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P63086

- MK01_RAT

UniProt

P63086 - MK01_RAT

Protein

Mitogen-activated protein kinase 1

Gene

Mapk1

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 126 (01 Oct 2014)
      Sequence version 3 (23 Jan 2007)
      Previous versions | rss
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    Functioni

    Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the 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. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Mediates phosphorylation of TPR in respons to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation By similarity.By similarity
    Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity By similarity.By similarity

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Cofactori

    Magnesium.By similarity

    Enzyme regulationi

    Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-183 and Tyr-185 in response to external stimuli like insulin or NGF. Both phosphorylations are required for activity. This phosphorylation causes dramatic conformational changes, which enable full activation and interaction of MAPK1/ERK2 with its substrates. Phosphorylation on Ser-27 by SGK1 results in its activation by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Dephosphorylated and inactivated by DUSP3, DUSP6 and DUSP9. Inactivated by pyrimidylpyrrole inhibitors.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei52 – 521ATP1 PublicationPROSITE-ProRule annotation
    Binding sitei106 – 1061Inhibitor; via amide nitrogen and carbonyl oxygen3 Publications
    Active sitei147 – 1471Proton acceptor
    Binding sitei164 – 1641Inhibitor3 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi29 – 379ATP1 PublicationPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: RGD
    2. kinase activity Source: RGD
    3. MAP kinase activity Source: UniProtKB
    4. mitogen-activated protein kinase kinase kinase binding Source: RGD
    5. protein binding Source: RGD
    6. protein kinase binding Source: RGD
    7. protein serine/threonine kinase activity Source: MGI
    8. RNA polymerase II carboxy-terminal domain kinase activity Source: Ensembl
    9. transcription factor binding Source: RGD

    GO - Biological processi

    1. apoptotic process Source: UniProtKB-KW
    2. B cell receptor signaling pathway Source: Ensembl
    3. caveolin-mediated endocytosis Source: UniProtKB
    4. cell cycle Source: UniProtKB-KW
    5. cellular response to DNA damage stimulus Source: Ensembl
    6. cellular response to organic substance Source: RGD
    7. cytosine metabolic process Source: Ensembl
    8. ERBB signaling pathway Source: Ensembl
    9. ERK1 and ERK2 cascade Source: Ensembl
    10. intracellular signal transduction Source: RGD
    11. labyrinthine layer blood vessel development Source: Ensembl
    12. lipopolysaccharide-mediated signaling pathway Source: Ensembl
    13. mammary gland epithelial cell proliferation Source: Ensembl
    14. MAPK cascade Source: RGD
    15. MAPK import into nucleus Source: RGD
    16. negative regulation of cell differentiation Source: Ensembl
    17. organ morphogenesis Source: Ensembl
    18. peptidyl-serine phosphorylation Source: MGI
    19. peptidyl-threonine phosphorylation Source: UniProtKB
    20. positive regulation of cell migration Source: RGD
    21. positive regulation of cell proliferation Source: RGD
    22. positive regulation of peptidyl-threonine phosphorylation Source: Ensembl
    23. positive regulation of transcription, DNA-templated Source: RGD
    24. positive regulation of translation Source: RGD
    25. protein phosphorylation Source: RGD
    26. regulation of cytoskeleton organization Source: UniProtKB
    27. regulation of early endosome to late endosome transport Source: UniProtKB
    28. regulation of Golgi inheritance Source: UniProtKB
    29. regulation of protein stability Source: UniProtKB
    30. regulation of stress-activated MAPK cascade Source: UniProtKB
    31. response to epidermal growth factor Source: UniProtKB
    32. response to estrogen Source: RGD
    33. response to exogenous dsRNA Source: Ensembl
    34. response to toxic substance Source: RGD
    35. sensory perception of pain Source: UniProtKB
    36. signal transduction Source: RGD
    37. T cell receptor signaling pathway Source: Ensembl

