Aliases for MAP2K1 Gene
External Ids for MAP2K1 Gene
Previous HGNC Symbols for MAP2K1 Gene
Previous GeneCards Identifiers for MAP2K1 Gene
The protein encoded by this gene is a member of the dual specificity protein kinase family, which acts as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon wide variety of extra- and intracellular signals. As an essential component of MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as proliferation, differentiation, transcription regulation and development. [provided by RefSeq, Jul 2008]
MAP2K1 is a dual-specificity kinase known for it's involvement in the ERK pathway by activation of ERK1 and ERK2. MAP2K1 activating mutations have been observed in a number of cancers including ovarian, melanoma and lung. These activating mutations are generally found in the N-terminal negative regulatory region or the ATP-binding region of the N-terminal lobe. Inhibitors of MEK genes have been shown to inhibit tumor growth in these cases.
GeneCards Summary for MAP2K1 Gene
MAP2K1 (Mitogen-Activated Protein Kinase Kinase 1) is a Protein Coding gene. Diseases associated with MAP2K1 include Cardiofaciocutaneous Syndrome 3 and Cardiofaciocutaneous Syndrome 1. Among its related pathways are Association Between Physico-Chemical Features and Toxicity Associated Pathways and Common Cytokine Receptor Gamma-Chain Family Signaling Pathways. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is MAP2K2.
UniProtKB/Swiss-Prot Summary for MAP2K1 Gene
Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. 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). Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis.