TAOK1_HUMAN
ID TAOK1_HUMAN Reviewed; 1001 AA.
AC Q7L7X3; A2RUT8; B7ZLV6; Q96L75; Q9H2K7; Q9H7S5; Q9P2I6;
DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Serine/threonine-protein kinase TAO1;
DE EC=2.7.11.1;
DE AltName: Full=Kinase from chicken homolog B;
DE Short=hKFC-B;
DE AltName: Full=MARK Kinase;
DE Short=MARKK;
DE AltName: Full=Prostate-derived sterile 20-like kinase 2;
DE Short=PSK-2;
DE Short=PSK2;
DE Short=Prostate-derived STE20-like kinase 2;
DE AltName: Full=Thousand and one amino acid protein kinase 1;
DE Short=TAOK1;
DE Short=hTAOK1;
GN Name=TAOK1; Synonyms=KIAA1361, MAP3K16, MARKK;
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), FUNCTION, TISSUE SPECIFICITY, AND
RP SUBCELLULAR LOCATION.
RX PubMed=13679851; DOI=10.1038/sj.onc.1206605;
RA Yustein J.T., Xia L., Kahlenburg J.M., Robinson D., Templeton D.,
RA Kung H.-J.;
RT "Comparative studies of a new subfamily of human Ste20-like kinases:
RT homodimerization, subcellular localization, and selective activation of
RT MKK3 and p38.";
RL Oncogene 22:6129-6141(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Jenkins S.G., D'Andrea R.J., Gamble J.R., Vadas M.A.;
RT "Characterization of human TAO1.";
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Matsuda A., Yoneta S.;
RT "T cell activating gene.";
RL Patent number WO2004058805, 15-JUL-2004.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVI. The
RT complete sequences of 150 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:65-73(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [7]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Brain;
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 [9]
RP TISSUE SPECIFICITY.
RX PubMed=9786855; DOI=10.1074/jbc.273.44.28625;
RA Hutchison M., Berman K.S., Cobb M.H.;
RT "Isolation of TAO1, a protein kinase that activates MEKs in stress-
RT activated protein kinase cascades.";
RL J. Biol. Chem. 273:28625-28632(1998).
RN [10]
RP FUNCTION.
RX PubMed=12665513; DOI=10.1074/jbc.m301173200;
RA Chen Z., Raman M., Chen L., Lee S.F., Gilman A.G., Cobb M.H.;
RT "TAO (thousand-and-one amino acid) protein kinases mediate signaling from
RT carbachol to p38 mitogen-activated protein kinase and ternary complex
RT factors.";
RL J. Biol. Chem. 278:22278-22283(2003).
RN [11]
RP FUNCTION, PROTEOLYTIC PROCESSING, AND MUTAGENESIS OF LYS-57 AND ASP-376.
RX PubMed=16407310; DOI=10.1074/jbc.m513769200;
RA Zihni C., Mitsopoulos C., Tavares I.A., Ridley A.J., Morris J.D.;
RT "Prostate-derived sterile 20-like kinase 2 (PSK2) regulates apoptotic
RT morphology via C-Jun N-terminal kinase and Rho kinase-1.";
RL J. Biol. Chem. 281:7317-7323(2006).
RN [12]
RP INTERACTION WITH MAP3K7.
RX PubMed=16893890; DOI=10.1074/jbc.m603627200;
RA Huangfu W.C., Omori E., Akira S., Matsumoto K., Ninomiya-Tsuji J.;
RT "Osmotic stress activates the TAK1-JNK pathway while blocking TAK1-mediated
RT NF-kappaB activation: TAO2 regulates TAK1 pathways.";
RL J. Biol. Chem. 281:28802-28810(2006).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-421, AND IDENTIFICATION BY
RP 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 [14]
RP FUNCTION, PHOSPHORYLATION BY ATM, INDUCTION, AND MUTAGENESIS OF ASP-169;
RP THR-643; THR-785 AND SER-990.
RX PubMed=17396146; DOI=10.1038/sj.emboj.7601668;
RA Raman M., Earnest S., Zhang K., Zhao Y., Cobb M.H.;
RT "TAO kinases mediate activation of p38 in response to DNA damage.";
RL EMBO J. 26:2005-2014(2007).
