The protein encoded by this gene is a member of the dual specificity protein kinase family, which acts as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of... See more...

Aliases for MAP2K1 Gene

Aliases for MAP2K1 Gene

  • Mitogen-Activated Protein Kinase Kinase 1 2 3 5
  • Dual Specificity Mitogen-Activated Protein Kinase Kinase 1 3 4
  • ERK Activator Kinase 1 3 4
  • MAPK/ERK Kinase 1 3 4
  • EC 2.7.12.2 4 54
  • MAPKK 1 3 4
  • PRKMK1 3 4
  • MEK 1 3 4
  • MEK1 3 4
  • MKK1 3 4
  • Protein Kinase, Mitogen-Activated, Kinase 1 (MAP Kinase Kinase 1) 3
  • MAP Kinase Kinase 1 4
  • MAPKK1 3
  • CFC3 3

External Ids for MAP2K1 Gene

Previous HGNC Symbols for MAP2K1 Gene

  • PRKMK1

Previous GeneCards Identifiers for MAP2K1 Gene

  • GC15U990039
  • GC15P059778
  • GC15P064258
  • GC15P064395
  • GC15P064356
  • GC15P064466
  • GC15P066679
  • GC15P043515

Summaries for MAP2K1 Gene

Entrez Gene Summary for MAP2K1 Gene

  • The protein encoded by this gene is a member of the dual specificity protein kinase family, which acts as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon wide variety of extra- and intracellular signals. As an essential component of MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as proliferation, differentiation, transcription regulation and development. [provided by RefSeq, Jul 2008]

CIViC Summary for MAP2K1 Gene

  • MAP2K1 is a dual-specificity kinase known for it's involvement in the ERK pathway by activation of ERK1 and ERK2. MAP2K1 activating mutations have been observed in a number of cancers including ovarian, melanoma and lung. These activating mutations are generally found in the N-terminal negative regulatory region or the ATP-binding region of the N-terminal lobe. Inhibitors of MEK genes have been shown to inhibit tumor growth in these cases.

GeneCards Summary for MAP2K1 Gene

MAP2K1 (Mitogen-Activated Protein Kinase Kinase 1) is a Protein Coding gene. Diseases associated with MAP2K1 include Cardiofaciocutaneous Syndrome 3 and Cardiofaciocutaneous Syndrome 1. Among its related pathways are Transcription Androgen Receptor nuclear signaling and VEGF Signaling Pathway. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is MAP2K2.

UniProtKB/Swiss-Prot Summary for MAP2K1 Gene

  • 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. 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.

Gene Wiki entry for MAP2K1 Gene

Additional gene information for MAP2K1 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for MAP2K1 Gene

Genomics for MAP2K1 Gene

GeneHancer (GH) Regulatory Elements for MAP2K1 Gene

Promoters and enhancers for MAP2K1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MAP2K1 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the MAP2K1 gene promoter:
  • ARP-1
  • COUP
  • COUP-TF
  • COUP-TF1
  • HNF-4alpha1
  • HNF-4alpha2
  • STAT3
  • USF-1:USF-2

Genomic Locations for MAP2K1 Gene

Genomic Locations for MAP2K1 Gene
chr15:66,386,817-66,492,312
(GRCh38/hg38)
Size:
105,496 bases
Orientation:
Plus strand
chr15:66,679,155-66,784,650
(GRCh37/hg19)
Size:
105,496 bases
Orientation:
Plus strand

Genomic View for MAP2K1 Gene

Genes around MAP2K1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MAP2K1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MAP2K1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MAP2K1 Gene

Proteins for MAP2K1 Gene

  • Protein details for MAP2K1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q02750-MP2K1_HUMAN
    Recommended name:
    Dual specificity mitogen-activated protein kinase kinase 1
    Protein Accession:
    Q02750

    Protein attributes for MAP2K1 Gene

    Size:
    393 amino acids
    Molecular mass:
    43439 Da
    Quaternary structure:
    • Found in a complex with at least BRAF, HRAS, MAP2K1, MAPK3/ERK1 and RGS14. Forms a heterodimer with MAP2K2/MEK2. Forms heterodimers with KSR2 which further dimerize to form tetramers. Interacts with ARBB2, LAMTOR3, MAPK1/ERK2, MORG1 and RAF1 (By similarity). Interacts with PPARG and with isoform 1 of VRK2 (PubMed:20679487, PubMed:17101779). Interacts with Yersinia yopJ (PubMed:16728640). Interacts with SGK1 (PubMed:19447520). Interacts with BIRC6/bruce (PubMed:18329369). Interacts with KSR1 (PubMed:10409742). Interacts with KAT7; the interaction promotes KAT7 phosphorylation (By similarity).

