ID MP2K1_MOUSE Reviewed; 393 AA. AC P31938; DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 27-MAR-2024, entry version 221. DE RecName: Full=Dual specificity mitogen-activated protein kinase kinase 1; DE Short=MAP kinase kinase 1; DE Short=MAPKK 1; DE EC=2.7.12.2; DE AltName: Full=ERK activator kinase 1; DE AltName: Full=MAPK/ERK kinase 1; DE Short=MEK 1; GN Name=Map2k1; Synonyms=Mek1, Prkmk1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE. RX PubMed=1411546; DOI=10.1126/science.1411546; RA Crews C.M., Alessandrini A., Erikson R.L.; RT "The primary structure of MEK, a protein kinase that phosphorylates the ERK RT gene product."; RL Science 258:478-480(1992). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP PROTEIN SEQUENCE OF 4-20; 71-84; 114-136; 206-234 AND 363-384. RC TISSUE=T-cell; RX PubMed=1381507; DOI=10.1073/pnas.89.17.8205; RA Crews C.M., Erikson R.L.; RT "Purification of a murine protein-tyrosine/threonine kinase that RT phosphorylates and activates the Erk-1 gene product: relationship to the RT fission yeast byr1 gene product."; RL Proc. Natl. Acad. Sci. U.S.A. 89:8205-8209(1992). RN [4] RP PROTEIN SEQUENCE OF 206-227; 270-291 AND 325-340, AND IDENTIFICATION BY RP MASS SPECTROMETRY. RC TISSUE=Hippocampus; RA Lubec G., Klug S.; RL Submitted (MAR-2007) to UniProtKB. RN [5] RP PHOSPHORYLATION AND ACTIVITY REGULATION. RX PubMed=8385802; DOI=10.1126/science.8385802; RA Lange-Carter C.A., Pleiman C.M., Gardner A.M., Blumer K.J., Johnson G.L.; RT "A divergence in the MAP kinase regulatory network defined by MEK kinase RT and Raf."; RL Science 260:315-319(1993). RN [6] RP CLEAVAGE BY ANTHRAX LETHAL FACTOR. RX PubMed=9563949; DOI=10.1126/science.280.5364.734; RA Duesbery N.S., Webb C.P., Leppla S.H., Gordon V.M., Klimpel K.R., RA Copeland T.D., Ahn N.G., Oskarsson M.K., Fukasawa K., Paull K.D., RA Vande Woude G.F.; RT "Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor."; RL Science 280:734-737(1998). RN [7] RP INTERACTION WITH KSR1, SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT RP SER-218. RX PubMed=10409742; DOI=10.1128/mcb.19.8.5523; RA Stewart S., Sundaram M., Zhang Y., Lee J., Han M., Guan K.L.; RT "Kinase suppressor of Ras forms a multiprotein signaling complex and RT modulates MEK localization."; RL Mol. Cell. Biol. 19:5523-5534(1999). RN [8] RP INTERACTION WITH MORG1. RX PubMed=15118098; DOI=10.1073/pnas.0305894101; RA Vomastek T., Schaeffer H.-J., Tarcsafalvi A., Smolkin M.E., RA Bissonette E.A., Weber M.J.; RT "Modular construction of a signaling scaffold: MORG1 interacts with RT components of the ERK cascade and links ERK signaling to specific RT agonists."; RL Proc. Natl. Acad. Sci. U.S.A. 101:6981-6986(2004). RN [9] RP DISRUPTION PHENOTYPE, FUNCTION, INTERACTION WITH MAP2K2/MEK2, RP PHOSPHORYLATION AT THR-292, AND MUTAGENESIS OF ASN-78 AND THR-292. RX PubMed=19219045; DOI=10.1038/nsmb.1564; RA Catalanotti F., Reyes G., Jesenberger V., Galabova-Kovacs G., RA de Matos Simoes R., Carugo O., Baccarini M.; RT "A Mek1-Mek2 heterodimer determines the strength and duration of the Erk RT signal."; RL Nat. Struct. Mol. Biol. 16:294-303(2009). RN [10] RP REVIEW ON FUNCTION. RX PubMed=9779990; DOI=10.1038/sj.onc.1202251; RA Dhanasekaran N., Premkumar Reddy E.; RT "Signaling by dual specificity kinases."; RL Oncogene 17:1447-1455(1998). RN [11] RP REVIEW ON ACTIVITY REGULATION. RX PubMed=15520807; DOI=10.1038/nrm1498; RA Wellbrock C., Karasarides M., Marais R.; RT "The RAF proteins take centre stage."; RL Nat. Rev. Mol. Cell Biol. 5:875-885(2004). RN [12] RP REVIEW ON FUNCTION. RX PubMed=19565474; DOI=10.1002/biof.52; RA Yao Z., Seger R.; RT "The ERK signaling cascade--views from different subcellular RT compartments."; RL BioFactors 35:407-416(2009). