ID KS6A3_MOUSE Reviewed; 740 AA. AC P18654; B1AXN4; Q03140; Q8K3J8; DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot. DT 25-MAR-2003, sequence version 2. DT 24-JAN-2024, entry version 219. DE RecName: Full=Ribosomal protein S6 kinase alpha-3; DE Short=S6K-alpha-3; DE EC=2.7.11.1 {ECO:0000269|PubMed:15109498}; DE AltName: Full=90 kDa ribosomal protein S6 kinase 3; DE Short=p90-RSK 3; DE Short=p90RSK3; DE AltName: Full=MAP kinase-activated protein kinase 1b; DE Short=MAPK-activated protein kinase 1b; DE Short=MAPKAP kinase 1b; DE Short=MAPKAPK-1b; DE AltName: Full=Ribosomal S6 kinase 2 {ECO:0000303|PubMed:15109498}; DE Short=RSK-2 {ECO:0000303|PubMed:15109498}; DE AltName: Full=pp90RSK2; GN Name=Rps6ka3; GN Synonyms=Mapkapk1b, Rps6ka-rs1, Rsk2 {ECO:0000303|PubMed:15109498}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=12016217; DOI=10.1074/jbc.m202663200; RA Chrestensen C.A., Sturgill T.W.; RT "Characterization of the p90 ribosomal S6 kinase 2 carboxyl-terminal domain RT as a protein kinase."; RL J. Biol. Chem. 277:27733-27741(2002). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 108-740. RX PubMed=2779569; DOI=10.1128/mcb.9.9.3850-3859.1989; RA Alcorta D.A., Crews C.M., Sweet L.J., Bankston L., Jones S.W., RA Erikson R.L.; RT "Sequence and expression of chicken and mouse rsk: homologs of Xenopus RT laevis ribosomal S6 kinase."; RL Mol. Cell. Biol. 9:3850-3859(1989). RN [4] RP ACTIVITY REGULATION, PHOSPHORYLATION AT SER-227 AND SER-386, AND RP MUTAGENESIS OF SER-227 AND SER-386. RX PubMed=10480933; DOI=10.1074/jbc.274.38.27168; RA Jensen C.J., Buch M.-B., Krag T.O., Hemmings B.A., Gammeltoft S., RA Froedin M.; RT "90-kDa ribosomal S6 kinase is phosphorylated and activated by 3- RT phosphoinositide-dependent protein kinase-1."; RL J. Biol. Chem. 274:27168-27176(1999). RN [5] RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF SER-386. RX PubMed=10856237; DOI=10.1093/emboj/19.12.2924; RA Froedin M., Jensen C.J., Merienne K., Gammeltoft S.; RT "A phosphoserine-regulated docking site in the protein kinase RSK2 that RT recruits and activates PDK1."; RL EMBO J. 19:2924-2934(2000). RN [6] RP FUNCTION IN PHOSPHORYLATION OF CDKN1B. RX PubMed=14504289; DOI=10.1074/jbc.m306614200; RA Fujita N., Sato S., Tsuruo T.; RT "Phosphorylation of p27Kip1 at threonine 198 by p90 ribosomal protein S6 RT kinases promotes its binding to 14-3-3 and cytoplasmic localization."; RL J. Biol. Chem. 278:49254-49260(2003). RN [7] RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE. RX PubMed=15109498; DOI=10.1016/s0092-8674(04)00344-7; RA Yang X., Matsuda K., Bialek P., Jacquot S., Masuoka H.C., Schinke T., RA Li L., Brancorsini S., Sassone-Corsi P., Townes T.M., Hanauer A., RA Karsenty G.; RT "ATF4 is a substrate of RSK2 and an essential regulator of osteoblast RT biology; implication for Coffin-Lowry Syndrome."; RL Cell 117:387-398(2004). RN [8] RP FUNCTION IN HEMATOPOIETIC TRANSFORMATION, PHOSPHORYLATION AT TYR-529, AND RP MUTAGENESIS OF TYR-529. RX PubMed=17785202; DOI=10.1016/j.ccr.2007.08.003; RA Kang S., Dong S., Gu T.L., Guo A., Cohen M.S., Lonial S., Khoury H.J., RA Fabbro D., Gilliland D.G., Bergsagel P.L., Taunton J., Polakiewicz R.D., RA Chen J.; RT "FGFR3 activates RSK2 to mediate hematopoietic transformation through RT tyrosine phosphorylation of RSK2 and activation of the MEK/ERK pathway."; RL Cancer Cell 12:201-214(2007). RN [9] RP FUNCTION IN TOLL-LIKE RECEPTOR SIGNALING, AND PHOSPHORYLATION AT SER-386. RX PubMed=17906627; DOI=10.1038/ni1517; RA Zaru R., Ronkina N., Gaestel M., Arthur J.S., Watts C.; RT "The MAPK-activated kinase Rsk controls an acute Toll-like receptor RT signaling response in dendritic cells and is activated through two distinct RT pathways."; RL Nat. Immunol. 