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Q02750

- MP2K1_HUMAN

UniProt

Q02750 - MP2K1_HUMAN

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Protein
Dual specificity mitogen-activated protein kinase kinase 1
Gene
MAP2K1, MEK1, PRKMK1
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei8 – 92Cleavage; by anthrax lethal factor
Binding sitei77 – 771Inhibitor; via carbonyl oxygen
Binding sitei78 – 781Inhibitor; via amide nitrogen and carbonyl oxygen
Binding sitei97 – 971ATP
Binding sitei97 – 971Inhibitor
Active sitei190 – 1901Proton acceptor By similarity
Binding sitei190 – 1901Inhibitor
Binding sitei194 – 1941Inhibitor; via carbonyl oxygen
Binding sitei208 – 2081ATP
Binding sitei208 – 2081Inhibitor
Binding sitei212 – 2121Inhibitor; via amide nitrogen

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi74 – 829ATP
Nucleotide bindingi143 – 1464ATP
Nucleotide bindingi150 – 1534ATP
Nucleotide bindingi192 – 1954ATP

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. MAP kinase kinase activity Source: UniProtKB
  3. protein binding Source: UniProtKB
  4. protein kinase activity Source: ProtInc
  5. protein serine/threonine kinase activator activity Source: UniProtKB
  6. protein serine/threonine kinase activity Source: Reactome
  7. protein serine/threonine/tyrosine kinase activity Source: UniProtKB
  8. protein tyrosine kinase activity Source: UniProtKB-KW
  9. receptor signaling protein tyrosine phosphatase activity Source: Ensembl

GO - Biological processi

  1. Fc-epsilon receptor signaling pathway Source: Reactome
  2. Golgi inheritance Source: Ensembl
  3. MAPK cascade Source: Reactome
  4. MyD88-dependent toll-like receptor signaling pathway Source: Reactome
  5. MyD88-independent toll-like receptor signaling pathway Source: Reactome
  6. Ras protein signal transduction Source: Reactome
  7. TRIF-dependent toll-like receptor signaling pathway Source: Reactome
  8. activation of MAPK activity Source: UniProtKB
  9. activation of MAPKK activity Source: Reactome
  10. axon guidance Source: Reactome
  11. cell cycle arrest Source: BHF-UCL
  12. cell motility Source: Ensembl
  13. cell proliferation Source: Ensembl
  14. cellular component movement Source: ProtInc
  15. cellular senescence Source: BHF-UCL
  16. chemotaxis Source: ProtInc
  17. epidermal growth factor receptor signaling pathway Source: Reactome
  18. fibroblast growth factor receptor signaling pathway Source: Reactome
  19. innate immune response Source: Reactome
  20. insulin receptor signaling pathway Source: Reactome
  21. keratinocyte differentiation Source: Ensembl
  22. labyrinthine layer development Source: Ensembl
  23. melanosome transport Source: Ensembl
  24. mitotic nuclear division Source: Ensembl
  25. negative regulation of cell proliferation Source: BHF-UCL
  26. negative regulation of homotypic cell-cell adhesion Source: Ensembl
  27. neurotrophin TRK receptor signaling pathway Source: Reactome
  28. placenta blood vessel development Source: Ensembl
  29. positive regulation of Ras GTPase activity Source: Ensembl
  30. positive regulation of Ras protein signal transduction Source: Ensembl
  31. positive regulation of cell differentiation Source: Ensembl
  32. positive regulation of cell migration Source: Ensembl
  33. positive regulation of gene expression Source: UniProt
  34. positive regulation of protein serine/threonine kinase activity Source: UniProtKB
  35. positive regulation of transcription elongation from RNA polymerase II promoter Source: Ensembl
  36. protein heterooligomerization Source: Ensembl
  37. regulation of Golgi inheritance Source: UniProtKB
  38. regulation of early endosome to late endosome transport Source: UniProtKB
  39. regulation of stress-activated MAPK cascade Source: UniProtKB
  40. regulation of vascular smooth muscle contraction Source: Ensembl
  41. response to axon injury Source: Ensembl
  42. response to glucocorticoid Source: Ensembl
  43. response to oxidative stress Source: Ensembl
  44. signal transduction Source: ProtInc
  45. small GTPase mediated signal transduction Source: Reactome
  46. stress-activated MAPK cascade Source: Reactome
  47. toll-like receptor 10 signaling pathway Source: Reactome
  48. toll-like receptor 2 signaling pathway Source: Reactome
  49. toll-like receptor 3 signaling pathway Source: Reactome
  50. toll-like receptor 4 signaling pathway Source: Reactome
  51. toll-like receptor 5 signaling pathway Source: Reactome
  52. toll-like receptor 9 signaling pathway Source: Reactome
  53. toll-like receptor TLR1:TLR2 signaling pathway Source: Reactome
  54. toll-like receptor TLR6:TLR2 signaling pathway Source: Reactome
  55. toll-like receptor signaling pathway Source: Reactome
  56. vesicle transport along microtubule Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.12.2. 2681.
ReactomeiREACT_1391. ERK1 activation.
REACT_22272. Signal transduction by L1.
REACT_22442. Interleukin-1 signaling.
REACT_614. RAF phosphorylates MEK.
REACT_9470. Signaling by FGFR.
REACT_962. MEK activation.
SignaLinkiQ02750.

