MK01_BOVIN
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 03-AUG-2022, entry version 178.
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 a variety of other signaling-related
CC molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as
CC RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK,
CC MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or
CC MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are
CC other substrates which enable the propagation the MAPK/ERK signal to
CC additional cytosolic and nuclear targets, thereby extending the
CC specificity of the cascade. Mediates phosphorylation of TPR in response
CC to EGF stimulation. May play a role in the spindle assembly checkpoint
CC (By similarity). Phosphorylates PML and promotes its interaction with
CC PIN1, leading to PML degradation. Phosphorylates CDK2AP2.
CC {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 -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. MAP kinase subfamily. {ECO:0000305}.
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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; P46196; -.
DR PRIDE; P46196; -.
DR Ensembl; ENSBTAT00000013623; ENSBTAP00000013623; ENSBTAG00000010312.
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; 741207at2759; -.
DR Proteomes; UP000009136; Chromosome 17.
DR Bgee; ENSBTAG00000010312; Expressed in temporal cortex and 105 other tissues.
DR GO; GO:0005901; C:caveola; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
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:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
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:0031143; C:pseudopodium; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0004707; F:MAP kinase activity; IBA:GO_Central.
DR GO; GO:0004708; F:MAP kinase kinase activity; IEA:Ensembl.
DR GO; GO:0019902; F:phosphatase binding; IEA:Ensembl.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IEA:Ensembl.
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:0008353; F:RNA polymerase II CTD heptapeptide repeat kinase activity; IEA:Ensembl.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0050853; P:B cell receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0060020; P:Bergmann glial cell differentiation; IEA:Ensembl.
DR GO; GO:0061308; P:cardiac neural crest cell development involved in heart development; IEA:Ensembl.
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:0034198; P:cellular response to amino acid starvation; IEA:Ensembl.
DR GO; GO:0071276; P:cellular response to cadmium ion; IEA:Ensembl.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IEA:Ensembl.
DR GO; GO:1903351; P:cellular response to dopamine; IEA:Ensembl.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; IEA:Ensembl.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
DR GO; GO:0019858; P:cytosine metabolic process; IEA:Ensembl.
DR GO; GO:0038127; P:ERBB signaling pathway; IEA:Ensembl.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0060324; P:face development; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0060716; P:labyrinthine layer blood vessel development; IEA:Ensembl.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0060291; P:long-term synaptic potentiation; IEA:Ensembl.
DR GO; GO:0060425; P:lung morphogenesis; IEA:Ensembl.
DR GO; GO:0033598; P:mammary gland epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0045596; P:negative regulation of cell differentiation; IEA:Ensembl.
DR GO; GO:0042473; P:outer ear morphogenesis; IEA:Ensembl.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:UniProtKB.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISS:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; IEA:Ensembl.
DR GO; GO:0120041; P:positive regulation of macrophage proliferation; IEA:Ensembl.
DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; IEA:Ensembl.
DR GO; GO:0051973; P:positive regulation of telomerase activity; IEA:Ensembl.
DR GO; GO:1904355; P:positive regulation of telomere capping; IEA:Ensembl.
DR GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0030641; P:regulation of cellular pH; IEA:Ensembl.
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:0030278; P:regulation of ossification; IEA:Ensembl.
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 GO; GO:0043330; P:response to exogenous dsRNA; IEA:Ensembl.
DR GO; GO:0035094; P:response to nicotine; IEA:Ensembl.
DR GO; GO:0051403; P:stress-activated MAPK cascade; IEA:Ensembl.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0048538; P:thymus development; IEA:Ensembl.
DR GO; GO:0030878; P:thyroid gland development; IEA:Ensembl.
DR GO; GO:0060440; P:trachea formation; IEA:Ensembl.
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 Pfam; PF00069; Pkinase; 1.
DR PRINTS; PR01770; ERK1ERK2MAPK.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 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
