ID KS6A1_HUMAN Reviewed; 735 AA. AC Q15418; A6NGG4; A8K9K7; B2RDY8; B7Z5J0; E9PRI4; Q5SVM5; Q5SVM8; Q5SVM9; AC Q96C05; Q9BQK2; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 16-APR-2002, sequence version 2. DT 11-DEC-2019, entry version 210. DE RecName: Full=Ribosomal protein S6 kinase alpha-1; DE Short=S6K-alpha-1; DE EC=2.7.11.1; DE AltName: Full=90 kDa ribosomal protein S6 kinase 1; DE Short=p90-RSK 1; DE Short=p90RSK1; DE Short=p90S6K; DE AltName: Full=MAP kinase-activated protein kinase 1a; DE Short=MAPK-activated protein kinase 1a; DE Short=MAPKAP kinase 1a; DE Short=MAPKAPK-1a; DE AltName: Full=Ribosomal S6 kinase 1; DE Short=RSK-1; GN Name=RPS6KA1; Synonyms=MAPKAPK1A, RSK1; 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 1), AND VARIANT THR-335. RX PubMed=8141249; DOI=10.1152/ajpcell.1994.266.2.c351; RA Moller D.E., Xia C.-H., Tang W., Zhu A.X., Jakubowski M.; RT "Human rsk isoforms: cloning and characterization of tissue-specific RT expression."; RL Am. J. Physiol. 266:C351-C359(1994). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). RC TISSUE=Testis, and Thyroid; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] 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 [4] 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Colon; 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 [6] RP SUBCELLULAR LOCATION. RX PubMed=9687510; DOI=10.1093/emboj/17.15.4426; RA Deak M., Clifton A.D., Lucocq J.M., Alessi D.R.; RT "Mitogen- and stress-activated protein kinase-1 (MSK1) is directly RT activated by MAPK and SAPK2/p38, and may mediate activation of CREB."; RL EMBO J. 17:4426-4441(1998). RN [7] RP FUNCTION, ACTIVITY REGULATION, AND PHOSPHORYLATION AT SER-221; THR-359; RP SER-363; SER-380; THR-573 AND SER-732. RX PubMed=9430688; DOI=10.1074/jbc.273.3.1496; RA Dalby K.N., Morrice N., Caudwell F.B., Avruch J., Cohen P.; RT "Identification of regulatory phosphorylation sites in mitogen-activated RT protein kinase (MAPK)-activated protein kinase-1a/p90rsk that are inducible RT by MAPK."; RL J. Biol. Chem. 273:1496-1505(1998). RN [8] RP FUNCTION IN PHOSPHORYLATION OF BAD. RX PubMed=10679322; DOI=10.1016/s0960-9822(00)00310-9; RA Shimamura A., Ballif B.A., Richards S.A., Blenis J.; RT "Rsk1 mediates a MEK-MAP kinase cell survival signal."; RL Curr. Biol. 10:127-135(2000). RN [9] RP FUNCTION IN PHOSPHORYLATION OF CEBPB. RX PubMed=11684016; DOI=10.1016/s1097-2765(01)00374-4; RA Buck M., Poli V., Hunter T., Chojkier M.; RT "C/EBPbeta phosphorylation by RSK creates a functional XEXD caspase RT inhibitory box critical for cell survival."; RL Mol. Cell 8:807-816(2001). RN [10] RP FUNCTION IN PHOSPHORYLATION OF ETV1/ER81, AND INTERACTION WITH ETV1/ER81. RX PubMed=12213813; DOI=10.1074/jbc.m205501200; RA Wu J., Janknecht R.; RT "Regulation of the ETS transcription factor ER81 by the 90-kDa ribosomal S6 RT kinase 1 and protein kinase A."; RL J. Biol. Chem. 277:42669-42679(2002). RN [11] RP INTERACTION WITH MAPK1 OR MAPK3. RX PubMed=12832467; DOI=10.1128/mcb.23.14.4796-4804.2003; RA Roux P.P., Richards S.A., Blenis J.; RT "Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates extracellular RT signal-regulated kinase docking and RSK activity."; RL Mol. Cell. Biol. 23:4796-4804(2003). RN [12] RP FUNCTION, INTERACTION WITH FGFR1, ACTIVITY REGULATION, AND SUBCELLULAR RP LOCATION. RX PubMed=15117958; DOI=10.1074/jbc.m311144200; RA Hu Y., Fang X., Dunham S.M., Prada C., Stachowiak E.K., Stachowiak M.K.; RT "90-kDa ribosomal S6 kinase is a direct target for the nuclear fibroblast RT growth factor receptor 1 (FGFR1): role in FGFR1 signaling."; RL J. Biol. Chem. 279:29325-29335(2004). RN [13] RP FUNCTION IN MTOR SIGNALING, AND INTERACTION WITH TSC2. RX PubMed=15342917; DOI=10.1073/pnas.0405659101; RA Roux P.P., Ballif B.A., Anjum R., Gygi S.P., Blenis J.; RT "Tumor-promoting phorbol esters and activated Ras inactivate the tuberous RT sclerosis tumor suppressor complex via p90 ribosomal S6 kinase."; RL Proc. Natl. Acad. Sci. U.S.A. 101:13489-13494(2004). RN [14] RP FUNCTION IN PHOSPHORYLATION OF DAPK1. RX PubMed=16213824; DOI=10.1016/j.cub.2005.08.050; RA Anjum R., Roux P.P., Ballif B.A., Gygi S.P., Blenis J.; RT "The tumor suppressor DAP kinase is a target of RSK-mediated survival RT signaling."; RL Curr. Biol. 15:1762-1767(2005). RN [15] RP FUNCTION IN PHOSPHORYLATION OF NR4A1/NUR77. RX PubMed=16223362; DOI=10.1042/bj20050967; RA Wingate A.D., Campbell D.G., Peggie M., Arthur J.S.; RT "Nur77 is phosphorylated in cells by RSK in response to mitogenic RT stimulation."; RL Biochem. J. 393:715-724(2006). RN [16] RP FUNCTION IN TRANSLATION REGULATION, AND FUNCTION IN PHOSPHORYLATION OF RP EIF4B. RX PubMed=16763566; DOI=10.1038/sj.emboj.7601166; RA Shahbazian D., Roux P.P., Mieulet V., Cohen M.S., Raught B., Taunton J., RA Hershey J.W., Blenis J., Pende M., Sonenberg N.; RT "The mTOR/PI3K and MAPK pathways converge on eIF4B to control its RT phosphorylation and activity."; RL EMBO J. 25:2781-2791(2006). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [18] RP FUNCTION IN PHOSPHORYLATION OF RPS6. RX PubMed=17360704; DOI=10.1074/jbc.m700906200; RA Roux P.P., Shahbazian D., Vu H., Holz M.K., Cohen M.S., Taunton J., RA Sonenberg N., Blenis J.; RT "RAS/ERK signaling promotes site-specific ribosomal protein S6 RT phosphorylation via RSK and stimulates cap-dependent translation."; RL J. Biol. Chem. 282:14056-14064(2007). RN [19] RP FUNCTION IN MTOR SIGNALING. RX PubMed=18722121; DOI=10.1016/j.cub.2008.07.078; RA Carriere A., Cargnello M., Julien L.A., Gao H., Bonneil E., Thibault P., RA Roux P.P.; RT "Oncogenic MAPK signaling stimulates mTORC1 activity by promoting RSK- RT mediated raptor phosphorylation."; RL Curr. Biol. 18:1269-1277(2008). RN [20] RP REVIEW ON FUNCTION, AND REVIEW ON ACTIVITY REGULATION. RX PubMed=18508509; DOI=10.2741/3003; RA Carriere A., Ray H., Blenis J., Roux P.P.; RT "The RSK factors of activating the Ras/MAPK signaling cascade."; RL Front. Biosci. 13:4258-4275(2008). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-359; SER-363 AND SER-380, AND 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 [22] RP REVIEW ON FUNCTION, AND REVIEW ON ACTIVITY REGULATION. RX PubMed=18813292; DOI=10.1038/nrm2509; RA Anjum R., Blenis J.; RT "The RSK family of kinases: emerging roles in cellular signalling."; RL Nat. Rev. Mol. Cell Biol. 9:747-758(2008). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-359; SER-363; SER-369 AND RP SER-380, AND 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 [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-54; SER-307; THR-359; RP SER-363; SER-369 AND SER-380, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-380, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [26] 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 [27] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-359 AND SER-363, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [28] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-359; SER-363; SER-369 AND RP SER-380, 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 [29] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-363 AND SER-380, AND RP IDENTIFICATION BY 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 [30] RP FUNCTION IN PHOSPHORYLATION OF EPHA2. RX PubMed=26158630; DOI=10.1038/ncomms8679; RA Zhou Y., Yamada N., Tanaka T., Hori T., Yokoyama S., Hayakawa Y., Yano S., RA Fukuoka J., Koizumi K., Saiki I., Sakurai H.; RT "Crucial roles of RSK in cell motility by catalysing serine phosphorylation RT of EphA2."; RL Nat. Commun. 6:7679-7679(2015). RN [31] RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 33-353 IN COMPLEX WITH INHIBITOR. RX PubMed=17965187; DOI=10.1110/ps.073123707; RA Ikuta M., Kornienko M., Byrne N., Reid J.C., Mizuarai S., Kotani H., RA Munshi S.K.; RT "Crystal structures of the N-terminal kinase domain of human RSK1 bound to RT three different ligands: Implications for the design of RSK1 specific RT inhibitors."; RL Protein Sci. 16:2626-2635(2007). RN [32] RP VARIANT [LARGE SCALE ANALYSIS] THR-335. 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 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. In fibroblast, is required for CC EGF-stimulated phosphorylation of CREB1, which results in the CC subsequent transcriptional activation of several immediate-early genes. CC In response to mitogenic stimulation (EGF and PMA), phosphorylates and CC activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the CC cofactor CREBBP. Upon insulin-derived signal, acts indirectly on the CC transcription regulation of several genes by phosphorylating GSK3B at CC 'Ser-9' and inhibiting its activity. Phosphorylates RPS6 in response to CC serum or EGF via an mTOR-independent mechanism and promotes translation CC initiation by facilitating assembly of the pre-initiation complex. In CC response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for CC the EIF3 complex and stimulating cap-dependent translation. Is involved CC in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 CC at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR CC signaling, and mediates phosphorylation of RPTOR, which regulates CC mTORC1 activity and may promote rapamycin-sensitive signaling CC independently of the PI3K/AKT pathway. Mediates cell survival by CC phosphorylating the pro-apoptotic