MAP2K6
entrez
5608
canonical
uniprot
P52564
canonical
ensembl
ENSG00000108984
resolver
ensp
ENSP00000467213
resolver
ensp
ENSP00000468348
resolver
genesymbol
MAP2K6
resolver
genesymbol_syn
MEK6
resolver
genesymbol_syn
MKK6
resolver
genesymbol_syn
PRKMK6
resolver
genesymbol_syn
SKK3
resolver
hgnc
HGNC:6846
resolver
uniprot
A8K3Y2
resolver
uniprot_entry
A8K3Y2_HUMAN
resolver
uniprot_entry
MP2K6_HUMAN
resolver
activity_regulation
ACTIVITY REGULATION: Activated by dual phosphorylation on Ser-207 and Thr-211 in response to a variety of cellular stresses, including UV radiation, osmotic shock, hypoxia, inflammatory cytokines, interferon gamma (IFNG), and less often by growth factors. MAP2K6/MKK6 is activated by the majority of M3Ks, such as MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K2/MEKK2, MAP3K3/MEKK3, MAP3K4/MEKK4, MAP3K7/TAK1, MAP3K11/MLK3 and MAP3K17/TAOK2. {ECO:0000269|PubMed:20364819, ECO:0000269|PubMed:8626699, ECO:0000269|PubMed:8663074}.
uniprot
proteins
amino_acid_sequence
MSQSKGKKRNPGLKIPKEAFEQPQTSSTPPRDLDSKACISIGNQNFEVKADDLEPIMELGRGAYGVVEKMRHVPSGQIMAVKRIRATVNSQEQKRLLMDLDISMRTVDCPFTVTFYGALFREGDVWICMELMDTSLDKFYKQVIDKGQTIPEDILGKIAVSIVKALEHLHSKLSVIHRDVKPSNVLINALGQVKMCDFGISGYLVDSVAKTIDAGCKPYMAPERINPELNQKGYSVKSDIWSLGITMIELAILRFPYDSWGTPFQQLKQVVEEPSPQLPADKFSAEFVDFTSQCLKKNSKERPTYPELMQHPFFTLHESKGTDVASFVKLILGD
uniprot
proteins
ec_number
2.7.12.2
uniprot
proteins
function
FUNCTION: Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. With MAP3K3/MKK3, catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinases p38 MAPK11, MAPK12, MAPK13 and MAPK14 and plays an important role in the regulation of cellular responses to cytokines and all kinds of stresses. Especially, MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK11 and MAPK13 induced by environmental stress, whereas MAP2K6/MKK6 is the major MAPK11 activator in response to TNF. MAP2K6/MKK6 also phosphorylates and activates PAK6. The p38 MAP kinase signal transduction pathway leads to direct activation of transcription factors. Nuclear targets of p38 MAP kinase include the transcription factors ATF2 and ELK1. Within the p38 MAPK signal transduction pathway, MAP3K6/MKK6 mediates phosphorylation of STAT4 through MAPK14 activation, and is therefore required for STAT4 activation and STAT4-regulated gene expression in response to IL-12 stimulation. The pathway is also crucial for IL-6-induced SOCS3 expression and down-regulation of IL-6-mediated gene induction; and for IFNG-dependent gene transcription. Has a role in osteoclast differentiation through NF-kappa-B transactivation by TNFSF11, and in endochondral ossification and since SOX9 is another likely downstream target of the p38 MAPK pathway. MAP2K6/MKK6 mediates apoptotic cell death in thymocytes. Acts also as a regulator for melanocytes dendricity, through the modulation of Rho family GTPases. {ECO:0000269|PubMed:10961885, ECO:0000269|PubMed:11727828, ECO:0000269|PubMed:15550393, ECO:0000269|PubMed:20869211, ECO:0000269|PubMed:8622669, ECO:0000269|PubMed:8626699, ECO:0000269|PubMed:8663074, ECO:0000269|PubMed:9218798}.
uniprot
proteins
mass_dalton
37492
uniprot
proteins
mutagenesis
MUTAGEN 207; /note="S->A: Decreased phosphorylation by MAP3K, leading to inactivation."; /evidence="ECO:0000269|PubMed:8622669"; MUTAGEN 207; /note="S->E: Mimics phosphorylation. Increased interaction with FBXO31. Constitutive activation according to PubMed:8622669, but not to PubMed:8621675."; /evidence="ECO:0000269|PubMed:24936062, ECO:0000269|PubMed:8621675, ECO:0000269|PubMed:8622669"; MUTAGEN 211; /note="T->A: Inactivation."; /evidence="ECO:0000269|PubMed:24936062, ECO:0000269|PubMed:8622669"; MUTAGEN 211; /note="T->E: Mimics phosphorylation. Increased interaction with FBXO31.Constitutive activation according to PubMed:8622669, but not to PubMed:8621675."; /evidence="ECO:0000269|PubMed:24936062, ECO:0000269|PubMed:8621675, ECO:0000269|PubMed:8622669
uniprot
proteins
post_translational_modification
PTM: Weakly autophosphorylated (PubMed:16728640, PubMed:24936062). Phosphorylated at Ser-207 and Thr-211 by the majority of M3Ks, such as MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K2/MEKK2, MAP3K3/MEKK3, MAP3K4/MEKK4, MAP3K7/TAK1, MAP3K11/MLK3 and MAP3K17/TAOK2 (PubMed:16728640, PubMed:24936062). {ECO:0000269|PubMed:16728640, ECO:0000269|PubMed:24936062}.; PTM: In response to genotoxic stress, MAP3K-phosphorylated MAP2K6 is ubiquitinated and degraded by the SCF(FBXO31) complex. {ECO:0000269|PubMed:24936062}.; PTM: (Microbial infection) Acetylation of Ser-207 and Thr-211 by Yersinia YopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway. {ECO:0000269|PubMed:16728640, ECO:0000269|PubMed:22802624}.
uniprot
proteins
protein_family
MAP kinase kinase subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
STE Ser/Thr protein kinase family
uniprot
proteins
pubmed
10094049
uniprot
proteins
pubmed
10347227
uniprot
proteins
pubmed
10497253
uniprot
proteins
pubmed
10961885
uniprot
proteins
pubmed
11104681
uniprot
proteins
pubmed
11279118
uniprot
proteins
pubmed
11460167
uniprot
proteins
pubmed
11689443
uniprot
proteins
pubmed
11727828
uniprot
proteins
pubmed
15229216
uniprot
proteins
pubmed
15375157
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15550393
uniprot
proteins
pubmed
15866172
uniprot
proteins
pubmed
16728640
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19141286
uniprot
proteins
pubmed
20364819
uniprot
proteins
pubmed
20869211
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22802624
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24936062
uniprot
proteins
pubmed
8621675
uniprot
proteins
pubmed
8622669
uniprot
proteins
pubmed
8626699
uniprot
proteins
pubmed
8663074
uniprot
proteins
pubmed
8861944
uniprot
proteins
pubmed
9218798
uniprot
proteins
pubmed
9768359
uniprot
proteins
pubmed
9779990
uniprot
proteins
pubmed
9841871
uniprot
proteins
sequence_length
334
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9768359}. Cytoplasm {ECO:0000269|PubMed:9768359}. Cytoplasm, cytoskeleton {ECO:0000269|PubMed:9768359}. Note=Binds to microtubules. {ECO:0000269|PubMed:9768359}.
uniprot
proteins