MK01_MOUSE
ID MK01_MOUSE Reviewed; 358 AA.
AC P63085; P27703; Q3V1U6;
DT 13-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Mitogen-activated protein kinase 1 {ECO:0000305};
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=MAP kinase isoform p42;
DE Short=p42-MAPK;
DE AltName: Full=Mitogen-activated protein kinase 2;
DE Short=MAP kinase 2;
DE Short=MAPK 2;
GN Name=Mapk1 {ECO:0000312|MGI:MGI:1346858}; Synonyms=Erk2, Mapk, Prkm1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=SWR/J; TISSUE=Fibroblast;
RX PubMed=1649458; DOI=10.1093/nar/19.13.3743;
RA Her J.-H., Wu J.-S., Rall T.B., Sturgill T.W., Weber M.J.;
RT "Sequence of pp42/MAP kinase, a serine/threonine kinase regulated by
RT tyrosine phosphorylation.";
RL Nucleic Acids Res. 19:3743-3743(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Brain, Head, Thymus, and Urinary bladder;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 54-65; 76-89; 137-162; 171-189; 193-201 AND 260-268,
RP AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=C57BL/6J, and OF1; TISSUE=Brain, and Hippocampus;
RA Lubec G., Klug S., Kang S.U., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 152-190.
RC STRAIN=CBA/J; TISSUE=Bone marrow;
RX PubMed=8444355; DOI=10.1016/0378-1119(93)90411-u;
RA Ershler M.A., Nagorskaya T.V., Visser J.W.M., Belyavsky A.V.;
RT "Novel CDC2-related protein kinases produced in murine hematopoietic stem
RT cells.";
RL Gene 124:305-306(1993).
RN [6]
RP PHOSPHORYLATION AT THR-183 AND TYR-185, AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=1849075; DOI=10.1002/j.1460-2075.1991.tb08021.x;
RA Payne D.M., Rossomando A.J., Martino P., Erickson A.K., Her J.-H.,
RA Shabanowitz J., Hunt D.F., Weber M.J., Sturgill T.W.;
RT "Identification of the regulatory phosphorylation sites in pp42/mitogen-
RT activated protein kinase (MAP kinase).";
RL EMBO J. 10:885-892(1991).
RN [7]
RP PHOSPHORYLATION AT THR-183 AND TYR-185, DEPHOSPHORYLATION BY DUSP1, AND
RP ACTIVITY REGULATION.
RX PubMed=8221888; DOI=10.1016/0092-8674(93)90383-2;
RA Sun H., Charles C.H., Lau L.F., Tonks N.K.;
RT "MKP-1 (3CH134), an immediate early gene product, is a dual specificity
RT phosphatase that dephosphorylates MAP kinase in vivo.";
RL Cell 75:487-493(1993).
RN [8]
RP PHOSPHORYLATION IN RESPONSE TO FLT3 SIGNALING.
RX PubMed=10080542; DOI=10.1002/jlb.65.3.372;
RA Zhang S., Mantel C., Broxmeyer H.E.;
RT "Flt3 signaling involves tyrosyl-phosphorylation of SHP-2 and SHIP and
RT their association with Grb2 and Shc in Baf3/Flt3 cells.";
RL J. Leukoc. Biol. 65:372-380(1999).
RN [9]
RP PHOSPHORYLATION IN RESPONSE TO FLT3 SIGNALING.
RX PubMed=11090077;
RA Mizuki M., Fenski R., Halfter H., Matsumura I., Schmidt R., Muller C.,
RA Gruning W., Kratz-Albers K., Serve S., Steur C., Buchner T., Kienast J.,
RA Kanakura Y., Berdel W.E., Serve H.;
RT "Flt3 mutations from patients with acute myeloid leukemia induce
RT transformation of 32D cells mediated by the Ras and STAT5 pathways.";
RL Blood 96:3907-3914(2000).
RN [10]
RP FUNCTION IN PHOSPHORYLATION OF PXN.
RX PubMed=10753946; DOI=10.1074/jbc.275.15.11333;
RA Ku H., Meier K.E.;
RT "Phosphorylation of paxillin via the ERK mitogen-activated protein kinase
RT cascade in EL4 thymoma cells.";
RL J. Biol. Chem. 275:11333-11340(2000).
