MKNK2_HUMAN
ID MKNK2_HUMAN Reviewed; 465 AA.
AC Q9HBH9; Q6GPI3; Q9HBH8; Q9UHR0; Q9Y2N6;
DT 30-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 3.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=MAP kinase-interacting serine/threonine-protein kinase 2;
DE EC=2.7.11.1;
DE AltName: Full=MAP kinase signal-integrating kinase 2;
DE Short=MAPK signal-integrating kinase 2;
DE Short=Mnk2;
GN Name=MKNK2; Synonyms=GPRK7, MNK2;
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 {ECO:0000312|EMBL:AAG26336.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4 AND 5), TISSUE SPECIFICITY,
RP AND INTERACTION WITH ESR2.
RC TISSUE=Fetal brain;
RX PubMed=11013076; DOI=10.1006/geno.2000.6299;
RA Slentz-Kesler K., Moore J.T., Lombard M., Zhang J., Hollingsworth R.,
RA Weiner M.P.;
RT "Identification of the human Mnk2 gene (MKNK2) through protein interaction
RT with estrogen receptor beta.";
RL Genomics 69:63-71(2000).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Adrenal gland;
RA Li Y., Shi J., Huang C., Ren S., Fu S., Zhou J., Yu Y., Xu S., Wang Y.,
RA Fu G., Chen Z., Han Z.;
RT "A novel gene expressed in human adrenal gland.";
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Uterus;
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 FUNCTION AS EIF4E KINASE, ACTIVITY REGULATION, ALTERNATIVE SPLICING,
RP PHOSPHORYLATION BY MAPK1/ERK2; MAPK11 AND MAPK14, AND INTERACTION WITH
RP EIF4G PROTEINS.
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 [6] {ECO:0000305}
RP FUNCTION, PHOSPHORYLATION AT THR-244; THR-249 AND THR-379, AND MUTAGENESIS
RP OF THR-244; THR-249 AND THR-379.
RC TISSUE=Leukocyte;
RX PubMed=11463832; DOI=10.1128/mcb.21.16.5500-5511.2001;
RA Knauf U., Tschopp C., Gram H.;
RT "Negative regulation of protein translation by mitogen-activated protein
RT kinase-interacting kinases 1 and 2.";
RL Mol. Cell. Biol. 21:5500-5511(2001).
RN [7]
RP FUNCTION AS EIF4E KINASE, ALTERNATIVE SPLICING, SUBCELLULAR LOCATION,
RP PHOSPHORYLATION, AND INTERACTION WITH EIF4E; EIF4G1 AND EIF4G2.
RX PubMed=12897141; DOI=10.1128/mcb.23.16.5692-5705.2003;
RA Scheper G.C., Parra J.L., Wilson M., Van Kollenburg B., Vertegaal A.C.O.,
RA Han Z.-G., Proud C.G.;
RT "The N and C termini of the splice variants of the human mitogen-activated
RT protein kinase-interacting kinase Mnk2 determine activity and
RT localization.";
RL Mol. Cell. Biol. 23:5692-5705(2003).
RN [8]
RP FUNCTION AS HNRNPA1 KINASE, AND ACTIVITY REGULATION.
RX PubMed=16111636; DOI=10.1016/j.immuni.2005.06.009;
RA Buxade M., Parra J.L., Rousseau S., Shpiro N., Marquez R., Morrice N.,
RA Bain J., Espel E., Proud C.G.;
RT "The Mnks are novel components in the control of TNF alpha biosynthesis and
RT phosphorylate and regulate hnRNP A1.";
RL Immunity 23:177-189(2005).
RN [9]
RP FUNCTION AS SFPQ/PSF KINASE.
RX PubMed=17965020; DOI=10.1074/jbc.m705286200;
RA Buxade M., Morrice N., Krebs D.L., Proud C.G.;
RT "The PSF.p54nrb complex is a novel Mnk substrate that binds the mRNA for
RT tumor necrosis factor alpha.";
RL J. Biol. Chem. 283:57-65(2008).
RN [10]
RP FUNCTION IN ARSENIC TRIOXIDE SIGNALING, AND PHOSPHORYLATION IN RESPONSE TO
RP ARSENIC TRIOXIDE.
