MP2K1_MOUSE
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 03-AUG-2022, entry version 212.
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, Pancreas,
RC 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). {ECO:0000250|UniProtKB:P29678,
CC ECO:0000250|UniProtKB:Q01986, ECO:0000250|UniProtKB:Q02750,
CC ECO:0000269|PubMed:15118098, ECO:0000269|PubMed:19219045,
CC 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}.
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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; 36.
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 iPTMnet; P31938; -.
DR PhosphoSitePlus; P31938; -.
DR SwissPalm; P31938; -.
DR UCD-2DPAGE; P31938; -.
DR EPD; P31938; -.
DR jPOST; P31938; -.
DR PaxDb; P31938; -.
DR PeptideAtlas; P31938; -.
DR PRIDE; P31938; -.
DR ProteomicsDB; 291393; -.
DR Antibodypedia; 3542; 3527 antibodies from 51 providers.
DR DNASU; 26395; -.
DR Ensembl; ENSMUST00000005066; ENSMUSP00000005066; ENSMUSG00000004936.
DR GeneID; 26395; -.
DR KEGG; mmu:26395; -.
DR UCSC; uc009qbp.1; mouse.
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; EAWASTF; -.
DR OrthoDB; 688282at2759; -.
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 78 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 270 other tissues.
DR ExpressionAtlas; P31938; baseline and differential.
DR Genevisible; P31938; MM.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0005938; C:cell cortex; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0005770; C:late endosome; TAS:UniProtKB.
DR GO; GO:0005874; C:microtubule; ISO:MGI.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
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; IMP: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:0008022; F:protein C-terminus 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:0047485; F:protein N-terminus 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; IEA:UniProtKB-KW.
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:0008283; P:cell population proliferation; ISO: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:0070371; P:ERK1 and ERK2 cascade; IGI:MGI.
DR GO; GO:0060324; P:face development; IGI:MGI.
DR GO; GO:0042593; P:glucose homeostasis; ISO:MGI.
DR GO; GO:0048313; P:Golgi inheritance; ISO:MGI.
DR GO; GO:0007507; P:heart development; IGI: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; IBA:GO_Central.
DR GO; GO:0032402; P:melanosome transport; ISO:MGI.
DR GO; GO:0000278; P:mitotic cell cycle; ISO: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: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: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:0043547; P:positive regulation of GTPase activity; ISO:MGI.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IMP:MGI.
DR GO; GO:1903800; P:positive regulation of miRNA maturation; ISO:MGI.
DR GO; GO:0045933; P:positive regulation of muscle contraction; ISO:MGI.
DR GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; 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 from RNA polymerase II promoter; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IMP: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: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:0047496; P:vesicle transport along microtubule; ISO:MGI.
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 Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
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 RAF-
FT dependent sites and prolonged ERK phosphorylation."
FT /evidence="ECO:0000269|PubMed:19219045"
FT MUTAGEN 292
FT /note="T->D: Results in hypophosphorylation of the RAF-
FT 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
