KS6A5_HUMAN
ID KS6A5_HUMAN Reviewed; 802 AA.
AC O75582; B7Z2Y5; O95316; Q96AF7;
DT 24-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 212.
DE RecName: Full=Ribosomal protein S6 kinase alpha-5;
DE Short=S6K-alpha-5;
DE EC=2.7.11.1;
DE AltName: Full=90 kDa ribosomal protein S6 kinase 5;
DE AltName: Full=Nuclear mitogen- and stress-activated protein kinase 1;
DE AltName: Full=RSK-like protein kinase;
DE Short=RSKL;
GN Name=RPS6KA5; Synonyms=MSK1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606 {ECO:0000312|EMBL:AAC69577.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ACTIVITY REGULATION,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF ASP-195 AND
RP ASP-565.
RC TISSUE=Pancreas {ECO:0000269|PubMed:9687510};
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 [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Placenta {ECO:0000269|PubMed:9873047};
RX PubMed=9873047; DOI=10.1074/jbc.274.2.1026;
RA New L., Zhao M., Li Y., Bassett W.W., Feng Y., Ludwig S., Padova F.D.,
RA Gram H., Han J.;
RT "Cloning and characterization of RLPK, a novel RSK-related protein
RT kinase.";
RL J. Biol. Chem. 274:1026-1032(1999).
RN [3] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND CHROMOSOMAL LOCATION.
RX PubMed=10702687; DOI=10.1159/000015441;
RA Jiang C., Yu L., Tu Q., Zhao Y., Zhang H., Zhao S.;
RT "Assignment of a member of the ribosomal protein S6 kinase family, RPS6KA5,
RT to human chromosome 14q31-q32.1 by radiation hybrid mapping.";
RL Cytogenet. Cell Genet. 87:261-262(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Caudate nucleus;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta {ECO:0000312|EMBL:AAH17187.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION.
RX PubMed=11909979; DOI=10.1128/mcb.22.8.2871-2881.2002;
RA Wiggin G.R., Soloaga A., Foster J.M., Murray-Tait V., Cohen P.,
RA Arthur J.S.;
RT "MSK1 and MSK2 are required for the mitogen- and stress-induced
RT phosphorylation of CREB and ATF1 in fibroblasts.";
RL Mol. Cell. Biol. 22:2871-2881(2002).
RN [8]
RP FUNCTION, AND INTERACTION WITH RELA.
RX PubMed=12628924; DOI=10.1093/emboj/cdg139;
RA Vermeulen L., De Wilde G., Van Damme P., Vanden Berghe W., Haegeman G.;
RT "Transcriptional activation of the NF-kappaB p65 subunit by mitogen- and
RT stress-activated protein kinase-1 (MSK1).";
RL EMBO J. 22:1313-1324(2003).
RN [9]
RP FUNCTION IN PHOSPHORYLATION OF HISTONE H3 AND HMGN1/HMG14.
RX PubMed=12773393; DOI=10.1093/emboj/cdg273;
RA Soloaga A., Thomson S., Wiggin G.R., Rampersaud N., Dyson M.H.,
RA Hazzalin C.A., Mahadevan L.C., Arthur J.S.;
RT "MSK2 and MSK1 mediate the mitogen- and stress-induced phosphorylation of
RT histone H3 and HMG-14.";
RL EMBO J. 22:2788-2797(2003).
RN [10]
RP FUNCTION IN PHOSPHORYLATION OF STAT3.
RX PubMed=12763138; DOI=10.1016/s0301-472x(03)00045-6;
RA Wierenga A.T., Vogelzang I., Eggen B.J., Vellenga E.;
RT "Erythropoietin-induced serine 727 phosphorylation of STAT3 in erythroid
RT cells is mediated by a MEK-, ERK-, and MSK1-dependent pathway.";
RL Exp. Hematol. 31:398-405(2003).
RN [11]
RP FUNCTION IN PHOSPHORYLATION OF ETV1/ER81, AND INTERACTION WITH CREBBP AND
RP EP300.
