(data stored in SCRATCH zone)

SWISSPROT: MAPK2_HUMAN

ID   MAPK2_HUMAN             Reviewed;         400 AA.
AC   P49137; Q5SY30; Q5SY41; Q8IYD6;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 1.
DT   11-DEC-2019, entry version 203.
DE   RecName: Full=MAP kinase-activated protein kinase 2;
DE            Short=MAPK-activated protein kinase 2;
DE            Short=MAPKAP kinase 2;
DE            Short=MAPKAP-K2;
DE            Short=MAPKAPK-2;
DE            Short=MK-2;
DE            Short=MK2;
DE            EC=2.7.11.1;
GN   Name=MAPKAPK2;
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] (ISOFORM 2).
RX   PubMed=8179591; DOI=10.1006/bbrc.1994.1566;
RA   Zu Y.-L., Wu F., Gilchrist A., Ai Y., Labadia M.E., Huang C.K.;
RT   "The primary structure of a human MAP kinase activated protein kinase 2.";
RL   Biochem. Biophys. Res. Commun. 200:1118-1124(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [3]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Skin, and Testis;
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   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 5-400 (ISOFORM 1), AND FUNCTION.
RX   PubMed=8280084; DOI=10.1042/bj2960843;
RA   Stokoe D., Caudwell B., Cohen P.T.W., Cohen P.;
RT   "The substrate specificity and structure of mitogen-activated protein (MAP)
RT   kinase-activated protein kinase-2.";
RL   Biochem. J. 296:843-849(1993).
RN   [6]
RP   FUNCTION IN PHOSPHORYLATION OF HSPB1.
RX   PubMed=8093612;
RA   Jakob U., Gaestel M., Engel K., Buchner J.;
RT   "Small heat shock proteins are molecular chaperones.";
RL   J. Biol. Chem. 268:1517-1520(1993).
RN   [7]
RP   PHOSPHORYLATION AT SER-9; THR-25; THR-222; SER-272 AND THR-334, AND
RP   MUTAGENESIS OF ASP-207; THR-222; SER-272 AND THR-334.
RX   PubMed=8846784; DOI=10.1002/j.1460-2075.1995.tb00280.x;
RA   Ben-Levy R., Leighton I.A., Doza Y.N., Attwood P., Morrice N.,
RA   Marshall C.J., Cohen P.;
RT   "Identification of novel phosphorylation sites required for activation of
RT   MAPKAP kinase-2.";
RL   EMBO J. 14:5920-5930(1995).
RN   [8]
RP   CATALYTIC ACTIVITY, AND FUNCTION IN PHOSPHORYLATION OF HSPB1.
RX   PubMed=8774846; DOI=10.1016/0014-5793(96)00816-2;
RA   Clifton A.D., Young P.R., Cohen P.;
RT   "A comparison of the substrate specificity of MAPKAP kinase-2 and MAPKAP
RT   kinase-3 and their activation by cytokines and cellular stress.";
RL   FEBS Lett. 392:209-214(1996).
RN   [9]
RP   FUNCTION IN PHOSPHORYLATION OF HSPB1.
RX   PubMed=10383393; DOI=10.1074/jbc.274.27.18947;
RA   Rogalla T., Ehrnsperger M., Preville X., Kotlyarov A., Lutsch G.,
RA   Ducasse C., Paul C., Wieske M., Arrigo A.P., Buchner J., Gaestel M.;
RT   "Regulation of Hsp27 oligomerization, chaperone function, and protective
RT   activity against oxidative stress/tumor necrosis factor alpha by
RT   phosphorylation.";
RL   J. Biol. Chem. 274:18947-18956(1999).
RN   [10]
RP   FUNCTION IN PHOSPHORYLATION OF HNRNPA0.
RX   PubMed=12456657; DOI=10.1093/emboj/cdf639;
RA   Rousseau S., Morrice N., Peggie M., Campbell D.G., Gaestel M., Cohen P.;
RT   "Inhibition of SAPK2a/p38 prevents hnRNP A0 phosphorylation by MAPKAP-K2
RT   and its interaction with cytokine mRNAs.";
RL   EMBO J. 21:6505-6514(2002).
RN   [11]
RP   FUNCTION IN PHOSPHORYLATION OF LOX5.
RX   PubMed=11844797; DOI=10.1074/jbc.m111945200;
RA   Werz O., Szellas D., Steinhilber D., Radmark O.;
RT   "Arachidonic acid promotes phosphorylation of 5-lipoxygenase at Ser-271 by
RT   MAPK-activated protein kinase 2 (MK2).";
RL   J. Biol. Chem. 277:14793-14800(2002).
RN   [12]
RP   FUNCTION IN PHOSPHORYLATION OF PABPC1.
RX   PubMed=12565831; DOI=10.1016/s0006-291x(03)00015-9;
RA   Bollig F., Winzen R., Gaestel M., Kostka S., Resch K., Holtmann H.;
RT   "Affinity purification of ARE-binding proteins identifies polyA-binding
RT   protein 1 as a potential substrate in MK2-induced mRNA stabilization.";
RL   Biochem. Biophys. Res. Commun. 301:665-670(2003).
RN   [13]
RP   FUNCTION.
RX   PubMed=14499342; DOI=10.1016/s0898-6568(03)00074-3;
RA   Coxon P.Y., Rane M.J., Uriarte S., Powell D.W., Singh S., Butt W., Chen Q.,
RA   McLeish K.R.;
RT   "MAPK-activated protein kinase-2 participates in p38 MAPK-dependent and
RT   ERK-dependent functions in human neutrophils.";
RL   Cell. Signal. 15:993-1001(2003).
