TNIK_HUMAN
ID TNIK_HUMAN Reviewed; 1360 AA.
AC Q9UKE5; A7E2A3; A8K4U1; D3DNQ6; O60298; Q8WUY7; Q9UKD8; Q9UKD9; Q9UKE0;
AC Q9UKE1; Q9UKE2; Q9UKE3; Q9UKE4;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=TRAF2 and NCK-interacting protein kinase;
DE EC=2.7.11.1;
GN Name=TNIK; Synonyms=KIAA0551;
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:AAF03782.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4; 5; 6; 7 AND 8), FUNCTION,
RP TISSUE SPECIFICITY, INTERACTION WITH TRAF2 AND NCK, AND
RP AUTOPHOSPHORYLATION.
RX PubMed=10521462; DOI=10.1074/jbc.274.43.30729;
RA Fu C.A., Shen M., Huang B.C., Lasaga J., Payan D.G., Luo Y.;
RT "TNIK, a novel member of the germinal center kinase family that activates
RT the c-Jun N-terminal kinase pathway and regulates the cytoskeleton.";
RL J. Biol. Chem. 274:30729-30737(1999).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. IX. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:31-39(1998).
RN [3] {ECO:0000305}
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
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=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [6] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-769, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=15144186; DOI=10.1021/ac035352d;
RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA Peters E.C.;
RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from
RT human T cells using immobilized metal affinity chromatography and tandem
RT mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [9]
RP FUNCTION, INTERACTION WITH RAP2A, SUBCELLULAR LOCATION,
RP AUTOPHOSPHORYLATION, AND MUTAGENESIS OF LYS-54.
RX PubMed=15342639; DOI=10.1074/jbc.m406370200;
RA Taira K., Umikawa M., Takei K., Myagmar B.-E., Shinzato M., Machida N.,
RA Uezato H., Nonaka S., Kariya K.;
RT "The Traf2- and Nck-interacting kinase as a putative effector of Rap2 to
RT regulate actin cytoskeleton.";
RL J. Biol. Chem. 279:49488-49496(2004).
RN [10]
RP INTERACTION WITH TANC1.
RX PubMed=18930710; DOI=10.1016/j.bbrc.2008.10.038;
RA Nonaka H., Takei K., Umikawa M., Oshiro M., Kuninaka K., Bayarjargal M.,
RA Asato T., Yamashiro Y., Uechi Y., Endo S., Suzuki T., Kariya K.;
RT "MINK is a Rap2 effector for phosphorylation of the postsynaptic scaffold
RT protein TANC1.";
RL Biochem. Biophys. Res. Commun. 377:573-578(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-640 AND SER-769, 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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-640; SER-688; SER-720 AND
RP SER-769, AND 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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-678 AND SER-680, 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 [14]
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 [15]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19061864; DOI=10.1016/j.bbrc.2008.11.107;
RA Uechi Y., Bayarjargal M., Umikawa M., Oshiro M., Takei K., Yamashiro Y.,
RA Asato T., Endo S., Misaki R., Taguchi T., Kariya K.;
RT "Rap2 function requires palmitoylation and recycling endosome
RT localization.";
RL Biochem. Biophys. Res. Commun. 378:732-737(2009).
RN [16]
RP SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-54;
RP 152-ARG-ASP-153 AND 171-ASP-PHE-172, INTERACTION WITH TCF7L2 AND CTNNB1,
RP TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=19816403; DOI=10.1038/emboj.2009.285;
RA Mahmoudi T., Li V.S.W., Ng S.S., Taouatas N., Vries R.G.J., Mohammed S.,
RA Heck A.J., Clevers H.;
RT "The kinase TNIK is an essential activator of Wnt target genes.";
RL EMBO J. 28:3329-3340(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-560; SER-640; SER-688;
RP SER-707; SER-720; SER-766 AND SER-769, AND IDENTIFICATION BY MASS
RP 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 [18]
RP FUNCTION, AND INTERACTION WITH NEDD4 AND RAP2A.
