TAOK2_HUMAN
ID TAOK2_HUMAN Reviewed; 1235 AA.
AC Q9UL54; A5PKY1; A7MCZ2; B2RN35; B7ZM88; O94957; Q6UW73; Q7LC09; Q9NSW2;
DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Serine/threonine-protein kinase TAO2;
DE EC=2.7.11.1;
DE AltName: Full=Kinase from chicken homolog C;
DE Short=hKFC-C;
DE AltName: Full=Prostate-derived sterile 20-like kinase 1;
DE Short=PSK-1;
DE Short=PSK1;
DE Short=Prostate-derived STE20-like kinase 1;
DE AltName: Full=Thousand and one amino acid protein kinase 2;
GN Name=TAOK2; Synonyms=KIAA0881, MAP3K17, PSK, PSK1;
GN ORFNames=UNQ2971/PRO7431;
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 MUTAGENESIS OF LYS-57.
RC TISSUE=Mammary carcinoma;
RX PubMed=10660600; DOI=10.1074/jbc.275.6.4311;
RA Moore T.M., Garg R., Johnson C., Coptcoat M.J., Ridley A.J., Morris J.D.H.;
RT "PSK, a novel STE20-like kinase derived from prostatic carcinoma that
RT activates the JNK MAPK pathway and regulates actin cytoskeletal
RT organisation.";
RL J. Biol. Chem. 275:4311-4322(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SELF-ASSOCIATION, TISSUE
RP SPECIFICITY, AND 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Fetal brain;
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 MRNA] (ISOFORM 3).
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
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; 2 AND 4).
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 957-1235 (ISOFORMS 1/3).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [10]
RP FUNCTION IN PHOSPHORYLATION OF MAP2K3 AND MAP2K6, AND INTERACTION WITH
RP MAP2K3 AND MAP2K6.
RX PubMed=11279118; DOI=10.1074/jbc.m100681200;
RA Chen Z., Cobb M.H.;
RT "Regulation of stress-responsive mitogen-activated protein (MAP) kinase
RT pathways by TAO2.";
RL J. Biol. Chem. 276:16070-16075(2001).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH TUBULINS, AND MUTAGENESIS
RP OF LYS-57.
RX PubMed=12639963; DOI=10.1074/jbc.m213064200;
RA Mitsopoulos C., Zihni C., Garg R., Ridley A.J., Morris J.D.;
RT "The prostate-derived sterile 20-like kinase (PSK) regulates microtubule
RT organization and stability.";
RL J. Biol. Chem. 278:18085-18091(2003).
RN [12]
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 [13]
RP FUNCTION, INTERACTION WITH MAP3K7, AND MUTAGENESIS OF LYS-57 AND ASP-169.
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 [14]
RP FUNCTION, PHOSPHORYLATION BY ATM, AND INDUCTION.
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 FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-181,
RP AUTOPHOSPHORYLATION, AND MUTAGENESIS OF LYS-57 AND ASP-919.
RX PubMed=17158878; DOI=10.1074/jbc.m608336200;
RA Zihni C., Mitsopoulos C., Tavares I.A., Baum B., Ridley A.J., Morris J.D.;
RT "Prostate-derived sterile 20-like kinase 1-alpha induces apoptosis.
RT JNK- and caspase-dependent nuclear localization is a requirement for
RT membrane blebbing.";
RL J. Biol. Chem. 282:6484-6493(2007).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9 AND SER-777, 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 [17]
RP ACTIVITY REGULATION.
RX PubMed=19226137; DOI=10.1021/jm8005806;
RA Anand R., Maksimoska J., Pagano N., Wong E.Y., Gimotty P.A., Diamond S.L.,
RA Meggers E., Marmorstein R.;
RT "Toward the development of a potent and selective organoruthenium mammalian
RT sterile 20 kinase inhibitor.";
RL J. Med. Chem. 52:1602-1611(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9 AND SER-181,
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1011 (ISOFORM 2), 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 [19]
RP ACTIVITY REGULATION.