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-286, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, and Spleen; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [14] RP REVIEW ON FUNCTION. RX PubMed=21779493; DOI=10.1177/1947601911407328; RA Wortzel I., Seger R.; RT "The ERK cascade: distinct functions within various subcellular RT organelles."; RL Genes Cancer 2:195-209(2011). RN [15] RP INTERACTION WITH KAT7. RX PubMed=23319590; DOI=10.1074/jbc.m112.426882; RA Zou C., Chen Y., Smith R.M., Snavely C., Li J., Coon T.A., Chen B.B., RA Zhao Y., Mallampalli R.K.; RT "SCF(Fbxw15) mediates histone acetyltransferase binding to origin RT recognition complex (HBO1) ubiquitin-proteasomal degradation to regulate RT cell proliferation."; RL J. Biol. Chem. 288:6306-6316(2013). CC -!- FUNCTION: Dual specificity protein kinase which acts as an essential CC component of the MAP kinase signal transduction pathway. Binding of CC extracellular ligands such as growth factors, cytokines and hormones to CC their cell-surface receptors activates RAS and this initiates RAF1 CC activation. RAF1 then further activates the dual-specificity protein CC kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 CC function specifically in the MAPK/ERK cascade, and catalyze the CC concomitant phosphorylation of a threonine and a tyrosine residue in a CC Thr-Glu-Tyr sequence located in the extracellular signal-regulated CC kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and CC further transduction of the signal within the MAPK/ERK cascade. CC Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 CC or KSR2 releases the inhibitory intramolecular interaction between KSR1 CC or KSR2 protein kinase and N-terminal domains which promotes KSR1 or CC KSR2-BRAF dimerization and BRAF activation (By similarity). Depending CC on the cellular context, this pathway mediates diverse biological CC functions such as cell growth, adhesion, survival and differentiation, CC predominantly through the regulation of transcription, metabolism and CC cytoskeletal rearrangements. One target of the MAPK/ERK cascade is CC peroxisome proliferator-activated receptor gamma (PPARG), a nuclear CC receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has CC been shown to export PPARG from the nucleus. The MAPK/ERK cascade is CC also involved in the regulation of endosomal dynamics, including CC lysosome processing and endosome cycling through the perinuclear CC recycling compartment (PNRC), as well as in the fragmentation of the CC Golgi apparatus during mitosis. {ECO:0000250|UniProtKB:Q02750, CC ECO:0000269|PubMed:19219045}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.12.2; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; CC EC=2.7.12.2; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.12.2; CC -!