8:1227-1235(2007). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-365; SER-369; SER-415 AND RP SER-715, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, Pancreas, RC Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [11] RP FUNCTION. RX PubMed=22827337; DOI=10.1042/bj20120938; RA Saha M., Carriere A., Cheerathodi M., Zhang X., Lavoie G., Rush J., RA Roux P.P., Ballif B.A.; RT "RSK phosphorylates SOS1 creating 14-3-3-docking sites and negatively RT regulating MAPK activation."; RL Biochem. J. 447:159-166(2012). RN [12] RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 399-740. RX PubMed=18084304; DOI=10.1038/nsmb1347; RA Malakhova M., Tereshko V., Lee S.Y., Yao K., Cho Y.Y., Bode A., Dong Z.; RT "Structural basis for activation of the autoinhibitory C-terminal kinase RT domain of p90 RSK2."; RL Nat. Struct. Mol. Biol. 15:112-113(2008). RN [13] RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 44-367. RX PubMed=19956600; DOI=10.1371/journal.pone.0008044; RA Malakhova M., Kurinov I., Liu K., Zheng D., D'Angelo I., Shim J.H., RA Steinman V., Bode A.M., Dong Z.; RT "Structural diversity of the active N-terminal kinase domain of p90 RT ribosomal S6 kinase 2."; RL PLoS ONE 4:E8044-E8044(2009). CC -!- FUNCTION: Serine/threonine-protein kinase that acts downstream of ERK CC (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and CC stress-induced activation of the transcription factors CREB1, ETV1/ER81 CC and NR4A1/NUR77, regulates translation through RPS6 and EIF4B CC phosphorylation, and mediates cellular proliferation, survival, and CC differentiation by modulating mTOR signaling and repressing pro- CC apoptotic function of BAD and DAPK1 (PubMed:10856237, PubMed:15109498). CC In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 CC and histone H3 at 'Ser-10', which results in the subsequent CC transcriptional activation of several immediate-early genes (By CC similarity). In response to mitogenic stimulation (EGF and PMA), CC phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription CC factors and the cofactor CREBBP (By similarity). Upon insulin-derived CC signal, acts indirectly on the transcription regulation of several CC genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity CC (By similarity). Phosphorylates RPS6 in response to serum or EGF via an CC mTOR-independent mechanism and promotes translation initiation by CC facilitating assembly of the preinitiation complex (By similarity). In CC response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for CC the EIF3 complex and stimulating cap-dependent translation (By CC similarity). Is involved in the mTOR nutrient-sensing pathway by CC directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits CC TSC2 ability to suppress mTOR signaling, and mediates phosphorylation CC of RPTOR, which regulates mTORC1 activity and may promote rapamycin- CC sensitive signaling independently of the PI3K/AKT pathway (By CC similarity). Mediates cell survival by phosphorylating the pro- CC apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic CC function (By similarity). Promotes the survival of hepatic stellate CC cells by phosphorylating