RX PubMed=20159944; DOI=10.1124/mol.109.061507;
RA McNeer J.L., Goussetis D.J., Sassano A., Dolniak B., Kroczynska B.,
RA Glaser H., Altman J.K., Platanias L.C.;
RT "Arsenic trioxide-dependent activation of thousand-and-one amino acid
RT kinase 2 and transforming growth factor-beta-activated kinase 1.";
RL Mol. Pharmacol. 77:828-835(2010).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-825 AND SER-827, 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9 AND SER-827, AND
RP 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 [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-414, AND IDENTIFICATION BY
RP 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).
CC -!- FUNCTION: Serine/threonine-protein kinase involved in different
CC processes such as membrane blebbing and apoptotic bodies formation DNA
CC damage response and MAPK14/p38 MAPK stress-activated MAPK cascade.
CC Phosphorylates itself, MBP, activated MAPK8, MAP2K3, MAP2K6 and
CC tubulins. Activates the MAPK14/p38 MAPK signaling pathway through the
CC specific activation and phosphorylation of the upstream MAP2K3 and
CC MAP2K6 kinases. In response to DNA damage, involved in the G2/M
CC transition DNA damage checkpoint by activating the p38/MAPK14 stress-
CC activated MAPK cascade, probably by mediating phosphorylation of
CC upstream MAP2K3 and MAP2K6 kinases. Isoform 1, but not isoform 2, plays
CC a role in apoptotic morphological changes, including cell contraction,
CC membrane blebbing and apoptotic bodies formation. This function, which
CC requires the activation of MAPK8/JNK and nuclear localization of C-
CC terminally truncated isoform 1, may be linked to the mitochondrial
CC CASP9-associated death pathway. Isoform 1 binds to microtubules and
CC affects their organization and stability independently of its kinase
CC activity. Prevents MAP3K7-mediated activation of CHUK, and thus NF-
CC kappa-B activation, but not that of MAPK8/JNK. May play a role in the
CC osmotic stress-MAPK8 pathway. Isoform 2, but not isoform 1, is required
CC for PCDH8 endocytosis. Following homophilic interactions between PCDH8
CC extracellular domains, isoform 2 phosphorylates and activates
CC MAPK14/p38 MAPK which in turn phosphorylates isoform 2. This process
CC leads to PCDH8 endocytosis and CDH2 cointernalization. Both isoforms
CC are involved in MAPK14 phosphorylation. {ECO:0000269|PubMed:10660600,
CC ECO:0000269|PubMed:11279118, ECO:0000269|PubMed:12639963,
CC ECO:0000269|PubMed:12665513, ECO:0000269|PubMed:13679851,
CC ECO:0000269|PubMed:16893890, ECO:0000269|PubMed:17158878,
CC ECO:0000269|PubMed:17396146}.
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; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Selectively inhibited by the enantiopure
CC organoruthenium inhibitor 9E1. Activated following arsenic trioxide
CC (As(2)O(3)) treatment. {ECO:0000269|PubMed:19226137,
CC ECO:0000269|PubMed:20159944}.
CC -!- SUBUNIT: Interacts with MAP2K3 and MAP2K6 (By similarity). Self-
CC associates. Interacts with tubulins through the C-terminal domain.
CC Interacts with MAP3K7 and interfers with MAP3K7-binding to CHUK and
CC thus prevents NF-kappa-B activation. Isoform 2 interacts with PCDH8;
CC this complex may also include CDH2 (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q9UL54; Q9UHD4: CIDEB; NbExp=3; IntAct=EBI-352832, EBI-7062247;
CC Q9UL54; Q9UPY8: MAPRE3; NbExp=3; IntAct=EBI-352832, EBI-726739;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000305}. Cytoplasm, cytoskeleton.