RX PubMed=12569367; DOI=10.1038/sj.onc.1206185;
RA Janknecht R.;
RT "Regulation of the ER81 transcription factor and its coactivators by
RT mitogen- and stress-activated protein kinase 1 (MSK1).";
RL Oncogene 22:746-755(2003).
RN [12]
RP FUNCTION IN PHOSPHORYLATION OF HISTONE H2A.
RX PubMed=15010469; DOI=10.1074/jbc.m400099200;
RA Zhang Y., Griffin K., Mondal N., Parvin J.D.;
RT "Phosphorylation of histone H2A inhibits transcription on chromatin
RT templates.";
RL J. Biol. Chem. 279:21866-21872(2004).
RN [13]
RP ACTIVITY REGULATION, PHOSPHORYLATION AT SER-212; SER-360; SER-376; SER-381;
RP THR-581; SER-750; SER-752 AND SER-758, AND MUTAGENESIS OF SER-212; SER-360;
RP SER-376 AND THR-581.
RX PubMed=15568999; DOI=10.1042/bj20041501;
RA McCoy C.E., Campbell D.G., Deak M., Bloomberg G.B., Arthur J.S.C.;
RT "MSK1 activity is controlled by multiple phosphorylation sites.";
RL Biochem. J. 387:507-517(2005).
RN [14]
RP PHOSPHORYLATION AT SER-647; SER-657; SER-695 AND THR-700, AND MUTAGENESIS
RP OF THR-700.
RX PubMed=17117922; DOI=10.1042/bj20061183;
RA McCoy C.E., Macdonald A., Morrice N.A., Campbell D.G., Deak M., Toth R.,
RA McIlrath J., Arthur J.S.;
RT "Identification of novel phosphorylation sites in MSK1 by precursor ion
RT scanning MS.";
RL Biochem. J. 402:491-501(2007).
RN [15]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18511904; DOI=10.1038/emboj.2008.95;
RA Beck I.M., Vanden Berghe W., Vermeulen L., Bougarne N., Vander Cruyssen B.,
RA Haegeman G., De Bosscher K.;
RT "Altered subcellular distribution of MSK1 induced by glucocorticoids
RT contributes to NF-kappaB inhibition.";
RL EMBO J. 27:1682-1693(2008).
RN [16]
RP REVIEW ON FUNCTION.
RX PubMed=18508628; DOI=10.2741/3122;
RA Arthur J.S.;
RT "MSK activation and physiological roles.";
RL Front. Biosci. 13:5866-5879(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-376, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [18]
RP REVIEW ON FUNCTION.
RX PubMed=19464896; DOI=10.1016/j.tibs.2009.02.007;
RA Vermeulen L., Vanden Berghe W., Beck I.M., De Bosscher K., Haegeman G.;
RT "The versatile role of MSKs in transcriptional regulation.";
RL Trends Biochem. Sci. 34:311-318(2009).
RN [19]
RP UBIQUITINATION.
RX PubMed=20596523; DOI=10.1371/journal.pone.0011332;
RA Del Rincon S.V., Rogers J., Widschwendter M., Sun D., Sieburg H.B.,
RA Spruck C.;
RT "Development and validation of a method for profiling post-translational
RT modification activities using protein microarrays.";
RL PLoS ONE 5:E11332-E11332(2010).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-376 AND SER-381, AND
RP IDENTIFICATION 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., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [21]
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 [22]
RP FUNCTION IN PHOSPHORYLATION OF TRIM7.
RX PubMed=25851810; DOI=10.1038/ncomms7782;
RA Chakraborty A., Diefenbacher M.E., Mylona A., Kassel O., Behrens A.;
RT "The E3 ubiquitin ligase Trim7 mediates c-Jun/AP-1 activation by Ras
RT signalling.";
RL Nat. Commun. 6:6782-6782(2015).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 2-348.
