MK14_MOUSE
ID MK14_MOUSE Reviewed; 360 AA.
AC P47811; B2KF37; B2KF38; O08666; Q3U6R5; Q3UZS3; Q8C289; Q9JLV8; Q9QZ80;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 231.
DE RecName: Full=Mitogen-activated protein kinase 14 {ECO:0000305};
DE Short=MAP kinase 14;
DE Short=MAPK 14;
DE EC=2.7.11.24 {ECO:0000269|PubMed:18669639, ECO:0000269|PubMed:22375048};
DE AltName: Full=CRK1;
DE AltName: Full=Mitogen-activated protein kinase p38 alpha;
DE Short=MAP kinase p38 alpha;
GN Name=Mapk14 {ECO:0000312|MGI:MGI:1346865}; Synonyms=Crk1, Csbp1, Csbp2;
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] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Liver;
RX PubMed=7914033; DOI=10.1126/science.7914033;
RA Han J., Lee J.-D., Bibbs L., Ulevitch R.J.;
RT "A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian
RT cells.";
RL Science 265:808-811(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Higashitsuji H., Fujita J.;
RL Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Kidney;
RA Faccio L., Fusco C., Zervos S.A.;
RT "Piccolo, a new alternative spliced form of p38/CSBP1/Mxi2 that is
RT specifically expressed in kidney and liver.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4).
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, Pituitary, and Thymus;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Liver;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 94-318 (ISOFORM 3).
RC TISSUE=Testis;
RA Yin Z., Li J., Sha J., Zhou Z., Lin M., Wang L.;
RL Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 154-186.
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 [9]
RP MUTAGENESIS.
RX PubMed=7839144; DOI=10.1126/science.7839144;
RA Derijard B., Raingeaud J., Barrett T., Wu I.-H., Han J., Ulevitch R.J.,
RA Davis R.J.;
RT "Independent human MAP-kinase signal transduction pathways defined by MEK
RT and MKK isoforms.";
RL Science 267:682-685(1995).
RN [10]
RP INTERACTION WITH PTPRR, AND SUBCELLULAR LOCATION.
RX PubMed=10601328; DOI=10.1083/jcb.147.6.1129;
RA Blanco-Aparicio C., Torres J., Pulido R.;
RT "A novel regulatory mechanism of MAP kinases activation and nuclear
RT translocation mediated by PKA and the PTP-SL tyrosine phosphatase.";
RL J. Cell Biol. 147:1129-1136(1999).
RN [11]
RP FUNCTION, AND ACTIVITY REGULATION.
RC TISSUE=Embryonic stem cell;
RX PubMed=10704466; DOI=10.1084/jem.191.5.859;
RA Allen M., Svensson L., Roach M., Hambor J., McNeish J., Gabel C.A.;
RT "Deficiency of the stress kinase p38alpha results in embryonic lethality:
RT characterization of the kinase dependence of stress responses of enzyme-
RT deficient embryonic stem cells.";
RL J. Exp. Med. 191:859-870(2000).
RN [12]
RP FUNCTION, AND SUBUNIT.
RC STRAIN=C57BL/6J;
RX PubMed=10943842; DOI=10.1016/s0092-8674(00)00027-1;
RA Tamura K., Sudo T., Senftleben U., Dadak A.M., Johnson R., Karin M.;
RT "Requirement for p38alpha in erythropoietin expression: a role for stress
RT kinases in erythropoiesis.";
RL Cell 102:221-231(2000).
RN [13]
RP FUNCTION IN ACTIVATION OF RPS6KA5/MSK1 AND RPS6KA4/MSK2.
RX PubMed=11909979; DOI=10.1128/mcb.22.8.2871-2881.2002;
RA Wiggin G.R., Soloaga A., Foster J.M., Murray-Tait V., Cohen P.,
RA Arthur J.S.;
RT "MSK1 and MSK2 are required for the mitogen- and stress-induced
RT phosphorylation of CREB and ATF1 in fibroblasts.";
RL Mol. Cell. Biol. 22:2871-2881(2002).
RN [14]
RP INTERACTION WITH SPAG9.
RX PubMed=12391307; DOI=10.1073/pnas.232310199;
RA Lee C.M., Onesime D., Reddy C.D., Dhanasekaran N., Reddy E.P.;
RT "JLP: a scaffolding protein that tethers JNK/p38MAPK signaling modules and
RT transcription factors.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:14189-14194(2002).
RN [15]
RP INTERACTION WITH DUSP2.
RX PubMed=16288922; DOI=10.1016/j.jmb.2005.10.006;
RA Zhang Q., Muller M., Chen C.H., Zeng L., Farooq A., Zhou M.M.;
RT "New insights into the catalytic activation of the MAPK phosphatase PAC-1
RT induced by its substrate MAPK ERK2 binding.";
RL J. Mol. Biol. 354:777-788(2005).
RN [16]
RP INTERACTION WITH GADD45A, PHOSPHORYLATION AT TYR-323, AUTOPHOSPHORYLATION,
RP ACTIVITY REGULATION, AND FUNCTION.
RX PubMed=15735649; DOI=10.1038/ni1176;
RA Salvador J.M., Mittelstadt P.R., Belova G.I., Fornace A.J. Jr.,
RA Ashwell J.D.;
RT "The autoimmune suppressor Gadd45alpha inhibits the T cell alternative p38
RT activation pathway.";
RL Nat. Immunol. 6:396-402(2005).
RN [17]
RP INTERACTION WITH SUPT20H.
RX PubMed=16751104; DOI=10.1016/j.cell.2006.03.048;
RA Zohn I.E., Li Y., Skolnik E.Y., Anderson K.V., Han J., Niswander L.;
RT "p38 and a p38-interacting protein are critical for downregulation of E-
RT cadherin during mouse gastrulation.";
RL Cell 125:957-969(2006).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-180 AND TYR-182, 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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-180 AND TYR-182, 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 [20]
RP PHOSPHORYLATION AT THR-180 AND TYR-182, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND CATALYTIC ACTIVITY.
RX PubMed=18669639; DOI=10.1074/jbc.m801703200;
RA Zhang Y.Y., Mei Z.Q., Wu J.W., Wang Z.X.;
RT "Enzymatic activity and substrate specificity of mitogen-activated protein
RT kinase p38alpha in different phosphorylation states.";
RL J. Biol. Chem. 283:26591-26601(2008).
RN [21]
RP REVIEW ON FUNCTION.
RX PubMed=12452429; DOI=10.1515/bc.2002.173;
RA Shi Y., Gaestel M.;
RT "In the cellular garden of forking paths: how p38 MAPKs signal for
RT downstream assistance.";
RL Biol. Chem. 383:1519-1536(2002).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-180 AND TYR-182, 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 [23]
RP REVIEW ON ACTIVITY REGULATION, AND REVIEW ON FUNCTION.
