ID MP2K1_RAT Reviewed; 393 AA.
AC Q01986; Q5EBD5;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 27-MAR-2024, entry version 201.
DE RecName: Full=Dual specificity mitogen-activated protein kinase kinase 1 {ECO:0000305};
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 {ECO:0000312|RGD:70495}; Synonyms=Mek1, Prkmk1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Kidney;
RX PubMed=8380494; DOI=10.1073/pnas.90.1.173;
RA Wu J., Harrison J.K., Vincent L.A., Haystead C., Haystead T.A.J.,
RA Michel H., Hunt D.F., Lynch K.R., Sturgill T.W.;
RT "Molecular structure of a protein-tyrosine/threonine kinase activating p42
RT mitogen-activated protein (MAP) kinase: MAP kinase kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:173-177(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8462694; DOI=10.1016/0014-5793(93)80596-m;
RA Otsu M., Terada Y., Okayama H.;
RT "Isolation of two members of the rat MAP kinase kinase gene family.";
RL FEBS Lett. 320:246-250(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC STRAIN=Sprague-Dawley;
RX PubMed=8406028; DOI=10.1016/0378-1119(93)90312-q;
RA Doering F., Drewes G., Berling B., Mandelkow E.M.;
RT "Cloning and sequencing of a cDNA encoding rat brain mitogen-activated
RT protein (MAP) kinase activator.";
RL Gene 131:303-304(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thymus;
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 [5]
RP PROTEIN SEQUENCE OF 206-227; 270-291 AND 325-340, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus;
RA Lubec G., Chen W.-Q.;
RL Submitted (APR-2007) to UniProtKB.
RN [6]
RP DOMAIN, INTERACTION WITH RAF1, AND ACTIVITY REGULATION.
RX PubMed=7565670; DOI=10.1128/mcb.15.10.5214;
RA Catling A.D., Schaeffer H.J., Reuter C.W., Reddy G.R., Weber M.J.;
RT "A proline-rich sequence unique to MEK1 and MEK2 is required for raf
RT binding and regulates MEK function.";
RL Mol. Cell. Biol. 15:5214-5225(1995).
RN [7]
RP INTERACTION WITH LAMTOR3, AND ACTIVITY REGULATION.
RX PubMed=9733512; DOI=10.1126/science.281.5383.1668;
RA Schaeffer H.J., Catling A.D., Eblen S.T., Collier L.S., Krauss A.,
RA Weber M.J.;
RT "MP1: a MEK binding partner that enhances enzymatic activation of the MAP
RT kinase cascade.";
RL Science 281:1668-1671(1998).
RN [8]
RP PHOSPHORYLATION, AND FUNCTION.
RX PubMed=10769026; DOI=10.1083/jcb.149.2.331;
RA Colanzi A., Deerinck T.J., Ellisman M.H., Malhotra V.;
RT "A specific activation of the mitogen-activated protein kinase kinase 1
RT (MEK1) is required for Golgi fragmentation during mitosis.";
RL J. Cell Biol. 149:331-339(2000).
RN [9]
RP INTERACTION WITH ARRB2.
RX PubMed=11226259; DOI=10.1073/pnas.041604898;
RA Luttrell L.M., Roudabush F.L., Choy E.W., Miller W.E., Field M.E.,
RA Pierce K.L., Lefkowitz R.J.;
RT "Activation and targeting of extracellular signal-regulated kinases by
RT beta-arrestin scaffolds.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:2449-2454(2001).
RN [10]
RP PHOSPHORYLATION AT SER-298, AND ACTIVITY REGULATION.
RX PubMed=12876277; DOI=10.1083/jcb.200212141;
RA Slack-Davis J.K., Eblen S.T., Zecevic M., Boerner S.A., Tarcsafalvi A.,
RA Diaz H.B., Marshall M.S., Weber M.J., Parsons J.T., Catling A.D.;
RT "PAK1 phosphorylation of MEK1 regulates fibronectin-stimulated MAPK
RT activation.";
RL J. Cell Biol. 162:281-291(2003).
RN [11]
RP PHOSPHORYLATION AT THR-292 AND SER-298, INTERACTION WITH MAPK1/ERK2, AND
RP ACTIVITY REGULATION.
