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Mitogen-activated protein kinase 14 (MAP kinase 14) (MAPK 14) (EC 2.7.11.24) (Cytokine suppressive anti-inflammatory drug-binding protein) (CSAID-binding protein) (CSBP) (MAP kinase MXI2) (MAX-interacting protein 2) (Mitogen-activated protein kinase p38 alpha) (MAP kinase p38 alpha) (Stress-activated protein kinase 2a) (SAPK2a)

 MK14_HUMAN              Reviewed;         360 AA.
Q16539; A6ZJ92; A8K6P4; B0LPH0; B5TY32; O60776; Q13083; Q14084;
Q8TDX0;
01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
23-JAN-2007, sequence version 3.
30-AUG-2017, entry version 212.
RecName: Full=Mitogen-activated protein kinase 14;
Short=MAP kinase 14;
Short=MAPK 14;
EC=2.7.11.24 {ECO:0000269|PubMed:11010976, ECO:0000269|PubMed:15284239, ECO:0000269|PubMed:7493921};
AltName: Full=Cytokine suppressive anti-inflammatory drug-binding protein;
Short=CSAID-binding protein;
Short=CSBP;
AltName: Full=MAP kinase MXI2;
AltName: Full=MAX-interacting protein 2;
AltName: Full=Mitogen-activated protein kinase p38 alpha;
Short=MAP kinase p38 alpha;
AltName: Full=Stress-activated protein kinase 2a;
Short=SAPK2a;
Name=MAPK14; Synonyms=CSBP, CSBP1, CSBP2, CSPB1, MXI2, SAPK2A;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS CSBP1 AND CSBP2), AND PARTIAL
PROTEIN SEQUENCE.
TISSUE=Peripheral blood;
PubMed=7997261; DOI=10.1038/372739a0;
Lee J.C., Laydon J.T., McDonnell P.C., Gallagher T.F., Kumar S.,
Green D., McNulty D., Blumenthal M.J., Heys R.J., Landvatter S.W.,
Strickler J.E., McLaughlin M.M., Siemens I.R., Fisher S.M., Livi G.P.,
White J.R., Adams J.L., Young P.R.;
"A protein kinase involved in the regulation of inflammatory cytokine
biosynthesis.";
Nature 372:739-746(1994).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CSBP2).
TISSUE=Liver;
PubMed=7696354; DOI=10.1016/0167-4889(95)00002-A;
Han J., Richter B., Li Z., Kravchenko V.V., Ulevitch R.J.;
"Molecular cloning of human p38 MAP kinase.";
Biochim. Biophys. Acta 1265:224-227(1995).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM MXI2).
PubMed=7479834; DOI=10.1073/pnas.92.23.10531;
Zervos A.S., Faccio L., Gatto J.P., Kyriakis J.M., Brent R.;
"Mxi2, a mitogen-activated protein kinase that recognizes and
phosphorylates Max protein.";
Proc. Natl. Acad. Sci. U.S.A. 92:10531-10534(1995).
[4]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CSBP2).
TISSUE=B-cell;
PubMed=10727080; DOI=10.3109/10425179909033952;
Herbison C.E., Sayer D.C., Bellgard M., Allcock R.J.N.,
Christiansen F.T., Price P.;
"Structure and polymorphism of two stress-activated protein kinase
genes centromeric of the MHC: SAPK2a and SAPK4.";
DNA Seq. 10:229-243(1999).
[5]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM EXIP), AND ENZYME REGULATION.
TISSUE=Renal cell carcinoma;
PubMed=11866441; DOI=10.1006/bbrc.2002.6529;
Sudo T., Yagasaki Y., Hama H., Watanabe N., Osada H.;
"Exip, a new alternative splicing variant of p38 alpha, can induce an
earlier onset of apoptosis in HeLa cells.";
Biochem. Biophys. Res. Commun. 291:838-843(2002).
[6]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
PubMed=19906316; DOI=10.1186/1471-2164-10-518;
Wang P., Yu P., Gao P., Shi T., Ma D.;
"Discovery of novel human transcript variants by analysis of intronic
single-block EST with polyadenylation site.";
BMC Genomics 10:518-518(2009).
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[8]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CSBP2).
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
Phelan M., Farmer A.;
"Cloning of human full-length CDSs in BD Creator(TM) system donor
vector.";
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
[9]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CSBP2).
Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
Korn B., Zuo D., Hu Y., LaBaer J.;
"Cloning of human full open reading frames in Gateway(TM) system entry
vector (pDONR201).";
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
[10]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
NHLBI resequencing and genotyping service (RS&G);
Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
[11]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=14574404; DOI=10.1038/nature02055;
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
"The DNA sequence and analysis of human chromosome 6.";
Nature 425:805-811(2003).
[12]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
[13]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CSBP2).
TISSUE=Placenta;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[14]
PROTEIN SEQUENCE OF 2-10.
TISSUE=Platelet;
PubMed=12665801; DOI=10.1038/nbt810;
Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
Thomas G.R., Vandekerckhove J.;
"Exploring proteomes and analyzing protein processing by mass
spectrometric identification of sorted N-terminal peptides.";
Nat. Biotechnol. 21:566-569(2003).
[15]
PROTEIN SEQUENCE OF 174-186.
PubMed=7923354; DOI=10.1016/0092-8674(94)90278-X;
Freshney N.W., Rawlinson L., Guesdon F., Jones E., Cowley S.,
Hsuan J., Saklatvala J.;
"Interleukin-1 activates a novel protein kinase cascade that results
in the phosphorylation of Hsp27.";
Cell 78:1039-1049(1994).
[16]
PHOSPHORYLATION AT THR-180 AND TYR-182, ENZYME REGULATION, AND
SUBCELLULAR LOCATION.
PubMed=7535770; DOI=10.1074/jbc.270.13.7420;
Raingeaud J., Gupta S., Rogers J.S., Dickens M., Han J.,
Ulevitch R.J., Davis R.J.;
"Pro-inflammatory cytokines and environmental stress cause p38
mitogen-activated protein kinase activation by dual phosphorylation on
tyrosine and threonine.";
J. Biol. Chem. 270:7420-7426(1995).
[17]
MUTAGENESIS OF ALA-34; LYS-53; ASP-168; THR-175; THR-180 AND TYR-182,
AND CATALYTIC ACTIVITY.
PubMed=7493921; DOI=10.1074/jbc.270.49.29043;
Kumar S., McLaughlin M.M., McDonnell P.C., Lee J.C., Livi G.P.,
Young P.R.;
"Human mitogen-activated protein kinase CSBP1, but not CSBP2,
complements a hog1 deletion in yeast.";
J. Biol. Chem. 270:29043-29046(1995).
[18]
PHOSPHORYLATION BY MAP2K3/MKK3 AND MAP2K6/MKK6, AND ENZYME REGULATION.
PubMed=8622669; DOI=10.1128/MCB.16.3.1247;
Raingeaud J., Whitmarsh A.J., Barrett T., Derijard B., Davis R.J.;
"MKK3- and MKK6-regulated gene expression is mediated by the p38
mitogen-activated protein kinase signal transduction pathway.";
Mol. Cell. Biol. 16:1247-1255(1996).
[19]
FUNCTION IN ACTIVATION OF RPS6KA5/MSK1.
PubMed=9687510; DOI=10.1093/emboj/17.15.4426;
Deak M., Clifton A.D., Lucocq J.M., Alessi D.R.;
"Mitogen- and stress-activated protein kinase-1 (MSK1) is directly
activated by MAPK and SAPK2/p38, and may mediate activation of CREB.";
EMBO J. 17:4426-4441(1998).
[20]
FUNCTION IN PHOSPHORYLATION OF ATF2; ELK1 AND MBP, AND ENZYME
REGULATION.
PubMed=9430721; DOI=10.1074/jbc.273.3.1741;
Enslen H., Raingeaud J., Davis R.J.;
"Selective activation of p38 mitogen-activated protein (MAP) kinase
isoforms by the MAP kinase kinases MKK3 and MKK6.";
J. Biol. Chem. 273:1741-1748(1998).
[21]
INTERACTION WITH RPS6KA4, FUNCTION IN PHOSPHORYLATION OF RPS6KA4, AND
SUBCELLULAR LOCATION.
PubMed=9792677; DOI=10.1074/jbc.273.45.29661;
Pierrat B., Correia J.D.S., Mary J.L., Tomas-Zuber M., Lesslauer W.;
"RSK-B, a novel ribosomal S6 kinase family member, is a CREB kinase
under dominant control of p38alpha mitogen-activated protein kinase
(p38alphaMAPK).";
J. Biol. Chem. 273:29661-29671(1998).
[22]
INTERACTION WITH DUSP10, AND ENZYME REGULATION.
PubMed=10391943; DOI=10.1074/jbc.274.28.19949;
Tanoue T., Moriguchi T., Nishida E.;
"Molecular cloning and characterization of a novel dual specificity
phosphatase, MKP-5.";
J. Biol. Chem. 274:19949-19956(1999).
[23]
FUNCTION IN PHOSPHORYLATION OF MEF2A.
PubMed=9858528; DOI=10.1128/MCB.19.1.21;
Zhao M., New L., Kravchenko V.V., Kato Y., Gram H., di Padova F.,
Olson E.N., Ulevitch R.J., Han J.-D.;
"Regulation of the MEF2 family of transcription factors by p38.";
Mol. Cell. Biol. 19:21-30(1999).
[24]
FUNCTION IN PHOSPHORYLATION OF MEF2A AND MEF2C.
PubMed=10330143; DOI=10.1128/MCB.19.6.4028;
Yang S.-H., Galanis A., Sharrocks A.D.;
"Targeting of p38 mitogen-activated protein kinases to MEF2
transcription factors.";
Mol. Cell. Biol. 19:4028-4038(1999).
[25]
FUNCTION.
TISSUE=Hepatoma;
PubMed=10943842; DOI=10.1016/S0092-8674(00)00027-1;
Tamura K., Sudo T., Senftleben U., Dadak A.M., Johnson R., Karin M.;
"Requirement for p38alpha in erythropoietin expression: a role for
stress kinases in erythropoiesis.";
Cell 102:221-231(2000).
[26]
FUNCTION (ISOFORM MXI2), COFACTOR, AND ENZYME REGULATION.
PubMed=10838079; DOI=10.1016/S0014-5793(00)01598-2;
Sanz V., Arozarena I., Crespo P.;
"Distinct carboxy-termini confer divergent characteristics to the
mitogen-activated protein kinase p38alpha and its splice isoform
Mxi2.";
FEBS Lett. 474:169-174(2000).
[27]
INTERACTION WITH CSNK2A1 AND CSNK2B, AND FUNCTION IN ACTIVATION OF
CASEIN KINASE II.
PubMed=10747897; DOI=10.1074/jbc.M000312200;
Sayed M., Kim S.O., Salh B.S., Issinger O.G., Pelech S.L.;
"Stress-induced activation of protein kinase CK2 by direct interaction
with p38 mitogen-activated protein kinase.";
J. Biol. Chem. 275:16569-16573(2000).
[28]
INTERACTION WITH MA2PK6/MKK6, PHOSPHORYLATION BY MAP2K6/MKK6,
AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-54, AND CATALYTIC ACTIVITY.
PubMed=11010976; DOI=10.1074/jbc.M007835200;
Alonso G., Ambrosino C., Jones M., Nebreda A.R.;
"Differential activation of p38 mitogen-activated protein kinase
isoforms depending on signal strength.";
J. Biol. Chem. 275:40641-40648(2000).
[29]
INTERACTION WITH DUSP1, AND ENZYME REGULATION.
PubMed=11278799; DOI=10.1074/jbc.M010966200;
Slack D.N., Seternes O.M., Gabrielsen M., Keyse S.M.;
"Distinct binding determinants for ERK2/p38alpha and JNK map kinases
mediate catalytic activation and substrate selectivity of map kinase
phosphatase-1.";
J. Biol. Chem. 276:16491-16500(2001).
[30]
INTERACTION WITH DUSP16, AND ENZYME REGULATION.
