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Protein Page:
P38G (human)

Overview
P38G a proline-directed ser/thr MAP kinase, and one of four p38 kinases that play important roles in cellular responses to inflammatory cytokines, DNA damage, oxidative stress, and some GPCRs. Directly activate transcription factors and of other downstream kinases including MSK1, MSK2, eEF2K, MK2, and PRAK. MSK1 and -2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli. MK2 and -3 control gene expression mostly at the post-transcriptional level. eEF2K is important for the elongation of mRNA during translation. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17, which then cleaves the ectodomain of TGF-alpha family ligands, a process leading to the activation of EGFR signaling and cell proliferation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, CHOPO, p53 and MEF2C and MEF2A. The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. Interacts directly with HDAC3 interacts directly and selectively to repress ATF2 transcriptional activity, and regulate TNF gene expression in LPS-stimulated cells. Plays a role in myoblast differentiation and also in the down-regulation of cyclin D1 in response to hypoxia in adrenal cells suggesting that it may inhibit cell proliferation while promoting differentiation. Regulates UV-induced checkpoint signaling and repair of UV-induced DNA damage and G2 arrest after gamma-radiation exposure. Involved in the regulation of GLUT1 expression and basal glucose uptake in L6 myotubes; and negatively regulates GLUT4 expression and contraction-mediated glucose uptake in adult skeletal muscle. C- Jun phosphorylation is stimulated by p38-alpha and inhibited by p38-gamma, leading to a distinct AP-1 regulation. Required for the normal kinetochore localization of PLK1, prevents chromosomal instability and supports mitotic cell viability. Positively regulates the expansion of transient amplifying myogenic precursor cells during muscle growth and regeneration. Its expression is down-regulation by p38-alpha activation. Highly expressed in skeletal muscle and heart. Note: This description may include information from UniProtKB.
Protein type: EC 2.7.11.24; Kinase, protein; Protein kinase, Ser/Thr (non-receptor); Protein kinase, CMGC; CMGC group; MAPK family; MAPK/p38 subfamily; p38 subfamily
Cellular Component: nucleoplasm; mitochondrion; cytoplasm; nucleolus; cytosol; nucleus
Molecular Function: MAP kinase activity; protein serine/threonine kinase activity; protein binding; magnesium ion binding; ATP binding
Biological Process: myoblast differentiation; peptidyl-serine phosphorylation; muscle development; muscle cell differentiation; nerve growth factor receptor signaling pathway; DNA damage induced protein phosphorylation; regulation of transcription, DNA-dependent; transcription, DNA-dependent; Ras protein signal transduction; positive regulation of muscle cell differentiation; signal transduction; cell cycle arrest
Reference #:  P53778 (UniProtKB)
Alt. Names/Synonyms: ERK-6; ERK3; ERK6; Extracellular signal-regulated kinase 6; MAP kinase 12; MAP kinase p38 gamma; MAPK 12; MAPK12; Mitogen-activated protein kinase 12; mitogen-activated protein kinase 3; Mitogen-activated protein kinase p38 gamma; MK12; P38GAMMA; PRKM12; SAPK-3; SAPK3; Stress-activated protein kinase 3
Gene Symbols: MAPK12
Molecular weight: 41,940 Da
Basal Isoelectric point: 5.98  Predict pI for various phosphorylation states
CST Pathways:  Angiogenesis  |  B Cell Receptor Signaling  |  NF-kB Signaling  |  Phospholipase Signaling  |  Regulation of P38 MAPKs  |  T Cell Receptor Signaling  |  TGF-├č Signaling  |  Toll-Like Receptor Signaling  |  Translation: eIF4E and p70S6K
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

P38G

Protein Structure Not Found.


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Modification Sites and Domains  

Modification Sites in Parent Protein, Orthologs, and Isoforms  
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

 
0 1 S2 ______MSsPPPARS
1 1 S3-p _____MSsPPPARSG
0 1 Y12 PPARSGFYRQEVTKT
0 4 S180-p GLARQADsEMtGyVV
2 202 T183-p RQADsEMtGyVVTRW
2 838 Y185-p ADsEMtGyVVTRWYR
  mouse

 
S2-p ______MssPPPARK
S3-p _____MssPPPARKG
Y12-p PPARKGFyRQEVTKT
S180 GLARQADSEMtGyVV
T183-p RQADSEMtGyVVTRW
Y185-p ADSEMtGyVVTRWYR
  rat

 
S2 ______MSSPPPARK
S3 _____MSSPPPARKG
Y12 PPARKGFYRQEVTKT
S180 GLARQADSEMtGyVV
T183-p RQADSEMtGyVVTRW
Y185-p ADSEMtGyVVTRWYR
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