RX PubMed=20159449; DOI=10.1016/j.neuron.2010.01.007;
RA Kawabe H., Neeb A., Dimova K., Young S.M. Jr., Takeda M.,
RA Katsurabayashi S., Mitkovski M., Malakhova O.A., Zhang D.E., Umikawa M.,
RA Kariya K., Goebbels S., Nave K.A., Rosenmund C., Jahn O., Rhee J.,
RA Brose N.;
RT "Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite
RT development.";
RL Neuron 65:358-372(2010).
RN [19]
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 [20]
RP FUNCTION.
RX PubMed=21690388; DOI=10.1073/pnas.1104128108;
RA Kaneko S., Chen X., Lu P., Yao X., Wright T.G., Rajurkar M., Kariya K.,
RA Mao J., Ip Y.T., Xu L.;
RT "Smad inhibition by the Ste20 kinase Misshapen.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:11127-11132(2011).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-326; SER-688 AND SER-769, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-570; SER-600; SER-608;
RP SER-610; SER-640; SER-678; SER-680; SER-688; SER-701; SER-707; SER-720;
RP SER-764; SER-769 AND SER-959, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=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-640 AND SER-680, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [24]
RP POSSIBLE INVOLVEMENT IN MRT54.
RX PubMed=27106596; DOI=10.1007/s00439-016-1671-9;
RA Anazi S., Shamseldin H.E., AlNaqeb D., Abouelhoda M., Monies D.,
RA Salih M.A., Al-Rubeaan K., Alkuraya F.S.;
RT "A null mutation in TNIK defines a novel locus for intellectual
RT disability.";
RL Hum. Genet. 135:773-778(2016).
RN [25]
RP VARIANTS [LARGE SCALE ANALYSIS] GLU-778; GLU-910 AND THR-999.
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 kinase that acts as an essential activator
CC of the Wnt signaling pathway. Recruited to promoters of Wnt target
CC genes and required to activate their expression. May act by
CC phosphorylating TCF4/TCF7L2. Appears to act upstream of the JUN N-
CC terminal pathway. May play a role in the response to environmental
CC stress. Part of a signaling complex composed of NEDD4, RAP2A and TNIK
CC which regulates neuronal dendrite extension and arborization during
CC development. More generally, it may play a role in cytoskeletal
CC rearrangements and regulate cell spreading. Phosphorylates SMAD1 on
CC Thr-322. {ECO:0000269|PubMed:10521462, ECO:0000269|PubMed:15342639,
CC ECO:0000269|PubMed:19061864, ECO:0000269|PubMed:19816403,
CC ECO:0000269|PubMed:20159449, ECO:0000269|PubMed:21690388}.
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:10521462};
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:10521462};
CC -!- SUBUNIT: Interacts (via the CNH domain) with RAP2A (GTP-bound form
CC preferentially); the interaction is direct and required for the
CC activation of TNIK by RAP2A. Interacts with NEDD4; recruits RAP2A to
CC NEDD4. Interacts with TRAF2 and NCK. Interacts with TCF7L2/TCF4 and
CC CTNNB1; the interaction is direct. Interacts with TANC1.
CC {ECO:0000269|PubMed:10521462, ECO:0000269|PubMed:15342639,
CC ECO:0000269|PubMed:18930710, ECO:0000269|PubMed:19816403,
CC ECO:0000269|PubMed:20159449}.
CC -!- INTERACTION:
CC Q9UKE5; P35222: CTNNB1; NbExp=3; IntAct=EBI-1051794, EBI-491549;
CC Q9UKE5; Q9NRI5: DISC1; NbExp=4; IntAct=EBI-1051794, EBI-529989;
CC Q9UKE5; O14920: IKBKB; NbExp=2; IntAct=EBI-1051794, EBI-81266;
CC Q9UKE5; O43318: MAP3K7; NbExp=3; IntAct=EBI-1051794, EBI-358684;
CC Q9UKE5; Q9NYJ8: TAB2; NbExp=3; IntAct=EBI-1051794, EBI-358708;
CC Q9UKE5; Q9NQB0: TCF7L2; NbExp=3; IntAct=EBI-1051794, EBI-924724;
CC Q9UKE5; Q12933: TRAF2; NbExp=2; IntAct=EBI-1051794, EBI-355744;
CC Q9UKE5; Q9Y4K3: TRAF6; NbExp=3; IntAct=EBI-1051794, EBI-359276;
CC Q9UKE5; P03230: LMP1; Xeno; NbExp=7; IntAct=EBI-1051794, EBI-6973030;
CC Q9UKE5; Q6F6B3: Tanc1; Xeno; NbExp=2; IntAct=EBI-1051794, EBI-2133582;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Recycling endosome.
