MAP2K2
The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is known to play a critical role in mitogen growth factor signal transduction. It phosphorylates and thus activates MAPK1/ERK2 and MAPK2/ERK3. The activation of this kinase itself is dependent on the Ser/Thr phosphorylation by MAP kinase kinase kinases. Mutations in this gene cause cardiofaciocutaneous syndrome (CFC syndrome), a disease characterized by heart defects, cognitive disability, and distinctive facial features similar to those found in Noonan syndrome. The inhibition or degradation of this kinase is also found to be involved in the pathogenesis of Yersinia and anthrax. A pseudogene, which is located on chromosome 7, has been identified for this gene. [provided by RefSeq, Jul 2008]
Full Name
Mitogen-Activated Protein Kinase Kinase 2
Function
Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases (By similarity).
Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation (PubMed:29433126).
Biological Process
ERK1 and ERK2 cascadeManual Assertion Based On ExperimentIMP:BHF-UCL
MAPK cascadeManual Assertion Based On ExperimentIBA:GO_Central
Peptidyl-serine autophosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of production of miRNAs involved in gene silencing by miRNAManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of protein serine/threonine kinase activityManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIMP:BHF-UCL
Regulation of early endosome to late endosome transportManual Assertion Based On ExperimentTAS:UniProtKB
Regulation of Golgi inheritanceManual Assertion Based On ExperimentTAS:UniProtKB
Regulation of stress-activated MAPK cascadeManual Assertion Based On ExperimentTAS:UniProtKB
Cellular Location
Cytoplasm
Membrane
Membrane localization is probably regulated by its interaction with KSR1.
Involvement in disease
Cardiofaciocutaneous syndrome 4 (CFC4):
A form of cardiofaciocutaneous syndrome, a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices.
PTM
MAPKK is itself dependent on Ser/Thr phosphorylation for activity catalyzed by MAP kinase kinase kinases (RAF or MEKK1). Phosphorylated by MAP2K1/MEK1 (By similarity).
(Microbial infection) Acetylation of Ser-222 and Ser-226 by Yersinia YopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway.
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Datasheet