Protein detail
MP2K1
Dual specificity mitogen-activated protein kinase kinase 1 (MAP kinase kinase 1) (MAPKK 1) (MKK1) (EC 2.7.12.2) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK 1)
Protein symbol MP2K1 | UniProt ID | EVMP score 0.60 |
Frequency 15 | Transmembrane count | Protein classification Cancer-related genesDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPredicted intracellular proteinsRAS pathway related proteins |
Basic Information
Protein Names
Dual specificity mitogen-activated protein kinase kinase 1 (MAP kinase kinase 1) (MAPKK 1) (MKK1) (EC 2.7.12.2) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK 1)
Protein Class
Cancer-related genesDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPredicted intracellular proteinsRAS pathway related proteins
Protein Function
- Kinases:STE Ser/Thr protein kinases
- Predicted intracellular proteins
- ENZYME proteins:Transferases
- Cancer-related genes:Mutated cancer genes
- Human disease related genes:Musculoskeletal diseases:Skeletal diseases
- RAS pathway related proteins
- Enzymes
- Cancer-related genes:Candidate cancer biomarkers
- Human disease related genes:Cancers:Cancers of haematopoietic and lymphoid tissues
- Human disease related genes:Congenital malformations:Other congenital malformations
- Disease related genes
- FDA approved drug targets:Small molecule drugs
Ensembl
Entrez Gene Symbol
Gene Synonym
MAPKK1MEK1PRKMK1
Gene Description
Mitogen-activated protein kinase kinase 1
Chromosome
15
Position
66386837-66491656
Frequency
15
EVMP Score
0.60
Fluorescence & Localization
Function & Pathway
Protein Function
- Kinases:STE Ser/Thr protein kinases
- Predicted intracellular proteins
- ENZYME proteins:Transferases
- Cancer-related genes:Mutated cancer genes
- Human disease related genes:Musculoskeletal diseases:Skeletal diseases
- RAS pathway related proteins
- Enzymes
- Cancer-related genes:Candidate cancer biomarkers
- Human disease related genes:Cancers:Cancers of haematopoietic and lymphoid tissues
- Human disease related genes:Congenital malformations:Other congenital malformations
- Disease related genes
- FDA approved drug targets:Small molecule drugs
Cellular Component
Molecular Function
- GO:0004672 protein kinase activity
- GO:0004674 protein serine/threonine kinase activity
- GO:0004708 MAP kinase kinase activity
- GO:0004712 protein serine/threonine/tyrosine kinase activity
- GO:0004713 protein tyrosine kinase activity
- GO:0005078 MAP-kinase scaffold activity
- GO:0005515 protein binding
- GO:0005524 ATP binding
- GO:0030295 protein kinase activator activity
- GO:0043539 protein serine/threonine kinase activator activity
- GO:0097110 scaffold protein binding
- GO:0106310 protein serine kinase activity
Biological Process
KEGG
- hsa01521 EGFR tyrosine kinase inhibitor resistance
- KEGG:hsa01522 Endocrine resistance
- KEGG:hsa04010 MAPK signaling pathway
- KEGG:hsa04012 ErbB signaling pathway
- KEGG:hsa04014 Ras signaling pathway
- KEGG:hsa04015 Rap1 signaling pathway
- KEGG:hsa04022 cGMP-PKG signaling pathway
- KEGG:hsa04024 cAMP signaling pathway
- KEGG:hsa04062 Chemokine signaling pathway
- KEGG:hsa04066 HIF-1 signaling pathway
- KEGG:hsa04068 FoxO signaling pathway
- KEGG:hsa04071 Sphingolipid signaling pathway
- KEGG:hsa04072 Phospholipase D signaling pathway
- KEGG:hsa04114 Oocyte meiosis
- KEGG:hsa04140 Autophagy - animal
- KEGG:hsa04148 Efferocytosis
- KEGG:hsa04150 mTOR signaling pathway
- KEGG:hsa04151 PI3K-Akt signaling pathway