RN [11]
RP INTERACTION WITH PEA15, SUBCELLULAR LOCATION, AND FUNCTION OF THE MAPK ERK
RP CASCADE.
RX PubMed=11702783; DOI=10.1016/s1534-5807(01)00035-1;
RA Formstecher E., Ramos J.W., Fauquet M., Calderwood D.A., Hsieh J.C.,
RA Canton B., Nguyen X.T., Barnier J.V., Camonis J., Ginsberg M.H.,
RA Chneiweiss H.;
RT "PEA-15 mediates cytoplasmic sequestration of ERK MAP kinase.";
RL Dev. Cell 1:239-250(2001).
RN [12]
RP FUNCTION IN PHOSPHORYLATION OF FOS, AND SUBCELLULAR LOCATION.
RX PubMed=12134156; DOI=10.1038/ncb822;
RA Murphy L.O., Smith S., Chen R.H., Fingar D.C., Blenis J.;
RT "Molecular interpretation of ERK signal duration by immediate early gene
RT products.";
RL Nat. Cell Biol. 4:556-564(2002).
RN [13]
RP INTERACTION WITH MORG1.
RX PubMed=15118098; DOI=10.1073/pnas.0305894101;
RA Vomastek T., Schaeffer H.-J., Tarcsafalvi A., Smolkin M.E.,
RA Bissonette E.A., Weber M.J.;
RT "Modular construction of a signaling scaffold: MORG1 interacts with
RT components of the ERK cascade and links ERK signaling to specific
RT agonists.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:6981-6986(2004).
RN [14]
RP PHOSPHORYLATION OF SPZ1.
RX PubMed=15899793; DOI=10.1158/0008-5472.can-04-3658;
RA Hsu S.-H., Hsieh-Li H.-M., Huang H.-Y., Huang P.-H., Li H.;
RT "bHLH-zip transcription factor Spz1 mediates mitogen-activated protein
RT kinase cell proliferation, transformation, and tumorigenesis.";
RL Cancer Res. 65:4041-4050(2005).
RN [15]
RP INTERACTION WITH GIT1, AND SUBCELLULAR LOCATION.
RX PubMed=15923189; DOI=10.1074/jbc.m502271200;
RA Yin G., Zheng Q., Yan C., Berk B.C.;
RT "GIT1 is a scaffold for ERK1/2 activation in focal adhesions.";
RL J. Biol. Chem. 280:27705-27712(2005).
RN [16]
RP INTERACTION WITH MKNK2.
RX PubMed=16162500; DOI=10.1074/jbc.m508356200;
RA Parra J.L., Buxade M., Proud C.G.;
RT "Features of the catalytic domains and C termini of the MAPK signal-
RT integrating kinases Mnk1 and Mnk2 determine their differing activities and
RT regulatory properties.";
RL J. Biol. Chem. 280:37623-37633(2005).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-183 AND TYR-185, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-183 AND TYR-185, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-183 AND TYR-185, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-183 AND TYR-185, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-183 AND TYR-185, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [22]
RP PHOSPHORYLATION IN RESPONSE TO FLT3 SIGNALING.
RX PubMed=21262971; DOI=10.1074/jbc.m110.205021;
RA Arora D., Stopp S., Bohmer S.A., Schons J., Godfrey R., Masson K.,
RA Razumovskaya E., Ronnstrand L., Tanzer S., Bauer R., Bohmer F.D.,
RA Muller J.P.;
RT "Protein-tyrosine phosphatase DEP-1 controls receptor tyrosine kinase FLT3
RT signaling.";
RL J. Biol. Chem. 286:10918-10929(2011).
RN [23]
RP REVIEW ON FUNCTION.
RX PubMed=16393692; DOI=10.1080/02699050500284218;
RA Yoon S., Seger R.;
RT "The extracellular signal-regulated kinase: multiple substrates regulate
RT diverse cellular functions.";
RL Growth Factors 24:21-44(2006).
RN [24]
RP REVIEW ON FUNCTION, AND REVIEW ON SUBCELLULAR LOCATION.
