Names & Taxonomy
- Uniprot ID:
- P53778
- Entry Name:
- MK12_HUMAN
- Status:
- reviewed
- Protein Names:
- Mitogen-activated protein kinase 12 (MAP kinase 12) (MAPK 12) (EC 2.7.11.24) (Extracellular signal-regulated kinase 6) (ERK-6) (Mitogen-activated protein kinase p38 gamma) (MAP kinase p38 gamma) (Stress-activated protein kinase 3)
- Gene Names:
- MAPK12 ERK6 SAPK3
- Gene Names Primary:
- MAPK12
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 367
- Sequence:
- MSSPPPARSGFYRQEVTKTAWEVRAVYRDLQPVGSGAYGAVCSAVDGRTGAKVAIKKLYRPFQSELFAKRAYRELRLLKHMRHENVIGLLDVFTPDETLDDFTDFYLVMPFMGTDLGKLMKHEKLGEDRIQFLVYQMLKGLRYIHAAGIIHRDLKPGNLAVNEDCELKILDFGLARQADSEMTGYVVTRWYRAPEVILNWMRYTQTVDIWSVGCIMAEMITGKTLFKGSDHLDQLKEIMKVTGTPPAEFVQRLQSDEAKNYMKGLPELEKKDFASILTNASPLAVNLLEKMLVLDAEQRVTAGEALAHPYFESLHDTEDEPQVQKYDDSFDDVDRTLDEWKRVTYKEVLSFKPPRQLGARVSKETPL
- Proteomes:
- UP000005640
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).
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 proinflammatory 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.
- Catalytic Activity:
- ATP + a protein = ADP + a phosphoprotein.
- Cofactor:
- COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
- Kinetics:
- BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=37 uM for ATP
- Enzyme Regulation:
- ENZYME 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-alpha.
- Active Site:
- ACT_SITE 153 153 Proton acceptor.
- Gene Ontology Go:
- cytoplasm
cytosol
mitochondrion
nucleoplasm
ATP binding
magnesium ion binding
MAP kinase activity
protein serine/threonine kinase activity
cell cycle arrest
DNA damage induced protein phosphorylation
mitochondrion organization
muscle cell differentiation
muscle organ development
myoblast differentiation
neurotrophin TRK receptor signaling pathway
organelle organization
peptidyl-serine phosphorylation
positive regulation of muscle cell differentiation
positive regulation of peptidase activity
Ras protein signal transduction
regulation of transcription, DNA-templated
signal transduction
transcription, DNA-templated
vascular endothelial growth factor receptor signaling pathway - Gene Ontology Biological Process:
- cell cycle arrest
DNA damage induced protein phosphorylation
mitochondrion organization
muscle cell differentiation
muscle organ development
myoblast differentiation
neurotrophin TRK receptor signaling pathway
organelle organization
peptidyl-serine phosphorylation
positive regulation of muscle cell differentiation
positive regulation of peptidase activity
Ras protein signal transduction
regulation of transcription, DNA-templated
signal transduction
transcription, DNA-templated
vascular endothelial growth factor receptor signaling pathway - Gene Ontology Molecular Function:
- ATP binding
magnesium ion binding
MAP kinase activity
protein serine/threonine kinase activity - Gene Ontology Cellular Component:
- cytoplasm
cytosol
mitochondrion
nucleoplasm - Keywords:
- 3D-structure
ATP-binding
Alternative splicing
Cell cycle
Complete proteome
Cytoplasm
Kinase
Magnesium
Metal-binding
Mitochondrion
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Serine/threonine-protein kinase
Stress response
Transcription
Transcription regulation
Transferase
Ubl conjugation - Interacts With:
- Q16512; P29074; Q8IUQ4