- ACTIVITY REGULATION: Ras proteins such as HRAS mediate the activation CC of RAF proteins such as RAF1 or BRAF which in turn activate CC extracellular signal-regulated kinases (ERK) through MAPK (mitogen- CC activated protein kinases) and ERK kinases MAP2K1/MEK1 and MAP2K2/MEK2. CC Activation occurs through phosphorylation of Ser-218 and Ser-222 (By CC similarity). MAP2K1/MEK1 binds KSR1 or KSR2 releasing the inhibitory CC intramolecular interaction between KSR1 or KSR2 protein kinase and N- CC terminal domains (By similarity). This allows KSR1 or KSR2 dimerization CC with BRAF leading to BRAF activation and phosphorylation of MAP2K1 (By CC similarity). MAP2K1/MEK1 is also the target of negative feed-back CC regulation by its substrate kinases, such as MAPK1/ERK2. These CC phosphorylate MAP2K1/MEK1 on Thr-292, thereby facilitating CC dephosphorylation of the activating residues Ser-218 and Ser-222. CC Inhibited by serine/threonine phosphatase 2A (By similarity). CC {ECO:0000250|UniProtKB:Q01986, ECO:0000250|UniProtKB:Q02750}. CC -!- SUBUNIT: Found in a complex with at least BRAF, HRAS, MAP2K1, CC MAPK3/ERK1 and RGS14 (By similarity). Forms a heterodimer with CC MAP2K2/MEK2 (PubMed:19219045). Forms heterodimers with KSR2 which CC further dimerize to form tetramers (By similarity). Interacts with KSR1 CC or KSR2 and BRAF; the interaction with KSR1 or KSR2 mediates KSR1-BRAF CC or KSR2-BRAF dimerization (By similarity). Interacts with ARBB2, CC LAMTOR3, MAPK1/ERK2 and RAF1 (By similarity). Interacts with MAPK1/ERK2 CC (By similarity). Interacts with MORG1 (PubMed:15118098). Interacts with CC PPARG (By similarity). Interacts with SGK1 (By similarity). Interacts CC with BIRC6/bruce (By similarity). Interacts with KAT7; the interaction CC promotes KAT7 phosphorylation (PubMed:23319590). Interacts with RAF1 CC and NEK10; the interaction is required for ERK1/2-signaling pathway CC activation in response to UV irradiation (By similarity). Interacts CC with TRAF3IP3 (By similarity). Interacts with MOS (By similarity). CC {ECO:0000250|UniProtKB:P29678, ECO:0000250|UniProtKB:Q01986, CC ECO:0000250|UniProtKB:Q02750, ECO:0000269|PubMed:15118098, CC ECO:0000269|PubMed:19219045, ECO:0000269|PubMed:23319590}. CC -!- INTERACTION: CC P31938; Q8CFP6: Dnajc27; NbExp=3; IntAct=EBI-298860, EBI-9548773; CC P31938; Q9ESN9-2: Mapk8ip3; NbExp=3; IntAct=EBI-298860, EBI-9549291; CC P31938; Q13526: PIN1; Xeno; NbExp=4; IntAct=EBI-298860, EBI-714158; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing CC center, centrosome {ECO:0000250|UniProtKB:Q02750}. Cytoplasm, CC cytoskeleton, microtubule organizing center, spindle pole body CC {ECO:0000250|UniProtKB:Q02750}. Cytoplasm CC {ECO:0000269|PubMed:10409742}. Nucleus {ECO:0000250|UniProtKB:Q02750}. CC Membrane {ECO:0000269|PubMed:10409742}; Peripheral membrane protein CC {ECO:0000269|PubMed:10409742}. Note=Localizes at centrosomes during CC prometaphase, midzone during anaphase and midbody during CC telophase/cytokinesis (By similarity). Membrane localization is CC probably regulated by its interaction with KSR1 (PubMed:10409742). CC {ECO:0000250|UniProtKB:Q02750, ECO:0000269|PubMed:10409742}. CC -!- DOMAIN: The proline-rich region localized between residues 270 and 307 CC is important for binding to RAF1 and activation of MAP2K1/MEK1. CC {ECO:0000250}. CC -!- PTM: Phosphorylation at Ser-218 and Ser-222 by MAP kinase kinase CC kinases (BRAF or MEKK1) positively regulates kinase activity CC (PubMed:8385802). Also phosphorylated at Thr-292 by MAPK1/ERK2 and at CC Ser-298 by PAK (PubMed:19219045). MAPK1/ERK2 phosphorylation of Thr-292 CC occurs in response to cellular adhesion and leads to inhibition of Ser- CC 298 phosphorylation by PAK (PubMed:19219045). Autophosphorylated at CC Ser-218 and Ser-222, autophosphosphorylation is promoted by NEK10 CC following UV irradiation (By similarity). CC {ECO:0000250|UniProtKB:Q02750, ECO:0000269|PubMed:19219045, CC ECO:0000269|PubMed:8385802}. CC -!