MAPKAPK2
entrez
9261
canonical
uniprot
P49137
canonical
ensembl
ENSG00000162889
resolver
ensp
ENSP00000294981
resolver
ensp
ENSP00000356070
resolver
genesymbol
MAPKAPK2
resolver
hgnc
HGNC:6887
resolver
uniprot
Q5SY30
resolver
uniprot
Q5SY41
resolver
uniprot
Q8IYD6
resolver
uniprot_entry
MAPK2_HUMAN
resolver
uniprot_sec
Q5SY30
resolver
uniprot_sec
Q5SY41
resolver
uniprot_sec
Q8IYD6
resolver
activity_regulation
ACTIVITY REGULATION: Activated following phosphorylation by p38-alpha/MAPK14 following various stresses. Inhibited following sumoylation. Specifically inhibited by pyrrolopyridine inhibitors.
uniprot
proteins
amino_acid_sequence
MLSNSQGQSPPVPFPAPAPPPQPPTPALPHPPAQPPPPPPQQFPQFHVKSGLQIKKNAIIDDYKVTSQVLGLGINGKVLQIFNKRTQEKFALKMLQDCPKARREVELHWRASQCPHIVRIVDVYENLYAGRKCLLIVMECLDGGELFSRIQDRGDQAFTEREASEIMKSIGEAIQYLHSINIAHRDVKPENLLYTSKRPNAILKLTDFGFAKETTSHNSLTTPCYTPYYVAPEVLGPEKYDKSCDMWSLGVIMYILLCGYPPFYSNHGLAISPGMKTRIRMGQYEFPNPEWSEVSEEVKMLIRNLLKTEPTQRMTITEFMNHPWIMQSTKVPQTPLHTSRVLKEDKERWEDVKEEMTSALATMRVDYEQIKIKKIEDASNPLLLKRRKKARALEAAALAH
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
FUNCTION: Stress-activated serine/threonine-protein kinase involved in cytokine production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, CEP131, ELAVL1, HNRNPA0, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Phosphorylates HSF1; leading to the interaction with HSP90 proteins and inhibiting HSF1 homotrimerization, DNA-binding and transactivation activities (PubMed:16278218). Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to the dissociation of HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impairment of their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to the regulation of the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity, leading to inhibition of dependent degradation of ARE-containing transcripts. Phosphorylates CEP131 in response to cellular stress induced by ultraviolet irradiation which promotes binding of CEP131 to 14-3-3 proteins and inhibits formation of novel centriolar satellites (PubMed:26616734). Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilization of GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. {ECO:0000269|PubMed:10383393, ECO:0000269|PubMed:11844797, ECO:0000269|PubMed:12456657, ECO:0000269|PubMed:12565831, ECO:0000269|PubMed:14499342, ECO:0000269|PubMed:14517288, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:15629715, ECO:0000269|PubMed:16278218, ECO:0000269|PubMed:16456544, ECO:0000269|PubMed:17481585, ECO:0000269|PubMed:18021073, ECO:0000269|PubMed:20932473, ECO:0000269|PubMed:26616734, ECO:0000269|PubMed:8093612, ECO:0000269|PubMed:8280084, ECO:0000269|PubMed:8774846}.
uniprot
proteins
mass_dalton
45568
uniprot
proteins
mutagenesis
MUTAGEN 93; /note="K->R: Kinase defective mutant, abolishes activity."; /evidence="ECO:0000269|PubMed:14517288"; MUTAGEN 207; /note="D->A: Kinase defective mutant, abolishes activity."; /evidence="ECO:0000269|PubMed:8846784"; MUTAGEN 222; /note="T->A: Strong decrease in kinase activity."; /evidence="ECO:0000269|PubMed:14517288, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:8846784"; MUTAGEN 222; /note="T->D: Mimicks phosphorylation state, leading to slight increase of basal kinase activity."; /evidence="ECO:0000269|PubMed:14517288, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:8846784"; MUTAGEN 222; /note="T->E: Mimicks phosphorylation state and constitutive protein kinase activity; when associated with E-334."; /evidence="ECO:0000269|PubMed:14517288, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:8846784"; MUTAGEN 272; /note="S->A: Strong decrease in kinase activity."; /evidence="ECO:0000269|PubMed:8846784"; MUTAGEN 272; /note="S->D: Mimicks phosphorylation state, leading to slight increase of basal kinase activity."; /evidence="ECO:0000269|PubMed:8846784"; MUTAGEN 334; /note="T->A: Slight decrease in kinase activity."; /evidence="ECO:0000269|PubMed:14517288, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:8846784"; MUTAGEN 334; /note="T->D,E: Mimicks phosphorylation state, leading to elevated basal kinase activity."; /evidence="ECO:0000269|PubMed:14517288, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:8846784"; MUTAGEN 334; /note="T->E: Mimicks phosphorylation state and constitutive protein kinase activity; when associated with E-222."; /evidence="ECO:0000269|PubMed:14517288, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:8846784"; MUTAGEN 353; /note="K->R: Induces decreased sumoylation and increase in protein kinase activity."; /evidence="ECO:0000269|PubMed:21131586
uniprot
proteins
post_translational_modification
PTM: Sumoylation inhibits the protein kinase activity. {ECO:0000269|PubMed:21131586}.; PTM: Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at Thr-222, Ser-272 and Thr-334. {ECO:0000269|PubMed:8846784}.
uniprot
proteins
protein_family
CAMK Ser/Thr protein kinase family
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
10383393
uniprot
proteins
pubmed
11844797
uniprot
proteins
pubmed
12171911
uniprot
proteins
pubmed
12456657
uniprot
proteins
pubmed
12565831
uniprot
proteins
pubmed
12791252
uniprot
proteins
pubmed
14499342
uniprot
proteins
pubmed
14517288
uniprot
proteins
pubmed
15014438
uniprot
proteins
pubmed
15094067
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15629715
uniprot
proteins
pubmed
16278218
uniprot
proteins
pubmed
16456544
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17255097
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17395714
uniprot
proteins
pubmed
17449059
uniprot
proteins
pubmed
17480064
uniprot
proteins
pubmed
17481585
uniprot
proteins
pubmed
17576063
uniprot
proteins
pubmed
18021073
uniprot
proteins
pubmed
18508601
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
20932473
uniprot
proteins
pubmed
21131586
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
26616734
uniprot
proteins
pubmed
8093612
uniprot
proteins
pubmed
8179591
uniprot
proteins
pubmed
8280084
uniprot
proteins
pubmed
8774846
uniprot
proteins
pubmed
8846784
uniprot
proteins
sequence_length
400
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20932473}. Nucleus {ECO:0000269|PubMed:20932473}. Note=Phosphorylation and subsequent activation releases the autoinhibitory helix, resulting in the export from the nucleus into the cytoplasm.
uniprot
proteins