RX PubMed=20626350; DOI=10.1042/bj20100323;
RA Cuadrado A., Nebreda A.R.;
RT "Mechanisms and functions of p38 MAPK signalling.";
RL Biochem. J. 429:403-417(2010).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-180 AND TYR-182, 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 [25]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
RX PubMed=9122194; DOI=10.1073/pnas.94.6.2327;
RA Wang Z., Harkins P.C., Ulevitch R.J., Han J., Cobb M.H., Goldsmith E.J.;
RT "The structure of mitogen-activated protein kinase p38 at 2.1-A
RT resolution.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:2327-2332(1997).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH MEF2A AND MAP2K3.
RX PubMed=12086621; DOI=10.1016/s1097-2765(02)00525-7;
RA Chang C.I., Xu B.E., Akella R., Cobb M.H., Goldsmith E.J.;
RT "Crystal structures of MAP kinase p38 complexed to the docking sites on its
RT nuclear substrate MEF2A and activator MKK3b.";
RL Mol. Cell 9:1241-1249(2002).
RN [27] {ECO:0007744|PDB:1YWR}
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
RX PubMed=15837310; DOI=10.1016/j.bmcl.2005.03.007;
RA Golebiowski A., Townes J.A., Laufersweiler M.J., Brugel T.A., Clark M.P.,
RA Clark C.M., Djung J.F., Laughlin S.K., Sabat M.P., Bookland R.G.,
RA VanRens J.C., De B., Hsieh L.C., Janusz M.J., Walter R.L., Webster M.E.,
RA Mekel M.J.;
RT "The development of monocyclic pyrazolone based cytokine synthesis
RT inhibitors.";
RL Bioorg. Med. Chem. Lett. 15:2285-2289(2005).
RN [28] {ECO:0007744|PDB:1YW2}
RP X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
RX PubMed=15837333; DOI=10.1016/j.bmcl.2005.02.066;
RA Laughlin S.K., Clark M.P., Djung J.F., Golebiowski A., Brugel T.A.,
RA Sabat M., Bookland R.G., Laufersweiler M.J., VanRens J.C., Townes J.A.,
RA De B., Hsieh L.C., Xu S.C., Walter R.L., Mekel M.J., Janusz M.J.;
RT "The development of new isoxazolone based inhibitors of tumor necrosis
RT factor-alpha (TNF-alpha) production.";
RL Bioorg. Med. Chem. Lett. 15:2399-2403(2005).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 2-360 IN COMPLEX WITH MAPKAPK2.
RX PubMed=17395714; DOI=10.1073/pnas.0701679104;
RA White A., Pargellis C.A., Studts J.M., Werneburg B.G., Farmer B.T. II;
RT "Molecular basis of MAPK-activated protein kinase 2:p38 assembly.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:6353-6358(2007).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (2.71 ANGSTROMS) IN COMPLEX WITH DUSP10, CATALYTIC
RP ACTIVITY, DEPHOSPHORYLATION BY DUSP10, AND INTERACTION WITH DUSP10.
RX PubMed=22375048; DOI=10.1126/scisignal.2002241;
RA Zhang Y.Y., Wu J.W., Wang Z.X.;
RT "A distinct interaction mode revealed by the crystal structure of the
RT kinase p38alpha with the MAPK binding domain of the phosphatase MKP5.";
RL Sci. Signal. 4:RA88-RA88(2011).
CC -!- FUNCTION: Serine/threonine kinase which acts as an essential component
CC of the MAP kinase signal transduction pathway. MAPK14 is one of the
CC four p38 MAPKs which play an important role in the cascades of cellular
CC responses evoked by extracellular stimuli such as pro-inflammatory
CC cytokines or physical stress leading to direct activation of
CC transcription factors. Accordingly, p38 MAPKs phosphorylate a broad
CC range of proteins and it has been estimated that they may have
CC approximately 200 to 300 substrates each. Some of the targets are
CC downstream kinases which are activated through phosphorylation and
CC further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2
CC can directly phosphorylate and activate transcription factors such as
CC CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but
CC can also phosphorylate histone H3 and the nucleosomal protein HMGN1.
CC RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid
CC induction of immediate-early genes in response to stress or mitogenic
CC stimuli, either by inducing chromatin remodeling or by recruiting the
CC transcription machinery. On the other hand, two other kinase targets,
CC MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene
CC expression mostly at the post-transcriptional level, by phosphorylating
CC ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is
CC important for the elongation of mRNA during translation. MKNK1/MNK1 and
CC MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein
CC synthesis by phosphorylating the initiation factor EIF4E2. MAPK14
CC interacts also with casein kinase II, leading to its activation through
CC autophosphorylation and further phosphorylation of TP53/p53. In the
CC cytoplasm, the p38 MAPK pathway is an important regulator of protein
CC turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis
CC whose proteasome-mediated degradation is regulated by p38 MAPK
CC phosphorylation. In a similar way, MAPK14 phosphorylates the ubiquitin
CC ligase SIAH2, regulating its activity towards EGLN3. MAPK14 may also
CC inhibit the lysosomal degradation pathway of autophagy by interfering
CC with the intracellular trafficking of the transmembrane protein ATG9.
CC Another function of MAPK14 is to regulate the endocytosis of membrane
CC receptors by different mechanisms that impinge on the small GTPase
CC RAB5A. In addition, clathrin-mediated EGFR internalization induced by
CC inflammatory cytokines and UV irradiation depends on MAPK14-mediated
CC phosphorylation of EGFR itself as well as of RAB5A effectors.
CC Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs
CC as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate
CC the membrane-associated metalloprotease ADAM17. Such phosphorylation is
CC required for ADAM17-mediated ectodomain shedding of TGF-alpha family
CC ligands, which results in the activation of EGFR signaling and cell
CC proliferation. Another p38 MAPK substrate is FGFR1. FGFR1 can be
CC translocated from the extracellular space into the cytosol and nucleus
CC of target cells, and regulates processes such as rRNA synthesis and
CC cell growth. FGFR1 translocation requires p38 MAPK activation. In the
CC nucleus, many transcription factors are phosphorylated and activated by
CC p38 MAPKs in response to different stimuli. Classical examples include
CC ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A. The
CC p38 MAPKs are emerging as important modulators of gene expression by
CC regulating chromatin modifiers and remodelers. The promoters of several
CC genes involved in the inflammatory response, such as IL6, IL8 and
CC IL12B, display a p38 MAPK-dependent enrichment of histone H3
CC phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells.
