ID TF7L2_HUMAN Reviewed; 619 AA. AC Q9NQB0; B4DRJ8; B9X074; C6ZRJ8; C6ZRK0; E2GH14; E2GH19; E2GH20; E2GH24; AC E2GH25; E9PFH9; F8W742; F8W7T5; O00185; Q9NQB1; Q9NQB2; Q9NQB3; Q9NQB4; AC Q9NQB5; Q9NQB6; Q9NQB7; Q9ULC2; DT 25-MAR-2003, integrated into UniProtKB/Swiss-Prot. DT 25-MAR-2003, sequence version 2. DT 24-JAN-2024, entry version 223. DE RecName: Full=Transcription factor 7-like 2; DE AltName: Full=HMG box transcription factor 4; DE AltName: Full=T-cell-specific transcription factor 4; DE Short=T-cell factor 4; DE Short=TCF-4; DE Short=hTCF-4; GN Name=TCF7L2; Synonyms=TCF4; 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] (ISOFORMS 8 AND 9), AND INTERACTION WITH CTNNB1. RC TISSUE=Fetus; RX PubMed=9065401; DOI=10.1126/science.275.5307.1784; RA Korinek V., Barker N., Morin P.J., van Wichen D., de Weger R., RA Kinzler K.W., Vogelstein B., Clevers H.; RT "Constitutive transcriptional activation by a beta-catenin-Tcf complex in RT APC-/- colon carcinoma."; RL Science 275:1784-1787(1997). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1; 2; 3; 4; 5; 6; 7 AND 9), AND RP VARIANT ASN-346. RX PubMed=10919662; RA Duval A., Rolland S., Tubacher E., Bui H., Thomas G., Hamelin R.; RT "The human T cell transcription factor-4 gene: structure, extensive RT characterization of alternative splicings, and mutational analysis in RT colorectal cancer cell lines."; RL Cancer Res. 60:3872-3879(2000). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 12; 13 AND 14), AND ALTERNATIVE RP SPLICING. RC TISSUE=Brain; RX PubMed=19602480; DOI=10.1093/hmg/ddp321; RA Prokunina-Olsson L., Welch C., Hansson O., Adhikari N., Scott L.J., RA Usher N., Tong M., Sprau A., Swift A., Bonnycastle L.L., Erdos M.R., He Z., RA Saxena R., Harmon B., Kotova O., Hoffman E.P., Altshuler D., Groop L., RA Boehnke M., Collins F.S., Hall J.L.; RT "Tissue-specific alternative splicing of TCF7L2."; RL Hum. Mol. Genet. 18:3795-3804(2009). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 6; 9; 13; 14; 15 AND 17), AND RP ALTERNATIVE SPLICING. RX PubMed=21256126; DOI=10.1016/j.yexcr.2011.01.015; RA Tsedensodnom O., Koga H., Rosenberg S.A., Nambotin S.B., Carroll J.J., RA Wands J.R., Kim M.; RT "Identification of T-cell factor-4 isoforms that contribute to the RT malignant phenotype of hepatocellular carcinoma cells."; RL Exp. Cell Res. 317:920-931(2011). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 9). RC TISSUE=Colon; RA Iseki H., Takeda A., Andou T., Takahashi N., Ban S., Kurochkin I.V., RA Okazaki Y., Koyama I.; RT "ALEX1, a putative tumor suppressor, is regulated by CREB-dependent Wnt RT signaling, and is silenced by promoter methylation in human colorectal RT cancer."; RL Submitted (JUN-2008) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 14). 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton 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 [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 10). RC TISSUE=Uterus; 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 [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 449-494. RC TISSUE=Gastric carcinoma; RA Saeki H., Tanaka S., Sugimachi K.; RT "Human TCF-4 splice form B."; RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases. RN [11] RP FUNCTION. RX PubMed=9727977; DOI=10.1126/science.281.5382.1509; RA He T.