RX PubMed=19565474; DOI=10.1002/biof.52;
RA Yao Z., Seger R.;
RT "The ERK signaling cascade--views from different subcellular
RT compartments.";
RL BioFactors 35:407-416(2009).
RN [25]
RP REVIEW ON ACTIVITY REGULATION, AND REVIEW ON FUNCTION.
RX PubMed=21779493; DOI=10.1177/1947601911407328;
RA Wortzel I., Seger R.;
RT "The ERK cascade: distinct functions within various subcellular
RT organelles.";
RL Genes Cancer 2:195-209(2011).
RN [26]
RP ISGYLATION.
RX PubMed=22022510; DOI=10.1371/journal.pone.0026068;
RA Maragno A.L., Pironin M., Alcalde H., Cong X., Knobeloch K.P., Tangy F.,
RA Zhang D.E., Ghysdael J., Quang C.T.;
RT "ISG15 modulates development of the erythroid lineage.";
RL PLoS ONE 6:E26068-E26068(2011).
RN [27]
RP INTERACTION WITH DUSP7.
RX PubMed=27783954; DOI=10.1016/j.celrep.2016.10.007;
RA Tischer T., Schuh M.;
RT "The phosphatase Dusp7 drives meiotic resumption and chromosome alignment
RT in mouse oocytes.";
RL Cell Rep. 17:1426-1437(2016).
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 Phosphorylates PML and promotes its interaction with PIN1, leading to
CC PML degradation. Phosphorylates CDK2AP2 (By similarity).
CC {ECO:0000250|UniProtKB:P28482, ECO:0000250|UniProtKB:P63086,
CC ECO:0000269|PubMed:10753946, ECO:0000269|PubMed:11702783,
CC ECO:0000269|PubMed:12134156, ECO:0000303|PubMed:16393692,
CC ECO:0000303|PubMed:19565474, ECO:0000303|PubMed:21779493}.
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-183 and Tyr-185 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-27 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.
CC {ECO:0000269|PubMed:8221888}.
CC -!- SUBUNIT: Binds both upstream activators and downstream substrates in
CC multimolecular complexes. This interaction inhibits its tyrosine-kinase
CC activity. Interacts with ADAM15, ARHGEF2, ARRB2, DAPK1 (via death
CC domain), HSF4, IER3, IPO7, NISCH, SGK1, and isoform 1 of NEK2.
CC Interacts (via phosphorylated form) with TPR (via C-terminal region and
CC phosphorylated form); the interaction requires dimerization of
CC MAPK1/ERK2 and increases following EGF stimulation (By similarity).
CC Interacts with MAP2K1 (By similarity). Interacts with DUSP6 (By
CC similarity). Interacts (phosphorylated form) with CAV2 ('Tyr-19'-
CC phosphorylated form); the interaction, promoted by insulin, leads to
CC nuclear location and MAPK1 activation. Interacts with DCC (By
CC similarity). Interacts with MORG1 (PubMed:15118098). Interacts with
CC PEA15 (PubMed:16162500). Interacts with MKNK2. MKNK2 isoform 1 binding
CC prevents from dephosphorylation and inactivation (PubMed:11702783). The
CC phosphorylated form interacts with PML. Interacts with STYX. Interacts
CC with CDK2AP2. Interacts with CAVIN4 (By similarity). Interacts with
CC DUSP7; the interaction enhances DUSP7 phosphatase activity
CC (PubMed:27783954). Interacts with GIT1; this interaction is necessary
CC for MAPK1 localization to focal adhesions (PubMed:15923189). Interacts
CC with ZNF263 (By similarity). {ECO:0000250|UniProtKB:P28482,
CC ECO:0000250|UniProtKB:P63086, ECO:0000269|PubMed:11702783,
CC ECO:0000269|PubMed:15118098, ECO:0000269|PubMed:15923189,
CC ECO:0000269|PubMed:16162500, ECO:0000269|PubMed:27783954}.