CC This phosphorylation enhances the accessibility of the cryptic NF-
CC kappa-B-binding sites marking promoters for increased NF-kappa-B
CC recruitment. Phosphorylates CDC25B and CDC25C which is required for
CC binding to 14-3-3 proteins and leads to initiation of a G2 delay after
CC ultraviolet radiation. Phosphorylates TIAR following DNA damage,
CC releasing TIAR from GADD45A mRNA and preventing mRNA degradation. The
CC p38 MAPKs may also have kinase-independent roles, which are thought to
CC be due to the binding to targets in the absence of phosphorylation.
CC Protein O-Glc-N-acylation catalyzed by the OGT is regulated by MAPK14,
CC and, although OGT does not seem to be phosphorylated by MAPK14, their
CC interaction increases upon MAPK14 activation induced by glucose
CC deprivation. This interaction may regulate OGT activity by recruiting
CC it to specific targets such as neurofilament H, stimulating its O-Glc-
CC N-acylation. Required in mid-fetal development for the growth of
CC embryo-derived blood vessels in the labyrinth layer of the placenta.
CC Also plays an essential role in developmental and stress-induced
CC erythropoiesis, through regulation of EPO gene expression.
CC Phosphorylates S100A9 at 'Thr-113' (By similarity).
CC {ECO:0000250|UniProtKB:Q16539, ECO:0000269|PubMed:10704466,
CC ECO:0000269|PubMed:10943842, ECO:0000269|PubMed:11909979,
CC ECO:0000269|PubMed:15735649}.
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 Evidence={ECO:0000269|PubMed:18669639, ECO:0000269|PubMed:22375048};
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; Evidence={ECO:0000269|PubMed:18669639,
CC ECO:0000269|PubMed:22375048};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- ACTIVITY REGULATION: Activated by cell stresses such as DNA damage,
CC heat shock, osmotic shock, anisomycin and sodium arsenite, as well as
CC pro-inflammatory stimuli such as bacterial lipopolysaccharide (LPS) and
CC interleukin-1. Activation occurs through dual phosphorylation of Thr-
CC 180 and Tyr-182 by either of two dual specificity kinases, MAP2K3/MKK3
CC or MAP2K6/MKK6, and potentially also MAP2K4/MKK4, as well as by TAB1-
CC mediated autophosphorylation. MAPK14 phosphorylated on both Thr-180 and
CC Tyr-182 is 10-20-fold more active than MAPK14 phosphorylated only on
CC Thr-180, whereas MAPK14 phosphorylated on Tyr-182 alone is inactive.
CC whereas Thr-180 is necessary for catalysis, Tyr-182 may be required for
CC auto-activation and substrate recognition. Phosphorylated at Tyr-323 by
CC ZAP70 in an alternative activation pathway in response to TCR signaling
CC in T-cells. This alternative pathway is inhibited by GADD45A. Inhibited
CC by dual specificity phosphatases, such as DUSP1, DUSP10, and DUSP16.
CC Specifically inhibited by the binding of pyridinyl-imidazole compounds,
CC which are cytokine-suppressive anti-inflammatory drugs (CSAID).
CC SB203580 is an inhibitor of MAPK14. {ECO:0000269|PubMed:10704466,
CC ECO:0000269|PubMed:15735649, ECO:0000269|PubMed:18669639}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=212 uM for ATP (when both Thr-180 and Tyr-182 are phosphorylated)
CC {ECO:0000269|PubMed:18669639};
CC KM=1669 uM for ATP (when only Thr-180 is phosphorylated)
CC {ECO:0000269|PubMed:18669639};
CC KM=656 uM for EGFR peptide as a substrate (when both Thr-180 and Tyr-
CC 182 are phosphorylated) {ECO:0000269|PubMed:18669639};
CC KM=2800 uM for EGFR peptide as a substrate (when only Thr-180 is
CC phosphorylated) {ECO:0000269|PubMed:18669639};
CC KM=2.03 uM for ATF2 as a substrate (when both Thr-180 and Tyr-182 are
CC phosphorylated) {ECO:0000269|PubMed:18669639};
CC KM=20.1 uM for ATF2 as a substrate (when only Thr-180 is
CC phosphorylated) {ECO:0000269|PubMed:18669639};
CC -!- SUBUNIT: Component of a signaling complex containing at least AKAP13,
CC PKN1, MAPK14, ZAK and MAP2K3. Within this complex, AKAP13 interacts
CC directly with PKN1, which in turn recruits MAPK14, MAP2K3 and ZAK (By
CC similarity). Binds to a kinase interaction motif within the protein
CC tyrosine phosphatase, PTPRR (By similarity). This interaction retains
CC MAPK14 in the cytoplasm and prevents nuclear accumulation (By
CC similarity). Interacts with SPAG9 and GADD45A (By similarity).
CC Interacts with CDC25B, CDC25C, DUSP1, DUSP10, DUSP16, NP60, SUPT20H and
CC TAB1. Interacts with casein kinase II subunits CSNK2A1 and CSNK2B.
CC Interacts with PPM1D. Interacts with CDK5RAP3; recruits PPM1D to MAPK14
CC and may regulate its dephosphorylation (By similarity). Interacts with
CC DUSP2; this interaction does not lead to catalytic activation of DUSP2
CC and dephosphrylation of MAPK14 (PubMed:16288922).
CC {ECO:0000250|UniProtKB:Q16539, ECO:0000269|PubMed:10601328,
CC ECO:0000269|PubMed:10943842, ECO:0000269|PubMed:12391307,
CC ECO:0000269|PubMed:15735649, ECO:0000269|PubMed:16288922,
CC ECO:0000269|PubMed:16751104, ECO:0000269|PubMed:22375048}.
CC -!- INTERACTION:
CC P47811; Q61233: Lcp1; NbExp=5; IntAct=EBI-298727, EBI-309345;
CC P47811; Q9WUI1: Mapk11; NbExp=10; IntAct=EBI-298727, EBI-645081;
CC P47811; P49138: Mapkapk2; NbExp=2; IntAct=EBI-298727, EBI-298776;
CC P47811; Q9WVS6: Prkn; NbExp=3; IntAct=EBI-298727, EBI-973635;
CC P47811; P55012: Slc12a2; NbExp=2; IntAct=EBI-298727, EBI-621078;
CC P47811; Q9Z1W9: Stk39; NbExp=2; IntAct=EBI-298727, EBI-444764;
CC P47811; Q99956: DUSP9; Xeno; NbExp=2; IntAct=EBI-298727, EBI-3906678;
CC P47811; P49137-1: MAPKAPK2; Xeno; NbExp=2; IntAct=EBI-298727, EBI-15629963;
CC P47811; P35236: PTPN7; Xeno; NbExp=2; IntAct=EBI-298727, EBI-2265723;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10601328}. Nucleus
CC {ECO:0000269|PubMed:10601328}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P47811-1; Sequence=Displayed;
CC Name=2; Synonyms=Piccolo;
CC IsoId=P47811-2; Sequence=VSP_004846, VSP_007545;
CC Name=3;
CC IsoId=P47811-3; Sequence=VSP_007544;
CC Name=4;
CC IsoId=P47811-4; Sequence=VSP_022359;
CC -!- TISSUE SPECIFICITY: Macrophages, monocytes, T- and B-lymphocytes.
