MAP2K1

Main article: Mitogen-activated protein kinase kinase

MAP2K1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1S9J, 2P55, 3DV3, 3DY7, 3E8N, 3EQB, 3EQC, 3EQD, 3EQF, 3EQG, 3EQH, 3EQI, 3MBL, 3ORN, 3OS3, 3PP1, 3SLS, 3V01, 3V04, 3VVH, 3W8Q, 3WIG, 3ZLS, 3ZLW, 3ZLX, 3ZLY, 3ZM4, 4AN2, 4AN3, 4AN9, 4ANB, 4ARK, 4LMN, 4MNE, 4U7Z, 4U80, 4U81, 5BX0
Identifiers
Aliases	MAP2K1, CFC3, MAPKK1, MEK1, MKK1, PRKMK1, mitogen-activated protein kinase kinase 1, MEL
External IDs	OMIM: 176872; MGI: 1346866; HomoloGene: 2063; GeneCards: MAP2K1; OMA:MAP2K1 - orthologs
Gene location (Human) Chr. Chromosome 15 (human) Band 15q22.31 Start 66,386,837 bp End 66,491,656 bp
Gene location (Mouse) Chr. Chromosome 9 (mouse) Band 9 C|9 34.55 cM Start 64,093,052 bp End 64,160,913 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte orbitofrontal cortex prefrontal cortex postcentral gyrus Brodmann area 46 Brodmann area 9 superior frontal gyrus nucleus accumbens Skeletal muscle tissue of rectus abdominis cingulate gyrus Top expressed in dentate gyrus of hippocampal formation granule cell olfactory tubercle nucleus accumbens superior frontal gyrus zygote hippocampus proper secondary oocyte temporal lobe amygdala primary visual cortex More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein N-terminus binding kinase activity protein C-terminus binding ATP binding transferase activity protein serine/threonine kinase activator activity protein binding protein serine/threonine/tyrosine kinase activity protein tyrosine kinase activity nucleotide binding MAP kinase kinase activity protein kinase activity protein serine/threonine kinase activity scaffold protein binding Cellular component membrane focal adhesion microtubule organizing center mitochondrion cytoskeleton nucleus endoplasmic reticulum late endosome Golgi apparatus early endosome cytoplasm cytosol plasma membrane Biological process regulation of protein phosphorylation positive regulation of axonogenesis positive regulation of protein serine/threonine kinase activity cellular senescence face development cerebellar cortex formation negative regulation of cell population proliferation thymus development cell motility negative regulation of gene expression heart development positive regulation of cell differentiation regulation of stress-activated MAPK cascade phosphorylation epithelial cell proliferation involved in lung morphogenesis chemotaxis thyroid gland development neuron differentiation trachea formation regulation of axon regeneration lung morphogenesis regulation of early endosome to late endosome transport labyrinthine layer development placenta blood vessel development keratinocyte differentiation MAPK cascade positive regulation of gene expression Bergmann glial cell differentiation peptidyl-tyrosine phosphorylation regulation of Golgi inheritance signal transduction positive regulation of production of miRNAs involved in gene silencing by miRNA positive regulation of ERK1 and ERK2 cascade positive regulation of transcription, DNA-templated regulation of mitotic cell cycle regulation of apoptotic process protein phosphorylation peptidyl-threonine phosphorylation ERK1 and ERK2 cascade stress-activated protein kinase signaling cascade activation of protein kinase activity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5604 26395 Ensembl ENSG00000169032 ENSMUSG00000004936 UniProt Q02750 P31938 RefSeq (mRNA) NM_002755 NM_008927 RefSeq (protein) NP_002746 NP_032953 Location (UCSC) Chr 15: 66.39 – 66.49 Mb Chr 9: 64.09 – 64.16 Mb PubMed search
Wikidata
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Dual specificity mitogen-activated protein kinase kinase 1 is an enzyme that in humans is encoded by the MAP2K1 gene.

Function

The protein encoded by this gene is a member of the dual-specificity protein kinase family that 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 activation by a wide variety of extra- and intracellular signals. As an essential component of the MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as proliferation, differentiation, transcription regulation and development. MAP2K1 is altered in 1.05% of all human cancers.

Meiosis

The genomes of diploid organisms in natural populations are highly polymorphic for insertions and deletions. During meiosis double-strand breaks (DSBs) that form within such polymorphic regions must be repaired by inter-sister chromatid exchange, rather than by inter-homolog exchange. Molecular-level studies of recombination during budding yeast meiosis have shown that recombination events initiated by DSBs in regions that lack corresponding sequences in the homolog are efficiently repaired by inter-sister chromatid recombination. This recombination occurs with the same timing as inter-homolog recombination, but with reduced (2- to 3-fold) yields of joint molecules.

MAP2K1 is also known as MEK1 (see Mitogen-activated protein kinase kinase). MEK1 is a meiotic chromosome-axis-associated kinase that is thought to slow down, but not entirely block, sister chromatid recombination. Loss of MEK1 allows inter-sister DSB repair and also inter-sister Holliday junction intermediates to increase. Despite the normal activity of MEK1 in reducing inter-sister chromatid recombination, such recombination still occurs frequently during normal budding yeast meiosis (although not as frequently as during mitosis), and up to one-third of all recombination events are between sister chromatids.

Interactions

MAP2K1 has been shown to interact with C-Raf, Phosphatidylethanolamine binding protein 1, MAP2K1IP1, GRB10, MAPK3, MAPK8IP3, MAPK1 MP1, and MAP3K1.

Further reading

• Wu J, Michel H, Rossomando A, Haystead T, Shabanowitz J, Hunt DF, Sturgill TW (1992). "Renaturation and partial peptide sequencing of mitogen-activated protein kinase (MAP kinase) activator from rabbit skeletal muscle". Biochem. J. 285 (3): 701–5. doi:10.1042/bj2850701. PMC 1132850. PMID 1379797.
• Rossomando AJ, Dent P, Sturgill TW, Marshak DR (1994). "Mitogen-activated protein kinase kinase 1 (MKK1) is negatively regulated by threonine phosphorylation". Mol Cell Biol. 14 (3): 1594–602. doi:10.1128/mcb.14.3.1594-1602.1994. PMC 358518. PMID 8114697.
• Seger R, Krebs EG (1995). "The MAPK signaling cascade". FASEB J. 9 (9): 726–35. doi:10.1096/fasebj.9.9.7601337. PMID 7601337. S2CID 23298305.
• Joseph AM, Kumar M, Mitra D (2005). "Nef: "necessary and enforcing factor" in HIV infection". Curr. HIV Res. 3 (1): 87–94. doi:10.2174/1570162052773013. PMID 15638726.
• Tanaka S, Nakamura K, Takahasi N, Suda T (2006). "Role of RANKL in physiological and pathological bone resorption and therapeutics targeting the RANKL-RANK signaling system". Immunol. Rev. 208: 30–49. doi:10.1111/j.0105-2896.2005.00327.x. PMID 16313339. S2CID 13811917.
• Stove V, Verhasselt B (2006). "Modelling thymic HIV-1 Nef effects". Curr. HIV Res. 4 (1): 57–64. doi:10.2174/157016206775197583. PMID 16454711.
• Galabova-Kovacs G, Kolbus A, Matzen D, et al. (2006). "ERK and beyond: insights from B-Raf and Raf-1 conditional knockouts". Cell Cycle. 5 (14): 1514–8. doi:10.4161/cc.5.14.2981. PMID 16861903.

External links

• GeneReviews/NCBI/NIH/UW entry on Noonan syndrome
• GeneReviews/NCBI/NIH/UW entry on Cardiofaciocutaneous Syndrome