RX PubMed=18299328; DOI=10.1074/jbc.m708816200;
RA Dolniak B., Katsoulidis E., Carayol N., Altman J.K., Redig A.J.,
RA Tallman M.S., Ueda T., Watanabe-Fukunaga R., Fukunaga R., Platanias L.C.;
RT "Regulation of arsenic trioxide-induced cellular responses by Mnk1 and
RT Mnk2.";
RL J. Biol. Chem. 283:12034-12042(2008).
RN [11]
RP IDENTIFICATION BY 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 [12]
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 [13]
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 [14]
RP ACTIVITY REGULATION.
RX PubMed=20722422; DOI=10.1021/jm1005513;
RA Oyarzabal J., Zarich N., Albarran M.I., Palacios I., Urbano-Cuadrado M.,
RA Mateos G., Reymundo I., Rabal O., Salgado A., Corrionero A., Fominaya J.,
RA Pastor J., Bischoff J.R.;
RT "Discovery of mitogen-activated protein kinase-interacting kinase 1
RT inhibitors by a comprehensive fragment-oriented virtual screening
RT approach.";
RL J. Med. Chem. 53:6618-6628(2010).
RN [15]
RP FUNCTION AS EIF4E KINASE, AND INTERACTION WITH EIF4G1.
RX PubMed=20823271; DOI=10.1128/mcb.00448-10;
RA Shveygert M., Kaiser C., Bradrick S.S., Gromeier M.;
RT "Regulation of eukaryotic initiation factor 4E (eIF4E) phosphorylation by
RT mitogen-activated protein kinase occurs through modulation of Mnk1-eIF4G
RT interaction.";
RL Mol. Cell. Biol. 30:5160-5167(2010).
RN [16]
RP ACTIVITY REGULATION.
RX PubMed=20664001; DOI=10.1124/mol.110.064642;
RA Altman J.K., Glaser H., Sassano A., Joshi S., Ueda T.,
RA Watanabe-Fukunaga R., Fukunaga R., Tallman M.S., Platanias L.C.;
RT "Negative regulatory effects of Mnk kinases in the generation of
RT chemotherapy-induced antileukemic responses.";
RL Mol. Pharmacol. 78:778-784(2010).
RN [17]
RP FUNCTION IN EIF4E PHOSPHORYLATION REGULATION, DEPHOSPHORYLATION BY PP2A,
RP AND ACTIVITY REGULATION.
RX PubMed=20927323; DOI=10.1593/neo.10704;
RA Li Y., Yue P., Deng X., Ueda T., Fukunaga R., Khuri F.R., Sun S.-Y.;
RT "Protein phosphatase 2A negatively regulates eukaryotic initiation factor
RT 4E phosphorylation and eIF4F assembly through direct dephosphorylation of
RT Mnk and eIF4E.";
RL Neoplasia 12:848-855(2010).
RN [18]
RP FUNCTION IN IFNGAMMA SIGNALING.
RX PubMed=21149447; DOI=10.1074/jbc.m110.197921;
RA Joshi S., Sharma B., Kaur S., Majchrzak B., Ueda T., Fukunaga R.,
RA Verma A.K., Fish E.N., Platanias L.C.;
RT "Essential role for Mnk kinases in type II interferon (IFNgamma) signaling
RT and its suppressive effects on normal hematopoiesis.";
RL J. Biol. Chem. 286:6017-6026(2011).
RN [19]
RP REVIEW.
RX PubMed=18508592; DOI=10.2741/3086;
RA Buxade M., Parra-Palau J.L., Proud C.G.;
RT "The Mnks: MAP kinase-interacting kinases (MAP kinase signal-integrating
RT kinases).";
RL Front. Biosci. 13:5359-5373(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-452, AND IDENTIFICATION BY
RP 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 [21]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 72-385 IN COMPLEX WITH ZINC, AND
RP SUBUNIT.
RX PubMed=16216586; DOI=10.1016/j.str.2005.07.013;
RA Jauch R., Jaekel S., Netter C., Schreiter K., Aicher B., Jaeckle H.,
RA Wahl M.C.;
RT "Crystal structures of the Mnk2 kinase domain reveal an inhibitory
RT conformation and a zinc binding site.";
RL Structure 13:1559-1568(2005).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.71 ANGSTROMS) OF 72-385 IN COMPLEX WITH ZINC AND
RP STAUROSPORINE, ACTIVITY REGULATION, AND MUTAGENESIS OF ASP-228.