CC Cytoplasm, cytoskeleton. Note=Associated with recycling endosomes and
CC the cytoskeletal fraction upon RAP2A overexpression.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Name=1;
CC IsoId=Q9UKE5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UKE5-2; Sequence=VSP_004889;
CC Name=3;
CC IsoId=Q9UKE5-3; Sequence=VSP_004890;
CC Name=4;
CC IsoId=Q9UKE5-4; Sequence=VSP_004891;
CC Name=5;
CC IsoId=Q9UKE5-5; Sequence=VSP_004889, VSP_004890;
CC Name=6;
CC IsoId=Q9UKE5-6; Sequence=VSP_004889, VSP_004891;
CC Name=7;
CC IsoId=Q9UKE5-7; Sequence=VSP_004890, VSP_004891;
CC Name=8;
CC IsoId=Q9UKE5-8; Sequence=VSP_004889, VSP_004890, VSP_004891;
CC -!- TISSUE SPECIFICITY: Expressed ubiquitously. Highest levels observed in
CC heart, brain and skeletal muscle. Expressed in normal colonic epithelia
CC and colorectal cancer tissues. {ECO:0000269|PubMed:10521462,
CC ECO:0000269|PubMed:19816403}.
CC -!- PTM: Autophosphorylated. Autophosphorylation is activated by RAP2A and
CC induces association to the cytoskeletal fraction.
CC -!- DISEASE: Intellectual developmental disorder, autosomal recessive 54
CC (MRT54) [MIM:617028]: A disorder characterized by significantly below
CC average general intellectual functioning associated with impairments in
CC adaptive behavior and manifested during the developmental period. MRT54
CC patients manifest intellectual disability, delayed speech and
CC hyperactivity. {ECO:0000269|PubMed:27106596}. Note=The disease may be
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA25477.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF172264; AAF03782.1; -; mRNA.
DR EMBL; AF172268; AAF03786.1; -; mRNA.
DR EMBL; AF172267; AAF03785.1; -; mRNA.
DR EMBL; AF172266; AAF03784.1; -; mRNA.
DR EMBL; AF172265; AAF03783.1; -; mRNA.
DR EMBL; AF172270; AAF03788.1; -; mRNA.
DR EMBL; AF172271; AAF03789.1; -; mRNA.
DR EMBL; AF172269; AAF03787.1; -; mRNA.
DR EMBL; AB011123; BAA25477.2; ALT_INIT; mRNA.
DR EMBL; AK291056; BAF83745.1; -; mRNA.
DR EMBL; AC026315; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC078793; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC092919; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC137517; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW78484.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78489.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78492.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78493.1; -; Genomic_DNA.
DR EMBL; BC019081; AAH19081.2; -; mRNA.
DR EMBL; BC150256; AAI50257.1; -; mRNA.
