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Q02750

- MP2K1_HUMAN

UniProt

Q02750 - MP2K1_HUMAN

Protein

Dual specificity mitogen-activated protein kinase kinase 1

Gene

MAP2K1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 163 (01 Oct 2014)
      Sequence version 2 (23 Jan 2007)
      Previous versions | rss
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    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.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei8 – 92Cleavage; by anthrax lethal factor
    Binding sitei77 – 771Inhibitor; via carbonyl oxygen8 Publications
    Binding sitei78 – 781Inhibitor; via amide nitrogen and carbonyl oxygen8 Publications
    Binding sitei97 – 971ATP6 PublicationsPROSITE-ProRule annotation
    Binding sitei97 – 971Inhibitor8 Publications
    Active sitei190 – 1901Proton acceptorPROSITE-ProRule annotation
    Binding sitei190 – 1901Inhibitor8 Publications
    Binding sitei194 – 1941Inhibitor; via carbonyl oxygen8 Publications
    Binding sitei208 – 2081ATP6 PublicationsPROSITE-ProRule annotation
    Binding sitei208 – 2081Inhibitor8 Publications
    Binding sitei212 – 2121Inhibitor; via amide nitrogen8 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi74 – 829ATP6 PublicationsPROSITE-ProRule annotation
    Nucleotide bindingi143 – 1464ATP6 PublicationsPROSITE-ProRule annotation
    Nucleotide bindingi150 – 1534ATP6 PublicationsPROSITE-ProRule annotation
    Nucleotide bindingi192 – 1954ATP6 PublicationsPROSITE-ProRule annotation

    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/tyrosine kinase activity Source: UniProtKB
    6. protein serine/threonine kinase activator activity Source: UniProtKB
    7. protein serine/threonine kinase activity Source: Reactome
    8. protein tyrosine kinase activity Source: UniProtKB-KW
    9. receptor signaling protein tyrosine phosphatase activity Source: Ensembl

    GO - Biological processi

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

    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.

    GO - Cellular componenti

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

    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.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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. 1 Publication
    Mutagenesisi150 – 1501S → A: No loss of activity. 1 Publication
    Mutagenesisi212 – 2121S → A: No loss of activity. 1 Publication
    Mutagenesisi218 – 2181S → A: Inactivation. 1 Publication
    Mutagenesisi222 – 2221S → A: Inactivation. 1 Publication

    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 – 11RemovedBy similarity
    Chaini2 – 393392Dual specificity mitogen-activated protein kinase kinase 1PRO_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 MAPK1By 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.3 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.By similarity13 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. 27 interactions.
    MINTiMINT-99632.
    STRINGi9606.ENSP00000302486.

    Structurei

    Secondary structure

    1
    393
    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.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ02750.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini68 – 361294Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

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

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi262 – 30746Pro-richAdd
    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

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    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. 1 PublicationVSP_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. 27 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

    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: October 1, 2014
    This is version 163 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