RX PubMed=15274926; DOI=10.1016/j.str.2004.02.040;
RA Smith K.J., Carter P.S., Bridges A., Horrocks P., Lewis C., Pettman G.,
RA Clarke A., Brown M., Hughes J., Wilkinson M., Bax B., Reith A.;
RT "The structure of MSK1 reveals a novel autoinhibitory conformation for a
RT dual kinase protein.";
RL Structure 12:1067-1077(2004).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 414-738.
RX PubMed=20382163; DOI=10.1016/j.jmb.2010.03.064;
RA Malakhova M., D'Angelo I., Kim H.G., Kurinov I., Bode A.M., Dong Z.;
RT "The crystal structure of the active form of the C-terminal kinase domain
RT of mitogen- and stress-activated protein kinase 1.";
RL J. Mol. Biol. 399:41-52(2010).
RN [25]
RP VARIANTS [LARGE SCALE ANALYSIS] ASN-554; LEU-574 AND CYS-599.
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 is required for the
CC mitogen or stress-induced phosphorylation of the transcription factors
CC CREB1 and ATF1 and for the regulation of the transcription factors
CC RELA, STAT3 and ETV1/ER81, and that contributes to gene activation by
CC histone phosphorylation and functions in the regulation of inflammatory
CC genes (PubMed:11909979, PubMed:12569367, PubMed:12763138,
CC PubMed:9687510, PubMed:18511904, PubMed:9873047). Phosphorylates CREB1
CC and ATF1 in response to mitogenic or stress stimuli such as UV-C
CC irradiation, epidermal growth factor (EGF) and anisomycin
CC (PubMed:11909979, PubMed:9873047). Plays an essential role in the
CC control of RELA transcriptional activity in response to TNF and upon
CC glucocorticoid, associates in the cytoplasm with the glucocorticoid
CC receptor NR3C1 and contributes to RELA inhibition and repression of
CC inflammatory gene expression (PubMed:12628924, PubMed:18511904). In
CC skeletal myoblasts is required for phosphorylation of RELA at 'Ser-276'
CC during oxidative stress (PubMed:12628924). In erythropoietin-stimulated
CC cells, is necessary for the 'Ser-727' phosphorylation of STAT3 and
CC regulation of its transcriptional potential (PubMed:12763138).
CC Phosphorylates ETV1/ER81 at 'Ser-191' and 'Ser-216', and thereby
CC regulates its ability to stimulate transcription, which may be
CC important during development and breast tumor formation
CC (PubMed:12569367). Directly represses transcription via phosphorylation
CC of 'Ser-1' of histone H2A (PubMed:15010469). Phosphorylates 'Ser-10' of
CC histone H3 in response to mitogenics, stress stimuli and EGF, which
CC results in the transcriptional activation of several immediate early
CC genes, including proto-oncogenes c-fos/FOS and c-jun/JUN
CC (PubMed:12773393). May also phosphorylate 'Ser-28' of histone H3
CC (PubMed:12773393). Mediates the mitogen- and stress-induced
CC phosphorylation of high mobility group protein 1 (HMGN1/HMG14)
CC (PubMed:12773393). In lipopolysaccharide-stimulated primary
CC macrophages, acts downstream of the Toll-like receptor TLR4 to limit
CC the production of pro-inflammatory cytokines (By similarity). Functions
CC probably by inducing transcription of the MAP kinase phosphatase DUSP1
CC and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and
CC ATF1 transcription factors (By similarity). Plays a role in neuronal
CC cell death by mediating the downstream effects of excitotoxic injury
CC (By similarity). Phosphorylates TRIM7 at 'Ser-107' in response to
CC growth factor signaling via the MEK/ERK pathway, thereby stimulating
CC its ubiquitin ligase activity (PubMed:25851810).
