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 24-JAN-2024, entry version 214. 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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 PDB; 7XZQ; X-ray; 2.09 A; A=11-314. DR PDB; 7XZR; X-ray; 2.26 A; A/B=11-314. DR PDBsum; 2X7F; -. DR PDBsum; 5AX9; -. DR PDBsum; 5CWZ; -. DR PDBsum; 5D7A; -. DR PDBsum; 6RA5; -. DR PDBsum; 6RA7; -. DR PDBsum; 7XZQ; -. DR PDBsum; 7XZR; -. DR AlphaFoldDB; Q9UKE5; -. DR SMR; Q9UKE5; -. DR BioGRID; 116682; 151. DR DIP; DIP-37562N; -. DR IntAct; Q9UKE5; 165. DR MINT; Q9UKE5; -. DR STRING; 9606.ENSP00000399511; -. DR BindingDB; Q9UKE5; -. DR ChEMBL; CHEMBL4527; -. DR DrugBank; DB12010; Fostamatinib. DR DrugCentral; Q9UKE5; -. DR GuidetoPHARMACOLOGY; 2244; -. DR GlyCosmos; Q9UKE5; 1 site, 1 glycan. DR GlyGen; Q9UKE5; 2 sites, 1 O-linked glycan (2 sites). 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; 9606-ENSP00000399511; -. DR PeptideAtlas; 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 Pumba; Q9UKE5; -. DR Antibodypedia; 2086; 631 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 AGR; HGNC:30765; -. 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; 2904475at2759; -. 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; 14 hits in 1193 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 192 other cell types or tissues. DR ExpressionAtlas; Q9UKE5; baseline and differential. 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:0030036; P:actin cytoskeleton organization; 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 CDD; cd06637; STKc_TNIK; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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 PANTHER; PTHR47096:SF1; CNH DOMAIN-CONTAINING PROTEIN; 1. DR PANTHER; PTHR47096; MISSHAPEN LIKE KINASE 1; 1. DR Pfam; PF00780; CNH; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00036; CNH; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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. DR Genevisible; Q9UKE5; HS. 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 HELIX 60..62 FT /evidence="ECO:0007829|PDB:7XZQ" 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 STRAND 179..182 FT /evidence="ECO:0007829|PDB:7XZQ" 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 //