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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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.  
3
  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB KW
MAP kinase kinase activitydefinition[GO:0004708]  
1
  • UniProtKB
Mitogen-activated protein kinase kinase kinase bindingdefinition[GO:0031435] silver  
1
  • Ortholog Compara
Protein bindingdefinition[GO:0005515]  
10
  • IntAct
  • UniProtKB
Protein C-terminus bindingdefinition[GO:0008022]  
1
  • MGI
Protein kinase activitydefinition[GO:0004672]  
1
  • PINC
Protein N-terminus bindingdefinition[GO:0047485]  
1
  • MGI
Protein serine/threonine kinase activator activitydefinition[GO:0043539]  
1
  • UniProtKB
Protein serine/threonine/tyrosine kinase activitydefinition[GO:0004712]  
1
  • UniProtKB
Protein tyrosine kinase activitydefinition[GO:0004713]  
1
  • UniProtKB KW
Ras GTPase bindingdefinition[GO:0017016] silver  
1
  • Ortholog Compara
Receptor signaling protein tyrosine phosphatase activitydefinition[GO:0004728] silver  
1
  • Ortholog Compara
GO biological process 
Activation of MAPK activitydefinition[GO:0000187]  
2
  • UniProtKB
  • AgBase
Cell cycle arrestdefinition[GO:0007050]  
1
  • BHF-UCL
Cell motilitydefinition[GO:0048870] silver  
1
  • Ortholog Compara
Cell proliferationdefinition[GO:0008283] silver  
1
  • Ortholog Compara
Cellular component movementdefinition[GO:0006928]  
1
  • PINC
Cellular senescencedefinition[GO:0090398]  
1
  • BHF-UCL
Chemotaxisdefinition[GO:0006935]  
1
  • PINC
Golgi inheritancedefinition[GO:0048313] silver  
1
  • Ortholog Compara
Keratinocyte differentiationdefinition[GO:0030216] silver  
1
  • Ortholog Compara
Labyrinthine layer developmentdefinition[GO:0060711] silver  
1
  • Ortholog Compara
Melanosome transportdefinition[GO:0032402] silver  
1
  • Ortholog Compara
Mitotic nuclear divisiondefinition[GO:0007067] silver  
1
  • Ortholog Compara
Negative regulation of cell proliferationdefinition[GO:0008285]  
1
  • BHF-UCL
Negative regulation of homotypic cell-cell adhesiondefinition[GO:0034111] silver  
1
  • Ortholog Compara
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
1
  • UniProtKB KW
Placenta blood vessel developmentdefinition[GO:0060674] silver  
1
  • Ortholog Compara
Positive regulation of cell differentiationdefinition[GO:0045597] silver  
1
  • Ortholog Compara
Positive regulation of cell migrationdefinition[GO:0030335] silver  
1
  • Ortholog Compara
Positive regulation of gene expressiondefinition[GO:0010628]  
1
  • UniProtKB
Positive regulation of protein serine/threonine kinase activitydefinition[GO:0071902]  
1
  • UniProtKB
Positive regulation of Ras GTPase activitydefinition[GO:0032320] silver  
1
  • Ortholog Compara
Positive regulation of Ras protein signal transductiondefinition[GO:0046579] silver  
1
  • Ortholog Compara
Positive regulation of transcription elongation from RNA polymerase II promoterdefinition[GO:0032968] silver  
1
  • Ortholog Compara
Protein heterooligomerizationdefinition[GO:0051291] silver  
1
  • Ortholog Compara
Regulation of early endosome to late endosome transportdefinition[GO:2000641]  
1
  • UniProtKB
Regulation of Golgi inheritancedefinition[GO:0090170]  
1
  • UniProtKB
Regulation of stress-activated MAPK cascadedefinition[GO:0032872]  
1
  • UniProtKB
Regulation of vascular smooth muscle contractiondefinition[GO:0003056] silver  
1
  • Ortholog Compara
Response to axon injurydefinition[GO:0048678] silver  
1
  • Ortholog Compara
Response to glucocorticoiddefinition[GO:0051384] silver  
1
  • Ortholog Compara
Response to oxidative stressdefinition[GO:0006979] silver  
1
  • Ortholog Compara
Signal transductiondefinition[GO:0007165]  
1
  • PINC
Vesicle transport along microtubuledefinition[GO:0047496] silver  
1
  • Ortholog 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.  
1
  • UniProtKB
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.  
1
  • UniProtKB
 
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:
ERK1 activation  REACT_1391  
Interleukin-1 signaling  REACT_22442  
MEK activation  REACT_962  
RAF phosphorylates MEK  REACT_614  
Signal transduction by L1  REACT_22272  
Signaling by FGFR  REACT_9470  
Uptake and function of anthrax toxins  REACT_228255  
 

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