Map2k1
entrez
170851
canonical
uniprot
Q01986
canonical
ensembl
ENSRNOG00000010176
resolver
ensembl
ENSRNOG00055024284
resolver
ensembl
ENSRNOG00060018969
resolver
ensembl
ENSRNOG00065006381
resolver
ensp
ENSRNOP00000084527
resolver
ensp
ENSRNOP00000086602
resolver
ensp
ENSRNOP00055034029
resolver
ensp
ENSRNOP00060027113
resolver
ensp
ENSRNOP00065007137
resolver
enst
ENSRNOT00000102833
resolver
enst
ENSRNOT00000120242
resolver
enst
ENSRNOT00055041789
resolver
enst
ENSRNOT00060033130
resolver
enst
ENSRNOT00065009833
resolver
genesymbol
Map2k1
resolver
genesymbol_syn
Mek1
resolver
genesymbol_syn
Prkmk1
resolver
uniprot
A0A8I6A1J3
resolver
uniprot
Q5EBD5
resolver
uniprot_entry
A0A8I6A1J3_RAT
resolver
uniprot_entry
MP2K1_RAT
resolver
uniprot_sec
Q5EBD5
resolver
activity_regulation
ACTIVITY REGULATION: Ras proteins such as HRAS mediate the activation of RAF proteins such as RAF1 or BRAF which in turn activate extracellular signal-regulated kinases (ERK) through MAPK (mitogen-activated protein kinases) and ERK kinases MAP2K1/MEK1 and MAP2K2/MEK2. Activation occurs through phosphorylation of Ser-218 and Ser-222. MAP2K1/MEK1 binds KSR1 or KSR2 releasing the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains (By similarity). This allows KSR1 or KSR2 dimerization with BRAF leading to BRAF activation and phosphorylation of MAP2K1 (By similarity). MAP2K1/MEK1 is also the target of negative feed-back regulation by its substrate kinases, such as MAPK1/ERK2. These phosphorylate MAP2K1/MEK1 on Thr-292, thereby facilitating dephosphorylation of the activating residues Ser-218 and Ser-222. Inhibited by serine/threonine phosphatase 2A. {ECO:0000250|UniProtKB:Q02750, ECO:0000269|PubMed:12876277, ECO:0000269|PubMed:14993270, ECO:0000269|PubMed:7565670, ECO:0000269|PubMed:9733512}.
uniprot
proteins
amino_acid_sequence
MPKKKPTPIQLNPAPDGSAVNGTSSAETNLEALQKKLEELELDEQQRKRLEAFLTQKQKVGELKDDDFEKISELGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKAGRIPEQILGKVSIAVIKGLTYLREKHKIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTRSYMSPERLQGTHYSVQSDIWSMGLSLVEMAVGRYPIPPPDAKELELLFGCQVEGDAAETPPRPRTPGRPLSSYGMDSRPPMAIFELLDYIVNEPPPKLPSGVFSLEFQDFVNKCLIKNPAERADLKQLMVHAFIKRSDAEEVDFAGWLCSTIGLNQPSTPTHAASI
uniprot
proteins
ec_number
2.7.12.2
uniprot
proteins
function
FUNCTION: 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. {ECO:0000250|UniProtKB:Q02750, ECO:0000269|PubMed:10769026, ECO:0000269|PubMed:19177150}.
uniprot
proteins
mass_dalton
43465
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-218 and Ser-222 by MAP kinase kinase kinases (BRAF or MEKK1) positively regulates kinase activity (PubMed:10769026). Also phosphorylated at Thr-292 by MAPK1/ERK2 and at Ser-298 by PAK (PubMed:12876277, PubMed:14993270). MAPK1/ERK2 phosphorylation of Thr-292 occurs in response to cellular adhesion and leads to inhibition of Ser-298 phosphorylation by PAK (PubMed:14993270). Autophosphorylated at Ser-218 and Ser-222, autophosphosphorylation is promoted by NEK10 following UV irradiation (By similarity). {ECO:0000250|UniProtKB:Q02750, ECO:0000269|PubMed:10769026, ECO:0000269|PubMed:12876277, ECO:0000269|PubMed:14993270}.
uniprot
proteins
protein_family
MAP kinase kinase subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
STE Ser/Thr protein kinase family
uniprot
proteins
pubmed
10769026
uniprot
proteins
pubmed
11226259
uniprot
proteins
pubmed
12876277
uniprot
proteins
pubmed
14993270
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15520807
uniprot
proteins
pubmed
19177150
uniprot
proteins
pubmed
19319189
uniprot
proteins
pubmed
19565474
uniprot
proteins
pubmed
21779493
uniprot
proteins
pubmed
22673903
uniprot
proteins
pubmed
7565670
uniprot
proteins
pubmed
8380494
uniprot
proteins
pubmed
8406028
uniprot
proteins
pubmed
8462694
uniprot
proteins
pubmed
9733512
uniprot
proteins
pubmed
9779990
uniprot
proteins
sequence_length
393
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250|UniProtKB:Q02750}. Cytoplasm, cytoskeleton, microtubule organizing center, spindle pole body {ECO:0000250|UniProtKB:Q02750}. Cytoplasm {ECO:0000250|UniProtKB:Q02750}. Nucleus {ECO:0000250|UniProtKB:Q02750}. Membrane {ECO:0000250|UniProtKB:Q02750}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q02750}. Note=Localizes at centrosomes during prometaphase, midzone during anaphase and midbody during telophase/cytokinesis. Membrane localization is probably regulated by its interaction with KSR1. {ECO:0000250|UniProtKB:Q02750}.
uniprot
proteins