Description: Homo sapiens mitogen-activated protein kinase 1 (MAPK1), transcript variant 1, mRNA. RefSeq Summary (NM_002745): This gene encodes a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. The activation of this kinase requires its phosphorylation by upstream kinases. Upon activation, this kinase translocates to the nucleus of the stimulated cells, where it phosphorylates nuclear targets. One study also suggests that this protein acts as a transcriptional repressor independent of its kinase activity. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Two alternatively spliced transcript variants encoding the same protein, but differing in the UTRs, have been reported for this gene. [provided by RefSeq, Jan 2014]. Transcript (Including UTRs) Position: hg19 chr22:22,113,947-22,221,970 Size: 108,024 Total Exon Count: 9 Strand: - Coding Region Position: hg19 chr22:22,123,493-22,221,730 Size: 98,238 Coding Exon Count: 8
ID:MK01_HUMAN DESCRIPTION: RecName: Full=Mitogen-activated protein kinase 1; Short=MAP kinase 1; Short=MAPK 1; EC=2.7.11.24; AltName: Full=ERT1; AltName: Full=Extracellular signal-regulated kinase 2; Short=ERK-2; AltName: Full=MAP kinase isoform p42; Short=p42-MAPK; AltName: Full=Mitogen-activated protein kinase 2; Short=MAP kinase 2; Short=MAPK 2; 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, 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. FUNCTION: 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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Magnesium (By similarity). ENZYME REGULATION: 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. SUBUNIT: Binds both upstream activators and downstream substrates in multimolecular complexes. Binds to HIV-1 Nef through its SH3 domain. This interaction inhibits its tyrosine-kinase activity. Interacts with ADAM15, ARHGEF2, ARRB2, DAPK1 (via death domain), HSF4, IER3, IPO7, DUSP6, NISCH, SGK1, and isoform 1 of NEK2. Interacts (phosphorylated form) with CAV2 ('Tyr-19'-phosphorylated form); the interaction, promoted by insulin, leads to nuclear location and MAPK1 activation. Interacts with MORG1, PEA15 and MKNK2 (By similarity). MKNK2 isoform 1 binding prevents from dephosphorylation and inactivation (By similarity). Interacts with DCC (By similarity). INTERACTION: P28562:DUSP1; NbExp=3; IntAct=EBI-959949, EBI-975493; SUBCELLULAR LOCATION: Nucleus. Cytoplasm, cytoskeleton, centrosome. Cytoplasm. 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. DOMAIN: The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases. PTM: Phosphorylated upon KIT and FLT3 signaling (By similarity). Dually phosphorylated on Thr-185 and Tyr-187, which activates the enzyme. Undergoes regulatory phosphorylation on additional residues such as Ser-246 and Ser-248 in the kinase insert domain (KID) These phosphorylations, which are probably mediated by more than one kinase, are important for binding of MAPK1/ERK2 to importin-7 (IPO7) and its nuclear translocation. In addition, autophosphorylation of Thr-190 was shown to affect the subcellular localization of MAPK1/ERK2 as well. Ligand-activated ALK induces tyrosine phosphorylation. Dephosphorylated by PTPRJ at Tyr-187. Phosphorylation on Ser-29 by SGK1 results in its activation by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. DUSP3 and DUSP6 dephosphorylate specifically MAPK1/ERK2 and MAPK3/ERK1 whereas DUSP9 dephosphorylates a broader range of MAPKs. SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. SIMILARITY: Contains 1 protein kinase domain. SEQUENCE CAUTION: Sequence=CAA77753.1; Type=Erroneous initiation; Note=Translation N-terminally extended; WEB RESOURCE: Name=Wikipedia; Note=Extracellular signal-regulated kinase entry; URL="http://en.wikipedia.org/wiki/Extracellular_signal-regulated_kinase";
Multiple Sclerosis Stephen Sawcer et al. Nature 2011, Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis., Nature.