Names & Taxonomyi

Protein namesi
Recommended name:
Dual specificity mitogen-activated protein kinase kinase 1 (EC:2.7.12.2)
Short name:
MAP kinase kinase 1
Short name:
MAPKK 1
Short name:
MKK1
Alternative name(s):
ERK activator kinase 1
MAPK/ERK kinase 1
Short name:
MEK 1
Gene namesi
Name:MAP2K1
Synonyms:MEK1, PRKMK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 15

Organism-specific databases

HGNCiHGNC:6840. MAP2K1.

Subcellular locationi

Cytoplasmcytoskeletonmicrotubule organizing centercentrosome. Cytoplasmcytoskeletonmicrotubule organizing centerspindle pole body. Cytoplasm. Nucleus
Note: Localizes at centrosomes during prometaphase, midzone during anaphase and midbody during telophase/cytokinesis.2 Publications

GO - Cellular componenti

  1. Golgi apparatus Source: UniProtKB
  2. cell cortex Source: Ensembl
  3. cytoplasm Source: HPA
  4. cytosol Source: UniProtKB
  5. dendrite cytoplasm Source: Ensembl
  6. early endosome Source: UniProtKB
  7. extracellular vesicular exosome Source: UniProt
  8. focal adhesion Source: UniProtKB
  9. late endosome Source: UniProtKB
  10. mitochondrion Source: UniProtKB
  11. nucleus Source: UniProtKB
  12. perikaryon Source: Ensembl
  13. perinuclear region of cytoplasm Source: Ensembl
  14. plasma membrane Source: HPA
  15. spindle pole body Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Involvement in diseasei

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.
Note: The disease is caused by mutations affecting the gene represented in this entry.2 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti53 – 531F → S in CFC3. 1 Publication
VAR_035093
Natural varianti128 – 1281G → V in CFC3. 1 Publication
VAR_069780
Natural varianti130 – 1301Y → C in CFC3. 1 Publication
VAR_035094

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi97 – 971K → R: Inactivation.
Mutagenesisi150 – 1501S → A: No loss of activity.
Mutagenesisi212 – 2121S → A: No loss of activity.
Mutagenesisi218 – 2181S → A: Inactivation.
Mutagenesisi222 – 2221S → A: Inactivation.