CC {ECO:0000250|UniProtKB:Q8C050, ECO:0000269|PubMed:11909979,
CC ECO:0000269|PubMed:12569367, ECO:0000269|PubMed:12628924,
CC ECO:0000269|PubMed:12763138, ECO:0000269|PubMed:12773393,
CC ECO:0000269|PubMed:15010469, ECO:0000269|PubMed:18511904,
CC ECO:0000269|PubMed:25851810, ECO:0000269|PubMed:9687510,
CC ECO:0000269|PubMed:9873047}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:12628924, ECO:0000269|PubMed:9687510,
CC ECO:0000269|PubMed:9873047};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:12628924,
CC ECO:0000269|PubMed:9687510, ECO:0000269|PubMed:9873047};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:12628924, ECO:0000269|PubMed:9687510,
CC ECO:0000269|PubMed:9873047};
CC -!- ACTIVITY REGULATION: Activated by phosphorylation at Ser-360, Thr-581
CC and Thr-700 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha, and by
CC further autophosphorylation of Ser-212, Ser-376 and Ser-381 by the
CC activated C-terminal kinase domain. The active N-terminal kinase domain
CC finally phosphorylates downstream substrates, as well as Ser-750, Ser-
CC 752 and Ser-758 in its own C-terminal region.
CC {ECO:0000269|PubMed:15568999, ECO:0000269|PubMed:9687510}.
CC -!- SUBUNIT: Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in
CC quiescent cells which transiently dissociates following mitogenic
CC stimulation. Also associates with MAPK14/p38-alpha. Activated RPS6KA5
CC associates with and phosphorylates the NF-kappa-B p65 subunit RELA.
CC Interacts with CREBBP and EP300. {ECO:0000269|PubMed:12569367,
CC ECO:0000269|PubMed:12628924}.
CC -!- INTERACTION:
CC O75582; Q9UI47-2: CTNNA3; NbExp=3; IntAct=EBI-73869, EBI-11962928;
CC O75582; Q9Y4C1: KDM3A; NbExp=3; IntAct=EBI-73869, EBI-2515339;
CC O75582; Q9NYL2: MAP3K20; NbExp=4; IntAct=EBI-73869, EBI-602273;
CC O75582-1; Q9Y4C1: KDM3A; NbExp=3; IntAct=EBI-16135973, EBI-2515339;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Predominantly nuclear.
CC Exported into cytoplasm in response to glucocorticoid.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O75582-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75582-2; Sequence=VSP_041837, VSP_041838;
CC Name=3;
CC IsoId=O75582-3; Sequence=VSP_057410;
CC -!- TISSUE SPECIFICITY: Widely expressed with high levels in heart, brain
CC and placenta. Less abundant in lung, kidney and liver.
CC {ECO:0000269|PubMed:9687510, ECO:0000269|PubMed:9873047}.
CC -!- PTM: Ser-376 and Thr-581 phosphorylation is required for kinase
CC activity. Ser-376 and Ser-212 are autophosphorylated by the C-terminal
CC kinase domain, and their phosphorylation is essential for the catalytic
CC activity of the N-terminal kinase domain. Phosphorylated at Ser-360,
CC Thr-581 and Thr-700 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha.
CC Autophosphorylated at Ser-750, Ser-752 and Ser-758 by the N-terminal
CC kinase domain. {ECO:0000269|PubMed:15568999,
CC ECO:0000269|PubMed:17117922}.
CC -!- PTM: Ubiquitinated. {ECO:0000269|PubMed:20596523}.
CC -!- MISCELLANEOUS: Enzyme activity requires the presence of both kinase
CC domains. {ECO:0000269|PubMed:9687510}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. S6 kinase subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC69577.1; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF074393; AAC31171.1; -; mRNA.
DR EMBL; AF080000; AAD23915.1; -; mRNA.
DR EMBL; AF090421; AAC69577.1; ALT_FRAME; mRNA.
DR EMBL; AK295266; BAH12021.1; -; mRNA.
DR EMBL; AL121784; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL133454; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL159191; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC017187; AAH17187.1; -; mRNA.
DR CCDS; CCDS45149.1; -. [O75582-2]
DR CCDS; CCDS81839.1; -. [O75582-3]
DR CCDS; CCDS9893.1; -. [O75582-1]
DR PIR; T13149; T13149.
