ID MK14_HUMAN Reviewed; 360 AA. AC Q16539; A6ZJ92; A8K6P4; B0LPH0; B5TY32; O60776; Q13083; Q14084; Q8TDX0; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 27-MAR-2024, entry version 259. 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:11010976, ECO:0000269|PubMed:15284239, ECO:0000269|PubMed:35857590, ECO:0000269|PubMed:7493921}; DE AltName: Full=Cytokine suppressive anti-inflammatory drug-binding protein; DE Short=CSAID-binding protein; DE Short=CSBP; DE AltName: Full=MAP kinase MXI2; DE AltName: Full=MAX-interacting protein 2; DE AltName: Full=Mitogen-activated protein kinase p38 alpha; DE Short=MAP kinase p38 alpha; DE AltName: Full=Stress-activated protein kinase 2a; DE Short=SAPK2a; GN Name=MAPK14 {ECO:0000312|HGNC:HGNC:6876}; GN Synonyms=CSBP, CSBP1, CSBP2, CSPB1, MXI2, SAPK2A; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS CSBP1 AND CSBP2), AND PARTIAL PROTEIN RP SEQUENCE. RC TISSUE=Peripheral blood; RX PubMed=7997261; DOI=10.1038/372739a0; RA Lee J.C., Laydon J.T., McDonnell P.C., Gallagher T.F., Kumar S., Green D., RA McNulty D., Blumenthal M.J., Heys R.J., Landvatter S.W., Strickler J.E., RA McLaughlin M.M., Siemens I.R., Fisher S.M., Livi G.P., White J.R., RA Adams J.L., Young P.R.; RT "A protein kinase involved in the regulation of inflammatory cytokine RT biosynthesis."; RL Nature 372:739-746(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CSBP2). RC TISSUE=Liver; RX PubMed=7696354; DOI=10.1016/0167-4889(95)00002-a; RA Han J., Richter B., Li Z., Kravchenko V.V., Ulevitch R.J.; RT "Molecular cloning of human p38 MAP kinase."; RL Biochim. Biophys. Acta 1265:224-227(1995). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM MXI2). RX PubMed=7479834; DOI=10.1073/pnas.92.23.10531; RA Zervos A.S., Faccio L., Gatto J.P., Kyriakis J.M., Brent R.; RT "Mxi2, a mitogen-activated protein kinase that recognizes and RT phosphorylates Max protein."; RL Proc. Natl. Acad. Sci. U.S.A. 92:10531-10534(1995). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CSBP2). RC TISSUE=B-cell; RX PubMed=10727080; DOI=10.3109/10425179909033952; RA Herbison C.E., Sayer D.C., Bellgard M., Allcock R.J.N., Christiansen F.T., RA Price P.; RT "Structure and polymorphism of two stress-activated protein kinase genes RT centromeric of the MHC: SAPK2a and SAPK4."; RL DNA Seq. 10:229-243(1999). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM EXIP), AND ACTIVITY REGULATION. RC TISSUE=Renal cell carcinoma; RX PubMed=11866441; DOI=10.1006/bbrc.2002.6529; RA Sudo T., Yagasaki Y., Hama H., Watanabe N., Osada H.; RT "Exip, a new alternative splicing variant of p38 alpha, can induce an RT earlier onset of apoptosis in HeLa cells."; RL Biochem. Biophys. Res. Commun. 291:838-843(2002). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5). RX PubMed=19906316; DOI=10.1186/1471-2164-10-518; RA Wang P., Yu P., Gao P., Shi T., Ma D.; RT "Discovery of novel human transcript variants by analysis of intronic RT single-block EST with polyadenylation site."; RL BMC Genomics 10:518-518(2009). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CSBP2). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CSBP2). RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., RA LaBaer J.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NHLBI resequencing and genotyping service (RS&G); RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [13] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CSBP2). RC TISSUE=Placenta; 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 [14] RP PROTEIN SEQUENCE OF 2-10. RC TISSUE=Platelet; RX PubMed=12665801; DOI=10.1038/nbt810; RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., RA Vandekerckhove J.; RT "Exploring proteomes and analyzing protein processing by mass spectrometric RT identification of sorted N-terminal peptides."; RL Nat. Biotechnol. 21:566-569(2003). RN [15] RP PROTEIN SEQUENCE OF 174-186. RX PubMed=7923354; DOI=10.1016/0092-8674(94)90278-x; RA Freshney N.W., Rawlinson L., Guesdon F., Jones E., Cowley S., Hsuan J., RA Saklatvala J.; RT "Interleukin-1 activates a novel protein kinase cascade that results in the RT phosphorylation of Hsp27."; RL Cell 78:1039-1049(1994). RN [16] RP PHOSPHORYLATION AT THR-180 AND TYR-182, ACTIVITY REGULATION, AND RP SUBCELLULAR LOCATION. RX PubMed=7535770; DOI=10.1074/jbc.270.13.7420; RA Raingeaud J., Gupta S., Rogers J.S., Dickens M., Han J., Ulevitch R.J., RA Davis R.J.; RT "Pro-inflammatory cytokines and environmental stress cause p38 mitogen- RT activated protein kinase activation by dual phosphorylation on tyrosine and RT threonine."; RL J. Biol. Chem. 270:7420-7426(1995). RN [17] RP MUTAGENESIS OF ALA-34; LYS-53; ASP-168; THR-175; THR-180 AND TYR-182, AND RP CATALYTIC ACTIVITY. RX PubMed=7493921; DOI=10.1074/jbc.270.49.29043; RA Kumar S., McLaughlin M.M., McDonnell P.C., Lee J.C., Livi G.P., Young P.R.; RT "Human mitogen-activated protein kinase CSBP1, but not CSBP2, complements a RT hog1 deletion in yeast."; RL J. Biol. Chem. 270:29043-29046(1995). RN [18] RP PHOSPHORYLATION BY MAP2K3/MKK3 AND MAP2K6/MKK6, AND ACTIVITY REGULATION. RX PubMed=8622669; DOI=10.1128/mcb.16.3.1247; RA Raingeaud J., Whitmarsh A.J., Barrett T., Derijard B., Davis R.J.; RT "MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen- RT activated protein kinase signal transduction pathway."; RL Mol. Cell. Biol. 16:1247-1255(1996). RN [19] RP FUNCTION IN ACTIVATION OF RPS6KA5/MSK1. RX PubMed=9687510; DOI=10.1093/emboj/17.15.4426; RA Deak M., Clifton A.D., Lucocq J.M., Alessi D.R.; RT "Mitogen- and stress-activated protein kinase-1 (MSK1) is directly RT activated by MAPK and SAPK2/p38, and may mediate activation of CREB."; RL EMBO J. 17:4426-4441(1998). RN [20] RP FUNCTION IN PHOSPHORYLATION OF ATF2; ELK1 AND MBP, AND ACTIVITY REGULATION. RX PubMed=9430721; DOI=10.1074/jbc.273.3.1741; RA Enslen H., Raingeaud J., Davis R.J.; RT "Selective activation of p38 mitogen-activated protein (MAP) kinase RT isoforms by the MAP kinase kinases MKK3 and MKK6."; RL J. Biol. Chem. 273:1741-1748(1998). RN [21] RP INTERACTION WITH RPS6KA4, FUNCTION IN PHOSPHORYLATION OF RPS6KA4, AND RP SUBCELLULAR LOCATION. RX PubMed=9792677; DOI=10.1074/jbc.273.45.29661; RA Pierrat B., Correia J.D.S., Mary J.L., Tomas-Zuber M., Lesslauer W.; RT "RSK-B, a novel ribosomal S6 kinase family member, is a CREB kinase under RT dominant control of p38alpha mitogen-activated protein kinase RT (p38alphaMAPK)."; RL J. Biol. Chem. 273:29661-29671(1998). RN [22] RP INTERACTION WITH DUSP10, AND ACTIVITY REGULATION. RX PubMed=10391943; DOI=10.1074/jbc.274.28.19949; RA Tanoue T., Moriguchi T., Nishida E.; RT "Molecular cloning and characterization of a novel dual specificity RT phosphatase, MKP-5."; RL J. Biol. Chem. 274:19949-19956(1999). RN [23] RP FUNCTION IN PHOSPHORYLATION OF MEF2A. RX PubMed=9858528; DOI=10.1128/mcb.19.1.21; RA Zhao M., New L., Kravchenko V.V., Kato Y., Gram H., di Padova F., RA Olson E.N., Ulevitch R.J., Han J.-D.; RT "Regulation of the MEF2 family of transcription factors by p38."; RL Mol. Cell. Biol. 19:21-30(1999). RN [24] RP FUNCTION IN PHOSPHORYLATION OF MEF2A AND MEF2C. RX PubMed=10330143; DOI=10.1128/mcb.19.6.4028; RA Yang S.-H., Galanis A., Sharrocks A.D.; RT "Targeting of p38 mitogen-activated protein kinases to MEF2 transcription RT factors."; RL Mol. Cell. Biol. 19:4028-4038(1999). RN [25] RP FUNCTION. RC TISSUE=Hepatoma; 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 [26] RP FUNCTION (ISOFORM MXI2), COFACTOR, AND ACTIVITY REGULATION. RX PubMed=10838079; DOI=10.1016/s0014-5793(00)01598-2; RA Sanz V., Arozarena I., Crespo P.; RT "Distinct carboxy-termini confer divergent characteristics to the mitogen- RT activated protein kinase p38alpha and its splice isoform Mxi2."; RL FEBS Lett. 474:169-174(2000). RN [27] RP INTERACTION WITH CSNK2A1 AND CSNK2B, AND FUNCTION IN ACTIVATION OF CASEIN RP KINASE II. RX PubMed=10747897; DOI=10.1074/jbc.m000312200; RA Sayed M., Kim S.O., Salh B.S., Issinger O.G., Pelech S.L.; RT "Stress-induced activation of protein kinase CK2 by direct interaction with RT p38 mitogen-activated protein kinase."; RL J. Biol. Chem. 275:16569-16573(2000). RN [28] RP INTERACTION WITH MA2PK6/MKK6, PHOSPHORYLATION BY MAP2K6/MKK6, RP AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-54, AND CATALYTIC ACTIVITY. RX PubMed=11010976; DOI=10.1074/jbc.m007835200; RA Alonso G., Ambrosino C., Jones M., Nebreda A.R.; RT "Differential activation of p38 mitogen-activated protein kinase isoforms RT depending on signal strength."; RL J. Biol. Chem. 275:40641-40648(2000). RN [29] RP INTERACTION WITH DUSP1, AND ACTIVITY REGULATION. RX PubMed=11278799; DOI=10.1074/jbc.m010966200; RA Slack D.N., Seternes O.M., Gabrielsen M., Keyse