CC Isoform 2 is specifically expressed in kidney and liver.
CC -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues
CC whose phosphorylation activates the MAP kinases.
CC -!- PTM: Dually phosphorylated on Thr-180 and Tyr-182 by the MAP2Ks
CC MAP2K3/MKK3, MAP2K4/MKK4 and MAP2K6/MKK6 in response to inflammatory
CC cytokines, environmental stress or growth factors, which activates the
CC enzyme. Dual phosphorylation can also be mediated by TAB1-mediated
CC autophosphorylation. TCR engagement in T-cells also leads to Tyr-323
CC phosphorylation by ZAP70. Dephosphorylated and inactivated by DUPS1,
CC DUSP10 and DUSP16. PPM1D also mediates dephosphorylation and
CC inactivation of MAPK14 (By similarity). {ECO:0000250|UniProtKB:Q16539,
CC ECO:0000269|PubMed:15735649, ECO:0000269|PubMed:18669639}.
CC -!- PTM: Acetylated at Lys-53 and Lys-152 by KAT2B and EP300. Acetylation
CC at Lys-53 increases the affinity for ATP and enhances kinase activity.
CC Lys-53 and Lys-152 are deacetylated by HDAC3 (By similarity).
CC {ECO:0000250|UniProtKB:Q16539}.
CC -!- PTM: Ubiquitinated. Ubiquitination leads to degradation by the
CC proteasome pathway (By similarity). {ECO:0000250|UniProtKB:Q16539}.
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; U10871; AAA20888.1; -; mRNA.
DR EMBL; D83073; BAA19741.1; -; mRNA.
DR EMBL; AF128892; AAF34818.1; -; mRNA.
DR EMBL; AK151348; BAE30324.1; -; mRNA.
DR EMBL; AK153025; BAE31659.1; -; mRNA.
DR EMBL; AK089059; BAC40726.1; -; mRNA.
DR EMBL; AK133684; BAE21782.1; -; mRNA.
DR EMBL; CT009661; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012235; AAH12235.1; -; mRNA.
DR EMBL; AF195850; AAF06348.1; -; mRNA.
DR EMBL; X65067; CAA46200.1; -; mRNA.
DR CCDS; CCDS28583.1; -. [P47811-1]
DR CCDS; CCDS50048.1; -. [P47811-3]
DR CCDS; CCDS50049.1; -. [P47811-4]
DR PIR; I49066; I49066.
DR RefSeq; NP_001161980.1; NM_001168508.1. [P47811-3]
DR RefSeq; NP_001161985.1; NM_001168513.1. [P47811-4]
DR RefSeq; NP_001161986.1; NM_001168514.1. [P47811-4]
DR RefSeq; NP_036081.1; NM_011951.3. [P47811-1]
DR PDB; 1LEW; X-ray; 2.30 A; A=1-360.
DR PDB; 1LEZ; X-ray; 2.30 A; A=1-360.
DR PDB; 1YW2; X-ray; 2.01 A; A=1-360.
DR PDB; 1YWR; X-ray; 1.95 A; A=1-360.
DR PDB; 2EWA; X-ray; 2.10 A; A=1-360.
DR PDB; 2GHL; X-ray; 2.10 A; A=5-352.
DR PDB; 2GHM; X-ray; 2.35 A; A=5-352.
DR PDB; 2GTM; X-ray; 1.90 A; A=5-352.
DR PDB; 2GTN; X-ray; 1.80 A; A=5-352.
DR PDB; 2OZA; X-ray; 2.70 A; B=2-360.
DR PDB; 2PUU; X-ray; 2.50 A; A=5-352.
DR PDB; 3P4K; X-ray; 2.30 A; A=1-360.
DR PDB; 3P5K; X-ray; 2.09 A; A=2-360.
DR PDB; 3P78; X-ray; 2.30 A; A=2-360.
DR PDB; 3P79; X-ray; 2.10 A; A=2-360.
DR PDB; 3P7A; X-ray; 2.31 A; A=2-360.
DR PDB; 3P7B; X-ray; 1.90 A; A=2-360.
DR PDB; 3P7C; X-ray; 2.30 A; A=2-360.
DR PDB; 3PY3; X-ray; 2.10 A; A=1-360.
DR PDB; 3TG1; X-ray; 2.71 A; A=1-360.
DR PDB; 4KA3; X-ray; 2.71 A; A=1-360.
DR PDB; 4LOO; X-ray; 1.95 A; A=1-360.
DR PDB; 4LOP; X-ray; 2.05 A; A/B/C/D=1-360.
DR PDB; 4LOQ; X-ray; 2.32 A; A/B/C/D=1-360.
DR PDB; 4TYH; X-ray; 3.00 A; B=6-353.
DR PDB; 5LAR; X-ray; 1.50 A; A=1-360.
DR PDB; 5NZZ; X-ray; 2.60 A; E/F/G/H=1-360.
DR PDB; 5O90; X-ray; 2.49 A; A=1-360.
DR PDB; 5R8U; X-ray; 1.48 A; A=1-360.
DR PDB; 5R8V; X-ray; 1.48 A; A=1-360.
DR PDB; 5R8W; X-ray; 1.50 A; A=1-360.
DR PDB; 5R8X; X-ray; 1.73 A; A=1-360.
DR PDB; 5R8Y; X-ray; 1.68 A; A=1-360.
DR PDB; 5R8Z; X-ray; 1.65 A; A=1-360.
DR PDB; 5R90; X-ray; 1.62 A; A=1-360.
DR PDB; 5R91; X-ray; 1.73 A; A=1-360.
DR PDB; 5R92; X-ray; 1.66 A; A=1-360.
DR PDB; 5R93; X-ray; 1.49 A; A=1-360.
DR PDB; 5R94; X-ray; 1.45 A; A=1-360.
DR PDB; 5R95; X-ray; 1.59 A; A=1-360.
DR PDB; 5R96; X-ray; 1.77 A; A=1-360.
DR PDB; 5R97; X-ray; 1.44 A; A=1-360.
DR PDB; 5R98; X-ray; 1.68 A; A=1-360.
DR PDB; 5R99; X-ray; 1.89 A; A=1-360.
