ID KS6A1_HUMAN Reviewed; 735 AA. AC Q15418; A6NGG4; A8K9K7; B2RDY8; B7Z5J0; E9PRI4; Q5SVM5; Q5SVM8; AC Q5SVM9; Q96C05; Q9BQK2; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 16-APR-2002, sequence version 2. DT 20-JUN-2018, entry version 198. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT THR-335. RX PubMed=8141249; 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA 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., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA 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., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA 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., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA 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 RT project: 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, ENZYME 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- RT activated protein kinase (MAPK)-activated protein kinase-1a/p90rsk RT that are inducible 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 RP 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 RT ribosomal S6 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 RT extracellular signal-regulated kinase docking and RSK activity."; RL Mol. Cell. Biol. 23:4796-4804(2003). RN [12] RP FUNCTION, INTERACTION WITH FGFR1, ENZYME 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., RA Stachowiak M.K.; RT "90-kDa ribosomal S6 kinase is a direct target for the nuclear RT fibroblast growth factor receptor 1 (FGFR1): role in FGFR1 RT 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 RT tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 RT 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., RA Taunton J., 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 RT phosphorylation 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., RA Thibault P., 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 ENZYME 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 RP SER-380, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 RT the kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [22] RP REVIEW ON FUNCTION, AND REVIEW ON ENZYME 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 RP AND SER-380, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 RP BY 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., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation 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., RA Buerckstuemmer T., 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., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome 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 RP AND SER-380, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver 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., RA Yano S., Fukuoka J., Koizumi K., Saiki I., Sakurai H.; RT "Crucial roles of RSK in cell motility by catalysing serine RT phosphorylation of EphA2."; RL Nat. Commun. 6:7679-7679(2015). RN [31] RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 33-353 IN COMPLEX WITH RP 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 RT bound to three different ligands: Implications for the design of RSK1 RT specific 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., RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., RA Yuen S.T., Leung S.Y., Wooster R., 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 CC ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic CC and stress-induced activation of the transcription factors CREB1, CC ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and CC EIF4B phosphorylation, and mediates cellular proliferation, CC survival, and differentiation by modulating mTOR signaling and CC repressing pro-apoptotic function of BAD and DAPK1. In fibroblast, CC is required for EGF-stimulated phosphorylation of CREB1, which CC results in the subsequent transcriptional activation of several CC immediate-early genes. In response to mitogenic stimulation (EGF CC and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 CC transcription factors and the cofactor CREBBP. Upon insulin- CC derived signal, acts indirectly on the transcription regulation of CC several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting CC its activity. Phosphorylates RPS6 in response to serum or EGF via CC an mTOR-independent mechanism and promotes translation initiation CC by facilitating assembly of the pre-initiation complex. In CC response to insulin, phosphorylates EIF4B, enhancing EIF4B CC affinity for the EIF3 complex and