mitogen activated protein kinase kinase 3 (MAP2K3, MAPK/ERK kinase 3, MEK3, PRKMK3)

Function: - MAP2K3 & MAP2K6 activate p38MAPKs - dual specificity kinase - activated by cytokines & environmental stress in vivo - catalyzes concomitant phosphorylation of Thr & Tyr in MAP kinase p38 - binds to DYRK1B/MIRK & increases its kinase activity - part of a complex with MAP3K3, RAC1 & CCM2 - interacts with Yersinia yopJ - activated by dual phosphorylation on Ser-218 & Thr-222 - autophosphorylated - phosphorylation on Ser-218 & Thr-222 by MEK kinases regulates positively the kinase activity - Yersinia yopJ may acetylate Ser/Thr residues, preventing phosphorylation & activation, thus blocking the MAPK signaling pathway ATP + a protein ADP + a phosphoprotein Structure: - belongs to the protein kinase superfamily, STE Ser/Thr protein kinase family, MAP kinase kinase subfamily - contains 1 protein kinase domain Alternative splicing: named isoforms=3 Expression: - abundant expression in skeletal muscle - widely expressed in other tissues Pathology: defects in MAP2K3 may be involved in colon cancer

Properties

SIZE: entity length = 347 aa MW = 39 kD STATE: active state MOTIF: kinase domain SITE: 64-325 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 70-78 ATP-binding site NAME: ATP-binding site SITE: 93-93 aspartate residue {D190} Ser phosphorylation site {S218} Thr phosphorylation site {T222}

References

UniProt :accession P46734

Databases & Figures

OMIM 602315 UniProt P46734 Pfam PF00069 Entrez Gene 5606 ENZYME 2.7.12.2 MAP kinase pathways