CEBPB in response to the hepatotoxin carbon CC tetrachloride (CCl4) (By similarity). Is involved in cell cycle CC regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CC CDKN1B association with 14-3-3 proteins and prevents its translocation CC to the nucleus and inhibition of G1 progression (PubMed:14504289). In CC LPS-stimulated dendritic cells, is involved in TLR4-induced CC macropinocytosis, and in myeloma cells, acts as effector of FGFR3- CC mediated transformation signaling, after direct phosphorylation at Tyr- CC 529 by FGFR3 (PubMed:17785202, PubMed:17906627). Negatively regulates CC EGF-induced MAPK1/3 phosphorylation via phosphorylation of SOS1 CC (PubMed:22827337). Phosphorylates SOS1 at 'Ser-1134' and 'Ser-1161' CC that create YWHAB and YWHAE binding sites and which contribute to the CC negative regulation of MAPK1/3 phosphorylation (PubMed:22827337). CC Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway CC controls cell migration (By similarity). Acts as a regulator of CC osteoblast differentiation by mediating phosphorylation of ATF4, CC thereby promoting ATF4 transactivation activity (PubMed:15109498). CC {ECO:0000250|UniProtKB:P51812, ECO:0000269|PubMed:10856237, CC ECO:0000269|PubMed:14504289, ECO:0000269|PubMed:15109498, CC ECO:0000269|PubMed:17785202, ECO:0000269|PubMed:17906627, CC ECO:0000269|PubMed:22827337}. 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:15109498}; 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; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; CC -!- ACTIVITY REGULATION: Upon extracellular signal or mitogen stimulation, CC phosphorylated at Thr-577 in the C-terminal kinase domain (CTKD) by CC MAPK1/ERK2 and MAPK3/ERK1. The activated CTKD then autophosphorylates CC Ser-386, allowing binding of PDPK1, which in turn phosphorylates Ser- CC 227 in the N-terminal kinase domain (NTDK) leading to the full CC activation of the protein and subsequent phosphorylation of the CC substrates by the NTKD (By similarity). {ECO:0000250}. CC -!- SUBUNIT: Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in CC quiescent cells. Transiently dissociates following mitogenic CC stimulation (By similarity). Interacts with NFATC4, ETV1/ER81 and FGFR1 CC (By similarity). {ECO:0000250}. CC -!- INTERACTION: CC P18654; P30309: cdc25-1-b; Xeno; NbExp=3; IntAct=EBI-397744, EBI-15888737; CC P18654; P28223-1: HTR2A; Xeno; NbExp=2; IntAct=EBI-397744, EBI-15573967; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P51812}. Cytoplasm CC {ECO:0000250|UniProtKB:P51812}. CC -!- TISSUE SPECIFICITY: Intestine, thymus, lung, heart and brain. CC -!- PTM: Activated by phosphorylation at Ser-227 by PDPK1. CC Autophosphorylated on Ser-386, as part of the activation process. May CC be phosphorylated at Thr-365 and Ser-369 by MAPK1/ERK2 and MAPK3/ERK1. CC Can also be activated via phosphorylation at Ser-386 by MAPKAPK2. CC {ECO:0000269|PubMed:10480933, ECO:0000269|PubMed:17785202, CC ECO:0000269|PubMed:17906627}. CC -!- PTM: N-terminal myristoylation results in an activated kinase in the CC absence of added growth factors. {ECO:0000250}. CC -!