RN   [14]
RP   FUNCTION IN PHOSPHORYLATION OF ELAVL1, AND MUTAGENESIS OF LYS-93; THR-222
RP   AND THR-334.
RX   PubMed=14517288; DOI=10.1128/mcb.23.20.7177-7188.2003;
RA   Tran H., Maurer F., Nagamine Y.;
RT   "Stabilization of urokinase and urokinase receptor mRNAs by HuR is linked
RT   to its cytoplasmic accumulation induced by activated mitogen-activated
RT   protein kinase-activated protein kinase 2.";
RL   Mol. Cell. Biol. 23:7177-7188(2003).
RN   [15]
RP   FUNCTION IN PHOSPHORYLATION OF ZFP36, AND MUTAGENESIS OF THR-222 AND
RP   THR-334.
RX   PubMed=15014438; DOI=10.1038/sj.emboj.7600163;
RA   Stoecklin G., Stubbs T., Kedersha N., Wax S., Rigby W.F., Blackwell T.K.,
RA   Anderson P.;
RT   "MK2-induced tristetraprolin:14-3-3 complexes prevent stress granule
RT   association and ARE-mRNA decay.";
RL   EMBO J. 23:1313-1324(2004).
RN   [16]
RP   INTERACTION WITH PHC2.
RX   PubMed=15094067; DOI=10.1016/s0014-5793(04)00351-5;
RA   Yannoni Y.M., Gaestel M., Lin L.L.;
RT   "P66(ShcA) interacts with MAPKAP kinase 2 and regulates its activity.";
RL   FEBS Lett. 564:205-211(2004).
RN   [17]
RP   FUNCTION IN PHOSPHORYLATION OF CDC25B AND CDC25C.
RX   PubMed=15629715; DOI=10.1016/j.molcel.2004.11.021;
RA   Manke I.A., Nguyen A., Lim D., Stewart M.Q., Elia A.E., Yaffe M.B.;
RT   "MAPKAP kinase-2 is a cell cycle checkpoint kinase that regulates the G2/M
RT   transition and S phase progression in response to UV irradiation.";
RL   Mol. Cell 17:37-48(2005).
RN   [18]
RP   FUNCTION IN PHOSPHORYLATION OF LIMK1.
RX   PubMed=16456544; DOI=10.1038/sj.emboj.7600973;
RA   Kobayashi M., Nishita M., Mishima T., Ohashi K., Mizuno K.;
RT   "MAPKAPK-2-mediated LIM-kinase activation is critical for VEGF-induced
RT   actin remodeling and cell migration.";
RL   EMBO J. 25:713-726(2006).
RN   [19]
RP   FUNCTION IN PHOSPHORYLATION OF HSF1, AND INTERACTION WITH HSF1.
RX   PubMed=16278218; DOI=10.1074/jbc.m505822200;
RA   Wang X., Khaleque M.A., Zhao M.J., Zhong R., Gaestel M., Calderwood S.K.;
RT   "Phosphorylation of HSF1 by MAPK-activated protein kinase 2 on serine 121,
RT   inhibits transcriptional activity and promotes HSP90 binding.";
RL   J. Biol. Chem. 281:782-791(2006).
RN   [20]
RP   FUNCTION IN PHOSPHORYLATION OF LSP1.
RX   PubMed=17481585; DOI=10.1016/j.bbrc.2007.04.104;
RA   Wu Y., Zhan L., Ai Y., Hannigan M., Gaestel M., Huang C.-K., Madri J.A.;
RT   "MAPKAPK2-mediated LSP1 phosphorylation and FMLP-induced neutrophil
RT   polarization.";
RL   Biochem. Biophys. Res. Commun. 358:170-175(2007).
RN   [21]
RP   FUNCTION IN PHOSPHORYLATION OF TAB3.
RX   PubMed=18021073; DOI=10.1042/bj20071149;
RA   Mendoza H., Campbell D.G., Burness K., Hastie J., Ronkina N., Shim J.H.,
RA   Arthur J.S., Davis R.J., Gaestel M., Johnson G.L., Ghosh S., Cohen P.;
RT   "Roles for TAB1 in regulating the IL-1-dependent phosphorylation of the
RT   TAB3 regulatory subunit and activity of the TAK1 complex.";
RL   Biochem. J. 409:711-722(2008).
RN   [22]
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   [23]
RP   FUNCTION IN PHOSPHORYLATION OF HNRNPA0 AND PARN, AND SUBCELLULAR LOCATION.
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   [24]
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   [25]
RP   SUMOYLATION AT LYS-353, AND MUTAGENESIS OF LYS-353.
RX   PubMed=21131586; DOI=10.1182/blood-2010-08-302281;
RA   Chang E., Heo K.S., Woo C.H., Lee H., Le N.T., Thomas T.N., Fujiwara K.,
RA   Abe J.;
RT   "MK2 SUMOylation regulates actin filament remodeling and subsequent
RT   migration in endothelial cells by inhibiting MK2 kinase and HSP27
RT   phosphorylation.";
RL   Blood 117:2527-2537(2011).
RN   [26]
RP   REVIEW.
RX   PubMed=18508601; DOI=10.2741/3095;
RA   Ronkina N., Kotlyarov A., Gaestel M.;
RT   "MK2 and MK3--a pair of isoenzymes?";
RL   Front. Biosci. 13:5511-5521(2008).