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Apoptosis, Cell cycle

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.11.24. 5301.
    ReactomeiREACT_194748. Senescence-Associated Secretory Phenotype (SASP).
    REACT_195028. Gastrin-CREB signalling pathway via PKC and MAPK.
    REACT_195202. FCERI mediated MAPK activation.
    REACT_196231. Advanced glycosylation endproduct receptor signaling.
    REACT_196390. RSK activation.
    REACT_196391. CREB phosphorylation through the activation of Ras.
    REACT_196425. Growth hormone receptor signaling.
    REACT_196755. Regulation of actin dynamics for phagocytic cup formation.
    REACT_198995. Negative regulation of FGFR signaling.
    REACT_203770. Oxidative Stress Induced Senescence.
    REACT_215142. Oncogene Induced Senescence.
    REACT_216489. Regulation of HSF1-mediated heat shock response.
    REACT_222166. Signaling by FGFR.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Mitogen-activated protein kinase 1 (EC:2.7.11.24)
    Short name:
    MAP kinase 1
    Short name:
    MAPK 1
    Alternative name(s):
    ERT1
    Extracellular signal-regulated kinase 2
    Short name:
    ERK-2
    MAP kinase isoform p42
    Short name:
    p42-MAPK
    Mitogen-activated protein kinase 2
    Short name:
    MAP kinase 2
    Short name:
    MAPK 2
    Gene namesi
    Name:Mapk1
    Synonyms:Erk2, Mapk, Prkm1
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 11

    Organism-specific databases

    RGDi70500. Mapk1.

    Subcellular locationi

    Cytoplasmcytoskeletonspindle By similarity. Nucleus By similarity. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity. Cytoplasm By similarity
    Note: Associated with the spindle during prometaphase and metaphase. PEA15-binding and phosphorylated DAPK1 promote its cytoplasmic retention. Phosphorylation at Ser- 244 and Ser-246 as well as autophosphorylation at Thr-188 promote nuclear localization.By similarity

    GO - Cellular componenti

    1. axon Source: RGD
    2. caveola Source: UniProtKB
    3. cytoplasm Source: UniProtKB
    4. cytoskeleton Source: UniProtKB
    5. cytosol Source: UniProtKB
    6. dendrite cytoplasm Source: RGD
    7. early endosome Source: UniProtKB
    8. focal adhesion Source: UniProtKB
    9. Golgi apparatus Source: UniProtKB
    10. late endosome Source: UniProtKB
    11. microtubule organizing center Source: UniProtKB-SubCell
    12. mitochondrion Source: UniProtKB
    13. mitotic spindle Source: UniProtKB
    14. nucleoplasm Source: UniProtKB
    15. nucleus Source: UniProtKB
    16. perikaryon Source: RGD
    17. protein complex Source: RGD
    18. pseudopodium Source: Ensembl

    Keywords - Cellular componenti

    Cytoplasm, Cytoskeleton, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi117 – 1171Q → A: Reduced affinity for DCC. Strongly reduced affinity for DCC; when associated with A-123. 1 Publication
    Mutagenesisi123 – 1231H → A: Reduced affinity for DCC. Strongly reduced affinity for DCC; when associated with A-117. 1 Publication
    Mutagenesisi155 – 1551L → A: Reduced affinity for DCC. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed1 Publication
    Chaini2 – 358357Mitogen-activated protein kinase 1PRO_0000186249Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanine1 Publication
    Modified residuei27 – 271Phosphoserine; by SGK1By similarity
    Modified residuei183 – 1831Phosphothreonine; by MAP2K1 and MAP2K2By similarity
    Modified residuei185 – 1851Phosphotyrosine; by MAP2K1 and MAP2K2By similarity
    Modified residuei188 – 1881Phosphothreonine; by autocatalysisBy similarity
    Modified residuei244 – 2441PhosphoserineBy similarity
    Modified residuei246 – 2461PhosphoserineBy similarity
    Modified residuei282 – 2821PhosphoserineBy similarity

    Post-translational modificationi

    Dually phosphorylated on Thr-183 and Tyr-185, which activates the enzyme. Phosphorylated upon FLT3 and KIT signaling. Ligand-activated ALK induces tyrosine phosphorylation By similarity. Dephosphorylated by PTPRJ at Tyr-185 By similarity. Autophosphorylated on threonine and tyrosine residues in vitro, which correlates with a slow and low level of activation. Phosphorylation on Ser-27 by SGK1 results in its activation by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2 By similarity.By similarity
    ISGylated.By similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiP63086.
    PRIDEiP63086.