PubMed=11359773; DOI=10.1074/jbc.M101981200;
Tanoue T., Yamamoto T., Maeda R., Nishida E.;
"A Novel MAPK phosphatase MKP-7 acts preferentially on JNK/SAPK and
p38 alpha and beta MAPKs.";
J. Biol. Chem. 276:26629-26639(2001).
[31]
FUNCTION AS MKNK2 KINASE.
PubMed=11154262; DOI=10.1128/MCB.21.3.743-754.2001;
Scheper G.C., Morrice N.A., Kleijn M., Proud C.G.;
"The mitogen-activated protein kinase signal-integrating kinase Mnk2
is a eukaryotic initiation factor 4E kinase with high levels of basal
activity in mammalian cells.";
Mol. Cell. Biol. 21:743-754(2001).
[32]
INTERACTION WITH CDC25B AND CDC25C, AND FUNCTION IN PHOSPHORYLATION OF
CDC25B AND CDC25C.
PubMed=11333986; DOI=10.1038/35075107;
Bulavin D.V., Higashimoto Y., Popoff I.J., Gaarde W.A., Basrur V.,
Potapova O., Appella E., Fornace A.J. Jr.;
"Initiation of a G2/M checkpoint after ultraviolet radiation requires
p38 kinase.";
Nature 411:102-107(2001).
[33]
INTERACTION WITH TAB1, AUTOPHOSPHORYLATION, ENZYME REGULATION, AND
CATALYTIC ACTIVITY.
PubMed=11847341; DOI=10.1126/science.1067289;
Ge B., Gram H., Di Padova F., Huang B., New L., Ulevitch R.J., Luo Y.,
Han J.;
"MAPKK-independent activation of p38alpha mediated by TAB1-dependent
autophosphorylation of p38alpha.";
Science 295:1291-1294(2002).
[34]
MUTAGENESIS OF TYR-69; ASP-176; ASP-177; ALA-320; PHE-327 AND TRP-337.
PubMed=15284239; DOI=10.1074/jbc.M404595200;
Diskin R., Askari N., Capone R., Engelberg D., Livnah O.;
"Active mutants of the human p38alpha mitogen-activated protein
kinase.";
J. Biol. Chem. 279:47040-47049(2004).
[35]
FUNCTION IN PHOSPHORYLATION OF S100A9.
PubMed=15905572; DOI=10.4049/jimmunol.174.11.7257;
Lominadze G., Rane M.J., Merchant M., Cai J., Ward R.A., McLeish K.R.;
"Myeloid-related protein-14 is a p38 MAPK substrate in human
neutrophils.";
J. Immunol. 174:7257-7267(2005).
[36]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=15592455; DOI=10.1038/nbt1046;
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
Zha X.-M., Polakiewicz R.D., Comb M.J.;
"Immunoaffinity profiling of tyrosine phosphorylation in cancer
cells.";
Nat. Biotechnol. 23:94-101(2005).
[37]
PHOSPHORYLATION AT TYR-323, AND ENZYME REGULATION.
PubMed=15735648; DOI=10.1038/ni1177;
Salvador J.M., Mittelstadt P.R., Guszczynski T., Copeland T.D.,
Yamaguchi H., Appella E., Fornace A.J. Jr., Ashwell J.D.;
"Alternative p38 activation pathway mediated by T cell receptor-
proximal tyrosine kinases.";
Nat. Immunol. 6:390-395(2005).
[38]
INTERACTION WITH TAB1, AUTOPHOSPHORYLATION, AND ENZYME REGULATION.
PubMed=15735649; DOI=10.1038/ni1176;
Salvador J.M., Mittelstadt P.R., Belova G.I., Fornace A.J. Jr.,
Ashwell J.D.;
"The autoimmune suppressor Gadd45alpha inhibits the T cell alternative
p38 activation pathway.";
Nat. Immunol. 6:396-402(2005).
[39]
INTERACTION WITH SUPT20H.
PubMed=16751104; DOI=10.1016/j.cell.2006.03.048;
Zohn I.E., Li Y., Skolnik E.Y., Anderson K.V., Han J., Niswander L.;
"p38 and a p38-interacting protein are critical for downregulation of
E-cadherin during mouse gastrulation.";
Cell 125:957-969(2006).
[40]
FUNCTION IN STRESS-INDUCED INTERNALIZATION OF EGFR.
PubMed=16932740; DOI=10.1038/sj.emboj.7601297;
Zwang Y., Yarden Y.;
"p38 MAP kinase mediates stress-induced internalization of EGFR:
implications for cancer chemotherapy.";
EMBO J. 25:4195-4206(2006).
[41]
FUNCTION IN PHOSPHORYLATION OF SIAH2, AND ENZYME REGULATION.
PubMed=17003045; DOI=10.1074/jbc.M606568200;
Khurana A., Nakayama K., Williams S., Davis R.J., Mustelin T.,
Ronai Z.;
"Regulation of the ring finger E3 ligase Siah2 by p38 MAPK.";
J. Biol. Chem. 281:35316-35326(2006).
[42]
INTERACTION WITH NP60.
PubMed=16352664; DOI=10.1242/jcs.02699;
Fu J., Yang Z., Wei J., Han J., Gu J.;
"Nuclear protein NP60 regulates p38 MAPK activity.";
J. Cell Sci. 119:115-123(2006).
[43]
FUNCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION, AND UBIQUITINATION.
PubMed=17724032; DOI=10.1074/jbc.M703857200;
Qi X., Pohl N.M., Loesch M., Hou S., Li R., Qin J.Z., Cuenda A.,
Chen G.;
"p38alpha antagonizes p38gamma activity through c-Jun-dependent
ubiquitin-proteasome pathways in regulating Ras transformation and
stress response.";
J. Biol. Chem. 282:31398-31408(2007).
[44]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-263, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Embryonic kidney;
PubMed=17525332; DOI=10.1126/science.1140321;
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
"ATM and ATR substrate analysis reveals extensive protein networks
responsive to DNA damage.";
Science 316:1160-1166(2007).
[45]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Platelet;
PubMed=18088087; DOI=10.1021/pr0704130;
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
Schuetz C., Walter U., Gambaryan S., Sickmann A.;
"Phosphoproteome of resting human platelets.";
J. Proteome Res. 7:526-534(2008).
[46]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-16, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
Greff Z., Keri G., Stemmann O., Mann M.;
"Kinase-selective enrichment enables quantitative phosphoproteomics of
the kinome across the cell cycle.";
Mol. Cell 31:438-448(2008).
[47]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-180 AND TYR-182, AND
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=18669648; DOI=10.1073/pnas.0805139105;
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
Elledge S.J., Gygi S.P.;
"A quantitative atlas of mitotic phosphorylation.";
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
[48]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
Mann M., Daub H.;
"Large-scale proteomics analysis of the human kinome.";
Mol. Cell. Proteomics 8:1751-1764(2009).
[49]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-180 AND TYR-182, AND
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Leukemic T-cell;
PubMed=19690332; DOI=10.1126/scisignal.2000007;
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
Rodionov V., Han D.K.;
"Quantitative phosphoproteomic analysis of T cell receptor signaling
reveals system-wide modulation of protein-protein interactions.";
Sci. Signal. 2:RA46-RA46(2009).
[50]
FUNCTION IN INHIBITION OF AUTOPHAGY.
PubMed=19893488; DOI=10.1038/emboj.2009.321;
Webber J.L., Tooze S.A.;
"Coordinated regulation of autophagy by p38alpha MAPK through mAtg9
and p38IP.";
EMBO J. 29:27-40(2010).
[51]
FUNCTION IN PHOSPHORYLATION OF TIAR.
PubMed=20932473; DOI=10.1016/j.molcel.2010.09.018;
Reinhardt H.C., Hasskamp P., Schmedding I., Morandell S.,
van Vugt M.A., Wang X., Linding R., Ong S.E., Weaver D., Carr S.A.,
Yaffe M.B.;
"DNA damage activates a spatially distinct late cytoplasmic cell-cycle
checkpoint network controlled by MK2-mediated RNA stabilization.";
Mol. Cell 40:34-49(2010).
[52]
INTERACTION WITH ADAM17, AND FUNCTION IN PHOSPHORYLATION OF ADAM17.
PubMed=20188673; DOI=10.1016/j.molcel.2010.01.034;
Xu P., Derynck R.;
"Direct activation of TACE-mediated ectodomain shedding by p38 MAP
kinase regulates EGF receptor-dependent cell proliferation.";
Mol. Cell 37:551-566(2010).
[53]
ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE
SCALE ANALYSIS] AT SER-2; THR-180 AND TYR-182, CLEAVAGE OF INITIATOR
METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS
SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=20068231; DOI=10.1126/scisignal.2000475;
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
Mann M.;
"Quantitative phosphoproteomics reveals widespread full
phosphorylation site occupancy during mitosis.";
Sci. Signal. 3:RA3-RA3(2010).
[54]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=21269460; DOI=10.1186/1752-0509-5-17;
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
"Initial characterization of the human central proteome.";
BMC Syst. Biol. 5:17-17(2011).
[55]
IDENTIFICATION IN A COMPLEX WITH AKAP13; PKN1; ZAK AND MAP2K3.
PubMed=21224381; DOI=10.1074/jbc.M110.185645;
Cariolato L., Cavin S., Diviani D.;
"A-kinase anchoring protein (AKAP)-Lbc anchors a PKN-based signaling
complex involved in alpha1-adrenergic receptor-induced p38
activation.";
J. Biol. Chem. 286:7925-7937(2011).
[56]
FUNCTION (MICROBIAL INFECTION).
TISSUE=T-cell;
PubMed=21586573; DOI=10.1074/jbc.M111.234062;
Peng H., Wang X., Barnes P.F., Tang H., Townsend J.C., Samten B.;
"The Mycobacterium tuberculosis early secreted antigenic target of 6
kDa inhibits T cell interferon-gamma production through the p38
mitogen-activated protein kinase pathway.";
J. Biol. Chem. 286:24508-24518(2011).
[57]
ACETYLATION AT LYS-53 AND LYS-152 BY KAT2B/PCAF AND EP300, AND
DEACETYLATION BY HDAC3.
PubMed=21444723; DOI=10.1128/MCB.01205-10;
Pillai V.B., Sundaresan N.R., Samant S.A., Wolfgeher D., Trivedi C.M.,
Gupta M.P.;
"Acetylation of a conserved lysine residue in the ATP binding pocket
of p38 augments its kinase activity during hypertrophy of
cardiomyocytes.";
Mol. Cell. Biol. 31:2349-2363(2011).
[58]
INTERACTION WITH CDK5RAP3 AND PPM1D, AND DEPHOSPHORYLATION BY PPM1D.
PubMed=21283629; DOI=10.1371/journal.pone.0016427;
An H., Lu X., Liu D., Yarbrough W.G.;
"LZAP inhibits p38 MAPK (p38) phosphorylation and activity by
facilitating p38 association with the wild-type p53 induced
phosphatase 1 (WIP1).";
PLoS ONE 6:E16427-E16427(2011).
[59]
REVIEW ON FUNCTION.
PubMed=12452429; DOI=10.1515/BC.2002.173;
Shi Y., Gaestel M.;
"In the cellular garden of forking paths: how p38 MAPKs signal for
downstream assistance.";
Biol. Chem. 383:1519-1536(2002).
[60]
REVIEW ON ENZYME REGULATION, AND REVIEW ON FUNCTION.
PubMed=20626350; DOI=10.1042/BJ20100323;
Cuadrado A., Nebreda A.R.;
"Mechanisms and functions of p38 MAPK signalling.";
Biochem. J. 429:403-417(2010).
[61]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; THR-180 AND TYR-182,
AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma, and Erythroleukemia;
PubMed=23186163; DOI=10.1021/pr300630k;
Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
Mohammed S.;
"Toward a comprehensive characterization of a human cancer cell
phosphoproteome.";
J. Proteome Res. 12:260-271(2013).
[62]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Liver;
PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
Wang L., Ye M., Zou H.;
"An enzyme assisted RP-RPLC approach for in-depth analysis of human
liver phosphoproteome.";
J. Proteomics 96:253-262(2014).
[63]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=25944712; DOI=10.1002/pmic.201400617;
Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M.,
Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
"N-terminome analysis of the human mitochondrial proteome.";
Proteomics 15:2519-2524(2015).