RX PubMed=14993270; DOI=10.1128/mcb.24.6.2308-2317.2004;
RA Eblen S.T., Slack-Davis J.K., Tarcsafalvi A., Parsons J.T., Weber M.J.,
RA Catling A.D.;
RT "Mitogen-activated protein kinase feedback phosphorylation regulates MEK1
RT complex formation and activation during cellular adhesion.";
RL Mol. Cell. Biol. 24:2308-2317(2004).
RN [12]
RP FUNCTION OF THE MAPK/ERK PATHWAY.
RX PubMed=19177150; DOI=10.1038/emboj.2008.308;
RA Nada S., Hondo A., Kasai A., Koike M., Saito K., Uchiyama Y., Okada M.;
RT "The novel lipid raft adaptor p18 controls endosome dynamics by anchoring
RT the MEK-ERK pathway to late endosomes.";
RL EMBO J. 28:477-489(2009).
RN [13]
RP IDENTIFICATION IN A COMPLEX WITH BRAF; HRAS; MAPK3 AND RGS14.
RX PubMed=19319189; DOI=10.1371/journal.pone.0004884;
RA Willard F.S., Willard M.D., Kimple A.J., Soundararajan M., Oestreich E.A.,
RA Li X., Sowa N.A., Kimple R.J., Doyle D.A., Der C.J., Zylka M.J.,
RA Snider W.D., Siderovski D.P.;
RT "Regulator of G-protein signaling 14 (RGS14) is a selective H-Ras
RT effector.";
RL PLoS ONE 4:E4884-E4884(2009).
RN [14]
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 [15]
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 [16]
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 [17]
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 [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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:10769026, ECO:0000269|PubMed:19177150}.
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.
CC MAP2K1/MEK1 binds KSR1 or KSR2 releasing the inhibitory intramolecular
CC interaction between KSR1 or KSR2 protein kinase and N-terminal domains
CC (By similarity). This allows KSR1 or KSR2 dimerization with BRAF
CC 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.
CC {ECO:0000250|UniProtKB:Q02750, ECO:0000269|PubMed:12876277,
CC ECO:0000269|PubMed:14993270, ECO:0000269|PubMed:7565670,
CC ECO:0000269|PubMed:9733512}.
CC -!- SUBUNIT: Found in a complex with at least BRAF, HRAS, MAP2K1,
CC MAPK3/ERK1 and RGS14 (PubMed:19319189). Forms a heterodimer with
CC MAP2K2/MEK2 (By similarity). Forms heterodimers with KSR2 which further
CC dimerize to form tetramers (By similarity). Interacts with KSR1 or KSR2
CC and BRAF; the interaction with KSR1 or KSR2 mediates KSR1-BRAF or KSR2-
CC BRAF dimerization (By similarity). Interacts with ARBB2, LAMTOR3,
CC MAPK1/ERK2 and RAF1 (PubMed:7565670, PubMed:9733512, PubMed:11226259,
CC PubMed:14993270). Interacts with MAPK1/ERK2 (By similarity). Interacts
CC with MORG1 (By similarity). Interacts with PPARG (By similarity).
CC Interacts with VRK2 (By similarity). Interacts with SGK1 (By
CC similarity). Interacts with BIRC6/bruce (By similarity). Interacts with
CC KAT7; the interaction promotes KAT7 phosphorylation (By similarity).
CC Interacts with RAF1 and NEK10; the interaction is required for ERK1/2-
CC signaling pathway activation in response to UV irradiation (By
CC similarity). Interacts with TRAF3IP3 (By similarity). Interacts with
CC MOS (By similarity). {ECO:0000250|UniProtKB:P29678,
CC ECO:0000250|UniProtKB:P31938, ECO:0000250|UniProtKB:Q02750,
CC ECO:0000269|PubMed:11226259, ECO:0000269|PubMed:14993270,
CC ECO:0000269|PubMed:19319189, ECO:0000269|PubMed:7565670,
CC ECO:0000269|PubMed:9733512}.
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:0000250|UniProtKB:Q02750}. Nucleus {ECO:0000250|UniProtKB:Q02750}.
CC Membrane {ECO:0000250|UniProtKB:Q02750}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q02750}. Note=Localizes at centrosomes during
CC prometaphase, midzone during anaphase and midbody during
CC telophase/cytokinesis. Membrane localization is probably regulated by
CC its interaction with KSR1. {ECO:0000250|UniProtKB:Q02750}.
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:0000269|PubMed:7565670}.