Keywords - Diseasei

Cardiomyopathy, Disease mutation, Ectodermal dysplasia, Mental retardation

Organism-specific databases

MIMi615279. phenotype.
Orphaneti1340. Cardiofaciocutaneous syndrome.
PharmGKBiPA30584.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed By similarity
Chaini2 – 393392Dual specificity mitogen-activated protein kinase kinase 1
PRO_0000086365Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei218 – 2181Phosphoserine; by RAF1 Publication
Modified residuei222 – 2221Phosphoserine; by RAF1 Publication
Modified residuei286 – 2861Phosphothreonine1 Publication
Modified residuei292 – 2921Phosphothreonine; by MAPK1 By similarity
Modified residuei298 – 2981Phosphoserine; by PAK1 Publication

Post-translational modificationi

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.2 Publications
Acetylation by Yersinia yopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ02750.
PaxDbiQ02750.
PeptideAtlasiQ02750.
PRIDEiQ02750.

PTM databases

PhosphoSiteiQ02750.

Miscellaneous databases

PMAP-CutDBQ02750.

Expressioni

Tissue specificityi

Widely expressed, with extremely low levels in brain.1 Publication

Gene expression databases

ArrayExpressiQ02750.
BgeeiQ02750.
CleanExiHS_MAP2K1.
GenevestigatoriQ02750.

Organism-specific databases

HPAiCAB003834.
HPA026430.

Interactioni

Subunit structurei

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.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BIRC6Q9NR092EBI-492564,EBI-1765160
BTRCQ9Y2973EBI-492564,EBI-307461
CFLARO15519-13EBI-492564,EBI-4567563
MAPK1P284822EBI-492564,EBI-959949
MAPK3P273612EBI-492564,EBI-73995
RAF1P040495EBI-492564,EBI-365996
VRK2Q86Y072EBI-492564,EBI-1207615
VRK2Q86Y07-12EBI-492564,EBI-1207633
YAP1P469373EBI-492564,EBI-1044059

Protein-protein interaction databases

BioGridi111590. 44 interactions.
DIPiDIP-201N.
IntActiQ02750. 26 interactions.
MINTiMINT-99632.
STRINGi9606.ENSP00000302486.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi44 – 5815
Helixi65 – 673
Beta strandi68 – 769
Beta strandi81 – 877
Turni88 – 903
Beta strandi93 – 1008
Helixi105 – 11511
Helixi116 – 1205
Beta strandi129 – 1357
Beta strandi138 – 1436
Helixi151 – 1588
Helixi163 – 18422
Helixi193 – 1953
Beta strandi196 – 1983
Turni200 – 2023
Beta strandi204 – 2063
Helixi213 – 2186
Turni220 – 2223
Helixi227 – 2293
Helixi232 – 2354
Helixi242 – 25817
Helixi268 – 2758
Helixi310 – 31910
Turni327 – 3293
Helixi332 – 34211
Turni346 – 3483
Helixi352 – 3565
Helixi359 – 3668
Helixi371 – 3799

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1S9JX-ray2.40A62-393[»]
2P55X-ray2.80A62-393[»]
3DV3X-ray2.30A62-382[»]
3DY7X-ray2.70A62-393[»]
3E8NX-ray2.50A62-393[»]
3EQBX-ray2.62A62-393[»]
3EQCX-ray1.80A35-393[»]
3EQDX-ray2.10A35-393[»]
3EQFX-ray2.70A35-393[»]
3EQGX-ray2.50A35-393[»]
3EQHX-ray2.00A35-393[»]
3EQIX-ray1.90A35-393[»]
3MBLX-ray2.60A62-382[»]
3ORNX-ray2.80A62-393[»]
3OS3X-ray2.80A62-393[»]
3PP1X-ray2.70A62-382[»]
3SLSX-ray2.30A/B45-263[»]
A/B308-383[»]
3V01X-ray2.70A62-393[»]
3V04X-ray2.70A62-393[»]
3VVHX-ray2.00A/B/C62-393[»]
3W8QX-ray2.20A39-382[»]
3WIGX-ray2.70A62-393[»]
3ZLSX-ray2.50A37-383[»]
3ZLWX-ray2.12A37-383[»]
3ZLXX-ray2.20A37-383[»]
3ZLYX-ray2.11A37-383[»]
3ZM4X-ray2.37A37-383[»]
4AN2X-ray2.50A61-392[»]
4AN3X-ray2.10A61-392[»]
4AN9X-ray2.80A61-392[»]
4ANBX-ray2.20A61-392[»]
4ARKX-ray2.60A62-393[»]
4LMNX-ray2.80A62-393[»]
4MNEX-ray2.85A/D/E/H62-393[»]
ProteinModelPortaliQ02750.
SMRiQ02750. Positions 39-382.

