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 27-MAR-2024, entry version 206. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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; 77. DR CORUM; Q9BUB5; -. DR ELM; Q9BUB5; -. DR IntAct; Q9BUB5; 63. DR MINT; Q9BUB5; -. DR STRING; 9606.ENSP00000498083; -. 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; 9606-ENSP00000361014; -. DR PeptideAtlas; Q9BUB5; -. DR ProteomicsDB; 79072; -. [Q9BUB5-1] DR ProteomicsDB; 79073; -. [Q9BUB5-2] DR ProteomicsDB; 79074; -. [Q9BUB5-3] DR Pumba; Q9BUB5; -. DR Antibodypedia; 32808; 639 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 AGR; HGNC:7110; -. 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; 2899709at2759; -. 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; 139 hits in 1194 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 207 other cell types or tissues. DR ExpressionAtlas; Q9BUB5; baseline and differential. 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:0006468; P:protein phosphorylation; IDA:UniProtKB. DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW. DR CDD; cd14174; STKc_Mnk1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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 PANTHER; PTHR24349:SF114; MAP KINASE-INTERACTING SERINE_THREONINE-PROTEIN KINASE 1; 1. DR PANTHER; PTHR24349; SERINE/THREONINE-PROTEIN KINASE; 1. DR Pfam; PF00069; Pkinase; 2. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; Q9BUB5; HS. 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 //