CC Nucleus. Note=Catalytically active full-length phosphorylated isoform 1
CC localizes to microtubules in the cytoplasm predominantly on microtubule
CC cables positioned around the nucleus. A C-terminally truncated form of
CC isoform 1 is present in the nucleus; isoform 2 and kinase-defective, as
CC well as full-length isoform 1 are excluded from the nucleus.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell projection, dendrite. Note=In
CC dendrites, colocalizes with PCDH8. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=PSK1-alpha, TAO2;
CC IsoId=Q9UL54-1; Sequence=Displayed;
CC Name=2; Synonyms=PSK1-beta;
CC IsoId=Q9UL54-2; Sequence=VSP_015969, VSP_015970;
CC Name=3;
CC IsoId=Q9UL54-3; Sequence=VSP_015967, VSP_015968;
CC Name=4;
CC IsoId=Q9UL54-4; Sequence=VSP_044894;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with a higher level of
CC expression in testis and brain. {ECO:0000269|PubMed:10660600,
CC ECO:0000269|PubMed:13679851}.
CC -!- PTM: Isoforms 1 and 2 are autophosphorylated.
CC -!- PTM: C-terminal cleavage of isoform 1 and subsequent nuclear
CC localization requires CASP9 activity.
CC -!- PTM: Autophosphorylated. Phosphorylated by ATM.
CC -!- PTM: [Isoform 2]: Phosphorylated on Ser-1031 by MAPK14. This
CC phosphorylation is required PCDH8 for endocytosis (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAQ89301.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA74904.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF061943; AAD45616.1; -; mRNA.
DR EMBL; AF263313; AAG38503.1; -; mRNA.
DR EMBL; AB020688; BAA74904.2; ALT_INIT; mRNA.
DR EMBL; AK291473; BAF84162.1; -; mRNA.
DR EMBL; AL137701; CAB70882.1; -; mRNA.
DR EMBL; AC093512; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471238; EAW79963.1; -; Genomic_DNA.
DR EMBL; CH471238; EAW79964.1; -; Genomic_DNA.
DR EMBL; BC136653; AAI36654.1; -; mRNA.
DR EMBL; BC136655; AAI36656.1; -; mRNA.
DR EMBL; BC142663; AAI42664.1; -; mRNA.
DR EMBL; BC144344; AAI44345.1; -; mRNA.
DR EMBL; BC151221; AAI51222.1; -; mRNA.
DR EMBL; BC152413; AAI52414.1; -; mRNA.
DR EMBL; AY358942; AAQ89301.1; ALT_INIT; mRNA.
DR CCDS; CCDS10662.1; -. [Q9UL54-2]
DR CCDS; CCDS10663.1; -. [Q9UL54-1]
DR CCDS; CCDS58448.1; -. [Q9UL54-4]
DR PIR; T46444; T46444.
DR RefSeq; NP_001238972.1; NM_001252043.1. [Q9UL54-4]
DR RefSeq; NP_004774.1; NM_004783.3. [Q9UL54-2]
DR RefSeq; NP_057235.2; NM_016151.3. [Q9UL54-1]
DR AlphaFoldDB; Q9UL54; -.
DR SMR; Q9UL54; -.
DR BioGRID; 114750; 51.
DR IntAct; Q9UL54; 44.
DR MINT; Q9UL54; -.
DR STRING; 9606.ENSP00000310094; -.
DR BindingDB; Q9UL54; -.
DR ChEMBL; CHEMBL1075195; -.
DR DrugBank; DB04522; Dexfosfoserine.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q9UL54; -.
DR iPTMnet; Q9UL54; -.
DR PhosphoSitePlus; Q9UL54; -.
DR BioMuta; TAOK2; -.
DR DMDM; 116242813; -.
DR EPD; Q9UL54; -.
DR jPOST; Q9UL54; -.
DR MassIVE; Q9UL54; -.
DR MaxQB; Q9UL54; -.
DR PaxDb; Q9UL54; -.
DR PeptideAtlas; Q9UL54; -.
DR PRIDE; Q9UL54; -.
DR ProteomicsDB; 7250; -.
DR ProteomicsDB; 84953; -. [Q9UL54-1]
DR ProteomicsDB; 84954; -. [Q9UL54-2]
DR ProteomicsDB; 84955; -. [Q9UL54-3]
DR Antibodypedia; 2082; 229 antibodies from 36 providers.