DR CCDS; CCDS46956.1; -. [Q9UKE5-1]
DR CCDS; CCDS54673.1; -. [Q9UKE5-8]
DR CCDS; CCDS54674.1; -. [Q9UKE5-5]
DR CCDS; CCDS54675.1; -. [Q9UKE5-6]
DR CCDS; CCDS54676.1; -. [Q9UKE5-2]
DR CCDS; CCDS54677.1; -. [Q9UKE5-7]
DR CCDS; CCDS54678.1; -. [Q9UKE5-3]
DR CCDS; CCDS54679.1; -. [Q9UKE5-4]
DR RefSeq; NP_001155032.1; NM_001161560.2. [Q9UKE5-4]
DR RefSeq; NP_001155033.1; NM_001161561.2. [Q9UKE5-2]
DR RefSeq; NP_001155034.1; NM_001161562.2. [Q9UKE5-6]
DR RefSeq; NP_001155035.1; NM_001161563.2. [Q9UKE5-3]
DR RefSeq; NP_001155036.1; NM_001161564.2. [Q9UKE5-7]
DR RefSeq; NP_001155037.1; NM_001161565.2. [Q9UKE5-5]
DR RefSeq; NP_001155038.1; NM_001161566.2. [Q9UKE5-8]
DR RefSeq; NP_055843.1; NM_015028.3. [Q9UKE5-1]
DR PDB; 2X7F; X-ray; 2.80 A; A/B/C/D/E=1-325.
DR PDB; 5AX9; X-ray; 2.40 A; A/B/C=11-314.
DR PDB; 5CWZ; X-ray; 2.90 A; A/B/C=11-314.
DR PDB; 5D7A; X-ray; 2.90 A; A/B/C=11-314.
DR PDB; 6RA5; X-ray; 2.90 A; A/B=11-314.
DR PDB; 6RA7; X-ray; 1.20 A; A=11-314.
DR PDBsum; 2X7F; -.
DR PDBsum; 5AX9; -.
DR PDBsum; 5CWZ; -.
DR PDBsum; 5D7A; -.
DR PDBsum; 6RA5; -.
DR PDBsum; 6RA7; -.
DR AlphaFoldDB; Q9UKE5; -.
DR SMR; Q9UKE5; -.
DR BioGRID; 116682; 113.
DR DIP; DIP-37562N; -.
DR IntAct; Q9UKE5; 153.
DR MINT; Q9UKE5; -.
DR STRING; 9606.ENSP00000399511; -.
DR BindingDB; Q9UKE5; -.
DR ChEMBL; CHEMBL4527; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q9UKE5; -.
DR GuidetoPHARMACOLOGY; 2244; -.
DR GlyGen; Q9UKE5; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9UKE5; -.
DR PhosphoSitePlus; Q9UKE5; -.
DR SwissPalm; Q9UKE5; -.
DR BioMuta; TNIK; -.
DR DMDM; 29840818; -.
DR EPD; Q9UKE5; -.
DR jPOST; Q9UKE5; -.
DR MassIVE; Q9UKE5; -.
DR MaxQB; Q9UKE5; -.
DR PaxDb; Q9UKE5; -.
DR PeptideAtlas; Q9UKE5; -.
DR PRIDE; Q9UKE5; -.
DR ProteomicsDB; 84769; -. [Q9UKE5-1]
DR ProteomicsDB; 84770; -. [Q9UKE5-2]
DR ProteomicsDB; 84771; -. [Q9UKE5-3]
DR ProteomicsDB; 84772; -. [Q9UKE5-4]
DR ProteomicsDB; 84773; -. [Q9UKE5-5]
DR ProteomicsDB; 84774; -. [Q9UKE5-6]
DR ProteomicsDB; 84775; -. [Q9UKE5-7]
DR ProteomicsDB; 84776; -. [Q9UKE5-8]
DR Antibodypedia; 2086; 565 antibodies from 33 providers.
DR DNASU; 23043; -.
DR Ensembl; ENST00000284483.12; ENSP00000284483.8; ENSG00000154310.17. [Q9UKE5-4]
DR Ensembl; ENST00000341852.10; ENSP00000345352.6; ENSG00000154310.17. [Q9UKE5-5]
DR Ensembl; ENST00000357327.9; ENSP00000349880.5; ENSG00000154310.17. [Q9UKE5-2]
DR Ensembl; ENST00000436636.7; ENSP00000399511.2; ENSG00000154310.17. [Q9UKE5-1]
DR Ensembl; ENST00000460047.5; ENSP00000418916.1; ENSG00000154310.17. [Q9UKE5-7]
DR Ensembl; ENST00000470834.5; ENSP00000419990.1; ENSG00000154310.17. [Q9UKE5-6]
DR Ensembl; ENST00000475336.5; ENSP00000418156.1; ENSG00000154310.17. [Q9UKE5-8]
DR Ensembl; ENST00000488470.5; ENSP00000418378.1; ENSG00000154310.17. [Q9UKE5-3]
DR GeneID; 23043; -.