[PubMed 21833088]
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.
ModBase Predicted Comparative 3D Structure on P28482
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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 h_ecmPathway - Erk and PI-3 Kinase Are Necessary for Collagen Binding in Corneal Epithelia h_mPRPathway - How Progesterone Initiates the Oocyte Maturation h_stat3Pathway - Stat3 Signaling Pathway h_At1rPathway - Angiotensin II mediated activation of JNK Pathway via Pyk2 dependent signaling h_biopeptidesPathway - Bioactive Peptide Induced Signaling Pathway h_erkPathway - Erk1/Erk2 Mapk Signaling pathway h_metPathway - Signaling of Hepatocyte Growth Factor Receptor h_pyk2Pathway - Links between Pyk2 and Map Kinases h_tffPathway - Trefoil Factors Initiate Mucosal Healing h_erk5Pathway - Role of Erk5 in Neuronal Survival h_ghPathway - Growth Hormone Signaling Pathway h_pparaPathway - Mechanism of Gene Regulation by Peroxisome Proliferators via PPARa(alpha) h_CCR3Pathway - CCR3 signaling in Eosinophils h_RacCycDPathway - Influence of Ras and Rho proteins on G1 to S Transition h_bArrestin-srcPathway - Roles of ¿-arrestin-dependent Recruitment of Src Kinases in GPCR Signaling h_cdk5Pathway - Phosphorylation of MEK1 by cdk5/p35 down regulates the MAP kinase pathway h_ceramidePathway - Ceramide Signaling Pathway h_edg1Pathway - Phospholipids as signalling intermediaries h_integrinPathway - Integrin Signaling Pathway h_nfatPathway - NFAT and Hypertrophy of the heart (Transcription in the broken heart) h_sam68Pathway - Regulation of Splicing through Sam68 h_il2rbPathway - IL-2 Receptor Beta Chain in T cell Activation h_cdMacPathway - Cadmium induces DNA synthesis and proliferation in macrophages h_malPathway - Role of MAL in Rho-Mediated Activation of SRF h_badPathway - Regulation of BAD phosphorylation h_crebPathway - Transcription factor CREB and its extracellular signals h_eif4Pathway - Regulation of eIF4e and p70 S6 Kinase h_mapkPathway - MAPKinase Signaling Pathway h_spryPathway - Sprouty regulation of tyrosine kinase signals h_cxcr4Pathway - CXCR4 Signaling Pathway h_fMLPpathway - fMLP induced chemokine gene expression in HMC-1 cells h_igf1rPathway - Multiple antiapoptotic pathways from IGF-1R signaling lead to BAD phosphorylation h_keratinocytePathway - Keratinocyte Differentiation h_sppaPathway - Aspirin Blocks Signaling Pathway Involved in Platelet Activation h_arenrf2Pathway - Oxidative Stress Induced Gene Expression Via Nrf2 h_fcer1Pathway - Fc Epsilon Receptor I Signaling in Mast Cells h_pelp1Pathway - Pelp1 Modulation of Estrogen Receptor Activity h_agrPathway - Agrin in Postsynaptic Differentiation h_barr-mapkPathway - Role of ¿-arrestins in the activation and targeting of MAP kinases h_hcmvPathway - Human Cytomegalovirus and Map Kinase Pathways h_her2Pathway - Role of ERBB2 in Signal Transduction and Oncology h_ptenPathway - PTEN dependent cell cycle arrest and apoptosis
Reactome (by CSHL, EBI, and GO)
Protein P28482 (Reactome details) participates in the following event(s):