- KEGG:hsa04210 Apoptosis
- KEGG:hsa04218 Cellular senescence
- KEGG:hsa04270 Vascular smooth muscle contraction
- KEGG:hsa04370 VEGF signaling pathway
- KEGG:hsa04371 Apelin signaling pathway
- KEGG:hsa04380 Osteoclast differentiation
- KEGG:hsa04510 Focal adhesion
- KEGG:hsa04517 IgSF CAM signaling
- KEGG:hsa04519 Cadherin signaling
- KEGG:hsa04540 Gap junction
- KEGG:hsa04550 Signaling pathways regulating pluripotency of stem cells
- KEGG:hsa04613 Neutrophil extracellular trap formation
- KEGG:hsa04620 Toll-like receptor signaling pathway
- KEGG:hsa04650 Natural killer cell mediated cytotoxicity
- KEGG:hsa04660 T cell receptor signaling pathway
- KEGG:hsa04662 B cell receptor signaling pathway
- KEGG:hsa04664 Fc epsilon RI signaling pathway
- KEGG:hsa04666 Fc gamma R-mediated phagosome formation
- KEGG:hsa04668 TNF signaling pathway
- KEGG:hsa04720 Long-term potentiation
- KEGG:hsa04722 Neurotrophin signaling pathway
- KEGG:hsa04725 Cholinergic synapse
- KEGG:hsa04726 Serotonergic synapse
- KEGG:hsa04730 Long-term depression
- KEGG:hsa04810 Regulation of actin cytoskeleton
- KEGG:hsa04910 Insulin signaling pathway
- KEGG:hsa04912 GnRH signaling pathway
- KEGG:hsa04914 Progesterone-mediated oocyte maturation
- KEGG:hsa04915 Estrogen signaling pathway
- KEGG:hsa04916 Melanogenesis
- KEGG:hsa04917 Prolactin signaling pathway
- KEGG:hsa04919 Thyroid hormone signaling pathway
- KEGG:hsa04921 Oxytocin signaling pathway
- KEGG:hsa04926 Relaxin signaling pathway
- KEGG:hsa04928 Parathyroid hormone synthesis, secretion and action
- KEGG:hsa04929 GnRH secretion
- KEGG:hsa04934 Cushing syndrome
- KEGG:hsa04935 Growth hormone synthesis, secretion and action
- KEGG:hsa05010 Alzheimer disease
- KEGG:hsa05022 Pathways of neurodegeneration - multiple diseases
- KEGG:hsa05034 Alcoholism
- KEGG:hsa05132 Salmonella infection
- KEGG:hsa05135 Yersinia infection
- KEGG:hsa05160 Hepatitis C
- KEGG:hsa05161 Hepatitis B
- KEGG:hsa05163 Human cytomegalovirus infection
- KEGG:hsa05164 Influenza A
- KEGG:hsa05165 Human papillomavirus infection
- KEGG:hsa05166 Human T-cell leukemia virus 1 infection
- KEGG:hsa05167 Kaposi sarcoma-associated herpesvirus infection
- KEGG:hsa05170 Human immunodeficiency virus 1 infection
- KEGG:hsa05200 Pathways in cancer
- KEGG:hsa05205 Proteoglycans in cancer
- KEGG:hsa05206 MicroRNAs in cancer
- KEGG:hsa05207 Chemical carcinogenesis - receptor activation
- KEGG:hsa05208 Chemical carcinogenesis - reactive oxygen species
- KEGG:hsa05210 Colorectal cancer
- KEGG:hsa05211 Renal cell carcinoma
- KEGG:hsa05212 Pancreatic cancer
- KEGG:hsa05213 Endometrial cancer
- KEGG:hsa05214 Glioma
- KEGG:hsa05215 Prostate cancer
- KEGG:hsa05216 Thyroid cancer
- KEGG:hsa05218 Melanoma
- KEGG:hsa05219 Bladder cancer
- KEGG:hsa05220 Chronic myeloid leukemia
- KEGG:hsa05221 Acute myeloid leukemia
- KEGG:hsa05223 Non-small cell lung cancer
- KEGG:hsa05224 Breast cancer
- KEGG:hsa05225 Hepatocellular carcinoma
- KEGG:hsa05226 Gastric cancer
- KEGG:hsa05230 Central carbon metabolism in cancer
- KEGG:hsa05231 Choline metabolism in cancer
- KEGG:hsa05235 PD-L1 expression and PD-1 checkpoint pathway in cancer
Reactome
- R-hsa-9824439 bacterial infection pathways
- R-hsa-1280215 cytokine signaling in immune system
- R-hsa-5663202 diseases of signal transduction by growth factor receptors and second messengers
- R-hsa-5663205 infectious disease
- R-hsa-168249 innate immune system
- R-hsa-448424 interleukin 17 signaling
