MAPK12
entrez
6300
canonical
uniprot
P53778
canonical
ensembl
ENSG00000188130
resolver
ensp
ENSP00000215659
resolver
ensp
ENSP00000479972
resolver
genesymbol
MAPK12
resolver
genesymbol_syn
ERK6
resolver
genesymbol_syn
SAPK3
resolver
hgnc
HGNC:6874
resolver
uniprot
Q14260
resolver
uniprot
Q6IC53
resolver
uniprot
Q99588
resolver
uniprot
Q99672
resolver
uniprot_entry
MK12_HUMAN
resolver
uniprot_sec
Q14260
resolver
uniprot_sec
Q6IC53
resolver
uniprot_sec
Q99588
resolver
uniprot_sec
Q99672
resolver
activity_regulation
ACTIVITY REGULATION: Activated by phosphorylation on threonine and tyrosine. MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK12 induced by environmental stress, whereas MAP2K6/MKK6 is the major MAPK12 activator in response to TNF. {ECO:0000269|PubMed:10212242, ECO:0000269|PubMed:9430721}.
uniprot
proteins
amino_acid_sequence
MSSPPPARSGFYRQEVTKTAWEVRAVYRDLQPVGSGAYGAVCSAVDGRTGAKVAIKKLYRPFQSELFAKRAYRELRLLKHMRHENVIGLLDVFTPDETLDDFTDFYLVMPFMGTDLGKLMKHEKLGEDRIQFLVYQMLKGLRYIHAAGIIHRDLKPGNLAVNEDCELKILDFGLARQADSEMTGYVVTRWYRAPEVILNWMRYTQTVDIWSVGCIMAEMITGKTLFKGSDHLDQLKEIMKVTGTPPAEFVQRLQSDEAKNYMKGLPELEKKDFASILTNASPLAVNLLEKMLVLDAEQRVTAGEALAHPYFESLHDTEDEPQVQKYDDSFDDVDRTLDEWKRVTYKEVLSFKPPRQLGARVSKETPL
uniprot
proteins
disease_involvement
DISEASE: Note=MAPK is overexpressed in highly metastatic breast cancer cell lines and its expression is preferentially associated with basal-like and metastatic phenotypes of breast tumor samples.
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. MAPK12 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 such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in myoblast differentiation and also in the down-regulation of cyclin D1 in response to hypoxia in adrenal cells suggesting MAPK12 may inhibit cell proliferation while promoting differentiation. Phosphorylates DLG1. Following osmotic shock, MAPK12 in the cell nucleus increases its association with nuclear DLG1, thereby causing dissociation of DLG1-SFPQ complexes. This function is independent of its catalytic activity and could affect mRNA processing and/or gene transcription to aid cell adaptation to osmolarity changes in the environment. Regulates UV-induced checkpoint signaling and repair of UV-induced DNA damage and G2 arrest after gamma-radiation exposure. MAPK12 is involved in the regulation of SLC2A1 expression and basal glucose uptake in L6 myotubes; and negatively regulates SLC2A4 expression and contraction-mediated glucose uptake in adult skeletal muscle. C-Jun (JUN) phosphorylation is stimulated by MAPK14 and inhibited by MAPK12, leading to a distinct AP-1 regulation. MAPK12 is required for the normal kinetochore localization of PLK1, prevents chromosomal instability and supports mitotic cell viability. MAPK12-signaling is also positively regulating the expansion of transient amplifying myogenic precursor cells during muscle growth and regeneration. {ECO:0000269|PubMed:10848581, ECO:0000269|PubMed:14592936, ECO:0000269|PubMed:17724032, ECO:0000269|PubMed:20605917, ECO:0000269|PubMed:21172807, ECO:0000269|PubMed:8633070, ECO:0000269|PubMed:9430721}.
uniprot
proteins
mass_dalton
41940
uniprot
proteins
mutagenesis
MUTAGEN 179; /note="D->A: Emulation of the active state."; /evidence="ECO:0000269|PubMed:15284239"; MUTAGEN 185; /note="Y->F: Loss of activity."; /evidence="ECO:0000269|PubMed:8633070"; MUTAGEN 330; /note="F->S: No effect."; /evidence="ECO:0000269|PubMed:15284239
uniprot
proteins
post_translational_modification
PTM: Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K3/MKK3 and MAP2K6/MKK6, which activates the enzyme. {ECO:0000269|PubMed:11010976, ECO:0000269|PubMed:17724032}.; PTM: Ubiquitinated. Ubiquitination leads to degradation by the proteasome pathway. {ECO:0000269|PubMed:17724032}.
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
10212242
uniprot
proteins
pubmed
10508788
uniprot
proteins
pubmed
10591208
uniprot
proteins
pubmed
10848581
uniprot
proteins
pubmed
11010976
uniprot
proteins
pubmed
11991731
uniprot
proteins
pubmed
12167088
uniprot
proteins
pubmed
14592936
uniprot
proteins
pubmed
15284239
uniprot
proteins
pubmed
15461802
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17724032
uniprot
proteins
pubmed
20605917
uniprot
proteins
pubmed
20626350
uniprot
proteins
pubmed
21172807
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21532888
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
27246854
uniprot
proteins
pubmed
8633070
uniprot
proteins
pubmed
8920915
uniprot
proteins
pubmed
9169156
uniprot
proteins
pubmed
9430721
uniprot
proteins
sequence_length
367
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Mitochondrion. Note=Mitochondrial when associated with SH3BP5. In skeletal muscle colocalizes with SNTA1 at the neuromuscular junction and throughout the sarcolemma (By similarity). {ECO:0000250}.
uniprot
proteins