RN [15]
RP POSSIBLE ROLE IN SPINDLE CHECKPOINT.
RX PubMed=17417629; DOI=10.1038/ncb1569;
RA Draviam V.M., Stegmeier F., Nalepa G., Sowa M.E., Chen J., Liang A.,
RA Hannon G.J., Sorger P.K., Harper J.W., Elledge S.J.;
RT "A functional genomic screen identifies a role for TAO1 kinase in spindle-
RT checkpoint signalling.";
RL Nat. Cell Biol. 9:556-564(2007).
RN [16]
RP FUNCTION.
RX PubMed=17900936; DOI=10.1016/j.cellbi.2007.08.006;
RA Wu M.F., Wang S.G.;
RT "Human TAO kinase 1 induces apoptosis in SH-SY5Y cells.";
RL Cell Biol. Int. 32:151-156(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-421 AND SER-965, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-421, AND IDENTIFICATION BY
RP 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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-421 AND SER-445, AND
RP 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 [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9; SER-421 AND THR-669, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [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 [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9 AND SER-421, AND
RP IDENTIFICATION BY 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 [23]
RP LACK OF ROLE IN SPINDLE CHECKPOINT.
RX PubMed=19904549; DOI=10.1007/s00412-009-0244-2;
RA Hubner N.C., Wang L.H., Kaulich M., Descombes P., Poser I., Nigg E.A.;
RT "Re-examination of siRNA specificity questions role of PICH and Tao1 in the
RT spindle checkpoint and identifies Mad2 as a sensitive target for small
RT RNAs.";
RL Chromosoma 119:149-165(2010).
RN [24]
RP LACK OF ROLE IN SPINDLE CHECKPOINT.
RX PubMed=20162290; DOI=10.1007/s00412-010-0261-1;
RA Westhorpe F.G., Diez M.A., Gurden M.D., Tighe A., Taylor S.S.;
RT "Re-evaluating the role of Tao1 in the spindle checkpoint.";
RL Chromosoma 119:371-379(2010).
RN [25]
RP PHOSPHORYLATION BY LRRK2.
RX PubMed=20949042; DOI=10.1371/journal.pone.0013191;
RA Zach S., Felk S., Gillardon F.;
RT "Signal transduction protein array analysis links LRRK2 to Ste20 kinases
RT and PKC zeta that modulate neuronal plasticity.";
RL PLoS ONE 5:E13191-E13191(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 SER-421, AND IDENTIFICATION BY
RP 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 SER-9; SER-421; SER-445 AND
RP SER-965, 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 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 VARIANT [LARGE SCALE ANALYSIS] THR-855.
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).
RN [31]
RP VARIANTS DDIB GLY-17; PHE-111; GLU-298; ALA-305; 544-GLN--THR-1001 DEL;
RP 781-GLU--THR-1001 DEL AND 830-GLU--THR-1001 DEL, AND INVOLVEMENT IN DDIB.
RX PubMed=31230721; DOI=10.1016/j.ajhg.2019.05.005;
RA Dulovic-Mahlow M., Trinh J., Kandaswamy K.K., Braathen G.J., Di Donato N.,
RA Rahikkala E., Beblo S., Werber M., Krajka V., Busk O.L., Baumann H.,
RA Al-Sannaa N.A., Hinrichs F., Affan R., Navot N., Al Balwi M.A., Oprea G.,
RA Holla O.L., Weiss M.E.R., Jamra R.A., Kahlert A.K., Kishore S., Tveten K.,
RA Vos M., Rolfs A., Lohmann K.;
RT "De Novo Variants in TAOK1 Cause Neurodevelopmental Disorders.";
RL Am. J. Hum. Genet. 105:213-220(2019).
RN [32]
RP VARIANTS DDIB ILE-150; ARG-167; 220-GLU--THR-1001 DEL; VAL-231; PHE-315;
RP PRO-548; 605-ARG--THR-1001 DEL; 607-GLN--THR-1001 DEL; 695-ARG--THR-1001
RP DEL; 702-ARG--THR-1001 DEL AND 709-ARG--THR-1001 DEL, FUNCTION, AND
RP CHARACTERIZATION OF VARIANTS DDIB ARG-167 AND PRO-548.