DR KEGG; hsa:23043; -.
DR MANE-Select; ENST00000436636.7; ENSP00000399511.2; NM_015028.4; NP_055843.1.
DR UCSC; uc003fhh.3; human. [Q9UKE5-1]
DR CTD; 23043; -.
DR DisGeNET; 23043; -.
DR GeneCards; TNIK; -.
DR HGNC; HGNC:30765; TNIK.
DR HPA; ENSG00000154310; Tissue enhanced (brain).
DR MalaCards; TNIK; -.
DR MIM; 610005; gene.
DR MIM; 617028; phenotype.
DR neXtProt; NX_Q9UKE5; -.
DR OpenTargets; ENSG00000154310; -.
DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability.
DR PharmGKB; PA134893180; -.
DR VEuPathDB; HostDB:ENSG00000154310; -.
DR eggNOG; KOG0587; Eukaryota.
DR GeneTree; ENSGT00950000183196; -.
DR InParanoid; Q9UKE5; -.
DR OMA; VSTHAQE; -.
DR OrthoDB; 533537at2759; -.
DR PhylomeDB; Q9UKE5; -.
DR TreeFam; TF105138; -.
DR PathwayCommons; Q9UKE5; -.
DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence.
DR SignaLink; Q9UKE5; -.
DR SIGNOR; Q9UKE5; -.
DR BioGRID-ORCS; 23043; 13 hits in 1114 CRISPR screens.
DR ChiTaRS; TNIK; human.
DR EvolutionaryTrace; Q9UKE5; -.
DR GeneWiki; TNIK; -.
DR GenomeRNAi; 23043; -.
DR Pharos; Q9UKE5; Tchem.
DR PRO; PR:Q9UKE5; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9UKE5; protein.
DR Bgee; ENSG00000154310; Expressed in cortical plate and 190 other tissues.
DR ExpressionAtlas; Q9UKE5; baseline and differential.
DR Genevisible; Q9UKE5; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0099092; C:postsynaptic density, intracellular component; IEA:Ensembl.
DR GO; GO:0098793; C:presynapse; IEA:Ensembl.
DR GO; GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
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:0031532; P:actin cytoskeleton reorganization; IDA:UniProtKB.
DR GO; GO:0007010; P:cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0000165; P:MAPK cascade; IBA:GO_Central.
DR GO; GO:0030033; P:microvillus assembly; 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:0001934; P:positive regulation of protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0048814; P:regulation of dendrite morphogenesis; IDA:UniProtKB.
DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0010243; P:response to organonitrogen compound; IEA:Ensembl.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR001180; CNH_dom.
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; PF00780; CNH; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00036; CNH; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50219; CNH; 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 3D-structure; Alternative splicing; ATP-binding; Cytoplasm; Cytoskeleton;
KW Endosome; Intellectual disability; Kinase; Neurogenesis;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Wnt signaling pathway.
