Human Gene MAP2K1 (ENST00000307102.10) from GENCODE V43
Description: Homo sapiens mitogen-activated protein kinase kinase 1 (MAP2K1), mRNA. (from RefSeq NM_002755) RefSeq Summary (NM_002755): 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]. Gencode Transcript: ENST00000307102.10 Gencode Gene: ENSG00000169032.11 Transcript (Including UTRs) Position: hg38 chr15:66,386,912-66,491,544 Size: 104,633 Total Exon Count: 11 Strand: + Coding Region Position: hg38 chr15:66,387,348-66,490,615 Size: 103,268 Coding Exon Count: 11
ID:MP2K1_HUMAN DESCRIPTION: RecName: Full=Dual specificity mitogen-activated protein kinase kinase 1; Short=MAP kinase kinase 1; Short=MAPKK 1; Short=MKK1; EC=220.127.116.11; AltName: Full=ERK activator kinase 1; AltName: Full=MAPK/ERK kinase 1; Short=MEK 1; FUNCTION: 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. 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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. ENZYME REGULATION: Ras proteins such as HRAS mediate the activation of RAF proteins such as RAF1 or BRAF which in turn activate extracellular signal-regulated kinases (ERK) through MAPK (mitogen-activated protein kinases) and ERK kinases MAP2K1/MEK1 and MAP2K2/MEK2. Activation occurs through phosphorylation of Ser- 218 and Ser-222. MAP2K1/MEK1 is also the target of negative feed- back regulation by its substrate kinases, such as MAPK1/ERK2. These phosphorylate MAP2K1/MEK1 on Thr-292, thereby facilitating dephosphorylation of the activating residues Ser-218 and Ser-222. Inhibited by serine/threonine phosphatase 2A (By similarity). Many inhibitors have been identified including pyrrole derivatives, TAK-733 (one of a series of 8-methylpyrido[2,3-d]pyrimidine- 4,7(3H,8H)-dione derivatives), CH4987655 and RDEA119/BAY 869766. SUBUNIT: Found in a complex with at least BRAF, HRAS1, MAP2K1, MAPK3/ERK1 and RGS14 (By similarity). Forms a heterodimer with MAP2K2/MEK2 (By similarity). Forms heterodimers with KSR2 which further dimerize to form tetramers (By similarity). Interacts with ARBB2, LAMTOR3, MAPK1/ERK2, MORG1 and RAF1 (By similarity). Interacts with PPARG and with isoform 1 of VRK2. Interacts with Yersinia yopJ. Interacts with SGK1. Interacts with BIRC6/bruce. INTERACTION: Q9NR09:BIRC6; NbExp=2; IntAct=EBI-492564, EBI-1765160; P04049:RAF1; NbExp=2; IntAct=EBI-492564, EBI-365996; Q86Y07:VRK2; NbExp=2; IntAct=EBI-492564, EBI-1207615; Q86Y07-1:VRK2; NbExp=2; IntAct=EBI-492564, EBI-1207633; SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, centrosome. Cytoplasm, cytoskeleton, spindle pole body. Cytoplasm. Nucleus. Note=Localizes at centrosomes during prometaphase, midzone during anaphase and midbody during telophase/cytokinesis. TISSUE SPECIFICITY: Widely expressed, with extremely low levels in brain. DOMAIN: The proline-rich region localized between residues 270 and 307 is important for binding to RAF1 and activation of MAP2K1/MEK1 (By similarity). PTM: Phosphorylation at Ser-218 and Ser-222 by MAP kinase kinase kinases (RAF or MEKK1) positively regulates kinase activity. Also phosphorylated at Thr-292 by MAPK1/ERK2 and at Ser-298 by PAK. MAPK1/ERK2 phosphorylation of Thr-292 occurs in response to cellular adhesion and leads to inhibition of Ser-298 phosphorylation by PAK. PTM: Acetylation by Yersinia yopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway. DISEASE: Defects in MAP2K1 are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:115150]; also known as cardio-facio- cutaneous syndrome. CFC syndrome is 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. The inheritance of CFC syndrome is autosomal dominant. SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily. SIMILARITY: Contains 1 protein kinase domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/MAP2K1";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q02750
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.