Miscellaneous databases

EvolutionaryTraceiQ02750.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini68 – 361294Protein kinase
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni77 – 782Inhibitor binding
Regioni144 – 1463Inhibitor binding
Regioni208 – 2125Inhibitor binding
Regioni270 – 30738RAF1-binding By similarity
Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi262 – 30746Pro-rich
Add
BLAST

Domaini

The proline-rich region localized between residues 270 and 307 is important for binding to RAF1 and activation of MAP2K1/MEK1 By similarity.

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000234206.
HOVERGENiHBG108518.
InParanoidiQ02750.
KOiK04368.
OMAiRDKHAIM.
OrthoDBiEOG7HF1KZ.
PhylomeDBiQ02750.
TreeFamiTF105137.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q02750-1) [UniParc]FASTAAdd to Basket

Also known as: MKK1a

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

MPKKKPTPIQ LNPAPDGSAV NGTSSAETNL EALQKKLEEL ELDEQQRKRL    50
EAFLTQKQKV GELKDDDFEK ISELGAGNGG VVFKVSHKPS GLVMARKLIH 100
LEIKPAIRNQ IIRELQVLHE CNSPYIVGFY GAFYSDGEIS ICMEHMDGGS 150
LDQVLKKAGR IPEQILGKVS IAVIKGLTYL REKHKIMHRD VKPSNILVNS 200
RGEIKLCDFG VSGQLIDSMA NSFVGTRSYM SPERLQGTHY SVQSDIWSMG 250
LSLVEMAVGR YPIPPPDAKE LELMFGCQVE GDAAETPPRP RTPGRPLSSY 300
GMDSRPPMAI FELLDYIVNE PPPKLPSGVF SLEFQDFVNK CLIKNPAERA 350
DLKQLMVHAF IKRSDAEEVD FAGWLCSTIG LNQPSTPTHA AGV 393
Length:393
Mass (Da):43,439
Last modified:January 23, 2007 - v2
Checksum:i0344118FFC842D51
GO
Isoform 2 (identifier: Q02750-2) [UniParc]FASTAAdd to Basket

Also known as: MKK1b

The sequence of this isoform differs from the canonical sequence as follows:
     147-172: Missing.

Show »
Length:367
Mass (Da):40,764
Checksum:i9944432D8705DEFD
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti53 – 531F → S in CFC3. 1 Publication
VAR_035093
Natural varianti128 – 1281G → V in CFC3. 1 Publication
VAR_069780
Natural varianti130 – 1301Y → C in CFC3. 1 Publication
VAR_035094

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei147 – 17226Missing in isoform 2.
VSP_040500Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L05624 mRNA. Translation: AAA36318.1.
L11284 mRNA. No translation available.
CCDSiCCDS10216.1. [Q02750-1]
PIRiA45100.
RefSeqiNP_002746.1. NM_002755.3. [Q02750-1]
XP_006720671.1. XM_006720608.1. [Q02750-2]
UniGeneiHs.145442.

