ID MK01_BOVIN Reviewed; 360 AA. AC P46196; A2VE60; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 27-MAR-2024, entry version 187. DE RecName: Full=Mitogen-activated protein kinase 1 {ECO:0000250|UniProtKB:P28482}; DE Short=MAP kinase 1; DE Short=MAPK 1; DE EC=2.7.11.24; DE AltName: Full=ERT1; DE AltName: Full=Extracellular signal-regulated kinase 2; DE Short=ERK-2; DE AltName: Full=Mitogen-activated protein kinase 2; DE Short=MAP kinase 2; DE Short=MAPK 2; GN Name=MAPK1 {ECO:0000250|UniProtKB:P28482}; Synonyms=ERK2, PRKM1; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Adrenal medulla; RA Ely C.M., Cox M.E., Her J., Parsons S.J.; RT "Cloning and sequencing of ERK2 from a bovine adrenal medulla cDNA RT library."; RL Submitted (JUL-1992) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Hereford; TISSUE=Fetal pons; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Serine/threonine kinase which acts as an essential component CC of the MAP kinase signal transduction pathway. MAPK1/ERK2 and CC MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK CC cascade. They participate also in a signaling cascade initiated by CC activated KIT and KITLG/SCF. Depending on the cellular context, the CC MAPK/ERK cascade mediates diverse biological functions such as cell CC growth, adhesion, survival and differentiation through the regulation CC of transcription, translation, cytoskeletal rearrangements. The CC MAPK/ERK cascade also plays a role in initiation and regulation of CC meiosis, mitosis, and postmitotic functions in differentiated cells by CC phosphorylating a number of transcription factors. About 160 substrates CC have already been discovered for ERKs. Many of these substrates are CC localized in the nucleus, and seem to participate in the regulation of CC transcription upon stimulation. However, other substrates are found in CC the cytosol as well as in other cellular organelles, and those are CC responsible for processes such as translation, mitosis and apoptosis. CC Moreover, the MAPK/ERK cascade is also involved in the regulation of CC the endosomal dynamics, including lysosome processing and endosome CC cycling through the perinuclear recycling compartment (PNRC); as well CC as in the fragmentation of the Golgi apparatus during mitosis. The CC substrates include transcription factors (such as ATF2, BCL6, ELK1, CC ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, CC GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such CC as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of CC translation (such as EIF4EBP1 and FXR1) and a variety of other CC signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein CC kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, CC RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, CC MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or CC DUSP16) are other substrates which enable the propagation the MAPK/ERK CC signal to additional cytosolic and nuclear targets, thereby extending CC the specificity of the cascade. Mediates phosphorylation of TPR in CC response to EGF stimulation. May play a role in the spindle assembly CC checkpoint (By similarity). Phosphorylates PML and promotes its CC interaction with PIN1, leading to PML degradation. Phosphorylates CC CDK2AP2. {ECO:0000250|UniProtKB:P28482, ECO:0000250|UniProtKB:P63085, CC ECO:0000250|UniProtKB:P63086}. CC -!- FUNCTION: Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] CC consensus sequence. Repress the expression of interferon gamma-induced CC genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, CC IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity CC is independent of kinase activity. {ECO:0000250|UniProtKB:P28482}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.24; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; CC EC=2.7.11.24; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; CC -!