MAP2K1 - Dual specificity mitogen-activated protein kinase kinase 1 - human protein (Function)
 
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MAP2K1 »  Dual specificity mitogen-activated protein kinase kinase 1   [ EC 2.7.12.2 ]  (MKK1)
 
Protein also known as:  ERK activator kinase 1.
Gene name:  MAP2K1
Entry whose protein(s) existence is based on evidence at protein level
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1 209 2
GENE REF ISO

Function

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Overview 
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.  
2
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524] silver  
  • IEAOrtholog Compara
MAP kinase kinase activitydefinition[GO:0004708]  
1
  • IDAUniProtKB
Mitogen-activated protein kinase kinase kinase bindingdefinition[GO:0031435] silver  
  • IEAOrtholog Compara
Protein bindingdefinition[GO:0005515]  
10
  • IPIIntAct
  • IPIUniProtKB
Protein kinase activitydefinition[GO:0004672]  
1
  • TASPINC
Protein serine/threonine kinase activator activitydefinition[GO:0043539]  
1
  • IDAUniProtKB
Protein serine/threonine/tyrosine kinase activitydefinition[GO:0004712]  
1
  • TASUniProtKB
Protein tyrosine kinase activitydefinition[GO:0004713]  
  • IEAUniProtKB KW
Ras GTPase bindingdefinition[GO:0017016] silver  
  • IEAOrtholog Compara
Receptor signaling protein tyrosine phosphatase activitydefinition[GO:0004728] silver  
  • IEAOrtholog Compara
GO biological process 
Activation of MAPK activitydefinition[GO:0000187]  
1
  • TASUniProtKB
Cell cycle arrestdefinition[GO:0007050]  
1
  • IMPBHF-UCL
Cell motilitydefinition[GO:0048870] silver  
  • IEAOrtholog Compara
Cell proliferationdefinition[GO:0008283] silver  
  • IEAOrtholog Compara
Cellular component movementdefinition[GO:0006928]  
1
  • TASPINC
Cellular senescencedefinition[GO:0090398]  
1
  • IMPBHF-UCL
Chemotaxisdefinition[GO:0006935]  
1
  • TASPINC
Golgi inheritancedefinition[GO:0048313] silver  
  • IEAOrtholog Compara
Keratinocyte differentiationdefinition[GO:0030216] silver  
  • IEAOrtholog Compara
Labyrinthine layer developmentdefinition[GO:0060711] silver  
  • IEAOrtholog Compara
Melanosome transportdefinition[GO:0032402] silver  
  • IEAOrtholog Compara
Mitosisdefinition[GO:0007067] silver  
  • IEAOrtholog Compara
Negative regulation of cell proliferationdefinition[GO:0008285]  
1
  • IDABHF-UCL
Negative regulation of homotypic cell-cell adhesiondefinition[GO:0034111] silver  
  • IEAOrtholog Compara
Placenta blood vessel developmentdefinition[GO:0060674] silver  
  • IEAOrtholog Compara
Positive regulation of cell differentiationdefinition[GO:0045597] silver  
  • IEAOrtholog Compara
Positive regulation of cell migrationdefinition[GO:0030335] silver  
  • IEAOrtholog Compara
Positive regulation of gene expressiondefinition[GO:0010628]  
1
  • IMPUniProtKB
Positive regulation of protein serine/threonine kinase activitydefinition[GO:0071902]  
1
  • IDAUniProtKB
Positive regulation of Ras GTPase activitydefinition[GO:0032320] silver  
  • IEAOrtholog Compara
Positive regulation of Ras protein signal transductiondefinition[GO:0046579] silver  
  • IEAOrtholog Compara
Positive regulation of transcription elongation from RNA polymerase II promoterdefinition[GO:0032968] silver  
  • IEAOrtholog Compara
Protein heterooligomerizationdefinition[GO:0051291] silver  
  • IEAOrtholog Compara
Regulation of early endosome to late endosome transportdefinition[GO:2000641]  
1
  • TASUniProtKB
Regulation of Golgi inheritancedefinition[GO:0090170]  
1
  • TASUniProtKB
Regulation of stress-activated MAPK cascadedefinition[GO:0032872]  
1
  • TASUniProtKB
Regulation of vascular smooth muscle contractiondefinition[GO:0003056] silver  
  • IEAOrtholog Compara
Response to axon injurydefinition[GO:0048678] silver  
  • IEAOrtholog Compara
Response to glucocorticoiddefinition[GO:0051384] silver  
  • IEAOrtholog Compara
Response to oxidative stressdefinition[GO:0006979] silver  
  • IEAOrtholog Compara
Signal transductiondefinition[GO:0007165]  
1
  • TASPINC
Vesicle transport along microtubuledefinition[GO:0047496] silver  
  • IEAOrtholog Compara
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.12.2: ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
It is regulated in the following manner
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.  
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Acute myeloid leukemia  hsa05221+5604  
B cell receptor signaling pathway  hsa04662+5604  
Bladder cancer  hsa05219+5604  
Chemokine signaling pathway  hsa04062+5604  
Cholinergic synapse  hsa04725+5604  
Chronic myeloid leukemia  hsa05220+5604  
Colorectal cancer  hsa05210+5604  
Dorso-ventral axis formation  hsa04320+5604  
Endometrial cancer  hsa05213+5604  
ErbB signaling pathway  hsa04012+5604  
Fc epsilon RI signaling pathway  hsa04664+5604  
Fc gamma R-mediated phagocytosis  hsa04666+5604  
Focal adhesion  hsa04510+5604  
Gap junction  hsa04540+5604  
Glioma  hsa05214+5604  
GnRH signaling pathway  hsa04912+5604  
Influenza A  hsa05164+5604  
Insulin signaling pathway  hsa04910+5604  
Long-term depression  hsa04730+5604  
Long-term potentiation  hsa04720+5604  
MAPK signaling pathway  hsa04010+5604  
Melanogenesis  hsa04916+5604  
Melanoma  hsa05218+5604  
Natural killer cell mediated cytotoxicity  hsa04650+5604  
Neurotrophin signaling pathway  hsa04722+5604  
Non-small cell lung cancer  hsa05223+5604  
Oocyte meiosis  hsa04114+5604  
Osteoclast differentiation  hsa04380+5604  
Pancreatic cancer  hsa05212+5604  
Pathways in cancer  hsa05200+5604  
Prion diseases  hsa05020+5604  
Progesterone-mediated oocyte maturation  hsa04914+5604  
Prostate cancer  hsa05215+5604  
Regulation of actin cytoskeleton  hsa04810+5604  
Renal cell carcinoma  hsa05211+5604  
T cell receptor signaling pathway  hsa04660+5604  
Thyroid cancer  hsa05216+5604  
Toll-like receptor signaling pathway  hsa04620+5604  
Vascular smooth muscle contraction  hsa04270+5604  
VEGF signaling pathway  hsa04370+5604  
According to Reactome, this protein belongs to the following pathways:
Developmental Biology  REACT_111045  
Disease  REACT_116125  
Immune System  REACT_6900  
Signal Transduction  REACT_111102  
TRAF6 Mediated Induction of proinflammatory cytokines  REACT_6782  
 

Keywords

Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Tyrosine-protein kinase  definition   [KW-0829]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: MAP2K1
GenomeRNAi: 5604
PRO: PR:Q02750
Chemistry
GuidetoPHARMACOLOGY: 2062