KS6A1_HUMAN
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 03-AUG-2022, entry version 223.
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 INTERACTION WITH KAPOSI'S SARCOMA-ASSOCIATED HERPESVIRUS/HHV-8 PROTEIN
RP ORF45 (MICROBIAL INFECTION), AND FUNCTION (MICROBIAL INFECTION).
RX PubMed=30842327; DOI=10.1128/jvi.02154-18;
RA Li X., Huang L., Xiao Y., Yao X., Long X., Zhu F., Kuang E.;
RT "Development of an ORF45-Derived Peptide To Inhibit the Sustained RSK
RT Activation and Lytic Replication of Kaposi's Sarcoma-Associated
RT Herpesvirus.";
RL J. Virol. 93:0-0(2019).
RN [32]
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 [33]
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 -!- FUNCTION: (Microbial infection) Promotes the late transcription and
CC translation of viral lytic genes during Kaposi's sarcoma-associated
CC herpesvirus/HHV-8 infection, when constitutively activated.
CC {ECO:0000269|PubMed:30842327}.
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 -!- SUBUNIT: (Microbial infection) Interacts with Kaposi's sarcoma-
CC associated herpesvirus/HHV-8 protein ORF45; this interaction allows
CC RPS6KA1 activation. {ECO:0000269|PubMed:30842327}.
CC -!- INTERACTION:
CC Q15418; O43823: AKAP8; NbExp=5; IntAct=EBI-963034, EBI-1237481;
CC Q15418; P46527: CDKN1B; NbExp=2; IntAct=EBI-963034, EBI-519280;
CC Q15418; P08238: HSP90AB1; NbExp=4; IntAct=EBI-963034, EBI-352572;
CC Q15418; P28482: MAPK1; NbExp=7; IntAct=EBI-963034, EBI-959949;
CC Q15418; P04271: S100B; NbExp=2; IntAct=EBI-963034, EBI-458391;
CC Q15418; Q14160: SCRIB; NbExp=3; IntAct=EBI-963034, EBI-357345;
CC Q15418; P50552: VASP; NbExp=4; IntAct=EBI-963034, EBI-748201;
CC Q15418; A1JU68: yopM; Xeno; NbExp=3; IntAct=EBI-963034, EBI-26365850;
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";
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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 PDB; 6TWY; X-ray; 2.30 A; C=725-735.
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 PDBsum; 6TWY; -.
DR AlphaFoldDB; Q15418; -.
DR SMR; Q15418; -.
DR BioGRID; 112109; 183.
DR DIP; DIP-29987N; -.
DR ELM; Q15418; -.
DR IntAct; Q15418; 65.
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 GlyGen; Q15418; 1 site, 1 O-linked glycan (1 site).
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 Antibodypedia; 2073; 1701 antibodies from 45 providers.
DR DNASU; 6195; -.
DR Ensembl; ENST00000374168.7; ENSP00000363283.2; ENSG00000117676.14. [Q15418-1]
DR Ensembl; ENST00000526792.5; ENSP00000431651.1; ENSG00000117676.14. [Q15418-3]
DR Ensembl; ENST00000530003.5; ENSP00000432281.1; ENSG00000117676.14. [Q15418-4]
DR Ensembl; ENST00000531382.5; ENSP00000435412.1; ENSG00000117676.14. [Q15418-2]
DR Ensembl; ENST00000628081.2; ENSP00000487553.1; ENSG00000281877.3. [Q15418-4]
DR Ensembl; ENST00000628256.2; ENSP00000487349.1; ENSG00000281877.3. [Q15418-2]
DR Ensembl; ENST00000629832.3; ENSP00000486881.1; ENSG00000281877.3. [Q15418-1]
DR Ensembl; ENST00000631108.2; ENSP00000487166.1; ENSG00000281877.3. [Q15418-3]
DR GeneID; 6195; -.
DR KEGG; hsa:6195; -.
DR MANE-Select; ENST00000374168.7; ENSP00000363283.2; NM_002953.4; NP_002944.2.
DR UCSC; uc001bmr.2; human. [Q15418-1]
DR UCSC; uc057dso.1; human.
DR CTD; 6195; -.
DR DisGeNET; 6195; -.
DR GeneCards; RPS6KA1; -.
DR HGNC; HGNC:10430; RPS6KA1.
DR HPA; ENSG00000117676; Low tissue specificity.
DR MIM; 601684; gene.
DR neXtProt; NX_Q15418; -.
DR OpenTargets; ENSG00000117676; -.
DR PharmGKB; PA34845; -.
DR VEuPathDB; HostDB:ENSG00000117676; -.
DR eggNOG; KOG0603; Eukaryota.
DR GeneTree; ENSGT00940000159314; -.
DR HOGENOM; CLU_000288_58_0_1; -.
DR InParanoid; Q15418; -.
DR OMA; ILEHSWV; -.
DR OrthoDB; 1132245at2759; -.
DR PhylomeDB; Q15418; -.
DR TreeFam; TF313438; -.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; Q15418; -.
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 BioGRID-ORCS; 6195; 26 hits in 1112 CRISPR screens.
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 blood and 101 other tissues.
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:0045202; C:synapse; IEA:GOC.
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:0106310; F:protein serine kinase activity; IEA:RHEA.