S.M.; RT "Distinct binding determinants for ERK2/p38alpha and JNK map kinases RT mediate catalytic activation and substrate selectivity of map kinase RT phosphatase-1."; RL J. Biol. Chem. 276:16491-16500(2001). RN [30] RP INTERACTION WITH DUSP16, AND ACTIVITY REGULATION. RX PubMed=11359773; DOI=10.1074/jbc.m101981200; RA Tanoue T., Yamamoto T., Maeda R., Nishida E.; RT "A Novel MAPK phosphatase MKP-7 acts preferentially on JNK/SAPK and p38 RT alpha and beta MAPKs."; RL J. Biol. Chem. 276:26629-26639(2001). RN [31] RP FUNCTION AS MKNK2 KINASE. RX PubMed=11154262; DOI=10.1128/mcb.21.3.743-754.2001; RA Scheper G.C., Morrice N.A., Kleijn M., Proud C.G.; RT "The mitogen-activated protein kinase signal-integrating kinase Mnk2 is a RT eukaryotic initiation factor 4E kinase with high levels of basal activity RT in mammalian cells."; RL Mol. Cell. Biol. 21:743-754(2001). RN [32] RP INTERACTION WITH CDC25B AND CDC25C, AND FUNCTION IN PHOSPHORYLATION OF RP CDC25B AND CDC25C. RX PubMed=11333986; DOI=10.1038/35075107; RA Bulavin D.V., Higashimoto Y., Popoff I.J., Gaarde W.A., Basrur V., RA Potapova O., Appella E., Fornace A.J. Jr.; RT "Initiation of a G2/M checkpoint after ultraviolet radiation requires p38 RT kinase."; RL Nature 411:102-107(2001). RN [33] RP INTERACTION WITH TAB1, AUTOPHOSPHORYLATION, ACTIVITY REGULATION, AND RP CATALYTIC ACTIVITY. RX PubMed=11847341; DOI=10.1126/science.1067289; RA Ge B., Gram H., Di Padova F., Huang B., New L., Ulevitch R.J., Luo Y., RA Han J.; RT "MAPKK-independent activation of p38alpha mediated by TAB1-dependent RT autophosphorylation of p38alpha."; RL Science 295:1291-1294(2002). RN [34] RP MUTAGENESIS OF TYR-69; ASP-176; ASP-177; ALA-320; PHE-327 AND TRP-337. RX PubMed=15284239; DOI=10.1074/jbc.m404595200; RA Diskin R., Askari N., Capone R., Engelberg D., Livnah O.; RT "Active mutants of the human p38alpha mitogen-activated protein kinase."; RL J. Biol. Chem. 279:47040-47049(2004). RN [35] RP FUNCTION IN PHOSPHORYLATION OF S100A9. RX PubMed=15905572; DOI=10.4049/jimmunol.174.11.7257; RA Lominadze G., Rane M.J., Merchant M., Cai J., Ward R.A., McLeish K.R.; RT "Myeloid-related protein-14 is a p38 MAPK substrate in human neutrophils."; RL J. Immunol. 174:7257-7267(2005). RN [36] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [37] RP PHOSPHORYLATION AT TYR-323, AND ACTIVITY REGULATION. RX PubMed=15735648; DOI=10.1038/ni1177; RA Salvador J.M., Mittelstadt P.R., Guszczynski T., Copeland T.D., RA Yamaguchi H., Appella E., Fornace A.J. Jr., Ashwell J.D.; RT "Alternative p38 activation pathway mediated by T cell receptor-proximal RT tyrosine kinases."; RL Nat. Immunol. 6:390-395(2005). RN [38] RP INTERACTION WITH TAB1, AUTOPHOSPHORYLATION, AND ACTIVITY REGULATION. 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 [39] 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 [40] RP FUNCTION IN STRESS-INDUCED INTERNALIZATION OF EGFR. RX PubMed=16932740; DOI=10.1038/sj.emboj.7601297; RA Zwang Y., Yarden Y.; RT "p38 MAP kinase mediates stress-induced internalization of EGFR: RT implications for cancer chemotherapy."; RL EMBO J. 25:4195-4206(2006). RN [41] RP FUNCTION IN PHOSPHORYLATION OF SIAH2, AND ACTIVITY REGULATION. RX PubMed=17003045; DOI=10.1074/jbc.m606568200; RA Khurana A., Nakayama K., Williams S., Davis R.J., Mustelin T., Ronai Z.; RT "Regulation of the ring finger E3 ligase Siah2 by p38 MAPK."; RL J. Biol. Chem. 281:35316-35326(2006). RN [42] RP INTERACTION WITH NP60. RX PubMed=16352664; DOI=10.1242/jcs.02699; RA Fu J., Yang Z., Wei J., Han J., Gu J.; RT "Nuclear protein NP60 regulates p38 MAPK activity."; RL J. Cell Sci. 119:115-123(2006). RN [43] RP FUNCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION, AND UBIQUITINATION. RX PubMed=17724032; DOI=10.1074/jbc.m703857200; RA Qi X., Pohl N.M., Loesch M., Hou S., Li R., Qin J.Z., Cuenda A., Chen G.; RT "p38alpha antagonizes p38gamma activity through c-Jun-dependent ubiquitin- RT proteasome pathways in regulating Ras transformation and stress response."; RL J. Biol. Chem. 282:31398-31408(2007). RN [44] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-263, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [45] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [46] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-16, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [47] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-180 AND TYR-182, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [48] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [49] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-180 AND TYR-182, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [50] RP FUNCTION IN INHIBITION OF AUTOPHAGY. RX PubMed=19893488; DOI=10.1038/emboj.2009.321; RA Webber J.L., Tooze S.A.; RT "Coordinated regulation of autophagy by p38alpha MAPK through mAtg9 and RT p38IP."; RL EMBO J. 29:27-40(2010). RN [51] RP FUNCTION IN PHOSPHORYLATION OF TIAR. RX PubMed=20932473; DOI=10.1016/j.molcel.2010.09.018; RA Reinhardt H.C., Hasskamp P., Schmedding I., Morandell S., van Vugt M.A., RA Wang X., Linding R., Ong S.E., Weaver D., Carr S.A., Yaffe M.B.; RT "DNA damage activates a spatially distinct late cytoplasmic cell-cycle RT checkpoint network controlled by MK2-mediated RNA stabilization."; RL Mol. Cell 40:34-49(2010). RN [52] RP INTERACTION WITH ADAM17, AND FUNCTION IN PHOSPHORYLATION OF ADAM17. RX PubMed=20188673; DOI=10.1016/j.molcel.2010.01.034; RA Xu P., Derynck R.; RT "Direct activation of TACE-mediated ectodomain shedding by p38 MAP kinase RT regulates EGF receptor-dependent cell proliferation."; RL Mol. Cell 37:551-566(2010). RN [53] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT SER-2; THR-180 AND TYR-182, CLEAVAGE OF INITIATOR METHIONINE RP [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE RP SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [54] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [55] RP IDENTIFICATION IN A COMPLEX WITH AKAP13; PKN1; ZAK AND MAP2K3. RX PubMed=21224381; DOI=10.1074/jbc.m110.185645; RA Cariolato L., Cavin S., Diviani D.; RT "A-kinase anchoring protein (AKAP)-Lbc anchors a PKN-based signaling RT complex involved in alpha1-adrenergic receptor-induced p38 activation."; RL J. Biol. Chem. 286:7925-7937(2011). RN [56] RP FUNCTION (MICROBIAL INFECTION). RC TISSUE=T-cell; RX PubMed=21586573; DOI=10.1074/jbc.m111.234062; RA Peng H., Wang X., Barnes P.F., Tang H., Townsend J.C., Samten B.; RT "The Mycobacterium tuberculosis early secreted antigenic target of 6 kDa RT inhibits T cell interferon-gamma production through the p38 mitogen- RT activated protein kinase pathway."; RL J. Biol. Chem. 286:24508-24518(2011). RN [57] RP ACETYLATION AT LYS-53 AND LYS-152 BY KAT2B/PCAF AND EP300, AND RP DEACETYLATION BY HDAC3. RX PubMed=21444723; DOI=10.1128/mcb.01205-10; RA Pillai V.B., Sundaresan N.R., Samant S.A., Wolfgeher D., Trivedi C.M., RA Gupta M.P.; RT "Acetylation of a conserved lysine residue in the ATP binding pocket of p38 RT augments its kinase activity during hypertrophy of cardiomyocytes."; RL Mol. Cell. Biol. 31:2349-2363(2011). RN [58] RP INTERACTION WITH CDK5RAP3 AND PPM1D, AND DEPHOSPHORYLATION BY PPM1D. RX PubMed=21283629; DOI=10.1371/journal.pone.0016427; RA An H., Lu X., Liu D., Yarbrough W.G.; RT "LZAP inhibits p38 MAPK (p38) phosphorylation and activity by facilitating RT p38 association with the wild-type p53 induced phosphatase 1 (WIP1)."; RL PLoS ONE 6:E16427-E16427(2011). RN [59] 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 [60] 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 [61] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; THR-180 AND TYR-182, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [62] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [63] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [64] RP SUBCELLULAR LOCATION. RX PubMed=30878395; DOI=10.1016/j.yjmcc.2019.03.005; RA Li C., Li J., Xue K., Zhang J., Wang C., Zhang Q., Chen X., Gao C., Yu X., RA Sun L.; RT "MicroRNA-143-3p promotes human cardiac fibrosis via targeting sprouty3 RT after myocardial infarction."; RL J. Mol. Cell. Cardiol. 129:281-292(2019). RN [65] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=35857590; DOI=10.1126/science.abl6324; RA Robinson K.S., Toh G.A., Rozario P., Chua R., Bauernfried S., Sun Z., RA Firdaus M.J., Bayat S., Nadkarni R., Poh Z.S., Tham K.C., Harapas C.R., RA Lim C.K., Chu W., Tay C.W.S., Tan K.Y., Zhao T., Bonnard C., Sobota R., RA Connolly J.E., Common J., Masters S.L., Chen K.W., Ho L., Wu B., RA Hornung V., Zhong F.L.; RT "ZAKalpha-driven ribotoxic stress response activates the human NLRP1 RT inflammasome."; RL Science 377:328-335(2022). RN [66] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS). RX PubMed=8910361; DOI=10.1074/jbc.271.44.27696; RA Wilson K.P., Fitzgibbon M.J., Caron P.R., Griffith J.P., Chen W., RA McCaffrey P.G., Chambers S.P., Su M.S.