Genome annotation databases

EnsembliENST00000307102; ENSP00000302486; ENSG00000169032. [Q02750-1]
GeneIDi5604.
KEGGihsa:5604.
UCSCiuc010bhq.3. human. [Q02750-1]

Polymorphism databases

DMDMi400274.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L05624 mRNA. Translation: AAA36318.1 .
L11284 mRNA. No translation available.
CCDSi CCDS10216.1. [Q02750-1 ]
PIRi A45100.
RefSeqi NP_002746.1. NM_002755.3. [Q02750-1 ]
XP_006720671.1. XM_006720608.1. [Q02750-2 ]
UniGenei Hs.145442.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1S9J X-ray 2.40 A 62-393 [» ]
2P55 X-ray 2.80 A 62-393 [» ]
3DV3 X-ray 2.30 A 62-382 [» ]
3DY7 X-ray 2.70 A 62-393 [» ]
3E8N X-ray 2.50 A 62-393 [» ]
3EQB X-ray 2.62 A 62-393 [» ]
3EQC X-ray 1.80 A 35-393 [» ]
3EQD X-ray 2.10 A 35-393 [» ]
3EQF X-ray 2.70 A 35-393 [» ]
3EQG X-ray 2.50 A 35-393 [» ]
3EQH X-ray 2.00 A 35-393 [» ]
3EQI X-ray 1.90 A 35-393 [» ]
3MBL X-ray 2.60 A 62-382 [» ]
3ORN X-ray 2.80 A 62-393 [» ]
3OS3 X-ray 2.80 A 62-393 [» ]
3PP1 X-ray 2.70 A 62-382 [» ]
3SLS X-ray 2.30 A/B 45-263 [» ]
A/B 308-383 [» ]
3V01 X-ray 2.70 A 62-393 [» ]
3V04 X-ray 2.70 A 62-393 [» ]
3VVH X-ray 2.00 A/B/C 62-393 [» ]
3W8Q X-ray 2.20 A 39-382 [» ]
3WIG X-ray 2.70 A 62-393 [» ]
3ZLS X-ray 2.50 A 37-383 [» ]
3ZLW X-ray 2.12 A 37-383 [» ]
3ZLX X-ray 2.20 A 37-383 [» ]
3ZLY X-ray 2.11 A 37-383 [» ]
3ZM4 X-ray 2.37 A 37-383 [» ]
4AN2 X-ray 2.50 A 61-392 [» ]
4AN3 X-ray 2.10 A 61-392 [» ]
4AN9 X-ray 2.80 A 61-392 [» ]
4ANB X-ray 2.20 A 61-392 [» ]
4ARK X-ray 2.60 A 62-393 [» ]
4LMN X-ray 2.80 A 62-393 [» ]
4MNE X-ray 2.85 A/D/E/H 62-393 [» ]
ProteinModelPortali Q02750.
SMRi Q02750. Positions 39-382.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 111590. 44 interactions.
DIPi DIP-201N.
IntActi Q02750. 26 interactions.
MINTi MINT-99632.
STRINGi 9606.ENSP00000302486.

Chemistry

BindingDBi Q02750.
ChEMBLi CHEMBL2111351.
GuidetoPHARMACOLOGYi 2062.

PTM databases

PhosphoSitei Q02750.

Polymorphism databases

DMDMi 400274.

Proteomic databases

MaxQBi Q02750.
PaxDbi Q02750.
PeptideAtlasi Q02750.
PRIDEi Q02750.

Protocols and materials databases

DNASUi 5604.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000307102 ; ENSP00000302486 ; ENSG00000169032 . [Q02750-1 ]
GeneIDi 5604.
KEGGi hsa:5604.
UCSCi uc010bhq.3. human. [Q02750-1 ]

Organism-specific databases

CTDi 5604.
GeneCardsi GC15P066679.
GeneReviewsi MAP2K1.
HGNCi HGNC:6840. MAP2K1.
HPAi CAB003834.
HPA026430.
MIMi 176872. gene.
615279. phenotype.
neXtProti NX_Q02750.
Orphaneti 1340. Cardiofaciocutaneous syndrome.
PharmGKBi PA30584.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000234206.
HOVERGENi HBG108518.
InParanoidi Q02750.
KOi K04368.
OMAi RDKHAIM.
OrthoDBi EOG7HF1KZ.
PhylomeDBi Q02750.
TreeFami TF105137.