proteins BAD and DAPK1 and CC suppressing their pro-apoptotic function. Promotes the survival of CC hepatic stellate cells by phosphorylating CEBPB in response to the CC hepatotoxin carbon tetrachloride (CCl4). Mediates induction of CC hepatocyte prolifration by TGFA through phosphorylation of CEBPB (By CC similarity). Is involved in cell cycle regulation by phosphorylating CC the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 CC proteins and prevents its translocation to the nucleus and inhibition CC of G1 progression. Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 CC signaling pathway controls cell migration (PubMed:26158630). CC {ECO:0000250|UniProtKB:P18653, ECO:0000250|UniProtKB:Q63531, CC ECO:0000269|PubMed:10679322, ECO:0000269|PubMed:11684016, CC ECO:0000269|PubMed:12213813, ECO:0000269|PubMed:15117958, CC ECO:0000269|PubMed:15342917, ECO:0000269|PubMed:16213824, CC ECO:0000269|PubMed:16223362, ECO:0000269|PubMed:16763566, CC ECO:0000269|PubMed:17360704, ECO:0000269|PubMed:18722121, CC ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:9430688}. 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 -!- 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; CC -!- ACTIVITY REGULATION: Upon extracellular signal or mitogen stimulation, CC phosphorylated at Thr-573 in the C-terminal kinase domain (CTKD) by CC MAPK1/ERK2 and MAPK3/ERK1. The activated CTKD then autophosphorylates CC Ser-380, allowing binding of PDPK1, which in turn phosphorylates Ser- CC 221 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. {ECO:0000269|PubMed:15117958, CC ECO:0000269|PubMed:9430688}. CC -!- SUBUNIT: Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in CC quiescent cells. Transiently dissociates following mitogenic CC stimulation. Interacts with ETV1/ER81 and FGFR1. CC {ECO:0000269|PubMed:12213813, ECO:0000269|PubMed:12832467, CC ECO:0000269|PubMed:15117958, ECO:0000269|PubMed:15342917, CC ECO:0000269|PubMed:17965187}. CC -!- INTERACTION: CC O43823:AKAP8; NbExp=5; IntAct=EBI-963034, EBI-1237481; CC P46527:CDKN1B; NbExp=2; IntAct=EBI-963034, EBI-519280; CC P08238:HSP90AB1; NbExp=2; IntAct=EBI-963034, EBI-352572; CC P28482:MAPK1; NbExp=3; IntAct=EBI-963034, EBI-959949; CC Q14160:SCRIB; NbExp=3; IntAct=EBI-963034, EBI-357345; CC P50552:VASP; NbExp=4; IntAct=EBI-963034, EBI-748201; CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q15418-1; Sequence=Displayed; CC Name=2; CC IsoId=Q15418-2; Sequence=VSP_041380; CC Name=3; CC IsoId=Q15418-3; Sequence=VSP_041580; CC Name=4 {ECO:0000305}; CC IsoId=Q15418-4; Sequence=VSP_057469; CC -!- PTM: Activated by phosphorylation at Ser-221 by PDPK1. CC Autophosphorylated on Ser-380, as part of the activation process. May CC be phosphorylated at Thr-359 and Ser-363 by MAPK1/ERK2 and MAPK3/ERK1. CC {ECO:0000269|PubMed:9430688}. CC -!- PTM: N-terminal myristoylation results in an activated kinase in the CC absence of added growth factors. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr CC protein kinase family. S6 kinase subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/RPS6KA1ID43477ch1p36.html"; 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; L07597; AAC82497.1; -; mRNA. DR EMBL; AK292722; BAF85411.1; -; mRNA. DR EMBL; AK299007; BAH12926.1; -; mRNA. DR EMBL; AK315730; BAG38085.1; -; mRNA. DR EMBL; AL109743; CAC36348.1; -; Genomic_DNA. DR EMBL; AL627313; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471059; EAX07799.1; -; Genomic_DNA. DR EMBL; BC014966; AAH14966.1; -; mRNA. DR CCDS; CCDS284.1; -. [Q15418-1] DR CCDS; CCDS30649.1; -. [Q15418-2] DR CCDS; CCDS81286.1; -. [Q15418-4] DR PIR; I51901; I51901. DR RefSeq; NP_001006666.1; NM_001006665.1. [Q15418-2] DR RefSeq; NP_001317370.1; NM_001330441.1. [Q15418-4] DR RefSeq; NP_002944.2; NM_002953.3. [Q15418-1] DR PDB; 2WNT; X-ray; 2.40 A; A/B=413-719. DR PDB; 2Z7Q; X-ray; 2.00 A; A=33-353. DR PDB; 2Z7R; X-ray; 2.00 A; A=33-353. DR PDB; 2Z7S; X-ray; 2.10 A; A=33-353. DR PDB; 3RNY; X-ray; 2.70 A; A/B=411-735. DR PDB; 3TEI; X-ray; 2.40 A; B=712-735. DR PDB; 4H3P; X-ray; 2.30 A; B/E=712-735. DR PDB; 4NIF; X-ray; 2.15 A; A/D=411-735. DR PDB; 5CSF; X-ray; 2.40 A; C=683-735. DR PDB; 5CSI; X-ray; 2.13 A; C=689-735. DR PDB; 5CSJ; X-ray; 2.70 A; C=696-735. DR PDB; 5CSN; X-ray; 2.95 A; C=683-720. DR PDB; 5N7D; X-ray; 2.30 A; C=688-735. DR PDB; 5N7F; X-ray; 2.30 A; C=688-735. DR PDB; 5N7G; X-ray; 2.95 A; C=729-735. DR PDB; 5V61; X-ray; 2.20 A; I=713-729. DR PDB; 5V62; X-ray; 1.90 A; I=713-729. DR PDBsum; 2WNT; -. DR PDBsum; 2Z7Q; -. DR PDBsum; 2Z7R; -. DR PDBsum; 2Z7S; -. DR PDBsum; 3RNY; -. DR PDBsum; 3TEI; -. DR PDBsum; 4H3P; -. DR PDBsum; 4NIF; -. DR PDBsum; 5CSF; -. DR PDBsum; 5CSI; -. DR PDBsum; 5CSJ; -. DR PDBsum; 5CSN; -. DR PDBsum; 5N7D; -. DR PDBsum; 5N7F; -. DR PDBsum; 5N7G; -. DR PDBsum; 5V61; -. DR PDBsum; 5V62; -. DR SMR; Q15418; -. DR BioGrid; 112109; 115. DR DIP; DIP-29987N; -. DR ELM; Q15418; -. DR IntAct; Q15418; 40. DR MINT; Q15418; -. DR STRING; 9606.ENSP00000435412; -. DR BindingDB; Q15418; -. DR ChEMBL; CHEMBL2553; -. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB04751; Purvalanol A. DR DrugCentral; Q15418; -. DR GuidetoPHARMACOLOGY; 1527; -. DR iPTMnet; Q15418; -. DR PhosphoSitePlus; Q15418; -. DR BioMuta; RPS6KA1; -. DR DMDM; 20178306; -. DR UCD-2DPAGE; Q15418; -. DR EPD; Q15418; -. DR jPOST; Q15418; -. DR MassIVE; Q15418; -. DR MaxQB; Q15418; -. DR PaxDb; Q15418; -. DR PeptideAtlas; Q15418; -. DR PRIDE; Q15418; -. DR ProteomicsDB; 23324; -. DR ProteomicsDB; 60583; -. [Q15418-1] DR ProteomicsDB; 60584; -. [Q15418-2] DR ProteomicsDB; 60585; -. [Q15418-3] DR DNASU; 6195; -. DR Ensembl; ENST00000374168; ENSP00000363283; ENSG00000117676. [Q15418-1] DR Ensembl; ENST00000526792; ENSP00000431651; ENSG00000117676. [Q15418-3] DR Ensembl; ENST00000530003; ENSP00000432281; ENSG00000117676. [Q15418-4] DR Ensembl; ENST00000531382; ENSP00000435412; ENSG00000117676. [Q15418-2] DR Ensembl; ENST00000628081; ENSP00000487553; ENSG00000281877. [Q15418-4] DR Ensembl; ENST00000628256; ENSP00000487349; ENSG00000281877. [Q15418-2] DR Ensembl; ENST00000629832; ENSP00000486881; ENSG00000281877. [Q15418-1] DR Ensembl; ENST00000631108; ENSP00000487166; ENSG00000281877. [Q15418-3] DR GeneID; 6195; -. DR KEGG; hsa:6195; -. DR