UniProtKB - Q01986 (MP2K1_RAT)
Dual specificity mitogen-activated protein kinase kinase 1
Map2k1
Functioni
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. Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation (By similarity).
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.
By similarity2 PublicationsCatalytic activityi
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 97 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 190 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 74 – 82 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: RGD
- MAP kinase kinase activity Source: RGD
- MAP-kinase scaffold activity Source: RGD
- mitogen-activated protein kinase kinase kinase binding Source: RGD
- protein-containing complex binding Source: RGD
- protein C-terminus binding Source: RGD
- protein kinase activator activity Source: RGD
- protein kinase binding Source: RGD
- protein N-terminus binding Source: RGD
- protein serine/threonine/tyrosine kinase activity Source: UniProtKB
- protein serine/threonine kinase activator activity Source: RGD
- protein serine/threonine kinase activity Source: RGD
- protein serine kinase activity Source: RHEA
- protein tyrosine kinase activity Source: UniProtKB-KW
- scaffold protein binding Source: RGD
- small GTPase binding Source: RGD
GO - Biological processi
- Bergmann glial cell differentiation Source: RGD
- cell motility Source: RGD
- cell population proliferation Source: RGD
- cellular senescence Source: RGD
- cerebellar cortex formation Source: RGD
- epithelial cell proliferation involved in lung morphogenesis Source: RGD
- ERK1 and ERK2 cascade Source: RGD
- face development Source: RGD
- glucose homeostasis Source: RGD
- Golgi inheritance Source: RGD
- heart development Source: RGD
- intracellular signal transduction Source: RGD
- keratinocyte differentiation Source: RGD
- labyrinthine layer development Source: RGD
- lung morphogenesis Source: RGD
- MAPK cascade Source: GO_Central
- melanosome transport Source: RGD
- mitotic cell cycle Source: RGD
- negative regulation of cell population proliferation Source: RGD
- negative regulation of gene expression Source: BHF-UCL
- negative regulation of homotypic cell-cell adhesion Source: RGD
- negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway Source: CAFA
- neuron differentiation Source: RGD
- neuron projection morphogenesis Source: RGD
- peptidyl-threonine phosphorylation Source: RGD
- placenta blood vessel development Source: RGD
- positive regulation of ATP biosynthetic process Source: CAFA
- positive regulation of autophagy Source: RGD
- positive regulation of axonogenesis Source: RGD
- positive regulation of cell differentiation Source: RGD
- positive regulation of cell migration Source: RGD
- positive regulation of ERK1 and ERK2 cascade Source: RGD
- positive regulation of gene expression Source: CAFA
- positive regulation of GTPase activity Source: RGD
- positive regulation of MAPK cascade Source: RGD
- positive regulation of muscle contraction Source: CAFA
- positive regulation of production of miRNAs involved in gene silencing by miRNA Source: RGD
- positive regulation of protein serine/threonine kinase activity Source: RGD
- positive regulation of Ras protein signal transduction Source: MGI
- positive regulation of transcription, DNA-templated Source: RGD
- positive regulation of transcription elongation from RNA polymerase II promoter Source: RGD
- protein phosphorylation Source: RGD
- regulation of axon regeneration Source: RGD
- regulation of cell cycle Source: RGD
- regulation of early endosome to late endosome transport Source: UniProtKB
- regulation of ERK1 and ERK2 cascade Source: RGD
- regulation of Golgi inheritance Source: UniProtKB
- regulation of neurotransmitter receptor localization to postsynaptic specialization membrane Source: SynGO
- regulation of stress-activated MAPK cascade Source: UniProtKB
- regulation of vascular associated smooth muscle contraction Source: RGD
- response to axon injury Source: RGD