Enzyme and pathway databases

BRENDAi 2.7.12.2. 2681.
Reactomei REACT_1391. ERK1 activation.
REACT_22272. Signal transduction by L1.
REACT_22442. Interleukin-1 signaling.
REACT_614. RAF phosphorylates MEK.
REACT_9470. Signaling by FGFR.
REACT_962. MEK activation.
SignaLinki Q02750.

Miscellaneous databases

ChiTaRSi MAP2K1. human.
EvolutionaryTracei Q02750.
GeneWikii MAP2K1.
GenomeRNAii 5604.
NextBioi 21776.
PMAP-CutDB Q02750.
PROi Q02750.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q02750.
Bgeei Q02750.
CleanExi HS_MAP2K1.
Genevestigatori Q02750.

Family and domain databases

InterProi IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view ]
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Human T-cell mitogen-activated protein kinase kinases are related to yeast signal transduction kinases."
    Seger R., Seger D., Lozeman F.J., Ahn N.G., Graves L.M., Campbell J.S., Ericsson L., Harrylock M., Jensen A.M., Krebs E.G.
    J. Biol. Chem. 267:25628-25631(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PARTIAL PROTEIN SEQUENCE, TISSUE SPECIFICITY.
    Tissue: T-cell.
  2. "Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2."
    Zheng C.-F., Guan K.-L.
    J. Biol. Chem. 268:11435-11439(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  3. "Activation of MEK family kinases requires phosphorylation of two conserved Ser/Thr residues."
    Zheng C.-F., Guan K.-L.
    EMBO J. 13:1123-1131(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-218 AND SER-222, MUTAGENESIS.
  4. Cited for: CLEAVAGE BY ANTHRAX LETHAL FACTOR, PROTEIN SEQUENCE OF 9-17.
  5. "Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor."
    Vitale G., Bernardi L., Napolitani G., Mock M., Montecucco C.
    Biochem. J. 352:739-745(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: CLEAVAGE BY ANTHRAX LETHAL FACTOR.
  6. "The MAP kinase pathway is required for entry into mitosis and cell survival."
    Liu X., Yan S., Zhou T., Terada Y., Erikson R.L.
    Oncogene 23:763-776(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, FUNCTION.
  7. "Role of group A p21-activated kinases in activation of extracellular-regulated kinase by growth factors."
    Beeser A., Jaffer Z.M., Hofmann C., Chernoff J.
    J. Biol. Chem. 280:36609-36615(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-298.
  8. "Yersinia YopJ acetylates and inhibits kinase activation by blocking phosphorylation."
    Mukherjee S., Keitany G., Li Y., Wang Y., Ball H.L., Goldsmith E.J., Orth K.
    Science 312:1211-1214(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH YOPJ, ACETYLATION.
  9. "Interaction with MEK causes nuclear export and downregulation of peroxisome proliferator-activated receptor gamma."
    Burgermeister E., Chuderland D., Hanoch T., Meyer M., Liscovitch M., Seger R.
    Mol. Cell. Biol. 27:803-817(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PPARG.
  10. "Final stages of cytokinesis and midbody ring formation are controlled by BRUCE."
    Pohl C., Jentsch S.
    Cell 132:832-845(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH BIRC6/BRUCE.
  11. "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
    Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
    Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-286, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  12. "Protein kinase SGK1 enhances MEK/ERK complex formation through the phosphorylation of ERK2: implication for the positive regulatory role of SGK1 on the ERK function during liver regeneration."
    Won M., Park K.A., Byun H.S., Kim Y.R., Choi B.L., Hong J.H., Park J., Seok J.H., Lee Y.H., Cho C.H., Song I.S., Kim Y.K., Shen H.M., Hur G.M.
    J. Hepatol. 51:67-76(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SGK1.
  13. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  14. "VRK2 inhibits mitogen-activated protein kinase signaling and inversely correlates with ErbB2 in human breast cancer."