stimulating cap-dependent CC translation. Is involved in the mTOR nutrient-sensing pathway by CC directly phosphorylating TSC2 at 'Ser-1798', which potently CC inhibits TSC2 ability to suppress mTOR signaling, and mediates CC phosphorylation of RPTOR, which regulates mTORC1 activity and may CC promote rapamycin-sensitive signaling independently of the CC PI3K/AKT pathway. Mediates cell survival by phosphorylating the CC pro-apoptotic proteins BAD and DAPK1 and suppressing their pro- CC apoptotic function. Promotes the survival of hepatic stellate CC cells by phosphorylating CEBPB in response to the hepatotoxin CC carbon tetrachloride (CCl4). Mediates induction of hepatocyte CC prolifration by TGFA through phosphorylation of CEBPB (By CC similarity). Is involved in cell cycle regulation by CC phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B CC association with 14-3-3 proteins and prevents its translocation to CC the nucleus and inhibition of G1 progression. Phosphorylates EPHA2 CC at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell CC migration (PubMed:26158630). {ECO:0000250|UniProtKB:P18653, CC ECO:0000250|UniProtKB:Q63531, ECO:0000269|PubMed:10679322, CC ECO:0000269|PubMed:11684016, ECO:0000269|PubMed:12213813, CC ECO:0000269|PubMed:15117958, ECO:0000269|PubMed:15342917, CC ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:16223362, CC ECO:0000269|PubMed:16763566, ECO:0000269|PubMed:17360704, CC ECO:0000269|PubMed:18722121, ECO:0000269|PubMed:26158630, CC ECO:0000269|PubMed:9430688}. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC -!- ENZYME REGULATION: Upon extracellular signal or mitogen CC stimulation, phosphorylated at Thr-573 in the C-terminal kinase CC domain (CTKD) by MAPK1/ERK2 and MAPK3/ERK1. The activated CTKD CC then autophosphorylates Ser-380, allowing binding of PDPK1, which CC in turn phosphorylates Ser-221 in the N-terminal kinase domain CC (NTDK) leading to the full activation of the protein and CC subsequent phosphorylation of the substrates by the NTKD. CC {ECO:0000269|PubMed:15117958, 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 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 Note=No experimental confirmation available.; 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. CC May be phosphorylated at Thr-359 and Ser-363 by MAPK1/ERK2 and CC MAPK3/ERK1. {ECO:0000269|PubMed:9430688}. CC -!- PTM: N-terminal myristoylation results in an activated kinase in CC the 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 CC and 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 UniGene; Hs.149957; -. 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 ProteinModelPortal; Q15418; -. DR SMR; Q15418; -. DR BioGrid; 112109; 76. DR DIP; DIP-29987N; -. DR ELM; Q15418; -. DR IntAct; Q15418; 33. DR MINT; Q15418; -. DR STRING; 9606.ENSP00000435412; -. DR BindingDB; Q15418; -. DR ChEMBL; CHEMBL2553; -. DR DrugBank; DB04751; Purvalanol A. DR GuidetoPHARMACOLOGY; 1527; -. DR iPTMnet; Q15418; -. DR PhosphoSitePlus; Q15418; -. DR BioMuta; RPS6KA1; -. DR DMDM; 20178306; -. DR UCD-2DPAGE; Q15418; -. DR EPD; Q15418; -. DR MaxQB; Q15418; -. DR PaxDb; Q15418; -. DR PeptideAtlas; Q15418; -. DR PRIDE; Q15418; -. DR ProteomicsDB; 60583; -. 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; ENSGT00920000148962; -. DR HOVERGEN; HBG108317; -. DR InParanoid; Q15418; -. DR KO; K04373; -. DR OMA; PWITQKD; -. DR OrthoDB; EOG091G05Z7; -. 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; CREB phosphorylation through the activation of Ras. 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 PRO; PR:Q15418; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; ENSG00000117676; -. DR CleanEx; HS_RPS6KA1; -. 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; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:HPA. 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:0016301; F:kinase activity; TAS:Reactome. 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: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: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 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; 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; KW Complete proteome; Cytoplasm; Kinase; Magnesium; Metal-binding; KW Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; KW Reference proteome; Repeat; Serine/threonine-protein kinase; KW Stress response; Transferase. FT CHAIN 1 735 Ribosomal protein S6 kinase alpha-1. FT /FTId=PRO_0000086198. FT DOMAIN 62 321 Protein kinase 1. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT DOMAIN 322 391 AGC-kinase C-terminal. FT DOMAIN 418 675 Protein kinase 2. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT NP_BIND 68 76 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT NP_BIND 424 432 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT ACT_SITE 187 187 Proton acceptor. {ECO:0000250}. FT ACT_SITE 535 535 Proton acceptor. {ECO:0000250}. FT BINDING 94 94 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT BINDING 447 447 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT MOD_RES 54 54 Phosphoserine. FT {ECO:0000244|PubMed:19369195}. FT MOD_RES 221 221 Phosphoserine; by PDPK1. FT {ECO:0000305|PubMed:9430688}. FT MOD_RES 307 307 Phosphoserine. FT {ECO:0000244|PubMed:19369195}. FT MOD_RES 359 359 Phosphothreonine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:18691976, FT ECO:0000244|PubMed:19369195, FT ECO:0000244|PubMed:21406692, FT ECO:0000244|PubMed:23186163, FT ECO:0000269|PubMed:9430688}. FT MOD_RES 363 363 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:18691976, FT ECO:0000244|PubMed:19369195, FT ECO:0000244|PubMed:21406692, FT ECO:0000244|PubMed:23186163, FT ECO:0000244|PubMed:24275569, FT ECO:0000269|PubMed:9430688}. FT MOD_RES 369 369 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19369195, FT ECO:0000244|PubMed:23186163}. FT MOD_RES 380 380 Phosphoserine; by autocatalysis. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:18691976, FT ECO:0000244|PubMed:19369195, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:23186163, FT ECO:0000244|PubMed:24275569, FT ECO:0000269|PubMed:9430688}. FT MOD_RES 573 573 Phosphothreonine. FT {ECO:0000269|PubMed:9430688}. FT MOD_RES 732 732 Phosphoserine. FT {ECO:0000269|PubMed:9430688}. FT VAR_SEQ 1 92 Missing (in isoform 3). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_041580. FT VAR_SEQ 1 36 MPLAQLKEPWPLMELVPLDPENGQTSGEEAGLQPSK -> M FT EQDPKPPRLRLWALIPWLPRKQRPRISQTSLPVPGPGSGPQ FT RDS (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_041380. FT VAR_SEQ 1 35 MPLAQLKEPWPLMELVPLDPENGQTSGEEAGLQPS -> MQ FT TPADFPRVERDLVPCPR (in isoform 4). FT /FTId=VSP_057469. FT VARIANT 335 335 K -> T (in dbSNP:rs2229712). FT {ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:8141249}. FT /FTId=VAR_021864. FT CONFLICT 609 609 A -> T (in Ref. 2; BAF85411). FT {ECO:0000305}. FT CONFLICT 619 619 S -> G (in Ref. 2; BAF85411). FT {ECO:0000305}. FT HELIX 59 61 {ECO:0000244|PDB:2Z7Q}. FT STRAND 62 71 {ECO:0000244|PDB:2Z7Q}. FT STRAND 74 81 {ECO:0000244|PDB:2Z7Q}. FT STRAND 83 86 {ECO:0000244|PDB:2Z7Q}. FT STRAND 90 96 {ECO:0000244|PDB:2Z7Q}. FT STRAND 127 133 {ECO:0000244|PDB:2Z7Q}. FT STRAND 136 141 {ECO:0000244|PDB:2Z7Q}. FT HELIX 149 156 {ECO:0000244|PDB:2Z7Q}. FT HELIX 161 180 {ECO:0000244|PDB:2Z7Q}. FT HELIX 190 192 {ECO:0000244|PDB:2Z7Q}. FT STRAND 193 195 {ECO:0000244|PDB:2Z7Q}. FT STRAND 197 199 {ECO:0000244|PDB:2Z7Q}. FT STRAND 201 203 {ECO:0000244|PDB:2Z7Q}. FT HELIX 226 228 {ECO:0000244|PDB:2Z7Q}. FT HELIX 231 234 {ECO:0000244|PDB:2Z7Q}. FT HELIX 241 257 {ECO:0000244|PDB:2Z7Q}. FT HELIX 267 276 {ECO:0000244|PDB:2Z7Q}. FT HELIX 287 296 {ECO:0000244|PDB:2Z7Q}. FT TURN 301 303 {ECO:0000244|PDB:2Z7Q}. FT STRAND 307 310 {ECO:0000244|PDB:2Z7Q}. FT HELIX 312 316 {ECO:0000244|PDB:2Z7Q}. FT HELIX 319 321 {ECO:0000244|PDB:2Z7Q}. FT HELIX 326 330 {ECO:0000244|PDB:2Z7Q}. FT STRAND 418 427 {ECO:0000244|PDB:4NIF}. FT STRAND 430 437 {ECO:0000244|PDB:4NIF}. FT TURN 438 441 {ECO:0000244|PDB:4NIF}. FT STRAND 442 450 {ECO:0000244|PDB:4NIF}. FT TURN 451 453 {ECO:0000244|PDB:4NIF}. FT HELIX 457 466 {ECO:0000244|PDB:4NIF}. FT STRAND 475 480 {ECO:0000244|PDB:4NIF}. FT STRAND 482 490 {ECO:0000244|PDB:4NIF}. FT HELIX 497 501 {ECO:0000244|PDB:4NIF}. FT STRAND 503 505 {ECO:0000244|PDB:3RNY}. FT HELIX 509 528 {ECO:0000244|PDB:4NIF}. FT HELIX 538 540 {ECO:0000244|PDB:4NIF}. FT STRAND 541 547 {ECO:0000244|PDB:4NIF}. FT HELIX 550 552 {ECO:0000244|PDB:4NIF}. FT STRAND 553 555 {ECO:0000244|PDB:4NIF}. FT TURN 574 576 {ECO:0000244|PDB:2WNT}. FT HELIX 583 609 {ECO:0000244|PDB:4NIF}. FT HELIX 622 631 {ECO:0000244|PDB:4NIF}. FT HELIX 639 642 {ECO:0000244|PDB:4NIF}. FT HELIX 646 655 {ECO:0000244|PDB:4NIF}. FT HELIX 660 662 {ECO:0000244|PDB:4NIF}. FT HELIX 666 671 {ECO:0000244|PDB:4NIF}. FT HELIX 673 676 {ECO:0000244|PDB:4NIF}. FT HELIX 678 680 {ECO:0000244|PDB:4NIF}. FT HELIX 691 706 {ECO:0000244|PDB:4NIF}. FT HELIX 717 719 {ECO:0000244|PDB:5V62}. FT HELIX 721 725 {ECO:0000244|PDB:5V62}. FT STRAND 733 735 {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 //