MKNK1_HUMAN
ID MKNK1_HUMAN Reviewed; 465 AA.
AC Q9BUB5; D3DQ20; D3DQ21; O00312; Q5TC06; Q5TC07; Q6V0N6;
DT 30-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=MAP kinase-interacting serine/threonine-protein kinase 1;
DE EC=2.7.11.1 {ECO:0000269|PubMed:11463832, ECO:0000269|PubMed:9155018};
DE AltName: Full=MAP kinase signal-integrating kinase 1;
DE Short=MAPK signal-integrating kinase 1;
DE Short=Mnk1;
GN Name=MKNK1; Synonyms=MNK1;
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:AAH02755.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, PHOSPHORYLATION BY MAPK3/ERK1, AND ACTIVITY REGULATION.
RC TISSUE=Cervix carcinoma;
RX PubMed=9155018; DOI=10.1093/emboj/16.8.1921;
RA Fukunaga R., Hunter T.;
RT "MNK1, a new MAP kinase-activated protein kinase, isolated by a novel
RT expression screening method for identifying protein kinase substrates.";
RL EMBO J. 16:1921-1933(1997).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, PHOSPHORYLATION AT THR-250; THR-255 AND THR-385, AND MUTAGENESIS
RP OF LYS-78; ASP-232; THR-250; THR-255 AND THR-385.
RC TISSUE=T-cell;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, TISSUE SPECIFICITY,
RP PHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=15350534; DOI=10.1016/j.yexcr.2004.06.006;
RA O'Loghlen A., Gonzalez V.M., Pineiro D., Perez-Morgado M.I., Salinas M.,
RA Martin M.E.;
RT "Identification and molecular characterization of Mnk1b, a splice variant
RT of human MAP kinase-interacting kinase Mnk1.";
RL Exp. Cell Res. 299:343-355(2004).
RN [4]
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 [5]
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 [6] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [7] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH EIF4G1 AND EIF4G2.
RX PubMed=9878069; DOI=10.1093/emboj/18.1.270;
RA Pyronnet S., Imataka H., Gingras A.-C., Fukunaga R., Hunter T.,
RA Sonenberg N.;
RT "Human eukaryotic translation initiation factor 4G (eIF4G) recruits mnk1 to
RT phosphorylate eIF4E.";
RL EMBO J. 18:270-279(1999).
RN [8]
RP PHOSPHORYLATION BY PAK2.
RX PubMed=15234964; DOI=10.1074/jbc.m407337200;
RA Orton K.C., Ling J., Waskiewicz A.J., Cooper J.A., Merrick W.C.,
RA Korneeva N.L., Rhoads R.E., Sonenberg N., Traugh J.A.;
RT "Phosphorylation of Mnk1 by caspase-activated Pak2/gamma-PAK inhibits
RT phosphorylation and interaction of eIF4G with Mnk.";
RL J. Biol. Chem. 279:38649-38657(2004).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-460, AND IDENTIFICATION BY
RP 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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-39; SER-221; SER-226 AND
RP THR-385, AND 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 [11]
RP VARIANTS [LARGE SCALE ANALYSIS] GLN-49; VAL-158; ASN-308 AND GLN-446.
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: May play a role in the response to environmental stress and
CC cytokines. Appears to regulate translation by phosphorylating EIF4E,
CC thus increasing the affinity of this protein for the 7-methylguanosine-
CC containing mRNA cap. {ECO:0000269|PubMed:11463832,
CC ECO:0000269|PubMed:15350534, ECO:0000269|PubMed:9155018,
CC ECO:0000269|PubMed:9878069}.
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, ECO:0000269|PubMed:9155018};
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 ECO:0000269|PubMed:9155018};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:11463832, ECO:0000269|PubMed:9155018};
CC -!- ACTIVITY REGULATION: Phosphorylated and activated by the p38 kinases
CC and kinases in the Erk pathway. {ECO:0000269|PubMed:9155018}.
CC -!- SUBUNIT: Interacts with the C-terminal regions of EIF4G1 and EIF4G2.