- R-hsa-446652 interleukin 1 family signaling
- R-hsa-9020702 interleukin 1 signaling
- R-hsa-373760 l1cam interactions
- R-hsa-5674135 map2k and mapk activation
- R-hsa-5684264 map3k8 tpl2 dependent mapk1 3 activation
- R-hsa-5684996 mapk1 mapk3 signaling
- R-hsa-110056 mapk3 erk1 activation
- R-hsa-5683057 mapk family signaling cascades
- R-hsa-166166 myd88 independent tlr4 cascade
- R-hsa-5674499 negative feedback regulation of mapk pathway
- R-hsa-5675221 negative regulation of mapk pathway
- R-hsa-9675108 nervous system development
- R-hsa-6802957 oncogenic mapk signaling
- R-hsa-169893 prolonged erk activation events
- R-hsa-5673000 raf activation
- R-hsa-112409 raf independent mapk1 3 activation
- R-hsa-6802952 signaling by braf and raf1 fusions
- R-hsa-449147 signaling by interleukins
- R-hsa-6802946 signaling by moderate kinase activity braf mutants
- R-hsa-166520 signaling by ntrks
- R-hsa-9006934 signaling by receptor tyrosine kinases
- R-hsa-187687 signalling to erks
- R-hsa-445144 signal transduction by l1
- R-hsa-168138 toll like receptor 9 tlr9 cascade
- R-hsa-168898 toll like receptor cascades
- R-hsa-168179 toll like receptor tlr1 tlr2 cascade
- R-hsa-5339562 uptake and actions of bacterial toxins
- R-hsa-5210891 uptake and function of anthrax toxins
Mediation Categories
Adhesion and uptake mediationClinical-translation mediationFusion and delivery mediationImmune mediationReceptor-signaling mediation
Relations & Evidence
Enzyme-Mediated Modification
83 records.
| Substrate Gene Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| MAP2K1 | MAP3K8 | P41279 | S | 244 | phosphorylation | SIGNOR_ProtMapperSIGNORProtMapper | ProtMapper:8131746SIGNOR:8131746 |
| MAP2K1 | MAP3K8 | P41279 | S | 248 | phosphorylation | SIGNOR_ProtMapperSIGNORProtMapper | ProtMapper:8131746SIGNOR:8131746 |
| MAP2K1 | MAP3K8 | P41279 | S | 24 | phosphorylation | PhosphoNetworks | |
| MAP2K1 | PDPK1 | O15530 | S | 222 | phosphorylation | SIGNORProtMapperRLIMS-P_ProtMapperKEAphosphoELMSIGNOR_ProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper | phosphoELM:15175348KEA:8394352SIGNOR:15175348KEA:8157000KEA:94178255KEA:15175348KEA:8621729KEA:8131746ProtMapper:15175348KEA:7731720KEA:15466476KEA:8039496KEA:7624324 |
| MAP2K1 | ZHX2 | Q9Y6X8 | S | 218 | phosphorylation | dbPTM | dbPTM:8131746 |
| MAP2K1 | ZHX2 | Q9Y6X8 | S | 222 | phosphorylation | dbPTM | dbPTM:17192257dbPTM:8131746 |
| MAP2K1 | MOS | P00540 | S | 222 | phosphorylation | PhosphoSiteSIGNOR | SIGNOR:7731726 |
| MAP2K1 | MOS | P00540 | S | 218 | phosphorylation | PhosphoSite | |
| MAP2K1 | BRAF | P15056 | S | 252 | phosphorylation | SIGNOR_ProtMapperSIGNORProtMapper | SIGNOR:8413257ProtMapper:8413257 |
| MAP2K1 | BRAF | P15056 | S | 248 | phosphorylation | SIGNOR_ProtMapperSIGNORProtMapper | SIGNOR:8413257ProtMapper:8413257 |
Ligand-Receptor Signaling
7 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| receptor | receptor | OmniPath | No | Yes | No | No | No |
| intracellular | intracellular | LOCATE | No | No | No | No | No |
| intracellular | intracellular | ComPPI | No | No | No | No | No |
| intracellular | intracellular | GO_Intercell | No | No | No | No | No |
| intracellular | intracellular | UniProt_location | No | No | No | No | No |
| intracellular | intracellular | OmniPath | No | No | No | No | No |
| receptor | receptor | scConnect | No | Yes | No | No | No |
Regulatory Interaction Network
31 records.
Protein Complex Composition
22 records.