-C., Sparks A.B., Rago C., Hermeking H., Zawel L., da Costa L.T., RA Morin P.J., Vogelstein B., Kinzler K.W.; RT "Identification of c-MYC as a target of the APC pathway."; RL Science 281:1509-1512(1998). RN [12] RP TISSUE SPECIFICITY, INTERACTION WITH CTNNB1, AND SUBCELLULAR LOCATION. RX PubMed=9916915; DOI=10.1016/s0002-9440(10)65247-9; RA Barker N., Huls G., Korinek V., Clevers H.; RT "Restricted high level expression of Tcf-4 protein in intestinal and RT mammary gland epithelium."; RL Am. J. Pathol. 154:29-35(1999). RN [13] RP INTERACTION WITH CTNNB1, AND MUTAGENESIS OF 10-ASP-ASP-11; ASP-16; GLU-17; RP 23-ASP-GLU-24 AND LEU-48. RX PubMed=10080941; DOI=10.1006/bbrc.1999.0379; RA Omer C.A., Miller P.J., Diehl R.E., Kral A.M.; RT "Identification of Tcf4 residues involved in high-affinity beta-catenin RT binding."; RL Biochem. Biophys. Res. Commun. 256:584-590(1999). RN [14] RP INTERACTION WITH TLE1; TLE2; TLE3 AND TLE4. RX PubMed=11266540; DOI=10.1093/nar/29.7.1410; RA Brantjes H., Roose J., van De Wetering M., Clevers H.; RT "All Tcf HMG box transcription factors interact with Groucho-related co- RT repressors."; RL Nucleic Acids Res. 29:1410-1419(2001). RN [15] RP FUNCTION. RX PubMed=12408868; DOI=10.1016/s0092-8674(02)01014-0; RA van de Wetering M., Sancho E., Verweij C., de Lau W., Oving I., RA Hurlstone A., van der Horn K., Batlle E., Coudreuse D., Haramis A.-P., RA Tjon-Pon-Fong M., Moerer P., van den Born M., Soete G., Pals S., Eilers M., RA Medema R., Clevers H.; RT "The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on RT colorectal cancer cells."; RL Cell 111:241-250(2002). RN [16] RP SUMOYLATION AT LYS-320, INTERACTION WITH PIAS4, FUNCTION, SUBCELLULAR RP LOCATION, AND MUTAGENESIS OF LYS-320 AND GLU-322. RX PubMed=12727872; DOI=10.1093/emboj/cdg204; RA Yamamoto H., Ihara M., Matsuura Y., Kikuchi A.; RT "Sumoylation is involved in beta-catenin-dependent activation of Tcf-4."; RL EMBO J. 22:2047-2059(2003). RN [17] RP INTERACTION WITH EP300. RX PubMed=12446687; DOI=10.1074/jbc.m210081200; RA Hecht A., Stemmler M.P.; RT "Identification of a promoter-specific transcriptional activation domain at RT the C-terminus of the Wnt effector protein T-cell factor 4."; RL J. Biol. Chem. 278:3776-3785(2003). RN [18] RP INTERACTION WITH NLK, PHOSPHORYLATION AT THR-201 AND/OR THR-212 BY NLK, AND RP MUTAGENESIS OF THR-201 AND THR-212. RX PubMed=12556497; DOI=10.1128/mcb.23.4.1379-1389.2003; RA Ishitani T., Ninomiya-Tsuji J., Matsumoto K.; RT "Regulation of lymphoid enhancer factor 1/T-cell factor by mitogen- RT activated protein kinase-related Nemo-like kinase-dependent phosphorylation RT in Wnt/beta-catenin signaling."; RL Mol. Cell. Biol. 23:1379-1389(2003). RN [19] RP INTERACTION WITH NLK. RX PubMed=16714285; DOI=10.1074/jbc.m602089200; RA Yamada M., Ohnishi J., Ohkawara B., Iemura S., Satoh K., Hyodo-Miura J., RA Kawachi K., Natsume T., Shibuya H.; RT "NARF, an nemo-like kinase (NLK)-associated ring finger protein regulates RT the ubiquitylation and degradation of T cell factor/lymphoid enhancer RT factor (TCF/LEF)."; RL J. Biol. Chem. 281:20749-20760(2006). RN [20] RP INVOLVEMENT