RX PubMed=33565190; DOI=10.1002/humu.24176;
RA van Woerden G.M., Bos M., de Konink C., Distel B., Avagliano Trezza R.,
RA Shur N.E., Baranano K., Mahida S., Chassevent A., Schreiber A., Erwin A.L.,
RA Gripp K.W., Rehman F., Brulleman S., McCormack R., de Geus G., Kalsner L.,
RA Sorlin A., Bruel A.L., Koolen D.A., Gabriel M.K., Rossi M.,
RA Fitzpatrick D.R., Wilkie A.O.M., Calpena E., Johnson D., Brooks A.,
RA van Slegtenhorst M., Fleischer J., Groepper D., Lindstrom K., Innes A.M.,
RA Goodwin A., Humberson J., Noyes A., Langley K.G., Telegrafi A., Blevins A.,
RA Hoffman J., Guillen Sacoto M.J., Juusola J., Monaghan K.G., Punj S.,
RA Simon M., Pfundt R., Elgersma Y., Kleefstra T.;
RT "TAOK1 is associated with neurodevelopmental disorder and essential for
RT neuronal maturation and cortical development.";
RL Hum. Mutat. 42:445-459(2021).
CC -!- FUNCTION: Serine/threonine-protein kinase involved in various processes
CC such as p38/MAPK14 stress-activated MAPK cascade, DNA damage response
CC and regulation of cytoskeleton stability. Phosphorylates MAP2K3, MAP2K6
CC and MARK2. Acts as an activator of the p38/MAPK14 stress-activated MAPK
CC cascade by mediating phosphorylation and subsequent activation of the
CC upstream MAP2K3 and MAP2K6 kinases. Involved in G-protein coupled
CC receptor signaling to p38/MAPK14. In response to DNA damage, involved
CC in the G2/M transition DNA damage checkpoint by activating the
CC p38/MAPK14 stress-activated MAPK cascade, probably by mediating
CC phosphorylation of MAP2K3 and MAP2K6. Acts as a regulator of
CC cytoskeleton stability by phosphorylating 'Thr-208' of MARK2, leading
CC to activate MARK2 kinase activity and subsequent phosphorylation and
CC detachment of MAPT/TAU from microtubules. Also acts as a regulator of
CC apoptosis: regulates apoptotic morphological changes, including cell
CC contraction, membrane blebbing and apoptotic bodies formation via
CC activation of the MAPK8/JNK cascade. Plays an essential role in the
CC regulation of neuronal development in the central nervous system
CC (PubMed:33565190). Also plays a role in the regulation of neuronal
CC migration to the cortical plate (By similarity).
CC {ECO:0000250|UniProtKB:Q5F2E8, ECO:0000269|PubMed:12665513,
CC ECO:0000269|PubMed:13679851, ECO:0000269|PubMed:16407310,
CC ECO:0000269|PubMed:17396146, ECO:0000269|PubMed:17900936,
CC ECO:0000269|PubMed:33565190}.
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 -!- ACTIVITY REGULATION: Serine/threonine-protein kinase activity is
CC inhibited by SPRED1.
CC -!- SUBUNIT: Self-associates. Interacts with MAP2K3 (By similarity).
CC Interacts with SPRED1 (By similarity). Interacts with TESK1; the
CC interaction inhibits TAOK1 kinase activity (By similarity). Interacts
CC with MAP3K7. {ECO:0000250, ECO:0000250|UniProtKB:O88664,
CC ECO:0000269|PubMed:16893890}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:13679851}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q7L7X3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7L7X3-2; Sequence=VSP_015964, VSP_015965, VSP_015966;
CC Name=3;
CC IsoId=Q7L7X3-3; Sequence=VSP_043706;
CC -!- TISSUE SPECIFICITY: Highly expressed in the testis, and to a lower
CC extent also expressed in brain, placenta, colon and skeletal muscle.