    Fernandez I.F., Blanco S., Lozano J., Lazo P.A.
    Mol. Cell. Biol. 30:4687-4697(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH VRK2.
  15. Cited for: REVIEW ON FUNCTION.
  16. Cited for: REVIEW ON ENZYME REGULATION.
  17. "The ERK signaling cascade--views from different subcellular compartments."
    Yao Z., Seger R.
    BioFactors 35:407-416(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.
  18. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  19. "The ERK cascade: distinct functions within various subcellular organelles."
    Wortzel I., Seger R.
    Genes Cancer 2:195-209(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.
  20. Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 62-392 IN COMPLEX WITH ATP AND INHIBITOR.
  21. Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 62-393 IN COMPLEX WITH ATP AND INHIBITOR.
  22. "2-Alkylamino- and alkoxy-substituted 2-amino-1,3,4-oxadiazoles-O-Alkyl benzohydroxamate esters replacements retain the desired inhibition and selectivity against MEK (MAP ERK kinase)."
    Warmus J.S., Flamme C., Zhang L.Y., Barrett S., Bridges A., Chen H., Gowan R., Kaufman M., Sebolt-Leopold J., Leopold W., Merriman R., Ohren J., Pavlovsky A., Przybranowski S., Tecle H., Valik H., Whitehead C., Zhang E.
    Bioorg. Med. Chem. Lett. 18:6171-6174(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.62 ANGSTROMS) OF 62-393 IN COMPLEX WITH ATP AND INHIBITOR.
  23. "Crystal structures of MEK1 binary and ternary complexes with nucleotides and inhibitors."
    Fischmann T.O., Smith C.K., Mayhood T.W., Myers J.E., Reichert P., Mannarino A., Carr D., Zhu H., Wong J., Yang R.S., Le H.V., Madison V.S.
    Biochemistry 48:2661-2674(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 35-393 IN COMPLEX WITH ADP AND INHIBITOR.
  24. "Beyond the MEK-pocket: can current MEK kinase inhibitors be utilized to synthesize novel type III NCKIs? Does the MEK-pocket exist in kinases other than MEK?"
    Tecle H., Shao J., Li Y., Kothe M., Kazmirski S., Penzotti J., Ding Y.H., Ohren J., Moshinsky D., Coli R., Jhawar N., Bora E., Jacques-O'Hagan S., Wu J.
    Bioorg. Med. Chem. Lett. 19:226-229(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 62-382 IN COMPLEX WITH ATP AND INHIBITOR.
  25. "RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer."
    Iverson C., Larson G., Lai C., Yeh L.T., Dadson C., Weingarten P., Appleby T., Vo T., Maderna A., Vernier J.M., Hamatake R., Miner J.N., Quart B.
    Cancer Res. 69:6839-6847(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 62-393 IN COMPLEX WITH ATP AND INHIBITOR.
  26. Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 62-382 IN COMPLEX WITH ADP AND INHIBITOR.
  27. "Discovery of TAK-733, a potent and selective MEK allosteric site inhibitor for the treatment of cancer."
    Dong Q., Dougan D.R., Gong X., Halkowycz P., Jin B., Kanouni T., O'Connell S.M., Scorah N., Shi L., Wallace M.B., Zhou F.
    Bioorg. Med. Chem. Lett. 21:1315-1319(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 62-382 IN COMPLEX WITH ATP AND INHIBITOR.
  28. Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 62-393.
  29. "Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome."
    Rodriguez-Viciana P., Tetsu O., Tidyman W.E., Estep A.L., Conger B.A., Cruz M.S., McCormick F., Rauen K.A.
    Science 311:1287-1290(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS CFC3 SER-53 AND CYS-130.
  30. Cited for: VARIANT CFC3 VAL-128.

Entry informationi

Entry nameiMP2K1_HUMAN
AccessioniPrimary (citable) accession number: Q02750
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: January 23, 2007
Last modified: September 3, 2014
This is version 162 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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