RN   [27]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-334, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=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   [28]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-334, AND IDENTIFICATION BY
RP   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   [29]
RP   FUNCTION.
RX   PubMed=26616734; DOI=10.1038/ncomms10075;
RA   Tollenaere M.A., Villumsen B.H., Blasius M., Nielsen J.C., Wagner S.A.,
RA   Bartek J., Beli P., Mailand N., Bekker-Jensen S.;
RT   "p38- and MK2-dependent signalling promotes stress-induced centriolar
RT   satellite remodelling via 14-3-3-dependent sequestration of CEP131/AZI1.";
RL   Nat. Commun. 6:10075-10075(2015).
RN   [30]
RP   X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH ADP AND
RP   STAUROSPORINE, AND CATALYTIC ACTIVITY.
RX   PubMed=12171911; DOI=10.1074/jbc.c200418200;
RA   Meng W., Swenson L.L., Fitzgibbon M.J., Hayakawa K., Ter Haar E.,
RA   Behrens A.E., Fulghum J.R., Lippke J.A.;
RT   "Structure of mitogen-activated protein kinase-activated protein (MAPKAP)
RT   kinase 2 suggests a bifunctional switch that couples kinase activation with
RT   nuclear export.";
RL   J. Biol. Chem. 277:37401-37405(2002).
RN   [31]
RP   X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
RX   PubMed=12791252; DOI=10.1016/s0969-2126(03)00092-3;
RA   Underwood K.W., Parris K.D., Federico E., Mosyak L., Czerwinski R.M.,
RA   Shane T., Taylor M., Svenson K., Liu Y., Hsiao C.L., Wolfrom S.,
RA   Maguire M., Malakian K., Telliez J.B., Lin L.L., Kriz R.W., Seehra J.,
RA   Somers W.S., Stahl M.L.;
RT   "Catalytically active MAP KAP kinase 2 structures in complex with
RT   staurosporine and ADP reveal differences with the autoinhibited enzyme.";
RL   Structure 11:627-636(2003).
RN   [32]
RP   X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 41-364 IN COMPLEX WITH
RP   CARBOLINE-BASED INHIBITORS.
RX   PubMed=17576063; DOI=10.1016/j.bmcl.2007.05.101;
RA   Wu J.P., Wang J., Abeywardane A., Andersen D., Emmanuel M., Gautschi E.,
RA   Goldberg D.R., Kashem M.A., Lukas S., Mao W., Martin L., Morwick T.,
RA   Moss N., Pargellis C., Patel U.R., Patnaude L., Peet G.W., Skow D.,
RA   Snow R.J., Ward Y., Werneburg B., White A.;
RT   "The discovery of carboline analogs as potent MAPKAP-K2 inhibitors.";
RL   Bioorg. Med. Chem. Lett. 17:4664-4669(2007).
RN   [33]
RP   X-RAY CRYSTALLOGRAPHY (4.0 ANGSTROMS) IN COMPLEX WITH MAPK14, AND
RP   INTERACTION WITH MAPK14.
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   [34]
RP   ERRATUM.
RA   ter Haar E., Prabhakar P., Liu X., Lepre C.;
RL   J. Biol. Chem. 282:14684-14684(2007).
RN   [35]
RP   X-RAY CRYSTALLOGRAPHY (3.8 ANGSTROMS) OF 45-371 IN COMPLEX WITH
RP   PYRROLOPYRIDINE INHIBITORS.
RX   PubMed=17480064; DOI=10.1021/jm0611004;
RA   Anderson D.R., Meyers M.J., Vernier W.F., Mahoney M.W., Kurumbail R.G.,
RA   Caspers N., Poda G.I., Schindler J.F., Reitz D.B., Mourey R.J.;
RT   "Pyrrolopyridine inhibitors of mitogen-activated protein kinase-activated
RT   protein kinase 2 (MK-2).";
RL   J. Med. Chem. 50:2647-2654(2007).
RN   [36]
RP   X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 41-364 IN COMPLEX WITH
RP   PYRROLOPYRIDINE INHIBITOR.
RX   PubMed=17449059; DOI=10.1016/j.jmb.2007.03.004;
RA   Hillig R.C., Eberspaecher U., Monteclaro F., Huber M., Nguyen D.,
RA   Mengel A., Muller-Tiemann B., Egner U.;
RT   "Structural basis for a high affinity inhibitor bound to protein kinase
RT   MK2.";
RL   J. Mol. Biol. 369:735-745(2007).
RN   [37]
RP   X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 47-400 IN COMPLEX WITH MAPK14, AND
RP   INTERACTION WITH MAPK14.
RX   PubMed=17395714; DOI=10.1073/pnas.0701679104;
RA   White A., Pargellis C.A., Studts J.M., Werneburg B.G., Farmer B.T. II;
RT   "Molecular basis of MAPK-activated protein kinase 2:p38 assembly.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:6353-6358(2007).
RN   [38]
RP   VARIANTS [LARGE SCALE ANALYSIS] GLY-173 AND SER-361.
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: Stress-activated serine/threonine-protein kinase involved in
CC       cytokine production, endocytosis, reorganization of the cytoskeleton,
CC       cell migration, cell cycle control, chromatin remodeling, DNA damage
CC       response and transcriptional regulation. Following stress, it is
CC       phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to
CC       phosphorylation of substrates. Phosphorylates serine in the peptide
CC       sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue.
