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Aliases for MAP2K1 Gene

Aliases for MAP2K1 Gene

  • Mitogen-Activated Protein Kinase Kinase 1 2 3
  • PRKMK1 3 4 6
  • MEK1 3 4 6
  • MKK1 3 4 6
  • ERK Activator Kinase 1 3 4
  • MAPK/ERK Kinase 1 3 4
  • EC 2.7.12.2 4 64
  • MAPKK 1 3 4
  • MEK 1 3 4
  • CFC3 3 6
  • Protein Kinase, Mitogen-Activated, Kinase 1 (MAP Kinase Kinase 1) 3
  • Dual Specificity Mitogen-Activated Protein Kinase Kinase 1 3
  • MAP Kinase Kinase 1 4
  • MAPKK1 3

External Ids for MAP2K1 Gene

Previous Symbols for MAP2K1 Gene

  • PRKMK1

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]

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 map2k1-related cardiofaciocutaneous syndrome. Among its related pathways are PI3K-Akt signaling pathway and PI-3K cascade. GO annotations related to this gene include protein serine/threonine kinase activity and protein tyrosine kinase activity. An important paralog of this gene is MAP2K7.

UniProtKB/Swiss-Prot 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

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MAP2K1 Gene

Genomics for MAP2K1 Gene

Genomic Location for MAP2K1 Gene

Start:
66,386,817 bp from pter
End:
66,492,312 bp from pter
Size:
105,496 bases
Orientation:
Plus strand

Genomic View for MAP2K1 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for MAP2K1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MAP2K1 Gene

Regulatory Elements 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
    Secondary Accessions:

    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 (By similarity). Forms a heterodimer with MAP2K2/MEK2 (By similarity). Forms heterodimers with KSR2 which further dimerize to form tetramers (By similarity). Interacts with ARBB2, LAMTOR3, MAPK1/ERK2, MORG1 and RAF1 (By similarity). Interacts with PPARG and with isoform 1 of VRK2. Interacts with Yersinia yopJ. Interacts with SGK1. Interacts with BIRC6/bruce.

    Three dimensional structures from OCA and Proteopedia for MAP2K1 Gene

    Alternative splice isoforms for MAP2K1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MAP2K1 Gene

Proteomics data for MAP2K1 Gene at MOPED

Post-translational modifications for MAP2K1 Gene

  • Acetylation by Yersinia yopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway.
  • 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.
  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys104, Lys192, Lys205, and Lys353

Other Protein References for MAP2K1 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Domains for MAP2K1 Gene

Gene Families for MAP2K1 Gene

HGNC:
  • MAP2K :Mitogen-activated protein kinase cascade / Kinase kinases
IUPHAR :

UniProtKB/Swiss-Prot:

MP2K1_HUMAN
Domain:
  • The proline-rich region localized between residues 270 and 307 is important for binding to RAF1 and activation of MAP2K1/MEK1.:
    • Q02750
  • Contains 1 protein kinase domain.:
    • Q02750
Family:
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.:
    • Q02750
genes like me logo Genes that share domains with MAP2K1: view

Function for MAP2K1 Gene

Molecular function for MAP2K1 Gene

GENATLAS Biochemistry: mitogen-activated protein kinase kinase 1,nucleocytoplasmic shuttling protein,involved in signal transduction
UniProtKB/Swiss-Prot CatalyticActivity: ATP + a protein = ADP + a phosphoprotein
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.
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.

Enzyme Numbers (IUBMB) for MAP2K1 Gene

Gene Ontology (GO) - Molecular Function for MAP2K1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity 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
GO:0004713 protein tyrosine kinase activity IEA --
genes like me logo Genes that share ontologies with MAP2K1: view
genes like me logo Genes that share phenotypes with MAP2K1: view

Animal Models for MAP2K1 Gene

MGI Knock Outs for MAP2K1:

No data available for Transcription Factor Targeting 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. Note=Localizes at centrosomes during prometaphase, midzone during anaphase and midbody during telophase/cytokinesis.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for MAP2K1 Gene COMPARTMENTS Subcellular localization image for MAP2K1 gene
Compartment Confidence
cytoskeleton 5
cytosol 5
endosome 5
golgi apparatus 5
mitochondrion 5
nucleus 5
plasma membrane 4
extracellular 2

Gene Ontology (GO) - Cellular Components for MAP2K1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus TAS 19565474
GO:0005737 cytoplasm IDA --
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 for MAP2K1 Gene