CC Also binds to dephosphorylated ERK1 and ERK2, and to the p38 kinases.
CC {ECO:0000269|PubMed:9878069}.
CC -!- INTERACTION:
CC Q9BUB5; P54253: ATXN1; NbExp=6; IntAct=EBI-73837, EBI-930964;
CC Q9BUB5; Q03060-25: CREM; NbExp=3; IntAct=EBI-73837, EBI-12884642;
CC Q9BUB5; P42858: HTT; NbExp=18; IntAct=EBI-73837, EBI-466029;
CC Q9BUB5; P28482: MAPK1; NbExp=10; IntAct=EBI-73837, EBI-959949;
CC Q9BUB5; Q16539: MAPK14; NbExp=5; IntAct=EBI-73837, EBI-73946;
CC Q9BUB5; Q96CV9: OPTN; NbExp=3; IntAct=EBI-73837, EBI-748974;
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm. Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1 {ECO:0000269|PubMed:11463832};
CC IsoId=Q9BUB5-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:9155018}; Synonyms=MNK1a;
CC IsoId=Q9BUB5-2; Sequence=VSP_007352;
CC Name=3; Synonyms=MNK1b;
CC IsoId=Q9BUB5-3; Sequence=VSP_007352, VSP_017515;
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:15350534}.
CC -!- PTM: Dual phosphorylation of Thr-250 and Thr-255 activates the kinase.
CC Phosphorylation of Thr-385 activates the kinase. MAPK3/ERK1 is one of
CC the kinases which activate MKNK1/MNK1. Phosphorylation by PAK2 leads to
CC a reduced phosphorylation of EIF4G1. {ECO:0000269|PubMed:11463832,
CC ECO:0000269|PubMed:15234964, ECO:0000269|PubMed:15350534,
CC ECO:0000269|PubMed:9155018}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; AB000409; BAA19885.1; -; mRNA.
DR EMBL; AY355461; AAQ84219.1; -; mRNA.
DR EMBL; AL136373; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX06900.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06902.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06904.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06905.1; -; Genomic_DNA.
DR EMBL; BC002755; AAH02755.1; -; mRNA.
DR RefSeq; NP_001129025.1; NM_001135553.2.
DR RefSeq; NP_003675.2; NM_003684.5.
DR RefSeq; NP_945324.1; NM_198973.3.
DR RefSeq; XP_006711063.1; XM_006711000.1.
DR RefSeq; XP_016858148.1; XM_017002659.1.
DR PDB; 2HW6; X-ray; 2.50 A; A/B=37-382.
DR PDB; 2Y9Q; X-ray; 1.55 A; B=434-451.
DR PDB; 5WVD; X-ray; 3.00 A; A/B=37-382.
DR PDBsum; 2HW6; -.
DR PDBsum; 2Y9Q; -.
DR PDBsum; 5WVD; -.
DR AlphaFoldDB; Q9BUB5; -.
DR SMR; Q9BUB5; -.
DR BioGRID; 114138; 57.
DR CORUM; Q9BUB5; -.
DR ELM; Q9BUB5; -.
DR IntAct; Q9BUB5; 63.
DR MINT; Q9BUB5; -.
DR STRING; 9606.ENSP00000361014; -.
DR BindingDB; Q9BUB5; -.
DR ChEMBL; CHEMBL4718; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q9BUB5; -.
DR GuidetoPHARMACOLOGY; 2104; -.
DR iPTMnet; Q9BUB5; -.
DR MetOSite; Q9BUB5; -.
DR PhosphoSitePlus; Q9BUB5; -.
DR BioMuta; MKNK1; -.
DR DMDM; 30316115; -.
DR EPD; Q9BUB5; -.
DR jPOST; Q9BUB5; -.
DR MassIVE; Q9BUB5; -.
DR MaxQB; Q9BUB5; -.
DR PaxDb; Q9BUB5; -.
DR PeptideAtlas; Q9BUB5; -.
DR PRIDE; Q9BUB5; -.