FT CHAIN 1..1360
FT /note="TRAF2 and NCK-interacting protein kinase"
FT /id="PRO_0000086761"
FT DOMAIN 25..289
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 1047..1334
FT /note="CNH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00795"
FT REGION 284..347
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 290..1047
FT /note="Mediates interaction with NEDD4"
FT /evidence="ECO:0000269|PubMed:20159449"
FT REGION 398..440
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 539..589
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 601..801
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 814..878
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 908..927
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 933..998
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 288..320
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 321..336
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 563..577
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 602..647
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 656..670
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 671..687
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 719..759
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 776..801
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 814..831
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 834..849
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 933..981
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 153
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 31..39
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 54
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 187
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P83510"
FT MOD_RES 324
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P83510"
FT MOD_RES 326
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 560
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 570
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 581
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P83510"
FT MOD_RES 600
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 608
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 610
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 640
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 678
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 680
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 688
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 701
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 707
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 720
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163"
FT MOD_RES 764
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 766
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 769
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:15144186,
FT ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 959
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 445..473
FT /note="Missing (in isoform 2, isoform 5, isoform 6 and
FT isoform 8)"
FT /evidence="ECO:0000303|PubMed:10521462,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_004889"
FT VAR_SEQ 537..591
FT /note="Missing (in isoform 3, isoform 5, isoform 7 and
FT isoform 8)"
FT /evidence="ECO:0000303|PubMed:10521462,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_004890"
FT VAR_SEQ 795..802
FT /note="Missing (in isoform 4, isoform 6, isoform 7 and
FT isoform 8)"
FT /evidence="ECO:0000303|PubMed:10521462"
FT /id="VSP_004891"
FT VARIANT 778
FT /note="K -> E (in dbSNP:rs55778284)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041231"
FT VARIANT 910
FT /note="G -> E (in dbSNP:rs35090763)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041232"
FT VARIANT 999