[64]
X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
PubMed=8910361; DOI=10.1074/jbc.271.44.27696;
Wilson K.P., Fitzgibbon M.J., Caron P.R., Griffith J.P., Chen W.,
McCaffrey P.G., Chambers S.P., Su M.S.-S.;
"Crystal structure of p38 mitogen-activated protein kinase.";
J. Biol. Chem. 271:27696-27700(1996).
[65]
X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
PubMed=9095200; DOI=10.1038/nsb0497-311;
Tong L., Pav S., White D.M., Rogers S., Crane K.M., Cywin C.L.,
Brown M.L., Pargellis C.A.;
"A highly specific inhibitor of human p38 MAP kinase binds in the ATP
pocket.";
Nat. Struct. Biol. 4:311-316(1997).
[66]
X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
PubMed=9753691; DOI=10.1016/S0969-2126(98)00113-0;
Wang Z., Canagarajah B.J., Boehm J.C., Kassisa S., Cobb M.H.,
Young P.R., Abdel-Meguid S., Adams J.L., Goldsmith E.J.;
"Structural basis of inhibitor selectivity in MAP kinases.";
Structure 6:1117-1128(1998).
[67]
X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS).
PubMed=10633045; DOI=10.1021/jm990401t;
Shewchuk L., Hassell A., Wisely B., Rocque W., Holmes W., Veal J.,
Kuyper L.F.;
"Binding mode of the 4-anilinoquinazoline class of protein kinase
inhibitor: X-ray crystallographic studies of 4-anilinoquinazolines
bound to cyclin-dependent kinase 2 and p38 kinase.";
J. Med. Chem. 43:133-138(2000).
[68]
X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS), AND ENZYME REGULATION.
PubMed=11896401; DOI=10.1038/nsb770;
Pargellis C., Tong L., Churchill L., Cirillo P.F., Gilmore T.,
Graham A.G., Grob P.M., Hickey E.R., Moss N., Pav S., Regan J.;
"Inhibition of p38 MAP kinase by utilizing a novel allosteric binding
site.";
Nat. Struct. Biol. 9:268-272(2002).
[69]
X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS), AND ENZYME REGULATION.
PubMed=12482439; DOI=10.1016/S0960-894X(02)00752-7;
Stelmach J.E., Liu L., Patel S.B., Pivnichny J.V., Scapin G.,
Singh S., Hop C.E., Wang Z., Strauss J.R., Cameron P.M., Nichols E.A.,
O'Keefe S.J., O'Neill E.A., Schmatz D.M., Schwartz C.D.,
Thompson C.M., Zaller D.M., Doherty J.B.;
"Design and synthesis of potent, orally bioavailable
dihydroquinazolinone inhibitors of p38 MAP kinase.";
Bioorg. Med. Chem. Lett. 13:277-280(2003).
[70]
X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS), AND ENZYME REGULATION.
PubMed=14561090; DOI=10.1021/jm0301787;
Trejo A., Arzeno H., Browner M., Chanda S., Cheng S., Comer D.D.,
Dalrymple S.A., Dunten P., Lafargue J., Lovejoy B., Freire-Moar J.,
Lim J., Mcintosh J., Miller J., Papp E., Reuter D., Roberts R.,
Sanpablo F., Saunders J., Song K., Villasenor A., Warren S.D.,
Welch M., Weller P., Whiteley P.E., Zeng L., Goldstein D.M.;
"Design and synthesis of 4-azaindoles as inhibitors of p38 MAP
kinase.";
J. Med. Chem. 46:4702-4713(2003).
[71]
X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
PubMed=12897767; DOI=10.1038/nsb949;
Fitzgerald C.E., Patel S.B., Becker J.W., Cameron P.M., Zaller D.,
Pikounis V.B., O'Keefe S.J., Scapin G.;
"Structural basis for p38alpha MAP kinase quinazolinone and pyridol-
pyrimidine inhibitor specificity.";
Nat. Struct. Biol. 10:764-769(2003).
[72]
X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS), AND ENZYME REGULATION.
PubMed=14726206;
Patel S.B., Cameron P.M., Frantz-Wattley B., O'Neill E., Becker J.W.,
Scapin G.;
"Lattice stabilization and enhanced diffraction in human p38 alpha
crystals by protein engineering.";
Biochim. Biophys. Acta 1696:67-73(2004).
[73]
X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 2-359 IN COMPLEX WITH
INHIBITOR.
PubMed=16342939; DOI=10.1021/bi051714v;
Sullivan J.E., Holdgate G.A., Campbell D., Timms D., Gerhardt S.,
Breed J., Breeze A.L., Bermingham A., Pauptit R.A., Norman R.A.,
Embrey K.J., Read J., VanScyoc W.S., Ward W.H.;
"Prevention of MKK6-dependent activation by binding to p38alpha MAP
kinase.";
Biochemistry 44:16475-16490(2005).
[74]
X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-359, AND ENZYME
REGULATION.
PubMed=15837335; DOI=10.1016/j.bmcl.2005.02.010;
Tamayo N., Liao L., Goldberg M., Powers D., Tudor Y.Y., Yu V.,
Wong L.M., Henkle B., Middleton S., Syed R., Harvey T., Jang G.,
Hungate R., Dominguez C.;
"Design and synthesis of potent pyridazine inhibitors of p38 MAP
kinase.";
Bioorg. Med. Chem. Lett. 15:2409-2413(2005).
[75]
X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS), AND ENZYME REGULATION.
PubMed=16169718; DOI=10.1016/j.bmcl.2005.08.038;
Michelotti E.L., Moffett K.K., Nguyen D., Kelly M.J., Shetty R.,
Chai X., Northrop K., Namboodiri V., Campbell B., Flynn G.A.,
Fujimoto T., Hollinger F.P., Bukhtiyarova M., Springman E.B.,
Karpusas M.;
"Two classes of p38alpha MAP kinase inhibitors having a common
diphenylether core but exhibiting divergent binding modes.";
Bioorg. Med. Chem. Lett. 15:5274-5279(2005).
[76]
X-RAY CRYSTALLOGRAPHY (2.16 ANGSTROMS) OF 2-359 IN COMPLEX WITH
INHIBITOR.
PubMed=15658854; DOI=10.1021/jm0495778;
Hartshorn M.J., Murray C.W., Cleasby A., Frederickson M., Tickle I.J.,
Jhoti H.;
"Fragment-based lead discovery using X-ray crystallography.";
J. Med. Chem. 48:403-413(2005).
[77]
X-RAY CRYSTALLOGRAPHY (4.0 ANGSTROMS) OF 2-359 IN COMPLEX WITH
MAPKAPK2.
PubMed=17255097; DOI=10.1074/jbc.M611165200;
ter Haar E., Prabhakar P., Liu X., Lepre C.;
"Crystal structure of the p38 alpha-MAPKAP kinase 2 heterodimer.";
J. Biol. Chem. 282:9733-9739(2007).
[78]
ERRATUM.
ter Haar E., Prabhakar P., Liu X., Lepre C.;
J. Biol. Chem. 282:14684-14684(2007).
[79]
VARIANTS [LARGE SCALE ANALYSIS] VAL-51; ARG-322 AND GLY-343.
PubMed=17344846; DOI=10.1038/nature05610;
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
"Patterns of somatic mutation in human cancer genomes.";
Nature 446:153-158(2007).
-!- FUNCTION: Serine/threonine kinase which acts as an essential
component of the MAP kinase signal transduction pathway. MAPK14 is
one of the four p38 MAPKs which play an important role in the
cascades of cellular responses evoked by extracellular stimuli
such as proinflammatory cytokines or physical stress leading to
direct activation of transcription factors. Accordingly, p38 MAPKs
phosphorylate a broad range of proteins and it has been estimated
that they may have approximately 200 to 300 substrates each. Some
of the targets are downstream kinases which are activated through
phosphorylation and further phosphorylate additional targets.
RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and
activate transcription factors such as CREB1, ATF1, the NF-kappa-B
isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate
histone H3 and the nucleosomal protein HMGN1. RPS6KA5/MSK1 and
RPS6KA4/MSK2 play important roles in the rapid induction of
immediate-early genes in response to stress or mitogenic stimuli,
either by inducing chromatin remodeling or by recruiting the
transcription machinery. On the other hand, two other kinase
targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control
of gene expression mostly at the post-transcriptional level, by
phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by
regulating EEF2K, which is important for the elongation of mRNA
during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases
activated by p38 MAPKs, regulate protein synthesis by
phosphorylating the initiation factor EIF4E2. MAPK14 interacts
also with casein kinase II, leading to its activation through
autophosphorylation and further phosphorylation of TP53/p53. In
the cytoplasm, the p38 MAPK pathway is an important regulator of
protein turnover. For example, CFLAR is an inhibitor of TNF-
induced apoptosis whose proteasome-mediated degradation is
regulated by p38 MAPK phosphorylation. In a similar way, MAPK14
phosphorylates the ubiquitin ligase SIAH2, regulating its activity
towards EGLN3. MAPK14 may also inhibit the lysosomal degradation
pathway of autophagy by interfering with the intracellular
trafficking of the transmembrane protein ATG9. Another function of
MAPK14 is to regulate the endocytosis of membrane receptors by
different mechanisms that impinge on the small GTPase RAB5A. In
addition, clathrin-mediated EGFR internalization induced by
inflammatory cytokines and UV irradiation depends on MAPK14-
mediated phosphorylation of EGFR itself as well as of RAB5A
effectors. Ectodomain shedding of transmembrane proteins is
regulated by p38 MAPKs as well. In response to inflammatory
stimuli, p38 MAPKs phosphorylate the membrane-associated
metalloprotease ADAM17. Such phosphorylation is required for
ADAM17-mediated ectodomain shedding of TGF-alpha family ligands,
which results in the activation of EGFR signaling and cell
proliferation. Another p38 MAPK substrate is FGFR1. FGFR1 can be
translocated from the extracellular space into the cytosol and
nucleus of target cells, and regulates processes such as rRNA
synthesis and cell growth. FGFR1 translocation requires p38 MAPK
activation. In the nucleus, many transcription factors are
phosphorylated and activated by p38 MAPKs in response to different
stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH,
DDIT3, TP53/p53 and MEF2C and MEF2A. The p38 MAPKs are emerging as
important modulators of gene expression by regulating chromatin
modifiers and remodelers. The promoters of several genes involved
in the inflammatory response, such as IL6, IL8 and IL12B, display
a p38 MAPK-dependent enrichment of histone H3 phosphorylation on
'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This
phosphorylation enhances the accessibility of the cryptic NF-
kappa-B-binding sites marking promoters for increased NF-kappa-B
recruitment. Phosphorylates CDC25B and CDC25C which is required
for binding to 14-3-3 proteins and leads to initiation of a G2
delay after ultraviolet radiation. Phosphorylates TIAR following
DNA damage, releasing TIAR from GADD45A mRNA and preventing mRNA
degradation. The p38 MAPKs may also have kinase-independent roles,
which are thought to be due to the binding to targets in the
absence of phosphorylation. Protein O-Glc-N-acylation catalyzed by
the OGT is regulated by MAPK14, and, although OGT does not seem to
be phosphorylated by MAPK14, their interaction increases upon
MAPK14 activation induced by glucose deprivation. This interaction
may regulate OGT activity by recruiting it to specific targets
such as neurofilament H, stimulating its O-Glc-N-acylation.