CC -!- INTERACTION:
CC P63085; Q62108: Dlg4; NbExp=4; IntAct=EBI-397697, EBI-300895;
CC P63085; Q9DBB1: Dusp6; NbExp=2; IntAct=EBI-397697, EBI-7812384;
CC P63085; Q03172: Hivep1; NbExp=4; IntAct=EBI-397697, EBI-646850;
CC P63085; P63085: Mapk1; NbExp=5; IntAct=EBI-397697, EBI-397697;
CC P63085; Q8CDB0: Mknk2; NbExp=23; IntAct=EBI-397697, EBI-646209;
CC P63085; Q8R332-1: Nup58; NbExp=3; IntAct=EBI-397697, EBI-646962;
CC P63085; Q62132: Ptprr; NbExp=5; IntAct=EBI-397697, EBI-6954051;
CC P63085; Q9Z2B9: Rps6ka4; NbExp=3; IntAct=EBI-397697, EBI-412887;
CC P63085; P49841: GSK3B; Xeno; NbExp=2; IntAct=EBI-397697, EBI-373586;
CC P63085; O95863: SNAI1; Xeno; NbExp=3; IntAct=EBI-397697, EBI-1045459;
CC P63085; A0A0F6AZL3: sseI; Xeno; NbExp=3; IntAct=EBI-397697, EBI-16463657;
CC P63085; G3G926: US2; Xeno; NbExp=8; IntAct=EBI-397697, EBI-11692733;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, spindle {ECO:0000250}.
CC Nucleus. Cytoplasm, cytoskeleton, microtubule organizing center,
CC centrosome {ECO:0000250}. Cytoplasm. Membrane, caveola
CC {ECO:0000250|UniProtKB:P63086}. Cell junction, focal adhesion
CC {ECO:0000269|PubMed:15923189}. Note=Associated with the spindle during
CC prometaphase and metaphase (By similarity). PEA15-binding and
CC phosphorylated DAPK1 promote its cytoplasmic retention. Phosphorylation
CC at Ser-244 and Ser-246 as well as autophosphorylation at Thr-188
CC promote nuclear localization (By similarity). Localization to focal
CC adhesions is stimulated by EGF (PubMed:15923189). {ECO:0000250,
CC ECO:0000269|PubMed:15923189}.
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues
CC whose phosphorylation activates the MAP kinases.
CC -!- PTM: Dually phosphorylated on Thr-183 and Tyr-185, which activates the
CC enzyme. Ligand-activated ALK induces tyrosine phosphorylation (By
CC similarity). Dephosphorylated by PTPRJ at Tyr-185 (By similarity).
CC Phosphorylated upon FLT3 and KIT signaling (By similarity).
CC Dephosphorylated by DUSP1 and DUSP2 at Thr-183 and Tyr-185 (By
CC similarity) (PubMed:8221888). {ECO:0000250,
CC ECO:0000250|UniProtKB:P28482, ECO:0000269|PubMed:8221888}.
CC -!- PTM: ISGylated. {ECO:0000269|PubMed:22022510}.
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; X58712; CAA41548.1; -; mRNA.
DR EMBL; AK035386; BAC29053.1; -; mRNA.
DR EMBL; AK048127; BAC33251.1; -; mRNA.
DR EMBL; AK087925; BAC40044.1; -; mRNA.
DR EMBL; AK132241; BAE21053.1; -; mRNA.
DR EMBL; BC058258; AAH58258.1; -; mRNA.
DR EMBL; D10939; BAA01733.1; -; mRNA.
DR CCDS; CCDS27992.1; -.
DR PIR; S16444; S16444.
DR RefSeq; NP_001033752.1; NM_001038663.1.
DR RefSeq; NP_036079.1; NM_011949.3.
DR RefSeq; XP_006522210.1; XM_006522147.3.
DR AlphaFoldDB; P63085; -.
DR BMRB; P63085; -.
DR SMR; P63085; -.
DR BioGRID; 204966; 84.
DR CORUM; P63085; -.
DR DIP; DIP-661N; -.
DR ELM; P63085; -.
DR IntAct; P63085; 41.
DR MINT; P63085; -.
DR STRING; 10090.ENSMUSP00000065983; -.
DR BindingDB; P63085; -.
DR ChEMBL; CHEMBL2207; -.
DR MoonDB; P63085; Predicted.
DR iPTMnet; P63085; -.
DR PhosphoSitePlus; P63085; -.