    Three dimensional structures from OCA and Proteopedia for MAP2K1 Gene

    Alternative splice isoforms for MAP2K1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MAP2K1 Gene

Selected DME Specific Peptides for MAP2K1 Gene

Q02750:
  • MARKLIHLE
  • KNPAERADLK
  • ILGKVSIAV
  • VDFAGWLC
  • HAFIKRS
  • LQKKLEEL
  • FYSDGEISICMEHMDGGSLDQVLK
  • KELELMFGC
  • CNSPYIV
  • LNQPSTPT
  • PEQILGKV
  • KVGELKDDDFE
  • GEIKLCDFGVSG
  • SELGAGNGGVVFKVSHKP
  • PIPPPDAKELE
  • ELELDEQQ
  • EFQDFVNKCL
  • MAIFELLDYIVNEPP
  • RLEAFLTQK
  • GRYPIPPPD
  • LIDSMANSFVGTRSYM

Post-translational modifications for MAP2K1 Gene

  • Phosphorylation at Ser-218 and Ser-222 by MAP kinase kinase kinases (RAF or MEKK1) positively regulates kinase activity. Also phosphorylated at Thr-292 by MAPK1/ERK2 and at Ser-298 by PAK. MAPK1/ERK2 phosphorylation of Thr-292 occurs in response to cellular adhesion and leads to inhibition of Ser-298 phosphorylation by PAK.
  • Acetylation by Yersinia yopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway.
  • Ubiquitination at Lys353
  • Modification sites at PhosphoSitePlus

Other Protein References for MAP2K1 Gene

Antibody Products

  • Abcam antibodies for MAP2K1

Domains & Families for MAP2K1 Gene

Gene Families for MAP2K1 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Enzymes
  • FDA approved drug targets
  • Predicted intracellular proteins

Protein Domains for MAP2K1 Gene

Suggested Antigen Peptide Sequences for MAP2K1 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ76051, highly similar to Homo sapiens mitogen-activated protein kinase kinase 1 (MAP2K1), mRNA (A4QPA9_HUMAN)
  • cDNA FLJ58770, highly similar to Dual specificity mitogen-activated protein kinase kinase 1 (EC 2.7.12.2) (B4DFY5_HUMAN)
  • MAPK/ERK kinase 1 (MP2K1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q02750

UniProtKB/Swiss-Prot:

MP2K1_HUMAN :
  • The proline-rich region localized between residues 270 and 307 is important for binding to RAF1 and activation of MAP2K1/MEK1.
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.
Domain:
  • The proline-rich region localized between residues 270 and 307 is important for binding to RAF1 and activation of MAP2K1/MEK1.
Family:
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.
genes like me logo Genes that share domains with MAP2K1: view

Function for MAP2K1 Gene

Molecular function for MAP2K1 Gene

UniProtKB/Swiss-Prot 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. 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.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.12.2;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.12.2;.
UniProtKB/Swiss-Prot EnzymeRegulation:
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 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 (By similarity). Many inhibitors have been identified including pyrrole derivatives, TAK-733 (one of a series of 8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione derivatives), CH4987655 and RDEA119/BAY 869766.
GENATLAS Biochemistry:
mitogen-activated protein kinase kinase 1,nucleocytoplasmic shuttling protein,involved in signal transduction