    2D gel databases

    World-2DPAGE0004:P63086.

    PTM databases

    PhosphoSiteiP63086.

    Expressioni

    Tissue specificityi

    Highest levels within the nervous system, expressed in different tissues, mostly in muscle, thymus and heart.

    Developmental stagei

    Increased expression during development.

    Gene expression databases

    GenevestigatoriP63086.

    Interactioni

    Subunit structurei

    Binds both upstream activators and downstream substrates in multimolecular complexes. Interacts with ADAM15, ARHGEF2, ARRB2, DAPK1 (via death domain), HSF4, IER3, IPO7, MKNK2, DUSP6, MORG1, NISCH, PEA15, SGK1, and isoform 1 of NEK2 By similarity. Interacts (phosphorylated form) with CAV2 ('Tyr-19'-phosphorylated form); the interaction, promoted by insulin, leads to nuclear location and MAPK1 activation By similarity. MKNK2 isoform 1 binding prevents from dephosphorylation and inactivation By similarity. Interacts with DCC. The phosphorylated form interacts with PML By similarity. Interacts with STYX By similarity.By similarity

    Protein-protein interaction databases

    BioGridi250505. 12 interactions.
    DIPiDIP-29117N.
    IntActiP63086. 6 interactions.
    MINTiMINT-100037.

    Structurei

    Secondary structure

    1
    358
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi10 – 123
    Beta strandi13 – 164
    Turni20 – 223
    Beta strandi23 – 319
    Beta strandi33 – 4210
    Turni43 – 464
    Beta strandi47 – 548
    Helixi56 – 583
    Helixi60 – 7516
    Beta strandi86 – 883
    Turni93 – 953
    Beta strandi99 – 1046
    Beta strandi107 – 1093
    Helixi110 – 1167
    Helixi121 – 14020
    Helixi150 – 1523
    Beta strandi153 – 1553
    Beta strandi161 – 1633
    Beta strandi170 – 1723
    Helixi174 – 1763
    Turni179 – 1813
    Helixi182 – 1843
    Helixi189 – 1913
    Helixi194 – 1985
    Beta strandi199 – 2013
    Helixi206 – 22116
    Helixi231 – 2333
    Helixi234 – 2429
    Helixi247 – 2515
    Helixi256 – 2638
    Helixi273 – 2764
    Beta strandi278 – 2803
    Helixi282 – 29110
    Turni296 – 2983
    Helixi302 – 3065
    Helixi309 – 3113
    Turni312 – 3143
    Helixi317 – 3193
    Helixi329 – 3313
    Helixi333 – 3353
    Helixi338 – 34811
    Helixi350 – 3523
    Helixi354 – 3563

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1ERKX-ray2.30A1-358[»]
    1GOLX-ray2.80A1-358[»]
    2ERKX-ray2.40A1-358[»]
    2FYSX-ray2.50A/B2-358[»]
    2GPHX-ray1.90A2-358[»]
    2Z7LX-ray2.41A1-358[»]
    3C9WX-ray2.50A/B2-358[»]
    3ERKX-ray2.10A1-358[»]
    3O71X-ray1.95A1-358[»]
    3QYIX-ray2.18A1-358[»]
    3QYWX-ray1.50A1-358[»]
    3QYZX-ray1.46A1-358[»]
    3R63X-ray1.70A1-358[»]
    3ZU7X-ray1.97A3-358[»]
    3ZUVX-ray2.72A/C3-358[»]
    4ERKX-ray2.20A1-358[»]
    4GSBX-ray1.80A1-358[»]
    4GT3X-ray1.68A1-358[»]
    4GVAX-ray1.83A1-358[»]
    4I5HX-ray1.90A2-358[»]
    4N4SX-ray2.20A/B2-358[»]
    ProteinModelPortaliP63086.
    SMRiP63086. Positions 10-353.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP63086.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini23 – 311289Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni103 – 1097Inhibitor-binding