- response to glucocorticoid Source: RGD
- response to oxidative stress Source: RGD
- thymus development Source: RGD
- thyroid gland development Source: RGD
- trachea formation Source: RGD
- triglyceride homeostasis Source: RGD
- vesicle transport along microtubule Source: RGD
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.12.2, 5301 |
Reactomei | R-RNO-110056, MAPK3 (ERK1) activation R-RNO-170968, Frs2-mediated activation R-RNO-445144, Signal transduction by L1 R-RNO-5673000, RAF activation R-RNO-5674135, MAP2K and MAPK activation R-RNO-5674499, Negative feedback regulation of MAPK pathway |
Names & Taxonomyi
Protein namesi | Recommended name: Dual specificity mitogen-activated protein kinase kinase 1Curated (EC:2.7.12.2)Short name: MAP kinase kinase 1 Short name: MAPKK 1 Alternative name(s): ERK activator kinase 1 MAPK/ERK kinase 1 Short name: MEK 1 |
Gene namesi | |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 70495, Map2k1 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm By similarity
Cytoskeleton
- centrosome By similarity
- spindle pole body By similarity
Nucleus
- Nucleus By similarity
Other locations
- Membrane By similarity; Peripheral membrane protein By similarity
Note: Localizes at centrosomes during prometaphase, midzone during anaphase and midbody during telophase/cytokinesis. Membrane localization is probably regulated by its interaction with KSR1.By similarity
Cytoskeleton
- microtubule organizing center Source: UniProtKB-SubCell
Cytosol
- cytosol Source: RGD
Endoplasmic reticulum
- endoplasmic reticulum Source: RGD
Endosome
- early endosome Source: UniProtKB
- late endosome Source: UniProtKB
Golgi apparatus
- Golgi apparatus Source: RGD
Mitochondrion
- mitochondrion Source: UniProtKB
Nucleus
- nucleus Source: UniProtKB
Plasma Membrane
- plasma membrane Source: RGD
Other locations
- axon Source: RGD
- cell cortex Source: RGD
- dendrite Source: RGD
- dendrite cytoplasm Source: RGD
- focal adhesion Source: UniProtKB
- glutamatergic synapse Source: SynGO
- perikaryon Source: RGD
- perinuclear region of cytoplasm Source: RGD
- postsynaptic density Source: SynGO
Keywords - Cellular componenti
Cytoplasm, Cytoskeleton, Membrane, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086369 | 1 – 393 | Dual specificity mitogen-activated protein kinase kinase 1Add BLAST | 393 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 218 | Phosphoserine; by RAFBy similarity | 1 | |
Modified residuei | 222 | Phosphoserine; by RAFBy similarity | 1 | |
Modified residuei | 286 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 292 | Phosphothreonine; by MAPK11 Publication | 1 | |
Modified residuei | 298 | Phosphoserine; by PAK2 Publications | 1 |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 8 – 9 | Cleavage; by anthrax lethal factorBy similarity | 2 |
Keywords - PTMi
PhosphoproteinProteomic databases
jPOSTi | Q01986 |
PaxDbi | Q01986 |
PTM databases
iPTMneti | Q01986 |
PhosphoSitePlusi | Q01986 |
Interactioni
Subunit structurei
Found in a complex with at least BRAF, HRAS, MAP2K1, MAPK3/ERK1 and RGS14 (PubMed:19319189).
Forms a heterodimer with MAP2K2/MEK2 (By similarity). Forms heterodimers with KSR2 which further dimerize to form tetramers (By similarity).
Interacts with KSR1 or KSR2 and BRAF; the interaction with KSR1 or KSR2 mediates KSR1-BRAF or KSR2-BRAF dimerization (By similarity).
Interacts with ARBB2, LAMTOR3, MAPK1/ERK2 and RAF1 (PubMed:7565670, PubMed:9733512, PubMed:11226259, PubMed:14993270).
Interacts with MAPK1/ERK2 (By similarity).
Interacts with MORG1 (By similarity).
Interacts with PPARG (By similarity).
Interacts with VRK2 (By similarity).
Interacts with SGK1 (By similarity).
Interacts with BIRC6/bruce (By similarity).
Interacts with KAT7; the interaction promotes KAT7 phosphorylation (By similarity).
Interacts with RAF1 and NEK10; the interaction is required for ERK1/2-signaling pathway activation in response to UV irradiation (By similarity).
Interacts with TRAF3IP3 (By similarity).