CC       Phosphorylates ALOX5, CDC25B, CDC25C, CEP131, ELAVL1, HNRNPA0,
CC       HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1,
CC       RPS6KA3, TAB3 and TTP/ZFP36. Phosphorylates HSF1; leading to the
CC       interaction with HSP90 proteins and inhibiting HSF1 homotrimerization,
CC       DNA-binding and transactivation activities (PubMed:16278218). Mediates
CC       phosphorylation of HSP27/HSPB1 in response to stress, leading to the
CC       dissociation of HSP27/HSPB1 from large small heat-shock protein (sHsps)
CC       oligomers and impairment of their chaperone activities and ability to
CC       protect against oxidative stress effectively. Involved in inflammatory
CC       response by regulating tumor necrosis factor (TNF) and IL6 production
CC       post-transcriptionally: acts by phosphorylating AU-rich elements
CC       (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading
CC       to the regulation of the stability and translation of TNF and IL6
CC       mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional
CC       regulator of TNF, promotes its binding to 14-3-3 proteins and reduces
CC       its ARE mRNA affinity, leading to inhibition of dependent degradation
CC       of ARE-containing transcripts. Phosphorylates CEP131 in response to
CC       cellular stress induced by ultraviolet irradiation which promotes
CC       binding of CEP131 to 14-3-3 proteins and inhibits formation of novel
CC       centriolar satellites (PubMed:26616734). Also involved in late G2/M
CC       checkpoint following DNA damage through a process of post-
CC       transcriptional mRNA stabilization: following DNA damage, relocalizes
CC       from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading
CC       to stabilization of GADD45A mRNA. Involved in toll-like receptor
CC       signaling pathway (TLR) in dendritic cells: required for acute TLR-
CC       induced macropinocytosis by phosphorylating and activating RPS6KA3.
CC       {ECO:0000269|PubMed:10383393, ECO:0000269|PubMed:11844797,
CC       ECO:0000269|PubMed:12456657, ECO:0000269|PubMed:12565831,
CC       ECO:0000269|PubMed:14499342, ECO:0000269|PubMed:14517288,
CC       ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:15629715,
CC       ECO:0000269|PubMed:16278218, ECO:0000269|PubMed:16456544,
CC       ECO:0000269|PubMed:17481585, ECO:0000269|PubMed:18021073,
CC       ECO:0000269|PubMed:20932473, ECO:0000269|PubMed:26616734,
CC       ECO:0000269|PubMed:8093612, ECO:0000269|PubMed:8280084,
CC       ECO:0000269|PubMed:8774846}.
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=2.7.11.1;
CC         Evidence={ECO:0000269|PubMed:12171911, ECO:0000269|PubMed:8774846};
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=2.7.11.1; Evidence={ECO:0000269|PubMed:12171911,
CC         ECO:0000269|PubMed:8774846};
CC   -!- ACTIVITY REGULATION: Activated following phosphorylation by p38-
CC       alpha/MAPK14 following various stresses. Inhibited following
CC       sumoylation. Specifically inhibited by pyrrolopyridine inhibitors.
CC   -!- SUBUNIT: Heterodimer with p38-alpha/MAPK14; this heterodimer forms a
CC       stable complex: molecules are positioned 'face to face' so that the
CC       ATP-binding sites of both kinases are at the heterodimer interface
CC       (PubMed:12171911, PubMed:17576063, PubMed:17255097, PubMed:17480064,
CC       PubMed:17449059, PubMed:17395714). Interacts with PHC2
CC       (PubMed:15094067). Interacts with HSF1 (PubMed:16278218).
CC       {ECO:0000269|PubMed:12171911, ECO:0000269|PubMed:15094067,
CC       ECO:0000269|PubMed:16278218, ECO:0000269|PubMed:17255097,
CC       ECO:0000269|PubMed:17395714, ECO:0000269|PubMed:17449059,
CC       ECO:0000269|PubMed:17480064, ECO:0000269|PubMed:17576063}.
CC   -!- INTERACTION:
CC       Q00613:HSF1; NbExp=5; IntAct=EBI-993299, EBI-719620;
CC       P04792:HSPB1; NbExp=3; IntAct=EBI-993299, EBI-352682;
CC       Q16539:MAPK14; NbExp=7; IntAct=EBI-993299, EBI-73946;
CC       P47811:Mapk14 (xeno); NbExp=2; IntAct=EBI-15629963, EBI-298727;
CC       Q9QWH1:Phc2 (xeno); NbExp=2; IntAct=EBI-993299, EBI-642357;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20932473}. Nucleus
CC       {ECO:0000269|PubMed:20932473}. Note=Phosphorylation and subsequent
CC       activation releases the autoinhibitory helix, resulting in the export
CC       from the nucleus into the cytoplasm.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P49137-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P49137-2; Sequence=VSP_004910;
CC   -!- TISSUE SPECIFICITY: Expressed in all tissues examined.
CC   -!- PTM: Sumoylation inhibits the protein kinase activity.
CC       {ECO:0000269|PubMed:21131586}.
CC   -!- PTM: Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at
CC       Thr-222, Ser-272 and Thr-334. {ECO:0000269|PubMed:8846784}.
CC   -!- MISCELLANEOUS: [Isoform 1]: Has a nuclear localization signal.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC       protein kinase family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/MAPKAPK2ID41295ch1q32.html";
DR   EMBL; U12779; AAA20851.1; -; mRNA.
DR   EMBL; AL591846; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471100; EAW93526.1; -; Genomic_DNA.
DR   EMBL; CH471100; EAW93529.1; -; Genomic_DNA.