IN T2D. RX PubMed=16415884; DOI=10.1038/ng1732; RA Grant S.F.A., Thorleifsson G., Reynisdottir I., Benediktsson R., RA Manolescu A., Sainz J., Helgason A., Stefansson H., Emilsson V., RA Helgadottir A., Styrkarsdottir U., Magnusson K.P., Walters G.B., RA Palsdottir E., Jonsdottir T., Gudmundsdottir T., Gylfason A., RA Saemundsdottir J., Wilensky R.L., Reilly M.P., Rader D.J., Bagger Y., RA Christiansen C., Gudnason V., Sigurdsson G., Thorsteinsdottir U., RA Gulcher J.R., Kong A., Stefansson K.; RT "Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of RT type 2 diabetes."; RL Nat. Genet. 38:320-323(2006). RN [21] RP INTERACTION WITH DDIT3. RX PubMed=16434966; DOI=10.1038/sj.onc.1209380; RA Horndasch M., Lienkamp S., Springer E., Schmitt A., Pavenstaedt H., RA Walz G., Gloy J.; RT "The C/EBP homologous protein CHOP (GADD153) is an inhibitor of Wnt/TCF RT signals."; RL Oncogene 25:3397-3407(2006). RN [22] RP INTERACTION WITH CCDC85B. RX PubMed=17873903; DOI=10.1038/sj.onc.1210801; RA Iwai A., Hijikata M., Hishiki T., Isono O., Chiba T., Shimotohno K.; RT "Coiled-coil domain containing 85B suppresses the beta-catenin activity in RT a p53-dependent manner."; RL Oncogene 27:1520-1526(2008). RN [23] RP INTERACTION WITH TNIK AND CTNNB1. 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 [24] RP FUNCTION, AND INTERACTION WITH MAD2L2. RX PubMed=19443654; DOI=10.1074/jbc.m109.005017; RA Hong C.F., Chou Y.T., Lin Y.S., Wu C.W.; RT "MAD2B, a novel TCF4-binding protein, modulates TCF4-mediated epithelial- RT mesenchymal transdifferentiation."; RL J. Biol. Chem. 284:19613-19622(2009). RN [25] RP INTERACTION WITH DAZAP2, AND SUBCELLULAR LOCATION. RX PubMed=19304756; DOI=10.1093/nar/gkp179; RA Lukas J., Mazna P., Valenta T., Doubravska L., Pospichalova V., RA Vojtechova M., Fafilek B., Ivanek R., Plachy J., Novak J., Korinek V.; RT "Dazap2 modulates transcription driven by the Wnt effector TCF-4."; RL Nucleic Acids Res. 37:3007-3020(2009). RN [26] RP INTERACTION WITH NLK AND ZIPK/DAPK3. RX PubMed=21454679; DOI=10.1074/jbc.m110.189829; RA Togi S., Ikeda O., Kamitani S., Nakasuji M., Sekine Y., Muromoto R., RA Nanbo A., Oritani K., Kawai T., Akira S., Matsuda T.; RT "Zipper-interacting protein kinase (ZIPK) modulates canonical Wnt/beta- RT catenin signaling through interaction with Nemo-like kinase and T-cell RT factor 4 (NLK/TCF4)."; RL J. Biol. Chem. 286:19170-19177(2011). RN [27] RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH FERMT2 AND CTNNB1, AND RP SUBCELLULAR LOCATION. RX PubMed=22699938; DOI=10.1038/embor.2012.88; RA Yu Y., Wu J., Wang Y., Zhao T., Ma B., Liu Y., Fang W., Zhu W.G., Zhang H.; RT "Kindlin 2 forms a transcriptional complex with beta-catenin and TCF4 to RT enhance Wnt signalling."; RL EMBO Rep. 13:750-758(2012). RN [28] RP INTERACTION WITH PML. RX PubMed=22155184; DOI=10.1053/j.gastro.2011.11.041; RA Satow R., Shitashige M., Jigami T., Fukami K., Honda K., Kitabayashi I., RA Yamada T.; RT "Beta-catenin inhibits promyelocytic leukemia protein tumor suppressor RT function in colorectal cancer cells."; RL Gastroenterology 142:572-581(2012). RN [29] RP INTERACTION WITH SPIN1. RX PubMed=22258766; DOI=10.1158/1541-7786.mcr-11-0440; RA Wang J.X., Zeng Q., Chen L., Du