By similarity5 PublicationsGO - Molecular functioni
- mitogen-activated protein kinase kinase kinase binding Source: RGD
- protein C-terminus binding Source: RGD
- protein kinase binding Source: RGD
- protein N-terminus binding Source: RGD
- scaffold protein binding Source: RGD
- small GTPase binding Source: RGD
Protein-protein interaction databases
BioGRIDi | 251005, 10 interactors |
CORUMi | Q01986 |
IntActi | Q01986, 2 interactors |
MINTi | Q01986 |
STRINGi | 10116.ENSRNOP00000013933 |
Chemistry databases
BindingDBi | Q01986 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 68 – 361 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 294 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 27 | DisorderedSequence analysisAdd BLAST | 27 | |
Regioni | 270 – 307 | RAF1-bindingAdd BLAST | 38 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0581, Eukaryota |
HOGENOMi | CLU_000288_63_23_1 |
InParanoidi | Q01986 |
OrthoDBi | 688282at2759 |
PhylomeDBi | Q01986 |
TreeFami | TF105137 |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
10 20 30 40 50
MPKKKPTPIQ LNPAPDGSAV NGTSSAETNL EALQKKLEEL ELDEQQRKRL
60 70 80 90 100
EAFLTQKQKV GELKDDDFEK ISELGAGNGG VVFKVSHKPS GLVMARKLIH
110 120 130 140 150
LEIKPAIRNQ IIRELQVLHE CNSPYIVGFY GAFYSDGEIS ICMEHMDGGS
160 170 180 190 200
LDQVLKKAGR IPEQILGKVS IAVIKGLTYL REKHKIMHRD VKPSNILVNS
210 220 230 240 250
RGEIKLCDFG VSGQLIDSMA NSFVGTRSYM SPERLQGTHY SVQSDIWSMG
260 270 280 290 300
LSLVEMAVGR YPIPPPDAKE LELLFGCQVE GDAAETPPRP RTPGRPLSSY
310 320 330 340 350
GMDSRPPMAI FELLDYIVNE PPPKLPSGVF SLEFQDFVNK CLIKNPAERA
360 370 380 390
DLKQLMVHAF IKRSDAEEVD FAGWLCSTIG LNQPSTPTHA ASI
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A0H2UHI2 | A0A0H2UHI2_RAT | Dual-specificity mitogen-activated ... | Map2k1 | 368 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Z16415 mRNA Translation: CAA78905.1 D13341 mRNA Translation: BAA02603.1 D14591 mRNA Translation: BAA03441.1 X62313 mRNA Translation: CAA44192.1 BC089772 mRNA Translation: AAH89772.1 |
PIRi | JN0840 |
RefSeqi | NP_113831.1, NM_031643.4 |
Genome annotation databases
GeneIDi | 170851 |
KEGGi | rno:170851 |
UCSCi | RGD:70495, rat |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Z16415 mRNA Translation: CAA78905.1 D13341 mRNA Translation: BAA02603.1 D14591 mRNA Translation: BAA03441.1 X62313 mRNA Translation: CAA44192.1 BC089772 mRNA Translation: AAH89772.1 |
PIRi | JN0840 |
RefSeqi | NP_113831.1, NM_031643.4 |
3D structure databases
SMRi | Q01986 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 251005, 10 interactors |
CORUMi | Q01986 |
IntActi | Q01986, 2 interactors |
MINTi | Q01986 |
STRINGi | 10116.ENSRNOP00000013933 |
Chemistry databases
BindingDBi | Q01986 |
ChEMBLi | CHEMBL3430876 |
PTM databases
iPTMneti | Q01986 |
PhosphoSitePlusi | Q01986 |
Proteomic databases
jPOSTi | Q01986 |
PaxDbi | Q01986 |
Genome annotation databases
GeneIDi | 170851 |
KEGGi | rno:170851 |
UCSCi | RGD:70495, rat |
Organism-specific databases
CTDi | 5604 |
RGDi | 70495, Map2k1 |
Phylogenomic databases
eggNOGi | KOG0581, Eukaryota |
HOGENOMi | CLU_000288_63_23_1 |
InParanoidi | Q01986 |
OrthoDBi | 688282at2759 |
PhylomeDBi | Q01986 |
TreeFami | TF105137 |
Enzyme and pathway databases
BRENDAi | 2.7.12.2, 5301 |
Reactomei | R-RNO-110056, MAPK3 (ERK1) activation R-RNO-170968, Frs2-mediated activation R-RNO-445144, Signal transduction by L1 R-RNO-5673000, RAF activation R-RNO-5674135, MAP2K and MAPK activation R-RNO-5674499, Negative feedback regulation of MAPK pathway |
Miscellaneous databases
PROi | PR:Q01986 |
Gene expression databases
Genevisiblei | Q01986, RN |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | MP2K1_RAT | |
Accessioni | Q01986Primary (citable) accession number: Q01986 Secondary accession number(s): Q5EBD5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 1, 1993 |
Last sequence update: | January 23, 2007 | |
Last modified: | February 23, 2022 | |
This is version 190 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families