DR SwissPalm; P63085; -.
DR EPD; P63085; -.
DR jPOST; P63085; -.
DR MaxQB; P63085; -.
DR PaxDb; P63085; -.
DR PeptideAtlas; P63085; -.
DR PRIDE; P63085; -.
DR ProteomicsDB; 295630; -.
DR Antibodypedia; 3785; 1901 antibodies from 55 providers.
DR DNASU; 26413; -.
DR Ensembl; ENSMUST00000069107; ENSMUSP00000065983; ENSMUSG00000063358.
DR Ensembl; ENSMUST00000115731; ENSMUSP00000111396; ENSMUSG00000063358.
DR Ensembl; ENSMUST00000232611; ENSMUSP00000156154; ENSMUSG00000063358.
DR GeneID; 26413; -.
DR KEGG; mmu:26413; -.
DR UCSC; uc007yjq.1; mouse.
DR CTD; 5594; -.
DR MGI; MGI:1346858; Mapk1.
DR VEuPathDB; HostDB:ENSMUSG00000063358; -.
DR eggNOG; KOG0660; Eukaryota.
DR GeneTree; ENSGT00940000156771; -.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; P63085; -.
DR OMA; SFFDFDY; -.
DR OrthoDB; 741207at2759; -.
DR PhylomeDB; P63085; -.
DR TreeFam; TF105097; -.
DR BRENDA; 2.7.11.24; 3474.
DR Reactome; R-MMU-111995; phospho-PLA2 pathway.
DR Reactome; R-MMU-112409; RAF-independent MAPK1/3 activation.
DR Reactome; R-MMU-112411; MAPK1 (ERK2) activation.
DR Reactome; R-MMU-1181150; Signaling by NODAL.
DR Reactome; R-MMU-1295596; Spry regulation of FGF signaling.
DR Reactome; R-MMU-1502540; Signaling by Activin.
DR Reactome; R-MMU-162658; Golgi Cisternae Pericentriolar Stack Reorganization.
DR Reactome; R-MMU-170968; Frs2-mediated activation.
DR Reactome; R-MMU-198753; ERK/MAPK targets.
DR Reactome; R-MMU-202670; ERKs are inactivated.
DR Reactome; R-MMU-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-MMU-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
DR Reactome; R-MMU-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-MMU-2559582; Senescence-Associated Secretory Phenotype (SASP).
DR Reactome; R-MMU-2559585; Oncogene Induced Senescence.
DR Reactome; R-MMU-2871796; FCERI mediated MAPK activation.
DR Reactome; R-MMU-3371453; Regulation of HSF1-mediated heat shock response.
DR Reactome; R-MMU-375165; NCAM signaling for neurite out-growth.
DR Reactome; R-MMU-437239; Recycling pathway of L1.
DR Reactome; R-MMU-445144; Signal transduction by L1.
DR Reactome; R-MMU-450341; Activation of the AP-1 family of transcription factors.
DR Reactome; R-MMU-456926; Thrombin signalling through proteinase activated receptors (PARs).
DR Reactome; R-MMU-5654726; Negative regulation of FGFR1 signaling.
DR Reactome; R-MMU-5654727; Negative regulation of FGFR2 signaling.
DR Reactome; R-MMU-5654732; Negative regulation of FGFR3 signaling.
DR Reactome; R-MMU-5654733; Negative regulation of FGFR4 signaling.
DR Reactome; R-MMU-5663213; RHO GTPases Activate WASPs and WAVEs.
DR Reactome; R-MMU-5668599; RHO GTPases Activate NADPH Oxidases.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR Reactome; R-MMU-5674135; MAP2K and MAPK activation.
DR Reactome; R-MMU-5674499; Negative feedback regulation of MAPK pathway.
DR Reactome; R-MMU-5675221; Negative regulation of MAPK pathway.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-MMU-74749; Signal attenuation.
DR Reactome; R-MMU-8939211; ESR-mediated signaling.
DR Reactome; R-MMU-9627069; Regulation of the apoptosome activity.
DR Reactome; R-MMU-9634635; Estrogen-stimulated signaling through PRKCZ.
DR Reactome; R-MMU-9634638; Estrogen-dependent nuclear events downstream of ESR-membrane signaling.