- DISRUPTION PHENOTYPE: Affects fibroblast shape and impairs haptotaxis CC and adhesion-dependent ERK-signaling. {ECO:0000269|PubMed:19219045}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr CC protein kinase family. MAP kinase kinase subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L02526; AAA39523.1; -; mRNA. DR EMBL; BC054754; AAH54754.1; -; mRNA. DR CCDS; CCDS23277.1; -. DR PIR; I59571; I59571. DR RefSeq; NP_032953.1; NM_008927.3. DR AlphaFoldDB; P31938; -. DR SMR; P31938; -. DR BioGRID; 204949; 37. DR CORUM; P31938; -. DR DIP; DIP-467N; -. DR IntAct; P31938; 8. DR MINT; P31938; -. DR STRING; 10090.ENSMUSP00000005066; -. DR BindingDB; P31938; -. DR ChEMBL; CHEMBL5860; -. DR GlyGen; P31938; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P31938; -. DR PhosphoSitePlus; P31938; -. DR SwissPalm; P31938; -. DR EPD; P31938; -. DR jPOST; P31938; -. DR PaxDb; 10090-ENSMUSP00000005066; -. DR PeptideAtlas; P31938; -. DR ProteomicsDB; 291393; -. DR Pumba; P31938; -. DR Antibodypedia; 3542; 3873 antibodies from 51 providers. DR DNASU; 26395; -. DR Ensembl; ENSMUST00000005066.9; ENSMUSP00000005066.9; ENSMUSG00000004936.9. DR GeneID; 26395; -. DR KEGG; mmu:26395; -. DR UCSC; uc009qbp.1; mouse. DR AGR; MGI:1346866; -. DR CTD; 5604; -. DR MGI; MGI:1346866; Map2k1. DR VEuPathDB; HostDB:ENSMUSG00000004936; -. DR eggNOG; KOG0581; Eukaryota. DR GeneTree; ENSGT00940000153487; -. DR HOGENOM; CLU_000288_63_23_1; -. DR InParanoid; P31938; -. DR OMA; LTPYDWH; -. DR OrthoDB; 2900742at2759; -. DR PhylomeDB; P31938; -. DR TreeFam; TF105137; -. DR BRENDA; 2.7.12.2; 3474. DR Reactome; R-MMU-110056; MAPK3 (ERK1) activation. DR Reactome; R-MMU-170968; Frs2-mediated activation. DR Reactome; R-MMU-445144; Signal transduction by L1. DR Reactome; R-MMU-5673000; RAF activation. DR Reactome; R-MMU-5674135; MAP2K and MAPK activation. DR Reactome; R-MMU-5674499; Negative feedback regulation of MAPK pathway. DR BioGRID-ORCS; 26395; 1 hit in 83 CRISPR screens. DR ChiTaRS; Map2k1; mouse. DR PRO; PR:P31938; -. DR Proteomes; UP000000589; Chromosome 9. DR RNAct; P31938; Protein. DR Bgee; ENSMUSG00000004936; Expressed in dentate gyrus of hippocampal formation granule cell and 274 other cell types or tissues. DR ExpressionAtlas; P31938; baseline and differential. DR GO; GO:0030424; C:axon; ISO:MGI. DR GO; GO:0005938; C:cell cortex; ISO:MGI. DR GO; GO:0005813; C:centrosome; IEA:UniProtKB-SubCell. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0030425; C:dendrite; ISO:MGI. DR GO; GO:0032839; C:dendrite cytoplasm; ISO:MGI. DR GO; GO:0005769; C:early endosome; TAS:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI. DR GO; GO:0005925; C:focal adhesion; TAS:UniProtKB. DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI. DR GO; GO:0005794; C:Golgi apparatus; TAS:UniProtKB. DR GO; GO:0005770; C:late endosome; TAS:UniProtKB. DR GO; GO:0005739; C:mitochondrion; TAS:UniProtKB. DR GO; GO:0005634; C:nucleus; TAS:UniProtKB. DR GO; GO:0043204; C:perikaryon; ISO:MGI. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; ISO:MGI. DR GO; GO:0014069; C:postsynaptic density; ISO:MGI. DR GO; GO:0005524; F:ATP binding; ISO:MGI. DR GO; GO:0004708; F:MAP kinase kinase activity; IDA:MGI. DR GO; GO:0005078; F:MAP-kinase scaffold activity; ISO:MGI. DR GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; ISO:MGI. DR GO; GO:0030295; F:protein kinase activator activity; ISO:MGI. DR GO; GO:0019901; F:protein kinase binding; ISO:MGI. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; ISO:MGI. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:MGI. DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; TAS:UniProtKB. DR GO; GO:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW. DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI. DR GO; GO:0097110; F:scaffold protein binding; ISO:MGI. DR GO; GO:0031267; F:small GTPase binding; ISO:MGI. DR GO; GO:0060020; P:Bergmann glial cell differentiation; IGI:MGI. DR GO; GO:0048870; P:cell motility; IMP:MGI. DR GO; GO:0090398; P:cellular senescence; ISO:MGI. DR GO; GO:0021697; P:cerebellar cortex formation; IGI:MGI. DR GO; GO:0035987; P:endodermal cell differentiation; IDA:MGI. DR GO; GO:0060502; P:epithelial cell proliferation involved in lung morphogenesis; IGI:MGI. DR GO; GO:0038133; P:ERBB2-ERBB3 signaling pathway; IDA:MGI. DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IGI:MGI. DR GO; GO:0060324; P:face development; IGI:MGI. DR GO; GO:0048313; P:Golgi inheritance; ISO:MGI. DR GO; GO:0007507; P:heart development; IGI:MGI. DR GO; GO:0008286; P:insulin receptor signaling pathway; ISO:MGI. DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; IMP:MGI. DR GO; GO:0030216; P:keratinocyte differentiation; IMP:MGI. DR GO; GO:0060711; P:labyrinthine layer development; IMP:MGI. DR GO; GO:0060425; P:lung morphogenesis; IGI:MGI. DR GO; GO:0000165; P:MAPK cascade; IMP:MGI. DR GO; GO:0032402; P:melanosome transport; ISO:MGI. DR GO; GO:0042552; P:myelination; IMP:MGI. DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI. DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI. DR GO; GO:0034111; P:negative regulation of homotypic cell-cell adhesion; ISO:MGI. DR GO; GO:1903298; P:negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway; ISO:MGI. DR GO; GO:0030182; P:neuron differentiation; IMP:MGI. DR GO; GO:0048812; P:neuron projection morphogenesis; ISO:MGI. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0060674; P:placenta blood vessel development; IMP:MGI. DR GO; GO:2001171; P:positive regulation of ATP biosynthetic process; ISO:MGI. DR GO; GO:0010508; P:positive regulation of autophagy; ISO:MGI. DR GO; GO:0050772; P:positive regulation of axonogenesis; IGI:MGI. DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISO:MGI. DR GO; GO:1903226; P:positive regulation of endodermal cell differentiation; IDA:MGI. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:MGI. DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IMP:MGI. DR GO; GO:0045933; P:positive regulation of muscle contraction; ISO:MGI. DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; ISO:MGI. DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; ISO:MGI. DR GO; GO:0048679; P:regulation of axon regeneration; IGI:MGI. DR GO; GO:2000641; P:regulation of early endosome to late endosome transport; TAS:UniProtKB. DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISO:MGI. DR GO; GO:0090170; P:regulation of Golgi inheritance; TAS:UniProtKB. DR GO; GO:0098696; P:regulation of neurotransmitter receptor