DR DNASU; 9344; -.
DR Ensembl; ENST00000279394.7; ENSP00000279394.3; ENSG00000149930.18. [Q9UL54-2]
DR Ensembl; ENST00000308893.9; ENSP00000310094.4; ENSG00000149930.18. [Q9UL54-1]
DR Ensembl; ENST00000416441.2; ENSP00000393048.2; ENSG00000149930.18. [Q9UL54-3]
DR Ensembl; ENST00000543033.5; ENSP00000440336.1; ENSG00000149930.18. [Q9UL54-4]
DR GeneID; 9344; -.
DR KEGG; hsa:9344; -.
DR MANE-Select; ENST00000308893.9; ENSP00000310094.4; NM_016151.4; NP_057235.2.
DR UCSC; uc002dva.3; human. [Q9UL54-1]
DR CTD; 9344; -.
DR DisGeNET; 9344; -.
DR GeneCards; TAOK2; -.
DR HGNC; HGNC:16835; TAOK2.
DR HPA; ENSG00000149930; Low tissue specificity.
DR MIM; 613199; gene.
DR neXtProt; NX_Q9UL54; -.
DR OpenTargets; ENSG00000149930; -.
DR PharmGKB; PA134907964; -.
DR VEuPathDB; HostDB:ENSG00000149930; -.
DR eggNOG; KOG0577; Eukaryota.
DR GeneTree; ENSGT00940000159991; -.
DR HOGENOM; CLU_276301_0_0_1; -.
DR InParanoid; Q9UL54; -.
DR OMA; YYARCLV; -.
DR OrthoDB; 617606at2759; -.
DR PhylomeDB; Q9UL54; -.
DR TreeFam; TF351444; -.
DR PathwayCommons; Q9UL54; -.
DR SignaLink; Q9UL54; -.
DR SIGNOR; Q9UL54; -.
DR BioGRID-ORCS; 9344; 13 hits in 1114 CRISPR screens.
DR ChiTaRS; TAOK2; human.
DR GeneWiki; TAOK2; -.
DR GenomeRNAi; 9344; -.
DR Pharos; Q9UL54; Tchem.
DR PRO; PR:Q9UL54; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9UL54; protein.
DR Bgee; ENSG00000149930; Expressed in right hemisphere of cerebellum and 135 other tissues.
DR Genevisible; Q9UL54; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IEA:Ensembl.
DR GO; GO:0030424; C:axon; ISS:ARUK-UCL.
DR GO; GO:0044295; C:axonal growth cone; ISS:ARUK-UCL.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0044294; C:dendritic growth cone; ISS:ARUK-UCL.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043005; C:neuron projection; ISS:ARUK-UCL.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0043235; C:receptor complex; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004709; F:MAP kinase kinase kinase activity; NAS:ARUK-UCL.
DR GO; GO:0031434; F:mitogen-activated protein kinase kinase binding; IPI:UniProtKB.
DR GO; GO:0038191; F:neuropilin binding; IPI:ARUK-UCL.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; TAS:ARUK-UCL.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA: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:0030036; P:actin cytoskeleton organization; IDA:UniProtKB.
DR GO; GO:0032147; P:activation of protein kinase activity; TAS:ARUK-UCL.
DR GO; GO:0006915; P:apoptotic process; NAS:UniProtKB.
DR GO; GO:0007409; P:axonogenesis; IGI:ARUK-UCL.
DR GO; GO:0150020; P:basal dendrite arborization; ISS:ARUK-UCL.
DR GO; GO:0150019; P:basal dendrite morphogenesis; ISS:ARUK-UCL.
DR GO; GO:0016477; P:cell migration; NAS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0048041; P:focal adhesion assembly; 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:0007095; P:mitotic G2 DNA damage checkpoint signaling; IMP:UniProtKB.
DR GO; GO:0048812; P:neuron projection morphogenesis; IBA:GO_Central.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IDA:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:UniProtKB.