DR RefSeq; NP_001309164.1; NM_001322235.1. [O75582-3]
DR RefSeq; NP_001309166.1; NM_001322237.1. [O75582-3]
DR RefSeq; NP_004746.2; NM_004755.3. [O75582-1]
DR RefSeq; NP_872198.1; NM_182398.2. [O75582-2]
DR PDB; 1VZO; X-ray; 1.80 A; A=2-348.
DR PDB; 3KN5; X-ray; 2.40 A; A/B=414-738.
DR PDB; 3KN6; X-ray; 2.00 A; A/B=414-738.
DR PDBsum; 1VZO; -.
DR PDBsum; 3KN5; -.
DR PDBsum; 3KN6; -.
DR AlphaFoldDB; O75582; -.
DR SMR; O75582; -.
DR BioGRID; 114676; 88.
DR DIP; DIP-30894N; -.
DR ELM; O75582; -.
DR IntAct; O75582; 86.
DR MINT; O75582; -.
DR STRING; 9606.ENSP00000479667; -.
DR BindingDB; O75582; -.
DR ChEMBL; CHEMBL4237; -.
DR DrugCentral; O75582; -.
DR GuidetoPHARMACOLOGY; 1523; -.
DR GlyGen; O75582; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O75582; -.
DR PhosphoSitePlus; O75582; -.
DR BioMuta; RPS6KA5; -.
DR EPD; O75582; -.
DR jPOST; O75582; -.
DR MassIVE; O75582; -.
DR MaxQB; O75582; -.
DR PaxDb; O75582; -.
DR PeptideAtlas; O75582; -.
DR PRIDE; O75582; -.
DR ProteomicsDB; 50098; -. [O75582-1]
DR ProteomicsDB; 50099; -. [O75582-2]
DR ProteomicsDB; 6477; -.
DR Antibodypedia; 83; 973 antibodies from 42 providers.
DR DNASU; 9252; -.
DR Ensembl; ENST00000418736.6; ENSP00000402787.2; ENSG00000100784.12. [O75582-2]
DR Ensembl; ENST00000536315.6; ENSP00000442803.2; ENSG00000100784.12. [O75582-3]
DR Ensembl; ENST00000614987.5; ENSP00000479667.1; ENSG00000100784.12. [O75582-1]
DR GeneID; 9252; -.
DR KEGG; hsa:9252; -.
DR MANE-Select; ENST00000614987.5; ENSP00000479667.1; NM_004755.4; NP_004746.2.
DR UCSC; uc001xys.4; human. [O75582-1]
DR UCSC; uc010twi.3; human.
DR CTD; 9252; -.
DR DisGeNET; 9252; -.
DR GeneCards; RPS6KA5; -.
DR HGNC; HGNC:10434; RPS6KA5.
DR HPA; ENSG00000100784; Low tissue specificity.
DR MIM; 603607; gene.
DR neXtProt; NX_O75582; -.
DR OpenTargets; ENSG00000100784; -.
DR PharmGKB; PA34849; -.
DR VEuPathDB; HostDB:ENSG00000100784; -.
DR eggNOG; KOG0603; Eukaryota.
DR GeneTree; ENSGT00940000156886; -.
DR InParanoid; O75582; -.
DR OMA; IMQRICR; -.
DR OrthoDB; 181575at2759; -.
DR PhylomeDB; O75582; -.
DR TreeFam; TF313438; -.
DR PathwayCommons; O75582; -.
DR Reactome; R-HSA-198753; ERK/MAPK targets.
DR Reactome; R-HSA-199920; CREB phosphorylation.
DR Reactome; R-HSA-375165; NCAM signaling for neurite out-growth.
DR Reactome; R-HSA-437239; Recycling pathway of L1.
DR Reactome; R-HSA-5621575; CD209 (DC-SIGN) signaling.
DR SABIO-RK; O75582; -.
DR SignaLink; O75582; -.
DR SIGNOR; O75582; -.