DR PDB; 5R9A; X-ray; 1.53 A; A=1-360.
DR PDB; 5R9B; X-ray; 1.66 A; A=1-360.
DR PDB; 5R9C; X-ray; 1.74 A; A=1-360.
DR PDB; 5R9D; X-ray; 1.69 A; A=1-360.
DR PDB; 5R9E; X-ray; 1.77 A; A=1-360.
DR PDB; 5R9F; X-ray; 1.99 A; A=1-360.
DR PDB; 5R9G; X-ray; 1.73 A; A=1-360.
DR PDB; 5R9H; X-ray; 1.49 A; A=1-360.
DR PDB; 5R9I; X-ray; 1.81 A; A=1-360.
DR PDB; 5R9J; X-ray; 1.52 A; A=1-360.
DR PDB; 5R9K; X-ray; 1.50 A; A=1-360.
DR PDB; 5R9L; X-ray; 1.47 A; A=1-360.
DR PDB; 5R9M; X-ray; 1.81 A; A=1-360.
DR PDB; 5R9N; X-ray; 1.69 A; A=1-360.
DR PDB; 5R9O; X-ray; 1.60 A; A=1-360.
DR PDB; 5R9P; X-ray; 1.72 A; A=1-360.
DR PDB; 5R9Q; X-ray; 1.65 A; A=1-360.
DR PDB; 5R9R; X-ray; 1.76 A; A=1-360.
DR PDB; 5R9S; X-ray; 1.70 A; A=1-360.
DR PDB; 5R9T; X-ray; 1.80 A; A=1-360.
DR PDB; 5R9U; X-ray; 1.67 A; A=1-360.
DR PDB; 5R9V; X-ray; 1.45 A; A=1-360.
DR PDB; 5R9W; X-ray; 1.89 A; A=1-360.
DR PDB; 5R9X; X-ray; 1.72 A; A=1-360.
DR PDB; 5R9Y; X-ray; 1.57 A; A=1-360.
DR PDB; 5R9Z; X-ray; 1.66 A; A=1-360.
DR PDB; 5RA0; X-ray; 1.91 A; A=1-360.
DR PDB; 5RA1; X-ray; 1.61 A; A=1-360.
DR PDB; 5RA2; X-ray; 1.57 A; A=1-360.
DR PDB; 5RA3; X-ray; 1.57 A; A=1-360.
DR PDB; 5RA4; X-ray; 1.59 A; A=1-360.
DR PDB; 5RA5; X-ray; 1.54 A; A=1-360.
DR PDB; 5RA6; X-ray; 1.86 A; A=1-360.
DR PDB; 5RA7; X-ray; 1.92 A; A=1-360.
DR PDB; 5RA8; X-ray; 1.78 A; A=1-360.
DR PDB; 5RA9; X-ray; 1.68 A; A=1-360.
DR PDB; 5UOJ; X-ray; 2.10 A; A=1-360.
DR PDB; 6SO1; X-ray; 1.66 A; A=1-360.
DR PDB; 6SO2; X-ray; 1.60 A; A=1-360.
DR PDB; 6SO4; X-ray; 1.51 A; A=1-360.
DR PDB; 6SOD; X-ray; 1.87 A; A=1-360.
DR PDB; 6SOI; X-ray; 1.55 A; A=1-359.
DR PDB; 6SOT; X-ray; 1.54 A; A=1-360.
DR PDB; 6SOU; X-ray; 1.50 A; A=1-360.
DR PDB; 6SOV; X-ray; 1.31 A; A=1-360.
DR PDB; 6SP9; X-ray; 1.22 A; A=1-360.
DR PDB; 6SPL; X-ray; 1.38 A; A=1-360.
DR PDB; 6Y4T; X-ray; 1.98 A; A=1-360.
DR PDB; 6Y4U; X-ray; 1.86 A; A=1-360.
DR PDB; 6Y4V; X-ray; 1.75 A; A=1-360.
DR PDB; 6Y4W; X-ray; 1.86 A; A=1-360.
DR PDB; 6Y4X; X-ray; 1.60 A; A=1-360.
DR PDB; 6Y6V; X-ray; 2.10 A; A=1-360.
DR PDB; 6Y7W; X-ray; 1.39 A; A=1-360.
DR PDB; 6Y7X; X-ray; 1.45 A; A=1-360.
DR PDB; 6Y7Y; X-ray; 1.51 A; A=1-360.
DR PDB; 6Y7Z; X-ray; 1.35 A; A=1-360.
DR PDB; 6Y80; X-ray; 1.24 A; A=1-360.
DR PDB; 6Y81; X-ray; 1.54 A; A=1-360.
DR PDB; 6Y82; X-ray; 1.44 A; A=1-360.
DR PDB; 6Y85; X-ray; 1.58 A; A=1-360.
DR PDB; 6Y8H; X-ray; 1.37 A; A=1-360.
DR PDB; 6YCU; X-ray; 1.35 A; A=1-360.
DR PDB; 6YCW; X-ray; 1.34 A; A=1-360.
DR PDB; 6YJC; X-ray; 1.74 A; A=1-360.
DR PDB; 6YK7; X-ray; 1.90 A; A=1-360.
DR PDB; 6ZWR; X-ray; 1.90 A; A=1-360.
DR PDB; 7BDO; X-ray; 2.70 A; A=1-360.
DR PDB; 7BDQ; X-ray; 2.75 A; A=1-360.
DR PDB; 7BE4; X-ray; 2.10 A; A=1-360.
DR PDB; 7BE5; X-ray; 1.80 A; A=1-360.
DR PDBsum; 1LEW; -.
DR PDBsum; 1LEZ; -.
DR PDBsum; 1YW2; -.
DR PDBsum; 1YWR; -.
DR PDBsum; 2EWA; -.
DR PDBsum; 2GHL; -.
DR PDBsum; 2GHM; -.
DR PDBsum; 2GTM; -.
DR PDBsum; 2GTN; -.
DR PDBsum; 2OZA; -.
DR PDBsum; 2PUU; -.
DR PDBsum; 3P4K; -.
DR PDBsum; 3P5K; -.
DR PDBsum; 3P78; -.
DR PDBsum; 3P79; -.
DR PDBsum; 3P7A; -.
DR PDBsum; 3P7B; -.
DR PDBsum; 3P7C; -.
DR PDBsum; 3PY3; -.
DR PDBsum; 3TG1; -.
DR PDBsum; 4KA3; -.
DR PDBsum; 4LOO; -.
DR PDBsum; 4LOP; -.
DR PDBsum; 4LOQ; -.
DR PDBsum; 4TYH; -.
DR PDBsum; 5LAR; -.
DR PDBsum; 5NZZ; -.