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi183 – 1853TXY

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi2 – 76Poly-Ala

    Domaini

    The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00550000074298.
    HOGENOMiHOG000233024.
    HOVERGENiHBG014652.
    InParanoidiP63086.
    KOiK04371.
    OMAiVCSAYDR.
    OrthoDBiEOG7M3J0K.
    PhylomeDBiP63086.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR003527. MAP_kinase_CS.
    IPR008349. MAPK_ERK1/2.
    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]
    PRINTSiPR01770. ERK1ERK2MAPK.
    SMARTiSM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS01351. MAPK. 1 hit.
    PS00107. 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.

    P63086-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAAAAAAGPE MVRGQVFDVG PRYTNLSYIG EGAYGMVCSA YDNLNKVRVA    50
    IKKISPFEHQ TYCQRTLREI KILLRFRHEN IIGINDIIRA PTIEQMKDVY 100
    IVQDLMETDL YKLLKTQHLS NDHICYFLYQ ILRGLKYIHS ANVLHRDLKP 150
    SNLLLNTTCD LKICDFGLAR VADPDHDHTG FLTEYVATRW YRAPEIMLNS 200
    KGYTKSIDIW SVGCILAEML SNRPIFPGKH YLDQLNHILG ILGSPSQEDL 250
    NCIINLKARN YLLSLPHKNK VPWNRLFPNA DSKALDLLDK MLTFNPHKRI 300
    EVEQALAHPY LEQYYDPSDE PIAEAPFKFD MELDDLPKEK LKELIFEETA 350
    RFQPGYRS 358
    Length:358
    Mass (Da):41,276
    Last modified:January 23, 2007 - v3
    Checksum:i3BBCF22471EDBA0B
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M64300 mRNA. Translation: AAA41124.1.
    PIRiA40033.
    RefSeqiNP_446294.1. NM_053842.1.
    XP_006248720.1. XM_006248658.1.
    XP_006248721.1. XM_006248659.1.
    XP_006248722.1. XM_006248660.1.
    UniGeneiRn.34914.

    Genome annotation databases

    EnsembliENSRNOT00000002533; ENSRNOP00000002533; ENSRNOG00000001849.
    GeneIDi116590.
    KEGGirno:116590.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M64300 mRNA. Translation: AAA41124.1 .
    PIRi A40033.
    RefSeqi NP_446294.1. NM_053842.1.
    XP_006248720.1. XM_006248658.1.
    XP_006248721.1. XM_006248659.1.
    XP_006248722.1. XM_006248660.1.
    UniGenei Rn.34914.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1ERK X-ray 2.30 A 1-358 [» ]
    1GOL X-ray 2.80 A 1-358 [» ]
    2ERK X-ray 2.40 A 1-358 [» ]
    2FYS X-ray 2.50 A/B 2-358 [» ]
    2GPH X-ray 1.90 A 2-358 [» ]
    2Z7L X-ray 2.41 A 1-358 [» ]
    3C9W X-ray 2.50 A/B 2-358 [» ]
    3ERK X-ray 2.10 A 1-358 [» ]
    3O71 X-ray 1.95 A 1-358 [» ]
    3QYI X-ray 2.18 A 1-358 [» ]
    3QYW X-ray 1.50 A 1-358 [» ]
    3QYZ X-ray 1.46 A 1-358 [» ]
    3R63 X-ray 1.70 A 1-358 [» ]
    3ZU7 X-ray 1.97 A 3-358 [» ]
    3ZUV X-ray 2.72 A/C 3-358 [» ]
    4ERK X-ray 2.20 A 1-358 [» ]
    4GSB X-ray 1.80 A 1-358 [» ]
    4GT3 X-ray 1.68 A 1-358 [» ]
    4GVA X-ray 1.83 A 1-358 [» ]
    4I5H X-ray 1.90 A 2-358 [» ]
    4N4S X-ray 2.20 A/B 2-358 [» ]
    ProteinModelPortali P63086.
    SMRi P63086. Positions 10-353.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 250505. 12 interactions.
    DIPi DIP-29117N.
    IntActi P63086. 6 interactions.
    MINTi MINT-100037.