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Isolation & Detection Technology
1 record.
| EV Isolation Method | Detection Method | Number of References | References |
|---|---|---|---|
| Differential UltracentrifugationSize Exclusion Chromatography | Mass spectrometry | 1 | 27605433 |
Sequence, Structure & Domains
Sequences
Length
393
Mass
43,439
Sequence
MPKKKPTPIQLNPAPDGSAVNGTSSAETNLEALQKKLEELELDEQQRKRLEAFLTQKQKVGELKDDDFEKISELGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKAGRIPEQILGKVSIAVIKGLTYLREKHKIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTRSYMSPERLQGTHYSVQSDIWSMGLSLVEMAVGRYPIPPPDAKELELMFGCQVEGDAAETPPRPRTPGRPLSSYGMDSRPPMAIFELLDYIVNEPPPKLPSGVFSLEFQDFVNKCLIKNPAERADLKQLMVHAFIKRSDAEEVDFAGWLCSTIGLNQPSTPTHAAGV
Alternative Products
Event=Alternative splicing; Named isoforms=2; Name=1; Synonyms=MKK1a; IsoId=Q02750-1; Sequence=Displayed; Name=2; Synonyms=MKK1b; IsoId=Q02750-2; Sequence=VSP_040500
Alternative Sequence
147..172; Missing (in isoform 2)
3D Structural Models
Turn
58..60; 88..91; 200..202; 327..329; 346..348
Helix
38..40; 44..57; 65..67; 105..115; 116..120; 151..158; 163..184; 193..195; 213..218; 221..223; 227..229; 232..236; 242..258; 268..275; 310..319; 332..341; 352..356; 359..366; 371..379
Beta Strand
68..76; 78..87; 92..100; 129..135; 138..144; 196..198; 204..206
3D Structure
Electron microscopy (14); X-ray crystallography (70)
Domain & Motif Annotations
Domain (CC)
The proline-rich region localized between residues 270 and 307 is important for binding to RAF1 and activation of MAP2K1/MEK1..
Domain (FT)
68..361; Protein kinase
Region
1..27; Disordered; 270..307; RAF1-binding
Protein Families
- Protein kinase superfamily
- STE Ser/Thr protein kinase family
- MAP kinase kinase subfamily
Sequence Similarities
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.
Clinical Relevance
Disease Involvement
Cancer-related genesCardiomyopathyDisease variantEctodermal dysplasiaFDA approved drug targetsIntellectual disability
Drug Targets
FDA approved drug targets
Drugs
CI-1040SELUMETINIBNULLMS432ZAPNOMETINIBMAP855ALPELISIBTRAMETINIB DIMETHYL SULFOXIDEZM447439COBIMETINIBAVUTOMETINIBREFAMETINIBAKT INHIBITOR MK2206RG-7167TAK-733BINIMETINIBAZD8330CETUXIMABGDC-0879TIZATERKIBCERITINIBMEK INHIBITOR RO4987655PANITUMUMABPIMASERTIBVANDETANIBCHEMBL:CHEMBL379975VEMURAFENIBRO-4987655DABRAFENIBTOZASERTIBDOVITINIBMEK INHIBITOR IIPP2BALAMAPIMODMIRDAMETINIBMEK INHIBITOR ISCH772984VTX-11ERAVOXERTINIBU0126SOTRASTAURINNVP-TAE684PD98059PD-0166285ARRY-300COBIMETINIB FUMARATEPLX-4720OMIPALISIBAZD-8330IRINOTECAN HYDROCHLORIDESORAFENIBGDC-0623ENCORAFENIBULIXERTINIBAS-703988E-6201ILORASERTIBDEL-22379BI-847325REGORAFENIBMETFORMINDASATINIB ANHYDROUSWX-554RG-1530CENISERTIBJNJ-7706621FLUOROURACILLEUCOVORIN CALCIUMLY3009120CHEMBL:CHEMBL546797STAUROSPORINESELUMETINIB SULFATECHEMBL:CHEMBL1956073COMPOUND 3 [PMID: 31804822]E6201TEMUTERKIBNEDOMETINIB
Interaction Protein
ENSG00000078061ENSG00000100030ENSG00000102882ENSG00000108953ENSG00000126934ENSG00000128245ENSG00000132155ENSG00000134308ENSG00000137693ENSG00000141068ENSG00000157764ENSG00000164924ENSG00000166913ENSG00000170027
Interaction Count
14
Interaction Dataset
biogrid_opencellintact_biogridintact_biogrid_opencell