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mitogen-activated protein kinase 12; extracellular signal-regulated kinase 6; ERK-6; ERK5; stress-activated protein kinase 3; mitogen-activated protein kinase p38 gamma; MAP kinase p38 gamma (MAPK12, ERK6, SAPK3)
Function:
- responds to activation by environmental stress & pro-inflammatory cytokines by phosphorylating downstream targets
- role in myoblast differentiation
- role in down-regulation of cyclin D1 in response to hypoxia in adrenal cells
- MAPK12 may inhibit cell proliferation while promoting differentiation
- phosphorylates myelin-basic protein
- activated by phosphorylation on Thr & Tyr (putative)
- dually phosphorylated on Thr-183 & Tyr-185, which activates the enzyme (putative)
- interacts with the PDZ domain of syntrophin SNTA1
- interacts with SH3BP5
Cofactor: binds 2 Mg+2
Structure:
- monomer
- the TXY motif contains the Thr & Tyr whose phosphorylation activates the MAP kinases
- belongs to the protein kinase superfamily, CMGC Ser/Thr protein kinase family, MAP kinase subfamily
- contains 1 protein kinase domain
Compartment:
- cytoplasm. mitochondrion
- mitochondrial when associated with SH3BP5
Expression: highly expressed in skeletal muscle & heart
Interactions
molecular events
General
p38MAPK subfamily
Properties
SIZE: entity length = 367 aa
MW = 42 kD
COMPARTMENT: mitochondria
cytoplasm
STATE: active state
MOTIF: kinase domain
SITE: 27-311
MOTIF: ATP-binding site
NAME: ATP-binding site
SITE: 33-41
Tyr phosphorylation site {Y27}
ATP-binding site
NAME: ATP-binding site
SITE: 56-56
aspartate residue {D153}
TXY {183-185}
Thr phosphorylation site {T183}
Tyr phosphorylation site {Y185}
References
UniProt :accession P53778
Component-of
dystrophin associated protein complex (DPC)
Databases & Figures
OMIM 602399
UniProt P53778
Pfam PF00069
Entrez Gene 6300
Kegg hsa:6300
ENZYME 2.7.11.24
MAP kinase pathways