DR   EMBL; BC036060; AAH36060.2; -; mRNA.
DR   EMBL; BC052584; AAH52584.1; -; mRNA.
DR   EMBL; X75346; CAA53094.1; -; mRNA.
DR   CCDS; CCDS1466.1; -. [P49137-2]
DR   CCDS; CCDS31001.1; -. [P49137-1]
DR   PIR; JC2204; JC2204.
DR   PIR; S39793; S39793.
DR   RefSeq; NP_004750.1; NM_004759.4. [P49137-2]
DR   RefSeq; NP_116584.2; NM_032960.3. [P49137-1]
DR   PDB; 1KWP; X-ray; 2.80 A; A/B=1-400.
DR   PDB; 1NXK; X-ray; 2.70 A; A/B/C/D=1-400.
DR   PDB; 1NY3; X-ray; 3.00 A; A=1-400.
DR   PDB; 2JBO; X-ray; 3.10 A; A=41-364.
DR   PDB; 2JBP; X-ray; 3.31 A; A/B/C/D/E/F/G/H/I/J/K/L=41-364.
DR   PDB; 2OKR; X-ray; 2.00 A; C/F=370-393.
DR   PDB; 2ONL; X-ray; 4.00 A; C/D=1-400.
DR   PDB; 2OZA; X-ray; 2.70 A; A=47-400.
DR   PDB; 2P3G; X-ray; 3.80 A; X=45-371.
DR   PDB; 2PZY; X-ray; 2.90 A; A/B/C/D=41-364.
DR   PDB; 3A2C; X-ray; 2.90 A; A/B/C/D/E/F/G/H/I/J/K/L=41-364.
DR   PDB; 3FPM; X-ray; 3.30 A; A=41-364.
DR   PDB; 3FYJ; X-ray; 3.80 A; X=45-371.
DR   PDB; 3FYK; X-ray; 3.50 A; X=45-371.
DR   PDB; 3GOK; X-ray; 3.20 A; A/B/C/D/E/F/G/H/I/J/K/L=41-364.
DR   PDB; 3KA0; X-ray; 2.90 A; A=47-366.
DR   PDB; 3KC3; X-ray; 2.90 A; A/B/C/D/E/F/G/H/I/J/K/L=41-364.
DR   PDB; 3KGA; X-ray; 2.55 A; A=47-364.
DR   PDB; 3M2W; X-ray; 2.41 A; A=47-364.
DR   PDB; 3M42; X-ray; 2.68 A; A=47-364.
DR   PDB; 3R2B; X-ray; 2.90 A; A/B/C/D/E/F/G/H/I/J/K/L=47-364.
DR   PDB; 3R2Y; X-ray; 3.00 A; A=46-364.
DR   PDB; 3R30; X-ray; 3.20 A; A=46-364.
DR   PDB; 3WI6; X-ray; 2.99 A; A/B/C/D/E/F=41-364.
DR   PDB; 4TYH; X-ray; 3.00 A; A=51-400.
DR   PDBsum; 1KWP; -.
DR   PDBsum; 1NXK; -.
DR   PDBsum; 1NY3; -.
DR   PDBsum; 2JBO; -.
DR   PDBsum; 2JBP; -.
DR   PDBsum; 2OKR; -.
DR   PDBsum; 2ONL; -.
DR   PDBsum; 2OZA; -.
DR   PDBsum; 2P3G; -.
DR   PDBsum; 2PZY; -.
DR   PDBsum; 3A2C; -.
DR   PDBsum; 3FPM; -.
DR   PDBsum; 3FYJ; -.
DR   PDBsum; 3FYK; -.
DR   PDBsum; 3GOK; -.
DR   PDBsum; 3KA0; -.
DR   PDBsum; 3KC3; -.
DR   PDBsum; 3KGA; -.
DR   PDBsum; 3M2W; -.
DR   PDBsum; 3M42; -.
DR   PDBsum; 3R2B; -.
DR   PDBsum; 3R2Y; -.
DR   PDBsum; 3R30; -.
DR   PDBsum; 3WI6; -.
DR   PDBsum; 4TYH; -.
DR   SMR; P49137; -.
DR   BioGrid; 114683; 69.
DR   DIP; DIP-35671N; -.
DR   ELM; P49137; -.
DR   IntAct; P49137; 16.
DR   MINT; P49137; -.
DR   STRING; 9606.ENSP00000356070; -.
DR   BindingDB; P49137; -.
DR   ChEMBL; CHEMBL2208; -.
DR   DrugBank; DB07430; (10R)-10-methyl-3-(6-methylpyridin-3-yl)-9,10,11,12-tetrahydro-8H-[1,4]diazepino[5',6':4,5]thieno[3,2-f]quinolin-8-one.
DR   DrugBank; DB07431; (3R)-3-(aminomethyl)-9-methoxy-1,2,3,4-tetrahydro-5H-[1]benzothieno[3,2-e][1,4]diazepin-5-one.
DR   DrugBank; DB07406; (4R)-N-[4-({[2-(DIMETHYLAMINO)ETHYL]AMINO}CARBONYL)-1,3-THIAZOL-2-YL]-4-METHYL-1-OXO-2,3,4,9-TETRAHYDRO-1H-BETA-CARBOLINE-6-CARBOXAMIDE.
DR   DrugBank; DB08358; 2-(2-QUINOLIN-3-YLPYRIDIN-4-YL)-1,5,6,7-TETRAHYDRO-4H-PYRROLO[3,2-C]PYRIDIN-4-ONE.