SuperPathways for MAP2K1 Gene

Superpath Contained pathways
1 IL-2 Pathway
2 Signaling by FGFR
3 IL-9 Signaling Pathways
4 Insulin receptor signalling cascade
5 Translation Insulin regulation of translation
genes like me logo Genes that share pathways with MAP2K1: view

Pathways by source 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:0000186 activation of MAPKK activity TAS --
GO:0000187 activation of MAPK activity TAS 19565474
GO:0002224 toll-like receptor signaling pathway TAS --
GO:0002755 MyD88-dependent toll-like receptor signaling pathway TAS --
genes like me logo Genes that share ontologies with MAP2K1: view

Compounds for MAP2K1 Gene

(4) ApexBio Compounds for MAP2K1 Gene

Compound Action Cas Number
FR 180204 Selective ERK inhibitor [865362-74-9]
VX-11e potent, selective, and orally bioavailable inhibitor of ERK [896720-20-0]
XMD17-109 novel, specific ERK-5 inhibitor with an EC50 4.2uM in HEK293 cells [1435488-37-1]
XMD8-92 highly selective ERK5/BMK1 inhibitor [1234480-50-2]

(2) HMDB Compounds for MAP2K1 Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
ADP
  • adenosindiphosphorsaeure
58-64-0

(120) Novoseek inferred chemical compound relationships for MAP2K1 Gene

Compound -log(P) Hits PubMed IDs
pd 98,059 94 115
pd-184352 82.5 11
sb 203580 80.5 46
ly294002 75.7 35
hymenialdisine 74.3 2

(1) PharmGKB related drug/compound annotations for MAP2K1 Gene

Drug/compound Annotation
trametinib
genes like me logo Genes that share compounds with MAP2K1: view

Transcripts for MAP2K1 Gene

mRNA/cDNA for MAP2K1 Gene

Unigene Clusters for MAP2K1 Gene

Mitogen-activated protein kinase kinase 1:
Representative Sequences:

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 for MAP2K1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for MAP2K1 Gene

SOURCE GeneReport for Unigene cluster for MAP2K1 Gene Hs.145442

mRNA Expression by UniProt/SwissProt for MAP2K1 Gene

Q02750-MP2K1_HUMAN
Tissue specificity: Widely expressed, with extremely low levels in brain.
genes like me logo Genes that share expressions with MAP2K1: view

Orthologs for MAP2K1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for MAP2K1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia MAP2K1 36
  • 98.64 (n)
  • 98.98 (a)
MAP2K1 37
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia MAP2K1 36
  • 94.49 (n)
  • 100 (a)
MAP2K1 37
  • 100 (a)
OneToOne
dog
(Canis familiaris)
Mammalia MAP2K1 36
  • 94.25 (n)
  • 99.47 (a)
MAP2K1 37
  • 99 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Map2k1 36
  • 90.67 (n)
  • 98.98 (a)
Map2k1 16
Map2k1 37
  • 99 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia MAP2K1 37
  • 97 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia MAP2K1 37
  • 80 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Map2k1 36
  • 91.26 (n)
  • 99.24 (a)
chicken
(Gallus gallus)
Aves MAP2K1 36
  • 81.51 (n)
  • 95.93 (a)
MAP2K1 37
  • 95 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia -- 37
  • 81 (a)
ManyToMany
African clawed frog
(Xenopus laevis)
Amphibia mek-2-prov 36
tropical clawed frog
(Silurana tropicalis)
Amphibia map2k1 36
  • 78.12 (n)
  • 92.62 (a)
Str.10686 36
zebrafish
(Danio rerio)
Actinopterygii Dr.25154 36
map2k1 36
  • 76.41 (n)
  • 88.97 (a)
map2k1 37
  • 88 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP001103 36
  • 61.1 (n)
  • 68.46 (a)
fruit fly
(Drosophila melanogaster)
Insecta Dsor1 36
  • 64.62 (n)
  • 67.88 (a)
Dsor1 37
  • 61 (a)
OneToMany
Dsor1 38
  • 66 (a)
worm
(Caenorhabditis elegans)
Secernentea mek-2 36
  • 52.46 (n)
  • 53.89 (a)
mek-2 37
  • 53 (a)
OneToMany
mek-2 38
  • 52 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes PBS2 37
  • 22 (a)
OneToMany
STE7 39
thale cress
(Arabidopsis thaliana)
eudicotyledons MEK1 36
  • 51.19 (n)
  • 43.93 (a)
rice
(Oryza sativa)
Liliopsida Os06g0147800 36
  • 49.4 (n)
  • 42.39 (a)
bread mold
(Neurospora crassa)
Ascomycetes NCU04612 36
  • 56.14 (n)
  • 51.58 (a)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes byr1 36
  • 49.9 (n)
  • 45.94 (a)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.141 36
sea squirt
(Ciona savignyi)
Ascidiacea CSA.8484 37
  • 65 (a)
OneToMany
Species with no ortholog for MAP2K1:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for MAP2K1 Gene