DR ProteomicsDB; 79072; -. [Q9BUB5-1]
DR ProteomicsDB; 79073; -. [Q9BUB5-2]
DR ProteomicsDB; 79074; -. [Q9BUB5-3]
DR Antibodypedia; 32808; 575 antibodies from 33 providers.
DR DNASU; 8569; -.
DR Ensembl; ENST00000649800.1; ENSP00000498083.1; ENSG00000079277.22. [Q9BUB5-1]
DR Ensembl; ENST00000650026.1; ENSP00000497380.1; ENSG00000079277.22. [Q9BUB5-3]
DR Ensembl; ENST00000650508.1; ENSP00000498143.1; ENSG00000079277.22. [Q9BUB5-2]
DR GeneID; 8569; -.
DR KEGG; hsa:8569; -.
DR UCSC; uc001cqb.5; human. [Q9BUB5-1]
DR CTD; 8569; -.
DR DisGeNET; 8569; -.
DR GeneCards; MKNK1; -.
DR HGNC; HGNC:7110; MKNK1.
DR HPA; ENSG00000079277; Tissue enhanced (pancreas).
DR MIM; 606724; gene.
DR neXtProt; NX_Q9BUB5; -.
DR OpenTargets; ENSG00000079277; -.
DR PharmGKB; PA30829; -.
DR VEuPathDB; HostDB:ENSG00000079277; -.
DR eggNOG; KOG0607; Eukaryota.
DR GeneTree; ENSGT00940000162886; -.
DR InParanoid; Q9BUB5; -.
DR OrthoDB; 669799at2759; -.
DR PhylomeDB; Q9BUB5; -.
DR TreeFam; TF314050; -.
DR PathwayCommons; Q9BUB5; -.
DR Reactome; R-HSA-1295596; Spry regulation of FGF signaling.
DR SignaLink; Q9BUB5; -.
DR SIGNOR; Q9BUB5; -.
DR BioGRID-ORCS; 8569; 137 hits in 1116 CRISPR screens.
DR ChiTaRS; MKNK1; human.
DR EvolutionaryTrace; Q9BUB5; -.
DR GeneWiki; MKNK1; -.
DR GenomeRNAi; 8569; -.
DR Pharos; Q9BUB5; Tchem.
DR PRO; PR:Q9BUB5; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9BUB5; protein.
DR Bgee; ENSG00000079277; Expressed in body of pancreas and 205 other tissues.
DR ExpressionAtlas; Q9BUB5; baseline and differential.
DR Genevisible; Q9BUB5; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
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:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:BHF-UCL.
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; IID00679; -.
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; 2.
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; ATP-binding; Cytoplasm; Kinase;
KW Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Translation regulation.
FT CHAIN 1..465
FT /note="MAP kinase-interacting serine/threonine-protein
FT kinase 1"
FT /id="PRO_0000086334"
FT DOMAIN 49..374
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 185..204
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 446..465
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 211
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 55..63
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 78
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:11463832"
FT MOD_RES 39
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 221
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 226
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 250
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:11463832"
FT MOD_RES 255
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:11463832"
FT MOD_RES 385
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:11463832,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 460
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT VAR_SEQ 165..205
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:15350534,
FT ECO:0000303|PubMed:9155018"
FT /id="VSP_007352"
FT VAR_SEQ 377..465
FT /note="QAPEKGLPTPQVLQRNSSTMDLTLFAAEAIALNRQLSQHEENELAEEPEALA
FT DGLCSMKLSPPCKSRLARRRALAQAGRGEDRSPPTAL -> EQQHNGPDALRS (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:15350534"
FT /id="VSP_017515"
FT VARIANT 49
FT /note="K -> Q (in dbSNP:rs56351860)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040801"
FT VARIANT 158
FT /note="L -> V (in dbSNP:rs56408722)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040802"
FT VARIANT 308
FT /note="D -> N (in dbSNP:rs55791614)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040803"
FT VARIANT 446
FT /note="R -> Q (in dbSNP:rs34881418)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040804"
FT MUTAGEN 78
FT /note="K->M: Loss of kinase activity; when associated with
FT D-232."