-S.; RT "Crystal structure of p38 mitogen-activated protein kinase."; RL J. Biol. Chem. 271:27696-27700(1996). RN [67] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS). RX PubMed=9095200; DOI=10.1038/nsb0497-311; RA Tong L., Pav S., White D.M., Rogers S., Crane K.M., Cywin C.L., Brown M.L., RA Pargellis C.A.; RT "A highly specific inhibitor of human p38 MAP kinase binds in the ATP RT pocket."; RL Nat. Struct. Biol. 4:311-316(1997). RN [68] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS). RX PubMed=9753691; DOI=10.1016/s0969-2126(98)00113-0; RA Wang Z., Canagarajah B.J., Boehm J.C., Kassisa S., Cobb M.H., Young P.R., RA Abdel-Meguid S., Adams J.L., Goldsmith E.J.; RT "Structural basis of inhibitor selectivity in MAP kinases."; RL Structure 6:1117-1128(1998). RN [69] RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS). RX PubMed=10633045; DOI=10.1021/jm990401t; RA Shewchuk L., Hassell A., Wisely B., Rocque W., Holmes W., Veal J., RA Kuyper L.F.; RT "Binding mode of the 4-anilinoquinazoline class of protein kinase RT inhibitor: X-ray crystallographic studies of 4-anilinoquinazolines bound to RT cyclin-dependent kinase 2 and p38 kinase."; RL J. Med. Chem. 43:133-138(2000). RN [70] RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS), AND ACTIVITY REGULATION. RX PubMed=11896401; DOI=10.1038/nsb770; RA Pargellis C., Tong L., Churchill L., Cirillo P.F., Gilmore T., Graham A.G., RA Grob P.M., Hickey E.R., Moss N., Pav S., Regan J.; RT "Inhibition of p38 MAP kinase by utilizing a novel allosteric binding RT site."; RL Nat. Struct. Biol. 9:268-272(2002). RN [71] RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS), AND ACTIVITY REGULATION. RX PubMed=12482439; DOI=10.1016/s0960-894x(02)00752-7; RA Stelmach J.E., Liu L., Patel S.B., Pivnichny J.V., Scapin G., Singh S., RA Hop C.E., Wang Z., Strauss J.R., Cameron P.M., Nichols E.A., O'Keefe S.J., RA O'Neill E.A., Schmatz D.M., Schwartz C.D., Thompson C.M., Zaller D.M., RA Doherty J.B.; RT "Design and synthesis of potent, orally bioavailable dihydroquinazolinone RT inhibitors of p38 MAP kinase."; RL Bioorg. Med. Chem. Lett. 13:277-280(2003). RN [72] RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS), AND ACTIVITY REGULATION. RX PubMed=14561090; DOI=10.1021/jm0301787; RA Trejo A., Arzeno H., Browner M., Chanda S., Cheng S., Comer D.D., RA Dalrymple S.A., Dunten P., Lafargue J., Lovejoy B., Freire-Moar J., Lim J., RA Mcintosh J., Miller J., Papp E., Reuter D., Roberts R., Sanpablo F., RA Saunders J., Song K., Villasenor A., Warren S.D., Welch M., Weller P., RA Whiteley P.E., Zeng L., Goldstein D.M.; RT "Design and synthesis of 4-azaindoles as inhibitors of p38 MAP kinase."; RL J. Med. Chem. 46:4702-4713(2003). RN [73] {ECO:0007744|PDB:1OUK, ECO:0007744|PDB:1OUY, ECO:0007744|PDB:1OVE} RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH INHIBITOR. RX PubMed=12897767; DOI=10.1038/nsb949; RA Fitzgerald C.E., Patel S.B., Becker J.W., Cameron P.M., Zaller D., RA Pikounis V.B., O'Keefe S.J., Scapin G.; RT "Structural basis for p38alpha MAP kinase quinazolinone and pyridol- RT pyrimidine inhibitor specificity."; RL Nat. Struct. Biol. 10:764-769(2003). RN [74] RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS), AND ACTIVITY REGULATION. RX PubMed=14726206; DOI=10.1016/j.bbapap.2003.09.009; RA Patel S.B., Cameron P.M., Frantz-Wattley B., O'Neill E., Becker J.W., RA Scapin G.; RT "Lattice stabilization and enhanced diffraction in human p38 alpha crystals RT by protein engineering."; RL Biochim. Biophys. Acta 1696:67-73(2004). RN [75] {ECO:0007744|PDB:2BAJ, ECO:0007744|PDB:2BAK, ECO:0007744|PDB:2BAL, ECO:0007744|PDB:2BAQ} RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 2-359 IN COMPLEX WITH INHIBITOR. RX PubMed=16342939; DOI=10.1021/bi051714v; RA Sullivan J.E., Holdgate G.A., Campbell D., Timms D., Gerhardt S., Breed J., RA Breeze A.L., Bermingham A., Pauptit R.A., Norman R.A., Embrey K.J., RA Read J., VanScyoc W.S., Ward W.H.; RT "Prevention of MKK6-dependent activation by binding to p38alpha MAP RT kinase."; RL Biochemistry 44:16475-16490(2005). RN [76] RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-359, AND ACTIVITY REGULATION. RX PubMed=15837335; DOI=10.1016/j.bmcl.2005.02.010; RA Tamayo N., Liao L., Goldberg M., Powers D., Tudor Y.Y., Yu V., Wong L.M., RA Henkle B., Middleton S., Syed R., Harvey T., Jang G., Hungate R., RA Dominguez C.; RT "Design and synthesis of potent pyridazine inhibitors of p38 MAP kinase."; RL Bioorg. Med. Chem. Lett. 15:2409-2413(2005). RN [77] RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS), AND ACTIVITY REGULATION. RX PubMed=16169718; DOI=10.1016/j.bmcl.2005.08.038; RA Michelotti E.L., Moffett K.K., Nguyen D., Kelly M.J., Shetty R., Chai X., RA Northrop K., Namboodiri V., Campbell B., Flynn G.A., Fujimoto T., RA Hollinger F.P., Bukhtiyarova M., Springman E.B., Karpusas M.; RT "Two classes of p38alpha MAP kinase inhibitors having a common RT diphenylether core but exhibiting divergent binding modes."; RL Bioorg. Med. Chem. Lett. 15:5274-5279(2005). RN [78] {ECO:0007744|PDB:1W7H, ECO:0007744|PDB:1WBO} RP X-RAY CRYSTALLOGRAPHY (2.16 ANGSTROMS) OF 2-359 IN COMPLEX WITH INHIBITOR. RX PubMed=15658854; DOI=10.1021/jm0495778; RA Hartshorn M.J., Murray C.W., Cleasby A., Frederickson M., Tickle I.J., RA Jhoti H.; RT "Fragment-based lead discovery using X-ray crystallography."; RL J. Med. Chem. 48:403-413(2005). RN [79] RP X-RAY CRYSTALLOGRAPHY (4.0 ANGSTROMS) OF 2-359 IN COMPLEX WITH MAPKAPK2. RX PubMed=17255097; DOI=10.1074/jbc.m611165200; RA ter Haar E., Prabhakar P., Liu X., Lepre C.; RT "Crystal structure of the p38 alpha-MAPKAP kinase 2 heterodimer."; RL J. Biol. Chem. 282:9733-9739(2007). RN [80] RP ERRATUM OF PUBMED:17255097. RA ter Haar E., Prabhakar P., Liu X., Lepre C.; RL J. Biol. Chem. 282:14684-14684(2007). RN [81] RP VARIANTS [LARGE SCALE ANALYSIS] VAL-51; ARG-322 AND GLY-343. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). 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 (PubMed:9687510, PubMed:9792677). RPS6KA5/MSK1 and RPS6KA4/MSK2 play CC important roles in the rapid induction of immediate-early genes in CC response to stress or mitogenic stimuli, either by inducing chromatin CC remodeling or by recruiting the transcription machinery CC (PubMed:9687510, PubMed:9792677). On the other hand, two other kinase CC targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of CC gene expression mostly at the post-transcriptional level, by CC phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating CC EEF2K, which is important for the elongation of mRNA during CC translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by CC p38 MAPKs, regulate protein synthesis by phosphorylating the initiation CC factor EIF4E2 (PubMed:11154262). MAPK14 interacts also with casein CC kinase II, leading to its activation through autophosphorylation and CC further phosphorylation of TP53/p53 (PubMed:10747897). 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 (PubMed:17003045). CC MAPK14 may also inhibit the lysosomal degradation pathway of autophagy CC by interfering with the intracellular trafficking of the transmembrane CC protein ATG9 (PubMed:19893488). Another function of MAPK14 is to CC regulate the endocytosis of membrane receptors by different mechanisms CC that impinge on the small GTPase RAB5A. In addition, clathrin-mediated CC EGFR internalization induced by inflammatory cytokines and UV CC irradiation depends on MAPK14-mediated phosphorylation of EGFR itself CC as well as of RAB5A effectors (PubMed:16932740). Ectodomain shedding of CC transmembrane proteins is regulated by p38 MAPKs as well. In response CC to inflammatory stimuli, p38 MAPKs phosphorylate the membrane- CC associated metalloprotease ADAM17 (PubMed:20188673). Such CC phosphorylation is required for ADAM17-mediated ectodomain shedding of CC TGF-alpha family ligands, which results in the activation of EGFR CC signaling and cell proliferation. Another p38 MAPK substrate is FGFR1. CC FGFR1 can be translocated from the extracellular space into the cytosol CC and nucleus of target cells, and regulates processes such as rRNA CC synthesis and cell growth. FGFR1 translocation requires p38 MAPK CC activation. In the nucleus, many transcription factors are CC phosphorylated and activated by p38 MAPKs in response to different CC stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, CC DDIT3, TP53/p53 and MEF2C and MEF2A (PubMed:9430721, PubMed:9858528, CC PubMed:10330143). The p38 MAPKs are