R-HSA-109858 MAP2K2 binds MAPK1 R-HSA-442737 Activation of MAPK R-HSA-445079 Phosphorylation of L1 by ERK R-HSA-109864 Dissociation of p-T,Y-MAPK1:p-S,T-MAP2K2 R-HSA-109862 MAP2K2 phosphorylates MAPK1 R-HSA-418170 Beta-arrestin-1 acts as scaffold for a PAR1 signalling complex R-HSA-418176 Beta-arrestin-2 acts as scaffold for a PAR1 signalling complex R-HSA-879362 AGER binds ERK1/2 R-HSA-5672972 MAP2Ks and MAPKs bind to the activated RAF complex R-HSA-5674132 WDR83:LAMTOR2:LAMTOR3 binds MAPK components R-HSA-5674366 IL17RD binds p-2S MAP2Ks and MAPKs R-HSA-6802912 High kinase activity BRAF mutants bind MAP2Ks and MAPKs R-HSA-6802914 RAS:GTP:moderate kinase activity p-RAF complexes bind MAP2Ks and MAPKs R-HSA-6802925 Mutant RAS:p-RAF complexes bind MAP2Ks and MAPKs R-HSA-6802934 p-BRAF and RAF fusion dimers bind MAP2Ks and MAPKs R-HSA-6802942 RAS:GTP:p-RAF complexes paradoxically bind MAP2Ks and MAPKs R-HSA-5674385 p-T,Y MAPKs dimerize R-HSA-5672980 Dissociation of RAS:RAF complex R-HSA-6802932 Dissociation of BRAF/RAF fusion complex R-HSA-6803227 Dissociation of high activity BRAF complexes R-HSA-6803230 Dissociation of moderate activity BRAF complexes R-HSA-6803233 Dissociation of oncogenic RAS:RAF complex R-HSA-6803234 Dissociation of paradoxically activated RAS:BRAF complexes R-HSA-111898 Phosphorylation of cPLA2 by ERK-2 R-HSA-444253 Phosphorylation by MAPK/ERK R-HSA-199959 ERKs are inactivated by protein phosphatase 2A R-HSA-203797 ERKs are inactivated by dual-specific phosphatases (DUSPs) R-HSA-5675373 Nuclear DUSPs dephosphorylate MAPKs R-HSA-6798751 Exocytosis of azurophil granule lumen proteins R-HSA-6800434 Exocytosis of ficolin-rich granule lumen proteins R-HSA-5675376 Cytosolic DUSPs dephosphorylate MAPKs R-HSA-5672978 RAF phosphorylates MAP2K dimer R-HSA-5672973 MAP2Ks phosphorylate MAPKs R-HSA-5674373 MAP2Ks phosphorylate MAPK at the Golgi membrane R-HSA-6802918 Activated MAP2Ks phosphorylate MAPKs downstream of inactive BRAF mutants R-HSA-6802943 RAS:GTP:inactive p-RAF complexes phosphorylate MAP2Ks R-HSA-6802919 RAS:GTP:moderate kinase activity p-RAF complexes phosphorylate MAP2Ks R-HSA-6802921 Activated MAP2Ks phosphorylate MAPKs downstream of moderate kinase activity BRAF mutants R-HSA-6802911 High kinase activity BRAF complexes phosphorylate MAP2Ks R-HSA-6802910 Activated MAP2Ks phosphorylate MAPKs downstream of high kinase activity BRAF mutants R-HSA-6802926 Mutant RAS:p-RAF complexes phosphorylate MAP2Ks R-HSA-6802922 Activated MAP2Ks phosphorylate MAPKs downstream of oncogenic RAS R-HSA-6802933 p-BRAF and RAF fusion dimers phosphorylate MAP2Ks R-HSA-6802935 MAPKs are phosphorylated downstream of BRAF and RAF fusion dimers R-HSA-109822 MAPK3,(MAPK1) phosphorylates GRB2-1:SOS1:p-Y427-SHC1 R-HSA-109823 MAPK3,(MAPK1) phosphorylates GRB2-1:SOS1:p-Y-IRS1,p-Y-IRS2 R-HSA-6811472 IER3 recruits MAPKs to PP2A-B56-beta,gamma R-HSA-6811454 MAPKs phosphorylate PP2A R-HSA-5675206 PEA15 binds MAPK monomers and dimers R-NUL-9009236 Activated ERKs phosphorylate Runx2 R-HSA-198746 ERK1/2/5 activate RSK1/2/3 R-HSA-168053 Phosphorylated MAPKs phosphorylate ATF-2 R-HSA-5654560 Activated