CC -!- PTM: Phosphorylation at Ser-218 and Ser-222 by MAP kinase kinase
CC kinases (BRAF or MEKK1) positively regulates kinase activity
CC (PubMed:10769026). Also phosphorylated at Thr-292 by MAPK1/ERK2 and at
CC Ser-298 by PAK (PubMed:12876277, PubMed:14993270). MAPK1/ERK2
CC phosphorylation of Thr-292 occurs in response to cellular adhesion and
CC leads to inhibition of Ser-298 phosphorylation by PAK
CC (PubMed:14993270). Autophosphorylated at Ser-218 and Ser-222,
CC autophosphosphorylation is promoted by NEK10 following UV irradiation
CC (By similarity). {ECO:0000250|UniProtKB:Q02750,
CC ECO:0000269|PubMed:10769026, ECO:0000269|PubMed:12876277,
CC ECO:0000269|PubMed:14993270}.
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; Z16415; CAA78905.1; -; mRNA.
DR EMBL; D13341; BAA02603.1; -; mRNA.
DR EMBL; D14591; BAA03441.1; -; mRNA.
DR EMBL; X62313; CAA44192.1; -; mRNA.
DR EMBL; BC089772; AAH89772.1; -; mRNA.
DR PIR; JN0840; JN0840.
DR RefSeq; NP_113831.1; NM_031643.4.
DR AlphaFoldDB; Q01986; -.
DR SMR; Q01986; -.
DR BioGRID; 251005; 10.
DR CORUM; Q01986; -.
DR IntAct; Q01986; 2.
DR MINT; Q01986; -.
DR STRING; 10116.ENSRNOP00000013933; -.
DR BindingDB; Q01986; -.
DR ChEMBL; CHEMBL3430876; -.
DR GlyGen; Q01986; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q01986; -.
DR PhosphoSitePlus; Q01986; -.
DR jPOST; Q01986; -.
DR PaxDb; 10116-ENSRNOP00000013933; -.
DR Ensembl; ENSRNOT00055041789; ENSRNOP00055034029; ENSRNOG00055024284.
DR Ensembl; ENSRNOT00060033130; ENSRNOP00060027113; ENSRNOG00060018969.
DR Ensembl; ENSRNOT00065009833; ENSRNOP00065007137; ENSRNOG00065006381.
DR GeneID; 170851; -.
DR KEGG; rno:170851; -.
DR UCSC; RGD:70495; rat.
DR AGR; RGD:70495; -.
DR CTD; 5604; -.
DR RGD; 70495; Map2k1.
DR eggNOG; KOG0581; Eukaryota.
DR HOGENOM; CLU_000288_63_23_1; -.
DR InParanoid; Q01986; -.
DR OrthoDB; 2900742at2759; -.
DR PhylomeDB; Q01986; -.
DR TreeFam; TF105137; -.
DR BRENDA; 2.7.12.2; 5301.
DR Reactome; R-RNO-110056; MAPK3 (ERK1) activation.
DR Reactome; R-RNO-170968; Frs2-mediated activation.
DR Reactome; R-RNO-445144; Signal transduction by L1.
DR Reactome; R-RNO-5673000; RAF activation.
DR Reactome; R-RNO-5674135; MAP2K and MAPK activation.
DR Reactome; R-RNO-5674499; Negative feedback regulation of MAPK pathway.
DR PRO; PR:Q01986; -.
DR Proteomes; UP000002494; Unplaced.
DR Genevisible; Q01986; RN.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0005938; C:cell cortex; IDA:RGD.
DR GO; GO:0005813; C:centrosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:UniProtKB.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0032839; C:dendrite cytoplasm; IDA:RGD.
DR GO; GO:0005769; C:early endosome; TAS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005925; C:focal adhesion; TAS:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005794; C:Golgi apparatus; TAS:UniProtKB.
DR GO; GO:0005770; C:late endosome; TAS:UniProtKB.
DR GO; GO:0016020; C:membrane; 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; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0014069; C:postsynaptic density; IDA:SynGO.
DR GO; GO:0005524; F:ATP binding; IDA:RGD.
DR GO; GO:0004708; F:MAP kinase kinase activity; IDA:RGD.
DR GO; GO:0005078; F:MAP-kinase scaffold activity; ISO:RGD.
DR GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; IDA:RGD.
DR GO; GO:0030295; F:protein kinase activator activity; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; IPI:RGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; ISO:RGD.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:RGD.
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; IPI:RGD.