DR   DrugBank; DB07728; 2-[2-(2-FLUOROPHENYL)PYRIDIN-4-YL]-1,5,6,7-TETRAHYDRO-4H-PYRROLO[3,2-C]PYRIDIN-4-ONE.
DR   DrugBank; DB07234; 3-{[(1R)-1-phenylethyl]amino}-4-(pyridin-4-ylamino)cyclobut-3-ene-1,2-dione.
DR   DrugBank; DB02010; Staurosporine.
DR   DrugCentral; P49137; -.
DR   GuidetoPHARMACOLOGY; 2094; -.
DR   iPTMnet; P49137; -.
DR   PhosphoSitePlus; P49137; -.
DR   SwissPalm; P49137; -.
DR   BioMuta; MAPKAPK2; -.
DR   DMDM; 1346538; -.
DR   EPD; P49137; -.
DR   jPOST; P49137; -.
DR   MassIVE; P49137; -.
DR   MaxQB; P49137; -.
DR   PaxDb; P49137; -.
DR   PeptideAtlas; P49137; -.
DR   PRIDE; P49137; -.
DR   ProteomicsDB; 55964; -. [P49137-1]
DR   ProteomicsDB; 55965; -. [P49137-2]
DR   DNASU; 9261; -.
DR   Ensembl; ENST00000294981; ENSP00000294981; ENSG00000162889. [P49137-2]
DR   Ensembl; ENST00000367103; ENSP00000356070; ENSG00000162889. [P49137-1]
DR   GeneID; 9261; -.
DR   KEGG; hsa:9261; -.
DR   UCSC; uc001hel.3; human. [P49137-1]
DR   CTD; 9261; -.
DR   DisGeNET; 9261; -.
DR   EuPathDB; HostDB:ENSG00000162889.10; -.
DR   GeneCards; MAPKAPK2; -.
DR   HGNC; HGNC:6887; MAPKAPK2.
DR   HPA; CAB010297; -.
DR   HPA; HPA045556; -.
DR   HPA; HPA063708; -.
DR   HPA; HPA064435; -.
DR   MIM; 602006; gene.
DR   neXtProt; NX_P49137; -.
DR   OpenTargets; ENSG00000162889; -.
DR   PharmGKB; PA30631; -.
DR   eggNOG; KOG0604; Eukaryota.
DR   eggNOG; ENOG410XP8F; LUCA.
DR   GeneTree; ENSGT00940000157261; -.
DR   HOGENOM; HOG000233031; -.
DR   InParanoid; P49137; -.
DR   KO; K04443; -.
DR   OMA; MKSRIRM; -.
DR   OrthoDB; 843707at2759; -.
DR   PhylomeDB; P49137; -.
DR   TreeFam; TF312891; -.
DR   BioCyc; MetaCyc:HS08751-MONOMER; -.
DR   BRENDA; 2.7.11.1; 2681.
DR   Reactome; R-HSA-171007; p38MAPK events.
DR   Reactome; R-HSA-199920; CREB phosphorylation.
DR   Reactome; R-HSA-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX).
DR   Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence.
DR   Reactome; R-HSA-3371453; Regulation of HSF1-mediated heat shock response.
DR   Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway.
DR   Reactome; R-HSA-450302; activated TAK1 mediates p38 MAPK activation.
DR   Reactome; R-HSA-450385; Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA.
DR   Reactome; R-HSA-450513; Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA.
DR   SignaLink; P49137; -.
DR   SIGNOR; P49137; -.
DR   ChiTaRS; MAPKAPK2; human.
DR   EvolutionaryTrace; P49137; -.
DR   GeneWiki; MAPKAPK2; -.
DR   GenomeRNAi; 9261; -.
DR   Pharos; P49137; Tchem.
DR   PRO; PR:P49137; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; P49137; protein.
DR   Bgee; ENSG00000162889; Expressed in 233 organ(s), highest expression level in apex of heart.
DR   Genevisible; P49137; HS.
DR   GO; GO:0005813; C:centrosome; IDA:HPA.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0009931; F:calcium-dependent protein serine/threonine kinase activity; IBA:GO_Central.
DR   GO; GO:0005516; F:calmodulin binding; IBA:GO_Central.
DR   GO; GO:0004683; F:calmodulin-dependent protein kinase activity; IBA:GO_Central.
DR   GO; GO:0051019; F:mitogen-activated protein kinase binding; IBA:GO_Central.
DR   GO; GO:0004672; F:protein kinase activity; TAS:ProtInc.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR   GO; GO:0070935; P:3'-UTR-mediated mRNA stabilization; IDA:UniProtKB.
DR   GO; GO:0000187; P:activation of MAPK activity; TAS:Reactome.
DR   GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:UniProtKB.
DR   GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IMP:BHF-UCL.
DR   GO; GO:0006954; P:inflammatory response; ISS:UniProtKB.
DR   GO; GO:0048839; P:inner ear development; IEA:Ensembl.
DR   GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR   GO; GO:0006691; P:leukotriene metabolic process; TAS:Reactome.
DR   GO; GO:0044351; P:macropinocytosis; ISS:UniProtKB.
DR   GO; GO:0000165; P:MAPK cascade; TAS:ProtInc.
DR   GO; GO:0038066; P:p38MAPK cascade; IEA:Ensembl.
DR   GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:BHF-UCL.
DR   GO; GO:0042535; P:positive regulation of tumor necrosis factor biosynthetic process; IEA:Ensembl.
DR   GO; GO:0046777; P:protein autophosphorylation; IBA:GO_Central.