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:0007268; P:chemical synaptic transmission; TAS:Reactome.
DR GO; GO:0072574; P:hepatocyte proliferation; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
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:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
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:0045893; P:positive regulation of transcription, DNA-templated; 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 Host-virus interaction; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Nucleus; Phosphoprotein; 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 /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT DOMAIN 418..675
FT /note="Protein kinase 2"
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 68..76
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 94
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 424..432
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 447
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 54
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|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:0007744|PubMed:19369195"
FT MOD_RES 359
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:9430688,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 363
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:9430688,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 369
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163"
FT MOD_RES 380
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:9430688,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
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:0007829|PDB:2Z7Q"
FT STRAND 62..71
FT /evidence="ECO:0007829|PDB:2Z7Q"
FT STRAND 74..81
FT /evidence="ECO:0007829|PDB:2Z7Q"
FT STRAND 83..86
FT /evidence="ECO:0007829|PDB:2Z7Q"
FT STRAND 90..96
FT /evidence="ECO:0007829|PDB:2Z7Q"
FT STRAND 127..133
FT /evidence="ECO:0007829|PDB:2Z7Q"
FT STRAND 136..141
FT /evidence="ECO:0007829|PDB:2Z7Q"
FT HELIX 149..156
FT /evidence="ECO:0007829|PDB:2Z7Q"
FT HELIX 161..180
FT /evidence="ECO:0007829|PDB:2Z7Q"
FT HELIX 190..192
FT /evidence="ECO:0007829|PDB:2Z7Q"
FT STRAND 193..195
FT /evidence="ECO:0007829|PDB:2Z7Q"
FT STRAND 197..199
FT /evidence="ECO:0007829|PDB:2Z7Q"
FT STRAND 201..203
FT /evidence="ECO:0007829|PDB:2Z7Q"
FT HELIX 226..228
FT /evidence="ECO:0007829|PDB:2Z7Q"
FT HELIX 231..234
FT /evidence="ECO:0007829|PDB:2Z7Q"
FT HELIX 241..257
FT /evidence="ECO:0007829|PDB:2Z7Q"
FT HELIX 267..276
FT /evidence="ECO:0007829|PDB:2Z7Q"
FT HELIX 287..296
FT /evidence="ECO:0007829|PDB:2Z7Q"
FT TURN 301..303
FT /evidence="ECO:0007829|PDB:2Z7Q"
FT STRAND 307..310
FT /evidence="ECO:0007829|PDB:2Z7Q"
FT HELIX 312..316
FT /evidence="ECO:0007829|PDB:2Z7Q"
FT HELIX 319..321
FT /evidence="ECO:0007829|PDB:2Z7Q"
FT HELIX 326..330
FT /evidence="ECO:0007829|PDB:2Z7Q"
FT STRAND 418..427
FT /evidence="ECO:0007829|PDB:4NIF"
FT STRAND 430..437
FT /evidence="ECO:0007829|PDB:4NIF"
FT TURN 438..441
FT /evidence="ECO:0007829|PDB:4NIF"
FT STRAND 442..450
FT /evidence="ECO:0007829|PDB:4NIF"
FT TURN 451..453
FT /evidence="ECO:0007829|PDB:4NIF"
FT HELIX 457..466
FT /evidence="ECO:0007829|PDB:4NIF"
FT STRAND 475..480
FT /evidence="ECO:0007829|PDB:4NIF"
FT STRAND 482..490
FT /evidence="ECO:0007829|PDB:4NIF"
FT HELIX 497..501
FT /evidence="ECO:0007829|PDB:4NIF"
FT STRAND 503..505
FT /evidence="ECO:0007829|PDB:3RNY"
FT HELIX 509..528
FT /evidence="ECO:0007829|PDB:4NIF"
FT HELIX 538..540
FT /evidence="ECO:0007829|PDB:4NIF"
FT STRAND 541..547
FT /evidence="ECO:0007829|PDB:4NIF"
FT HELIX 550..552
FT /evidence="ECO:0007829|PDB:4NIF"
FT STRAND 553..555
FT /evidence="ECO:0007829|PDB:4NIF"
FT TURN 574..576
FT /evidence="ECO:0007829|PDB:2WNT"
FT HELIX 583..609
FT /evidence="ECO:0007829|PDB:4NIF"
FT HELIX 622..631
FT /evidence="ECO:0007829|PDB:4NIF"
FT HELIX 639..642
FT /evidence="ECO:0007829|PDB:4NIF"
FT HELIX 646..655
FT /evidence="ECO:0007829|PDB:4NIF"
FT HELIX 660..662
FT /evidence="ECO:0007829|PDB:4NIF"
FT HELIX 666..671
FT /evidence="ECO:0007829|PDB:4NIF"
FT HELIX 673..676
FT /evidence="ECO:0007829|PDB:4NIF"
FT HELIX 678..680
FT /evidence="ECO:0007829|PDB:4NIF"
FT HELIX 691..706
FT /evidence="ECO:0007829|PDB:4NIF"
FT HELIX 717..719
FT /evidence="ECO:0007829|PDB:5V62"
FT HELIX 721..725
FT /evidence="ECO:0007829|PDB:5V62"
FT STRAND 733..735
FT /evidence="ECO:0007829|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