CC {ECO:0000269|PubMed:13679851, ECO:0000269|PubMed:9786855}.
CC -!- INDUCTION: In response to DNA damage. {ECO:0000269|PubMed:17396146}.
CC -!- PTM: Proteolytically processed by caspase-3 (CASP3).
CC {ECO:0000269|PubMed:16407310}.
CC -!- PTM: Autophosphorylated (By similarity). Phosphorylated by ATM in
CC response to DNA damage. Phosphorylated by LRRK2. {ECO:0000250,
CC ECO:0000269|PubMed:17396146, ECO:0000269|PubMed:20949042}.
CC -!- DISEASE: Developmental delay with or without intellectual impairment or
CC behavioral abnormalities (DDIB) [MIM:619575]: An autosomal dominant
CC disorder characterized by a highly variable phenotype of developmental
CC delay, intellectual disability, learning or behavioral problems,
CC muscular hypotonia, and neonatal feeding difficulties.
CC {ECO:0000269|PubMed:31230721, ECO:0000269|PubMed:33565190}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily. {ECO:0000305}.
CC -!- CAUTION: Was initially thought to play a role in the spindle checkpoint
CC (PubMed:17417629). However, it was later shown that it is not the case
CC and that phenotypes initially observed are the cause of the siRNA used
CC that has an off-target effect resulting in MAD2L1 inhibition
CC (PubMed:19904549 and PubMed:20162290). {ECO:0000305|PubMed:17417629}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA92599.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF263312; AAG38502.1; -; mRNA.
DR EMBL; AY049015; AAL12217.1; -; mRNA.
DR EMBL; CQ834802; CAH05616.1; -; mRNA.
DR EMBL; AB037782; BAA92599.1; ALT_INIT; mRNA.
DR EMBL; AK024376; BAB14901.1; -; mRNA.
DR EMBL; AC068025; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC068588; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC090698; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471159; EAW51188.1; -; Genomic_DNA.
DR EMBL; BC133039; AAI33040.1; -; mRNA.
DR EMBL; BC144067; AAI44068.1; -; mRNA.
DR CCDS; CCDS32601.1; -. [Q7L7X3-1]
DR CCDS; CCDS56024.1; -. [Q7L7X3-3]
DR RefSeq; NP_065842.1; NM_020791.2. [Q7L7X3-1]
DR RefSeq; NP_079418.1; NM_025142.1. [Q7L7X3-3]
DR RefSeq; XP_011523362.1; XM_011525060.2.
DR AlphaFoldDB; Q7L7X3; -.
DR SMR; Q7L7X3; -.
DR BioGRID; 121607; 32.
DR DIP; DIP-39709N; -.
DR IntAct; Q7L7X3; 24.
DR MINT; Q7L7X3; -.
DR STRING; 9606.ENSP00000261716; -.
DR BindingDB; Q7L7X3; -.
DR ChEMBL; CHEMBL5261; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q7L7X3; -.
DR GuidetoPHARMACOLOGY; 2233; -.
DR GlyGen; Q7L7X3; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q7L7X3; -.
DR MetOSite; Q7L7X3; -.
DR PhosphoSitePlus; Q7L7X3; -.
DR BioMuta; TAOK1; -.
DR DMDM; 74759012; -.
DR EPD; Q7L7X3; -.
DR jPOST; Q7L7X3; -.
DR MassIVE; Q7L7X3; -.
DR MaxQB; Q7L7X3; -.
DR PaxDb; Q7L7X3; -.
DR PeptideAtlas; Q7L7X3; -.
DR PRIDE; Q7L7X3; -.
DR ProteomicsDB; 68829; -. [Q7L7X3-1]
DR ProteomicsDB; 68830; -. [Q7L7X3-2]
DR ProteomicsDB; 68831; -. [Q7L7X3-3]
DR Antibodypedia; 2089; 390 antibodies from 32 providers.
DR DNASU; 57551; -.
DR Ensembl; ENST00000261716.8; ENSP00000261716.3; ENSG00000160551.12. [Q7L7X3-1]
DR Ensembl; ENST00000536202.1; ENSP00000438819.1; ENSG00000160551.12. [Q7L7X3-3]
DR GeneID; 57551; -.
