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Overview

Uniprot IDQ01986
Protein NameDual specificity mitogen-activated protein kinase kinase 1
Gene NameMap2k1
OrganismRattus norvegicus

Kla Sites from experimental identification

Position Flanking peptide
104 KLIHLEIKPAIRNQI
36 NLEALQKKLEELELD
57 LEAFLTQKQKVGELK
88 VVFKVSHKPSGLVMA
97 SGLVMARKLIHLEIK

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

Protein Sequence

10 MPKKKPTPIQ 20 LNPAPDGSAV 30 NGTSSAETNL 40 EALQKKLEEL 50 ELDEQQRKRL 60 EAFLTQKQKV 70 GELKDDDFEK 80 ISELGAGNGG 90 VVFKVSHKPS 100 GLVMARKLIH 110 LEIKPAIRNQ 120 IIRELQVLHE 130 CNSPYIVGFY 140 GAFYSDGEIS 150 ICMEHMDGGS 160 LDQVLKKAGR 170 IPEQILGKVS 180 IAVIKGLTYL 190 REKHKIMHRD 200 VKPSNILVNS 210 RGEIKLCDFG 220 VSGQLIDSMA 230 NSFVGTRSYM 240 SPERLQGTHY 250 SVQSDIWSMG 260 LSLVEMAVGR 270 YPIPPPDAKE 280 LELLFGCQVE 290 GDAAETPPRP 300 RTPGRPLSSY 310 GMDSRPPMAI 320 FELLDYIVNE 330 PPPKLPSGVF 340 SLEFQDFVNK 350 CLIKNPAERA 360 DLKQLMVHAF 370 IKRSDAEEVD 380 FAGWLCSTIG 390 LNQPSTPTHA ASI

Gene Ontology

Classification GO ID Description
Cellular Component GO:0030424 axon
Molecular Function GO:0043539 protein serine/threonine kinase activator activity
Molecular Function GO:0004674 protein serine/threonine kinase activity
Molecular Function GO:0004712 protein serine/threonine/tyrosine kinase activity
Molecular Function GO:0004713 protein tyrosine kinase activity
Molecular Function GO:0044877 protein-containing complex binding
Molecular Function GO:0097110 scaffold protein binding
Molecular Function GO:0031267 small GTPase binding
Biological Process GO:0060020 Bergmann glial cell differentiation
Biological Process GO:0048870 cell motility
Biological Process GO:0090398 cellular senescence
Biological Process GO:0021697 cerebellar cortex formation
Biological Process GO:0060502 epithelial cell proliferation involved in lung morphogenesis
Biological Process GO:0038127 ERBB signaling pathway
Biological Process GO:0038133 ERBB2-ERBB3 signaling pathway
Biological Process GO:0070371 ERK1 and ERK2 cascade
Biological Process GO:0060324 face development
Biological Process GO:0048313 Golgi inheritance
Biological Process GO:0007507 heart development
Biological Process GO:0008286 insulin receptor signaling pathway
Biological Process GO:0048009 insulin-like growth factor receptor signaling pathway
Biological Process GO:0035556 intracellular signal transduction
Biological Process GO:0030216 keratinocyte differentiation
Biological Process GO:0060711 labyrinthine layer development
Biological Process GO:0060425 lung morphogenesis
Biological Process GO:0000165 MAPK cascade
Biological Process GO:0032402 melanosome transport
Biological Process GO:0042552 myelination
Biological Process GO:0008285 negative regulation of cell population proliferation
Biological Process GO:0010629 negative regulation of gene expression
Biological Process GO:0034111 negative regulation of homotypic cell-cell adhesion
Biological Process GO:1903298 negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway
Biological Process GO:0007528 neuromuscular junction development
Biological Process GO:0030182 neuron differentiation
Biological Process GO:0048812 neuron projection morphogenesis
Biological Process GO:0060674 placenta blood vessel development
Biological Process GO:2001171 positive regulation of ATP biosynthetic process
Biological Process GO:0010508 positive regulation of autophagy
Biological Process GO:0050772 positive regulation of axonogenesis
Biological Process GO:0045597 positive regulation of cell differentiation
Biological Process GO:0030335 positive regulation of cell migration
Biological Process GO:0045893 positive regulation of DNA-templated transcription
Biological Process GO:0070374 positive regulation of ERK1 and ERK2 cascade
Biological Process GO:0010628 positive regulation of gene expression
Biological Process GO:0043547 positive regulation of GTPase activity
Biological Process GO:0043410 positive regulation of MAPK cascade
Biological Process GO:0045933 positive regulation of muscle contraction
Biological Process GO:0071902 positive regulation of protein serine/threonine kinase activity
Biological Process GO:0046579 positive regulation of Ras protein signal transduction
Biological Process GO:0032968 positive regulation of transcription elongation by RNA polymerase II
Biological Process GO:0006468 protein phosphorylation
Biological Process GO:0048679 regulation of axon regeneration
Biological Process GO:2000641 regulation of early endosome to late endosome transport
Biological Process GO:0070372 regulation of ERK1 and ERK2 cascade
Biological Process GO:0090170 regulation of Golgi inheritance
Biological Process GO:0098696 regulation of neurotransmitter receptor localization to postsynaptic specialization membrane
Biological Process GO:0032872 regulation of stress-activated MAPK cascade
Biological Process GO:0003056 regulation of vascular associated smooth muscle contraction
Biological Process GO:0048678 response to axon injury
Biological Process GO:0051384 response to glucocorticoid
Biological Process GO:0006979 response to oxidative stress
Biological Process GO:0014044 Schwann cell development
Biological Process GO:0048538 thymus development
Biological Process GO:0030878 thyroid gland development
Biological Process GO:0060440 trachea formation
Biological Process GO:0070328 triglyceride homeostasis
Biological Process GO:0047496 vesicle transport along microtubule
Cellular Component GO:0005938 cell cortex
Cellular Component GO:0005813 centrosome
Cellular Component GO:0036064 ciliary basal body
Cellular Component GO:0005829 cytosol
Cellular Component GO:0030425 dendrite
Cellular Component GO:0032839 dendrite cytoplasm
Cellular Component GO:0005769 early endosome
Cellular Component GO:0005783 endoplasmic reticulum
Cellular Component GO:0005925 focal adhesion
Cellular Component GO:0098978 glutamatergic synapse
Cellular Component GO:0005794 Golgi apparatus
Cellular Component GO:0005770 late endosome
Cellular Component GO:0005874 microtubule
Cellular Component GO:0005739 mitochondrion
Cellular Component GO:0005634 nucleus
Cellular Component GO:0043204 perikaryon
Cellular Component GO:0048471 perinuclear region of cytoplasm
Cellular Component GO:0005886 plasma membrane
Cellular Component GO:0014069 postsynaptic density
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0004708 MAP kinase kinase activity
Molecular Function GO:0005078 MAP-kinase scaffold activity
Molecular Function GO:0031435 mitogen-activated protein kinase kinase kinase binding
Molecular Function GO:0030295 protein kinase activator activity
Molecular Function GO:0019901 protein kinase binding
Molecular Function GO:0106310 protein serine kinase activity

Reference

[1] Chen Y, Sun W, Sun Z, Zhao H, Wu T et al.. Effect of electroacupuncture on hippocampal protein lactylation in a rat model of vascular dementia.. Front Neurol 16:1629474. 2025. PMID: 40963935.