DR PDBsum; 5O90; -.
DR PDBsum; 5R8U; -.
DR PDBsum; 5R8V; -.
DR PDBsum; 5R8W; -.
DR PDBsum; 5R8X; -.
DR PDBsum; 5R8Y; -.
DR PDBsum; 5R8Z; -.
DR PDBsum; 5R90; -.
DR PDBsum; 5R91; -.
DR PDBsum; 5R92; -.
DR PDBsum; 5R93; -.
DR PDBsum; 5R94; -.
DR PDBsum; 5R95; -.
DR PDBsum; 5R96; -.
DR PDBsum; 5R97; -.
DR PDBsum; 5R98; -.
DR PDBsum; 5R99; -.
DR PDBsum; 5R9A; -.
DR PDBsum; 5R9B; -.
DR PDBsum; 5R9C; -.
DR PDBsum; 5R9D; -.
DR PDBsum; 5R9E; -.
DR PDBsum; 5R9F; -.
DR PDBsum; 5R9G; -.
DR PDBsum; 5R9H; -.
DR PDBsum; 5R9I; -.
DR PDBsum; 5R9J; -.
DR PDBsum; 5R9K; -.
DR PDBsum; 5R9L; -.
DR PDBsum; 5R9M; -.
DR PDBsum; 5R9N; -.
DR PDBsum; 5R9O; -.
DR PDBsum; 5R9P; -.
DR PDBsum; 5R9Q; -.
DR PDBsum; 5R9R; -.
DR PDBsum; 5R9S; -.
DR PDBsum; 5R9T; -.
DR PDBsum; 5R9U; -.
DR PDBsum; 5R9V; -.
DR PDBsum; 5R9W; -.
DR PDBsum; 5R9X; -.
DR PDBsum; 5R9Y; -.
DR PDBsum; 5R9Z; -.
DR PDBsum; 5RA0; -.
DR PDBsum; 5RA1; -.
DR PDBsum; 5RA2; -.
DR PDBsum; 5RA3; -.
DR PDBsum; 5RA4; -.
DR PDBsum; 5RA5; -.
DR PDBsum; 5RA6; -.
DR PDBsum; 5RA7; -.
DR PDBsum; 5RA8; -.
DR PDBsum; 5RA9; -.
DR PDBsum; 5UOJ; -.
DR PDBsum; 6SO1; -.
DR PDBsum; 6SO2; -.
DR PDBsum; 6SO4; -.
DR PDBsum; 6SOD; -.
DR PDBsum; 6SOI; -.
DR PDBsum; 6SOT; -.
DR PDBsum; 6SOU; -.
DR PDBsum; 6SOV; -.
DR PDBsum; 6SP9; -.
DR PDBsum; 6SPL; -.
DR PDBsum; 6Y4T; -.
DR PDBsum; 6Y4U; -.
DR PDBsum; 6Y4V; -.
DR PDBsum; 6Y4W; -.
DR PDBsum; 6Y4X; -.
DR PDBsum; 6Y6V; -.
DR PDBsum; 6Y7W; -.
DR PDBsum; 6Y7X; -.
DR PDBsum; 6Y7Y; -.
DR PDBsum; 6Y7Z; -.
DR PDBsum; 6Y80; -.
DR PDBsum; 6Y81; -.
DR PDBsum; 6Y82; -.
DR PDBsum; 6Y85; -.
DR PDBsum; 6Y8H; -.
DR PDBsum; 6YCU; -.
DR PDBsum; 6YCW; -.
DR PDBsum; 6YJC; -.
DR PDBsum; 6YK7; -.
DR PDBsum; 6ZWR; -.
DR PDBsum; 7BDO; -.
DR PDBsum; 7BDQ; -.
DR PDBsum; 7BE4; -.
DR PDBsum; 7BE5; -.
DR AlphaFoldDB; P47811; -.
DR BMRB; P47811; -.
DR SMR; P47811; -.
DR BioGRID; 204969; 180.
DR DIP; DIP-31073N; -.
DR ELM; P47811; -.
DR IntAct; P47811; 27.
DR MINT; P47811; -.
DR STRING; 10090.ENSMUSP00000004990; -.
DR BindingDB; P47811; -.
DR ChEMBL; CHEMBL2336; -.
DR iPTMnet; P47811; -.
DR PhosphoSitePlus; P47811; -.
DR CPTAC; non-CPTAC-3479; -.
DR EPD; P47811; -.
DR jPOST; P47811; -.
DR MaxQB; P47811; -.
DR PaxDb; P47811; -.
DR PeptideAtlas; P47811; -.
DR PRIDE; P47811; -.
DR ProteomicsDB; 295631; -. [P47811-1]
DR ProteomicsDB; 295632; -. [P47811-2]
DR ProteomicsDB; 295633; -. [P47811-3]
DR ProteomicsDB; 295634; -. [P47811-4]
DR Antibodypedia; 4142; 2350 antibodies from 54 providers.
DR DNASU; 26416; -.
DR Ensembl; ENSMUST00000004990; ENSMUSP00000004990; ENSMUSG00000053436. [P47811-3]
DR Ensembl; ENSMUST00000062694; ENSMUSP00000061958; ENSMUSG00000053436. [P47811-1]
DR Ensembl; ENSMUST00000114752; ENSMUSP00000110400; ENSMUSG00000053436. [P47811-4]
DR Ensembl; ENSMUST00000114754; ENSMUSP00000110402; ENSMUSG00000053436. [P47811-4]
DR Ensembl; ENSMUST00000114758; ENSMUSP00000110406; ENSMUSG00000053436. [P47811-2]
DR GeneID; 26416; -.
DR KEGG; mmu:26416; -.
DR UCSC; uc008brl.2; mouse. [P47811-1]
DR CTD; 1432; -.
DR MGI; MGI:1346865; Mapk14.
DR VEuPathDB; HostDB:ENSMUSG00000053436; -.
DR eggNOG; KOG0660; Eukaryota.
DR GeneTree; ENSGT00940000155325; -.
DR InParanoid; P47811; -.
DR OMA; YTDLNPV; -.
DR OrthoDB; 683132at2759; -.
DR PhylomeDB; P47811; -.
DR TreeFam; TF105100; -.
DR BRENDA; 2.7.11.24; 3474.
DR Reactome; R-MMU-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-MMU-171007; p38MAPK events.
DR Reactome; R-MMU-198753; ERK/MAPK targets.
DR Reactome; R-MMU-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-MMU-376172; DSCAM interactions.
DR Reactome; R-MMU-418592; ADP signalling through P2Y purinoceptor 1.
DR Reactome; R-MMU-432142; Platelet sensitization by LDL.
DR Reactome; R-MMU-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-MMU-450302; activated TAK1 mediates p38 MAPK activation.
