino_acid_sequence
MSGPRAGFYRQELNKTVWEVPQRLQGLRPVGSGAYGSVCSAYDARLRQKVAVKKLSRPFQSLIHARRTYRELRLLKHLKHENVIGLLDVFTPATSIEDFSEVYLVTTLMGADLNNIVKCQALSDEHVQFLVYQLLRGLKYIHSAGIIHRDLKPSNVAVNEDCELRILDFGLARQADEEMTGYVATRWYRAPEIMLNWMHYNQTVDIWSVGCIMAELLQGKALFPGSDYIDQLKRIMEVVGTPSPEVLAKISSEHARTYIQSLPPMPQKDLSSIFRGANPLAIDLLGRMLVLDSDQRVSAAEALAHAYFSQYHDPEDEPEAEPYDESVEAKERTLEEWKELTYQEVLSFKPPEPPKPPGSLEIEQ
uniprot
proteins
ec_number
2.7.11.24
uniprot
proteins
function
FUNCTION: Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:12452429, PubMed:20626350, PubMed:35857590). 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 pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors (PubMed:12452429, PubMed:20626350, PubMed:35857590). Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each (PubMed:12452429, PubMed:20626350, PubMed:35857590). MAPK11 functions are mostly redundant with those of MAPK14 (PubMed:12452429, PubMed:20626350, PubMed:35857590). Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets (PubMed:12452429, PubMed:20626350). 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 (PubMed:9687510). 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 (PubMed:11154262). 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 (PubMed:10330143, PubMed:15356147, PubMed:9430721). The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers (PubMed:10330143, PubMed:15356147, PubMed:9430721). 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 NLRP1 downstream of MAP3K20/ZAK in response to UV-B irradiation and ribosome collisions, promoting activation of the NLRP1 inflammasome and pyroptosis (PubMed:35857590). Phosphorylates methyltransferase DOT1L on 'Ser-834', 'Thr-900', 'Ser-902', 'Thr-984', 'Ser-1001', 'Ser-1009' and 'Ser-1104' (PubMed:38270553). {ECO:0000269|PubMed:10330143, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:15356147, ECO:0000269|PubMed:35857590, ECO:0000269|PubMed:38270553, ECO:0000269|PubMed:9430721, ECO:0000269|PubMed:9687510, ECO:0000303|PubMed:12452429, ECO:0000303|PubMed:20626350}.
uniprot
proteins
mass_dalton
41357
uniprot
proteins
mutagenesis
MUTAGEN 180; /note="T->A: Inactivation."; /evidence="ECO:0000269|PubMed:15356147"; MUTAGEN 182; /note="Y->F: Inactivation."; /evidence="ECO:0000269|PubMed:15356147
uniprot
proteins
post_translational_modification
PTM: Dually phosphorylated on Thr-180 and Tyr-182 by MAP2K3/MKK3, MAP2K4/MKK4 and MAP2K6/MKK6, which activates the enzyme. {ECO:0000269|PubMed:15356147}.
uniprot
proteins
protein_family
CMGC Ser/Thr protein kinase family
uniprot
proteins
protein_family
MAP kinase subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
10330143
uniprot
proteins
pubmed
10591208
uniprot
proteins
pubmed
11154262
uniprot
proteins
pubmed
11359773
uniprot
proteins
pubmed
12452429
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15356147
uniprot
proteins
pubmed
15461802
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19622861
uniprot
proteins
pubmed
20626350
uniprot
proteins
pubmed
35857590
uniprot
proteins
pubmed
38270553
uniprot
proteins
pubmed
8663524
uniprot
proteins
pubmed
9207191
uniprot
proteins
pubmed
9218798
uniprot
proteins
pubmed
9235954
uniprot
proteins
pubmed
9430721
uniprot
proteins
pubmed
9687510
uniprot
proteins
sequence_length
364
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
uniprot
proteins