DR Reactome; R-MMU-982772; Growth hormone receptor signaling.
DR BioGRID-ORCS; 26413; 10 hits in 76 CRISPR screens.
DR ChiTaRS; Mapk1; mouse.
DR PRO; PR:P63085; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; P63085; protein.
DR Bgee; ENSMUSG00000063358; Expressed in dentate gyrus of hippocampal formation granule cell and 274 other tissues.
DR ExpressionAtlas; P63085; baseline and differential.
DR Genevisible; P63085; MM.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0005901; C:caveola; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:AgBase.
DR GO; GO:0005856; C:cytoskeleton; TAS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:BHF-UCL.
DR GO; GO:0032839; C:dendrite cytoplasm; ISO:MGI.
DR GO; GO:0005769; C:early endosome; TAS:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; TAS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; TAS:UniProtKB.
DR GO; GO:0005770; C:late endosome; TAS:UniProtKB.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0072686; C:mitotic spindle; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:AgBase.
DR GO; GO:0043204; C:perikaryon; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0031143; C:pseudopodium; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0003690; F:double-stranded DNA binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0016301; F:kinase activity; IDA:MGI.
DR GO; GO:0004707; F:MAP kinase activity; IDA:MGI.
DR GO; GO:0004708; F:MAP kinase kinase activity; IMP:MGI.
DR GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; ISO:MGI.
DR GO; GO:0019902; F:phosphatase binding; IPI:UniProtKB.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IMP:MGI.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0008353; F:RNA polymerase II CTD heptapeptide repeat kinase activity; IDA:UniProtKB.
DR GO; GO:0007568; P:aging; ISO:MGI.
DR GO; GO:0009887; P:animal organ morphogenesis; IDA:MGI.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0050853; P:B cell receptor signaling pathway; IDA:MGI.
DR GO; GO:0060020; P:Bergmann glial cell differentiation; IGI:MGI.
DR GO; GO:0061308; P:cardiac neural crest cell development involved in heart development; IGI:MGI.
DR GO; GO:0072584; P:caveolin-mediated endocytosis; TAS:UniProtKB.
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; ISO:MGI.
DR GO; GO:0071276; P:cellular response to cadmium ion; ISO:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:MGI.
DR GO; GO:1903351; P:cellular response to dopamine; ISO:MGI.
DR GO; GO:0071310; P:cellular response to organic substance; ISO:MGI.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; ISO:MGI.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IGI:MGI.
DR GO; GO:0019858; P:cytosine metabolic process; IDA:MGI.
DR GO; GO:0046697; P:decidualization; ISO:MGI.
DR GO; GO:0015966; P:diadenosine tetraphosphate biosynthetic process; ISO:MGI.
DR GO; GO:0038127; P:ERBB signaling pathway; ISO:MGI.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IGI:MGI.
DR GO; GO:0060324; P:face development; IMP:MGI.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:MGI.
DR GO; GO:0060716; P:labyrinthine layer blood vessel development; IMP:MGI.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IDA:MGI.
DR GO; GO:0060291; P:long-term synaptic potentiation; IGI:MGI.
DR GO; GO:0060425; P:lung morphogenesis; IGI:MGI.
DR GO; GO:0033598; P:mammary gland epithelial cell proliferation; IDA:MGI.
DR GO; GO:0000165; P:MAPK cascade; IDA:MGI.
DR GO; GO:0045596; P:negative regulation of cell differentiation; IGI:MGI.
DR GO; GO:0014032; P:neural crest cell development; IGI:MGI.
DR GO; GO:0042473; P:outer ear morphogenesis; IGI:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:UniProtKB.
DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; ISO:MGI.
DR GO; GO:0120041; P:positive regulation of macrophage proliferation; ISO:MGI.
DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; ISO:MGI.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; ISO:MGI.
DR GO; GO:0051973; P:positive regulation of telomerase activity; ISO:MGI.
DR GO; GO:1904355; P:positive regulation of telomere capping; ISO:MGI.
DR GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0045727; P:positive regulation of translation; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
DR GO; GO:0030641; P:regulation of cellular pH; IMP:MGI.