Required in mid-fetal development for the growth of embryo-derived
blood vessels in the labyrinth layer of the placenta. Also plays
an essential role in developmental and stress-induced
erythropoiesis, through regulation of EPO gene expression. Isoform
MXI2 activation is stimulated by mitogens and oxidative stress and
only poorly phosphorylates ELK1 and ATF2. Isoform EXIP may play a
role in the early onset of apoptosis. Phosphorylates S100A9 at
'Thr-113'. {ECO:0000269|PubMed:10330143,
ECO:0000269|PubMed:10747897, ECO:0000269|PubMed:10943842,
ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:11333986,
ECO:0000269|PubMed:15905572, ECO:0000269|PubMed:16932740,
ECO:0000269|PubMed:17003045, ECO:0000269|PubMed:17724032,
ECO:0000269|PubMed:19893488, ECO:0000269|PubMed:20188673,
ECO:0000269|PubMed:20932473, ECO:0000269|PubMed:9430721,
ECO:0000269|PubMed:9687510, ECO:0000269|PubMed:9792677,
ECO:0000269|PubMed:9858528}.
-!- FUNCTION: (Microbial infection) Activated by phosphorylation by
M.tuberculosis EsxA in T-cells leading to inhibition of IFN-gamma
production; phosphorylation is apparent within 15 minute and is
inhibited by kinase-specific inhibitors SB203580 and siRNA
(PubMed:21586573). {ECO:0000269|PubMed:21586573}.
-!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
{ECO:0000269|PubMed:11010976}.
-!- COFACTOR:
Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
Evidence={ECO:0000269|PubMed:10838079};
-!- ENZYME REGULATION: Activated by cell stresses such as DNA damage,
heat shock, osmotic shock, anisomycin and sodium arsenite, as well
as pro-inflammatory stimuli such as bacterial lipopolysaccharide
(LPS) and interleukin-1. Activation occurs through dual
phosphorylation of Thr-180 and Tyr-182 by either of two dual
specificity kinases, MAP2K3/MKK3 or MAP2K6/MKK6, and potentially
also MAP2K4/MKK4, as well as by TAB1-mediated autophosphorylation.
MAPK14 phosphorylated on both Thr-180 and Tyr-182 is 10-20-fold
more active than MAPK14 phosphorylated only on Thr-180, whereas
MAPK14 phosphorylated on Tyr-182 alone is inactive. whereas Thr-
180 is necessary for catalysis, Tyr-182 may be required for auto-
activation and substrate recognition. Phosphorylated at Tyr-323 by
ZAP70 in an alternative activation pathway in response to TCR
signaling in T-cells. This alternative pathway is inhibited by
GADD45A. Inhibited by dual specificity phosphatases, such as
DUSP1, DUSP10, and DUSP16. Specifically inhibited by the binding
of pyridinyl-imidazole compounds, which are cytokine-suppressive
anti-inflammatory drugs (CSAID). Isoform Mxi2 is 100-fold less
sensitive to these agents than the other isoforms and is not
inhibited by DUSP1. Isoform Exip is not activated by MAP2K6.
SB203580 is an inhibitor of MAPK14. {ECO:0000269|PubMed:10391943,
ECO:0000269|PubMed:10838079, ECO:0000269|PubMed:11278799,
ECO:0000269|PubMed:11359773, ECO:0000269|PubMed:11847341,
ECO:0000269|PubMed:11866441, ECO:0000269|PubMed:11896401,
ECO:0000269|PubMed:12482439, ECO:0000269|PubMed:14561090,
ECO:0000269|PubMed:14726206, ECO:0000269|PubMed:15735648,
ECO:0000269|PubMed:15735649, ECO:0000269|PubMed:15837335,
ECO:0000269|PubMed:16169718, ECO:0000269|PubMed:17003045,
ECO:0000269|PubMed:7535770, ECO:0000269|PubMed:8622669,
ECO:0000269|PubMed:9430721}.
-!- SUBUNIT: Component of a signaling complex containing at least
AKAP13, PKN1, MAPK14, ZAK and MAP2K3. Within this complex, AKAP13
interacts directly with PKN1, which in turn recruits MAPK14,
MAP2K3 and ZAK (PubMed:21224381). Binds to a kinase interaction
motif within the protein tyrosine phosphatase, PTPRR (By
similarity). This interaction retains MAPK14 in the cytoplasm and
prevents nuclear accumulation (By similarity). Interacts with
SPAG9 and GADD45A (By similarity). Interacts with CDC25B, CDC25C,
DUSP1, DUSP10, DUSP16, NP60, SUPT20H and TAB1. Interacts with
casein kinase II subunits CSNK2A1 and CSNK2B. Interacts with
PPM1D. Interacts with CDK5RAP3; recruits PPM1D to MAPK14 and may
regulate its dephosphorylation (PubMed:21283629).
{ECO:0000250|UniProtKB:P47811, ECO:0000269|PubMed:10391943,
ECO:0000269|PubMed:10747897, ECO:0000269|PubMed:11010976,
ECO:0000269|PubMed:11278799, ECO:0000269|PubMed:11333986,
ECO:0000269|PubMed:11359773, ECO:0000269|PubMed:11847341,
ECO:0000269|PubMed:12897767, ECO:0000269|PubMed:15658854,
ECO:0000269|PubMed:15735649, ECO:0000269|PubMed:16342939,
ECO:0000269|PubMed:16352664, ECO:0000269|PubMed:16751104,
ECO:0000269|PubMed:17255097, ECO:0000269|PubMed:20188673,
ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:21283629,
ECO:0000269|PubMed:9792677}.
-!- INTERACTION:
P31749:AKT1; NbExp=2; IntAct=EBI-73946, EBI-296087;
P28562:DUSP1; NbExp=4; IntAct=EBI-73946, EBI-975493;
Q99956:DUSP9; NbExp=3; IntAct=EBI-73946, EBI-3906678;
P46734:MAP2K3; NbExp=2; IntAct=EBI-73946, EBI-602462;
P28482:MAPK1; NbExp=5; IntAct=EBI-6932370, EBI-959949;
P27361:MAPK3; NbExp=5; IntAct=EBI-73946, EBI-73995;
P49137:MAPKAPK2; NbExp=7; IntAct=EBI-73946, EBI-993299;
Q16644:MAPKAPK3; NbExp=5; IntAct=EBI-73946, EBI-1384657;
Q9BUB5:MKNK1; NbExp=3; IntAct=EBI-73946, EBI-73837;
Q9HBH9:MKNK2; NbExp=3; IntAct=EBI-73946, EBI-2864341;
P49790:NUP153; NbExp=2; IntAct=EBI-6932370, EBI-286779;
P35813:PPM1A; NbExp=2; IntAct=EBI-73946, EBI-989143;
Q15256:PTPRR; NbExp=3; IntAct=EBI-73946, EBI-2265659;
P06400:RB1; NbExp=4; IntAct=EBI-73946, EBI-491274;
O75676:RPS6KA4; NbExp=4; IntAct=EBI-73946, EBI-73933;
Q8NEM7:SUPT20H; NbExp=5; IntAct=EBI-73946, EBI-946984;
Q15750:TAB1; NbExp=2; IntAct=EBI-73946, EBI-358643;
Q92574:TSC1; NbExp=2; IntAct=EBI-73946, EBI-1047085;
Q07352:ZFP36L1; NbExp=2; IntAct=EBI-73946, EBI-721823;
O43257:ZNHIT1; NbExp=7; IntAct=EBI-73946, EBI-347522;
-!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:7535770}.
Nucleus {ECO:0000269|PubMed:7535770}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=5;
Name=CSBP2;
IsoId=Q16539-1; Sequence=Displayed;
Name=CSBP1;
IsoId=Q16539-2; Sequence=VSP_004842;
Name=Mxi2;
IsoId=Q16539-3; Sequence=VSP_004844;
Name=Exip; Synonyms=Exon skip;
IsoId=Q16539-4; Sequence=VSP_004843, VSP_004845;
Name=5;
IsoId=Q16539-5; Sequence=VSP_057194;
-!- TISSUE SPECIFICITY: Brain, heart, placenta, pancreas and skeletal
muscle. Expressed to a lesser extent in lung, liver and kidney.
-!- DOMAIN: The TXY motif contains the threonine and tyrosine residues
whose phosphorylation activates the MAP kinases.
-!- PTM: Dually phosphorylated on Thr-180 and Tyr-182 by the MAP2Ks
MAP2K3/MKK3, MAP2K4/MKK4 and MAP2K6/MKK6 in response to
inflammatory citokines, environmental stress or growth factors,
which activates the enzyme. Dual phosphorylation can also be
mediated by TAB1-mediated autophosphorylation. TCR engagement in
T-cells also leads to Tyr-323 phosphorylation by ZAP70.
Dephosphorylated and inactivated by DUPS1, DUSP10 and DUSP16.
PPM1D also mediates dephosphorylation and inactivation of MAPK14
(PubMed:21283629). {ECO:0000269|PubMed:11010976,
ECO:0000269|PubMed:15735648, ECO:0000269|PubMed:17724032,
ECO:0000269|PubMed:21283629, ECO:0000269|PubMed:7535770,
ECO:0000269|PubMed:8622669}.
-!- PTM: Acetylated at Lys-53 and Lys-152 by KAT2B and EP300.
Acetylation at Lys-53 increases the affinity for ATP and enhances
kinase activity. Lys-53 and Lys-152 are deacetylated by HDAC3.
{ECO:0000269|PubMed:21444723}.
-!- PTM: Ubiquitinated. Ubiquitination leads to degradation by the
proteasome pathway. {ECO:0000269|PubMed:17724032}.
-!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC
Ser/Thr protein kinase family. MAP kinase subfamily.
{ECO:0000305}.
-!- WEB RESOURCE: Name=Wikipedia; Note=P38 mitogen-activated protein
kinases entry;
URL="https://en.wikipedia.org/wiki/P38_mitogen-activated_protein_kinases";
-!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
and Haematology;
URL="http://atlasgeneticsoncology.org/Genes/MAPK14ID41292ch6p21.html";
-----------------------------------------------------------------------
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EMBL; L35263; AAA57455.1; -; mRNA.
EMBL; L35264; AAA57456.1; -; mRNA.
EMBL; L35253; AAA74301.1; -; mRNA.
EMBL; U19775; AAC50329.1; -; mRNA.
EMBL; AF100544; AAF36770.1; -; mRNA.
EMBL; AB074150; BAB85654.1; -; mRNA.
EMBL; FJ032367; ACI00233.1; -; mRNA.
EMBL; AK291709; BAF84398.1; -; mRNA.
EMBL; BT006933; AAP35579.1; -; mRNA.
EMBL; CR536505; CAG38743.1; -; mRNA.
EMBL; EU332860; ABY87549.1; -; Genomic_DNA.
EMBL; Z95152; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; CH471081; EAX03869.1; -; Genomic_DNA.
EMBL; BC000092; AAH00092.1; -; mRNA.
EMBL; BC031574; AAH31574.1; -; mRNA.
CCDS; CCDS4815.1; -. [Q16539-2]
CCDS; CCDS4816.1; -. [Q16539-1]
CCDS; CCDS4817.1; -. [Q16539-4]
PIR; S53536; S53536.
RefSeq; NP_001306.1; NM_001315.2. [Q16539-2]
RefSeq; NP_620581.1; NM_139012.2. [Q16539-1]
RefSeq; NP_620582.1; NM_139013.2. [Q16539-3]
RefSeq; NP_620583.1; NM_139014.2. [Q16539-4]
UniGene; Hs.485233; -.
PDB; 1A9U; X-ray; 2.50 A; A=1-360.
PDB; 1BL6; X-ray; 2.50 A; A=1-360.
PDB; 1BL7; X-ray; 2.50 A; A=1-360.
PDB; 1BMK; X-ray; 2.40 A; A=1-360.
PDB; 1DI9; X-ray; 2.60 A; A=1-360.
PDB; 1IAN; X-ray; 2.00 A; A=2-360.
PDB; 1KV1; X-ray; 2.50 A; A=1-360.
PDB; 1KV2; X-ray; 2.80 A; A=1-360.
PDB; 1M7Q; X-ray; 2.40 A; A=1-360.
PDB; 1OUK; X-ray; 2.50 A; A=1-360.
PDB; 1OUY; X-ray; 2.50 A; A=1-360.