DR KEGG; hsa:57551; -.
DR MANE-Select; ENST00000261716.8; ENSP00000261716.3; NM_020791.4; NP_065842.1.
DR UCSC; uc002hdz.3; human. [Q7L7X3-1]
DR CTD; 57551; -.
DR DisGeNET; 57551; -.
DR GeneCards; TAOK1; -.
DR HGNC; HGNC:29259; TAOK1.
DR HPA; ENSG00000160551; Low tissue specificity.
DR MalaCards; TAOK1; -.
DR MIM; 610266; gene.
DR MIM; 619575; phenotype.
DR neXtProt; NX_Q7L7X3; -.
DR OpenTargets; ENSG00000160551; -.
DR Orphanet; 178469; Autosomal dominant non-syndromic intellectual disability.
DR PharmGKB; PA134872946; -.
DR VEuPathDB; HostDB:ENSG00000160551; -.
DR eggNOG; KOG0577; Eukaryota.
DR GeneTree; ENSGT00940000155796; -.
DR HOGENOM; CLU_000288_2_2_1; -.
DR InParanoid; Q7L7X3; -.
DR OMA; XAKVMAN; -.
DR PhylomeDB; Q7L7X3; -.
DR TreeFam; TF351444; -.
DR PathwayCommons; Q7L7X3; -.
DR Reactome; R-HSA-141444; Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal.
DR Reactome; R-HSA-2467813; Separation of Sister Chromatids.
DR Reactome; R-HSA-2500257; Resolution of Sister Chromatid Cohesion.
DR Reactome; R-HSA-5663220; RHO GTPases Activate Formins.
DR Reactome; R-HSA-68877; Mitotic Prometaphase.
DR Reactome; R-HSA-9648025; EML4 and NUDC in mitotic spindle formation.
DR SignaLink; Q7L7X3; -.
DR SIGNOR; Q7L7X3; -.
DR BioGRID-ORCS; 57551; 55 hits in 1127 CRISPR screens.
DR ChiTaRS; TAOK1; human.
DR GeneWiki; TAOK1; -.
DR GenomeRNAi; 57551; -.
DR Pharos; Q7L7X3; Tchem.
DR PRO; PR:Q7L7X3; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q7L7X3; protein.
DR Bgee; ENSG00000160551; Expressed in corpus callosum and 196 other tissues.
DR ExpressionAtlas; Q7L7X3; baseline and differential.
DR Genevisible; Q7L7X3; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0015630; C:microtubule cytoskeleton; IMP:ARUK-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IMP:ARUK-UCL.
DR GO; GO:0043014; F:alpha-tubulin binding; IDA:ARUK-UCL.
DR GO; GO:0005524; F:ATP binding; NAS:HGNC-UCL.
DR GO; GO:0048487; F:beta-tubulin binding; IDA:ARUK-UCL.
DR GO; GO:0016301; F:kinase activity; IDA:ARUK-UCL.
DR GO; GO:0004672; F:protein kinase activity; ISS:ARUK-UCL.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; ISS:ARUK-UCL.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0048156; F:tau protein binding; NAS:ARUK-UCL.
DR GO; GO:0050321; F:tau-protein kinase activity; NAS:ARUK-UCL.
DR GO; GO:0016740; F:transferase activity; NAS:HGNC-UCL.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0021954; P:central nervous system neuron development; IMP:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0097194; P:execution phase of apoptosis; IDA:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0000165; P:MAPK cascade; IBA:GO_Central.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IMP:ARUK-UCL.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; IMP:UniProtKB.
DR GO; GO:0007026; P:negative regulation of microtubule depolymerization; IMP:ARUK-UCL.
DR GO; GO:0070050; P:neuron cellular homeostasis; IMP:ARUK-UCL.
DR GO; GO:0048812; P:neuron projection morphogenesis; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; IDA:ARUK-UCL.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IDA:UniProtKB.
DR GO; GO:1901985; P:positive regulation of protein acetylation; IMP:ARUK-UCL.
