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Protein Page:
P38G (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitylation
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

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: Protein kinase, CMGC; EC; Protein kinase, Ser/Thr (non-receptor); Kinase, protein; CMGC group; MAPK family; MAPK/p38 subfamily; p38 subfamily
Chromosomal Location of Human Ortholog: 22q13.33
Cellular Component: cytoplasm; cytosol; mitochondrion; nucleoplasm
Molecular Function: ATP binding; magnesium ion binding; MAP kinase activity; protein binding; protein serine/threonine kinase activity
Biological Process: cell cycle arrest; DNA damage induced protein phosphorylation; MAPKKK cascade; muscle development; myoblast differentiation; peptidyl-serine phosphorylation; positive regulation of muscle cell differentiation; regulation of transcription, DNA-dependent; signal transduction; transcription, DNA-dependent; vascular endothelial growth factor receptor signaling pathway
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-ß Signaling  |  Toll-Like Receptor Signaling  |  Translation: eIF4E and p70S6K
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Modification Sites and Domains Show Modification Legend
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Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend

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LTP: 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.


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


0 1 S2 ______MSsPPPARS
1 2 S3‑p _____MSsPPPARSG
0 4 S180‑p GLARQADsEMtGyVV
2 196 T183‑p RQADsEMtGyVVTRW
2 819 Y185‑p ADsEMtGyVVTRWYR

S2‑p ______MssPPPARK
S3‑p _____MssPPPARKG

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