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P46196

- MK01_BOVIN

UniProt

P46196 - MK01_BOVIN

Protein

Mitogen-activated protein kinase 1

Gene

MAPK1

Organism
Bos taurus (Bovine)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 128 (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. May play a role in the spindle assembly checkpoint By similarity. 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-185 and Tyr-187 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-29 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 By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei54 – 541ATPPROSITE-ProRule annotation
    Binding sitei54 – 541InhibitorBy similarity
    Binding sitei108 – 1081Inhibitor; via amide nitrogen and carbonyl oxygenBy similarity
    Binding sitei114 – 1141InhibitorBy similarity
    Active sitei149 – 1491Proton acceptorPROSITE-ProRule annotation
    Binding sitei154 – 1541InhibitorBy similarity
    Binding sitei166 – 1661InhibitorBy similarity
    Binding sitei167 – 1671InhibitorBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi31 – 399ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. MAP kinase activity Source: UniProtKB-EC
    3. protein serine/threonine kinase activity Source: UniProtKB
    4. RNA polymerase II carboxy-terminal domain kinase activity Source: Ensembl

    GO - Biological processi

    1. apoptotic process Source: UniProtKB-KW
    2. B cell receptor signaling pathway Source: Ensembl
    3. cell cycle Source: UniProtKB-KW
    4. cellular response to DNA damage stimulus Source: Ensembl
    5. cytosine metabolic process Source: Ensembl
    6. ERBB signaling pathway Source: Ensembl
    7. ERK1 and ERK2 cascade Source: Ensembl
    8. labyrinthine layer blood vessel development Source: Ensembl
    9. lipopolysaccharide-mediated signaling pathway Source: Ensembl
    10. mammary gland epithelial cell proliferation Source: Ensembl
    11. negative regulation of cell differentiation Source: Ensembl
    12. organ morphogenesis Source: Ensembl
    13. peptidyl-serine phosphorylation Source: UniProtKB
    14. peptidyl-threonine phosphorylation Source: UniProtKB
    15. positive regulation of peptidyl-threonine phosphorylation Source: Ensembl
    16. regulation of protein stability Source: UniProtKB
    17. response to epidermal growth factor Source: UniProtKB
    18. response to exogenous dsRNA Source: Ensembl
    19. 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

    ReactomeiREACT_202074. FCERI mediated MAPK activation.
    REACT_202837. Signaling by FGFR.
    REACT_203126. phospho-PLA2 pathway.
    REACT_203215. Senescence-Associated Secretory Phenotype (SASP).
    REACT_204725. Advanced glycosylation endproduct receptor signaling.
    REACT_205036. Gastrin-CREB signalling pathway via PKC and MAPK.
    REACT_207562. Negative regulation of FGFR signaling.
    REACT_209393. Growth hormone receptor signaling.
    REACT_210032. ERK2 activation.
    REACT_211475. Regulation of actin dynamics for phagocytic cup formation.
    REACT_215912. Thrombin signalling through proteinase activated receptors (PARs).
    REACT_216684. Signal transduction by L1.
    REACT_217282. NCAM signaling for neurite out-growth.
    REACT_217767. Oncogene Induced Senescence.
    REACT_218305. CREB phosphorylation through the activation of Ras.
    REACT_218726. Regulation of HSF1-mediated heat shock response.
    REACT_220172. Golgi Cisternae Pericentriolar Stack Reorganization.
    REACT_220398. ERKs are inactivated.
    REACT_221197. Activation of the AP-1 family of transcription factors.
    REACT_222627. RSK activation.
    REACT_223433. Recycling pathway of L1.
    REACT_225657. Oxidative Stress Induced Senescence.
    REACT_226850. ERK/MAPK targets.

    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
    Mitogen-activated protein kinase 2
    Short name:
    MAP kinase 2
    Short name:
    MAPK 2
    Gene namesi
    Name:MAPK1
    Synonyms:ERK2, PRKM1
    OrganismiBos taurus (Bovine)
    Taxonomic identifieri9913 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
    ProteomesiUP000009136: Unplaced

    Subcellular locationi

    Nucleus By similarity. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity. Cytoplasm By similarity. Cytoplasmcytoskeletonspindle By similarity
    Note: PEA15-binding and phosphorylated DAPK1 promote its cytoplasmic retention. Phosphorylation at Ser-246 and Ser-248 as well as autophosphorylation at Thr-190 promote nuclear localization. Associated with the spindle during prometaphase and metaphase.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. cytosol Source: Ensembl
    3. microtubule organizing center Source: UniProtKB-SubCell
    4. mitochondrion Source: Ensembl
    5. mitotic spindle Source: UniProtKB
    6. nucleus Source: UniProtKB
    7. pseudopodium Source: Ensembl

    Keywords - Cellular componenti

    Cytoplasm, Cytoskeleton, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 360359Mitogen-activated protein kinase 1PRO_0000186246Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanineBy similarity
    Modified residuei29 – 291Phosphoserine; by SGK1By similarity
    Modified residuei185 – 1851Phosphothreonine; by MAP2K1 and MAP2K2By similarity
    Modified residuei187 – 1871Phosphotyrosine; by MAP2K1 and MAP2K2By similarity
    Modified residuei190 – 1901Phosphothreonine; by autocatalysisBy similarity
    Modified residuei246 – 2461PhosphoserineBy similarity
    Modified residuei248 – 2481PhosphoserineBy similarity
    Modified residuei284 – 2841PhosphoserineBy similarity

    Post-translational modificationi

    Dually phosphorylated on Thr-185 and Tyr-187, which activates the enzyme. Phosphorylated upon FLT3 and KIT signaling By similarity. Phosphorylation on Ser-29 by SGK1 results in its activation by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2 By similarity. Phosphorylation at Ser-246 and Ser-248 as well as autophosphorylation at Thr-190 promote nuclear localization. Ligand-activated ALK induces tyrosine phosphorylation By similarity. Dephosphorylated by PTPRJ at Tyr-187 By similarity.By similarity
    ISGylated.By similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PRIDEiP46196.