Enzyme Numbers (IUBMB) for MAP2K1 Gene

Phenotypes From GWAS Catalog for MAP2K1 Gene

Gene Ontology (GO) - Molecular Function for MAP2K1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0004672 protein kinase activity IEA,TAS 10570282
GO:0004674 protein serine/threonine kinase activity TAS --
GO:0004708 MAP kinase kinase activity IDA 8388392
GO:0004712 protein serine/threonine/tyrosine kinase activity TAS 19565474
genes like me logo Genes that share ontologies with MAP2K1: view
genes like me logo Genes that share phenotypes with MAP2K1: view

Human Phenotype Ontology for MAP2K1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for MAP2K1 Gene

MGI Knock Outs for MAP2K1:

Animal Model Products

  • Taconic Biosciences Mouse Models for MAP2K1

CRISPR Products

miRNA for MAP2K1 Gene

miRTarBase miRNAs that target MAP2K1

Clone Products

No data available for Transcription Factor Targets and HOMER Transcription for MAP2K1 Gene

Localization for MAP2K1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MAP2K1 Gene

Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton, microtubule organizing center, spindle pole body. Cytoplasm. Nucleus. Membrane; Peripheral membrane protein. Note=Localizes at centrosomes during prometaphase, midzone during anaphase and midbody during telophase/cytokinesis (PubMed:14737111). Membrane localization is probably regulated by its interaction with KSR1 (PubMed:10409742). {ECO:0000269 PubMed:10409742, ECO:0000269 PubMed:14737111}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for MAP2K1 gene
Compartment Confidence
plasma membrane 5
mitochondrion 5
nucleus 5
endoplasmic reticulum 5
endosome 5
cytosol 5
golgi apparatus 5
cytoskeleton 4
extracellular 2
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (4)
  • Plasma membrane (4)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for MAP2K1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus TAS 19565474
GO:0005737 cytoplasm IBA 21873635
GO:0005739 mitochondrion TAS 19565474
GO:0005769 early endosome TAS 19565474
GO:0005770 late endosome TAS 19565474
genes like me logo Genes that share ontologies with MAP2K1: view

Pathways & Interactions for MAP2K1 Gene

PathCards logo

SuperPathways for MAP2K1 Gene

SuperPathway Contained pathways
1 RET signaling
2 Activated TLR4 signalling
3 IL-2 Pathway
.59
.59
.54
.51
.49
.48
.47
.44
.43
.37
.36
.35
.34
4 Regulation of lipid metabolism Insulin signaling-generic cascades
5 Common Cytokine Receptor Gamma-Chain Family Signaling Pathways
genes like me logo Genes that share pathways with MAP2K1: view

Pathways by source for MAP2K1 Gene

103 Qiagen pathways for MAP2K1 Gene
  • 14-3-3 Induced Intracellular Signaling
  • 4-1BB Pathway
  • Activation of cAMP-Dependent PKA
  • Activation of PKA through GPCR
  • Activation of PKC through GPCR
1 Cell Signaling Technology pathway for MAP2K1 Gene
1 GeneTex pathway for MAP2K1 Gene

SIGNOR curated interactions for MAP2K1 Gene

Gene Ontology (GO) - Biological Process for MAP2K1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade TAS --
GO:0000187 activation of MAPK activity TAS,IDA 19565474
GO:0006468 protein phosphorylation IEA,IDA 28166211
GO:0006935 chemotaxis TAS 10570282
GO:0007050 cell cycle arrest IMP 9765203
genes like me logo Genes that share ontologies with MAP2K1: view

Drugs & Compounds for MAP2K1 Gene

(143) Drugs for MAP2K1 Gene - From: DrugBank, PharmGKB, ApexBio, DGIdb, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Trametinib Approved Pharma Target, antagonist, inhibitor, Biomarker MEK 1/2 inhibitor, MEK Inhibitors, Kinase Inhibitors, Mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitors 179
cobimetinib Approved, Investigational Pharma Target, inhibitor Selective MEK inhibitor 0
bosutinib Approved Pharma Target, inhibitor Kinase Inhibitors, SRC/BCR-ABL tyrosine kinase inhibitors 0
Dabrafenib Approved, Investigational Pharma Inhibition, inhibitor BRAF kinase inhibitor, Kinase Inhibitors, Mutant BRAF Kinase 108
Sorafenib Approved, Investigational Pharma inhibitors, inhibitor Raf kinases and tyrosine kinases inhibitor, RAF, VEGFR2, and PDGFR-beta inhibitors, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors 762