RX PubMed=16917500; DOI=10.1038/sj.emboj.7601285;
RA Jauch R., Cho M.-K., Jaekel S., Netter C., Schreiter K., Aicher B.,
RA Zweckstetter M., Jaeckle H., Wahl M.C.;
RT "Mitogen-activated protein kinases interacting kinases are autoinhibited by
RT a reprogrammed activation segment.";
RL EMBO J. 25:4020-4032(2006).
RN [23]
RP VARIANT [LARGE SCALE ANALYSIS] ASN-73.
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-protein kinase that phosphorylates SFPQ/PSF,
CC HNRNPA1 and EIF4E. May play a role in the response to environmental
CC stress and cytokines. Appears to regulate translation by
CC phosphorylating EIF4E, thus increasing the affinity of this protein for
CC the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A-
CC inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from
CC cytoplasm to nucleus. Isoform 1 displays a high basal kinase activity,
CC but isoform 2 exhibits a very low kinase activity. Acts as a mediator
CC of the suppressive effects of IFNgamma on hematopoiesis. Negative
CC regulator for signals that control generation of arsenic trioxide
CC As(2)O(3)-dependent apoptosis and anti-leukemic responses. Involved in
CC anti-apoptotic signaling in response to serum withdrawal.
CC {ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:11463832,
CC ECO:0000269|PubMed:12897141, ECO:0000269|PubMed:16111636,
CC ECO:0000269|PubMed:17965020, ECO:0000269|PubMed:18299328,
CC ECO:0000269|PubMed:20823271, ECO:0000269|PubMed:20927323,
CC ECO:0000269|PubMed:21149447}.
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:11463832};
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:11463832};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:11463832};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Note=Binds 1 zinc ion per subunit.;
CC -!- ACTIVITY REGULATION: Inhibited by CGP57380 and staurosporine. Activated
CC by phosphorylation in a negative-feedback regulatory manner in response
CC to chemotherapy (e.g. cytarabine) and thus impairs the generation of
CC antileukemic responses. {ECO:0000269|PubMed:11154262,
CC ECO:0000269|PubMed:16111636, ECO:0000269|PubMed:16917500,
CC ECO:0000269|PubMed:20664001, ECO:0000269|PubMed:20722422,
CC ECO:0000269|PubMed:20927323}.
CC -!- SUBUNIT: Monomer. Interacts with the C-terminal regions of EIF4G1 and
CC EIF4G2; this interaction is promoted when MAPK pathways are repressed
CC but repressed upon ERK proteins activation. Also binds to
CC dephosphorylated MAPK3/ERK1 and MAPK1/ERK2. Isoform 1 interaction with
CC phosphorylated MAPK3/ERK1 and MAPK1/ERK2 protects it from
CC dephosphorylation and inactivation. Isoform 2 interacts with ESR2 and
CC EIF4E in the nucleus. {ECO:0000269|PubMed:11013076,
CC ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:12897141,
CC ECO:0000269|PubMed:16216586, ECO:0000269|PubMed:16917500,
CC ECO:0000269|PubMed:20823271}.
CC -!- INTERACTION:
CC Q9HBH9; Q16539: MAPK14; NbExp=4; IntAct=EBI-2864341, EBI-73946;
CC Q9HBH9-2; P46379-2: BAG6; NbExp=3; IntAct=EBI-14141314, EBI-10988864;
CC Q9HBH9-2; O14901: KLF11; NbExp=3; IntAct=EBI-14141314, EBI-948266;
CC Q9HBH9-2; Q14696: MESD; NbExp=3; IntAct=EBI-14141314, EBI-6165891;
CC Q9HBH9-2; P25786: PSMA1; NbExp=3; IntAct=EBI-14141314, EBI-359352;
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus, PML body.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1 {ECO:0000269|PubMed:11013076}; Synonyms=2a
CC {ECO:0000303|PubMed:11013076};
CC IsoId=Q9HBH9-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:11013076}; Synonyms=2b
CC {ECO:0000303|PubMed:11013076};
CC IsoId=Q9HBH9-2; Sequence=VSP_007353, VSP_007354;
CC Name=3 {ECO:0000303|PubMed:11013076};
CC IsoId=Q9HBH9-3; Sequence=Not described;
CC Name=4 {ECO:0000303|PubMed:11013076};
CC IsoId=Q9HBH9-4; Sequence=Not described;
CC Name=5 {ECO:0000303|PubMed:11013076};
CC IsoId=Q9HBH9-5; Sequence=Not described;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in all tissues examined.
