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)
Entry name MP2K1 | UniProt ID | EVMP confidence score 0.60 |
Supporting publications (n) 15 | Transmembrane count | Protein classification Cancer-related genesDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPredicted intracellular proteinsRAS pathway related proteins |
EVMP confidence score
Annotation confidence score; open for threshold definitions.
Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40Basic Information11
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 (7)
Cancer-related genesDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPredicted intracellular proteinsRAS pathway related proteins
Protein Function (12)
- 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
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Ensembl
Entrez Gene Symbol
Gene Synonym (3)
MAPKK1MEK1PRKMK1
Gene Description
Mitogen-activated protein kinase kinase 1
Chromosome
15
Position
66386837-66491656
Supporting publications (n)
15
EVMP confidence score
0.60
Function & Pathway7
Protein Function (12)
- 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
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Cellular Component (10)
Molecular Function (12)
- 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
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Biological Process (3)
KEGG (92)
- 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
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Reactome (34)
- 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
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Mediation Categories (5)
Adhesion and uptake mediationClinical-translation mediationFusion and delivery mediationImmune mediationReceptor-signaling mediation
Relations & Evidence144
Enzyme-Mediated Modification (83)
83 records.
| Substrate Gene Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| MAP2K1 | MAPK1 | P28482 | S | 231 | phosphorylation | PhosphoNetworks | |
| MAP2K1 | MAPK1 | P28482 | S | 218 | phosphorylation | NCI-PID_ProtMapperProtMapper | ProtMapper:19541618 |
| MAP2K1 | MAPK1 | P28482 | S | 222 | phosphorylation | NCI-PID_ProtMapperProtMapper | ProtMapper:19541618 |
| MAP2K1 | MAPK1 | P28482 | T | 386 | phosphorylation | PhosphoNetworksSparser_ProtMapperphosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPSIGNORProtMapperRLIMS-P_ProtMapperKEAphosphoELMSIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper | ProtMapper:10567369KEA:8157000SIGNOR:10567369ProtMapper:17254543phosphoELM:10567369KEA:10567369 |
| MAP2K1 | MAPK1 | P28482 | T | 292 | phosphorylation | PhosphoNetworksphosphoELM_MIMPPhosphoSite_MIMPMIMPNCI-PID_ProtMapperHPRD_MIMPSIGNORProtMapperHPRDRLIMS-P_ProtMapperReactome_ProtMapperKEAphosphoELMSIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper | ProtMapper:19219045HPRD:12594221KEA:12594221KEA:8157000ProtMapper:17928366SIGNOR:14993270ProtMapper:8013650phosphoELM:10567369KEA:9351825HPRD:8157000KEA:10567369ProtMapper:14993270 |
| MAP2K1 | MAPK1 | P28482 | T | 286 | phosphorylation | PhosphoSitePhosphoNetworksPhosphoSite_ProtMapperProtMapper | |
| MAP2K1 | PAK1 | Q13153 | S | 298 | phosphorylation | Sparser_ProtMapperphosphoELM_MIMPPhosphoSite_MIMPMIMPNCI-PID_ProtMapperHPRD_MIMPSIGNORProtMapperHPRDRLIMS-P_ProtMapperKEAphosphoELMSIGNOR_ProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper | HPRD:9351825phosphoELM:12876277phosphoELM:9351825KEA:7873542ProtMapper:22981863ProtMapper:11435472ProtMapper:25794709ProtMapper:23162738KEA:12876277ProtMapper:21371233ProtMapper:18940914SIGNOR:12876277ProtMapper:23701950ProtMapper:19595712phosphoELM:14993270ProtMapper:27542844ProtMapper:12876277ProtMapper:9351825KEA:16129686ProtMapper:29551131ProtMapper:18593598ProtMapper:22105362ProtMapper:28225038ProtMapper:21248166phosphoELM:16129686KEA:9351825ProtMapper:18668521 |
| MAP2K1 | PAK1 | Q13153 | S | 299 | phosphorylation | KEA | KEA:7873542KEA:12876277 |
| MAP2K1 | CDK1 | P06493 | T | 286 | phosphorylation | phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPSIGNORProtMapperRLIMS-P_ProtMapperReactome_ProtMapperKEAphosphoELMSIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper | KEA:11684694ProtMapper:25971971KEA:12609978SIGNOR:8114697phosphoELM:11684694ProtMapper:8114697 |
| MAP2K1 | CDK1 | P06493 | T | 292 | phosphorylation | phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPSIGNORProtMapperRLIMS-P_ProtMapperReactome_ProtMapperSIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper | SIGNOR:8114697ProtMapper:8114697 |
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Ligand-Receptor Signaling (7)
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)
31 records.