(49) Additional Compounds for MAP2K1 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
Full agonist, Agonist, Partial agonist, Antagonist, Gating inhibitor 58-64-0

(2) Tocris Compounds for MAP2K1 Gene

Compound Action Cas Number
10Z-Hymenialdisine Pan kinase inhibitor; potently inhibits MEK1 82005-12-7
BIX 02189 Selective MEK5 and ERK5 inhibitor 1265916-41-3

(37) ApexBio Compounds for MAP2K1 Gene

Compound Action Cas Number
10Z-Hymenialdisine 82005-12-7
Arctigenin Anti-inflammatory, antiproliferative 7770-78-7
AZD6244 (Selumetinib) MEK inhibitor 606143-52-6
AZD8330 MEK 1/2 inhibitor 869357-68-6
BI-847325 dual inhibitor of MEK and Aurora kinases 1207293-36-4
BIX 02188 MEK5 inhibitor,potent and selective 1094614-84-2
BIX 02189 Selective MEK5 inhibitor 1094614-85-3
Cobimetinib Selective MEK inhibitor 934660-93-2
Cobimetinib (racemate) Selective MEK inhibitor 934662-91-6
Cobimetinib (R-enantiomer) Selective MEK inhibitor 934660-94-3
FR 180204 ERK inhibitor 865362-74-9
GDC-0623 MEK1 inhibitor, potent and ATP-uncompetitive 1168091-68-6
GDC-0994 ERK1/2 inhibitor 1453848-26-4
MEK inhibitor Potent MEK inhibitor, Antitumor agent 334951-92-7
MEK Inhibitor Set For phosphorylation and dephosphorylation applications
MEK162 (ARRY-162, ARRY-438162) MEK1/2 inhibitor,potent and selective 606143-89-9
PD 198306 MEK inhibitor 212631-61-3
PD 334581 548756-68-9
PD0325901 MEK inhibitor 391210-10-9
PD184352 (CI-1040) Selective MEK inhibitor 212631-79-3
PD318088 Allosteric MEK1/2 inhibitor, non-ATP competitive 391210-00-7
PD98059 MEK inhibitor,selective and reversible 167869-21-8
Pimasertib (AS-703026) MEK1/2 inhibitor 1236699-92-5
Refametinib MEK 1/ MEK 2 inhibitor 923032-37-5
Refametinib R enantiomer MEK1/2 allosteric inhibitor 923032-38-6
RO4987655 MEK inhibitor 874101-00-5
RO5126766(CH5126766) Raf/MEK dual inhibitor 946128-88-7
SCH772984 ERK1 and ERK2 inhibitor 942183-80-4
SCH772984 HCl
SCH772984 TFA
SL-327 Selective MEK1/2 inhibitor 305350-87-2
TAK-733 MEK allosteric site inhibitor 1035555-63-5
Trametinib (GSK1120212) MEK1 and MEK2 inhibitor, potent and selective 871700-17-3
Trametinib DMSO solvate Allosteric MEK1/MEK2 kinase inhibitor 1187431-43-1
U0124 108923-79-1
U0126-EtOH MEK1/2 inhibitor 1173097-76-1
Vemurafenib (PLX4032, RG7204) BRAF kinase inhibitor 918504-65-1
genes like me logo Genes that share compounds with MAP2K1: view

Transcripts for MAP2K1 Gene

mRNA/cDNA for MAP2K1 Gene

(1) REFSEQ mRNAs :
(12) Additional mRNA sequences :
(190) Selected AceView cDNA sequences:
(3) Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for MAP2K1 Gene

No ASD Table

Relevant External Links for MAP2K1 Gene

GeneLoc Exon Structure for
MAP2K1
ECgene alternative splicing isoforms for
MAP2K1

Expression for MAP2K1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for MAP2K1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for MAP2K1 Gene

This gene is overexpressed in Frontal cortex (12.5), Bone marrow mesenchymal stem cell (10.0), and Brain (7.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for MAP2K1 Gene