Tchem MAPK12 Mitogen-activated protein kinase 12

Protein Summary

Description

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. Activation of members of the mitogen-activated protein kinase family is a major mechanism for transduction of extracellular signals. Stress-activated protein kinases are one subclass of MAP kinases. The protein encoded by this gene functions as a signal transducer during differentiation of myoblasts to myotubes. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P53778
• Q14260
• Q6IC53
• Q99588
• Q99672
• MAP kinase 12

Gene Name

• MAPK12

Ensembl ID

• ENST00000215659
• ENSP00000215659
• ENSG00000188130
• ENST00000622558
• ENSP00000479972

Symbol

• ERK6
• SAPK3
• ERK3
• ERK6
• ERK-6
• SAPK3
• PRKM12
• SAPK-3
• MAPK 12
• P38GAMMA

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	0.98
kinase perturbation	0.88
protein domain	0.85
biological process	0.84
PubMedID	0.76

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Mitogen-activated Protein Kinase 12

DTO Classes

Protein / Kinase / Protein Kinase / Cmgc Group / Mapk Family / P38 Subfamily / Mitogen-activated Protein Kinase 12

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 132.42   (req: < 5)

Gene RIFs: 44   (req: <= 3)

Antibodies: 496   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 132.42   (req: >= 5)

Gene RIFs: 44   (req: > 3)

Antibodies: 496   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 15

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 7

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0