- ACTIVITY REGULATION: Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on CC Thr-185 and Tyr-187 in response to external stimuli like insulin or CC NGF. Both phosphorylations are required for activity. This CC phosphorylation causes dramatic conformational changes, which enable CC full activation and interaction of MAPK1/ERK2 with its substrates. CC Phosphorylation on Ser-29 by SGK1 results in its activation by CC enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. CC Dephosphorylated and inactivated by DUSP1, DUSP3, DUSP6 and DUSP9. CC Inactivated by pyrimidylpyrrole inhibitors (By similarity). CC {ECO:0000250}. CC -!- SUBUNIT: Binds both upstream activators and downstream substrates in CC multimolecular complexes. Interacts with ADAM15, ARHGEF2, ARRB2, DAPK1 CC (via death domain), HSF4, IER3, IPO7, MKNK2, MORG1, NISCH, PEA15, SGK1, CC and isoform 1 of NEK2. Interacts (via phosphorylated form) with TPR CC (via C-terminal region and phosphorylated form); the interaction CC requires dimerization of MAPK1/ERK2 and increases following EGF CC stimulation (By similarity). Interacts with MAP2K1 (By similarity). CC Interacts with DUSP6 (By similarity). Interacts (phosphorylated form) CC with CAV2 ('Tyr-19'-phosphorylated form); the interaction, promoted by CC insulin, leads to nuclear location and MAPK1 activation. MKNK2 isoform CC 1 binding prevents from dephosphorylation and inactivation. Interacts CC with DCC. The phosphorylated form interacts with PML. Interacts with CC STYX. Interacts with CDK2AP2. Interacts with CAVIN4. Interacts with CC DUSP7; the interaction enhances DUSP7 phosphatase activity. Interacts CC with GIT1; this interaction is necessary for MAPK1 localization to CC focal adhesions (By similarity). Interacts with ZNF263 (By similarity). CC {ECO:0000250|UniProtKB:P28482, ECO:0000250|UniProtKB:P63085, CC ECO:0000250|UniProtKB:P63086}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Cytoplasm, cytoskeleton, CC microtubule organizing center, centrosome {ECO:0000250}. Cytoplasm CC {ECO:0000250|UniProtKB:P63086}. Cytoplasm, cytoskeleton, spindle CC {ECO:0000250}. Membrane, caveola {ECO:0000250|UniProtKB:P63086}. Cell CC junction, focal adhesion {ECO:0000250|UniProtKB:P63085}. Note=PEA15- CC binding and phosphorylated DAPK1 promote its cytoplasmic retention. CC Phosphorylation at Ser-246 and Ser-248 as well as autophosphorylation CC at Thr-190 promote nuclear localization. Associated with the spindle CC during prometaphase and metaphase. {ECO:0000250}. CC -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues CC whose phosphorylation activates the MAP kinases. CC -!- PTM: Dually phosphorylated on Thr-185 and Tyr-187, which activates the CC enzyme. Phosphorylated upon FLT3 and KIT signaling (By similarity). CC Phosphorylation on Ser-29 by SGK1 results in its activation by CC enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2 (By CC similarity). Phosphorylation at Ser-246 and Ser-248 as well as CC autophosphorylation at Thr-190 promote nuclear localization. Ligand- CC activated ALK induces tyrosine phosphorylation (By similarity). CC Dephosphorylated by PTPRJ at Tyr-187 (By similarity). Dephosphorylated CC by DUSP1 and DUSP2 at Thr-185 and Tyr-187 (By similarity). CC {ECO:0000250, ECO:0000250|UniProtKB:P28482, CC ECO:0000250|UniProtKB:P63085}. CC -!- PTM: ISGylated. {ECO:0000250}. CC -!