DR GO; GO:0051493; P:regulation of cytoskeleton organization; TAS:UniProtKB.
DR GO; GO:0051090; P:regulation of DNA-binding transcription factor activity; NAS:UniProtKB.
DR GO; GO:2000641; P:regulation of early endosome to late endosome transport; TAS:UniProtKB.
DR GO; GO:0090170; P:regulation of Golgi inheritance; TAS:UniProtKB.
DR GO; GO:0030278; P:regulation of ossification; IGI:MGI.
DR GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB.
DR GO; GO:0032872; P:regulation of stress-activated MAPK cascade; TAS:UniProtKB.
DR GO; GO:0070849; P:response to epidermal growth factor; ISS:UniProtKB.
DR GO; GO:0043627; P:response to estrogen; ISO:MGI.
DR GO; GO:0043330; P:response to exogenous dsRNA; IDA:MGI.
DR GO; GO:0032496; P:response to lipopolysaccharide; IDA:MGI.
DR GO; GO:0035094; P:response to nicotine; IGI:ARUK-UCL.
DR GO; GO:0009636; P:response to toxic substance; ISO:MGI.
DR GO; GO:0019233; P:sensory perception of pain; ISO:MGI.
DR GO; GO:0007165; P:signal transduction; ISO:MGI.
DR GO; GO:0051403; P:stress-activated MAPK cascade; ISO:MGI.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IDA:MGI.
DR GO; GO:0048538; P:thymus development; IGI:MGI.
DR GO; GO:0030878; P:thyroid gland development; IGI:MGI.
DR GO; GO:0060440; P:trachea formation; IGI:MGI.
DR GO; GO:0006351; P:transcription, DNA-templated; NAS:UniProtKB.
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 1: Evidence at protein level;
KW Acetylation; Apoptosis; ATP-binding; Cell cycle; Cell junction; Cytoplasm;
KW Cytoskeleton; Direct protein sequencing; Kinase; Membrane;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P28482"
FT CHAIN 2..358
FT /note="Mitogen-activated protein kinase 1"
FT /id="PRO_0000186248"
FT DOMAIN 23..311
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOTIF 183..185
FT /note="TXY"
FT ACT_SITE 147
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 29..37
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 52
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 27
FT /note="Phosphoserine; by SGK1"
FT /evidence="ECO:0000250|UniProtKB:P28482"
FT MOD_RES 183
FT /note="Phosphothreonine; by MAP2K1 and MAP2K2"
FT /evidence="ECO:0000269|PubMed:1849075,
FT ECO:0007744|PubMed:17242355, ECO:0007744|PubMed:17947660,
FT ECO:0007744|PubMed:18034455, ECO:0007744|PubMed:19131326,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 185
FT /note="Phosphotyrosine; by MAP2K1 and MAP2K2"
FT /evidence="ECO:0000269|PubMed:1849075,
FT ECO:0007744|PubMed:17242355, ECO:0007744|PubMed:17947660,
FT ECO:0007744|PubMed:18034455, ECO:0007744|PubMed:19131326,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 188
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P28482"
FT MOD_RES 244
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P28482"
FT MOD_RES 246
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P28482"
FT MOD_RES 282
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P28482"
SQ SEQUENCE 358 AA; 41276 MW; 3BBCF22471EDBA0B CRC64;
MAAAAAAGPE MVRGQVFDVG PRYTNLSYIG EGAYGMVCSA YDNLNKVRVA IKKISPFEHQ
TYCQRTLREI KILLRFRHEN IIGINDIIRA PTIEQMKDVY IVQDLMETDL YKLLKTQHLS
NDHICYFLYQ ILRGLKYIHS ANVLHRDLKP SNLLLNTTCD LKICDFGLAR VADPDHDHTG
FLTEYVATRW YRAPEIMLNS KGYTKSIDIW SVGCILAEML SNRPIFPGKH YLDQLNHILG
ILGSPSQEDL NCIINLKARN YLLSLPHKNK VPWNRLFPNA DSKALDLLDK MLTFNPHKRI
EVEQALAHPY LEQYYDPSDE PIAEAPFKFD MELDDLPKEK LKELIFEETA RFQPGYRS
