ID   MK01_XENLA              Reviewed;         361 AA.
AC   P26696; Q5D061;
DT   01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT   14-NOV-2006, sequence version 3.
DT   27-MAR-2024, entry version 150.
DE   RecName: Full=Mitogen-activated protein kinase 1;
DE            Short=MAP kinase 1;
DE            Short=MAPK 1;
DE            EC=2.7.11.24;
DE   AltName: Full=M phase MAP kinase;
DE   AltName: Full=Myelin basic protein kinase;
DE            Short=MBP kinase;
DE   AltName: Full=Myelin xP42 protein kinase;
GN   Name=mapk1; Synonyms=mpk1;
OS   Xenopus laevis (African clawed frog).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX   NCBI_TaxID=8355;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Ovary;
RX   PubMed=1708093; DOI=10.1128/mcb.11.5.2517-2528.1991;
RA   Posada J., Sanghera J., Pelech S., Aebersold R., Cooper J.A.;
RT   "Tyrosine phosphorylation and activation of homologous protein kinases
RT   during oocyte maturation and mitogenic activation of fibroblasts.";
RL   Mol. Cell. Biol. 11:2517-2528(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, ACTIVITY
RP   REGULATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC   TISSUE=Oocyte;
RX   PubMed=1714387; DOI=10.1002/j.1460-2075.1991.tb07809.x;
RA   Gotoh Y., Moriyama K., Matsuda S., Okumura E., Kishimoto T., Kawasaki H.,
RA   Suzuki K., Yahara I., Sakai H., Nishida E.;
RT   "Xenopus M phase MAP kinase: isolation of its cDNA and activation by MPF.";
RL   EMBO J. 10:2661-2668(1991).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Tail bud;
RG   NIH - Xenopus Gene Collection (XGC) project;
RL   Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   PHOSPHORYLATION AT THR-188 AND TYR-190, MUTAGENESIS OF LYS-57; ILE-86;
RP   THR-188 AND TYR-190, AND ACTIVITY REGULATION.
RX   PubMed=1313186; DOI=10.1126/science.1313186;
RA   Posada J., Cooper J.A.;
RT   "Requirements for phosphorylation of MAP kinase during meiosis in Xenopus
RT   oocytes.";
RL   Science 255:212-215(1992).
RN   [5]
RP   FUNCTION, SUBCELLULAR LOCATION, AND ACTIVITY REGULATION.
RX   PubMed=9128253; DOI=10.1083/jcb.137.2.433;
RA   Wang X.M., Zhai Y., Ferrell J.E. Jr.;
RT   "A role for mitogen-activated protein kinase in the spindle assembly
RT   checkpoint in XTC cells.";
RL   J. Cell Biol. 137:433-443(1997).
RN   [6]
RP   FUNCTION, AND ACTIVITY REGULATION.
RX   PubMed=11854404; DOI=10.1091/mbc.01-11-0553;
RA   Sohaskey M.L., Ferrell J.E. Jr.;
RT   "Activation of p42 mitogen-activated protein kinase (MAPK), but not c-Jun
RT   NH(2)-terminal kinase, induces phosphorylation and stabilization of MAPK
RT   phosphatase XCL100 in Xenopus oocytes.";
RL   Mol. Biol. Cell 13:454-468(2002).
RN   [7]
RP   INTERACTION WITH CDK2AP2.
RX   PubMed=12944431; DOI=10.1242/dev.00731;
RA   Terret M.E., Lefebvre C., Djiane A., Rassinier P., Moreau J., Maro B.,
RA   Verlhac M.H.;
RT   "DOC1R: a MAP kinase substrate that control microtubule organization of
RT   metaphase II mouse oocytes.";
RL   Development 130:5169-5177(2003).
CC   -!- FUNCTION: Serine/threonine kinase which acts as an essential component
CC       of the MAP kinase signal transduction pathway. Plays an important role
CC       in the MAPK/ERK cascade. Depending on the cellular context, this
CC       cascade mediates diverse biological functions such as cell growth,
CC       adhesion, survival and differentiation through the regulation of
CC       transcription, translation, cytoskeletal rearrangements. The MAPK/ERK
CC       cascade also plays a role in initiation and regulation of meiosis,
CC       mitosis, and postmitotic functions in differentiated cells by
CC       phosphorylating a number of transcription factors. Many of the
CC       substrates are localized in the nucleus, and seem to participate in the
CC       regulation of transcription upon stimulation. However, other substrates
CC       are found in the cytosol as well as in other cellular organelles, and
CC       those are responsible for processes such as translation, mitosis and
CC       apoptosis. Moreover, the MAPK/ERK cascade is also involved in the
CC       regulation of the endosomal dynamics, including lysosome processing and
CC       endosome cycling through the perinuclear recycling compartment (PNRC);
CC       as well as in the fragmentation of the Golgi apparatus during mitosis.
CC       Phosphorylates microtubule-associated protein 2 (MAP2), myelin basic
CC       protein (MBP) and Elk-1. Phosphorylates dual specificity protein
CC       phosphatase 1 (DUSP1) during meiosis, increasing its stability.
CC       Activated by M phase promoting factor (MPF). Plays a role in the
CC       spindle assembly checkpoint. {ECO:0000269|PubMed:11854404,
CC       ECO:0000269|PubMed:1714387, ECO:0000269|PubMed:9128253}.
