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P29678

- MP2K1_RABIT

UniProt

P29678 - MP2K1_RABIT

Protein

Dual specificity mitogen-activated protein kinase kinase 1

Gene

MAP2K1

Organism
Oryctolagus cuniculus (Rabbit)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 111 (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 By similarity.By similarity

    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.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei8 – 92Cleavage; by anthrax lethal factorBy similarity
    Binding sitei97 – 971ATP1 PublicationPROSITE-ProRule annotation
    Active sitei190 – 1901Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi74 – 829ATP1 PublicationPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. protein serine/threonine kinase activity Source: UniProtKB-KW
    3. protein tyrosine kinase activity Source: UniProtKB-KW

    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. 1749.

    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
    Alternative name(s):
    ERK activator kinase 1
    MAPK/ERK kinase 1
    Short name:
    MEK 1
    Gene namesi
    Name:MAP2K1
    Synonyms:MEK1, PRKMK1
    OrganismiOryctolagus cuniculus (Rabbit)
    Taxonomic identifieri9986 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
    ProteomesiUP000001811: Unplaced

    Subcellular locationi

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

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. microtubule organizing center Source: UniProtKB-SubCell
    3. nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Cytoskeleton, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed1 Publication
    Chaini2 – 393392Dual specificity mitogen-activated protein kinase kinase 1PRO_0000086368Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei218 – 2181Phosphoserine; by RAF2 Publications
    Modified residuei222 – 2221Phosphoserine; by RAF2 Publications
    Modified residuei286 – 2861PhosphothreonineBy similarity
    Modified residuei292 – 2921Phosphothreonine; by MAPK1By similarity
    Modified residuei298 – 2981Phosphoserine; by PAKBy similarity

    Post-translational modificationi

    Phosphorylation at Ser-218 and Ser-222 by MAP kinase kinase kinases (RAF or MEKK1) regulates positively the 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.By similarity

    Keywords - PTMi

    Phosphoprotein

    Interactioni

    Subunit structurei

    Found in a complex with at least BRAF, HRAS, MAP2K1, MAPK3/ERK1 and RGS14. Forms a heterodimer with MAP2K2/MEK2. Forms heterodimers with KSR2 which further dimerize to form tetramers. Interacts with ARRB2, LAMTOR3, MAPK1/ERK2, MORG1, RAF1, PPARG and VRK2. Interacts with SGK1. Interacts with BIRC6/bruce.By similarity

    Protein-protein interaction databases

    DIPiDIP-40535N.
    IntActiP29678. 1 interaction.
    STRINGi9986.ENSOCUP00000007582.

    Structurei

    Secondary structure

    1
    393
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi44 – 5512
    Turni56 – 594
    Turni65 – 673
    Beta strandi73 – 753
    Turni88 – 914
    Beta strandi95 – 1006
    Helixi105 – 11511
    Helixi116 – 1205
    Beta strandi129 – 1335
    Beta strandi136 – 1438
    Helixi151 – 1566
    Helixi163 – 18422
    Helixi193 – 1953
    Beta strandi196 – 1983
    Beta strandi204 – 2063
    Helixi213 – 2186
    Helixi232 – 2365
    Helixi242 – 25817
    Helixi271 – 2733
    Helixi310 – 31910
    Turni327 – 3293
    Helixi332 – 34110
    Turni346 – 3483
    Helixi352 – 3565
    Helixi359 – 3668
    Helixi371 – 3755
    Turni376 – 3783

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2Y4IX-ray3.46C1-393[»]
    ProteinModelPortaliP29678.
    SMRiP29678. Positions 62-382.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

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

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    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 the 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.

    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]

    Sequencei

    Sequence statusi: Complete.

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

    P29678-1 [UniParc]FASTAAdd to Basket

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    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 PPPKLPSAVF SLEFQDFVNK CLIKNPAERA 350
    DLKQLMVHAF IKRSDAEEVD FAGWLCSTIG LNQPSTPTHA AGV 393
    Length:393
    Mass (Da):43,453
    Last modified:January 23, 2007 - v2
    Checksum:i0341B42FF9218D51
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Z30163 mRNA. Translation: CAA82912.1.
    PIRiS42068.
    RefSeqiNP_001076098.1. NM_001082629.1.
    UniGeneiOcu.3187.

    Genome annotation databases

    GeneIDi100009316.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Z30163 mRNA. Translation: CAA82912.1 .
    PIRi S42068.
    RefSeqi NP_001076098.1. NM_001082629.1.
    UniGenei Ocu.3187.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2Y4I X-ray 3.46 C 1-393 [» ]
    ProteinModelPortali P29678.
    SMRi P29678. Positions 62-382.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-40535N.
    IntActi P29678. 1 interaction.
    STRINGi 9986.ENSOCUP00000007582.

    Chemistry

    BindingDBi P29678.
    ChEMBLi CHEMBL5740.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 100009316.

    Organism-specific databases

    CTDi 5604.

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000234206.
    HOVERGENi HBG108518.

    Enzyme and pathway databases

    BRENDAi 2.7.12.2. 1749.

    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. "Identification of the sites in MAP kinase kinase-1 phosphorylated by p74raf-1."
      Alessi D.R., Saito Y., Campbell D.G., Cohen P., Sithanadam G., Rapp U., Ashworth A., Marshall C.J., Cowley S.
      EMBO J. 13:1610-1619(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION AT SER-218 AND SER-222 BY RAF.
    2. "The amino acid sequence of a mammalian MAP kinase kinase."
      Ashworth A., Nakielny S., Cohen P., Marshall C.
      Oncogene 7:2555-2556(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 16-393, PARTIAL PROTEIN SEQUENCE.
      Tissue: Brain and Skeletal muscle.
    3. "MAP kinase kinase from rabbit skeletal muscle. A novel dual specificity enzyme showing homology to yeast protein kinases involved in pheromone-dependent signal transduction."
      Nakielny S., Campbell D.G., Cohen P.
      FEBS Lett. 308:183-189(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 2-16; 85-96 AND 190-201.
      Tissue: Skeletal muscle.
    4. "Renaturation and partial peptide sequencing of mitogen-activated protein kinase (MAP kinase) activator from rabbit skeletal muscle."
      Wu J., Michel H., Rossomando A., Haystead T., Shabanowitz J., Hunt D.F., Sturgill T.W.
      Biochem. J. 285:701-705(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 85-96 AND 190-201.
      Tissue: Skeletal muscle.
    5. "A Raf-induced allosteric transition of KSR stimulates phosphorylation of MEK."
      Brennan D.F., Dar A.C., Hertz N.T., Chao W.C., Burlingame A.L., Shokat K.M., Barford D.
      Nature 472:366-369(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.46 ANGSTROMS) IN COMPLEX WITH ATP AND HUMAN KSR2, PHOSPHORYLATION.

    Entry informationi

    Entry nameiMP2K1_RABIT
    AccessioniPrimary (citable) accession number: P29678
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 1, 1993
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 111 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

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

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3