PDB; 1OVE; X-ray; 2.10 A; A=1-360.
PDB; 1OZ1; X-ray; 2.10 A; A=1-360.
PDB; 1R39; X-ray; 2.30 A; A=1-360.
PDB; 1R3C; X-ray; 2.00 A; A=1-360.
PDB; 1W7H; X-ray; 2.21 A; A=2-360.
PDB; 1W82; X-ray; 2.20 A; A=2-360.
PDB; 1W83; X-ray; 2.50 A; A=2-360.
PDB; 1W84; X-ray; 2.20 A; A=2-360.
PDB; 1WBN; X-ray; 2.40 A; A=2-360.
PDB; 1WBO; X-ray; 2.16 A; A=2-360.
PDB; 1WBS; X-ray; 1.80 A; A=2-360.
PDB; 1WBT; X-ray; 2.00 A; A=2-360.
PDB; 1WBV; X-ray; 2.00 A; A=2-360.
PDB; 1WBW; X-ray; 2.41 A; A=2-360.
PDB; 1WFC; X-ray; 2.30 A; A=1-360.
PDB; 1YQJ; X-ray; 2.00 A; A=2-360.
PDB; 1ZYJ; X-ray; 2.00 A; A=1-360.
PDB; 1ZZ2; X-ray; 2.00 A; A=1-360.
PDB; 1ZZL; X-ray; 2.00 A; A=4-354.
PDB; 2BAJ; X-ray; 2.25 A; A=2-360.
PDB; 2BAK; X-ray; 2.20 A; A=2-360.
PDB; 2BAL; X-ray; 2.10 A; A=2-360.
PDB; 2BAQ; X-ray; 2.80 A; A=2-360.
PDB; 2FSL; X-ray; 1.70 A; X=2-360.
PDB; 2FSM; X-ray; 1.86 A; X=2-360.
PDB; 2FSO; X-ray; 1.83 A; X=2-360.
PDB; 2FST; X-ray; 1.45 A; X=2-360.
PDB; 2GFS; X-ray; 1.75 A; A=2-360.
PDB; 2I0H; X-ray; 2.00 A; A=1-360.
PDB; 2LGC; NMR; -; A=2-354.
PDB; 2NPQ; X-ray; 1.80 A; A=2-360.
PDB; 2OKR; X-ray; 2.00 A; A/D=2-360.
PDB; 2ONL; X-ray; 4.00 A; A/B=2-360.
PDB; 2QD9; X-ray; 1.70 A; A=2-360.
PDB; 2RG5; X-ray; 2.40 A; A=2-360.
PDB; 2RG6; X-ray; 1.72 A; A=2-360.
PDB; 2Y8O; X-ray; 1.95 A; A=1-360.
PDB; 2YIS; X-ray; 2.00 A; A=2-360.
PDB; 2YIW; X-ray; 2.00 A; A=2-360.
PDB; 2YIX; X-ray; 2.30 A; A=4-354.
PDB; 2ZAZ; X-ray; 1.80 A; A=1-360.
PDB; 2ZB0; X-ray; 2.10 A; A=1-360.
PDB; 2ZB1; X-ray; 2.50 A; A=1-360.
PDB; 3BV2; X-ray; 2.40 A; A=2-360.
PDB; 3BV3; X-ray; 2.59 A; A=2-360.
PDB; 3BX5; X-ray; 2.40 A; A=2-360.
PDB; 3C5U; X-ray; 2.80 A; A=2-360.
PDB; 3CTQ; X-ray; 1.95 A; A=5-352.
PDB; 3D7Z; X-ray; 2.10 A; A=1-360.
PDB; 3D83; X-ray; 1.90 A; A=1-360.
PDB; 3DS6; X-ray; 2.90 A; A/B/C/D=1-360.
PDB; 3DT1; X-ray; 2.80 A; A=1-360.
PDB; 3E92; X-ray; 2.00 A; A=1-360.
PDB; 3E93; X-ray; 2.00 A; A=1-360.
PDB; 3FC1; X-ray; 2.40 A; X=1-360.
PDB; 3FI4; X-ray; 2.20 A; A=1-360.
PDB; 3FKL; X-ray; 2.00 A; A=1-360.
PDB; 3FKN; X-ray; 2.00 A; A=1-360.
PDB; 3FKO; X-ray; 2.00 A; A=1-360.
PDB; 3FL4; X-ray; 1.80 A; A=1-360.
PDB; 3FLN; X-ray; 1.90 A; C=1-360.
PDB; 3FLQ; X-ray; 1.90 A; A=1-360.
PDB; 3FLS; X-ray; 2.30 A; A=1-360.
PDB; 3FLW; X-ray; 2.10 A; A=1-360.
PDB; 3FLY; X-ray; 1.80 A; A=1-360.
PDB; 3FLZ; X-ray; 2.23 A; A=1-360.
PDB; 3FMH; X-ray; 1.90 A; A=1-360.
PDB; 3FMJ; X-ray; 2.00 A; A=1-360.
PDB; 3FMK; X-ray; 1.70 A; A=1-360.
PDB; 3FML; X-ray; 2.10 A; A=1-360.
PDB; 3FMM; X-ray; 2.00 A; A=1-360.
PDB; 3FMN; X-ray; 1.90 A; A=1-360.
PDB; 3FSF; X-ray; 2.10 A; A=1-360.
PDB; 3FSK; X-ray; 2.00 A; A=1-360.
PDB; 3GC7; X-ray; 1.80 A; A=1-360.
PDB; 3GCP; X-ray; 2.25 A; A=2-360.
PDB; 3GCQ; X-ray; 2.00 A; A=2-360.
PDB; 3GCS; X-ray; 2.10 A; A=2-360.
PDB; 3GCU; X-ray; 2.10 A; A/B=2-360.
PDB; 3GCV; X-ray; 2.30 A; A=2-360.
PDB; 3GFE; X-ray; 2.10 A; A=1-360.
PDB; 3GI3; X-ray; 2.40 A; A=1-360.
PDB; 3HA8; X-ray; 2.48 A; A=1-360.
PDB; 3HEC; X-ray; 2.50 A; A=5-352.
PDB; 3HEG; X-ray; 2.20 A; A=5-352.
PDB; 3HL7; X-ray; 1.88 A; A=1-360.
PDB; 3HLL; X-ray; 1.95 A; A=1-360.
PDB; 3HP2; X-ray; 2.15 A; A=1-360.
PDB; 3HP5; X-ray; 2.30 A; A=1-360.
PDB; 3HRB; X-ray; 2.20 A; A=2-360.
PDB; 3HUB; X-ray; 2.25 A; A=2-360.
PDB; 3HUC; X-ray; 1.80 A; A=2-360.
PDB; 3HV3; X-ray; 2.00 A; A=2-360.
PDB; 3HV4; X-ray; 2.60 A; A/B=2-360.
PDB; 3HV5; X-ray; 2.25 A; A/B=2-360.
PDB; 3HV6; X-ray; 1.95 A; A=2-360.
PDB; 3HV7; X-ray; 2.40 A; A=2-360.
PDB; 3HVC; X-ray; 2.10 A; A=1-360.
PDB; 3IPH; X-ray; 2.10 A; A=1-360.
PDB; 3ITZ; X-ray; 2.25 A; A=1-360.
PDB; 3IW5; X-ray; 2.50 A; A=2-360.
PDB; 3IW6; X-ray; 2.10 A; A=2-360.
PDB; 3IW7; X-ray; 2.40 A; A=2-360.
PDB; 3IW8; X-ray; 2.00 A; A=2-360.
PDB; 3K3I; X-ray; 1.70 A; A=5-352.
PDB; 3K3J; X-ray; 2.00 A; A=1-360.
PDB; 3KF7; X-ray; 2.00 A; A=1-360.
PDB; 3KQ7; X-ray; 1.80 A; A=1-360.
PDB; 3L8S; X-ray; 2.35 A; A=2-360.
PDB; 3L8X; X-ray; 2.15 A; A=2-360.
PDB; 3LFA; X-ray; 2.10 A; A=2-360.
PDB; 3LFB; X-ray; 2.60 A; A=2-360.
PDB; 3LFC; X-ray; 2.80 A; A=2-360.
PDB; 3LFD; X-ray; 3.40 A; A=2-360.
PDB; 3LFE; X-ray; 2.30 A; A=2-360.
PDB; 3LFF; X-ray; 1.50 A; A=2-360.
PDB; 3LHJ; X-ray; 3.31 A; A=1-360.
PDB; 3MGY; X-ray; 2.10 A; A=1-360.
PDB; 3MH0; X-ray; 2.00 A; A=1-360.
PDB; 3MH1; X-ray; 2.20 A; A=1-360.
PDB; 3MH2; X-ray; 2.30 A; A=1-360.
PDB; 3MH3; X-ray; 2.20 A; A=1-360.
PDB; 3MPA; X-ray; 2.10 A; A=1-360.
PDB; 3MPT; X-ray; 1.89 A; A=1-360.
PDB; 3MVL; X-ray; 2.80 A; A/B=2-360.
PDB; 3MVM; X-ray; 2.00 A; A/B=2-360.
PDB; 3MW1; X-ray; 2.80 A; A=2-360.
PDB; 3NEW; X-ray; 2.51 A; A=1-360.
PDB; 3NNU; X-ray; 2.40 A; A=1-354.
PDB; 3NNV; X-ray; 2.10 A; A=1-354.
PDB; 3NNW; X-ray; 1.89 A; A=1-354.
PDB; 3NNX; X-ray; 2.28 A; A=1-354.
PDB; 3NWW; X-ray; 2.09 A; A=2-360.
PDB; 3O8P; X-ray; 2.10 A; A=1-360.
PDB; 3O8T; X-ray; 2.00 A; A=1-360.
PDB; 3O8U; X-ray; 2.10 A; A=1-360.
PDB; 3OBG; X-ray; 2.80 A; A=1-360.
PDB; 3OBJ; X-ray; 2.40 A; A=1-360.
PDB; 3OC1; X-ray; 2.59 A; A=1-360.
PDB; 3OCG; X-ray; 2.21 A; A=2-360.
PDB; 3OD6; X-ray; 2.68 A; X=1-360.
PDB; 3ODY; X-ray; 2.20 A; X=1-360.
PDB; 3ODZ; X-ray; 2.30 A; X=1-360.
PDB; 3OEF; X-ray; 1.60 A; X=1-360.
PDB; 3PG3; X-ray; 2.00 A; A=2-360.
PDB; 3QUD; X-ray; 2.00 A; A=2-360.
PDB; 3QUE; X-ray; 2.70 A; A=2-360.
PDB; 3RIN; X-ray; 2.20 A; A=1-360.
PDB; 3ROC; X-ray; 1.70 A; A=1-360.
PDB; 3S3I; X-ray; 1.80 A; A=4-352.
PDB; 3S4Q; X-ray; 2.27 A; A=2-360.
PDB; 3U8W; X-ray; 2.15 A; A=1-360.
PDB; 3UVP; X-ray; 2.40 A; A=2-360.
PDB; 3UVQ; X-ray; 2.20 A; A=2-360.
PDB; 3UVR; X-ray; 2.10 A; A=2-360.
PDB; 3ZS5; X-ray; 1.60 A; A=2-360.
PDB; 3ZSG; X-ray; 1.89 A; A=2-360.
PDB; 3ZSH; X-ray; 2.05 A; A=2-360.
PDB; 3ZSI; X-ray; 2.40 A; A=2-360.
PDB; 3ZYA; X-ray; 1.90 A; A=1-360.
PDB; 4A9Y; X-ray; 2.20 A; A=2-360.
PDB; 4AA0; X-ray; 1.80 A; A=2-360.
PDB; 4AA4; X-ray; 2.30 A; A=2-360.
PDB; 4AA5; X-ray; 2.38 A; A=2-360.
PDB; 4AAC; X-ray; 2.50 A; A=2-360.
PDB; 4DLI; X-ray; 1.91 A; A=2-360.
PDB; 4DLJ; X-ray; 2.60 A; A=2-360.