DR GO; GO:0031954; P:positive regulation of protein autophosphorylation; TAS:ARUK-UCL.
DR GO; GO:0032874; P:positive regulation of stress-activated MAPK cascade; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; TAS:ARUK-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0006612; P:protein targeting to membrane; NAS:UniProtKB.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISS:ARUK-UCL.
DR GO; GO:0001558; P:regulation of cell growth; NAS:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; IDA:UniProtKB.
DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0051403; P:stress-activated MAPK cascade; IDA:UniProtKB.
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; ATP-binding; Cell projection; Coiled coil; Cytoplasm;
KW Cytoplasmic vesicle; Cytoskeleton; Kinase; Magnesium; Membrane;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..1235
FT /note="Serine/threonine-protein kinase TAO2"
FT /id="PRO_0000086733"
FT TRANSMEM 965..985
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 987..1007
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1012..1032
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1043..1063
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1166..1186
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 28..281
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 318..457
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 732..777
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 804..835
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 891..939
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1198..1235
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 486..547
FT /evidence="ECO:0000255"
FT COILED 574..601
FT /evidence="ECO:0000255"
FT COILED 681..713
FT /evidence="ECO:0000255"
FT COMPBIAS 344..373
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 374..395
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 920..938
FT /note="Pro 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:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163"
FT MOD_RES 181
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17158878,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 414
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 656
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6ZQ29"
FT MOD_RES 777
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 825
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 827
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..173
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_015967"
FT VAR_SEQ 174..218
FT /note="SIMAPANSFVGTPYWMAPEVILAMDEGQYDGKVDVWSLGITCIEL -> MMG
FT TSQGHVARKSRNWGLNPSRLSSIPLSSTPCHLSPSSLSPFSV (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_015968"
FT VAR_SEQ 745..1049
FT /note="VRAGQRPPGLPLPIPGALGPPNTGTPIEQQPCSPGQEAVLDQRMLGEEEEAV
FT GERRILGKEGATLEPKQQRILGEESGAPSPSPQKHGSLVDEEVWGLPEEIEELRVPSLV
FT PQERSIVGQEEAGTWSLWGKEDESLLDEEFELGWVQGPALTPVPEEEEEEEEGAPIGTP
FT RDPGDGCPSPDIPPEPPPTHLRPCPASQLPGLLSHGLLAGLSFAVGSSSGLLPLLLLLL
FT LPLLAAQGGGGLQAALLALEVGLVGLGASYLLLCTALHLPSSLFLLLAQGTALGAVLGL
FT SWRRGLMGVPLGLGAAW -> SKELQIKKQFQETCKIQTRQYKALRAHLLETTPKAQHK
FT SLLKRLKEEQTRKLAILAEQYDQSISEMLSSQALRLDETQEAEFQALRQQLQQELELLN
FT AYQSKIKIRTESQHERELRELEQRVALRRALLEQRVEEELLALQTGRSERIRSLLERQA
FT REIEAFDAESMRLGFSSMALGGIPAEAAAQGYPAPPPAPAWPSRPVPRSGAHWSHGPPP
FT PGMPPPAWRQPSLLAPPGPPNWLGPPTQSGTPRGGALLLLRNSPQPLRRAASGGSGSEN
FT VGPPAAAVPGPLSRSTSVASHILNGSSHFYS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10048485,
FT ECO:0000303|PubMed:13679851, ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_015969"
FT VAR_SEQ 745..857
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_044894"
FT VAR_SEQ 1050..1235
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10048485,
FT ECO:0000303|PubMed:13679851, ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_015970"
FT MUTAGEN 57
FT /note="K->A: Loss of kinase activity. In isoform 1,
FT excluded from the nucleus. No effect on microtubule-
FT binding."
FT /evidence="ECO:0000269|PubMed:10660600,
FT ECO:0000269|PubMed:12639963, ECO:0000269|PubMed:16893890,
FT ECO:0000269|PubMed:17158878"
FT MUTAGEN 169
FT /note="D->A: Loss of kinase activity; No effect on MAP3K7-
FT mediated activation of NF-kappa-B."