DR BioGRID-ORCS; 9252; 8 hits in 1108 CRISPR screens.
DR ChiTaRS; RPS6KA5; human.
DR EvolutionaryTrace; O75582; -.
DR GeneWiki; RPS6KA5; -.
DR GenomeRNAi; 9252; -.
DR Pharos; O75582; Tchem.
DR PRO; PR:O75582; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; O75582; protein.
DR Bgee; ENSG00000100784; Expressed in secondary oocyte and 204 other tissues.
DR ExpressionAtlas; O75582; baseline and differential.
DR Genevisible; O75582; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0044024; F:histone kinase activity (H2A-S1 specific); IDA:UniProtKB.
DR GO; GO:0035175; F:histone kinase activity (H3-S10 specific); IMP:UniProtKB.
DR GO; GO:0044022; F:histone kinase activity (H3-S28 specific); IMP: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:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0016572; P:histone phosphorylation; IDA:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0070498; P:interleukin-1-mediated signaling pathway; IMP:BHF-UCL.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0001818; P:negative regulation of cytokine production; TAS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0032793; P:positive regulation of CREB transcription factor activity; TAS:UniProtKB.
DR GO; GO:0035066; P:positive regulation of histone acetylation; IMP:BHF-UCL.
DR GO; GO:0033129; P:positive regulation of histone phosphorylation; IMP:BHF-UCL.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0043687; P:post-translational protein modification; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB.
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; Cytoplasm;
KW Inflammatory response; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Stress response; Transferase;
KW Ubl conjugation.
FT CHAIN 1..802
FT /note="Ribosomal protein S6 kinase alpha-5"
FT /id="PRO_0000086207"
FT DOMAIN 49..318
FT /note="Protein kinase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 319..387
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT DOMAIN 426..687
FT /note="Protein kinase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 741..802
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 752..802
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 177
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 544
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 55..63
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 81
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 432..440
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 455
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 212
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15568999"
FT MOD_RES 360
FT /note="Phosphoserine; by MAPK1, MAPK3 and MAPK14"
FT /evidence="ECO:0000269|PubMed:15568999"
FT MOD_RES 376
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15568999,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231"
FT MOD_RES 381
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15568999,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 581
FT /note="Phosphothreonine; by MAPK1, MAPK3 and MAPK14"
FT /evidence="ECO:0000269|PubMed:15568999"
FT MOD_RES 647
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17117922"
FT MOD_RES 657
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17117922"
FT MOD_RES 691
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8C050"
FT MOD_RES 695
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17117922"
FT MOD_RES 700
FT /note="Phosphothreonine; by MAPK1, MAPK3 and MAPK14"
FT /evidence="ECO:0000269|PubMed:17117922"
FT MOD_RES 750
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15568999"
FT MOD_RES 752
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15568999"
FT MOD_RES 758
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15568999"
FT MOD_RES 798
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8C050"
FT VAR_SEQ 1..79
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057410"
FT VAR_SEQ 549
FT /note="N -> V (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_041837"
FT VAR_SEQ 550..802
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_041838"
FT VARIANT 190
FT /note="H -> R (in dbSNP:rs34699345)"
FT /id="VAR_051634"
FT VARIANT 554
FT /note="D -> N (in dbSNP:rs55911249)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040634"
FT VARIANT 574
FT /note="P -> L (in dbSNP:rs34604933)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040635"
FT VARIANT 599
FT /note="Y -> C (in dbSNP:rs55968863)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040636"
FT MUTAGEN 195
FT /note="D->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:9687510"
FT MUTAGEN 212
FT /note="S->A: Inactivates the N-terminal kinase domain."
FT /evidence="ECO:0000269|PubMed:15568999"
FT MUTAGEN 360
FT /note="S->A: Decreases kinase activity by 60% in response
FT to PMA and UV-C."
FT /evidence="ECO:0000269|PubMed:15568999"
FT MUTAGEN 376
FT /note="S->A: Loss of kinase activity, and decreases the
FT phosphorylation of S-360 and T-581."