FT /evidence="ECO:0000269|PubMed:11463832"
FT MUTAGEN 232
FT /note="D->A: Loss of kinase activity; when associated with
FT K-78."
FT /evidence="ECO:0000269|PubMed:11463832"
FT MUTAGEN 250
FT /note="T->A: Loss of kinase activity; when associated with
FT T-255."
FT /evidence="ECO:0000269|PubMed:11463832"
FT MUTAGEN 255
FT /note="T->A: Loss of kinase activity; when associated with
FT T-250."
FT /evidence="ECO:0000269|PubMed:11463832"
FT MUTAGEN 385
FT /note="T->D: Constitutively active."
FT /evidence="ECO:0000269|PubMed:11463832"
FT HELIX 44..46
FT /evidence="ECO:0007829|PDB:2HW6"
FT STRAND 48..57
FT /evidence="ECO:0007829|PDB:2HW6"
FT STRAND 59..68
FT /evidence="ECO:0007829|PDB:2HW6"
FT TURN 69..71
FT /evidence="ECO:0007829|PDB:2HW6"
FT STRAND 74..81
FT /evidence="ECO:0007829|PDB:2HW6"
FT HELIX 87..101
FT /evidence="ECO:0007829|PDB:2HW6"
FT STRAND 110..115
FT /evidence="ECO:0007829|PDB:2HW6"
FT STRAND 117..125
FT /evidence="ECO:0007829|PDB:2HW6"
FT HELIX 132..139
FT /evidence="ECO:0007829|PDB:2HW6"
FT HELIX 144..163
FT /evidence="ECO:0007829|PDB:2HW6"
FT HELIX 214..216
FT /evidence="ECO:0007829|PDB:2HW6"
FT STRAND 217..220
FT /evidence="ECO:0007829|PDB:2HW6"
FT STRAND 227..230
FT /evidence="ECO:0007829|PDB:2HW6"
FT STRAND 271..274
FT /evidence="ECO:0007829|PDB:2HW6"
FT HELIX 277..296
FT /evidence="ECO:0007829|PDB:2HW6"
FT HELIX 337..340
FT /evidence="ECO:0007829|PDB:2HW6"
FT STRAND 341..343
FT /evidence="ECO:0007829|PDB:5WVD"
FT HELIX 345..354
FT /evidence="ECO:0007829|PDB:2HW6"
FT TURN 359..361
FT /evidence="ECO:0007829|PDB:2HW6"
FT HELIX 365..370
FT /evidence="ECO:0007829|PDB:2HW6"
FT TURN 372..375
FT /evidence="ECO:0007829|PDB:2HW6"
FT HELIX 439..441
FT /evidence="ECO:0007829|PDB:2Y9Q"
FT HELIX 443..449
FT /evidence="ECO:0007829|PDB:2Y9Q"
SQ SEQUENCE 465 AA; 51342 MW; CAE225C35DCB2B43 CRC64;
MVSSQKLEKP IEMGSSEPLP IADGDRRRKK KRRGRATDSL PGKFEDMYKL TSELLGEGAY
AKVQGAVSLQ NGKEYAVKII EKQAGHSRSR VFREVETLYQ CQGNKNILEL IEFFEDDTRF
YLVFEKLQGG SILAHIQKQK HFNEREASRV VRDVAAALDF LHTKDKVSLC HLGWSAMAPS
GLTAAPTSLG SSDPPTSASQ VAGTTGIAHR DLKPENILCE SPEKVSPVKI CDFDLGSGMK
LNNSCTPITT PELTTPCGSA EYMAPEVVEV FTDQATFYDK RCDLWSLGVV LYIMLSGYPP
FVGHCGADCG WDRGEVCRVC QNKLFESIQE GKYEFPDKDW AHISSEAKDL ISKLLVRDAK
QRLSAAQVLQ HPWVQGQAPE KGLPTPQVLQ RNSSTMDLTL FAAEAIALNR QLSQHEENEL
AEEPEALADG LCSMKLSPPC KSRLARRRAL AQAGRGEDRS PPTAL