DR Reactome; R-MMU-450341; Activation of the AP-1 family of transcription factors.
DR Reactome; R-MMU-525793; Myogenesis.
DR Reactome; R-MMU-5668599; RHO GTPases Activate NADPH Oxidases.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR Reactome; R-MMU-6804756; Regulation of TP53 Activity through Phosphorylation.
DR SABIO-RK; P47811; -.
DR BioGRID-ORCS; 26416; 9 hits in 78 CRISPR screens.
DR ChiTaRS; Mapk14; mouse.
DR EvolutionaryTrace; P47811; -.
DR PRO; PR:P47811; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; P47811; protein.
DR Bgee; ENSMUSG00000053436; Expressed in granulocyte and 267 other tissues.
DR ExpressionAtlas; P47811; baseline and differential.
DR Genevisible; P47811; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0016607; C:nuclear speck; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000922; C:spindle pole; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0016301; F:kinase activity; IDA:MGI.
DR GO; GO:0004707; F:MAP kinase activity; IDA:UniProtKB.
DR GO; GO:0048273; F:mitogen-activated protein kinase p38 binding; ISO:MGI.
DR GO; GO:0051525; F:NFAT protein binding; IPI:BHF-UCL.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0019903; F:protein phosphatase 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:MGI.
DR GO; GO:0001525; P:angiogenesis; IMP:MGI.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0060348; P:bone development; IMP:MGI.
DR GO; GO:0001502; P:cartilage condensation; IMP:AgBase.
DR GO; GO:0000902; P:cell morphogenesis; IGI:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:MGI.
DR GO; GO:0071479; P:cellular response to ionizing radiation; ISO:MGI.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISO:MGI.
DR GO; GO:0071223; P:cellular response to lipoteichoic acid; ISO:MGI.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:MGI.
DR GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; ISO:MGI.
DR GO; GO:0098586; P:cellular response to virus; ISO:MGI.
DR GO; GO:0002062; P:chondrocyte differentiation; IDA:MGI.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; IMP:MGI.
DR GO; GO:0019395; P:fatty acid oxidation; IMP:MGI.
DR GO; GO:0046323; P:glucose import; IMP:MGI.
DR GO; GO:0006006; P:glucose metabolic process; IMP:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IDA:MGI.
DR GO; GO:0000165; P:MAPK cascade; IMP:MGI.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:AgBase.
DR GO; GO:0035331; P:negative regulation of hippo signaling; ISO:MGI.
DR GO; GO:0001649; P:osteoblast differentiation; IMP:MGI.
DR GO; GO:0030316; P:osteoclast differentiation; IMP:BHF-UCL.
DR GO; GO:0038066; P:p38MAPK cascade; IDA:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0001890; P:placenta development; IMP:MGI.
DR GO; GO:0090336; P:positive regulation of brown fat cell differentiation; IMP:MGI.
DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; IGI:MGI.
DR GO; GO:0031281; P:positive regulation of cyclase activity; ISO:MGI.
DR GO; GO:0045648; P:positive regulation of erythrocyte differentiation; IMP:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:MGI.
DR GO; GO:0046326; P:positive regulation of glucose import; IMP:MGI.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; ISO:MGI.
DR GO; GO:0045663; P:positive regulation of myoblast differentiation; IMP:UniProtKB.
DR GO; GO:1901741; P:positive regulation of myoblast fusion; IMP:UniProtKB.
DR GO; GO:0010831; P:positive regulation of myotube differentiation; IMP:UniProtKB.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IMP:MGI.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
DR GO; GO:1900015; P:regulation of cytokine production involved in inflammatory response; ISO:MGI.
DR GO; GO:0030278; P:regulation of ossification; IDA:MGI.
DR GO; GO:0099179; P:regulation of synaptic membrane adhesion; IDA:SynGO.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0002021; P:response to dietary excess; IMP:MGI.
DR GO; GO:0032868; P:response to insulin; IMP:MGI.
DR GO; GO:0032496; P:response to lipopolysaccharide; IDA:MGI.
DR GO; GO:0032495; P:response to muramyl dipeptide; IDA:MGI.
DR GO; GO:0035994; P:response to muscle stretch; IMP:MGI.
DR GO; GO:0042770; P:signal transduction in response to DNA damage; ISO:MGI.
DR GO; GO:0007519; P:skeletal muscle tissue development; IMP:MGI.
DR GO; GO:0048863; P:stem cell differentiation; IDA:MGI.
DR GO; GO:0051403; P:stress-activated MAPK cascade; ISO:MGI.
DR GO; GO:0090400; P:stress-induced premature senescence; ISO:MGI.
DR GO; GO:0051146; P:striated muscle cell differentiation; IGI:MGI.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0007178; P:transmembrane receptor protein serine/threonine kinase signaling pathway; IGI:MGI.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; ISO:MGI.
DR CDD; cd07877; STKc_p38alpha; 1.
DR IDEAL; IID50045; -.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR003527; MAP_kinase_CS.
DR InterPro; IPR008352; MAPK_p38-like.
DR InterPro; IPR038784; p38alpha.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR Pfam; PF00069; Pkinase; 1.
DR PRINTS; PR01773; P38MAPKINASE.
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.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; ATP-binding;
KW Cytoplasm; Direct protein sequencing; Kinase; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Stress response; Transcription; Transcription regulation; Transferase;
KW Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q16539"
FT CHAIN 2..360
FT /note="Mitogen-activated protein kinase 14"
FT /id="PRO_0000186292"
FT DOMAIN 24..308
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOTIF 180..182
FT /note="TXY"
FT ACT_SITE 168
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 30..38
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 53
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q16539"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16539"
FT MOD_RES 16
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q16539"
FT MOD_RES 53
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q16539"
FT MOD_RES 152
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q16539"
FT MOD_RES 180
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18669639,
FT ECO:0007744|PubMed:17242355, ECO:0007744|PubMed:17947660,
FT ECO:0007744|PubMed:18034455, ECO:0007744|PubMed:21183079"
FT MOD_RES 180
FT /note="Phosphothreonine; by MAP2K3, MAP2K4, MAP2K6 and
FT autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 182
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:18669639,
FT ECO:0007744|PubMed:17242355, ECO:0007744|PubMed:17947660,
FT ECO:0007744|PubMed:18034455, ECO:0007744|PubMed:21183079"
FT MOD_RES 182
FT /note="Phosphotyrosine; by MAP2K3, MAP2K4, MAP2K6 and
FT autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 323
FT /note="Phosphotyrosine; by ZAP70"
FT /evidence="ECO:0000250|UniProtKB:Q16539"
FT VAR_SEQ 1..77
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_022359"
FT VAR_SEQ 230..254
FT /note="DQLKLILRLVGTPGAELLKKISSES -> NQLQQIMRLTGTPPAYLINRMPS
FT HE (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072, ECO:0000303|Ref.2,
FT ECO:0000303|Ref.7"
FT /id="VSP_007544"
FT VAR_SEQ 255..278
FT /note="ARNYIQSLAQMPKMNFANVFIGAN -> DAKP (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_004846"
FT VAR_SEQ 279..360
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_007545"
FT MUTAGEN 180
FT /note="T->A: Phosphorylation blocked."