CC Isoform 2 is expressed at higher levels in the ovary than is isoform 1.
CC {ECO:0000269|PubMed:11013076}.
CC -!- PTM: Dual phosphorylation of Thr-244 and Thr-249 activates the kinase.
CC Phosphorylation of Thr-379 activates the kinase. Phosphorylated upon
CC arsenic trioxide As(2)O(3) treatment. Phosphorylated by MAPK1/ERK2,
CC MAPK11 and MAPK14. Dephosphorylated by PP2A.
CC {ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:11463832,
CC ECO:0000269|PubMed:12897141, ECO:0000269|PubMed:18299328}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; AF237775; AAG26336.1; -; mRNA.
DR EMBL; AF237776; AAG26337.1; -; mRNA.
DR EMBL; AF125532; AAF17226.1; -; mRNA.
DR EMBL; BC073140; AAH73140.1; -; mRNA.
DR CCDS; CCDS12079.1; -. [Q9HBH9-2]
DR CCDS; CCDS12080.1; -. [Q9HBH9-1]
DR RefSeq; NP_060042.2; NM_017572.3. [Q9HBH9-2]
DR RefSeq; NP_951009.1; NM_199054.2. [Q9HBH9-1]
DR PDB; 2AC3; X-ray; 2.10 A; A=72-385.
DR PDB; 2AC5; X-ray; 3.20 A; A=72-385.
DR PDB; 2HW7; X-ray; 2.71 A; A=72-385.
DR PDB; 6CJ5; X-ray; 2.80 A; A=72-385.
DR PDB; 6CJE; X-ray; 3.36 A; A=72-385.
DR PDB; 6CJH; X-ray; 3.60 A; A=72-385.
DR PDB; 6CJW; X-ray; 3.38 A; A=72-385.
DR PDB; 6CJY; X-ray; 3.05 A; A=72-385.
DR PDB; 6CK3; X-ray; 2.90 A; A=72-385.
DR PDB; 6CK6; X-ray; 3.32 A; A=72-385.
DR PDB; 6CKI; X-ray; 2.95 A; A=72-385.
DR PDB; 6JLR; X-ray; 2.90 A; A=72-385.
DR PDBsum; 2AC3; -.
DR PDBsum; 2AC5; -.
DR PDBsum; 2HW7; -.
DR PDBsum; 6CJ5; -.
DR PDBsum; 6CJE; -.
DR PDBsum; 6CJH; -.
DR PDBsum; 6CJW; -.
DR PDBsum; 6CJY; -.
DR PDBsum; 6CK3; -.
DR PDBsum; 6CK6; -.
DR PDBsum; 6CKI; -.
DR PDBsum; 6JLR; -.
DR AlphaFoldDB; Q9HBH9; -.
DR SMR; Q9HBH9; -.
DR BioGRID; 109130; 43.
DR IntAct; Q9HBH9; 43.
DR STRING; 9606.ENSP00000250896; -.
DR BindingDB; Q9HBH9; -.
DR ChEMBL; CHEMBL4204; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q9HBH9; -.
DR GuidetoPHARMACOLOGY; 2105; -.
DR iPTMnet; Q9HBH9; -.
DR PhosphoSitePlus; Q9HBH9; -.
DR BioMuta; MKNK2; -.
DR DMDM; 90102033; -.
DR EPD; Q9HBH9; -.
DR jPOST; Q9HBH9; -.
DR MassIVE; Q9HBH9; -.
DR MaxQB; Q9HBH9; -.
DR PaxDb; Q9HBH9; -.
DR PeptideAtlas; Q9HBH9; -.
DR PRIDE; Q9HBH9; -.
DR ProteomicsDB; 81554; -. [Q9HBH9-1]
DR ProteomicsDB; 81555; -. [Q9HBH9-2]
DR Antibodypedia; 10678; 309 antibodies from 30 providers.
DR DNASU; 2872; -.
DR Ensembl; ENST00000250896.9; ENSP00000250896.3; ENSG00000099875.16. [Q9HBH9-1]
DR Ensembl; ENST00000309340.11; ENSP00000309485.6; ENSG00000099875.16. [Q9HBH9-2]
DR GeneID; 2872; -.