DR GO; GO:0032874; P:positive regulation of stress-activated MAPK cascade; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:ARUK-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISS:ARUK-UCL.
DR GO; GO:0051493; P:regulation of cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; ISS:ARUK-UCL.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; ATP-binding; Coiled coil; Cytoplasm;
KW Disease variant; DNA damage; DNA repair; Intellectual disability; Kinase;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..1001
FT /note="Serine/threonine-protein kinase TAO1"
FT /id="PRO_0000086728"
FT DOMAIN 28..281
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 324..433
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 567..587
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 911..1001
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 458..651
FT /evidence="ECO:0000255"
FT COILED 754..877
FT /evidence="ECO:0000255"
FT COMPBIAS 340..374
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 400..415
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 958..1001
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 151
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 34..42
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 57
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 421
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 445
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 669
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 965
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..174
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_015964"
FT VAR_SEQ 569..716
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_043706"
FT VAR_SEQ 569..572
FT /note="ELNE -> VLMS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_015965"
FT VAR_SEQ 573..1001
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_015966"
FT VARIANT 17
FT /note="E -> G (in DDIB)"
FT /evidence="ECO:0000269|PubMed:31230721"
FT /id="VAR_086415"
FT VARIANT 111
FT /note="S -> F (in DDIB)"
FT /evidence="ECO:0000269|PubMed:31230721"
FT /id="VAR_086416"
FT VARIANT 150
FT /note="R -> I (in DDIB)"
FT /evidence="ECO:0000269|PubMed:33565190"
FT /id="VAR_086417"
FT VARIANT 167
FT /note="L -> R (in DDIB; affects neuron maturation and
FT migration)"
FT /evidence="ECO:0000269|PubMed:33565190"
FT /id="VAR_086418"
FT VARIANT 220..1001
FT /note="Missing (in DDIB)"
FT /evidence="ECO:0000269|PubMed:33565190"
FT /id="VAR_086419"
FT VARIANT 231
FT /note="M -> V (in DDIB; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:33565190"
FT /id="VAR_086420"
FT VARIANT 298
FT /note="K -> E (in DDIB)"
FT /evidence="ECO:0000269|PubMed:31230721"
FT /id="VAR_086421"
FT VARIANT 305
FT /note="D -> A (in DDIB)"
FT /evidence="ECO:0000269|PubMed:31230721"
FT /id="VAR_086422"
FT VARIANT 315
FT /note="L -> F (in DDIB; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:33565190"
FT /id="VAR_086423"
FT VARIANT 544..1001
FT /note="Missing (in DDIB)"
FT /evidence="ECO:0000269|PubMed:31230721"
FT /id="VAR_086424"
FT VARIANT 548
FT /note="L -> P (in DDIB; affects neuron maturation and
FT migration)"
FT /evidence="ECO:0000269|PubMed:33565190"
FT /id="VAR_086425"
FT VARIANT 605..1001
FT /note="Missing (in DDIB)"
FT /evidence="ECO:0000269|PubMed:33565190"
FT /id="VAR_086426"
FT VARIANT 607..1001
FT /note="Missing (in DDIB)"
FT /evidence="ECO:0000269|PubMed:33565190"
FT /id="VAR_086427"
FT VARIANT 695..1001
FT /note="Missing (in DDIB)"
FT /evidence="ECO:0000269|PubMed:33565190"
FT /id="VAR_086428"
FT VARIANT 702..1001
FT /note="Missing (in DDIB)"
FT /evidence="ECO:0000269|PubMed:33565190"
FT /id="VAR_086429"
FT VARIANT 709..1001
FT /note="Missing (in DDIB)"
FT /evidence="ECO:0000269|PubMed:33565190"
FT /id="VAR_086430"
FT VARIANT 781..1001
FT /note="Missing (in DDIB)"
FT /evidence="ECO:0000269|PubMed:31230721"
FT /id="VAR_086431"
FT VARIANT 830..1001
FT /note="Missing (in DDIB)"
FT /evidence="ECO:0000269|PubMed:31230721"
FT /id="VAR_086432"
FT VARIANT 855
FT /note="A -> T (in dbSNP:rs34151057)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041204"
FT MUTAGEN 57
FT /note="K->A: Abolishes kinase activity, ability to activate
FT the MAPK8/JNK cascade and cleavage by caspase-3 (CASP3)."