FT /note="A -> T (in dbSNP:rs17857452)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041233"
FT MUTAGEN 54
FT /note="K->A: Kinase dead. Loss of autophosphorylation and
FT loss of function in cytoskeleton regulation."
FT /evidence="ECO:0000269|PubMed:15342639,
FT ECO:0000269|PubMed:19816403"
FT MUTAGEN 152..153
FT /note="RD->AA: Loss of autophosphorylation."
FT /evidence="ECO:0000269|PubMed:19816403"
FT MUTAGEN 171..172
FT /note="DF->AA: Loss of autophosphorylation."
FT /evidence="ECO:0000269|PubMed:19816403"
FT HELIX 15..17
FT /evidence="ECO:0007829|PDB:6RA7"
FT TURN 22..24
FT /evidence="ECO:0007829|PDB:6RA7"
FT STRAND 25..31
FT /evidence="ECO:0007829|PDB:6RA7"
FT HELIX 32..34
FT /evidence="ECO:0007829|PDB:6RA7"
FT STRAND 37..44
FT /evidence="ECO:0007829|PDB:6RA7"
FT TURN 45..47
FT /evidence="ECO:0007829|PDB:6RA7"
FT STRAND 50..58
FT /evidence="ECO:0007829|PDB:6RA7"
FT TURN 60..62
FT /evidence="ECO:0007829|PDB:5AX9"
FT HELIX 63..76
FT /evidence="ECO:0007829|PDB:6RA7"
FT STRAND 85..91
FT /evidence="ECO:0007829|PDB:6RA7"
FT STRAND 95..97
FT /evidence="ECO:0007829|PDB:5AX9"
FT STRAND 99..106
FT /evidence="ECO:0007829|PDB:6RA7"
FT HELIX 113..118
FT /evidence="ECO:0007829|PDB:6RA7"
FT HELIX 121..123
FT /evidence="ECO:0007829|PDB:6RA7"
FT HELIX 127..146
FT /evidence="ECO:0007829|PDB:6RA7"
FT HELIX 156..158
FT /evidence="ECO:0007829|PDB:6RA7"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:6RA7"
FT STRAND 167..169
FT /evidence="ECO:0007829|PDB:6RA7"
FT TURN 173..175
FT /evidence="ECO:0007829|PDB:2X7F"
FT HELIX 192..194
FT /evidence="ECO:0007829|PDB:6RA7"
FT HELIX 197..200
FT /evidence="ECO:0007829|PDB:6RA7"
FT TURN 201..204
FT /evidence="ECO:0007829|PDB:6RA7"
FT HELIX 213..228
FT /evidence="ECO:0007829|PDB:6RA7"
FT TURN 232..235
FT /evidence="ECO:0007829|PDB:6RA7"
FT HELIX 238..244
FT /evidence="ECO:0007829|PDB:6RA7"
FT TURN 245..247
FT /evidence="ECO:0007829|PDB:6RA7"
FT STRAND 256..258
FT /evidence="ECO:0007829|PDB:6RA5"
FT HELIX 260..269
FT /evidence="ECO:0007829|PDB:6RA7"
FT HELIX 274..276
FT /evidence="ECO:0007829|PDB:6RA7"
FT HELIX 280..284
FT /evidence="ECO:0007829|PDB:6RA7"
FT HELIX 287..290
FT /evidence="ECO:0007829|PDB:6RA7"
FT HELIX 295..313
FT /evidence="ECO:0007829|PDB:6RA7"
SQ SEQUENCE 1360 AA; 154943 MW; 3590BC2905A72C3D CRC64;
MASDSPARSL DEIDLSALRD PAGIFELVEL VGNGTYGQVY KGRHVKTGQL AAIKVMDVTG
DEEEEIKQEI NMLKKYSHHR NIATYYGAFI KKNPPGMDDQ LWLVMEFCGA GSVTDLIKNT
KGNTLKEEWI AYICREILRG LSHLHQHKVI HRDIKGQNVL LTENAEVKLV DFGVSAQLDR
TVGRRNTFIG TPYWMAPEVI ACDENPDATY DFKSDLWSLG ITAIEMAEGA PPLCDMHPMR
ALFLIPRNPA PRLKSKKWSK KFQSFIESCL VKNHSQRPAT EQLMKHPFIR DQPNERQVRI
QLKDHIDRTK KKRGEKDETE YEYSGSEEEE EENDSGEPSS ILNLPGESTL RRDFLRLQLA
NKERSEALRR QQLEQQQREN EEHKRQLLAE RQKRIEEQKE QRRRLEEQQR REKELRKQQE
REQRRHYEEQ MRREEERRRA EHEQEYIRRQ LEEEQRQLEI LQQQLLHEQA LLLEYKRKQL
EEQRQAERLQ RQLKQERDYL VSLQHQRQEQ RPVEKKPLYH YKEGMSPSEK PAWAKEVEER
SRLNRQSSPA MPHKVANRIS DPNLPPRSES FSISGVQPAR TPPMLRPVDP QIPHLVAVKS
QGPALTASQS VHEQPTKGLS GFQEALNVTS HRVEMPRQNS DPTSENPPLP TRIEKFDRSS
WLRQEEDIPP KVPQRTTSIS PALARKNSPG NGSALGPRLG SQPIRASNPD LRRTEPILES
PLQRTSSGSS SSSSTPSSQP SSQGGSQPGS QAGSSERTRV RANSKSEGSP VLPHEPAKVK
PEESRDITRP SRPASYKKAI DEDLTALAKE LRELRIEETN RPMKKVTDYS SSSEESESSE
EEEEDGESET HDGTVAVSDI PRLIPTGAPG SNEQYNVGMV GTHGLETSHA DSFSGSISRE
GTLMIRETSG EKKRSGHSDS NGFAGHINLP DLVQQSHSPA GTPTEGLGRV STHSQEMDSG
TEYGMGSSTK ASFTPFVDPR VYQTSPTDED EEDEESSAAA LFTSELLRQE QAKLNEARKI
SVVNVNPTNI RPHSDTPEIR KYKKRFNSEI LCAALWGVNL LVGTENGLML LDRSGQGKVY
NLINRRRFQQ MDVLEGLNVL VTISGKKNKL RVYYLSWLRN RILHNDPEVE KKQGWITVGD
LEGCIHYKVV KYERIKFLVI ALKNAVEIYA WAPKPYHKFM AFKSFADLQH KPLLVDLTVE
EGQRLKVIFG SHTGFHVIDV DSGNSYDIYI PSHIQGNITP HAIVILPKTD GMEMLVCYED
EGVYVNTYGR ITKDVVLQWG EMPTSVAYIH SNQIMGWGEK AIEIRSVETG HLDGVFMHKR
AQRLKFLCER NDKVFFASVR SGGSSQVFFM TLNRNSMMNW