ERK1/2 threonine-phosphorylates FGFR1-associated FRS2. R-HSA-5654562 Activated ERK1/2 threonine-phosphorylates FGFR2-associated FRS2 R-HSA-5654565 Activated ERK1/2 threonine-phosphorylates FGFR3-associated FRS2. R-HSA-5654566 Activated ERK1/2 threonine-phosphorylates FGFR4-associated FRS2. R-HSA-2029469 p-ERK phosphorylates WAVEs and ABI R-HSA-3371531 Constitutive phosphorylation by pERK1/2 R-HSA-2422927 MAPK3-3 or MAPK1 phosphorylate GORASP2 R-HSA-5674496 Activated MAPKs phosphorylate MAP2K1 R-HSA-5675194 Activated MAPK phosphorylates RAF1 R-HSA-5675198 Activated MAPKs phosphorylate BRAF R-HSA-198731 ERK1/2 activates ELK1 R-HSA-198756 ERK1/2 phosphorylates MSK1 R-HSA-450325 c-FOS activation by phospho ERK1/2 R-HSA-3132737 MAPKs phosphorylate ETS1 and ETS2 R-HSA-3209160 Activated ERKs phosphorylate ERF R-HSA-3857329 MAPK3 (ERK1) and MAPK1 (ERK2) phosphorylate CEBPB R-HSA-9009208 Activated ERKs phosphorylate RUNX2 R-HSA-112411 MAPK1 (ERK2) activation R-HSA-442742 CREB phosphorylation through the activation of Ras R-HSA-437239 Recycling pathway of L1 R-HSA-445144 Signal transduction by L1 R-HSA-456926 Thrombin signalling through proteinase activated receptors (PARs) R-HSA-879415 Advanced glycosylation endproduct receptor signaling R-HSA-982772 Growth hormone receptor signaling R-HSA-5674135 MAP2K and MAPK activation R-HSA-6802948 Signaling by high-kinase activity BRAF mutants R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants R-HSA-6802949 Signaling by RAS mutants R-HSA-6802952 Signaling by BRAF and RAF fusions R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF R-HSA-112409 RAF-independent MAPK1/3 activation R-HSA-438064 Post NMDA receptor activation events R-HSA-5673001 RAF/MAP kinase cascade R-HSA-373760 L1CAM interactions R-HSA-111995 phospho-PLA2 pathway R-HSA-444257 RSK activation R-HSA-198753 ERK/MAPK targets R-HSA-202670 ERKs are inactivated R-HSA-5675221 Negative regulation of MAPK pathway R-HSA-6798695 Neutrophil degranulation R-HSA-76002 Platelet activation, signaling and aggregation R-HSA-168249 Innate Immune System R-HSA-1280215 Cytokine Signaling in Immune system R-HSA-6802957 Oncogenic MAPK signaling R-HSA-74749 Signal attenuation R-HSA-5684996 MAPK1/MAPK3 signaling R-HSA-442755 Activation of NMDA receptor and postsynaptic events R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-HSA-422475 Axon guidance R-HSA-111996 Ca-dependent events R-HSA-198725 Nuclear Events (kinase and transcription factor activation) R-HSA-450282 MAPK targets/ Nuclear events mediated by MAP kinases R-HSA-881907 Gastrin-CREB signalling pathway via PKC and MAPK R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP) R-HSA-450341 Activation of the AP-1 family of transcription factors R-HSA-109582 Hemostasis R-HSA-168256 Immune System R-HSA-5663202 Diseases of signal transduction R-HSA-74751 Insulin receptor signalling cascade R-HSA-5683057 MAPK family signaling cascades R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission R-HSA-199418 Negative regulation of the PI3K/AKT network R-HSA-5654726 Negative regulation of FGFR1 signaling R-HSA-5654727 