localization to postsynaptic specialization membrane; ISO:MGI. DR GO; GO:0032872; P:regulation of stress-activated MAPK cascade; TAS:UniProtKB. DR GO; GO:0003056; P:regulation of vascular associated smooth muscle contraction; ISO:MGI. DR GO; GO:0048678; P:response to axon injury; ISO:MGI. DR GO; GO:0051384; P:response to glucocorticoid; ISO:MGI. DR GO; GO:0006979; P:response to oxidative stress; ISO:MGI. DR GO; GO:0014044; P:Schwann cell development; IMP:MGI. DR GO; GO:0048538; P:thymus development; IGI:MGI. DR GO; GO:0030878; P:thyroid gland development; IGI:MGI. DR GO; GO:0060440; P:trachea formation; IGI:MGI. DR GO; GO:0070328; P:triglyceride homeostasis; ISO:MGI. DR GO; GO:0044342; P:type B pancreatic cell proliferation; IMP:MGI. DR GO; GO:0047496; P:vesicle transport along microtubule; ISO:MGI. DR CDD; cd06650; PKc_MEK1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR47448; DUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE DSOR1-LIKE PROTEIN; 1. DR PANTHER; PTHR47448:SF2; MITOGEN-ACTIVATED PROTEIN KINASE KINASE 1; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR UCD-2DPAGE; P31938; -. DR Genevisible; P31938; MM. PE 1: Evidence at protein level; KW ATP-binding; Cytoplasm; Cytoskeleton; Direct protein sequencing; Kinase; KW Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; KW Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase. FT CHAIN 1..393 FT /note="Dual specificity mitogen-activated protein kinase FT kinase 1" FT /id="PRO_0000086366" FT DOMAIN 68..361 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 1..27 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 270..307 FT /note="RAF1-binding" FT /evidence="ECO:0000250" FT ACT_SITE 190 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 74..82 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 97 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT SITE 8..9 FT /note="Cleavage; by anthrax lethal factor" FT /evidence="ECO:0000250" FT MOD_RES 218 FT /note="Phosphoserine; by RAF" FT /evidence="ECO:0000269|PubMed:10409742" FT MOD_RES 222 FT /note="Phosphoserine; by RAF" FT /evidence="ECO:0000250|UniProtKB:Q02750" FT MOD_RES 286 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 292 FT /note="Phosphothreonine; by MAPK1" FT /evidence="ECO:0000250|UniProtKB:Q01986" FT MOD_RES 298 FT /note="Phosphoserine; by PAK" FT /evidence="ECO:0000250|UniProtKB:Q02750" FT MUTAGEN 78 FT /note="N->G: Impairs interaction with MAP2K2/MEK2." FT /evidence="ECO:0000269|PubMed:19219045" FT MUTAGEN 292 FT /note="T->A: Results in hyperphosphorylation of the FT RAF-dependent sites and prolonged ERK phosphorylation." FT /evidence="ECO:0000269|PubMed:19219045" FT MUTAGEN 292 FT /note="T->D: Results in hypophosphorylation of the FT RAF-dependent sites and faster ERK inactivation." FT /evidence="ECO:0000269|PubMed:19219045" FT CONFLICT 374 FT /note="W -> Q (in Ref. 3; AA sequence)" FT /evidence="ECO:0000305" SQ SEQUENCE 393 AA; 43474 MW; 01D1D18572AE40E7 CRC64; MPKKKPTPIQ LNPAPDGSAV NGTSSAETNL EALQKKLEEL ELDEQQRKRL EAFLTQKQKV GELKDDDFEK ISELGAGNGG VVFKVSHKPS GLVMARKLIH LEIKPAIRNQ IIRELQVLHE CNSPYIVGFY GAFYSDGEIS ICMEHMDGGS LDQVLKKAGR IPEQILGKVS IAVIKGLTYL REKHKIMHRD VKPSNILVNS RGEIKLCDFG VSGQLIDSMA NSFVGTRSYM SPERLQGTHY SVQSDIWSMG LSLVEMAVGR YPIPPPDAKE LELLFGCHVE GDAAETPPRP RTPGRPLSSY GMDSRPPMAI FELLDYIVNE PPPKLPSGVF SLEFQDFVNK CLIKNPAERA DLKQLMVHAF IKRSDAEEVD FAGWLCSTIG LNQPSTPTHA ASI //