MK14_HUMAN
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 03-AUG-2022, entry version 250.
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: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 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 [66]
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 [67]
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 [68]
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 [69]
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 [70]
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 [71]
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 [72] {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 [73]
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 [74] {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 [75]
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 [76]
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 [77] {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 [78]
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 [79]
RP ERRATUM OF PUBMED:17255097.
RA ter Haar E., Prabhakar P., Liu X., Lepre C.;
RL J. Biol. Chem. 282:14684-14684(2007).
RN [80]
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 RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid
CC induction of immediate-early genes in response to stress or mitogenic
CC stimuli, either by inducing chromatin remodeling or by recruiting the
CC transcription machinery. On the other hand, two other kinase targets,
CC MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene
CC expression mostly at the post-transcriptional level, by phosphorylating
CC ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is
CC important for the elongation of mRNA during translation. MKNK1/MNK1 and
CC MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein
CC synthesis by phosphorylating the initiation factor EIF4E2. MAPK14
CC interacts also with casein kinase II, leading to its activation through
CC autophosphorylation and further phosphorylation of TP53/p53. In the
CC cytoplasm, the p38 MAPK pathway is an important regulator of protein
CC turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis
CC whose proteasome-mediated degradation is regulated by p38 MAPK
CC phosphorylation. In a similar way, MAPK14 phosphorylates the ubiquitin
CC ligase SIAH2, regulating its activity towards EGLN3. MAPK14 may also
CC inhibit the lysosomal degradation pathway of autophagy by interfering
CC with the intracellular trafficking of the transmembrane protein ATG9.
CC Another function of MAPK14 is to regulate the endocytosis of membrane
CC receptors by different mechanisms that impinge on the small GTPase
CC RAB5A. In addition, clathrin-mediated EGFR internalization induced by
CC inflammatory cytokines and UV irradiation depends on MAPK14-mediated
CC phosphorylation of EGFR itself as well as of RAB5A effectors.
CC Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs
CC as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate
CC the membrane-associated metalloprotease ADAM17. Such phosphorylation is
CC required for ADAM17-mediated ectodomain shedding of TGF-alpha family
CC ligands, which results in the activation of EGFR signaling and cell
CC proliferation. Another p38 MAPK substrate is FGFR1. FGFR1 can be
CC translocated from the extracellular space into the cytosol and nucleus
CC of target cells, and regulates processes such as rRNA synthesis and
CC cell growth. FGFR1 translocation requires p38 MAPK activation. In the
CC nucleus, many transcription factors are phosphorylated and activated by
CC p38 MAPKs in response to different stimuli. Classical examples include
CC ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A. The
CC p38 MAPKs are emerging as important modulators of gene expression by
CC regulating chromatin modifiers and remodelers. The promoters of several
CC genes involved in the inflammatory response, such as IL6, IL8 and
CC IL12B, display a p38 MAPK-dependent enrichment of histone H3
CC phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells.
CC This phosphorylation enhances the accessibility of the cryptic NF-
CC kappa-B-binding sites marking promoters for increased NF-kappa-B
CC recruitment. Phosphorylates CDC25B and CDC25C which is required for
CC binding to 14-3-3 proteins and leads to initiation of a G2 delay after
CC ultraviolet radiation. Phosphorylates TIAR following DNA damage,
CC releasing TIAR from GADD45A mRNA and preventing mRNA degradation. The
CC p38 MAPKs may also have kinase-independent roles, which are thought to
CC be due to the binding to targets in the absence of phosphorylation.
CC Protein O-Glc-N-acylation catalyzed by the OGT is regulated by MAPK14,
CC and, although OGT does not seem to be phosphorylated by MAPK14, their
CC interaction increases upon MAPK14 activation induced by glucose
CC deprivation. This interaction may regulate OGT activity by recruiting
CC it to specific targets such as neurofilament H, stimulating its O-Glc-
CC N-acylation. Required in mid-fetal development for the growth of
CC embryo-derived blood vessels in the labyrinth layer of the placenta.
CC Also plays an essential role in developmental and stress-induced
CC erythropoiesis, through regulation of EPO gene expression. Isoform MXI2
CC activation is stimulated by mitogens and oxidative stress and only
CC poorly phosphorylates ELK1 and ATF2. Isoform EXIP may play a role in
CC the early onset of apoptosis. Phosphorylates S100A9 at 'Thr-113'.
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:9430721, ECO:0000269|PubMed:9687510,
CC ECO:0000269|PubMed:9792677, 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};
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 -!- 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="http://atlasgeneticsoncology.org/Genes/MAPK14ID41292ch6p21.html";
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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 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 AlphaFoldDB; Q16539; -.
DR BMRB; Q16539; -.
DR SMR; Q16539; -.
DR BioGRID; 107819; 269.
DR CORUM; Q16539; -.
DR DIP; DIP-30987N; -.
DR ELM; Q16539; -.
DR IntAct; Q16539; 158.
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-878; -.
DR CPTAC; CPTAC-879; -.
DR EPD; Q16539; -.
DR jPOST; Q16539; -.
DR MassIVE; Q16539; -.
DR MaxQB; Q16539; -.
DR PaxDb; Q16539; -.
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 Antibodypedia; 4142; 2350 antibodies from 54 providers.
DR CPTC; Q16539; 3 antibodies.
DR DNASU; 1432; -.
DR Ensembl; ENST00000229794.9; ENSP00000229794.4; ENSG00000112062.11. [Q16539-1]
DR Ensembl; ENST00000229795.7; ENSP00000229795.3; ENSG00000112062.11. [Q16539-2]
DR Ensembl; ENST00000310795.8; ENSP00000308669.4; ENSG00000112062.11. [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 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; YTDLNPV; -.
DR OrthoDB; 683132at2759; -.
DR PhylomeDB; Q16539; -.
DR TreeFam; TF105100; -.
DR BioCyc; MetaCyc:HS03507-MON; -.
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; 73 hits in 1131 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 203 other tissues.
DR ExpressionAtlas; Q16539; baseline and differential.
DR Genevisible; Q16539; HS.
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; IBA:GO_Central.
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: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; ISS:UniProtKB.
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: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 IDEAL; IID00280; -.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR003527; MAP_kinase_CS.
DR InterPro; IPR008352; MAPK_p38-like.
DR InterPro; IPR038784; p38alpha.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR Pfam; PF00069; Pkinase; 1.
DR PRINTS; PR01773; P38MAPKINASE.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS01351; MAPK; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; ATP-binding;
KW Cytoplasm; Direct protein sequencing; Kinase; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Stress response; Transcription; Transcription regulation; Transferase;
KW Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO: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