DR   GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc.
DR   GO; GO:1900034; P:regulation of cellular response to heat; TAS:Reactome.
DR   GO; GO:0032675; P:regulation of interleukin-6 production; ISS:UniProtKB.
DR   GO; GO:0043488; P:regulation of mRNA stability; TAS:Reactome.
DR   GO; GO:0032680; P:regulation of tumor necrosis factor production; IDA:UniProtKB.
DR   GO; GO:0034097; P:response to cytokine; IDA:UniProtKB.
DR   GO; GO:0032496; P:response to lipopolysaccharide; ISS:UniProtKB.
DR   GO; GO:0002224; P:toll-like receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IMP:BHF-UCL.
DR   Gene3D; 4.10.1170.10; -; 1.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR027442; MAPKAPK_C.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   Pfam; PF00069; Pkinase; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; SSF56112; 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE   1: Evidence at protein level;
DR   PRODOM; P49137.
DR   SWISS-2DPAGE; P49137.
KW   3D-structure; Alternative splicing; ATP-binding; Cytoplasm; DNA damage;
KW   Isopeptide bond; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein;
KW   Polymorphism; Reference proteome; Serine/threonine-protein kinase;
KW   Transferase; Ubl conjugation.
FT   CHAIN           1..400
FT                   /note="MAP kinase-activated protein kinase 2"
FT                   /id="PRO_0000086288"
FT   DOMAIN          64..325
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   NP_BIND         70..78
FT                   /note="ATP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          139..141
FT                   /note="Staurosporine binding"
FT   REGION          328..364
FT                   /note="Autoinhibitory helix"
FT                   /evidence="ECO:0000250"
FT   REGION          366..390
FT                   /note="p38 MAPK-binding site"
FT   MOTIF           356..365
FT                   /note="Nuclear export signal (NES)"
FT   MOTIF           371..374
FT                   /note="Bipartite nuclear localization signal 1"
FT   MOTIF           385..389
FT                   /note="Bipartite nuclear localization signal 2"
FT   COMPBIAS        10..40
FT                   /note="Pro-rich"
FT   COMPBIAS        35..40
FT                   /note="Poly-Pro"
FT   ACT_SITE        186
FT                   /note="Proton acceptor"
FT   BINDING         93
FT                   /note="ATP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         9
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:8846784"
FT   MOD_RES         25
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000269|PubMed:8846784"
FT   MOD_RES         222
FT                   /note="Phosphothreonine; by MAPK14"
FT                   /evidence="ECO:0000269|PubMed:8846784"
FT   MOD_RES         272
FT                   /note="Phosphoserine; by MAPK14"
FT                   /evidence="ECO:0000269|PubMed:8846784"
FT   MOD_RES         328
FT                   /note="Phosphoserine; by autocatalysis"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         334
FT                   /note="Phosphothreonine; by MAPK14"
FT                   /evidence="ECO:0000244|PubMed:23186163,
FT                   ECO:0000244|PubMed:24275569, ECO:0000269|PubMed:8846784"
FT   CROSSLNK        353
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO)"
FT                   /evidence="ECO:0000269|PubMed:21131586"
FT   VAR_SEQ         354..400
FT                   /note="EEMTSALATMRVDYEQIKIKKIEDASNPLLLKRRKKARALEAAALAH -> G
FT                   CLHDKNSDQATWLTRL (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:8179591"
FT                   /id="VSP_004910"
FT   VARIANT         173
FT                   /note="A -> G (in dbSNP:rs35671930)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_040753"
FT   VARIANT         361
FT                   /note="A -> S (in dbSNP:rs55894011)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_040754"
FT   MUTAGEN         93
FT                   /note="K->R: Kinase defective mutant, abolishes activity."
FT                   /evidence="ECO:0000269|PubMed:14517288"
FT   MUTAGEN         207
FT                   /note="D->A: Kinase defective mutant, abolishes activity."
FT                   /evidence="ECO:0000269|PubMed:8846784"
FT   MUTAGEN         222
FT                   /note="T->A: Strong decrease in kinase activity."
FT                   /evidence="ECO:0000269|PubMed:14517288,
FT                   ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:8846784"
FT   MUTAGEN         222
FT                   /note="T->D: Mimicks phosphorylation state, leading to
FT                   slight increase of basal kinase activity."
FT                   /evidence="ECO:0000269|PubMed:14517288,
FT                   ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:8846784"
FT   MUTAGEN         222
FT                   /note="T->E: Mimicks phosphorylation state and constitutive
FT                   protein kinase activity; when associated with E-334."
FT                   /evidence="ECO:0000269|PubMed:14517288,
FT                   ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:8846784"
FT   MUTAGEN         272
FT                   /note="S->A: Strong decrease in kinase activity."
FT                   /evidence="ECO:0000269|PubMed:8846784"
FT   MUTAGEN         272
FT                   /note="S->D: Mimicks phosphorylation state, leading to
FT                   slight increase of basal kinase activity."
FT                   /evidence="ECO:0000269|PubMed:8846784"
FT   MUTAGEN         334
FT                   /note="T->A: Slight decrease in kinase activity."
FT                   /evidence="ECO:0000269|PubMed:14517288,
FT                   ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:8846784"
FT   MUTAGEN         334
FT                   /note="T->D,E: Mimicks phosphorylation state, leading to
FT                   elevated basal kinase activity."