PDB; 4E5A; X-ray; 1.87 A; X=1-360.
PDB; 4E5B; X-ray; 2.00 A; A=1-360.
PDB; 4E6A; X-ray; 2.09 A; A=1-360.
PDB; 4E6C; X-ray; 2.39 A; A=1-360.
PDB; 4E8A; X-ray; 2.70 A; A=1-360.
PDB; 4EH2; X-ray; 2.00 A; A=2-360.
PDB; 4EH3; X-ray; 2.40 A; A=2-360.
PDB; 4EH4; X-ray; 2.50 A; A=2-360.
PDB; 4EH5; X-ray; 2.00 A; A=2-360.
PDB; 4EH6; X-ray; 2.10 A; A=2-360.
PDB; 4EH7; X-ray; 2.10 A; A=2-360.
PDB; 4EH8; X-ray; 2.20 A; A=2-360.
PDB; 4EH9; X-ray; 2.10 A; A=2-360.
PDB; 4EHV; X-ray; 1.60 A; A=2-360.
PDB; 4EWQ; X-ray; 2.10 A; A=2-360.
PDB; 4F9W; X-ray; 2.00 A; A=2-360.
PDB; 4F9Y; X-ray; 1.85 A; A=2-360.
PDB; 4FA2; X-ray; 2.00 A; A=2-360.
PDB; 4GEO; X-ray; 1.66 A; A=2-360.
PDB; 4KIN; X-ray; 1.97 A; A/B/C/D=2-360.
PDB; 4KIP; X-ray; 2.27 A; A/B=2-360.
PDB; 4KIQ; X-ray; 2.50 A; A/B/C/D=2-360.
PDB; 4L8M; X-ray; 2.10 A; A=2-360.
PDB; 4R3C; X-ray; 2.06 A; A=2-360.
PDB; 4ZTH; X-ray; 2.15 A; A=2-360.
PDB; 5ETA; X-ray; 2.80 A; A/B=1-360.
PDB; 5ETC; X-ray; 2.42 A; A=1-360.
PDB; 5ETF; X-ray; 2.40 A; A=1-360.
PDB; 5ETI; X-ray; 2.80 A; A=1-360.
PDB; 5ML5; X-ray; 1.90 A; A=1-360.
PDB; 5TBE; X-ray; 2.44 A; A=1-360.
PDB; 5TCO; X-ray; 2.10 A; A=2-360.
PDBsum; 1A9U; -.
PDBsum; 1BL6; -.
PDBsum; 1BL7; -.
PDBsum; 1BMK; -.
PDBsum; 1DI9; -.
PDBsum; 1IAN; -.
PDBsum; 1KV1; -.
PDBsum; 1KV2; -.
PDBsum; 1M7Q; -.
PDBsum; 1OUK; -.
PDBsum; 1OUY; -.
PDBsum; 1OVE; -.
PDBsum; 1OZ1; -.
PDBsum; 1R39; -.
PDBsum; 1R3C; -.
PDBsum; 1W7H; -.
PDBsum; 1W82; -.
PDBsum; 1W83; -.
PDBsum; 1W84; -.
PDBsum; 1WBN; -.
PDBsum; 1WBO; -.
PDBsum; 1WBS; -.
PDBsum; 1WBT; -.
PDBsum; 1WBV; -.
PDBsum; 1WBW; -.
PDBsum; 1WFC; -.
PDBsum; 1YQJ; -.
PDBsum; 1ZYJ; -.
PDBsum; 1ZZ2; -.
PDBsum; 1ZZL; -.
PDBsum; 2BAJ; -.
PDBsum; 2BAK; -.
PDBsum; 2BAL; -.
PDBsum; 2BAQ; -.
PDBsum; 2FSL; -.
PDBsum; 2FSM; -.
PDBsum; 2FSO; -.
PDBsum; 2FST; -.
PDBsum; 2GFS; -.
PDBsum; 2I0H; -.
PDBsum; 2LGC; -.
PDBsum; 2NPQ; -.
PDBsum; 2OKR; -.
PDBsum; 2ONL; -.
PDBsum; 2QD9; -.
PDBsum; 2RG5; -.
PDBsum; 2RG6; -.
PDBsum; 2Y8O; -.
PDBsum; 2YIS; -.
PDBsum; 2YIW; -.
PDBsum; 2YIX; -.
PDBsum; 2ZAZ; -.
PDBsum; 2ZB0; -.
PDBsum; 2ZB1; -.
PDBsum; 3BV2; -.
PDBsum; 3BV3; -.
PDBsum; 3BX5; -.
PDBsum; 3C5U; -.
PDBsum; 3CTQ; -.
PDBsum; 3D7Z; -.
PDBsum; 3D83; -.
PDBsum; 3DS6; -.
PDBsum; 3DT1; -.
PDBsum; 3E92; -.
PDBsum; 3E93; -.
PDBsum; 3FC1; -.
PDBsum; 3FI4; -.
PDBsum; 3FKL; -.
PDBsum; 3FKN; -.
PDBsum; 3FKO; -.
PDBsum; 3FL4; -.
PDBsum; 3FLN; -.
PDBsum; 3FLQ; -.
PDBsum; 3FLS; -.
PDBsum; 3FLW; -.
PDBsum; 3FLY; -.
PDBsum; 3FLZ; -.
PDBsum; 3FMH; -.
PDBsum; 3FMJ; -.
PDBsum; 3FMK; -.
PDBsum; 3FML; -.
PDBsum; 3FMM; -.
PDBsum; 3FMN; -.
PDBsum; 3FSF; -.
PDBsum; 3FSK; -.
PDBsum; 3GC7; -.
PDBsum; 3GCP; -.
PDBsum; 3GCQ; -.
PDBsum; 3GCS; -.
PDBsum; 3GCU; -.
PDBsum; 3GCV; -.
PDBsum; 3GFE; -.
PDBsum; 3GI3; -.
PDBsum; 3HA8; -.
PDBsum; 3HEC; -.
PDBsum; 3HEG; -.
PDBsum; 3HL7; -.
PDBsum; 3HLL; -.
PDBsum; 3HP2; -.
PDBsum; 3HP5; -.
PDBsum; 3HRB; -.
PDBsum; 3HUB; -.
PDBsum; 3HUC; -.
PDBsum; 3HV3; -.
PDBsum; 3HV4; -.
PDBsum; 3HV5; -.
PDBsum; 3HV6; -.
PDBsum; 3HV7; -.
PDBsum; 3HVC; -.
PDBsum; 3IPH; -.
PDBsum; 3ITZ; -.
PDBsum; 3IW5; -.
PDBsum; 3IW6; -.
PDBsum; 3IW7; -.
PDBsum; 3IW8; -.
PDBsum; 3K3I; -.
PDBsum; 3K3J; -.
PDBsum; 3KF7; -.
PDBsum; 3KQ7; -.
PDBsum; 3L8S; -.
PDBsum; 3L8X; -.
PDBsum; 3LFA; -.
PDBsum; 3LFB; -.
PDBsum; 3LFC; -.
PDBsum; 3LFD; -.
PDBsum; 3LFE; -.
PDBsum; 3LFF; -.
PDBsum; 3LHJ; -.
PDBsum; 3MGY; -.
PDBsum; 3MH0; -.
PDBsum; 3MH1; -.
PDBsum; 3MH2; -.
PDBsum; 3MH3; -.
PDBsum; 3MPA; -.
PDBsum; 3MPT; -.
PDBsum; 3MVL; -.
PDBsum; 3MVM; -.
PDBsum; 3MW1; -.
PDBsum; 3NEW; -.
PDBsum; 3NNU; -.
PDBsum; 3NNV; -.
PDBsum; 3NNW; -.
PDBsum; 3NNX; -.
PDBsum; 3NWW; -.
PDBsum; 3O8P; -.
PDBsum; 3O8T; -.
PDBsum; 3O8U; -.
PDBsum; 3OBG; -.
PDBsum; 3OBJ; -.
PDBsum; 3OC1; -.
PDBsum; 3OCG; -.
PDBsum; 3OD6; -.
PDBsum; 3ODY; -.
PDBsum; 3ODZ; -.
PDBsum; 3OEF; -.
PDBsum; 3PG3; -.
PDBsum; 3QUD; -.
PDBsum; 3QUE; -.
PDBsum; 3RIN; -.
PDBsum; 3ROC; -.
PDBsum; 3S3I; -.
PDBsum; 3S4Q; -.
PDBsum; 3U8W; -.
PDBsum; 3UVP; -.
PDBsum; 3UVQ; -.
PDBsum; 3UVR; -.
PDBsum; 3ZS5; -.
PDBsum; 3ZSG; -.
PDBsum; 3ZSH; -.
PDBsum; 3ZSI; -.
PDBsum; 3ZYA; -.
PDBsum; 4A9Y; -.
PDBsum; 4AA0; -.
PDBsum; 4AA4; -.
PDBsum; 4AA5; -.
PDBsum; 4AAC; -.
PDBsum; 4DLI; -.
PDBsum; 4DLJ; -.
PDBsum; 4E5A; -.
PDBsum; 4E5B; -.
PDBsum; 4E6A; -.
PDBsum; 4E6C; -.
PDBsum; 4E8A; -.
PDBsum; 4EH2; -.
PDBsum; 4EH3; -.
PDBsum; 4EH4; -.
PDBsum; 4EH5; -.
PDBsum; 4EH6; -.
PDBsum; 4EH7; -.
PDBsum; 4EH8; -.
PDBsum; 4EH9; -.
PDBsum; 4EHV; -.
PDBsum; 4EWQ; -.
PDBsum; 4F9W; -.
PDBsum; 4F9Y; -.
PDBsum; 4FA2; -.
PDBsum; 4GEO; -.
PDBsum; 4KIN; -.
PDBsum; 4KIP; -.
PDBsum; 4KIQ; -.
PDBsum; 4L8M; -.
PDBsum; 4R3C; -.
PDBsum; 4ZTH; -.
PDBsum; 5ETA; -.
PDBsum; 5ETC; -.
PDBsum; 5ETF; -.
PDBsum; 5ETI; -.
PDBsum; 5ML5; -.
PDBsum; 5TBE; -.
PDBsum; 5TCO; -.
ProteinModelPortal; Q16539; -.
SMR; Q16539; -.
BioGrid; 107819; 208.
DIP; DIP-30987N; -.
ELM; Q16539; -.
IntAct; Q16539; 100.
MINT; MINT-126546; -.
STRING; 9606.ENSP00000229794; -.
BindingDB; Q16539; -.
ChEMBL; CHEMBL260; -.
DrugBank; DB02277; 1-(5-Tert-Butyl-2-Methyl-2h-Pyrazol-3-Yl)-3-(4-Chloro-Phenyl)-Urea.
DrugBank; DB03044; 1-(5-Tert-Butyl-2-P-Tolyl-2h-Pyrazol-3-Yl)-3-[4-(2-Morpholin-4-Yl-Ethoxy)-Naphthalen-1-Yl]-Urea.
DrugBank; DB06882; 1-[1-(3-aminophenyl)-3-tert-butyl-1H-pyrazol-5-yl]-3-naphthalen-1-ylurea.
DrugBank; DB08395; 2-(ETHOXYMETHYL)-4-(4-FLUOROPHENYL)-3-[2-(2-HYDROXYPHENOXY)PYRIMIDIN-4-YL]ISOXAZOL-5(2H)-ONE.
DrugBank; DB03110; 2-Chlorophenol.
DrugBank; DB07942; 2-fluoro-4-[4-(4-fluorophenyl)-1H-pyrazol-3-yl]pyridine.
DrugBank; DB07943; 2-{4-[5-(4-chlorophenyl)-4-pyrimidin-4-yl-1H-pyrazol-3-yl]piperidin-1-yl}-2-oxoethanol.
DrugBank; DB08093; 3-(1-NAPHTHYLMETHOXY)PYRIDIN-2-AMINE.
DrugBank; DB02352; 3-(Benzyloxy)Pyridin-2-Amine.
