ID:MK03_MOUSE DESCRIPTION: RecName: Full=Mitogen-activated protein kinase 3; Short=MAP kinase 3; Short=MAPK 3; EC=2.7.11.24; AltName: Full=ERT2; AltName: Full=Extracellular signal-regulated kinase 1; Short=ERK-1; AltName: Full=Insulin-stimulated MAP2 kinase; AltName: Full=MAP kinase isoform p44; Short=p44-MAPK; AltName: Full=MNK1; AltName: Full=Microtubule-associated protein 2 kinase; AltName: Full=p44-ERK1; FUNCTION: 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 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, 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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Magnesium (By similarity). ENZYME REGULATION: Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-203 and Tyr-205 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. Dephosphorylated and inactivated by DUSP3, DUSP6 and DUSP9. SUBUNIT: Binds both upstream activators and downstream substrates in multimolecular complexes. Found in a complex with at least BRAF, HRAS1, MAP2K1/MEK1, MAPK3 and RGS14 (By similarity). Interacts with ADAM15, ARRB2, CANX, DAPK1 (via death domain), HSF4, IER3, MAP2K1/MEK1, NISCH, and SGK1 (By similarity). Interacts with MORG1, PEA15 and MKNK2. MKNK2 isoform 1 binding prevents from dephosphorylation and inactivation. SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Autophosphorylation at Thr-207 promotes nuclear localization (By similarity). PEA15- binding redirects the biological outcome of MAPK3 kinase-signaling by sequestering MAPK3 into the cytoplasm. DOMAIN: The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases. PTM: Dually phosphorylated on Thr-203 and Tyr-205, which activates the enzyme. Ligand-activated ALK induces tyrosine phosphorylation (By similarity). Dephosphorylated by PTPRJ at Tyr-205 (By similarity). Autophosphorylated on threonine and tyrosine residues in vitro. Phosphorylated upon FLT3 and KIT signaling (By similarity). SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. SIMILARITY: Contains 1 protein kinase domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF00069 - Protein kinase domain PF07714 - Protein tyrosine kinase
SCOP Domains: 56112 - Protein kinase-like (PK-like)
ModBase Predicted Comparative 3D Structure on Q63844
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
BioCarta from NCI Cancer Genome Anatomy Project m_il2rbPathway - IL-2 Receptor Beta Chain in T cell Activation m_CCR3Pathway - CCR3 signaling in Eosinophils m_badPathway - Regulation of BAD phosphorylation m_dspPathway - Regulation of MAP Kinase Pathways Through Dual Specificity Phosphatases m_erk5Pathway - Role of Erk5 in Neuronal Survival m_il3Pathway - IL 3 signaling pathway m_insulinPathway - Insulin Signaling Pathway m_integrinPathway - Integrin Signaling Pathway m_nfatPathway - NFAT and Hypertrophy of the heart (Transcription in the broken heart) m_ptenPathway - PTEN dependent cell cycle arrest and apoptosis m_rasPathway - Ras Signaling Pathway m_ecmPathway - Erk and PI-3 Kinase Are Necessary for Collagen Binding in Corneal Epithelia m_At1rPathway - Angiotensin II mediated activation of JNK Pathway via Pyk2 dependent signaling m_RacCycDPathway - Influence of Ras and Rho proteins on G1 to S Transition m_TPOPathway - TPO Signaling Pathway m_barr-mapkPathway - Role of ¿-arrestins in the activation and targeting of MAP kinases m_cdk5Pathway - Phosphorylation of MEK1 by cdk5/p35 down regulates the MAP kinase pathway m_ceramidePathway - Ceramide Signaling Pathway m_erkPathway - Erk1/Erk2 Mapk Signaling pathway m_il2Pathway - IL 2 signaling pathway m_bArrestin-srcPathway - Roles of ¿-arrestin-dependent Recruitment of Src Kinases in GPCR Signaling m_eif4Pathway - Regulation of eIF4e and p70 S6 Kinase m_gpcrPathway - Signaling Pathway from G-Protein Families m_mapkPathway - MAPKinase Signaling Pathway m_pelp1Pathway - Pelp1 Modulation of Estrogen Receptor Activity m_spryPathway - Sprouty regulation of tyrosine kinase signals m_mPRPathway - How Progesterone Initiates the Oocyte Maturation m_stat3Pathway - Stat3 Signaling Pathway m_bcrPathway - BCR Signaling Pathway m_crebPathway - Transcription factor CREB and its extracellular signals m_dreampathway - Repression of Pain Sensation by the Transcriptional Regulator DREAM m_egfPathway - EGF Signaling Pathway m_hcmvPathway - Human Cytomegalovirus and Map Kinase Pathways m_malPathway - Role of MAL in Rho-Mediated Activation of SRF m_ngfPathway - Nerve growth factor pathway (NGF) m_pdgfPathway - PDGF Signaling Pathway m_tcrPathway - T Cell Receptor Signaling Pathway m_edg1Pathway - Phospholipids as signalling intermediaries m_epoPathway - EPO Signaling Pathway m_igf1rPathway - Multiple antiapoptotic pathways from IGF-1R signaling lead to BAD phosphorylation m_keratinocytePathway - Keratinocyte Differentiation m_pyk2Pathway - Links between Pyk2 and Map Kinases m_cdMacPathway - Cadmium induces DNA synthesis and proliferation in macrophages m_fcer1Pathway - Fc Epsilon Receptor I Signaling in Mast Cells m_her2Pathway - Role of ERBB2 in Signal Transduction and Oncology m_il6Pathway - IL 6 signaling pathway m_sam68Pathway - Regulation of Splicing through Sam68 m_tffPathway - Trefoil Factors Initiate Mucosal Healing m_ghPathway - Growth Hormone Signaling Pathway m_agrPathway - Agrin in Postsynaptic Differentiation m_biopeptidesPathway - Bioactive Peptide Induced Signaling Pathway m_cxcr4Pathway - CXCR4 Signaling Pathway m_fMLPpathway - fMLP induced chemokine gene expression in HMC-1 cells m_gleevecpathway - Inhibition of Cellular Proliferation by Gleevec m_igf1Pathway - IGF-1 Signaling Pathway m_metPathway - Signaling of Hepatocyte Growth Factor Receptor m_nkcellsPathway - Ras-Independent pathway in NK cell-mediated cytotoxicity m_tgfbPathway - TGF beta signaling pathway
Reactome (by CSHL, EBI, and GO)
Protein Q63844 (Reactome details) participates in the following event(s):
US Server
