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 27-MAR-2024, entry version 240. 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}; GN 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, RC Pancreas, 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 CC Tyr-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 PDB; 7PVU; X-ray; 2.15 A; A/B=1-359. DR PDB; 7Z6I; X-ray; 2.25 A; AAA=1-359. DR PDB; 7Z9T; X-ray; 2.60 A; AAA/BBB=1-359. DR PDB; 8ACM; X-ray; 2.14 A; AAA=1-359. DR PDB; 8ACO; X-ray; 2.65 A; AAA=1-359. DR PDB; 8EFJ; X-ray; 2.31 A; A=2-360. 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 PDBsum; 7PVU; -. DR PDBsum; 7Z6I; -. DR PDBsum; 7Z9T; -. DR PDBsum; 8ACM; -. DR PDBsum; 8ACO; -. DR PDBsum; 8EFJ; -. 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 SwissPalm; P47811; -. DR CPTAC; non-CPTAC-3479; -. DR EPD; P47811; -. DR jPOST; P47811; -. DR MaxQB; P47811; -. DR PaxDb; 10090-ENSMUSP00000004990; -. DR PeptideAtlas; P47811; -. DR ProteomicsDB; 295631; -. [P47811-1] DR ProteomicsDB; 295632; -. [P47811-2] DR ProteomicsDB; 295633; -. [P47811-3] DR ProteomicsDB; 295634; -. [P47811-4] DR Pumba; P47811; -. DR Antibodypedia; 4142; 2724 antibodies from 54 providers. DR DNASU; 26416; -. DR Ensembl; ENSMUST00000004990.14; ENSMUSP00000004990.7; ENSMUSG00000053436.16. [P47811-3] DR Ensembl; ENSMUST00000062694.16; ENSMUSP00000061958.9; ENSMUSG00000053436.16. [P47811-1] DR Ensembl; ENSMUST00000114752.3; ENSMUSP00000110400.2; ENSMUSG00000053436.16. [P47811-4] DR Ensembl; ENSMUST00000114754.8; ENSMUSP00000110402.2; ENSMUSG00000053436.16. [P47811-4] DR Ensembl; ENSMUST00000114758.9; ENSMUSP00000110406.2; ENSMUSG00000053436.16. [P47811-2] DR GeneID; 26416; -. DR KEGG; mmu:26416; -. DR UCSC; uc008brl.2; mouse. [P47811-1] DR AGR; MGI:1346865; -. DR CTD; 1432; -. DR MGI; MGI:1346865; Mapk14. DR VEuPathDB; HostDB:ENSMUSG00000053436; -. DR eggNOG; KOG0660; Eukaryota. DR GeneTree; ENSGT00940000155325; -. DR InParanoid; P47811; -. DR OMA; NRYTDLN; -. DR OrthoDB; 158564at2759; -. 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; 11 hits in 83 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 271 other cell types or tissues. DR ExpressionAtlas; P47811; baseline and differential. 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: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: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:0071493; P:cellular response to UV-B; ISO: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:0006974; P:DNA damage response; IDA: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: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:1900015; P:regulation of cytokine production involved in inflammatory response; ISO:MGI. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA: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: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:0031098; P:stress-activated protein kinase signaling 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 Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR IDEAL; IID50045; -. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR003527; MAP_kinase_CS. DR InterPro; IPR038784; MAPK14. DR InterPro; IPR008352; MAPK_p38-like. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR PANTHER; PTHR24055; MITOGEN-ACTIVATED PROTEIN KINASE; 1. DR PANTHER; PTHR24055:SF110; MITOGEN-ACTIVATED PROTEIN KINASE 14; 1. DR Pfam; PF00069; Pkinase; 1. DR PRINTS; PR01773; P38MAPKINASE. 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 Genevisible; P47811; MM. 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 //