FT /evidence="ECO:0000269|PubMed:16893890"
FT MUTAGEN 919
FT /note="D->N: No effect on kinase activity, nor on JNK
FT activation, but severe reduction in nuclear localization
FT and apoptotic membrane blebbing."
FT /evidence="ECO:0000269|PubMed:17158878"
FT CONFLICT 189
FT /note="M -> T (in Ref. 7; AAI51222/AAI42664)"
FT /evidence="ECO:0000305"
FT CONFLICT 1211
FT /note="R -> H (in Ref. 1; AAD45616)"
FT /evidence="ECO:0000305"
FT MOD_RES Q9UL54-2:1011
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES Q9UL54-2:1031
FT /note="Phosphoserine"
FT /evidence="ECO:0000250"
SQ SEQUENCE 1235 AA; 138251 MW; 211852E690934307 CRC64;
MPAGGRAGSL KDPDVAELFF KDDPEKLFSD LREIGHGSFG AVYFARDVRN SEVVAIKKMS
YSGKQSNEKW QDIIKEVRFL QKLRHPNTIQ YRGCYLREHT AWLVMEYCLG SASDLLEVHK
KPLQEVEIAA VTHGALQGLA YLHSHNMIHR DVKAGNILLS EPGLVKLGDF GSASIMAPAN
SFVGTPYWMA PEVILAMDEG QYDGKVDVWS LGITCIELAE RKPPLFNMNA MSALYHIAQN
ESPVLQSGHW SEYFRNFVDS CLQKIPQDRP TSEVLLKHRF VLRERPPTVI MDLIQRTKDA
VRELDNLQYR KMKKILFQEA PNGPGAEAPE EEEEAEPYMH RAGTLTSLES SHSVPSMSIS
ASSQSSSVNS LADASDNEEE EEEEEEEEEE EEGPEAREMA MMQEGEHTVT SHSSIIHRLP
GSDNLYDDPY QPEITPSPLQ PPAAPAPTST TSSARRRAYC RNRDHFATIR TASLVSRQIQ
EHEQDSALRE QLSGYKRMRR QHQKQLLALE SRLRGEREEH SARLQRELEA QRAGFGAEAE
KLARRHQAIG EKEARAAQAE ERKFQQHILG QQKKELAALL EAQKRTYKLR KEQLKEELQE
NPSTPKREKA EWLLRQKEQL QQCQAEEEAG LLRRQRQYFE LQCRQYKRKM LLARHSLDQD
LLREDLNKKQ TQKDLECALL LRQHEATREL ELRQLQAVQR TRAELTRLQH QTELGNQLEY
NKRREQELRQ KHAAQVRQQP KSLKVRAGQR PPGLPLPIPG ALGPPNTGTP IEQQPCSPGQ
EAVLDQRMLG EEEEAVGERR ILGKEGATLE PKQQRILGEE SGAPSPSPQK HGSLVDEEVW
GLPEEIEELR VPSLVPQERS IVGQEEAGTW SLWGKEDESL LDEEFELGWV QGPALTPVPE
EEEEEEEGAP IGTPRDPGDG CPSPDIPPEP PPTHLRPCPA SQLPGLLSHG LLAGLSFAVG
SSSGLLPLLL LLLLPLLAAQ GGGGLQAALL ALEVGLVGLG ASYLLLCTAL HLPSSLFLLL
AQGTALGAVL GLSWRRGLMG VPLGLGAAWL LAWPGLALPL VAMAAGGRWV RQQGPRVRRG
ISRLWLRVLL RLSPMAFRAL QGCGAVGDRG LFALYPKTNK DGFRSRLPVP GPRRRNPRTT
QHPLALLARV WVLCKGWNWR LARASQGLAS HLPPWAIHTL ASWGLLRGER PTRIPRLLPR
SQRQLGPPAS RQPLPGTLAG RRSRTRQSRA LPPWR