| Source Protein Symbol | Source UniProt ID | Target Protein Symbol | Target UniProt ID | Is Directed | Is Stimulation | Is Inhibition | Database | References |
|---|---|---|---|---|---|---|---|---|
| MP2K1 | Q02750 | MYRF | Q9Y2G1 | Yes | No | Yes | SIGNOR | SIGNOR:30496175 |
| MP2K1 | Q02750 | TET2 | Q6N021 | Yes | Yes | No | SIGNOR | SIGNOR:38461173 |
| MP2K1 | Q02750 | CASP9 | P55211 | Yes | No | Yes | phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetPhosphoPointSIGNORProtMapperHPRDPhosphoSite_KEAKEAHPRD_KEASIGNOR_ProtMapperHPRD-phos | KEA:12792650ProtMapper:12792650HPRD-phos:12792650HPRD-phos:18669648ProtMapper:18669648HPRD:12792650SIGNOR:12792650 |
| CDK1 | P06493 | MP2K1 | Q02750 | Yes | No | Yes | phosphoELM_MIMPPhosphoSite_MIMPMIMPPhosphoSite_ProtMapperHPRD_MIMPPhosphoSite_norefSIGNORiPTMnetProtMapperRLIMS-P_ProtMapperReactome_ProtMapperKEAphosphoELM_KEAphosphoELMSIGNOR_ProtMapperNetworKIN_KEA | KEA:11684694ProtMapper:25971971KEA:12609978SIGNOR:8114697KEA:17570479phosphoELM:11684694ProtMapper:8114697 |
| MP2K1 | Q02750 | TAL1 | P17542 | Yes | No | Yes | phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetSIGNORProtMapperPhosphoSite_KEAKEASIGNOR_ProtMapper | ProtMapper:11904294KEA:8423803SIGNOR:11904294 |
| MP2K1 | Q02750 | GSK3B | P49841 | Yes | Yes | No | PhosphoNetworksphosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetSIGNORProtMapperPhosphoSite_KEAKEAphosphoELM_KEAphosphoELMSIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper | PhosphoSite:21105670KEA:16964243PhosphoSite:14617795phosphoELM:15020233KEA:15020233ProtMapper:15020233PhosphoSite:35019937PhosphoSite:18547980KEA:17081983PhosphoSite:30711629PhosphoSite:17188038SIGNOR:15020233KEA:8382613KEA:17192257 |
| M3K21 | Q5TCX8 | MP2K1 | Q02750 | Yes | Yes | No | SIGNOR_ProtMapperiPTMnetSIGNORProtMapper | SIGNOR:23319808ProtMapper:23319808 |
| GIT1 | Q9Y2X7 | MP2K1 | Q02750 | Yes | Yes | No | REACH_ProtMapperSIGNORProtMapper | ProtMapper:25794709SIGNOR:23325602 |
| COMPLEX:Q00535_Q15078 | MP2K1 | Q02750 | Yes | No | Yes | SIGNOR | SIGNOR:11684694 | |
| MP2K1 | Q02750 | ARRB2 | P32121 | Yes | Yes | No | iPTMnetSIGNORProtMapperInnateDBSIGNOR_ProtMapper | ProtMapper:28169830SIGNOR:28169830InnateDB:11226259 |
Protein Complex Composition (22)
22 records.
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Isolation & Detection Technology (1)
1 record.
| EV Isolation Method | Detection Method | Number of References | References |
|---|---|---|---|
| Differential UltracentrifugationSize Exclusion Chromatography | Mass spectrometry | 1 | 27605433 |
Sequence, Structure & Domains14
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 (3)
- 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 Relevance7
Disease Involvement (6)
Cancer-related genesCardiomyopathyDisease variantEctodermal dysplasiaFDA approved drug targetsIntellectual disability
Drug Targets
FDA approved drug targets
Drugs (77)
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 (14)
ENSG00000078061ENSG00000100030ENSG00000102882ENSG00000108953ENSG00000126934ENSG00000128245ENSG00000132155ENSG00000134308ENSG00000137693ENSG00000141068ENSG00000157764ENSG00000164924ENSG00000166913ENSG00000170027
Interaction Count
14
Interaction Dataset (3)
biogrid_opencellintact_biogridintact_biogrid_opencell
Supporting Publications15
| PMID | Title | Abstract |
|---|---|---|
| 38490958 | Proteomic analysis of ascitic extracellular vesicles describes tumour microenvironment and predicts patient survival in ovarian cancer. | No abstract available |
| 38644352 | The tumour-derived extracellular vesicle proteome varies by endometrial cancer histology and is confounded by an obesogenic environment. | No abstract available |
| 38731868 | The Deep Proteomics Approach Identified Extracellular Vesicular Proteins Correlated to Extracellular Matrix in Type One and Two Endometrial Cancer. | No abstract available |
| 40091455 | Potential Role of Menstrual Fluid-Derived Small Extracellular Vesicle Proteins in Endometriosis Pathogenesiss. | No abstract available |
| 41201090 | Identification of molecular markers and exploration of the oncogenic role of exomeres in hepatocellular carcinoma. | No abstract available |
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