DR GO; GO:0097110; F:scaffold protein binding; ISO:RGD.
DR GO; GO:0031267; F:small GTPase binding; IPI:RGD.
DR GO; GO:0060020; P:Bergmann glial cell differentiation; ISO:RGD.
DR GO; GO:0048870; P:cell motility; ISO:RGD.
DR GO; GO:0090398; P:cellular senescence; ISO:RGD.
DR GO; GO:0021697; P:cerebellar cortex formation; ISO:RGD.
DR GO; GO:0035987; P:endodermal cell differentiation; ISO:RGD.
DR GO; GO:0060502; P:epithelial cell proliferation involved in lung morphogenesis; ISO:RGD.
DR GO; GO:0038133; P:ERBB2-ERBB3 signaling pathway; ISO:RGD.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:0060324; P:face development; ISO:RGD.
DR GO; GO:0048313; P:Golgi inheritance; IMP:RGD.
DR GO; GO:0007507; P:heart development; ISO:RGD.
DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; TAS:RGD.
DR GO; GO:0030216; P:keratinocyte differentiation; ISO:RGD.
DR GO; GO:0060711; P:labyrinthine layer development; ISO:RGD.
DR GO; GO:0060425; P:lung morphogenesis; ISO:RGD.
DR GO; GO:0000165; P:MAPK cascade; ISO:RGD.
DR GO; GO:0032402; P:melanosome transport; IDA:RGD.
DR GO; GO:0042552; P:myelination; ISO:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; IGI:BHF-UCL.
DR GO; GO:0034111; P:negative regulation of homotypic cell-cell adhesion; IMP:RGD.
DR GO; GO:1903298; P:negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway; IMP:CAFA.
DR GO; GO:0030182; P:neuron differentiation; IMP:RGD.
DR GO; GO:0048812; P:neuron projection morphogenesis; IMP:RGD.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0060674; P:placenta blood vessel development; ISO:RGD.
DR GO; GO:2001171; P:positive regulation of ATP biosynthetic process; IMP:CAFA.
DR GO; GO:0010508; P:positive regulation of autophagy; IDA:RGD.
DR GO; GO:0050772; P:positive regulation of axonogenesis; ISO:RGD.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:RGD.
DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISO:RGD.
DR GO; GO:1903226; P:positive regulation of endodermal cell differentiation; ISO:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:CAFA.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:RGD.
DR GO; GO:0045933; P:positive regulation of muscle contraction; IMP:CAFA.
DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; IMP:MGI.
DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; IMP:RGD.
DR GO; GO:0048679; P:regulation of axon regeneration; ISO:RGD.
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; IDA:RGD.
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; IDA:SynGO.
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; IMP:RGD.
DR GO; GO:0048678; P:response to axon injury; IMP:RGD.
DR GO; GO:0051384; P:response to glucocorticoid; IDA:RGD.
DR GO; GO:0006979; P:response to oxidative stress; IDA:RGD.
DR GO; GO:0014044; P:Schwann cell development; ISO:RGD.
DR GO; GO:0048538; P:thymus development; ISO:RGD.
DR GO; GO:0030878; P:thyroid gland development; ISO:RGD.
DR GO; GO:0060440; P:trachea formation; ISO:RGD.
DR GO; GO:0070328; P:triglyceride homeostasis; IDA:RGD.
DR GO; GO:0044342; P:type B pancreatic cell proliferation; ISO:RGD.
DR GO; GO:0047496; P:vesicle transport along microtubule; IDA:RGD.
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.
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_0000086369"
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 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:0000250|UniProtKB:Q02750"
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:0000250|UniProtKB:Q02750"
FT MOD_RES 292
FT /note="Phosphothreonine; by MAPK1"
FT /evidence="ECO:0000269|PubMed:14993270"
FT MOD_RES 298
FT /note="Phosphoserine; by PAK"
FT /evidence="ECO:0000269|PubMed:12876277,
FT ECO:0000269|PubMed:14993270"
SQ SEQUENCE 393 AA; 43465 MW; A1C8D18FFC852D51 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 LELLFGCQVE GDAAETPPRP RTPGRPLSSY
GMDSRPPMAI FELLDYIVNE PPPKLPSGVF SLEFQDFVNK CLIKNPAERA DLKQLMVHAF
IKRSDAEEVD FAGWLCSTIG LNQPSTPTHA ASI
//