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: Activated by tyrosine phosphorylation during the M
CC       phase of the meiotic cell cycle. Dephosphorylated and inactivated by
CC       DUSP1. {ECO:0000269|PubMed:11854404, ECO:0000269|PubMed:1313186,
CC       ECO:0000269|PubMed:1714387, ECO:0000269|PubMed:9128253}.
CC   -!- SUBUNIT: Interacts with CDK2AP2 (PubMed:12944431).
CC       {ECO:0000269|PubMed:12944431}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC       center, centrosome {ECO:0000250}. Cytoplasm
CC       {ECO:0000269|PubMed:9128253}. Cytoplasm, cytoskeleton, spindle
CC       {ECO:0000269|PubMed:9128253}. Note=Associated with the spindle during
CC       prometaphase and metaphase in cultured XTC cells.
CC   -!- TISSUE SPECIFICITY: Expressed in the central nervous system, kidney,
CC       liver, intestine and the hematopoietic system. Also found in heart,
CC       muscle, pancreas and lung. {ECO:0000269|PubMed:1714387}.
CC   -!- DEVELOPMENTAL STAGE: Is expressed in the early oocyte and is maintained
CC       at a constant level during embryogenesis. Its level declines at the
CC       mid-blastula transition. {ECO:0000269|PubMed:1714387}.
CC   -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues
CC       whose phosphorylation activates the MAP kinases.
CC   -!- PTM: Dually phosphorylated on Thr-188 and Tyr-190, which activates the
CC       enzyme. {ECO:0000269|PubMed:1313186}.
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; M60977; AAA50002.1; -; mRNA.
DR   EMBL; X59813; CAA42482.1; -; mRNA.
DR   EMBL; BC060748; AAH60748.1; -; mRNA.
DR   PIR; A39754; A39754.
DR   RefSeq; NP_001083548.1; NM_001090079.1.
DR   AlphaFoldDB; P26696; -.
DR   SMR; P26696; -.
DR   BioGRID; 100311; 3.
DR   IntAct; P26696; 1.
DR   MINT; P26696; -.
DR   iPTMnet; P26696; -.
DR   MaxQB; P26696; -.
DR   DNASU; 398985; -.
DR   GeneID; 398985; -.
DR   KEGG; xla:398985; -.
DR   AGR; Xenbase:XB-GENE-865273; -.
DR   CTD; 398985; -.
DR   OMA; SFFDFDY; -.
DR   OrthoDB; 158564at2759; -.
DR   BRENDA; 2.7.11.24; 6725.
DR   Proteomes; UP000186698; Chromosome 1S.
DR   Bgee; 398985; Expressed in brain and 19 other cell types or tissues.
DR   GO; GO:0005813; C:centrosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0072686; C:mitotic spindle; IDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; 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:0007094; P:mitotic spindle assembly checkpoint signaling; IMP:UniProtKB.
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:0031647; P:regulation of protein stability; IDA:UniProtKB.
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   1: Evidence at protein level;
KW   Apoptosis; ATP-binding; Cell cycle; Cytoplasm; Cytoskeleton;
KW   Direct protein sequencing; Kinase; Nucleotide-binding; Phosphoprotein;
KW   Reference proteome; Serine/threonine-protein kinase; Transferase.
FT   CHAIN           1..361
FT                   /note="Mitogen-activated protein kinase 1"
FT                   /id="PRO_0000186250"
FT   DOMAIN          28..316
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOTIF           188..190
FT                   /note="TXY"
FT   ACT_SITE        152
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   BINDING         34..42
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         57
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000305"
FT   MOD_RES         188
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000269|PubMed:1313186"
FT   MOD_RES         190
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000269|PubMed:1313186"
FT   MUTAGEN         57
FT                   /note="K->R: Inactivation."
FT                   /evidence="ECO:0000269|PubMed:1313186"
FT   MUTAGEN         86
FT                   /note="I->Y: Inactivation."
FT                   /evidence="ECO:0000269|PubMed:1313186"
FT   MUTAGEN         188
FT                   /note="T->V,D: No effect on Tyr phosphorylation."
FT                   /evidence="ECO:0000269|PubMed:1313186"
FT   MUTAGEN         190
FT                   /note="Y->F: Affects Thr phosphorylation."
FT                   /evidence="ECO:0000269|PubMed:1313186"
FT   CONFLICT        5..7
FT                   /note="GAA -> AAS (in Ref. 1; AAA50002)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        29
FT                   /note="I -> T (in Ref. 1; AAA50002)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        32
FT                   /note="A -> S (in Ref. 1; AAA50002)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        47..49
FT                   /note="DNV -> CNI (in Ref. 1; AAA50002)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   361 AA;  41257 MW;  D14EFF145A183EC6 CRC64;
     MAAAGAASNP GGGPEMVRGQ AFDVGPRYIN LAYIGEGAYG MVCSAHDNVN KVRVAIKKIS
     PFEHQTYCQR TLREIKILLR FKHENIIGIN DIIRAPTIEQ MKDVYIVQDL METDLYKLLK
     TQHLSNDHIC YFLYQILRGL KYIHSANVLH RDLKPSNLLL NTTCDLKICD FGLARVADPD
     HDHTGFLTEY VATRWYRAPE IMLNSKGYTK SIDIWSVGCI LAEMLSNRPI FPGKHYLDQL
     NHILGILGSP SQEDLNCIIN LKARNYLLSL PHKNKVPWNR LFPNADPKAL DLLDKMLTFN
     PHKRIEVEAA LAHPYLEQYY DPSDEPVAEA PFKFEMELDD LPKETLKELI FEETARFQPG
     Y
//