DR KEGG; hsa:2872; -.
DR MANE-Select; ENST00000250896.9; ENSP00000250896.3; NM_199054.3; NP_951009.1.
DR UCSC; uc002lus.3; human. [Q9HBH9-1]
DR CTD; 2872; -.
DR DisGeNET; 2872; -.
DR GeneCards; MKNK2; -.
DR HGNC; HGNC:7111; MKNK2.
DR HPA; ENSG00000099875; Tissue enhanced (skeletal muscle, tongue).
DR MIM; 605069; gene.
DR neXtProt; NX_Q9HBH9; -.
DR OpenTargets; ENSG00000099875; -.
DR PharmGKB; PA30830; -.
DR VEuPathDB; HostDB:ENSG00000099875; -.
DR eggNOG; KOG0607; Eukaryota.
DR GeneTree; ENSGT00940000154587; -.
DR InParanoid; Q9HBH9; -.
DR OMA; NKMTEVT; -.
DR PhylomeDB; Q9HBH9; -.
DR PathwayCommons; Q9HBH9; -.
DR SignaLink; Q9HBH9; -.
DR SIGNOR; Q9HBH9; -.
DR BioGRID-ORCS; 2872; 16 hits in 1120 CRISPR screens.
DR ChiTaRS; MKNK2; human.
DR EvolutionaryTrace; Q9HBH9; -.
DR GeneWiki; MKNK2; -.
DR GenomeRNAi; 2872; -.
DR Pharos; Q9HBH9; Tchem.
DR PRO; PR:Q9HBH9; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9HBH9; protein.
DR Bgee; ENSG00000099875; Expressed in superior surface of tongue and 206 other tissues.
DR ExpressionAtlas; Q9HBH9; baseline and differential.
DR Genevisible; Q9HBH9; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0071243; P:cellular response to arsenic-containing substance; IDA:UniProtKB.
DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IEA:Ensembl.
DR GO; GO:0030097; P:hemopoiesis; IDA:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0046777; P:protein autophosphorylation; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW.
DR IDEAL; IID00680; -.
DR InterPro; IPR011009; Kinase-like_dom_sf.
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;
KW 3D-structure; Alternative splicing; Apoptosis; ATP-binding; Cytoplasm;
KW Kinase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase; Translation regulation; Zinc.
FT CHAIN 1..465
FT /note="MAP kinase-interacting serine/threonine-protein
FT kinase 2"
FT /id="PRO_0000086336"
FT DOMAIN 84..388
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 23..72
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 60..66
FT /note="Nuclear localization signal"
FT MOTIF 444..448
FT /note="MAP kinase binding"
FT /evidence="ECO:0000250"
FT ACT_SITE 205
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 90..98
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 113
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 160..162
FT /ligand="staurosporine"
FT /ligand_id="ChEBI:CHEBI:57491"
FT BINDING 209
FT /ligand="staurosporine"
FT /ligand_id="ChEBI:CHEBI:57491"
FT /evidence="ECO:0000269|PubMed:16917500"
FT BINDING 299
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:16216586,
FT ECO:0000269|PubMed:16917500"
FT BINDING 311
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:16216586,
FT ECO:0000269|PubMed:16917500"
FT BINDING 314
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:16216586,
FT ECO:0000269|PubMed:16917500"
FT MOD_RES 74
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CDB0"
FT MOD_RES 244
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:11463832"
FT MOD_RES 249
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:11463832"
FT MOD_RES 379
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:11463832"
FT MOD_RES 437
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CDB0"
FT MOD_RES 440
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CDB0"
FT MOD_RES 452
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 386..414
FT /note="NSCAKDLTSFAAEAIAMNRQLAQHDEDLA -> WDSHFLLPPHPCRIHVRPG
FT GLVRTVTVNE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11013076,
FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.2"
FT /id="VSP_007353"
FT VAR_SEQ 415..465
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11013076,
FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.2"
FT /id="VSP_007354"
FT VARIANT 10
FT /note="Q -> K (in dbSNP:rs3746101)"
FT /id="VAR_051648"
FT VARIANT 73
FT /note="D -> N (in dbSNP:rs56158214)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040805"
FT VARIANT 428
FT /note="R -> Q (in dbSNP:rs34475638)"
FT /id="VAR_051649"
FT MUTAGEN 228
FT /note="D->G: Reduced phosphorylation."