DrugBank; DB08730; 3-FLUORO-5-MORPHOLIN-4-YL-N-[1-(2-PYRIDIN-4-YLETHYL)-1H-INDOL-6-YL]BENZAMIDE.
DrugBank; DB08091; 3-FLUORO-5-MORPHOLIN-4-YL-N-[3-(2-PYRIDIN-4-YLETHYL)-1H-INDOL-5-YL]BENZAMIDE.
DrugBank; DB08092; 3-fluoro-N-1H-indol-5-yl-5-morpholin-4-ylbenzamide.
DrugBank; DB04632; 4-(2-HYDROXYBENZYLAMINO)-N-(3-(4-FLUOROPHENOXY)PHENYL)PIPERIDINE-1-SULFONAMIDE.
DrugBank; DB08522; 4-(4-FLUOROPHENYL)-1-CYCLOROPROPYLMETHYL-5-(4-PYRIDYL)-IMIDAZOLE.
DrugBank; DB03980; 4-(Fluorophenyl)-1-Cyclopropylmethyl-5-(2-Amino-4-Pyrimidinyl)Imidazole.
DrugBank; DB07829; 4-[3-(4-FLUOROPHENYL)-1H-PYRAZOL-4-YL]PYRIDINE.
DrugBank; DB07607; 4-[5-(3-IODO-PHENYL)-2-(4-METHANESULFINYL-PHENYL)-1H-IMIDAZOL-4-YL]-PYRIDINE.
DrugBank; DB08521; 4-[5-(4-FLUORO-PHENYL)-2-(4-METHANESULFINYL-PHENYL)-3H-IMIDAZOL-4-YL]-PYRIDINE.
DrugBank; DB01761; 4-[5-[2-(1-Phenyl-Ethylamino)-Pyrimidin-4-Yl]-1-Methyl-4-(3-Trifluoromethylphenyl)-1h-Imidazol-2-Yl]-Piperidine.
DrugBank; DB07459; 4-PHENOXY-N-(PYRIDIN-2-YLMETHYL)BENZAMIDE.
DrugBank; DB01988; 6((S)-3-Benzylpiperazin-1-Yl)-3-(Naphthalen-2-Yl)-4-(Pyridin-4-Yl)Pyrazine.
DrugBank; DB08423; [5-AMINO-1-(4-FLUOROPHENYL)-1H-PYRAZOL-4-YL][3-(PIPERIDIN-4-YLOXY)PHENYL]METHANONE.
DrugBank; DB01953; Inhibitor of P38 Kinase.
DrugBank; DB05157; KC706.
DrugBank; DB08064; N-(3-TERT-BUTYL-1H-PYRAZOL-5-YL)-N'-{4-CHLORO-3-[(PYRIDIN-3-YLOXY)METHYL]PHENYL}UREA.
DrugBank; DB08068; N-[4-CHLORO-3-(PYRIDIN-3-YLOXYMETHYL)-PHENYL]-3-FLUORO-.
DrugBank; DB07307; N-cyclopropyl-4-methyl-3-[1-(2-methylphenyl)phthalazin-6-yl]benzamide.
DrugBank; DB08351; N-cyclopropyl-4-methyl-3-{2-[(2-morpholin-4-ylethyl)amino]quinazolin-6-yl}benzamide.
DrugBank; DB04338; SB220025.
DrugBank; DB05412; SCIO-469.
DrugBank; DB04797; Triazolopyridine.
DrugBank; DB05470; VX-702.
GuidetoPHARMACOLOGY; 1499; -.
iPTMnet; Q16539; -.
PhosphoSitePlus; Q16539; -.
BioMuta; MAPK14; -.
OGP; Q16539; -.
EPD; Q16539; -.
MaxQB; Q16539; -.
PaxDb; Q16539; -.
PeptideAtlas; Q16539; -.
PRIDE; Q16539; -.
DNASU; 1432; -.
Ensembl; ENST00000229794; ENSP00000229794; ENSG00000112062. [Q16539-1]
Ensembl; ENST00000229795; ENSP00000229795; ENSG00000112062. [Q16539-2]
Ensembl; ENST00000310795; ENSP00000308669; ENSG00000112062. [Q16539-4]
GeneID; 1432; -.
KEGG; hsa:1432; -.
UCSC; uc003olp.4; human. [Q16539-1]
CTD; 1432; -.
DisGeNET; 1432; -.
GeneCards; MAPK14; -.
HGNC; HGNC:6876; MAPK14.
HPA; CAB010285; -.
HPA; CAB040578; -.
HPA; HPA051825; -.
MIM; 600289; gene.
neXtProt; NX_Q16539; -.
OpenTargets; ENSG00000112062; -.
PharmGKB; PA30621; -.
eggNOG; KOG0660; Eukaryota.
eggNOG; ENOG410XNY0; LUCA.
GeneTree; ENSGT00550000074271; -.
HOGENOM; HOG000233024; -.
HOVERGEN; HBG014652; -.
InParanoid; Q16539; -.
KO; K04441; -.
OMA; EQFQQVY; -.
OrthoDB; EOG091G08QL; -.
PhylomeDB; Q16539; -.
TreeFam; TF105100; -.
BioCyc; MetaCyc:HS03507-MONOMER; -.
BRENDA; 2.7.11.24; 2681.
Reactome; R-HSA-168638; NOD1/2 Signaling Pathway.
Reactome; R-HSA-171007; p38MAPK events.
Reactome; R-HSA-198753; ERK/MAPK targets.
Reactome; R-HSA-2151209; Activation of PPARGC1A (PGC-1alpha) by phosphorylation.
Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence.
Reactome; R-HSA-375170; CDO in myogenesis.
Reactome; R-HSA-376172; DSCAM interactions.
Reactome; R-HSA-418592; ADP signalling through P2Y purinoceptor 1.
Reactome; R-HSA-432142; Platelet sensitization by LDL.
Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway.
Reactome; R-HSA-450302; activated TAK1 mediates p38 MAPK activation.
Reactome; R-HSA-450341; Activation of the AP-1 family of transcription factors.
Reactome; R-HSA-450604; KSRP (KHSRP) binds and destabilizes mRNA.
Reactome; R-HSA-6798695; Neutrophil degranulation.
Reactome; R-HSA-6804756; Regulation of TP53 Activity through Phosphorylation.
SignaLink; Q16539; -.
SIGNOR; Q16539; -.
ChiTaRS; MAPK14; human.
EvolutionaryTrace; Q16539; -.
GeneWiki; MAPK14; -.
GenomeRNAi; 1432; -.
PRO; PR:Q16539; -.
Proteomes; UP000005640; Chromosome 6.
Bgee; ENSG00000112062; -.
CleanEx; HS_MAPK14; -.
ExpressionAtlas; Q16539; baseline and differential.
Genevisible; Q16539; HS.
GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
GO; GO:0005829; C:cytosol; TAS:Reactome.
GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
GO; GO:0005576; C:extracellular region; TAS:Reactome.
GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
GO; GO:0016607; C:nuclear speck; IDA:HPA.
GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
GO; GO:0005634; C:nucleus; ISS:UniProtKB.
GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
GO; GO:0000922; C:spindle pole; IEA:Ensembl.
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
GO; GO:0004707; F:MAP kinase activity; IDA:UniProtKB.
GO; GO:0004708; F:MAP kinase kinase activity; TAS:ProtInc.
GO; GO:0048273; F:mitogen-activated protein kinase p38 binding; IPI:UniProtKB.
GO; GO:0051525; F:NFAT protein binding; ISS:BHF-UCL.
GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB.
GO; GO:0004674; F:protein serine/threonine kinase activity; TAS:Reactome.
GO; GO:0070935; P:3'-UTR-mediated mRNA stabilization; TAS:UniProtKB.
GO; GO:0000187; P:activation of MAPK activity; TAS:Reactome.
GO; GO:0001525; P:angiogenesis; IEA:Ensembl.
GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
GO; GO:0001502; P:cartilage condensation; IEA:Ensembl.
GO; GO:0000902; P:cell morphogenesis; IEA:Ensembl.
GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
GO; GO:0071479; P:cellular response to ionizing radiation; IMP:BHF-UCL.
GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:MGI.
GO; GO:0071223; P:cellular response to lipoteichoic acid; IMP:UniProtKB.
GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IMP:BHF-UCL.
GO; GO:0098586; P:cellular response to virus; IMP:UniProtKB.
GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
GO; GO:0002062; P:chondrocyte differentiation; IEA:Ensembl.
GO; GO:0000077; P:DNA damage checkpoint; IEA:Ensembl.
GO; GO:0019395; P:fatty acid oxidation; IEA:Ensembl.
GO; GO:0006006; P:glucose metabolic process; IEA:Ensembl.
GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IEA:Ensembl.
GO; GO:0006928; P:movement of cell or subcellular component; TAS:ProtInc.
GO; GO:0014835; P:myoblast differentiation involved in skeletal muscle regeneration; IEA:Ensembl.
GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IEA:Ensembl.
GO; GO:0043312; P:neutrophil degranulation; TAS:Reactome.
GO; GO:0030316; P:osteoclast differentiation; ISS:BHF-UCL.
GO; GO:0038066; P:p38MAPK cascade; ISS:UniProtKB.
GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:BHF-UCL.
GO; GO:0001890; P:placenta development; IEA:Ensembl.
GO; GO:0090336; P:positive regulation of brown fat cell differentiation; IEA:Ensembl.
GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; IEA:Ensembl.
GO; GO:0031281; P:positive regulation of cyclase activity; IMP:CACAO.
GO; GO:0002741; P:positive regulation of cytokine secretion involved in immune response; IEA:Ensembl.
GO; GO:0045648; P:positive regulation of erythrocyte differentiation; IMP:BHF-UCL.
GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
GO; GO:0046326; P:positive regulation of glucose import; IEA:Ensembl.
GO; GO:2001184; P:positive regulation of interleukin-12 secretion; IMP:UniProtKB.
GO; GO:0010759; P:positive regulation of macrophage chemotaxis; IEA:Ensembl.
GO; GO:1905050; P:positive regulation of metallopeptidase activity; IEA:Ensembl.
GO; GO:0051149; P:positive regulation of muscle cell differentiation; TAS:Reactome.
GO; GO:0045663; P:positive regulation of myoblast differentiation; ISS:UniProtKB.
GO; GO:1901741; P:positive regulation of myoblast fusion; ISS:UniProtKB.
GO; GO:0010831; P:positive regulation of myotube differentiation; ISS:UniProtKB.
GO; GO:0042307; P:positive regulation of protein import into nucleus; IEA:Ensembl.
GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IMP:BHF-UCL.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
GO; GO:0007265; P:Ras protein signal transduction; TAS:Reactome.
GO; GO:1900015; P:regulation of cytokine production involved in inflammatory response; IDA:CACAO.
GO; GO:0030278; P:regulation of ossification; IEA:Ensembl.
GO; GO:0051090; P:regulation of sequence-specific DNA binding transcription factor activity; TAS:Reactome.
GO; GO:1901796; P:regulation of signal transduction by p53 class mediator; TAS:Reactome.
GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; ISS:UniProtKB.
GO; GO:0032495; P:response to muramyl dipeptide; IEA:Ensembl.
GO; GO:0035994; P:response to muscle stretch; IEA:Ensembl.
GO; GO:0007165; P:signal transduction; TAS:ProtInc.
GO; GO:0042770; P:signal transduction in response to DNA damage; IMP:BHF-UCL.
GO; GO:0007519; P:skeletal muscle tissue development; IEA:Ensembl.
GO; GO:0090400; P:stress-induced premature senescence; IMP:BHF-UCL.
GO; GO:0051146; P:striated muscle cell differentiation; IEA:Ensembl.
GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
GO; GO:0007178; P:transmembrane receptor protein serine/threonine kinase signaling pathway; IEA:Ensembl.
GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IMP:BHF-UCL.
InterPro; IPR011009; Kinase-like_dom.
InterPro; IPR003527; MAP_kinase_CS.
InterPro; IPR008352; MAPK_p38.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR017441; Protein_kinase_ATP_BS.