    Chemistry

    BindingDBi P63086.
    ChEMBLi CHEMBL2111356.

    PTM databases

    PhosphoSitei P63086.

    2D gel databases

    World-2DPAGE 0004:P63086.

    Proteomic databases

    PaxDbi P63086.
    PRIDEi P63086.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000002533 ; ENSRNOP00000002533 ; ENSRNOG00000001849 .
    GeneIDi 116590.
    KEGGi rno:116590.

    Organism-specific databases

    CTDi 5594.
    RGDi 70500. Mapk1.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00550000074298.
    HOGENOMi HOG000233024.
    HOVERGENi HBG014652.
    InParanoidi P63086.
    KOi K04371.
    OMAi VCSAYDR.
    OrthoDBi EOG7M3J0K.
    PhylomeDBi P63086.

    Enzyme and pathway databases

    BRENDAi 2.7.11.24. 5301.
    Reactomei REACT_194748. Senescence-Associated Secretory Phenotype (SASP).
    REACT_195028. Gastrin-CREB signalling pathway via PKC and MAPK.
    REACT_195202. FCERI mediated MAPK activation.
    REACT_196231. Advanced glycosylation endproduct receptor signaling.
    REACT_196390. RSK activation.
    REACT_196391. CREB phosphorylation through the activation of Ras.
    REACT_196425. Growth hormone receptor signaling.
    REACT_196755. Regulation of actin dynamics for phagocytic cup formation.
    REACT_198995. Negative regulation of FGFR signaling.
    REACT_203770. Oxidative Stress Induced Senescence.
    REACT_215142. Oncogene Induced Senescence.
    REACT_216489. Regulation of HSF1-mediated heat shock response.
    REACT_222166. Signaling by FGFR.

    Miscellaneous databases

    EvolutionaryTracei P63086.
    NextBioi 304409.
    PROi P63086.