- PTM: Ubiquitinated by TRIM15 via 'Lys-63'-linked ubiquitination; CC leading to activation. Deubiquitinated by CYLD. CC {ECO:0000250|UniProtKB:P27361}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr CC protein kinase family. MAP kinase subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Z14089; CAA78467.1; -; mRNA. DR EMBL; BC133588; AAI33589.2; -; mRNA. DR PIR; S25011; S25011. DR RefSeq; NP_786987.1; NM_175793.2. DR AlphaFoldDB; P46196; -. DR BMRB; P46196; -. DR SMR; P46196; -. DR STRING; 9913.ENSBTAP00000013623; -. DR iPTMnet; P46196; -. DR PaxDb; 9913-ENSBTAP00000013623; -. DR Ensembl; ENSBTAT00000013623.6; ENSBTAP00000013623.6; ENSBTAG00000010312.6. DR GeneID; 327672; -. DR KEGG; bta:327672; -. DR CTD; 5594; -. DR VEuPathDB; HostDB:ENSBTAG00000010312; -. DR VGNC; VGNC:31212; MAPK1. DR eggNOG; KOG0660; Eukaryota. DR GeneTree; ENSGT00940000156771; -. DR HOGENOM; CLU_000288_181_1_1; -. DR InParanoid; P46196; -. DR OMA; SFFDFDY; -. DR OrthoDB; 158564at2759; -. DR Reactome; R-BTA-111995; phospho-PLA2 pathway. DR Reactome; R-BTA-112409; RAF-independent MAPK1/3 activation. DR Reactome; R-BTA-112411; MAPK1 (ERK2) activation. DR Reactome; R-BTA-1181150; Signaling by NODAL. DR Reactome; R-BTA-1295596; Spry regulation of FGF signaling. DR Reactome; R-BTA-1502540; Signaling by Activin. DR Reactome; R-BTA-162658; Golgi Cisternae Pericentriolar Stack Reorganization. DR Reactome; R-BTA-170968; Frs2-mediated activation. DR Reactome; R-BTA-198753; ERK/MAPK targets. DR Reactome; R-BTA-202670; ERKs are inactivated. DR Reactome; R-BTA-2029482; Regulation of actin dynamics for phagocytic cup formation. DR Reactome; R-BTA-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity. DR Reactome; R-BTA-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription. DR Reactome; R-BTA-2559580; Oxidative Stress Induced Senescence. DR Reactome; R-BTA-2559582; Senescence-Associated Secretory Phenotype (SASP). DR Reactome; R-BTA-2559585; Oncogene Induced Senescence. DR Reactome; R-BTA-2871796; FCERI mediated MAPK activation. DR Reactome; R-BTA-3371453; Regulation of HSF1-mediated heat shock response. DR Reactome; R-BTA-375165; NCAM signaling for neurite out-growth. DR Reactome; R-BTA-437239; Recycling pathway of L1. DR Reactome; R-BTA-445144; Signal transduction by L1. DR Reactome; R-BTA-450341; Activation of the AP-1 family of transcription factors. DR Reactome; R-BTA-456926; Thrombin signalling through proteinase activated receptors (PARs). DR Reactome; R-BTA-5654726; Negative regulation of FGFR1 signaling. DR Reactome; R-BTA-5654727; Negative regulation of FGFR2 signaling. DR Reactome; R-BTA-5654732; Negative regulation of FGFR3 signaling. DR Reactome; R-BTA-5654733; Negative regulation of FGFR4 signaling. DR Reactome; R-BTA-5663213; RHO GTPases Activate WASPs and WAVEs. DR Reactome; R-BTA-5668599; RHO GTPases Activate NADPH Oxidases. DR Reactome; R-BTA-5673001; RAF/MAP kinase cascade. DR Reactome; R-BTA-5674135; MAP2K and MAPK activation. DR Reactome; R-BTA-5674499; Negative feedback regulation of MAPK pathway. DR Reactome; R-BTA-5675221; Negative regulation of MAPK pathway. DR Reactome; R-BTA-6798695; Neutrophil degranulation. DR Reactome; R-BTA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. DR Reactome; R-BTA-74749; Signal attenuation. DR Reactome; R-BTA-877300; Interferon gamma signaling. DR Reactome; R-BTA-881907; Gastrin-CREB signalling pathway via PKC and MAPK. DR Reactome; R-BTA-8939211; ESR-mediated signaling. DR Reactome; R-BTA-9627069; Regulation of the apoptosome activity. DR Reactome; R-BTA-9634635; Estrogen-stimulated signaling through PRKCZ. DR Reactome; R-BTA-9634638; Estrogen-dependent nuclear events downstream of ESR-membrane signaling. DR Reactome; R-BTA-9732724; IFNG signaling activates MAPKs. DR Reactome; R-BTA-982772; Growth hormone receptor signaling. DR Proteomes; UP000009136; Chromosome 17. DR Bgee; ENSBTAG00000010312; Expressed in temporal cortex and 105 other cell types or tissues. DR GO; GO:0005901; C:caveola; ISS:UniProtKB. DR GO; GO:0005813; C:centrosome; IEA:UniProtKB-SubCell. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005769; C:early endosome; IEA:UniProt. DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell. DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProt. DR GO; GO:0005770; C:late endosome; IEA:UniProt. DR GO; GO:0072686; C:mitotic spindle; ISS:UniProtKB. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004707; F:MAP kinase activity; IEA:UniProtKB-EC. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0072584; P:caveolin-mediated endocytosis; IEA:UniProt. DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW. DR GO; GO:0007166; P:cell surface receptor signaling pathway; IBA:GO_Central. DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central. DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:UniProtKB. DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISS:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB. DR GO; GO:0051493; P:regulation of cytoskeleton organization; IEA:UniProt. DR GO; GO:2000641; P:regulation of early endosome to late endosome transport; IEA:UniProt. DR GO; GO:0090170; P:regulation of Golgi inheritance; IEA:UniProt. DR GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB. DR GO; GO:0032872; P:regulation of stress-activated MAPK cascade; IEA:UniProt. DR GO; GO:0070849; P:response to epidermal growth factor; ISS:UniProtKB. DR CDD; cd07849; STKc_ERK1_2_like; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR003527; MAP_kinase_CS. DR InterPro; IPR008349; MAPK_ERK1/2. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR24055; MITOGEN-ACTIVATED PROTEIN KINASE; 1. DR PANTHER; PTHR24055:SF599; MITOGEN-ACTIVATED PROTEIN KINASE 1; 1. DR Pfam; PF00069; Pkinase; 1. DR PRINTS; PR01770; ERK1ERK2MAPK. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS01351; MAPK; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. PE 2: Evidence at transcript level; KW Acetylation; Apoptosis; ATP-binding; Cell cycle; Cell junction; Cytoplasm; KW Cytoskeleton; Kinase; Membrane; Nucleotide-binding; Nucleus; KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; KW Transferase; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:P28482" FT CHAIN 2..360 FT /note="Mitogen-activated protein kinase 1" FT /id="PRO_0000186246" FT DOMAIN 25..313 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOTIF 185..187 FT /note="TXY" FT ACT_SITE 149 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 31..39 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 54 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000250|UniProtKB:P28482" FT MOD_RES 29 FT /note="Phosphoserine; by SGK1" FT /evidence="ECO:0000250|UniProtKB:P28482" FT MOD_RES 185 FT /note="Phosphothreonine; by MAP2K1 and MAP2K2" FT /evidence="ECO:0000250|UniProtKB:P28482" FT MOD_RES 187 FT /note="Phosphotyrosine; by MAP2K1 and MAP2K2" FT /evidence="ECO:0000250|UniProtKB:P28482" FT MOD_RES 190 FT /note="Phosphothreonine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P28482" FT MOD_RES 246 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P28482" FT MOD_RES 248 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P28482" FT MOD_RES 284 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P28482" SQ SEQUENCE 360 AA; 41376 MW; E85D0B2A4E9549DE CRC64; MAAAAAAGAG PEMVRGQVFD VGPRYTNLSY IGEGAYGMVC SAYDNVNKVR VAIKKISPFE HQTYCQRTLR EIKILLRFRH ENIIGINDII RAPTIEQMKD VYIVQDLMET DLYKLLKTQH LSNDHICYFL YQILRGLKYI HSANVLHRDL KPSNLLLNTT CDLKICDFGL ARVADPDHDH TGFLTEYVAT RWYRAPEIML NSKGYTKSID IWSVGCILAE MLSNRPIFPG KHYLDQLNHI LGILGSPSQE DLNCIINLKA RNYLLSLPHK NKVPWNRLFP NADSKALDLL DKMLTFNPHK RIEVEQALAH PYLEQYYDPS DEPVAEAPFK FDMELDDLPK EKLKELIFEE TARFQPGYRS //