UCSC; uc001bmr.2; human. [Q15418-1] DR UCSC; uc057dso.1; human. DR CTD; 6195; -. DR DisGeNET; 6195; -. DR EuPathDB; HostDB:ENSG00000117676.13; -. DR GeneCards; RPS6KA1; -. DR HGNC; HGNC:10430; RPS6KA1. DR HPA; CAB003852; -. DR HPA; HPA007981; -. DR MIM; 601684; gene. DR neXtProt; NX_Q15418; -. DR OpenTargets; ENSG00000117676; -. DR PharmGKB; PA34845; -. DR eggNOG; KOG0598; Eukaryota. DR eggNOG; ENOG410XNPH; LUCA. DR GeneTree; ENSGT00940000159314; -. DR InParanoid; Q15418; -. DR KO; K04373; -. DR OMA; GGNWDTI; -. DR OrthoDB; 1132245at2759; -. DR PhylomeDB; Q15418; -. DR TreeFam; TF313438; -. DR BRENDA; 2.7.11.1; 2681. DR Reactome; R-HSA-198753; ERK/MAPK targets. DR Reactome; R-HSA-199920; CREB phosphorylation. DR Reactome; R-HSA-2559582; Senescence-Associated Secretory Phenotype (SASP). DR Reactome; R-HSA-437239; Recycling pathway of L1. DR Reactome; R-HSA-442742; CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling. DR Reactome; R-HSA-444257; RSK activation. DR Reactome; R-HSA-881907; Gastrin-CREB signalling pathway via PKC and MAPK. DR SABIO-RK; Q15418; -. DR SignaLink; Q15418; -. DR SIGNOR; Q15418; -. DR ChiTaRS; RPS6KA1; human. DR EvolutionaryTrace; Q15418; -. DR GeneWiki; RPS6KA1; -. DR GenomeRNAi; 6195; -. DR Pharos; Q15418; Tchem. DR PRO; PR:Q15418; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q15418; protein. DR Bgee; ENSG00000117676; Expressed in 190 organ(s), highest expression level in blood. DR ExpressionAtlas; Q15418; baseline and differential. DR Genevisible; Q15418; HS. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IDA:UniProtKB. DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0004712; F:protein serine/threonine/tyrosine 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:0072574; P:hepatocyte proliferation; ISS:UniProtKB. DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB. DR GO; GO:0045597; P:positive regulation of cell differentiation; TAS:UniProtKB. DR GO; GO:0030307; P:positive regulation of cell growth; TAS:UniProtKB. DR GO; GO:2000491; P:positive regulation of hepatic stellate cell activation; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL. DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central. DR GO; GO:0043620; P:regulation of DNA-templated transcription in response to stress; TAS:UniProtKB. DR GO; GO:0043555; P:regulation of translation in response to stress; TAS:UniProtKB. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR CDD; cd05582; STKc_RSK_N; 1. DR DisProt; DP01508; -. 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; IPR041906; RSK_N. DR InterPro; IPR008271; Ser/Thr_kinase_AS. 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; SSF56112; 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. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cell cycle; Cytoplasm; KW Kinase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus; KW Phosphoprotein; Polymorphism; Reference proteome; Repeat; KW Serine/threonine-protein kinase; Stress response; Transferase. FT CHAIN 1..735 FT /note="Ribosomal protein S6 kinase alpha-1" FT /id="PRO_0000086198" FT DOMAIN 62..321 FT /note="Protein kinase 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 322..391 FT /note="AGC-kinase C-terminal" FT DOMAIN 418..675 FT /note="Protein kinase 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT NP_BIND 68..76 FT /note="ATP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT NP_BIND 424..432 FT /note="ATP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT ACT_SITE 187 FT /note="Proton acceptor" FT /evidence="ECO:0000250" FT ACT_SITE 535 FT /note="Proton acceptor" FT /evidence="ECO:0000250" FT BINDING 94 FT /note="ATP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 447 FT /note="ATP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 54 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:19369195" FT MOD_RES 221 FT /note="Phosphoserine; by PDPK1" FT /evidence="ECO:0000305|PubMed:9430688" FT MOD_RES 307 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:19369195" FT MOD_RES 359 FT /note="Phosphothreonine" FT /evidence="ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:18691976, ECO:0000244|PubMed:19369195, FT ECO:0000244|PubMed:21406692, ECO:0000244|PubMed:23186163, FT ECO:0000269|PubMed:9430688" FT MOD_RES 363 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:18691976, ECO:0000244|PubMed:19369195, FT ECO:0000244|PubMed:21406692, ECO:0000244|PubMed:23186163, FT ECO:0000244|PubMed:24275569, ECO:0000269|PubMed:9430688" FT MOD_RES 369 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19369195, ECO:0000244|PubMed:23186163" FT MOD_RES 380 FT /note="Phosphoserine; by autocatalysis" FT /evidence="ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:18691976, ECO:0000244|PubMed:19369195, FT ECO:0000244|PubMed:20068231, ECO:0000244|PubMed:23186163, FT ECO:0000244|PubMed:24275569, ECO:0000269|PubMed:9430688" FT MOD_RES 573 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:9430688" FT MOD_RES 732 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:9430688" FT VAR_SEQ 1..92 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_041580" FT VAR_SEQ 1..36 FT /note="MPLAQLKEPWPLMELVPLDPENGQTSGEEAGLQPSK -> MEQDPKPPRLRL FT WALIPWLPRKQRPRISQTSLPVPGPGSGPQRDS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_041380" FT VAR_SEQ 1..35 FT /note="MPLAQLKEPWPLMELVPLDPENGQTSGEEAGLQPS -> MQTPADFPRVERD FT LVPCPR (in isoform 4)" FT /id="VSP_057469" FT VARIANT 335 FT /note="K -> T (in dbSNP:rs2229712)" FT /evidence="ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:8141249" FT /id="VAR_021864" FT CONFLICT 609 FT /note="A -> T (in Ref. 2; BAF85411)" FT /evidence="ECO:0000305" FT CONFLICT 619 FT /note="S -> G (in Ref. 2; BAF85411)" FT /evidence="ECO:0000305" FT HELIX 59..61 FT /evidence="ECO:0000244|PDB:2Z7Q" FT STRAND 62..71 FT /evidence="ECO:0000244|PDB:2Z7Q" FT STRAND 74..81 FT /evidence="ECO:0000244|PDB:2Z7Q" FT STRAND 83..86 FT /evidence="ECO:0000244|PDB:2Z7Q" FT STRAND 90..96 FT /evidence="ECO:0000244|PDB:2Z7Q" FT STRAND 127..133 FT /evidence="ECO:0000244|PDB:2Z7Q" FT STRAND 136..141 FT /evidence="ECO:0000244|PDB:2Z7Q" FT HELIX 149..156 FT /evidence="ECO:0000244|PDB:2Z7Q" FT HELIX 161..180 FT /evidence="ECO:0000244|PDB:2Z7Q" FT HELIX 190..192 FT /evidence="ECO:0000244|PDB:2Z7Q" FT STRAND 193..195 FT /evidence="ECO:0000244|PDB:2Z7Q" FT STRAND 197..199 FT /evidence="ECO:0000244|PDB:2Z7Q" FT STRAND 201..203 FT /evidence="ECO:0000244|PDB:2Z7Q" FT HELIX 226..228 FT /evidence="ECO:0000244|PDB:2Z7Q" FT HELIX 231..234 FT /evidence="ECO:0000244|PDB:2Z7Q" FT HELIX 241..257 FT /evidence="ECO:0000244|PDB:2Z7Q" FT HELIX 267..276 FT /evidence="ECO:0000244|PDB:2Z7Q" FT HELIX 287..296 FT /evidence="ECO:0000244|PDB:2Z7Q" FT TURN 301..303 FT /evidence="ECO:0000244|PDB:2Z7Q" FT STRAND 307..310 FT /evidence="ECO:0000244|PDB:2Z7Q" FT HELIX 312..316 FT /evidence="ECO:0000244|PDB:2Z7Q" FT HELIX 319..321 FT /evidence="ECO:0000244|PDB:2Z7Q" FT HELIX 326..330 FT /evidence="ECO:0000244|PDB:2Z7Q" FT STRAND 418..427 FT /evidence="ECO:0000244|PDB:4NIF" FT STRAND 430..437 FT /evidence="ECO:0000244|PDB:4NIF" FT TURN 438..441 FT /evidence="ECO:0000244|PDB:4NIF" FT STRAND 442..450 FT /evidence="ECO:0000244|PDB:4NIF" FT TURN 451..453 FT /evidence="ECO:0000244|PDB:4NIF" FT HELIX 457..466 FT /evidence="ECO:0000244|PDB:4NIF" FT STRAND 475..480 FT /evidence="ECO:0000244|PDB:4NIF" FT STRAND 482..490 FT /evidence="ECO:0000244|PDB:4NIF" FT HELIX 497..501 FT /evidence="ECO:0000244|PDB:4NIF" FT STRAND 503..505 FT /evidence="ECO:0000244|PDB:3RNY" FT HELIX 509..528 FT /evidence="ECO:0000244|PDB:4NIF" FT HELIX 538..540 FT /evidence="ECO:0000244|PDB:4NIF" FT STRAND 541..547 FT /evidence="ECO:0000244|PDB:4NIF" FT HELIX 550..552 FT /evidence="ECO:0000244|PDB:4NIF" FT STRAND 553..555 FT /evidence="ECO:0000244|PDB:4NIF" FT TURN 574..576 FT /evidence="ECO:0000244|PDB:2WNT" FT HELIX 583..609 FT /evidence="ECO:0000244|PDB:4NIF" FT HELIX 622..631 FT /evidence="ECO:0000244|PDB:4NIF" FT HELIX 639..642 FT /evidence="ECO:0000244|PDB:4NIF" FT HELIX 646..655 FT /evidence="ECO:0000244|PDB:4NIF" FT HELIX 660..662 FT /evidence="ECO:0000244|PDB:4NIF" FT HELIX 666..671 FT /evidence="ECO:0000244|PDB:4NIF" FT HELIX 673..676 FT /evidence="ECO:0000244|PDB:4NIF" FT HELIX 678..680 FT /evidence="ECO:0000244|PDB:4NIF" FT HELIX 691..706 FT /evidence="ECO:0000244|PDB:4NIF" FT HELIX 717..719 FT /evidence="ECO:0000244|PDB:5V62" FT HELIX 721..725 FT /evidence="ECO:0000244|PDB:5V62" FT STRAND 733..735 FT /evidence="ECO:0000244|PDB:5N7D" SQ SEQUENCE 735 AA; 82723 MW; 765731A4442A53DF CRC64; MPLAQLKEPW PLMELVPLDP ENGQTSGEEA GLQPSKDEGV LKEISITHHV KAGSEKADPS HFELLKVLGQ GSFGKVFLVR KVTRPDSGHL YAMKVLKKAT LKVRDRVRTK MERDILADVN HPFVVKLHYA FQTEGKLYLI LDFLRGGDLF TRLSKEVMFT EEDVKFYLAE LALGLDHLHS LGIIYRDLKP ENILLDEEGH IKLTDFGLSK EAIDHEKKAY SFCGTVEYMA PEVVNRQGHS HSADWWSYGV LMFEMLTGSL PFQGKDRKET MTLILKAKLG MPQFLSTEAQ SLLRALFKRN PANRLGSGPD GAEEIKRHVF YSTIDWNKLY RREIKPPFKP AVAQPDDTFY FDTEFTSRTP KDSPGIPPSA GAHQLFRGFS FVATGLMEDD GKPRAPQAPL HSVVQQLHGK NLVFSDGYVV KETIGVGSYS ECKRCVHKAT NMEYAVKVID KSKRDPSEEI EILLRYGQHP NIITLKDVYD DGKHVYLVTE LMRGGELLDK ILRQKFFSER EASFVLHTIG KTVEYLHSQG VVHRDLKPSN ILYVDESGNP ECLRICDFGF AKQLRAENGL LMTPCYTANF VAPEVLKRQG YDEGCDIWSL GILLYTMLAG YTPFANGPSD TPEEILTRIG SGKFTLSGGN WNTVSETAKD LVSKMLHVDP HQRLTAKQVL QHPWVTQKDK LPQSQLSHQD LQLVKGAMAA TYSALNSSKP TPQLKPIESS ILAQRRVRKL PSTTL //