emerging as important modulators of CC gene expression by regulating chromatin modifiers and remodelers. The CC promoters of several genes involved in the inflammatory response, such CC as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of CC histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated CC myeloid cells. This phosphorylation enhances the accessibility of the CC cryptic NF-kappa-B-binding sites marking promoters for increased NF- CC kappa-B recruitment. Phosphorylates CDC25B and CDC25C which is required CC for binding to 14-3-3 proteins and leads to initiation of a G2 delay CC after ultraviolet radiation (PubMed:11333986). Phosphorylates TIAR CC following DNA damage, releasing TIAR from GADD45A mRNA and preventing CC mRNA degradation (PubMed:20932473). The p38 MAPKs may also have kinase- CC independent roles, which are thought to be due to the binding to CC targets in the absence of phosphorylation. Protein O-Glc-N-acylation CC catalyzed by the OGT is regulated by MAPK14, and, although OGT does not CC seem to be phosphorylated by MAPK14, their interaction increases upon CC MAPK14 activation induced by glucose deprivation. This interaction may CC regulate OGT activity by recruiting it to specific targets such as CC neurofilament H, stimulating its O-Glc-N-acylation. Required in mid- CC fetal development for the growth of embryo-derived blood vessels in the CC labyrinth layer of the placenta. Also plays an essential role in CC developmental and stress-induced erythropoiesis, through regulation of CC EPO gene expression (PubMed:10943842). Isoform MXI2 activation is CC stimulated by mitogens and oxidative stress and only poorly CC phosphorylates ELK1 and ATF2. Isoform EXIP may play a role in the early CC onset of apoptosis. Phosphorylates S100A9 at 'Thr-113' CC (PubMed:15905572). Phosphorylates NLRP1 downstream of MAP3K20/ZAK in CC response to UV-B irradiation and ribosome collisions, promoting CC activation of the NLRP1 inflammasome and pyroptosis (PubMed:35857590). CC {ECO:0000269|PubMed:10330143, ECO:0000269|PubMed:10747897, CC ECO:0000269|PubMed:10943842, ECO:0000269|PubMed:11154262, CC ECO:0000269|PubMed:11333986, ECO:0000269|PubMed:15905572, CC ECO:0000269|PubMed:16932740, ECO:0000269|PubMed:17003045, CC ECO:0000269|PubMed:17724032, ECO:0000269|PubMed:19893488, CC ECO:0000269|PubMed:20188673, ECO:0000269|PubMed:20932473, CC ECO:0000269|PubMed:35857590, ECO:0000269|PubMed:9430721, CC ECO:0000269|PubMed:9687510, ECO:0000269|PubMed:9792677, CC ECO:0000269|PubMed:9858528}. CC -!- FUNCTION: (Microbial infection) Activated by phosphorylation by CC M.tuberculosis EsxA in T-cells leading to inhibition of IFN-gamma CC production; phosphorylation is apparent within 15 minutes and is CC inhibited by kinase-specific inhibitors SB203580 and siRNA CC (PubMed:21586573). {ECO:0000269|PubMed:21586573}. 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:11010976, ECO:0000269|PubMed:35857590}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990; CC Evidence={ECO:0000269|PubMed:11010976, ECO:0000269|PubMed:35857590}; 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:11010976, CC ECO:0000269|PubMed:35857590}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609; CC Evidence={ECO:0000269|PubMed:11010976, ECO:0000269|PubMed:35857590}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:10838079}; 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). Isoform CC Mxi2 is 100-fold less sensitive to these agents than the other isoforms CC and is not inhibited by DUSP1. Isoform Exip is not activated by MAP2K6. CC SB203580 is an inhibitor of MAPK14. {ECO:0000269|PubMed:10391943, CC ECO:0000269|PubMed:10838079, ECO:0000269|PubMed:11278799, CC ECO:0000269|PubMed:11359773, ECO:0000269|PubMed:11847341, CC ECO:0000269|PubMed:11866441, ECO:0000269|PubMed:11896401, CC ECO:0000269|PubMed:12482439, ECO:0000269|PubMed:14561090, CC ECO:0000269|PubMed:14726206, ECO:0000269|PubMed:15735648, CC ECO:0000269|PubMed:15735649, ECO:0000269|PubMed:15837335, CC ECO:0000269|PubMed:16169718, ECO:0000269|PubMed:17003045, CC ECO:0000269|PubMed:7535770, ECO:0000269|PubMed:8622669, CC ECO:0000269|PubMed:9430721}. 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 CC (PubMed:21224381). Binds to a kinase interaction motif within the CC protein tyrosine phosphatase, PTPRR (By similarity). This interaction CC retains 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 (PubMed:21283629). Interacts CC with DUSP2; this interaction does not lead to catalytic activation of CC DUSP2 and dephosphrylation of MAPK14 (By similarity). CC {ECO:0000250|UniProtKB:P47811, ECO:0000269|PubMed:10391943, CC ECO:0000269|PubMed:10747897, ECO:0000269|PubMed:11010976, CC ECO:0000269|PubMed:11278799, ECO:0000269|PubMed:11333986, CC ECO:0000269|PubMed:11359773, ECO:0000269|PubMed:11847341, CC ECO:0000269|PubMed:12897767, ECO:0000269|PubMed:15658854, CC ECO:0000269|PubMed:15735649, ECO:0000269|PubMed:16342939, CC ECO:0000269|PubMed:16352664, ECO:0000269|PubMed:16751104, CC ECO:0000269|PubMed:17255097, ECO:0000269|PubMed:20188673, CC ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:21283629, CC ECO:0000269|PubMed:9792677}. CC -!- INTERACTION: CC Q16539; P48730-2: CSNK1D; NbExp=3; IntAct=EBI-73946, EBI-9087876; CC Q16539; P28562: DUSP1; NbExp=4; IntAct=EBI-73946, EBI-975493; CC Q16539; Q99956: DUSP9; NbExp=4; IntAct=EBI-73946, EBI-3906678; CC Q16539; P68104: EEF1A1; NbExp=3; IntAct=EBI-73946, EBI-352162; CC Q16539; P46734: MAP2K3; NbExp=5; IntAct=EBI-73946, EBI-602462; CC Q16539; P52564: MAP2K6; NbExp=3; IntAct=EBI-73946, EBI-448135; CC Q16539; P27361: MAPK3; NbExp=5; IntAct=EBI-73946, EBI-73995; CC Q16539; P49137: MAPKAPK2; NbExp=10; IntAct=EBI-73946, EBI-993299; CC Q16539; Q16644: MAPKAPK3; NbExp=10; IntAct=EBI-73946, EBI-1384657; CC Q16539; Q9BUB5: MKNK1; NbExp=5; IntAct=EBI-73946, EBI-73837; CC Q16539; Q9HBH9: MKNK2; NbExp=4; IntAct=EBI-73946, EBI-2864341; CC Q16539; P35813: PPM1A; NbExp=2; IntAct=EBI-73946, EBI-989143; CC Q16539; Q15256: PTPRR; NbExp=3; IntAct=EBI-73946, EBI-2265659; CC Q16539; P06400: RB1; NbExp=4; IntAct=EBI-73946, EBI-491274; CC Q16539; O75676: RPS6KA4; NbExp=6; IntAct=EBI-73946, EBI-73933; CC Q16539; Q8NEM7: SUPT20H; NbExp=5; IntAct=EBI-73946, EBI-946984; CC Q16539; Q92574: TSC1; NbExp=2; IntAct=EBI-73946, EBI-1047085; CC Q16539; Q07352: ZFP36L1; NbExp=2; IntAct=EBI-73946, EBI-721823; CC Q16539; O43257: ZNHIT1; NbExp=7; IntAct=EBI-73946, EBI-347522; CC Q16539-1; P22736-1: NR4A1; NbExp=5; IntAct=EBI-15834191, EBI-16085263; CC Q16539-1; Q15256-1: PTPRR; NbExp=6; IntAct=EBI-15834191, EBI-16067395; CC Q16539-1; P54830-1: Ptpn5; Xeno; NbExp=6; IntAct=EBI-15834191, EBI-16067443; CC Q16539-3; P28482: MAPK1; NbExp=5; IntAct=EBI-6932370, EBI-959949; CC Q16539-3; P49790: NUP153; NbExp=2; IntAct=EBI-6932370, EBI-286779; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:7535770}. Nucleus CC {ECO:0000269|PubMed:30878395, ECO:0000269|PubMed:7535770}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=CSBP2; CC IsoId=Q16539-1; Sequence=Displayed; CC Name=CSBP1; CC IsoId=Q16539-2; Sequence=VSP_004842; CC Name=Mxi2; CC IsoId=Q16539-3; Sequence=VSP_004844; CC Name=Exip; Synonyms=Exon skip; CC IsoId=Q16539-4; Sequence=VSP_004843, VSP_004845; CC Name=5; CC IsoId=Q16539-5; Sequence=VSP_057194; CC -!- TISSUE SPECIFICITY: Brain, heart, placenta, pancreas and skeletal CC muscle. Expressed to a lesser extent in lung, liver and kidney. 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 citokines, 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 (PubMed:21283629). {ECO:0000269|PubMed:11010976, CC ECO:0000269|PubMed:15735648, ECO:0000269|PubMed:17724032, CC ECO:0000269|PubMed:21283629, ECO:0000269|PubMed:7535770, CC ECO:0000269|PubMed:8622669}. 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. CC {ECO:0000269|PubMed:21444723}. CC -!