FT /evidence="ECO:0000269|PubMed:16917500"
FT MUTAGEN 244
FT /note="T->A: Loss of kinase activity; when associated with
FT T-249."
FT /evidence="ECO:0000269|PubMed:11463832"
FT MUTAGEN 249
FT /note="T->A: Loss of kinase activity; when associated with
FT T-244."
FT /evidence="ECO:0000269|PubMed:11463832"
FT MUTAGEN 379
FT /note="T->D: Constitutively active."
FT /evidence="ECO:0000269|PubMed:11463832"
FT CONFLICT 261
FT /note="V -> L (in Ref. 2; AAF17226)"
FT /evidence="ECO:0000305"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:6CK3"
FT TURN 79..81
FT /evidence="ECO:0007829|PDB:2AC3"
FT STRAND 83..85
FT /evidence="ECO:0007829|PDB:2HW7"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:6CK3"
FT STRAND 94..102
FT /evidence="ECO:0007829|PDB:2AC3"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:2AC3"
FT STRAND 109..116
FT /evidence="ECO:0007829|PDB:2AC3"
FT STRAND 119..121
FT /evidence="ECO:0007829|PDB:6CJ5"
FT HELIX 123..135
FT /evidence="ECO:0007829|PDB:2AC3"
FT STRAND 145..151
FT /evidence="ECO:0007829|PDB:2AC3"
FT STRAND 154..160
FT /evidence="ECO:0007829|PDB:2AC3"
FT HELIX 167..174
FT /evidence="ECO:0007829|PDB:2AC3"
FT HELIX 179..198
FT /evidence="ECO:0007829|PDB:2AC3"
FT HELIX 208..210
FT /evidence="ECO:0007829|PDB:2AC3"
FT STRAND 211..214
FT /evidence="ECO:0007829|PDB:2AC3"
FT STRAND 216..219
FT /evidence="ECO:0007829|PDB:2AC3"
FT STRAND 221..224
FT /evidence="ECO:0007829|PDB:2AC3"
FT HELIX 254..256
FT /evidence="ECO:0007829|PDB:2AC3"
FT HELIX 259..264
FT /evidence="ECO:0007829|PDB:2AC3"
FT HELIX 267..272
FT /evidence="ECO:0007829|PDB:2AC3"
FT HELIX 273..275
FT /evidence="ECO:0007829|PDB:2AC3"
FT HELIX 276..290
FT /evidence="ECO:0007829|PDB:2AC3"
FT HELIX 312..324
FT /evidence="ECO:0007829|PDB:2AC3"
FT HELIX 331..334
FT /evidence="ECO:0007829|PDB:2AC3"
FT HELIX 339..348
FT /evidence="ECO:0007829|PDB:2AC3"
FT TURN 353..355
FT /evidence="ECO:0007829|PDB:2AC3"
FT HELIX 359..364
FT /evidence="ECO:0007829|PDB:2AC3"
FT TURN 366..368
FT /evidence="ECO:0007829|PDB:2HW7"
SQ SEQUENCE 465 AA; 51875 MW; D6D4BE6C541012B1 CRC64;
MVQKKPAELQ GFHRSFKGQN PFELAFSLDQ PDHGDSDFGL QCSARPDMPA SQPIDIPDAK
KRGKKKKRGR ATDSFSGRFE DVYQLQEDVL GEGAHARVQT CINLITSQEY AVKIIEKQPG
HIRSRVFREV EMLYQCQGHR NVLELIEFFE EEDRFYLVFE KMRGGSILSH IHKRRHFNEL
EASVVVQDVA SALDFLHNKG IAHRDLKPEN ILCEHPNQVS PVKICDFDLG SGIKLNGDCS
PISTPELLTP CGSAEYMAPE VVEAFSEEAS IYDKRCDLWS LGVILYILLS GYPPFVGRCG
SDCGWDRGEA CPACQNMLFE SIQEGKYEFP DKDWAHISCA AKDLISKLLV RDAKQRLSAA
QVLQHPWVQG CAPENTLPTP MVLQRNSCAK DLTSFAAEAI AMNRQLAQHD EDLAEEEAAG
QGQPVLVRAT SRCLQLSPPS QSKLAQRRQR ASLSSAPVVL VGDHA