- DISRUPTION PHENOTYPE: Mice were born at expected Mendelian ratio but CC display decreased bone mass (PubMed:15109498). Embryos and pups show a CC delay in mineralization of the skull with frontal, parietal, and CC interparietal bones of reduced size (PubMed:15109498). Mice also CC display a significant reduction in long bone length at one month of age CC (PubMed:15109498). {ECO:0000269|PubMed:15109498}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr CC protein kinase family. S6 kinase subfamily. {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; AY083469; AAM00022.1; -; mRNA. DR EMBL; AL808146; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS30502.1; -. DR PIR; C32571; C32571. DR PIR; S30504; S30504. DR RefSeq; NP_683747.1; NM_148945.2. DR PDB; 2QR7; X-ray; 2.00 A; A=399-740. DR PDB; 2QR8; X-ray; 2.00 A; A=399-740. DR PDB; 3G51; X-ray; 1.80 A; A=44-367. DR PDB; 3UBD; X-ray; 1.53 A; A=45-346. DR PDB; 4EL9; X-ray; 1.55 A; A=45-346. DR PDB; 4GUE; X-ray; 1.80 A; A=45-346. DR PDB; 4M8T; X-ray; 3.00 A; A=399-740. DR PDB; 4MAO; X-ray; 2.60 A; A=399-740. DR PDB; 5O1S; X-ray; 1.90 A; A=400-740. DR PDBsum; 2QR7; -. DR PDBsum; 2QR8; -. DR PDBsum; 3G51; -. DR PDBsum; 3UBD; -. DR PDBsum; 4EL9; -. DR PDBsum; 4GUE; -. DR PDBsum; 4M8T; -. DR PDBsum; 4MAO; -. DR PDBsum; 5O1S; -. DR AlphaFoldDB; P18654; -. DR SMR; P18654; -. DR BioGRID; 225783; 16. DR CORUM; P18654; -. DR DIP; DIP-31554N; -. DR ELM; P18654; -. DR IntAct; P18654; 8. DR MINT; P18654; -. DR STRING; 10090.ENSMUSP00000033671; -. DR BindingDB; P18654; -. DR ChEMBL; CHEMBL3297641; -. DR GlyGen; P18654; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P18654; -. DR PhosphoSitePlus; P18654; -. DR SwissPalm; P18654; -. DR EPD; P18654; -. DR jPOST; P18654; -. DR MaxQB; P18654; -. DR PaxDb; 10090-ENSMUSP00000033671; -. DR PeptideAtlas; P18654; -. DR ProteomicsDB; 265029; -. DR Pumba; P18654; -. DR Antibodypedia; 1004; 706 antibodies from 36 providers. DR DNASU; 110651; -. DR Ensembl; ENSMUST00000033671.13; ENSMUSP00000033671.7; ENSMUSG00000031309.16. DR GeneID; 110651; -. DR KEGG; mmu:110651; -. DR UCSC; uc009usj.2; mouse. DR AGR; MGI:104557; -. DR CTD; 6197; -. DR MGI; MGI:104557; Rps6ka3. DR VEuPathDB; HostDB:ENSMUSG00000031309; -. DR eggNOG; KOG0603; Eukaryota. DR GeneTree; ENSGT00940000159370; -. DR InParanoid; P18654; -. DR OMA; XQLHRNS; -. DR OrthoDB; 5489497at2759; -. DR PhylomeDB; P18654; -. DR TreeFam; TF313438; -. DR Reactome; R-MMU-198753; ERK/MAPK targets. DR Reactome; R-MMU-199920; CREB phosphorylation. DR Reactome; R-MMU-2559582; Senescence-Associated Secretory Phenotype (SASP). DR Reactome; R-MMU-442742; CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling. DR Reactome; R-MMU-444257; RSK activation. DR Reactome; R-MMU-881907; Gastrin-CREB signalling pathway via PKC and MAPK. DR BioGRID-ORCS; 110651; 5 hits in 83 CRISPR screens. DR ChiTaRS; Rps6ka3; mouse. DR EvolutionaryTrace; P18654; -. DR PRO; PR:P18654; -. DR Proteomes; UP000000589; Chromosome X. DR RNAct; P18654; Protein. DR Bgee; ENSMUSG00000031309; Expressed in trigeminal ganglion and 257 other cell types or tissues. DR ExpressionAtlas; P18654; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0005730; C:nucleolus; ISO:MGI. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; ISO:MGI. DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:MGI. DR GO; GO:0004711; F:ribosomal protein S6 kinase activity; IBA:GO_Central. DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW. DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI. DR GO; GO:0032496; P:response to lipopolysaccharide; IMP:UniProtKB. DR GO; GO:0002224; P:toll-like receptor signaling pathway; IMP:UniProtKB. DR CDD; cd14176; STKc_RSK2_C; 1. DR CDD; cd05582; STKc_RSK_N; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 2. DR InterPro; IPR000961; AGC-kinase_C. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR017892; Pkinase_C. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR016239; Ribosomal_S6_kinase_II. DR InterPro; IPR041905; RPS6KA3_C. DR InterPro; IPR041906; RSK_N. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR24351; RIBOSOMAL PROTEIN S6 KINASE; 1. DR PANTHER; PTHR24351:SF58; RIBOSOMAL PROTEIN S6 KINASE ALPHA-3; 1. DR Pfam; PF00069; Pkinase; 2. DR Pfam; PF00433; Pkinase_C; 1. DR PIRSF; PIRSF000606; Ribsml_S6_kin_2; 1. DR SMART; SM00133; S_TK_X; 1. DR SMART; SM00220; S_TKc; 2. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 2. DR PROSITE; PS51285; AGC_KINASE_CTER; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 2. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 2. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 2. DR Genevisible; P18654; MM. PE 1: Evidence at protein level; KW 3D-structure; ATP-binding; Cell cycle; Cytoplasm; Kinase; KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat; KW Serine/threonine-protein kinase; Stress response; Transferase. FT CHAIN 1..740 FT /note="Ribosomal protein S6 kinase alpha-3" FT /id="PRO_0000086204" FT DOMAIN 68..327 FT /note="Protein kinase 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 328..397 FT /note="AGC-kinase C-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618" FT DOMAIN 422..679 FT /note="Protein kinase 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 1..41 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 193 FT /note="Proton acceptor" FT /evidence="ECO:0000250" FT ACT_SITE 539 FT /note="Proton acceptor" FT /evidence="ECO:0000250" FT BINDING 74..82 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 100 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 428..436 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 451 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 227 FT /note="Phosphoserine; by PDPK1" FT /evidence="ECO:0000269|PubMed:10480933" FT MOD_RES 365 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 369 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 375 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P51812" FT MOD_RES 386 FT /note="Phosphoserine; by autocatalysis and MAPKAPK2" FT /evidence="ECO:0000269|PubMed:10480933, FT ECO:0000269|PubMed:17906627" FT MOD_RES 415 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 529 FT /note="Phosphotyrosine; by FGFR3" FT /evidence="ECO:0000269|PubMed:17785202" FT MOD_RES 556 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P51812" FT MOD_RES 715 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MUTAGEN 227 FT /note="S->E: Loss of phosphorylation and activation by FT PDPK1." FT /evidence="ECO:0000269|PubMed:10480933" FT MUTAGEN 386 FT /note="S->A: Loss of phosphorylation by PDPK1; loss of FT activation by PDPK1 and EGF." FT /evidence="ECO:0000269|PubMed:10480933, FT ECO:0000269|PubMed:10856237" FT MUTAGEN 386 FT /note="S->E: Loss of interaction with PDPK1 and FT phosphorylation at S-227." FT /evidence="ECO:0000269|PubMed:10480933, FT ECO:0000269|PubMed:10856237" FT MUTAGEN 529 FT /note="Y->F: Attenuates activation by MAPK1/ERK1 and FT MAPK3/ERK2." FT /evidence="ECO:0000269|PubMed:17785202" FT STRAND 50..56 FT /evidence="ECO:0007829|PDB:3UBD" FT HELIX 65..67 FT /evidence="ECO:0007829|PDB:3UBD" FT STRAND 68..75 FT /evidence="ECO:0007829|PDB:3UBD" FT HELIX 77..79 FT /evidence="ECO:0007829|PDB:3UBD" FT STRAND 81..87 FT /evidence="ECO:0007829|PDB:3UBD" FT