Negative regulation of FGFR2 signaling R-HSA-5654732 Negative regulation of FGFR3 signaling R-HSA-5654733 Negative regulation of FGFR4 signaling R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation R-HSA-5663213 RHO GTPases Activate WASPs and WAVEs R-HSA-3371453 Regulation of HSF1-mediated heat shock response R-HSA-162658 Golgi Cisternae Pericentriolar Stack Reorganization R-HSA-5674499 Negative feedback regulation of MAPK pathway R-HSA-1266738 Developmental Biology R-HSA-112043 PLC beta mediated events R-HSA-375165 NCAM signaling for neurite out-growth R-HSA-2559580 Oxidative Stress Induced Senescence R-HSA-2871796 FCERI mediated MAPK activation R-HSA-2559585 Oncogene Induced Senescence R-HSA-8940973 RUNX2 regulates osteoblast differentiation R-HSA-8939211 ESR-mediated signaling R-HSA-187037 Signaling by NTRK1 (TRKA) R-HSA-450294 MAP kinase activation R-HSA-416476 G alpha (q) signalling events R-HSA-2559583 Cellular Senescence R-HSA-1643685 Disease R-HSA-74752 Signaling by Insulin receptor R-HSA-162582 Signal Transduction R-HSA-112315 Transmission across Chemical Synapses R-HSA-1257604 PIP3 activates AKT signaling R-HSA-5654736 Signaling by FGFR1 R-HSA-5654738 Signaling by FGFR2 R-HSA-5654741 Signaling by FGFR3 R-HSA-5654743 Signaling by FGFR4 R-HSA-2029480 Fcgamma receptor (FCGR) dependent phagocytosis R-HSA-195258 RHO GTPase Effectors R-HSA-3371556 Cellular response to heat stress R-HSA-68875 Mitotic Prophase R-HSA-112040 G-protein mediated events R-HSA-2454202 Fc epsilon receptor (FCERI) signaling R-HSA-8941326 RUNX2 regulates bone development R-HSA-9006931 Signaling by Nuclear Receptors R-HSA-166520 Signaling by NTRKs R-HSA-166058 MyD88:Mal cascade initiated on plasma membrane R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade R-HSA-448424 Interleukin-17 signaling R-HSA-937061 TRIF(TICAM1)-mediated TLR4 signaling R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation R-HSA-975871 MyD88 cascade initiated on plasma membrane R-HSA-388396 GPCR downstream signalling R-HSA-2262752 Cellular responses to stress R-HSA-9006934 Signaling by Receptor Tyrosine Kinases R-HSA-112316 Neuronal System R-HSA-9006925 Intracellular signaling by second messengers R-HSA-190236 Signaling by FGFR R-HSA-194315 Signaling by Rho GTPases R-HSA-68886 M Phase R-HSA-111885 Opioid Signalling R-HSA-8878166 Transcriptional regulation by RUNX2 R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade R-HSA-168898 Toll-Like Receptors Cascades R-HSA-449147 Signaling by Interleukins R-HSA-166166 MyD88-independent TLR4 cascade R-HSA-975155 MyD88 dependent cascade initiated on endosome R-HSA-168142 Toll Like Receptor 10 (TLR10) Cascade R-HSA-168176 Toll Like Receptor 5 (TLR5) Cascade R-HSA-372790 Signaling by GPCR R-HSA-8953897 Cellular responses to external stimuli R-HSA-69278 Cell Cycle (Mitotic) R-HSA-418594 G alpha (i) signalling events R-HSA-212436 Generic Transcription Pathway R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade R-HSA-1640170 Cell Cycle R-HSA-73857 RNA Polymerase II Transcription R-HSA-74160 Gene expression (Transcription)
US Server