FT /evidence="ECO:0000269|PubMed:16407310"
FT MUTAGEN 169
FT /note="D->A: Loss of serine/threonine-protein kinase
FT activity."
FT /evidence="ECO:0000269|PubMed:17396146"
FT MUTAGEN 376
FT /note="D->N: Does not abolish cleavage by caspase-3
FT (CASP3)."
FT /evidence="ECO:0000269|PubMed:16407310"
FT MUTAGEN 643
FT /note="T->A: Abolishes phosphorylation by ATM; when
FT associated with A-785 and A-990."
FT /evidence="ECO:0000269|PubMed:17396146"
FT MUTAGEN 785
FT /note="T->A: Abolishes phosphorylation by ATM; when
FT associated with A-643 and A-990."
FT /evidence="ECO:0000269|PubMed:17396146"
FT MUTAGEN 990
FT /note="S->A: Abolishes phosphorylation by ATM; when
FT associated with A-643 and A-785."
FT /evidence="ECO:0000269|PubMed:17396146"
FT CONFLICT 251
FT /note="S -> T (in Ref. 5; BAB14901)"
FT /evidence="ECO:0000305"
FT CONFLICT 257
FT /note="F -> S (in Ref. 1; AAG38502)"
FT /evidence="ECO:0000305"
FT CONFLICT 860
FT /note="R -> C (in Ref. 1; AAG38502)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1001 AA; 116070 MW; 82941DEAEADC7651 CRC64;
MPSTNRAGSL KDPEIAELFF KEDPEKLFTD LREIGHGSFG AVYFARDVRT NEVVAIKKMS
YSGKQSTEKW QDIIKEVKFL QRIKHPNSIE YKGCYLREHT AWLVMEYCLG SASDLLEVHK
KPLQEVEIAA ITHGALQGLA YLHSHTMIHR DIKAGNILLT EPGQVKLADF GSASMASPAN
SFVGTPYWMA PEVILAMDEG QYDGKVDVWS LGITCIELAE RKPPLFNMNA MSALYHIAQN
ESPTLQSNEW SDYFRNFVDS CLQKIPQDRP TSEELLKHIF VLRERPETVL IDLIQRTKDA
VRELDNLQYR KMKKLLFQEA HNGPAVEAQE EEEEQDHGVG RTGTVNSVGS NQSIPSMSIS
ASSQSSSVNS LPDVSDDKSE LDMMEGDHTV MSNSSVIHLK PEEENYREEG DPRTRASDPQ
SPPQVSRHKS HYRNREHFAT IRTASLVTRQ MQEHEQDSEL REQMSGYKRM RRQHQKQLMT
LENKLKAEMD EHRLRLDKDL ETQRNNFAAE MEKLIKKHQA AMEKEAKVMS NEEKKFQQHI
QAQQKKELNS FLESQKREYK LRKEQLKEEL NENQSTPKKE KQEWLSKQKE NIQHFQAEEE
ANLLRRQRQY LELECRRFKR RMLLGRHNLE QDLVREELNK RQTQKDLEHA MLLRQHESMQ
ELEFRHLNTI QKMRCELIRL QHQTELTNQL EYNKRREREL RRKHVMEVRQ QPKSLKSKEL
QIKKQFQDTC KIQTRQYKAL RNHLLETTPK SEHKAVLKRL KEEQTRKLAI LAEQYDHSIN
EMLSTQALRL DEAQEAECQV LKMQLQQELE LLNAYQSKIK MQAEAQHDRE LRELEQRVSL
RRALLEQKIE EEMLALQNER TERIRSLLER QAREIEAFDS ESMRLGFSNM VLSNLSPEAF
SHSYPGASGW SHNPTGGPGP HWGHPMGGPP QAWGHPMQGG PQPWGHPSGP MQGVPRGSSM
GVRNSPQALR RTASGGRTEQ GMSRSTSVTS QISNGSHMSY T