TURN 91..94 FT /evidence="ECO:0007829|PDB:3UBD" FT STRAND 96..111 FT /evidence="ECO:0007829|PDB:3UBD" FT HELIX 121..124 FT /evidence="ECO:0007829|PDB:3G51" FT STRAND 133..139 FT /evidence="ECO:0007829|PDB:3UBD" FT STRAND 142..147 FT /evidence="ECO:0007829|PDB:3UBD" FT HELIX 156..162 FT /evidence="ECO:0007829|PDB:3UBD" FT HELIX 167..186 FT /evidence="ECO:0007829|PDB:3UBD" FT HELIX 196..198 FT /evidence="ECO:0007829|PDB:3UBD" FT STRAND 199..201 FT /evidence="ECO:0007829|PDB:3UBD" FT STRAND 207..216 FT /evidence="ECO:0007829|PDB:3UBD" FT HELIX 232..234 FT /evidence="ECO:0007829|PDB:3UBD" FT HELIX 237..241 FT /evidence="ECO:0007829|PDB:3UBD" FT HELIX 248..263 FT /evidence="ECO:0007829|PDB:3UBD" FT HELIX 273..282 FT /evidence="ECO:0007829|PDB:3UBD" FT HELIX 293..302 FT /evidence="ECO:0007829|PDB:3UBD" FT HELIX 307..309 FT /evidence="ECO:0007829|PDB:3UBD" FT TURN 315..317 FT /evidence="ECO:0007829|PDB:3UBD" FT HELIX 318..322 FT /evidence="ECO:0007829|PDB:3UBD" FT HELIX 325..327 FT /evidence="ECO:0007829|PDB:3UBD" FT HELIX 332..336 FT /evidence="ECO:0007829|PDB:3UBD" FT HELIX 418..421 FT /evidence="ECO:0007829|PDB:5O1S" FT STRAND 422..427 FT /evidence="ECO:0007829|PDB:5O1S" FT STRAND 435..441 FT /evidence="ECO:0007829|PDB:5O1S" FT TURN 442..444 FT /evidence="ECO:0007829|PDB:5O1S" FT STRAND 447..454 FT /evidence="ECO:0007829|PDB:5O1S" FT TURN 455..457 FT /evidence="ECO:0007829|PDB:5O1S" FT HELIX 461..470 FT /evidence="ECO:0007829|PDB:5O1S" FT STRAND 479..484 FT /evidence="ECO:0007829|PDB:5O1S" FT STRAND 486..493 FT /evidence="ECO:0007829|PDB:5O1S" FT STRAND 498..500 FT /evidence="ECO:0007829|PDB:4M8T" FT HELIX 501..506 FT /evidence="ECO:0007829|PDB:5O1S" FT HELIX 513..532 FT /evidence="ECO:0007829|PDB:5O1S" FT HELIX 542..544 FT /evidence="ECO:0007829|PDB:5O1S" FT STRAND 545..551 FT /evidence="ECO:0007829|PDB:5O1S" FT HELIX 554..556 FT /evidence="ECO:0007829|PDB:5O1S" FT STRAND 557..559 FT /evidence="ECO:0007829|PDB:5O1S" FT HELIX 562..564 FT /evidence="ECO:0007829|PDB:4M8T" FT HELIX 587..613 FT /evidence="ECO:0007829|PDB:5O1S" FT STRAND 614..616 FT /evidence="ECO:0007829|PDB:5O1S" FT STRAND 619..621 FT /evidence="ECO:0007829|PDB:5O1S" FT HELIX 626..634 FT /evidence="ECO:0007829|PDB:5O1S" FT HELIX 643..647 FT /evidence="ECO:0007829|PDB:5O1S" FT HELIX 650..659 FT /evidence="ECO:0007829|PDB:5O1S" FT TURN 664..666 FT /evidence="ECO:0007829|PDB:5O1S" FT HELIX 670..673 FT /evidence="ECO:0007829|PDB:5O1S" FT HELIX 677..680 FT /evidence="ECO:0007829|PDB:5O1S" FT HELIX 682..684 FT /evidence="ECO:0007829|PDB:5O1S" FT HELIX 696..711 FT /evidence="ECO:0007829|PDB:5O1S" SQ SEQUENCE 740 AA; 83694 MW; 0CD54E5918567007 CRC64; MPLAQLADPW QKMAVESPSD SAENGQQIMD EPMGEEEINP QTEEGSIKEI AITHHVKEGH EKADPSQFEL LKVLGQGSFG KVFLVKKISG SDARQLYAMK VLKKATLKVR DRVRTKMERD ILVEVNHPFI VKLHYAFQTE GKLYLILDFL RGGDLFTRLS KEVMFTEEDV KFYLAELALA LDHLHSLGII YRDLKPENIL LDEEGHIKLT DFGLSKESID HEKKAYSFCG TVEYMAPEVV NRRGHTQSAD WWSFGVLMFE MLTGTLPFQG KDRKETMTMI LKAKLGMPQF LSPEAQSLLR MLFKRNPANR LGAGPDGVEE IKRHSFFSTI DWNKLYRREI HPPFKPATGR PEDTFYFDPE FTAKTPKDSP GIPPSANAHQ LFRGFSFVAI TSDDESQAMQ TVGVHSIVQQ LHRNSIQFTD GYEVKEDIGV GSYSVCKRCI HKATNMEFAV KIIDKSKRDP TEEIEILLRY GQHPNIITLK DVYDDGKYVY VVTELMKGGE LLDKILRQKF FSEREASAVL FTITKTVEYL HAQGVVHRDL KPSNILYVDE SGNPESIRIC DFGFAKQLRA ENGLLMTPCY TANFVAPEVL KRQGYDAACD IWSLGVLLYT MLTGYTPFAN GPDDTPEEIL ARIGSGKFSL SGGYWNSVSD TAKDLVSKML HVDPHQRLTA ALVLRHPWIV HWDQLPQYQL NRQDAPHLVK GAMAATYSAL NRNQSPVLEP VGRSTLAQRR GIKKITSTAL //