FT /evidence="ECO:0000269|PubMed:15568999"
FT MUTAGEN 565
FT /note="D->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:9687510"
FT MUTAGEN 581
FT /note="T->A: Loss of kinase activity, and blocks
FT phosphorylation of S-212; S-376 and S-381 in response to
FT PMA and UV-C."
FT /evidence="ECO:0000269|PubMed:15568999"
FT MUTAGEN 700
FT /note="T->A,D: Strongly reduces phosphorylation of T-581 in
FT response to PMA and UV-C."
FT /evidence="ECO:0000269|PubMed:17117922"
FT CONFLICT 452..453
FT /note="FA -> LQ (in Ref. 3; AAC69577)"
FT /evidence="ECO:0000305"
FT CONFLICT 532
FT /note="V -> L (in Ref. 3; AAC69577)"
FT /evidence="ECO:0000305"
FT CONFLICT 538
FT /note="V -> L (in Ref. 3; AAC69577)"
FT /evidence="ECO:0000305"
FT CONFLICT 757..758
FT /note="SS -> RG (in Ref. 3; AAC69577)"
FT /evidence="ECO:0000305"
FT STRAND 26..31
FT /evidence="ECO:0007829|PDB:1VZO"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:1VZO"
FT STRAND 49..57
FT /evidence="ECO:0007829|PDB:1VZO"
FT TURN 58..60
FT /evidence="ECO:0007829|PDB:1VZO"
FT STRAND 61..68
FT /evidence="ECO:0007829|PDB:1VZO"
FT TURN 72..75
FT /evidence="ECO:0007829|PDB:1VZO"
FT STRAND 77..94
FT /evidence="ECO:0007829|PDB:1VZO"
FT HELIX 95..97
FT /evidence="ECO:0007829|PDB:1VZO"
FT HELIX 101..109
FT /evidence="ECO:0007829|PDB:1VZO"
FT STRAND 117..123
FT /evidence="ECO:0007829|PDB:1VZO"
FT STRAND 126..131
FT /evidence="ECO:0007829|PDB:1VZO"
FT HELIX 139..146
FT /evidence="ECO:0007829|PDB:1VZO"
FT HELIX 151..170
FT /evidence="ECO:0007829|PDB:1VZO"
FT HELIX 180..182
FT /evidence="ECO:0007829|PDB:1VZO"
FT STRAND 183..185
FT /evidence="ECO:0007829|PDB:1VZO"
FT STRAND 191..194
FT /evidence="ECO:0007829|PDB:1VZO"
FT STRAND 196..201
FT /evidence="ECO:0007829|PDB:1VZO"
FT HELIX 204..210
FT /evidence="ECO:0007829|PDB:1VZO"
FT HELIX 212..214
FT /evidence="ECO:0007829|PDB:1VZO"
FT HELIX 222..225
FT /evidence="ECO:0007829|PDB:1VZO"
FT HELIX 235..250
FT /evidence="ECO:0007829|PDB:1VZO"
FT HELIX 264..273
FT /evidence="ECO:0007829|PDB:1VZO"
FT HELIX 284..293
FT /evidence="ECO:0007829|PDB:1VZO"
FT HELIX 298..300
FT /evidence="ECO:0007829|PDB:1VZO"
FT TURN 306..308
FT /evidence="ECO:0007829|PDB:1VZO"
FT HELIX 309..313
FT /evidence="ECO:0007829|PDB:1VZO"
FT HELIX 316..318
FT /evidence="ECO:0007829|PDB:1VZO"
FT HELIX 323..327