- PTM: Ubiquitinated. Ubiquitination leads to degradation by the CC proteasome pathway. {ECO:0000269|PubMed:17724032}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr CC protein kinase family. MAP kinase subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=P38 mitogen-activated protein CC kinases entry; CC URL="https://en.wikipedia.org/wiki/P38_mitogen-activated_protein_kinases"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/41292/MAPK14"; 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; L35263; AAA57455.1; -; mRNA. DR EMBL; L35264; AAA57456.1; -; mRNA. DR EMBL; L35253; AAA74301.1; -; mRNA. DR EMBL; U19775; AAC50329.1; -; mRNA. DR EMBL; AF100544; AAF36770.1; -; mRNA. DR EMBL; AB074150; BAB85654.1; -; mRNA. DR EMBL; FJ032367; ACI00233.1; -; mRNA. DR EMBL; AK291709; BAF84398.1; -; mRNA. DR EMBL; BT006933; AAP35579.1; -; mRNA. DR EMBL; CR536505; CAG38743.1; -; mRNA. DR EMBL; EU332860; ABY87549.1; -; Genomic_DNA. DR EMBL; Z95152; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471081; EAX03869.1; -; Genomic_DNA. DR EMBL; BC000092; AAH00092.1; -; mRNA. DR EMBL; BC031574; AAH31574.1; -; mRNA. DR CCDS; CCDS4815.1; -. [Q16539-2] DR CCDS; CCDS4816.1; -. [Q16539-1] DR CCDS; CCDS4817.1; -. [Q16539-4] DR PIR; S53536; S53536. DR RefSeq; NP_001306.1; NM_001315.2. [Q16539-2] DR RefSeq; NP_620581.1; NM_139012.2. [Q16539-1] DR RefSeq; NP_620582.1; NM_139013.2. [Q16539-3] DR RefSeq; NP_620583.1; NM_139014.2. [Q16539-4] DR PDB; 1A9U; X-ray; 2.50 A; A=1-360. DR PDB; 1BL6; X-ray; 2.50 A; A=1-360. DR PDB; 1BL7; X-ray; 2.50 A; A=1-360. DR PDB; 1BMK; X-ray; 2.40 A; A=1-360. DR PDB; 1DI9; X-ray; 2.60 A; A=1-360. DR PDB; 1IAN; X-ray; 2.00 A; A=2-360. DR PDB; 1KV1; X-ray; 2.50 A; A=1-360. DR PDB; 1KV2; X-ray; 2.80 A; A=1-360. DR PDB; 1M7Q; X-ray; 2.40 A; A=1-360. DR PDB; 1OUK; X-ray; 2.50 A; A=1-360. DR PDB; 1OUY; X-ray; 2.50 A; A=1-360. DR PDB; 1OVE; X-ray; 2.10 A; A=1-360. DR PDB; 1OZ1; X-ray; 2.10 A; A=1-360. DR PDB; 1R39; X-ray; 2.30 A; A=1-360. DR PDB; 1R3C; X-ray; 2.00 A; A=1-360. DR PDB; 1W7H; X-ray; 2.21 A; A=2-360. DR PDB; 1W82; X-ray; 2.20 A; A=2-360. DR PDB; 1W83; X-ray; 2.50 A; A=2-360. DR PDB; 1W84; X-ray; 2.20 A; A=2-360. DR PDB; 1WBN; X-ray; 2.40 A; A=2-360. DR PDB; 1WBO; X-ray; 2.16 A; A=2-360. DR PDB; 1WBS; X-ray; 1.80 A; A=2-360. DR PDB; 1WBT; X-ray; 2.00 A; A=2-360. DR PDB; 1WBV; X-ray; 2.00 A; A=2-360. DR PDB; 1WBW; X-ray; 2.41 A; A=2-360. DR PDB; 1WFC; X-ray; 2.30 A; A=1-360. DR PDB; 1YQJ; X-ray; 2.00 A; A=2-360. DR PDB; 1ZYJ; X-ray; 2.00 A; A=1-360. DR PDB; 1ZZ2; X-ray; 2.00 A; A=1-360. DR PDB; 1ZZL; X-ray; 2.00 A; A=4-354. DR PDB; 2BAJ; X-ray; 2.25 A; A=2-360. DR PDB; 2BAK; X-ray; 2.20 A; A=2-360. DR PDB; 2BAL; X-ray; 2.10 A; A=2-360. DR PDB; 2BAQ; X-ray; 2.80 A; A=2-360. DR PDB; 2FSL; X-ray; 1.70 A; X=2-360. DR PDB; 2FSM; X-ray; 1.86 A; X=2-360. DR PDB; 2FSO; X-ray; 1.83 A; X=2-360. DR PDB; 2FST; X-ray; 1.45 A; X=2-360. DR PDB; 2GFS; X-ray; 1.75 A; A=2-360. DR PDB; 2I0H; X-ray; 2.00 A; A=1-360. DR PDB; 2LGC; NMR; -; A=2-354. DR PDB; 2NPQ; X-ray; 1.80 A; A=2-360. DR PDB; 2OKR; X-ray; 2.00 A; A/D=2-360. DR PDB; 2ONL; X-ray; 4.00 A; A/B=2-360. DR PDB; 2QD9; X-ray; 1.70 A; A=2-360. DR PDB; 2RG5; X-ray; 2.40 A; A=2-360. DR PDB; 2RG6; X-ray; 1.72 A; A=2-360. DR PDB; 2Y8O; X-ray; 1.95 A; A=1-360. DR PDB; 2YIS; X-ray; 2.00 A; A=2-360. DR PDB; 2YIW; X-ray; 2.00 A; A=2-360. DR PDB; 2YIX; X-ray; 2.30 A; A=4-354. DR PDB; 2ZAZ; X-ray; 1.80 A; A=1-360. DR PDB; 2ZB0; X-ray; 2.10 A; A=1-360. DR PDB; 2ZB1; X-ray; 2.50 A; A=1-360. DR PDB; 3BV2; X-ray; 2.40 A; A=2-360. DR PDB; 3BV3; X-ray; 2.59 A; A=2-360. DR PDB; 3BX5; X-ray; 2.40 A; A=2-360. DR PDB; 3C5U; X-ray; 2.80 A; A=2-360. DR PDB; 3CTQ; X-ray; 1.95 A; A=5-352. DR PDB; 3D7Z; X-ray; 2.10 A; A=1-360. DR PDB; 3D83; X-ray; 1.90 A; A=1-360. DR PDB; 3DS6; X-ray; 2.90 A; A/B/C/D=1-360. DR PDB; 3DT1; X-ray; 2.80 A; A=1-360. DR PDB; 3E92; X-ray; 2.00 A; A=1-360. DR PDB; 3E93; X-ray; 2.00 A; A=1-360. DR PDB; 3FC1; X-ray; 2.40 A; X=1-360. DR PDB; 3FI4; X-ray; 2.20 A; A=1-360. DR PDB; 3FKL; X-ray; 2.00 A; A=1-360. DR PDB; 3FKN; X-ray; 2.00 A; A=1-360. DR PDB; 3FKO; X-ray; 2.00 A; A=1-360. DR PDB; 3FL4; X-ray; 1.80 A; A=1-360. DR PDB; 3FLN; X-ray; 1.90 A; C=1-360. DR PDB; 3FLQ; X-ray; 1.90 A; A=1-360. DR PDB; 3FLS; X-ray; 2.30 A; A=1-360. DR PDB; 3FLW; X-ray; 2.10 A; A=1-360. DR PDB; 3FLY; X-ray; 1.80 A; A=1-360. DR PDB; 3FLZ; X-ray; 2.23 A; A=1-360. DR PDB; 3FMH; X-ray; 1.90 A; A=1-360. DR PDB; 3FMJ; X-ray; 2.00 A; A=1-360. DR PDB; 3FMK; X-ray; 1.70 A; A=1-360. DR PDB; 3FML; X-ray; 2.10 A; A=1-360. DR PDB; 3FMM; X-ray; 2.00 A; A=1-360. DR PDB; 3FMN; X-ray; 1.90 A; A=1-360. DR PDB; 3FSF; X-ray; 2.10 A; A=1-360. DR PDB; 3FSK; X-ray; 2.00 A; A=1-360. DR PDB; 3GC7; X-ray; 1.80 A; A=1-360. DR PDB; 3GCP; X-ray; 2.25 A; A=2-360. DR PDB; 3GCQ; X-ray; 2.00 A; A=2-360. DR PDB; 3GCS; X-ray; 2.10 A; A=2-360. DR PDB; 3GCU; X-ray; 2.10 A; A/B=2-360. DR PDB; 3GCV; X-ray; 2.30 A; A=2-360. DR PDB; 3GFE; X-ray; 2.10 A; A=1-360. DR PDB; 3GI3; X-ray; 2.40 A; A=1-360. DR PDB; 3HA8; X-ray; 2.48 A; A=1-360. DR PDB; 3HEC; X-ray; 2.50 A; A=5-352. DR PDB; 3HEG; X-ray; 2.20 A; A=5-352. DR PDB; 3HL7; X-ray; 1.88 A; A=1-360. DR PDB; 3HLL; X-ray; 1.95 A; A=1-360. DR PDB; 3HP2; X-ray; 2.15 A; A=1-360. DR PDB; 3HP5; X-ray; 2.30 A; A=1-360. DR PDB; 3HRB; X-ray; 2.20 A; A=2-360. DR PDB; 3HUB; X-ray; 2.25 A; A=2-360. DR PDB; 3HUC; X-ray; 1.80 A; A=2-360. DR PDB; 3HV3; X-ray; 2.00 A; A=2-360. DR PDB; 3HV4; X-ray; 2.60 A; A/B=2-360. DR PDB; 3HV5; X-ray; 2.25 A; A/B=2-360. DR PDB; 3HV6; X-ray; 1.95 A; A=2-360. DR PDB; 3HV7; X-ray; 2.40 A; A=2-360. DR PDB; 3HVC; X-ray; 2.10 A; A=1-360. DR PDB; 3IPH; X-ray; 2.10 A; A=1-360. DR PDB; 3ITZ; X-ray; 2.25 A; A=1-360. DR PDB; 3IW5; X-ray; 2.50 A; A=2-360. DR PDB; 3IW6; X-ray; 2.10 A; A=2-360. DR PDB; 3IW7; X-ray; 2.40 A; A=2-360. DR PDB; 3IW8; X-ray; 2.00 A; A=2-360. DR PDB; 3K3I; X-ray; 1.70 A; A=5-352. DR PDB; 3K3J; X-ray; 2.00 A; A=1-360. DR PDB; 3KF7; X-ray; 2.00 A; A=1-360. DR PDB; 3KQ7; X-ray; 1.80 A; A=1-360. DR PDB; 3L8S; X-ray; 2.35 A; A=2-360. DR PDB; 3L8X; X-ray; 2.15 A; A=2-360. DR PDB; 3LFA; X-ray; 2.10 A; A=2-360. DR PDB; 3LFB; X-ray; 2.60 A; A=2-360. DR PDB; 3LFC; X-ray; 2.80 A; A=2-360. DR PDB; 3LFD; X-ray; 3.40 A; A=2-360. DR PDB; 3LFE; X-ray; 2.30 A; A=2-360. DR PDB; 3LFF; X-ray; 1.50 A; A=2-360. DR PDB; 3LHJ; X-ray; 3.31 A; A=1-360. DR PDB; 3MGY; X-ray; 2.10 A; A=1-360. DR PDB; 3MH0; X-ray; 2.00 A; A=1-360. DR PDB; 3MH1; X-ray; 2.20 A; A=1-360. DR PDB; 3MH2; X-ray; 2.30 A; A=1-360. DR PDB; 3MH3; X-ray; 2.20 A; A=1-360. DR PDB; 3MPA; X-ray; 2.10 A; A=1-360. DR PDB; 3MPT; X-ray; 1.89 A; A=1-360. DR PDB; 3MVL; X-ray; 2.80 A; A/B=2-360. DR PDB; 3MVM; X-ray; 2.00 A; A/B=2-360. DR PDB; 3MW1; X-ray; 2.80 A; A=2-360. DR PDB; 3NEW; X-ray; 2.51 A; A=1-360. DR PDB; 3NNU; X-ray; 2.40 A; A=1-354. DR PDB; 3NNV; X-ray; 2.10 A; A=1-354. DR PDB; 3NNW; X-ray; 1.89 A; A=1-354. DR PDB; 3NNX; X-ray; 2.28 A; A=1-354. DR PDB; 3NWW; X-ray; 2.09 A; A=2-360. DR PDB; 3O8P; X-ray; 2.10 A; A=1-360. DR PDB; 3O8T; X-ray; 2.00 A; A=1-360. DR PDB; 3O8U; X-ray; 2.10 A; A=1-360. DR PDB; 3OBG; X-ray; 2.80 A; A=1-360. DR PDB; 3OBJ; X-ray; 2.40 A; A=1-360. DR PDB; 3OC1; X-ray; 2.59 A; A=1-360. DR PDB; 3OCG; X-ray; 2.21 A; A=2-360. DR PDB; 3OD6; X-ray; 2.68 A; X=1-360. DR PDB; 3ODY; X-ray; 2.20 A; X=1-360. DR PDB; 3ODZ; X-ray; 2.30 A; X=1-360. DR PDB; 3OEF; X-ray; 1.60 A; X=1-360. DR PDB; 3PG3; X-ray; 2.00 A; A=2-360. DR PDB; 3QUD; X-ray; 2.00 A; A=2-360. DR PDB; 3QUE; X-ray; 2.70 A; A=2-360. DR PDB; 3RIN; X-ray; 2.20 A; A=1-360. DR PDB; 3ROC; X-ray; 1.70 A; A=1-360. DR PDB; 3S3I; X-ray; 1.80 A; A=4-352. DR PDB; 3S4Q; X-ray; 2.27 A; A=2-360. DR PDB; 3U8W; X-ray; 2.15 A; A=1-360. DR PDB; 3UVP; X-ray; 2.40 A; A=2-360. DR PDB; 3UVQ; X-ray; 2.20 A; A=2-360. DR PDB; 3UVR; X-ray; 2.10 A; A=2-360. DR PDB; 3ZS5; X-ray; 1.60 A; A=2-360. DR PDB; 3ZSG; X-ray; 1.89 A; A=2-360. DR PDB; 3ZSH; X-ray; 2.05 A; A=2-360. DR PDB; 3ZSI; X-ray; 2.40 A; A=2-360. DR PDB; 3ZYA; X-ray; 1.90 A; A=1-360. DR PDB; 4A9Y; X-ray; 2.20 A; A=2-360. DR PDB; 4AA0; X-ray; 1.80 A; A=2-360. DR PDB; 4AA4; X-ray; 2.30 A; A=2-360. DR PDB; 4AA5; X-ray; 2.38 A; A=2-360. DR PDB; 4AAC; X-ray; 2.50 A; A=2-360. DR PDB; 4DLI; X-ray; 1.91 A; A=2-360. DR PDB; 4DLJ; X-ray; 2.60 A; A=2-360. DR PDB; 4E5A; X-ray; 1.87 A; X=1-360. DR PDB; 4E5B; X-ray; 2.00 A; A=1-360. DR PDB; 4E6A; X-ray; 2.09 A; A=1-360. DR PDB; 4E6C; X-ray; 2.39 A; A=1-360. DR PDB; 4E8A; X-ray; 2.70 A; A=1-360. DR PDB; 4EH2; X-ray; 2.00 A; A=2-360. DR PDB; 4EH3; X-ray; 2.40 A; A=2-360. DR PDB; 4EH4; X-ray; 2.50 A; A=2-360. DR PDB; 4EH5; X-ray; 2.00 A; A=2-360. DR PDB; 4EH6; X-ray; 2.10 A; A=2-360. DR PDB; 4EH7; X-ray; 2.10 A; A=2-360. DR PDB; 4EH8; X-ray; 2.20 A; A=2-360. DR PDB; 4EH9; X-ray; 2.10 A; A=2-360. DR PDB; 4EHV; X-ray; 1.60 A; A=2-360. DR PDB; 4EWQ; X-ray; 2.10 A; A=2-360. DR PDB; 4F9W; X-ray; 2.00 A; A=2-360. DR PDB; 4F9Y; X-ray; 1.85 A; A=2-360. DR PDB; 4FA2; X-ray; 2.00 A; A=2-360. DR PDB; 4GEO; X-ray; 1.66 A; A=2-360. DR PDB; 4KIN; X-ray; 1.97 A; A/B/C/D=2-360. DR PDB; 4KIP; X-ray; 2.27 A; A/B=2-360. DR PDB; 4KIQ; X-ray; 2.50 A; A/B/C/D=2-360. DR PDB; 4L8M; X-ray; 2.10 A; A=2-360. DR PDB; 4R3C; X-ray; 2.06 A; A=2-360. DR PDB; 4ZTH; X-ray; 2.15 A; A=2-360. DR PDB; 5ETA; X-ray; 2.80 A; A/B=1-360. DR PDB; 5ETC; X-ray; 2.42 A; A=1-360. DR PDB; 5ETF; X-ray; 2.40 A; A=1-360. DR PDB; 5ETI; X-ray; 2.80 A; A=1-360. DR PDB; 5ML5; X-ray; 1.90 A; A=1-360. DR PDB; 5MTX; X-ray; 1.80 A; A=1-360. DR PDB; 5MTY; X-ray; 2.31 A; A=1-360. DR PDB; 5MZ3; X-ray; 2.15 A; A=1-360. DR PDB; 5N63; X-ray; 2.40 A; A=1-360. DR PDB; 5N64; X-ray; 2.40 A; A=1-360. DR PDB; 5N65; X-ray; 2.00 