    Gene expression databases

    Genevestigatori P63086.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR003527. MAP_kinase_CS.
    IPR008349. MAPK_ERK1/2.
    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 ]
    PRINTSi PR01770. ERK1ERK2MAPK.
    SMARTi SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS01351. MAPK. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF."
      Boulton T.G., Nye S.H., Robbins D.J., Ip N.Y., Radziejewska E., Morgenbesser S.D., DePinho R.A., Panayotatos N., Cobb M.H., Yancopoulos G.D.
      Cell 65:663-675(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: Sprague-Dawley.
      Tissue: Brain.
    2. Bienvenut W.V., von Kriegsheim A.F., Kolch W.
      Submitted (AUG-2006) to UniProtKB
      Cited for: PROTEIN SEQUENCE OF 2-13; 69-75; 137-170; 193-201 AND 341-351, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY.
      Tissue: Pheochromocytoma.
    3. Lubec G., Kang S.U.
      Submitted (JUL-2007) to UniProtKB
      Cited for: PROTEIN SEQUENCE OF 163-170, IDENTIFICATION BY MASS SPECTROMETRY.
      Strain: Sprague-Dawley.
      Tissue: Brain.
    4. "Microtubule-associated protein 2 kinases, ERK1 and ERK2, undergo autophosphorylation on both tyrosine and threonine residues: implications for their mechanism of activation."
      Seger R., Ahn N.G., Boulton T.G., Yancopoulos G.D., Panayotatos N., Radziejewska E., Ericsson L., Bratlien R.L., Cobb M.H., Krebs E.G.
      Proc. Natl. Acad. Sci. U.S.A. 88:6142-6146(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: AUTOPHOSPHORYLATION.
    5. "PHAS-I as a link between mitogen-activated protein kinase and translation initiation."
      Lin T.-A., Kong X., Haystead T.A.J., Pause A., Belsham G.J., Sonenberg N., Lawrence J.C. Jr.
      Science 266:653-656(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION OF EIF4EBP1.
    6. "Activation and targeting of extracellular signal-regulated kinases by beta-arrestin scaffolds."
      Luttrell L.M., Roudabush F.L., Choy E.W., Miller W.E., Field M.E., Pierce K.L., Lefkowitz R.J.
      Proc. Natl. Acad. Sci. U.S.A. 98:2449-2454(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ARRB2.
    7. "Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites."
      Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.
      Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    8. "Identification of pY19-caveolin-2 as a positive regulator of insulin-stimulated actin cytoskeleton-dependent mitogenesis."
      Kwon H., Jeong K., Pak Y.
      J. Cell. Mol. Med. 13:1549-1564(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CAV2.
    9. "Caveolin-2 regulation of STAT3 transcriptional activation in response to insulin."
      Kwon H., Jeong K., Hwang E.M., Park J.-Y., Hong S.-G., Choi W.-S., Pak Y.
      Biochim. Biophys. Acta 1793:1325-1333(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CAV2.
    10. "The extracellular signal-regulated kinase: multiple substrates regulate diverse cellular functions."
      Yoon S., Seger R.
      Growth Factors 24:21-44(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION.
    11. "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, REVIEW ON SUBCELLULAR LOCATION.
    12. "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 ENZYME REGULATION, REVIEW ON FUNCTION.
    13. "Atomic structure of the MAP kinase ERK2 at 2.3-A resolution."
      Zhang F., Strand A., Robbins D., Cobb M.H., Goldsmith E.J.
      Nature 367:704-710(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
    14. "Mutation of position 52 in ERK2 creates a nonproductive binding mode for adenosine 5'-triphosphate."
      Robinson M.J., Harkins P.C., Zhang J., Baer R., Haycock J.W., Cobb M.H., Goldsmith E.J.
      Biochemistry 35:5641-5646(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) IN COMPLEX WITH ATP.
    15. "Activation mechanism of the MAP kinase ERK2 by dual phosphorylation."
      Canagarajah B.J., Khokhlatchev A., Cobb M.H., Goldsmith E.J.
      Cell 90:859-869(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
    16. Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
    17. "Structural basis of docking interactions between ERK2 and MAP kinase phosphatase 3."
      Liu S., Sun J.P., Zhou B., Zhang Z.Y.
      Proc. Natl. Acad. Sci. U.S.A. 103:5326-5331(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 2-357, INTERACTION WITH DUSP6.
    18. "Docking interactions induce exposure of activation loop in the MAP kinase ERK2."
      Zhou T., Sun L., Humphreys J., Goldsmith E.J.
      Structure 14:1011-1019(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 2-357.
    19. "Molecular modeling and crystal structure of ERK2-hypothemycin complexes."
      Rastelli G., Rosenfeld R., Reid R., Santi D.V.
      J. Struct. Biol. 164:18-23(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 2-358 IN COMPLEX WITH INHIBITOR.
    20. "Identification of a key element for hydrogen-bonding patterns between protein kinases and their inhibitors."
      Katayama N., Orita M., Yamaguchi T., Hisamichi H., Kuromitsu S., Kurihara H., Sakashita H., Matsumoto Y., Fujita S., Niimi T.
      Proteins 73:795-801(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.41 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
    21. "Phosphorylation of DCC by ERK2 is facilitated by direct docking of the receptor P1 domain to the kinase."
      Ma W., Shang Y., Wei Z., Wen W., Wang W., Zhang M.
      Structure 18:1502-1511(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH DCC, FUNCTION IN PHOSPHORYLATION OF DCC, INTERACTION WITH DCC, MUTAGENESIS OF GLN-117; HIS-123 AND LEU-155.

    Entry informationi

    Entry nameiMK01_RAT
    AccessioniPrimary (citable) accession number: P63086
    Secondary accession number(s): P27703
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 13, 2004
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 126 of the entry and version 3 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