ENSEMBL:
Gene Tree for MAP2K1 (if available)
TreeFam:
Gene Tree for MAP2K1 (if available)

Paralogs for MAP2K1 Gene

Paralogs for MAP2K1 Gene

Pseudogenes.org Pseudogenes for MAP2K1 Gene

genes like me logo Genes that share paralogs with MAP2K1: view

Variants for MAP2K1 Gene

Sequence variations from dbSNP and Humsavar for MAP2K1 Gene

SNP ID Clin Chr 15 pos Sequence Context AA Info Type MAF
rs745796 -- 66,406,242(+) AATTA(C/T)ATTGC intron-variant
rs749771 -- 66,408,238(-) GGGAA(A/C)TAAGA intron-variant
rs752252 -- 66,433,277(+) AGCTG(C/T)CTCAG intron-variant
rs752253 -- 66,434,027(-) GGCTC(C/T)TGGTA intron-variant
rs752404 -- 66,407,380(+) TCAGG(C/T)TTCAG intron-variant

Structural Variations from Database of Genomic Variants (DGV) for MAP2K1 Gene

Variant ID Type Subtype PubMed ID
nsv833045 CNV Gain 17160897
esv2749791 CNV Deletion 23290073
esv2749792 CNV Deletion 23290073
dgv455e199 CNV Deletion 23128226

Relevant External Links for MAP2K1 Gene

HapMap Linkage Disequilibrium report
MAP2K1
Human Gene Mutation Database (HGMD)
MAP2K1
Locus Specific Mutation Databases (LSDB)
MAP2K1

Disorders for MAP2K1 Gene

(1) OMIM Diseases for MAP2K1 Gene (176872)

UniProtKB/Swiss-Prot

MP2K1_HUMAN
  • Cardiofaciocutaneous syndrome 3 (CFC3) [MIM:615279]: A form of cardiofaciocutaneous syndrome, a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. Distinctive features of CFC3 include macrostomia and horizontal shape of palpebral fissures. {ECO:0000269 PubMed:16439621, ECO:0000269 PubMed:18042262}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(2) University of Copenhagen DISEASES for MAP2K1 Gene

(53) Novoseek inferred disease relationships for MAP2K1 Gene

Disease -log(P) Hits PubMed IDs
cfc syndrome 88.6 7
noonan syndrome 68.1 3
anthrax 43 3
tumors 37.9 40
leukemia 35.5 4

Relevant External Links for MAP2K1

GeneTests
MAP2K1
GeneReviews
MAP2K1
Genetic Association Database (GAD)
MAP2K1
Human Genome Epidemiology (HuGE) Navigator
MAP2K1
genes like me logo Genes that share disorders with MAP2K1: view

Publications for MAP2K1 Gene

  1. Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2. (PMID: 8388392) Zheng C.-F. … Guan K.-L. (J. Biol. Chem. 1993) 2 3 4 23
  2. Activation of MEK family kinases requires phosphorylation of two conserved Ser/Thr residues. (PMID: 8131746) Zheng C.-F. … Guan K.-L. (EMBO J. 1994) 3 4 23
  3. Structures of human MAP kinase kinase 1 (MEK1) and MEK2 describe novel noncompetitive kinase inhibition. (PMID: 15543157) Ohren J.F. … Hasemann C.A. (Nat. Struct. Mol. Biol. 2004) 3 4 23
  4. Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: molecular diversity and associated phenotypic spectrum. (PMID: 19206169) Sarkozy A. … Tartaglia M. (Hum. Mutat. 2009) 3 23 49
  5. Spectrum of MEK1 and MEK2 gene mutations in cardio-facio-cutaneous syndrome and genotype-phenotype correlations. (PMID: 19156172) Dentici M.L. … Dallapiccola B. (Eur. J. Hum. Genet. 2009) 3 23 49

Products for MAP2K1 Gene

Sources for MAP2K1 Gene

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