FT /evidence="ECO:0007829|PDB:1VZO"
FT HELIX 418..422
FT /evidence="ECO:0007829|PDB:3KN6"
FT STRAND 423..425
FT /evidence="ECO:0007829|PDB:3KN6"
FT STRAND 432..435
FT /evidence="ECO:0007829|PDB:3KN6"
FT STRAND 438..445
FT /evidence="ECO:0007829|PDB:3KN6"
FT TURN 446..448
FT /evidence="ECO:0007829|PDB:3KN6"
FT STRAND 451..458
FT /evidence="ECO:0007829|PDB:3KN6"
FT HELIX 459..461
FT /evidence="ECO:0007829|PDB:3KN6"
FT HELIX 462..474
FT /evidence="ECO:0007829|PDB:3KN6"
FT TURN 475..477
FT /evidence="ECO:0007829|PDB:3KN6"
FT STRAND 484..489
FT /evidence="ECO:0007829|PDB:3KN6"
FT STRAND 491..498
FT /evidence="ECO:0007829|PDB:3KN6"
FT HELIX 506..512
FT /evidence="ECO:0007829|PDB:3KN6"
FT HELIX 518..537
FT /evidence="ECO:0007829|PDB:3KN6"
FT HELIX 547..549
FT /evidence="ECO:0007829|PDB:3KN6"
FT STRAND 550..553
FT /evidence="ECO:0007829|PDB:3KN6"
FT STRAND 560..563
FT /evidence="ECO:0007829|PDB:3KN6"
FT HELIX 602..617
FT /evidence="ECO:0007829|PDB:3KN6"
FT HELIX 634..641
FT /evidence="ECO:0007829|PDB:3KN6"
FT TURN 642..644
FT /evidence="ECO:0007829|PDB:3KN6"
FT HELIX 651..654
FT /evidence="ECO:0007829|PDB:3KN6"
FT HELIX 658..668
FT /evidence="ECO:0007829|PDB:3KN6"
FT TURN 672..674
FT /evidence="ECO:0007829|PDB:3KN6"
FT TURN 678..680
FT /evidence="ECO:0007829|PDB:3KN6"
FT HELIX 685..687
FT /evidence="ECO:0007829|PDB:3KN6"
FT HELIX 700..728
FT /evidence="ECO:0007829|PDB:3KN6"
SQ SEQUENCE 802 AA; 89865 MW; 76C27D0F6639BFA4 CRC64;
MEEEGGSSGG AAGTSADGGD GGEQLLTVKH ELRTANLTGH AEKVGIENFE LLKVLGTGAY
GKVFLVRKIS GHDTGKLYAM KVLKKATIVQ KAKTTEHTRT ERQVLEHIRQ SPFLVTLHYA
FQTETKLHLI LDYINGGELF THLSQRERFT EHEVQIYVGE IVLALEHLHK LGIIYRDIKL
ENILLDSNGH VVLTDFGLSK EFVADETERA YSFCGTIEYM APDIVRGGDS GHDKAVDWWS
LGVLMYELLT GASPFTVDGE KNSQAEISRR ILKSEPPYPQ EMSALAKDLI QRLLMKDPKK
RLGCGPRDAD EIKEHLFFQK INWDDLAAKK VPAPFKPVIR DELDVSNFAE EFTEMDPTYS
PAALPQSSEK LFQGYSFVAP SILFKRNAAV IDPLQFHMGV ERPGVTNVAR SAMMKDSPFY
QHYDLDLKDK PLGEGSFSIC RKCVHKKSNQ AFAVKIISKR MEANTQKEIT ALKLCEGHPN
IVKLHEVFHD QLHTFLVMEL LNGGELFERI KKKKHFSETE ASYIMRKLVS AVSHMHDVGV
VHRDLKPENL LFTDENDNLE IKIIDFGFAR LKPPDNQPLK TPCFTLHYAA PELLNQNGYD
ESCDLWSLGV ILYTMLSGQV PFQSHDRSLT CTSAVEIMKK IKKGDFSFEG EAWKNVSQEA
KDLIQGLLTV DPNKRLKMSG LRYNEWLQDG SQLSSNPLMT PDILGSSGAA VHTCVKATFH
AFNKYKREGF CLQNVDKAPL AKRRKMKKTS TSTETRSSSS ESSHSSSSHS HGKTTPTKTL
QPSNPADSNN PETLFQFSDS VA