    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 By similarity. The phosphorylated form interacts with PML By similarity. Interacts with STYX By similarity.By similarity

    Protein-protein interaction databases

    STRINGi9913.ENSBTAP00000013623.

    Structurei

    3D structure databases

    ProteinModelPortaliP46196.
    SMRiP46196. Positions 8-357.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini25 – 313289Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni105 – 1084Inhibitor-bindingBy similarity
    Regioni153 – 1542Inhibitor-bindingBy similarity

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi185 – 1873TXY

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi2 – 98Poly-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.
    HOVERGENiHBG014652.
    KOiK04371.

    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.

    P46196-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAAAAAAGAG PEMVRGQVFD VGPRYTNLSY IGEGAYGMVC SAYDNVNKVR    50
    VAIKKISPFE HQTYCQRTLR EIKILLRFRH ENIIGINDII RAPTIEQMKD 100
    VYIVQDLMET DLYKLLKTQH LSNDHICYFL YQILRGLKYI HSANVLHRDL 150
    KPSNLLLNTT CDLKICDFGL ARVADPDHDH TGFLTEYVAT RWYRAPEIML 200
    NSKGYTKSID IWSVGCILAE MLSNRPIFPG KHYLDQLNHI LGILGSPSQE 250
    DLNCIINLKA RNYLLSLPHK NKVPWNRLFP NADSKALDLL DKMLTFNPHK 300
    RIEVEQALAH PYLEQYYDPS DEPVAEAPFK FDMELDDLPK EKLKELIFEE 350
    TARFQPGYRS 360
    Length:360
    Mass (Da):41,376
    Last modified:January 23, 2007 - v3
    Checksum:iE85D0B2A4E9549DE
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Z14089 mRNA. Translation: CAA78467.1.
    BC133588 mRNA. Translation: AAI33589.2.
    PIRiS25011.
    RefSeqiNP_786987.1. NM_175793.2.
    UniGeneiBt.109487.

    Genome annotation databases

    GeneIDi327672.
    KEGGibta:327672.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Z14089 mRNA. Translation: CAA78467.1 .
    BC133588 mRNA. Translation: AAI33589.2 .
    PIRi S25011.
    RefSeqi NP_786987.1. NM_175793.2.
    UniGenei Bt.109487.

    3D structure databases

    ProteinModelPortali P46196.
    SMRi P46196. Positions 8-357.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9913.ENSBTAP00000013623.

    Proteomic databases

    PRIDEi P46196.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 327672.
    KEGGi bta:327672.

    Organism-specific databases

    CTDi 5594.

    Phylogenomic databases

    eggNOGi COG0515.
    HOVERGENi HBG014652.
    KOi K04371.

    Enzyme and pathway databases

    Reactomei REACT_202074. FCERI mediated MAPK activation.
    REACT_202837. Signaling by FGFR.
    REACT_203126. phospho-PLA2 pathway.
    REACT_203215. Senescence-Associated Secretory Phenotype (SASP).
    REACT_204725. Advanced glycosylation endproduct receptor signaling.
    REACT_205036. Gastrin-CREB signalling pathway via PKC and MAPK.
    REACT_207562. Negative regulation of FGFR signaling.
    REACT_209393. Growth hormone receptor signaling.
    REACT_210032. ERK2 activation.
    REACT_211475. Regulation of actin dynamics for phagocytic cup formation.
    REACT_215912. Thrombin signalling through proteinase activated receptors (PARs).
    REACT_216684. Signal transduction by L1.
    REACT_217282. NCAM signaling for neurite out-growth.
    REACT_217767. Oncogene Induced Senescence.
    REACT_218305. CREB phosphorylation through the activation of Ras.
    REACT_218726. Regulation of HSF1-mediated heat shock response.
    REACT_220172. Golgi Cisternae Pericentriolar Stack Reorganization.
    REACT_220398. ERKs are inactivated.
    REACT_221197. Activation of the AP-1 family of transcription factors.
    REACT_222627. RSK activation.
    REACT_223433. Recycling pathway of L1.
    REACT_225657. Oxidative Stress Induced Senescence.
    REACT_226850. ERK/MAPK targets.

    Miscellaneous databases

    NextBioi 20810137.

    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. "Cloning and sequencing of ERK2 from a bovine adrenal medulla cDNA library."
      Ely C.M., Cox M.E., Her J., Parsons S.J.
      Submitted (JUL-1992) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Adrenal medulla.
    2. NIH - Mammalian Gene Collection (MGC) project
      Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: Hereford.
      Tissue: Fetal pons.

    Entry informationi

    Entry nameiMK01_BOVIN
    AccessioniPrimary (citable) accession number: P46196
    Secondary accession number(s): A2VE60
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1995
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 128 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

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3