MAPK12 - Mitogen-activated protein kinase 12 - human protein (Function)
 
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MAPK12 »  Mitogen-activated protein kinase 12   [ EC 2.7.11.24 ]  (MAPK 12)
 
Protein also known as:  Mitogen-activated protein kinase p38 gamma (MAP kinase p38 gamma).
Gene name:  MAPK12
Entry whose protein(s) existence is based on evidence at protein level
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1 104 2
GENE REF ISO

Function

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Overview 
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.  
7
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524] silver  
  • IEAOrtholog Compara
Magnesium ion bindingdefinition[GO:0000287]  
1
  • IDAUniProtKB
MAP kinase activitydefinition[GO:0004707]  
  • IEAEC 2 GO
Protein bindingdefinition[GO:0005515]  
2
  • IPIUniProtKB
  • IPIIntAct
Protein serine/threonine kinase activitydefinition[GO:0004674]  
2
  • IDABHF-UCL
  • IDAUniProtKB
GO biological process 
Cell cycle arrestdefinition[GO:0007050]  
1
  • TASPINC
DNA damage induced protein phosphorylationdefinition[GO:0006975]  
1
  • TASPINC
MAPK cascadedefinition[GO:0000165] silver  
  • IEAOrtholog Compara
Muscle organ developmentdefinition[GO:0007517]  
1
  • TASPINC
Myoblast differentiationdefinition[GO:0045445]  
1
  • IDAUniProtKB
Peptidyl-serine phosphorylationdefinition[GO:0018105]  
1
  • IDABHF-UCL
Regulation of transcription, DNA-templateddefinition[GO:0006355]  
  • IEAUniProtKB KW
Signal transductiondefinition[GO:0007165]  
1
  • TASPINC
Transcription, DNA-templateddefinition[GO:0006351]  
  • IEAUniProtKB KW
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.24: ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
It requires the following cofactor
Binds 2 magnesium ions.  
1
  • CuratedUniProtKB
It is regulated in the following manner
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.  
2
  • CuratedUniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathways:
Amyotrophic lateral sclerosis (ALS)  hsa05014+6300  
Chagas disease (American trypanosomiasis)  hsa05142+6300  
Dopaminergic synapse  hsa04728+6300  
Epithelial cell signaling in Helicobacter pylori infection  hsa05120+6300  
Fc epsilon RI signaling pathway  hsa04664+6300  
GnRH signaling pathway  hsa04912+6300  
Hepatitis C  hsa05160+6300  
Influenza A  hsa05164+6300  
Leishmaniasis  hsa05140+6300  
Leukocyte transendothelial migration  hsa04670+6300  
MAPK signaling pathway  hsa04010+6300  
Neurotrophin signaling pathway  hsa04722+6300  
NOD-like receptor signaling pathway  hsa04621+6300  
Oocyte meiosis  hsa04114+6300  
Osteoclast differentiation  hsa04380+6300  
Pertussis  hsa05133+6300  
Progesterone-mediated oocyte maturation  hsa04914+6300  
RIG-I-like receptor signaling pathway  hsa04622+6300  
Salmonella infection  hsa05132+6300  
Shigellosis  hsa05131+6300  
T cell receptor signaling pathway  hsa04660+6300  
Toll-like receptor signaling pathway  hsa04620+6300  
Toxoplasmosis  hsa05145+6300  
Tuberculosis  hsa05152+6300  
VEGF signaling pathway  hsa04370+6300  
According to Reactome, this protein belongs to the following pathways:
Activation of PPARGC1A (PGC-1alpha) by phosphorylation  REACT_200686  
CDO in myogenesis  REACT_21402  
DSCAM interactions  REACT_25299  
NOD1/2 Signaling Pathway  REACT_75776  
p38MAPK events  REACT_12065  
 

Biophysicochemical properties

Kinetic parameters
KM 313 uM for EGFR substrate peptide
KM 37 uM for ATP
KM 254 uM for GST-ATF2

Keywords

Biological process 
Cell cycle  definition   [KW-0131]
Stress response  definition   [KW-0346]
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: MAPK12
GenomeRNAi: 6300
PRO: PR:P53778
Chemistry
GuidetoPHARMACOLOGY: 1501