A; A=1-360. DR PDB; 5N66; X-ray; 2.40 A; A=1-360. DR PDB; 5N67; X-ray; 1.90 A; A=1-360. DR PDB; 5N68; X-ray; 1.85 A; A=1-360. DR PDB; 5O8U; X-ray; 2.00 A; A=1-360. DR PDB; 5O8V; X-ray; 2.00 A; A=1-360. DR PDB; 5OMG; X-ray; 2.00 A; A=1-360. DR PDB; 5OMH; X-ray; 2.50 A; A=1-360. DR PDB; 5TBE; X-ray; 2.44 A; A=1-360. DR PDB; 5TCO; X-ray; 2.10 A; A=2-360. DR PDB; 5WJJ; X-ray; 1.60 A; A=1-360. DR PDB; 5XYX; X-ray; 2.61 A; A=1-360. DR PDB; 5XYY; X-ray; 1.70 A; A=1-360. DR PDB; 6ANL; X-ray; 2.00 A; A=1-360. DR PDB; 6HWT; X-ray; 1.70 A; A=2-360. DR PDB; 6HWU; X-ray; 2.30 A; A=2-360. DR PDB; 6HWV; X-ray; 1.70 A; A=2-360. DR PDB; 6M95; X-ray; 1.80 A; A=1-360. DR PDB; 6M9L; X-ray; 2.45 A; A=1-360. DR PDB; 6OHD; X-ray; 2.50 A; A=1-360. DR PDB; 6QDZ; X-ray; 1.73 A; A=1-360. DR PDB; 6QE1; X-ray; 1.85 A; A=1-360. DR PDB; 6QYX; X-ray; 1.66 A; A=1-166, A=197-360. DR PDB; 6RFO; X-ray; 1.70 A; A=167-196. DR PDB; 6SFI; X-ray; 1.60 A; A=1-360. DR PDB; 6SFJ; X-ray; 1.95 A; A=1-360. DR PDB; 6SFK; X-ray; 1.80 A; A=1-360. DR PDB; 6SFO; X-ray; 1.75 A; A=1-360. DR PDB; 6TCA; X-ray; 3.70 A; B/D/F/H=1-360. DR PDB; 6ZQS; X-ray; 1.95 A; A=1-360. DR PDB; 6ZWP; X-ray; 1.90 A; A=1-360. DR PDB; 8A8M; EM; 4.00 A; A=1-360. DR PDBsum; 1A9U; -. DR PDBsum; 1BL6; -. DR PDBsum; 1BL7; -. DR PDBsum; 1BMK; -. DR PDBsum; 1DI9; -. DR PDBsum; 1IAN; -. DR PDBsum; 1KV1; -. DR PDBsum; 1KV2; -. DR PDBsum; 1M7Q; -. DR PDBsum; 1OUK; -. DR PDBsum; 1OUY; -. DR PDBsum; 1OVE; -. DR PDBsum; 1OZ1; -. DR PDBsum; 1R39; -. DR PDBsum; 1R3C; -. DR PDBsum; 1W7H; -. DR PDBsum; 1W82; -. DR PDBsum; 1W83; -. DR PDBsum; 1W84; -. DR PDBsum; 1WBN; -. DR PDBsum; 1WBO; -. DR PDBsum; 1WBS; -. DR PDBsum; 1WBT; -. DR PDBsum; 1WBV; -. DR PDBsum; 1WBW; -. DR PDBsum; 1WFC; -. DR PDBsum; 1YQJ; -. DR PDBsum; 1ZYJ; -. DR PDBsum; 1ZZ2; -. DR PDBsum; 1ZZL; -. DR PDBsum; 2BAJ; -. DR PDBsum; 2BAK; -. DR PDBsum; 2BAL; -. DR PDBsum; 2BAQ; -. DR PDBsum; 2FSL; -. DR PDBsum; 2FSM; -. DR PDBsum; 2FSO; -. DR PDBsum; 2FST; -. DR PDBsum; 2GFS; -. DR PDBsum; 2I0H; -. DR PDBsum; 2LGC; -. DR PDBsum; 2NPQ; -. DR PDBsum; 2OKR; -. DR PDBsum; 2ONL; -. DR PDBsum; 2QD9; -. DR PDBsum; 2RG5; -. DR PDBsum; 2RG6; -. DR PDBsum; 2Y8O; -. DR PDBsum; 2YIS; -. DR PDBsum; 2YIW; -. DR PDBsum; 2YIX; -. DR PDBsum; 2ZAZ; -. DR PDBsum; 2ZB0; -. DR PDBsum; 2ZB1; -. DR PDBsum; 3BV2; -. DR PDBsum; 3BV3; -. DR PDBsum; 3BX5; -. DR PDBsum; 3C5U; -. DR PDBsum; 3CTQ; -. DR PDBsum; 3D7Z; -. DR PDBsum; 3D83; -. DR PDBsum; 3DS6; -. DR PDBsum; 3DT1; -. DR PDBsum; 3E92; -. DR PDBsum; 3E93; -. DR PDBsum; 3FC1; -. DR PDBsum; 3FI4; -. DR PDBsum; 3FKL; -. DR PDBsum; 3FKN; -. DR PDBsum; 3FKO; -. DR PDBsum; 3FL4; -. DR PDBsum; 3FLN; -. DR PDBsum; 3FLQ; -. DR PDBsum; 3FLS; -. DR PDBsum; 3FLW; -. DR PDBsum; 3FLY; -. DR PDBsum; 3FLZ; -. DR PDBsum; 3FMH; -. DR PDBsum; 3FMJ; -. DR PDBsum; 3FMK; -. DR PDBsum; 3FML; -. DR PDBsum; 3FMM; -. DR PDBsum; 3FMN; -. DR PDBsum; 3FSF; -. DR PDBsum; 3FSK; -. DR PDBsum; 3GC7; -. DR PDBsum; 3GCP; -. DR PDBsum; 3GCQ; -. DR PDBsum; 3GCS; -. DR PDBsum; 3GCU; -. DR PDBsum; 3GCV; -. DR PDBsum; 3GFE; -. DR PDBsum; 3GI3; -. DR PDBsum; 3HA8; -. DR PDBsum; 3HEC; -. DR PDBsum; 3HEG; -. DR PDBsum; 3HL7; -. DR PDBsum; 3HLL; -. DR PDBsum; 3HP2; -. DR PDBsum; 3HP5; -. DR PDBsum; 3HRB; -. DR PDBsum; 3HUB; -. DR PDBsum; 3HUC; -. DR PDBsum; 3HV3; -. DR PDBsum; 3HV4; -. DR PDBsum; 3HV5; -. DR PDBsum; 3HV6; -. DR PDBsum; 3HV7; -. DR PDBsum; 3HVC; -. DR PDBsum; 3IPH; -. DR PDBsum; 3ITZ; -. DR PDBsum; 3IW5; -. DR PDBsum; 3IW6; -. DR PDBsum; 3IW7; -. DR PDBsum; 3IW8; -. DR PDBsum; 3K3I; -. DR PDBsum; 3K3J; -. DR PDBsum; 3KF7; -. DR PDBsum; 3KQ7; -. DR PDBsum; 3L8S; -. DR PDBsum; 3L8X; -. DR PDBsum; 3LFA; -. DR PDBsum; 3LFB; -. DR PDBsum; 3LFC; -. DR PDBsum; 3LFD; -. DR PDBsum; 3LFE; -. DR PDBsum; 3LFF; -. DR PDBsum; 3LHJ; -. DR PDBsum; 3MGY; -. DR PDBsum; 3MH0; -. DR PDBsum; 3MH1; -. DR PDBsum; 3MH2; -. DR PDBsum; 3MH3; -. DR PDBsum; 3MPA; -. DR PDBsum; 3MPT; -. DR PDBsum; 3MVL; -. DR PDBsum; 3MVM; -. DR PDBsum; 3MW1; -. DR PDBsum; 3NEW; -. DR PDBsum; 3NNU; -. DR PDBsum; 3NNV; -. DR PDBsum; 3NNW; -. DR PDBsum; 3NNX; -. DR PDBsum; 3NWW; -. DR PDBsum; 3O8P; -. DR PDBsum; 3O8T; -. DR PDBsum; 3O8U; -. DR PDBsum; 3OBG; -. DR PDBsum; 3OBJ; -. DR PDBsum; 3OC1; -. DR PDBsum; 3OCG; -. DR PDBsum; 3OD6; -. DR PDBsum; 3ODY; -. DR PDBsum; 3ODZ; -. DR PDBsum; 3OEF; -. DR PDBsum; 3PG3; -. DR PDBsum; 3QUD; -. DR PDBsum; 3QUE; -. DR PDBsum; 3RIN; -. DR PDBsum; 3ROC; -. DR PDBsum; 3S3I; -. DR PDBsum; 3S4Q; -. DR PDBsum; 3U8W; -. DR PDBsum; 3UVP; -. DR PDBsum; 3UVQ; -. DR PDBsum; 3UVR; -. DR PDBsum; 3ZS5; -. DR PDBsum; 3ZSG; -. DR PDBsum; 3ZSH; -. DR PDBsum; 3ZSI; -. DR PDBsum; 3ZYA; -. DR PDBsum; 4A9Y; -. DR PDBsum; 4AA0; -. DR PDBsum; 4AA4; -. DR PDBsum; 4AA5; -. DR PDBsum; 4AAC; -. DR PDBsum; 4DLI; -. DR PDBsum; 4DLJ; -. DR PDBsum; 4E5A; -. DR PDBsum; 4E5B; -. DR PDBsum; 4E6A; -. DR PDBsum; 4E6C; -. DR PDBsum; 4E8A; -. DR PDBsum; 4EH2; -. DR PDBsum; 4EH3; -. DR PDBsum; 4EH4; -. DR PDBsum; 4EH5; -. DR PDBsum; 4EH6; -. DR PDBsum; 4EH7; -. DR PDBsum; 4EH8; -. DR PDBsum; 4EH9; -. DR PDBsum; 4EHV; -. DR PDBsum; 4EWQ; -. DR PDBsum; 4F9W; -. DR PDBsum; 4F9Y; -. DR PDBsum; 4FA2; -. DR PDBsum; 4GEO; -. DR PDBsum; 4KIN; -. DR PDBsum; 4KIP; -. DR PDBsum; 4KIQ; -. DR PDBsum; 4L8M; -. DR PDBsum; 4R3C; -. DR PDBsum; 4ZTH; -. DR PDBsum; 5ETA; -. DR PDBsum; 5ETC; -. DR PDBsum; 5ETF; -. DR PDBsum; 5ETI; -. DR PDBsum; 5ML5; -. DR PDBsum; 5MTX; -. DR PDBsum; 5MTY; -. DR PDBsum; 5MZ3; -. DR PDBsum; 5N63; -. DR PDBsum; 5N64; -. DR PDBsum; 5N65; -. DR PDBsum; 5N66; -. DR PDBsum; 5N67; -. DR PDBsum; 5N68; -. DR PDBsum; 5O8U; -. DR PDBsum; 5O8V; -. DR PDBsum; 5OMG; -. DR PDBsum; 5OMH; -. DR PDBsum; 5TBE; -. DR PDBsum; 5TCO; -. DR PDBsum; 5WJJ; -. DR PDBsum; 5XYX; -. DR PDBsum; 5XYY; -. DR PDBsum; 6ANL; -. DR PDBsum; 6HWT; -. DR PDBsum; 6HWU; -. DR PDBsum; 6HWV; -. DR PDBsum; 6M95; -. DR PDBsum; 6M9L; -. DR PDBsum; 6OHD; -. DR PDBsum; 6QDZ; -. DR PDBsum; 6QE1; -. DR PDBsum; 6QYX; -. DR PDBsum; 6RFO; -. DR PDBsum; 6SFI; -. DR PDBsum; 6SFJ; -. DR PDBsum; 6SFK; -. DR PDBsum; 6SFO; -. DR PDBsum; 6TCA; -. DR PDBsum; 6ZQS; -. DR PDBsum; 6ZWP; -. DR PDBsum; 8A8M; -. DR AlphaFoldDB; Q16539; -. DR BMRB; Q16539; -. DR EMDB; EMD-15233; -. DR SASBDB; Q16539; -. DR SMR; Q16539; -. DR BioGRID; 107819; 306. DR CORUM; Q16539; -. DR DIP; DIP-30987N; -. DR ELM; Q16539; -. DR IntAct; Q16539; 159. DR MINT; Q16539; -. DR STRING; 9606.ENSP00000229795; -. DR BindingDB; Q16539; -. DR ChEMBL; CHEMBL260; -. DR DrugBank; DB02873; 1-(2,6-Dichlorophenyl)-5-(2,4-Difluorophenyl)-7-Piperazin-1-Yl-3,4-Dihydroquinazolin-2(1h)-One. DR DrugBank; DB01948; 1-(2,6-Dichlorophenyl)-5-(2,4-Difluorophenyl)-7-Piperidin-4-Yl-3,4-Dihydroquinolin-2(1h)-One. DR DrugBank; DB02277; 1-(5-Tert-Butyl-2-Methyl-2h-Pyrazol-3-Yl)-3-(4-Chloro-Phenyl)-Urea. DR DrugBank; DB06882; 1-[1-(3-aminophenyl)-3-tert-butyl-1H-pyrazol-5-yl]-3-naphthalen-1-ylurea. DR DrugBank; DB08097; 2-(2,6-DIFLUOROPHENOXY)-N-(2-FLUOROPHENYL)-9-ISOPROPYL-9H-PURIN-8-AMINE. DR DrugBank; DB08395; 2-(ETHOXYMETHYL)-4-(4-FLUOROPHENYL)-3-[2-(2-HYDROXYPHENOXY)PYRIMIDIN-4-YL]ISOXAZOL-5(2H)-ONE. DR DrugBank; DB03110; 2-Chlorophenol. DR DrugBank; DB07942; 2-fluoro-4-[4-(4-fluorophenyl)-1H-pyrazol-3-yl]pyridine. DR DrugBank; DB08093; 3-(1-NAPHTHYLMETHOXY)PYRIDIN-2-AMINE. DR DrugBank; DB08095; 3-(2-CHLOROPHENYL)-1-(2-{[(1S)-2-HYDROXY-1,2-DIMETHYLPROPYL]AMINO}PYRIMIDIN-4-YL)-1-(4-METHOXYPHENYL)UREA. DR DrugBank; DB02195; 3-(4-Fluorophenyl)-1-Hydroxy-2-(Pyridin-4-Yl)-1h-Pyrrolo[3,2-B]Pyridine. DR DrugBank; DB02352; 3-(Benzyloxy)Pyridin-2-Amine. DR DrugBank; DB08730; 3-FLUORO-5-MORPHOLIN-4-YL-N-[1-(2-PYRIDIN-4-YLETHYL)-1H-INDOL-6-YL]BENZAMIDE. DR DrugBank; DB08091; 3-FLUORO-5-MORPHOLIN-4-YL-N-[3-(2-PYRIDIN-4-YLETHYL)-1H-INDOL-5-YL]BENZAMIDE. DR DrugBank; DB08092; 3-fluoro-N-1H-indol-5-yl-5-morpholin-4-ylbenzamide. DR DrugBank; DB04632; 4-(2-HYDROXYBENZYLAMINO)-N-(3-(4-FLUOROPHENOXY)PHENYL)PIPERIDINE-1-SULFONAMIDE. DR DrugBank; DB08522; 4-(4-FLUOROPHENYL)-1-CYCLOROPROPYLMETHYL-5-(4-PYRIDYL)-IMIDAZOLE. DR DrugBank; DB03980; 4-(Fluorophenyl)-1-Cyclopropylmethyl-5-(2-Amino-4-Pyrimidinyl)Imidazole. DR DrugBank; DB07829; 4-[3-(4-FLUOROPHENYL)-1H-PYRAZOL-4-YL]PYRIDINE. DR DrugBank; DB02984; 4-[3-Methylsulfanylanilino]-6,7-Dimethoxyquinazoline. DR DrugBank; DB08521; 4-[4-(4-Fluorophenyl)-2-[4-[(R)-methylsulfinyl]phenyl]-1H-imidazol-5-yl]pyridine. DR DrugBank; DB07607; 4-[5-(3-IODO-PHENYL)-2-(4-METHANESULFINYL-PHENYL)-1H-IMIDAZOL-4-YL]-PYRIDINE. DR DrugBank; DB01761; 4-[5-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-1-methyl-4-(3-trifluoromethylphenyl)-1H-imidazol-2-yl]-piperidine. DR DrugBank; DB07459; 4-PHENOXY-N-(PYRIDIN-2-YLMETHYL)BENZAMIDE. DR DrugBank; DB07832; 4-{4-[(5-hydroxy-2-methylphenyl)amino]quinolin-7-yl}-1,3-thiazole-2-carbaldehyde. DR DrugBank; DB01988; 6((S)-3-Benzylpiperazin-1-Yl)-3-(Naphthalen-2-Yl)-4-(Pyridin-4-Yl)Pyrazine. DR DrugBank; DB08352; 6-[4-(2-fluorophenyl)-1,3-oxazol-5-yl]-N-(1-methylethyl)-1,3-benzothiazol-2-amine. DR DrugBank; DB08096; 8-(2-CHLOROPHENYLAMINO)-2-(2,6-DIFLUOROPHENYLAMINO)-9-ETHYL-9H-PURINE-1,7-DIIUM. DR DrugBank; DB08424; [5-AMINO-1-(4-FLUOROPHENYL)-1H-PYRAZOL-4-YL](3-{[(2R)-2,3-DIHYDROXYPROPYL]OXY}PHENYL)METHANONE. DR DrugBank; DB08423; [5-AMINO-1-(4-FLUOROPHENYL)-1H-PYRAZOL-4-YL][3-(PIPERIDIN-4-YLOXY)PHENYL]METHANONE. DR DrugBank; DB01254; Dasatinib. DR DrugBank; DB03044; Doramapimod. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB01953; Inhibitor of P38 Kinase. DR DrugBank; DB05157; KC706. DR DrugBank; DB01017; Minocycline. DR DrugBank; DB08242; N,4-dimethyl-3-[(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)amino]benzamide. DR DrugBank; DB07833; N-(3-cyanophenyl)-2'-methyl-5'-(5-methyl-1,3,4-oxadiazol-2-yl)-4-biphenylcarboxamide. DR DrugBank; DB08064; N-(3-TERT-BUTYL-1H-PYRAZOL-5-YL)-N'-{4-CHLORO-3-[(PYRIDIN-3-YLOXY)METHYL]PHENYL}UREA. DR DrugBank; DB07834; N-(cyclopropylmethyl)-2'-methyl-5'-(5-methyl-1,3,4-oxadiazol-2-yl)biphenyl-4-carboxamide. DR DrugBank; DB01807; N-[(3Z)-5-Tert-butyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-ylidene]-N'-(4-chlorophenyl)urea. DR DrugBank; DB06991; N-[2-methyl-5-(methylcarbamoyl)phenyl]-2-{[(1R)-1-methylpropyl]amino}-1,3-thiazole-5-carboxamide. DR DrugBank; DB08068; N-[4-CHLORO-3-(PYRIDIN-3-YLOXYMETHYL)-PHENYL]-3-FLUORO. DR DrugBank; DB07811; N-cyclopropyl-2',6-dimethyl-4'-(5-methyl-1,3,4-oxadiazol-2-yl)biphenyl-3-carboxamide. DR DrugBank; DB08349; N-cyclopropyl-3-{[1-(2,4-difluorophenyl)-7-methyl-6-oxo-6,7-dihydro-1H-pyrazolo[3,4-b]pyridin-4-yl]amino}-4-methylbenzamide. DR DrugBank; DB07307; N-cyclopropyl-4-methyl-3-[1-(2-methylphenyl)phthalazin-6-yl]benzamide. DR DrugBank; DB08351; N-cyclopropyl-4-methyl-3-{2-[(2-morpholin-4-ylethyl)amino]quinazolin-6-yl}benzamide. DR DrugBank; DB06940; N-ethyl-4-{[5-(methoxycarbamoyl)-2-methylphenyl]amino}-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxamide. DR DrugBank; DB07138; Neflamapimod. DR DrugBank; DB07835; N~3~-cyclopropyl-N~4~'-(cyclopropylmethyl)-6-methylbiphenyl-3,4'-dicarboxamide. DR DrugBank; DB07941; PH-797804. DR DrugBank; DB06518; R-1487. DR DrugBank; DB04338; SB220025. DR DrugBank; DB07943; SD-0006. DR DrugBank; DB05412; Talmapimod. DR DrugBank; DB04797; Triazolopyridine. DR DrugBank; DB05470; VX-702. DR DrugCentral; Q16539; -. DR GuidetoPHARMACOLOGY; 1499; -. DR GlyGen; Q16539; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q16539; -. DR MetOSite; Q16539; -. DR PhosphoSitePlus; Q16539; -. DR BioMuta; MAPK14; -. DR OGP; Q16539; -. DR CPTAC; CPTAC-1325; -. DR CPTAC; CPTAC-1355; -. DR CPTAC; CPTAC-1356; -. DR CPTAC; CPTAC-3005; -. DR CPTAC; CPTAC-3006; -. DR CPTAC; CPTAC-878; -. DR CPTAC; CPTAC-879; -. DR CPTAC; non-CPTAC-5408; -. DR CPTAC; non-CPTAC-5699; -. DR CPTAC; non-CPTAC-5700; -. DR CPTAC; non-CPTAC-5701; -. DR EPD; Q16539; -. DR jPOST; Q16539; -. DR MassIVE; Q16539; -. DR MaxQB; Q16539; -. DR PaxDb; 9606-ENSP00000229795; -. DR PeptideAtlas; Q16539; -. DR PRIDE; Q16539; -. DR ProteomicsDB; 60901; -. [Q16539-1] DR ProteomicsDB; 60902; -. [Q16539-2] DR ProteomicsDB; 60903; -. [Q16539-3] DR ProteomicsDB; 60904; -. [Q16539-4] DR Pumba; Q16539; -. DR Antibodypedia; 4142; 2724 antibodies from 54 providers. DR CPTC; Q16539; 3 antibodies. DR DNASU; 1432; -. DR Ensembl; ENST00000229794.9; ENSP00000229794.4; ENSG00000112062.12. [Q16539-1] DR Ensembl; ENST00000229795.8; ENSP00000229795.3; ENSG00000112062.12. [Q16539-2] DR Ensembl; ENST00000310795.8; ENSP00000308669.4; ENSG00000112062.12. [Q16539-4] DR GeneID; 1432; -. DR KEGG; hsa:1432; -. DR MANE-Select; ENST00000229794.9; ENSP00000229794.4; NM_139012.3; NP_620581.1. DR UCSC; uc003olp.4; human. [Q16539-1] DR AGR; HGNC:6876; -. DR CTD; 1432; -. DR DisGeNET; 1432; -. DR GeneCards; MAPK14; -. DR HGNC; HGNC:6876; MAPK14. DR HPA; ENSG00000112062; Low tissue specificity. DR MIM; 600289; gene. DR neXtProt; NX_Q16539; -. DR OpenTargets; ENSG00000112062; -. DR PharmGKB; PA30621; -. DR VEuPathDB; HostDB:ENSG00000112062; -. DR eggNOG; KOG0660; Eukaryota. DR GeneTree; ENSGT00940000155325; -. DR InParanoid; Q16539; -. DR OMA; NRYTDLN; -. DR OrthoDB; 158564at2759; -. DR PhylomeDB; Q16539; -. DR TreeFam; TF105100; -. DR BioCyc; MetaCyc:HS03507-MONOMER; -. DR BRENDA; 2.7.11.24; 2681. DR PathwayCommons; Q16539; -. DR Reactome; R-HSA-168638; NOD1/2 Signaling Pathway. DR Reactome; R-HSA-171007; p38MAPK events. DR Reactome; R-HSA-198753; ERK/MAPK targets. DR Reactome; R-HSA-2151209; Activation of PPARGC1A (PGC-1alpha) by phosphorylation. DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence. DR Reactome; R-HSA-376172; DSCAM interactions. DR Reactome; R-HSA-418592; ADP signalling through P2Y purinoceptor 1. DR Reactome; R-HSA-432142; Platelet sensitization by LDL. DR Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway. DR Reactome; R-HSA-450302; activated TAK1 mediates p38 MAPK activation. DR Reactome; R-HSA-450341; Activation of the AP-1 family of transcription factors. DR Reactome; R-HSA-450604; KSRP (KHSRP) binds and destabilizes mRNA. DR Reactome; R-HSA-525793; Myogenesis. DR Reactome; R-HSA-5668599; RHO GTPases Activate NADPH Oxidases. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-6804756; Regulation of TP53 Activity through Phosphorylation. DR Reactome; R-HSA-9662834; CD163 mediating an anti-inflammatory response. DR SignaLink; Q16539; -. DR SIGNOR; Q16539; -. DR BioGRID-ORCS; 1432; 83 hits in 1217 CRISPR screens. DR ChiTaRS; MAPK14; human. DR EvolutionaryTrace; Q16539; -. DR GeneWiki; MAPK14; -. DR GenomeRNAi; 1432; -. DR Pharos; Q16539; Tchem. DR PRO; PR:Q16539; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q16539; Protein. DR Bgee; ENSG00000112062; Expressed in buccal mucosa cell and 205 other cell types or tissues. DR ExpressionAtlas; Q16539; baseline and differential. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl. DR GO; GO:0016607; C:nuclear speck; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome. DR GO; GO:0000922; C:spindle pole; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL. DR GO; GO:0004707; F:MAP kinase activity; IDA:UniProtKB. DR GO; GO:0004708; F:MAP kinase kinase activity; TAS:ProtInc. DR GO; GO:0048273; F:mitogen-activated protein kinase p38 binding; IPI:UniProtKB. DR GO; GO:0051525; F:NFAT protein binding; ISS:BHF-UCL. DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0070935; P:3'-UTR-mediated mRNA stabilization; TAS:UniProtKB. DR GO; GO:0001525; P:angiogenesis; IEA:Ensembl. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0060348; P:bone development; IEA:Ensembl. DR GO; GO:0001502; P:cartilage condensation; IEA:Ensembl. DR GO; GO:0000902; P:cell morphogenesis; IEA:Ensembl. DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc. DR GO; GO:0071479; P:cellular response to ionizing radiation; IMP:BHF-UCL. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:MGI. DR GO; GO:0071223; P:cellular response to lipoteichoic acid; IMP:UniProtKB. DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl. DR GO; GO:0071493; P:cellular response to UV-B; IDA:UniProtKB. DR GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IMP:BHF-UCL. DR GO; GO:0098586; P:cellular response to virus; IMP:UniProtKB. DR GO; GO:0090398; P:cellular senescence; TAS:Reactome. DR GO; GO:0006935; P:chemotaxis; TAS:ProtInc. DR GO; GO:0002062; P:chondrocyte differentiation; IEA:Ensembl. DR GO; GO:0000077; P:DNA damage checkpoint signaling; IEA:Ensembl. DR GO; GO:0019395; P:fatty acid oxidation; IEA:Ensembl. DR GO; GO:0046323; P:glucose import; IEA:Ensembl. DR GO; GO:0006006; P:glucose metabolic process; IEA:Ensembl. DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB. DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IEA:Ensembl. DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IEA:Ensembl. DR GO; GO:0035331; P:negative regulation of hippo signaling; IMP:FlyBase. DR GO; GO:0002862; P:negative regulation of inflammatory response to antigenic stimulus; TAS:Reactome. DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl. DR GO; GO:0030316; P:osteoclast differentiation; ISS:BHF-UCL. DR GO; GO:0038066; P:p38MAPK cascade; IDA:UniProt. DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:BHF-UCL. DR GO; GO:0001890; P:placenta development; IEA:Ensembl. DR GO; GO:0030168; P:platelet activation; TAS:Reactome. DR GO; GO:0090336; P:positive regulation of brown fat cell differentiation; IEA:Ensembl. DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; IEA:Ensembl. DR GO; GO:0031281; P:positive regulation of cyclase activity; IMP:CACAO. DR GO; GO:0045648; P:positive regulation of erythrocyte differentiation; IMP:BHF-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB. DR GO; GO:0046326; P:positive regulation of glucose import; IEA:Ensembl. DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IMP:UniProtKB. DR GO; GO:0051149; P:positive regulation of muscle cell differentiation; TAS:Reactome. DR GO; GO:0045663; P:positive regulation of myoblast differentiation; ISS:UniProtKB. DR GO; GO:1901741; P:positive regulation of myoblast fusion; ISS:UniProtKB. DR GO; GO:0010831; P:positive regulation of myotube differentiation; ISS:UniProtKB. DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IEA:Ensembl. DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IMP:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:1900015; P:regulation of cytokine production involved in inflammatory response; IDA:CACAO. DR GO; GO:0030278; P:regulation of ossification; IEA:Ensembl. DR GO; GO:0099179; P:regulation of synaptic membrane adhesion; IEA:Ensembl. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:UniProtKB. DR GO; GO:0002021; P:response to dietary excess; IEA:Ensembl. DR GO; GO:0032868; P:response to insulin; IEA:Ensembl. DR GO; GO:0032495; P:response to muramyl dipeptide; IEA:Ensembl. DR GO; GO:0035994; P:response to muscle stretch; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0042770; P:signal transduction in response to DNA damage; IMP:BHF-UCL. DR GO; GO:0007519; P:skeletal muscle tissue development; IEA:Ensembl. DR GO; GO:0048863; P:stem cell differentiation; IEA:Ensembl. DR GO; GO:0051403; P:stress-activated MAPK cascade; IDA:UniProtKB. DR GO; GO:0031098; P:stress-activated protein kinase signaling cascade; IDA:UniProt. DR GO; GO:0090400; P:stress-induced premature senescence; IMP:BHF-UCL. DR GO; GO:0051146; P:striated muscle cell differentiation; IEA:Ensembl. DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0007178; P:transmembrane receptor protein serine/threonine kinase signaling pathway; IEA:Ensembl. DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IMP:BHF-UCL. DR CDD; cd07877; STKc_p38alpha; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR IDEAL; IID00280; -. 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; Q16539; HS. 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:0000269|PubMed:12665801, FT ECO:0007744|PubMed:20068231" FT CHAIN 2..360 FT /note="Mitogen-activated protein kinase 14" FT /id="PRO_0000186291" 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 BINDING 30..38 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 53 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 2 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 16 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18691976" FT MOD_RES 53 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:21444723" FT MOD_RES 152 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:21444723" FT MOD_RES 180 FT /note="Phosphothreonine; by MAP2K3, MAP2K4, MAP2K6 and FT autocatalysis" FT /evidence="ECO:0000269|PubMed:7535770, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 182 FT /note="Phosphotyrosine; by MAP2K3, MAP2K4, MAP2K6 and FT autocatalysis" FT /evidence="ECO:0000269|PubMed:7535770, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 263 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:17525332" FT MOD_RES 323 FT /note="Phosphotyrosine; by ZAP70" FT /evidence="ECO:0000269|PubMed:15735648" FT VAR_SEQ 230..254 FT /note="DQLKLILRLVGTPGAELLKKISSES -> NQLQQIMRLTGTPPAYLINRMPS FT HE (in isoform CSBP1)" FT /evidence="ECO:0000303|PubMed:7997261" FT /id="VSP_004842" FT VAR_SEQ 255..360 FT /note="ARNYIQSLTQMPKMNFANVFIGANPLAVDLLEKMLVLDSDKRITAAQALAHA FT YFAQYHDPDDEPVADPYDQSFESRDLLIDEWKSLTYDEVISFVPPPLDQEEMES -> V FT S (in isoform 5)" FT /evidence="ECO:0000303|PubMed:19906316" FT /id="VSP_057194" FT VAR_SEQ 255..307 FT /note="ARNYIQSLTQMPKMNFANVFIGANPLAVDLLEKMLVLDSDKRITAAQALAHA FT Y -> LSTCWRRCLYWTQIRELQRPKPLHMPTLLSTTILMMNQWPILMISPLKAGTSL FT (in isoform Exip)" FT /evidence="ECO:0000303|PubMed:11866441" FT /id="VSP_004843" FT VAR_SEQ 281..360 FT /note="AVDLLEKMLVLDSDKRITAAQALAHAYFAQYHDPDDEPVADPYDQSFESRDL FT LIDEWKSLTYDEVISFVPPPLDQEEMES -> GKLTIYPHLMDIELVMI (in FT isoform Mxi2)" FT /evidence="ECO:0000303|PubMed:7479834" FT /id="VSP_004844" FT VAR_SEQ 308..360 FT /note="Missing (in isoform Exip)" FT /evidence="ECO:0000303|PubMed:11866441" FT /id="VSP_004845" FT VARIANT 51 FT /note="A -> V (in a gastric adenocarcinoma sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042270" FT VARIANT 322 FT /note="P -> R (in a lung adenocarcinoma sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042271" FT VARIANT 343 FT /note="D -> G (in dbSNP:rs45496794)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042272" FT MUTAGEN 34 FT /note="A->V: Lowered kinase activity." FT /evidence="ECO:0000269|PubMed:7493921" FT MUTAGEN 53 FT /note="K->R: Loss of kinase activity." FT /evidence="ECO:0000269|PubMed:7493921" FT MUTAGEN 54 FT /note="K->R: Impairs MAP2K6/MKK6-dependent FT autophosphorylation." FT /evidence="ECO:0000269|PubMed:11010976" FT MUTAGEN 69 FT /note="Y->H: Lowered kinase activity." FT /evidence="ECO:0000269|PubMed:15284239" FT MUTAGEN 168 FT /note="D->A: Loss of kinase activity." FT /evidence="ECO:0000269|PubMed:7493921" FT MUTAGEN 175 FT /note="T->A: No effect on either the kinase activity or FT tyrosine phosphorylation." FT /evidence="ECO:0000269|PubMed:7493921" FT MUTAGEN 176 FT /note="D->A: Emulation of the active state. Increase in FT activity; when associated with S-327 or L-327." FT /evidence="ECO:0000269|PubMed:15284239" FT MUTAGEN 177 FT /note="D->A: Loss of kinase activity." FT /evidence="ECO:0000269|PubMed:15284239" FT MUTAGEN 180 FT /note="T->E: Loss of kinase activity." FT /evidence="ECO:0000269|PubMed:7493921" FT MUTAGEN 182 FT /note="Y->F: Loss of kinase activity." FT /evidence="ECO:0000269|PubMed:7493921" FT MUTAGEN 320 FT /note="A->T: Lowered kinase activity." FT /evidence="ECO:0000269|PubMed:15284239" FT MUTAGEN 327 FT /note="F->L: Emulation of the active state. Increase in FT activity; when associated with A-176." FT /evidence="ECO:0000269|PubMed:15284239" FT MUTAGEN 327 FT /note="F->S: Emulation of the active state. Increase in FT activity; when associated with A-176." FT /evidence="ECO:0000269|PubMed:15284239" FT MUTAGEN 337 FT /note="W->R: Loss of kinase activity." FT /evidence="ECO:0000269|PubMed:15284239" FT CONFLICT 67 FT /note="R -> G (in Ref. 7; BAF84398)" FT /evidence="ECO:0000305" FT STRAND 8..13 FT /evidence="ECO:0007829|PDB:2FST" FT STRAND 16..21 FT /evidence="ECO:0007829|PDB:2FST" FT STRAND 24..29 FT /evidence="ECO:0007829|PDB:2FST" FT HELIX 31..33 FT /evidence="ECO:0007829|PDB:6SFI" FT TURN 34..36 FT /evidence="ECO:0007829|PDB:3BV2" FT STRAND 38..43 FT /evidence="ECO:0007829|PDB:2FST" FT TURN 44..47 FT /evidence="ECO:0007829|PDB:2FST" FT STRAND 48..54 FT /evidence="ECO:0007829|PDB:2FST" FT HELIX 62..77 FT /evidence="ECO:0007829|PDB:2FST" FT STRAND 87..90 FT /evidence="ECO:0007829|PDB:2FST" FT HELIX 96..98 FT /evidence="ECO:0007829|PDB:2FST" FT STRAND 103..107 FT /evidence="ECO:0007829|PDB:2FST" FT STRAND 110..112 FT /evidence="ECO:0007829|PDB:3LFF" FT TURN 113..115 FT /evidence="ECO:0007829|PDB:4GEO" FT TURN 116..119 FT /evidence="ECO:0007829|PDB:3LFF" FT HELIX 124..143 FT /evidence="ECO:0007829|PDB:2FST" FT HELIX 153..155 FT /evidence="ECO:0007829|PDB:2FST" FT STRAND 156..158 FT /evidence="ECO:0007829|PDB:2FST" FT TURN 160..162 FT /evidence="ECO:0007829|PDB:2RG6" FT STRAND 164..166 FT /evidence="ECO:0007829|PDB:2FST" FT STRAND 168..170 FT /evidence="ECO:0007829|PDB:4GEO" FT HELIX 173..175 FT /evidence="ECO:0007829|PDB:1ZZL" FT TURN 176..179 FT /evidence="ECO:0007829|PDB:5XYY" FT STRAND 180..182 FT /evidence="ECO:0007829|PDB:3FMK" FT TURN 185..188 FT /evidence="ECO:0007829|PDB:3LFF" FT HELIX 191..194 FT /evidence="ECO:0007829|PDB:2FST" FT STRAND 197..199 FT /evidence="ECO:0007829|PDB:4EHV" FT HELIX 204..218 FT /evidence="ECO:0007829|PDB:2FST" FT HELIX 228..239 FT /evidence="ECO:0007829|PDB:2FST" FT HELIX 244..247 FT /evidence="ECO:0007829|PDB:2FST" FT HELIX 253..260 FT /evidence="ECO:0007829|PDB:2FST" FT HELIX 270..273 FT /evidence="ECO:0007829|PDB:2FST" FT TURN 274..276 FT /evidence="ECO:0007829|PDB:2FST" FT HELIX 279..288 FT /evidence="ECO:0007829|PDB:2FST" FT HELIX 293..295 FT /evidence="ECO:0007829|PDB:2FST" FT HELIX 299..303 FT /evidence="ECO:0007829|PDB:2FST" FT HELIX 306..308 FT /evidence="ECO:0007829|PDB:2FST" FT TURN 309..311 FT /evidence="ECO:0007829|PDB:2FST" FT HELIX 314..316 FT /evidence="ECO:0007829|PDB:2FST" FT HELIX 325..327 FT /evidence="ECO:0007829|PDB:2FST" FT HELIX 334..347 FT /evidence="ECO:0007829|PDB:2FST" SQ 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 //