Pfam; PF00069; Pkinase; 1.
PRINTS; PR01773; P38MAPKINASE.
SMART; SM00220; S_TKc; 1.
SUPFAM; SSF56112; SSF56112; 1.
PROSITE; PS01351; MAPK; 1.
PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
1: Evidence at protein level;
3D-structure; Acetylation; Alternative splicing; Apoptosis;
ATP-binding; Complete proteome; Cytoplasm; Direct protein sequencing;
Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism;
Reference proteome; Serine/threonine-protein kinase; Stress response;
Transcription; Transcription regulation; Transferase; Ubl conjugation.
INIT_MET 1 1 Removed. {ECO:0000244|PubMed:20068231,
ECO:0000269|PubMed:12665801}.
CHAIN 2 360 Mitogen-activated protein kinase 14.
/FTId=PRO_0000186291.
DOMAIN 24 308 Protein kinase. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
NP_BIND 30 38 ATP.
REGION 70 71 Inhibitor-binding.
REGION 106 110 Inhibitor-binding.
REGION 168 169 Inhibitor-binding.
MOTIF 180 182 TXY.
ACT_SITE 168 168 Proton acceptor.
BINDING 35 35 Inhibitor. {ECO:0000269|PubMed:12897767,
ECO:0000269|PubMed:15658854,
ECO:0000269|PubMed:16342939}.
BINDING 53 53 ATP.
BINDING 53 53 Inhibitor. {ECO:0000269|PubMed:12897767,
ECO:0000269|PubMed:15658854,
ECO:0000269|PubMed:16342939}.
BINDING 71 71 Inhibitor. {ECO:0000269|PubMed:12897767,
ECO:0000269|PubMed:15658854,
ECO:0000269|PubMed:16342939}.
BINDING 109 109 Inhibitor; via amide nitrogen and
carbonyl oxygen.
{ECO:0000269|PubMed:12897767,
ECO:0000269|PubMed:15658854,
ECO:0000269|PubMed:16342939}.
BINDING 154 154 Inhibitor; via carbonyl oxygen.
{ECO:0000269|PubMed:12897767,
ECO:0000269|PubMed:15658854,
ECO:0000269|PubMed:16342939}.
BINDING 168 168 Inhibitor; via amide nitrogen and
carbonyl oxygen.
{ECO:0000269|PubMed:12897767,
ECO:0000269|PubMed:15658854,
ECO:0000269|PubMed:16342939}.
BINDING 197 197 Inhibitor. {ECO:0000269|PubMed:12897767,
ECO:0000269|PubMed:15658854,
ECO:0000269|PubMed:16342939}.
BINDING 252 252 Inhibitor; via amide nitrogen.
{ECO:0000269|PubMed:12897767,
ECO:0000269|PubMed:15658854,
ECO:0000269|PubMed:16342939}.
MOD_RES 2 2 N-acetylserine.
{ECO:0000244|PubMed:20068231}.
MOD_RES 2 2 Phosphoserine.
{ECO:0000244|PubMed:20068231,
ECO:0000244|PubMed:23186163}.
MOD_RES 16 16 Phosphothreonine.
{ECO:0000244|PubMed:18691976}.
MOD_RES 53 53 N6-acetyllysine.
{ECO:0000269|PubMed:21444723}.
MOD_RES 152 152 N6-acetyllysine.
{ECO:0000269|PubMed:21444723}.
MOD_RES 180 180 Phosphothreonine; by MAP2K3, MAP2K4,
MAP2K6 and autocatalysis.
{ECO:0000244|PubMed:18669648,
ECO:0000244|PubMed:19690332,
ECO:0000244|PubMed:20068231,
ECO:0000244|PubMed:23186163,
ECO:0000269|PubMed:7535770}.
MOD_RES 182 182 Phosphotyrosine; by MAP2K3, MAP2K4,
MAP2K6 and autocatalysis.
{ECO:0000244|PubMed:18669648,
ECO:0000244|PubMed:19690332,
ECO:0000244|PubMed:20068231,
ECO:0000244|PubMed:23186163,
ECO:0000269|PubMed:7535770}.
MOD_RES 263 263 Phosphothreonine.
{ECO:0000244|PubMed:17525332}.
MOD_RES 323 323 Phosphotyrosine; by ZAP70.
{ECO:0000269|PubMed:15735648}.
VAR_SEQ 230 254 DQLKLILRLVGTPGAELLKKISSES -> NQLQQIMRLTGT
PPAYLINRMPSHE (in isoform CSBP1).
{ECO:0000303|PubMed:7997261}.
/FTId=VSP_004842.
VAR_SEQ 255 360 ARNYIQSLTQMPKMNFANVFIGANPLAVDLLEKMLVLDSDK
RITAAQALAHAYFAQYHDPDDEPVADPYDQSFESRDLLIDE
WKSLTYDEVISFVPPPLDQEEMES -> VS (in
isoform 5).
{ECO:0000303|PubMed:19906316}.
/FTId=VSP_057194.
VAR_SEQ 255 307 ARNYIQSLTQMPKMNFANVFIGANPLAVDLLEKMLVLDSDK
RITAAQALAHAY -> LSTCWRRCLYWTQIRELQRPKPLHM
PTLLSTTILMMNQWPILMISPLKAGTSL (in isoform
Exip). {ECO:0000303|PubMed:11866441}.
/FTId=VSP_004843.
VAR_SEQ 281 360 AVDLLEKMLVLDSDKRITAAQALAHAYFAQYHDPDDEPVAD
PYDQSFESRDLLIDEWKSLTYDEVISFVPPPLDQEEMES
-> GKLTIYPHLMDIELVMI (in isoform Mxi2).
{ECO:0000303|PubMed:7479834}.
/FTId=VSP_004844.
VAR_SEQ 308 360 Missing (in isoform Exip).
{ECO:0000303|PubMed:11866441}.
/FTId=VSP_004845.
VARIANT 51 51 A -> V (in a gastric adenocarcinoma
sample; somatic mutation).
{ECO:0000269|PubMed:17344846}.
/FTId=VAR_042270.
VARIANT 322 322 P -> R (in a lung adenocarcinoma sample;
somatic mutation).
{ECO:0000269|PubMed:17344846}.
/FTId=VAR_042271.
VARIANT 343 343 D -> G (in dbSNP:rs45496794).
{ECO:0000269|PubMed:17344846}.
/FTId=VAR_042272.
MUTAGEN 34 34 A->V: Lowered kinase activity.
{ECO:0000269|PubMed:7493921}.
MUTAGEN 53 53 K->R: Loss of kinase activity.
{ECO:0000269|PubMed:7493921}.
MUTAGEN 54 54 K->R: Impairs MAP2K6/MKK6-dependent
autophosphorylation.
{ECO:0000269|PubMed:11010976}.
MUTAGEN 69 69 Y->H: Lowered kinase activity.
{ECO:0000269|PubMed:15284239}.
MUTAGEN 168 168 D->A: Loss of kinase activity.
{ECO:0000269|PubMed:7493921}.
MUTAGEN 175 175 T->A: No effect on either the kinase
activity or tyrosine phosphorylation.
{ECO:0000269|PubMed:7493921}.
MUTAGEN 176 176 D->A: Emulation of the active state.
Increase in activity; when associated
with S-327 or L-327.
{ECO:0000269|PubMed:15284239}.
MUTAGEN 177 177 D->A: Loss of kinase activity.
{ECO:0000269|PubMed:15284239}.
MUTAGEN 180 180 T->E: Loss of kinase activity.
{ECO:0000269|PubMed:7493921}.
MUTAGEN 182 182 Y->F: Loss of kinase activity.
{ECO:0000269|PubMed:7493921}.
MUTAGEN 320 320 A->T: Lowered kinase activity.
{ECO:0000269|PubMed:15284239}.
MUTAGEN 327 327 F->L: Emulation of the active state.
Increase in activity; when associated
with A-176.
{ECO:0000269|PubMed:15284239}.
MUTAGEN 327 327 F->S: Emulation of the active state.
Increase in activity; when associated
with A-176.
{ECO:0000269|PubMed:15284239}.
MUTAGEN 337 337 W->R: Loss of kinase activity.
{ECO:0000269|PubMed:15284239}.
CONFLICT 67 67 R -> G (in Ref. 7; BAF84398).
{ECO:0000305}.
STRAND 8 13 {ECO:0000244|PDB:2FST}.
STRAND 16 21 {ECO:0000244|PDB:2FST}.
STRAND 24 29 {ECO:0000244|PDB:2FST}.
HELIX 31 33 {ECO:0000244|PDB:2GFS}.
TURN 34 36 {ECO:0000244|PDB:3BV2}.
STRAND 38 43 {ECO:0000244|PDB:2FST}.
TURN 44 47 {ECO:0000244|PDB:2FST}.
STRAND 48 54 {ECO:0000244|PDB:2FST}.
HELIX 62 77 {ECO:0000244|PDB:2FST}.
STRAND 87 90 {ECO:0000244|PDB:2FST}.
HELIX 96 98 {ECO:0000244|PDB:2FST}.
STRAND 103 107 {ECO:0000244|PDB:2FST}.
STRAND 110 112 {ECO:0000244|PDB:3LFF}.
TURN 113 115 {ECO:0000244|PDB:4GEO}.
TURN 116 119 {ECO:0000244|PDB:3LFF}.
HELIX 124 143 {ECO:0000244|PDB:2FST}.
HELIX 153 155 {ECO:0000244|PDB:2FST}.
STRAND 156 158 {ECO:0000244|PDB:2FST}.
TURN 160 162 {ECO:0000244|PDB:2RG6}.
STRAND 164 166 {ECO:0000244|PDB:2FST}.
STRAND 168 170 {ECO:0000244|PDB:4GEO}.
HELIX 173 175 {ECO:0000244|PDB:1ZZL}.
HELIX 177 179 {ECO:0000244|PDB:2GFS}.
STRAND 180 182 {ECO:0000244|PDB:3FMK}.
TURN 185 188 {ECO:0000244|PDB:3LFF}.
HELIX 191 194 {ECO:0000244|PDB:2FST}.
STRAND 197 199 {ECO:0000244|PDB:4EHV}.
HELIX 204 218 {ECO:0000244|PDB:2FST}.
HELIX 228 239 {ECO:0000244|PDB:2FST}.
HELIX 244 247 {ECO:0000244|PDB:2FST}.
HELIX 253 260 {ECO:0000244|PDB:2FST}.
HELIX 270 273 {ECO:0000244|PDB:2FST}.
TURN 274 276 {ECO:0000244|PDB:2FST}.
HELIX 279 288 {ECO:0000244|PDB:2FST}.
HELIX 293 295 {ECO:0000244|PDB:2FST}.
HELIX 299 303 {ECO:0000244|PDB:2FST}.
HELIX 306 308 {ECO:0000244|PDB:2FST}.
TURN 309 311 {ECO:0000244|PDB:2FST}.
HELIX 314 316 {ECO:0000244|PDB:2FST}.
HELIX 325 327 {ECO:0000244|PDB:2FST}.
HELIX 334 347 {ECO:0000244|PDB:2FST}.
SEQUENCE 360 AA; 41293 MW; 286C81D0487618B3 CRC64;
MSQERPTFYR QELNKTIWEV PERYQNLSPV GSGAYGSVCA AFDTKTGLRV AVKKLSRPFQ
SIIHAKRTYR ELRLLKHMKH ENVIGLLDVF TPARSLEEFN DVYLVTHLMG ADLNNIVKCQ
KLTDDHVQFL IYQILRGLKY IHSADIIHRD LKPSNLAVNE DCELKILDFG LARHTDDEMT
GYVATRWYRA PEIMLNWMHY NQTVDIWSVG CIMAELLTGR TLFPGTDHID QLKLILRLVG
TPGAELLKKI SSESARNYIQ SLTQMPKMNF ANVFIGANPL AVDLLEKMLV LDSDKRITAA
QALAHAYFAQ YHDPDDEPVA DPYDQSFESR DLLIDEWKSL TYDEVISFVP PPLDQEEMES


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