FT /evidence="ECO:0000269|PubMed:7839144"
FT MUTAGEN 182
FT /note="Y->F: Phosphorylation blocked."
FT /evidence="ECO:0000269|PubMed:7839144"
FT CONFLICT 98
FT /note="E -> G (in Ref. 7; AAF06348)"
FT /evidence="ECO:0000305"
FT CONFLICT 107..108
FT /note="HL -> LS (in Ref. 7; AAF06348)"
FT /evidence="ECO:0000305"
FT CONFLICT 115
FT /note="N -> R (in Ref. 7; AAF06348)"
FT /evidence="ECO:0000305"
FT CONFLICT 124
FT /note="D -> G (in Ref. 7; AAF06348)"
FT /evidence="ECO:0000305"
FT CONFLICT 159..162
FT /note="NEDC -> TQVI (in Ref. 7; AAF06348)"
FT /evidence="ECO:0000305"
FT CONFLICT 166
FT /note="I -> L (in Ref. 7; AAF06348)"
FT /evidence="ECO:0000305"
FT CONFLICT 202
FT /note="Q -> R (in Ref. 7; AAF06348)"
FT /evidence="ECO:0000305"
FT CONFLICT 211..212
FT /note="CI -> GF (in Ref. 7; AAF06348)"
FT /evidence="ECO:0000305"
FT CONFLICT 224
FT /note="P -> L (in Ref. 7; AAF06348)"
FT /evidence="ECO:0000305"
FT CONFLICT 271
FT /note="A -> P (in Ref. 7; AAF06348)"
FT /evidence="ECO:0000305"
FT CONFLICT 299
FT /note="A -> V (in Ref. 7; AAF06348)"
FT /evidence="ECO:0000305"
FT CONFLICT 315
FT /note="D -> Y (in Ref. 7; AAF06348)"
FT /evidence="ECO:0000305"
FT STRAND 8..13
FT /evidence="ECO:0007829|PDB:6SP9"
FT STRAND 16..21
FT /evidence="ECO:0007829|PDB:6SP9"
FT STRAND 24..33
FT /evidence="ECO:0007829|PDB:6SP9"
FT STRAND 36..43
FT /evidence="ECO:0007829|PDB:6SP9"
FT TURN 44..47
FT /evidence="ECO:0007829|PDB:6SP9"
FT STRAND 48..57
FT /evidence="ECO:0007829|PDB:6SP9"
FT HELIX 62..77
FT /evidence="ECO:0007829|PDB:6SP9"
FT STRAND 87..90
FT /evidence="ECO:0007829|PDB:6SP9"
FT HELIX 96..98
FT /evidence="ECO:0007829|PDB:6SP9"
FT STRAND 103..107
FT /evidence="ECO:0007829|PDB:6SP9"
FT STRAND 110..112
FT /evidence="ECO:0007829|PDB:5LAR"
FT HELIX 113..117
FT /evidence="ECO:0007829|PDB:6SP9"
FT STRAND 118..120
FT /evidence="ECO:0007829|PDB:6Y8H"
FT HELIX 124..143
FT /evidence="ECO:0007829|PDB:6SP9"
FT HELIX 153..155
FT /evidence="ECO:0007829|PDB:6SP9"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:6SP9"
FT STRAND 164..166
FT /evidence="ECO:0007829|PDB:6SP9"
FT STRAND 172..175
FT /evidence="ECO:0007829|PDB:2GTM"
FT HELIX 177..179
FT /evidence="ECO:0007829|PDB:5R97"
FT STRAND 180..182
FT /evidence="ECO:0007829|PDB:5R97"
FT HELIX 184..187
FT /evidence="ECO:0007829|PDB:5R97"
FT HELIX 191..194
FT /evidence="ECO:0007829|PDB:6SP9"
FT STRAND 197..199
FT /evidence="ECO:0007829|PDB:2GTN"
FT HELIX 204..218
FT /evidence="ECO:0007829|PDB:6SP9"
FT HELIX 228..239
FT /evidence="ECO:0007829|PDB:6SP9"
FT HELIX 244..247
FT /evidence="ECO:0007829|PDB:6SP9"
FT HELIX 253..261
FT /evidence="ECO:0007829|PDB:6SP9"
FT HELIX 270..272
FT /evidence="ECO:0007829|PDB:6SP9"
FT TURN 274..276
FT /evidence="ECO:0007829|PDB:6Y4X"
FT HELIX 279..288
FT /evidence="ECO:0007829|PDB:6SP9"
FT HELIX 293..295
FT /evidence="ECO:0007829|PDB:6Y80"
FT HELIX 299..303
FT /evidence="ECO:0007829|PDB:6SP9"
FT HELIX 306..308
FT /evidence="ECO:0007829|PDB:6SP9"
FT TURN 309..311
FT /evidence="ECO:0007829|PDB:6SP9"
FT HELIX 314..316
FT /evidence="ECO:0007829|PDB:6SP9"
FT HELIX 326..329
FT /evidence="ECO:0007829|PDB:6SP9"
FT HELIX 334..347
FT /evidence="ECO:0007829|PDB:6SP9"
FT CONFLICT P47811-3:238
FT /note="L -> M (in Ref. 2; BAA19741)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 360 AA; 41287 MW; DFB03EBCE97BB51A CRC64;
MSQERPTFYR QELNKTIWEV PERYQNLSPV GSGAYGSVCA AFDTKTGHRV AVKKLSRPFQ
SIIHAKRTYR ELRLLKHMKH ENVIGLLDVF TPARSLEEFN DVYLVTHLMG ADLNNIVKCQ
KLTDDHVQFL IYQILRGLKY IHSADIIHRD LKPSNLAVNE DCELKILDFG LARHTDDEMT
GYVATRWYRA PEIMLNWMHY NQTVDIWSVG CIMAELLTGR TLFPGTDHID QLKLILRLVG
TPGAELLKKI SSESARNYIQ SLAQMPKMNF ANVFIGANPL AVDLLEKMLV LDSDKRITAA
QALAHAYFAQ YHDPDDEPVA DPYDQSFESR DLLIDEWKSL TYDEVISFVP PPLDQEEMES