FT                   /evidence="ECO:0000269|PubMed:14517288,
FT                   ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:8846784"
FT   MUTAGEN         334
FT                   /note="T->E: Mimicks phosphorylation state and constitutive
FT                   protein kinase activity; when associated with E-222."
FT                   /evidence="ECO:0000269|PubMed:14517288,
FT                   ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:8846784"
FT   MUTAGEN         353
FT                   /note="K->R: Induces decreased sumoylation and increase in
FT                   protein kinase activity."
FT                   /evidence="ECO:0000269|PubMed:21131586"
FT   CONFLICT        116
FT                   /note="H -> D (in Ref. 5; CAA53094)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        247..248
FT                   /note="WS -> LV (in Ref. 5; CAA53094)"
FT                   /evidence="ECO:0000305"
FT   HELIX           45..47
FT                   /evidence="ECO:0000244|PDB:1NXK"
FT   STRAND          48..50
FT                   /evidence="ECO:0000244|PDB:1NXK"
FT   HELIX           59..61
FT                   /evidence="ECO:0000244|PDB:3M2W"
FT   STRAND          63..73
FT                   /evidence="ECO:0000244|PDB:3M2W"
FT   STRAND          76..83
FT                   /evidence="ECO:0000244|PDB:3M2W"
FT   TURN            84..86
FT                   /evidence="ECO:0000244|PDB:3M2W"
FT   STRAND          89..96
FT                   /evidence="ECO:0000244|PDB:3M2W"
FT   HELIX           99..111
FT                   /evidence="ECO:0000244|PDB:3M2W"
FT   STRAND          114..117
FT                   /evidence="ECO:0000244|PDB:3FYK"
FT   STRAND          120..128
FT                   /evidence="ECO:0000244|PDB:3M2W"
FT   STRAND          131..138
FT                   /evidence="ECO:0000244|PDB:3M2W"
FT   STRAND          143..145
FT                   /evidence="ECO:0000244|PDB:1NXK"
FT   HELIX           146..152
FT                   /evidence="ECO:0000244|PDB:3M2W"
FT   HELIX           160..179
FT                   /evidence="ECO:0000244|PDB:3M2W"
FT   HELIX           189..191
FT                   /evidence="ECO:0000244|PDB:3M2W"
FT   STRAND          192..198
FT                   /evidence="ECO:0000244|PDB:3M2W"
FT   STRAND          203..205
FT                   /evidence="ECO:0000244|PDB:3M2W"
FT   STRAND          212..214
FT                   /evidence="ECO:0000244|PDB:3WI6"
FT   STRAND          228..230
FT                   /evidence="ECO:0000244|PDB:3FPM"
FT   HELIX           232..234
FT                   /evidence="ECO:0000244|PDB:1NXK"
FT   HELIX           239..242
FT                   /evidence="ECO:0000244|PDB:3M2W"
FT   HELIX           243..258
FT                   /evidence="ECO:0000244|PDB:3M2W"
FT   STRAND          264..266
FT                   /evidence="ECO:0000244|PDB:4TYH"
FT   STRAND          267..269
FT                   /evidence="ECO:0000244|PDB:1KWP"
FT   HELIX           275..281
FT                   /evidence="ECO:0000244|PDB:1NXK"
FT   STRAND          283..285
FT                   /evidence="ECO:0000244|PDB:2OZA"
FT   HELIX           288..291
FT                   /evidence="ECO:0000244|PDB:3M2W"
FT   HELIX           296..305
FT                   /evidence="ECO:0000244|PDB:3M2W"
FT   TURN            310..312
FT                   /evidence="ECO:0000244|PDB:3M2W"
FT   HELIX           316..320
FT                   /evidence="ECO:0000244|PDB:3M2W"
FT   HELIX           323..326
FT                   /evidence="ECO:0000244|PDB:3M2W"
FT   HELIX           328..330
FT                   /evidence="ECO:0000244|PDB:3M2W"
FT   STRAND          335..337
FT                   /evidence="ECO:0000244|PDB:3M42"
FT   HELIX           338..344
FT                   /evidence="ECO:0000244|PDB:3M2W"
FT   HELIX           346..348
FT                   /evidence="ECO:0000244|PDB:3M2W"
FT   HELIX           349..363
FT                   /evidence="ECO:0000244|PDB:3M2W"
FT   TURN            375..377
FT                   /evidence="ECO:0000244|PDB:2OKR"
FT   HELIX           381..389
FT                   /evidence="ECO:0000244|PDB:2OKR"
SQ   SEQUENCE   400 AA;  45568 MW;  E4EFFF11CCF288DC CRC64;
     MLSNSQGQSP PVPFPAPAPP PQPPTPALPH PPAQPPPPPP QQFPQFHVKS GLQIKKNAII
     DDYKVTSQVL GLGINGKVLQ IFNKRTQEKF ALKMLQDCPK ARREVELHWR ASQCPHIVRI
     VDVYENLYAG RKCLLIVMEC LDGGELFSRI QDRGDQAFTE REASEIMKSI GEAIQYLHSI
     NIAHRDVKPE NLLYTSKRPN AILKLTDFGF AKETTSHNSL TTPCYTPYYV APEVLGPEKY
     DKSCDMWSLG VIMYILLCGY PPFYSNHGLA ISPGMKTRIR MGQYEFPNPE WSEVSEEVKM
     LIRNLLKTEP TQRMTITEFM NHPWIMQSTK VPQTPLHTSR VLKEDKERWE DVKEEMTSAL
     ATMRVDYEQI KIKKIEDASN PLLLKRRKKA RALEAAALAH
//

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