J.C., Yan X.L., Yuan H.F., Zhai C., RA Zhou J.N., Jia Y.L., Yue W., Pei X.T.; RT "SPINDLIN1 promotes cancer cell proliferation through activation of RT WNT/TCF-4 signaling."; RL Mol. Cancer Res. 10:326-335(2012). RN [30] RP INTERACTION WITH XIAP/BIRC4 AND TLE3. RX PubMed=22304967; DOI=10.1016/j.molcel.2011.12.032; RA Hanson A.J., Wallace H.A., Freeman T.J., Beauchamp R.D., Lee L.A., Lee E.; RT "XIAP monoubiquitylates Groucho/TLE to promote canonical Wnt signaling."; RL Mol. Cell 45:619-628(2012). RN [31] RP INTERACTION WITH SPIN1. RX PubMed=24589551; DOI=10.1101/gad.233239.113; RA Su X., Zhu G., Ding X., Lee S.Y., Dou Y., Zhu B., Wu W., Li H.; RT "Molecular basis underlying histone H3 lysine-arginine methylation pattern RT readout by Spin/Ssty repeats of Spindlin1."; RL Genes Dev. 28:622-636(2014). RN [32] 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 [33] RP INVOLVEMENT IN T2D. RX PubMed=24390345; DOI=10.1038/nature12828; RG The SIGMA Type 2 Diabetes Consortium; RT "Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes RT in Mexico."; RL Nature 506:97-101(2014). RN [34] RP INTERACTION WITH CTNNB1. RX PubMed=28829046; DOI=10.1038/cr.2017.107; RA Lu Y., Xie S., Zhang W., Zhang C., Gao C., Sun Q., Cai Y., Xu Z., Xiao M., RA Xu Y., Huang X., Wu X., Liu W., Wang F., Kang Y., Zhou T.; RT "Twa1/Gid8 is a beta-catenin nuclear retention factor in Wnt signaling and RT colorectal tumorigenesis."; RL Cell Res. 27:1422-1440(2017). RN [35] RP INTERACTION WITH C11ORF84/SPINDOC AND SPIN1. RX PubMed=29061846; DOI=10.1074/jbc.m117.814913; RA Bae N., Gao M., Li X., Premkumar T., Sbardella G., Chen J., Bedford M.T.; RT "A transcriptional coregulator, SPIN-DOC, attenuates the coactivator RT activity of Spindlin1."; RL J. Biol. Chem. 292:20808-20817(2017). RN [36] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-22 AND LYS-539, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [37] RP INTERACTION WITH CTNNB1. RX PubMed=29739711; DOI=10.1016/j.ebiom.2018.04.026; RA Han F., Liu W.B., Shi X.Y., Yang J.T., Zhang X., Li Z.M., Jiang X., Yin L., RA Li J.J., Huang C.S., Cao J., Liu J.Y.; RT "SOX30 Inhibits Tumor Metastasis through Attenuating Wnt-Signaling via RT Transcriptional and Posttranslational Regulation of beta-Catenin in Lung RT Cancer."; RL EBioMedicine 31:253-266(2018). RN [38] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 12-49 IN COMPLEX WITH THE RP ARMADILLO REPEAT REGION OF CTNNB1, AND MUTAGENESIS OF GLU-24; GLU-26; RP GLU-28 AND GLU-29. RX PubMed=11713475; DOI=10.1038/nsb718; RA Graham T.A., Ferkey D.M., Mao F., Kimelman D., Xu W.; RT "Tcf4 can specifically recognize beta-catenin using alternative RT conformations."; RL Nat. Struct. Biol. 8:1048-1052(2001). RN [39] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 8-54 IN COMPLEX WITH THE ARMADILLO RP REPEAT REGION OF CTNNB1, AND MUTAGENESIS OF ILE-19 AND PHE-21. RX PubMed=11713476; DOI=10.1038/nsb720; RA Poy F., Lepourcelet M., Shivdasani R.A., Eck M.J.; RT "Structure of a human Tcf4-beta-catenin complex."; RL Nat. Struct. Biol. 8:1053-1057(2001). RN [40] RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 1-53 IN COMPLEX WITH BCL9 AND RP CTNNB1, AND INTERACTION WITH CTNNB1. RX PubMed=17052462; DOI=10.1016/j.molcel.2006.09.001; RA Sampietro J., Dahlberg C.L., Cho U.S., Hinds T.R., Kimelman D., Xu W.; RT "Crystal structure of a beta-catenin/BCL9/Tcf4 complex."; RL Mol. Cell 24:293-300(2006). RN [41] RP VARIANT [LARGE SCALE ANALYSIS] CYS-465. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Participates in the Wnt signaling pathway and modulates MYC CC expression by binding to its promoter in a sequence-specific manner. CC Acts as a repressor in the absence of CTNNB1, and as activator in its CC presence. Activates transcription from promoters with several copies of CC the Tcf motif 5'-CCTTTGATC-3' in the presence of CTNNB1. TLE1, TLE2, CC TLE3 and TLE4 repress transactivation mediated by TCF7L2/TCF4 and CC CTNNB1. Expression of dominant-negative mutants results in cell-cycle CC arrest in G1. Necessary for the maintenance of the epithelial stem-cell CC compartment of the small intestine. {ECO:0000269|PubMed:12408868, CC ECO:0000269|PubMed:12727872, ECO:0000269|PubMed:19443654, CC ECO:0000269|PubMed:22699938, ECO:0000269|PubMed:9727977}. CC -!- SUBUNIT: Interacts with TGFB1I1 (By similarity). Interacts with CTNNB1 CC (via the armadillo repeat); forms stable transcription complex CC (PubMed:9065401, PubMed:9916915, PubMed:10080941, PubMed:19816403, CC PubMed:28829046, PubMed:29739711, PubMed:17052462). Interacts with CC EP300. Interacts with NLK. Interacts with CCDC85B (probably through the CC HMG box); prevents interaction with CTNNB1. Interacts with TNIK. CC Interacts with MAD2L2; prevents TCF7L2/TCF4 binding to CC promZIPK/DAPK3oters, negatively modulating its transcriptional CC activity. Interacts with ZIPK/DAPK3. Interacts with XIAP/BIRC4 and CC TLE3. Interacts with DDIT3/CHOP. The CTNNB1 and TCF7L2/TCF4 complex CC interacts with PML (isoform PML-4). Identified in a complex with CTNNB1 CC and FERMT2. Interacts with SPIN1 (PubMed:22258766, PubMed:24589551, CC PubMed:29061846). Interacts with C11orf84/SPINDOC in a SPIN1-dependent CC manner (PubMed:29061846). Interacts with DAZAP2; the interaction CC results in localization of DAZAP2 to the nucleus (PubMed:19304756). CC {ECO:0000250|UniProtKB:Q924A0, ECO:0000269|PubMed:10080941, CC ECO:0000269|PubMed:11266540, ECO:0000269|PubMed:12446687, CC ECO:0000269|PubMed:12556497, ECO:0000269|PubMed:12727872, CC ECO:0000269|PubMed:16434966, ECO:0000269|PubMed:16714285, CC ECO:0000269|PubMed:17052462, ECO:0000269|PubMed:17873903, CC ECO:0000269|PubMed:19304756, ECO:0000269|PubMed:19443654, CC ECO:0000269|PubMed:19816403, ECO:0000269|PubMed:21454679, CC ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22258766, CC ECO:0000269|PubMed:22304967, ECO:0000269|PubMed:22699938, CC ECO:0000269|PubMed:24589551, ECO:0000269|PubMed:28829046, CC ECO:0000269|PubMed:29061846, ECO:0000269|PubMed:29739711, CC ECO:0000269|PubMed:9065401, ECO:0000269|PubMed:9916915}. CC -!- INTERACTION: CC Q9NQB0; P35222: CTNNB1; NbExp=27; IntAct=EBI-924724, EBI-491549; CC Q9NQB0; Q9UER7: DAXX; NbExp=5; IntAct=EBI-924724, EBI-77321; CC Q9NQB0; Q14526: HIC1; NbExp=6; IntAct=EBI-924724, EBI-2507362; CC Q9NQB0; Q13761: RUNX3; NbExp=14; IntAct=EBI-924724, EBI-925990; CC Q9NQB0; Q9UKE5: TNIK; NbExp=3; IntAct=EBI-924724, EBI-1051794; CC Q9NQB0; P12956: XRCC6; NbExp=10; IntAct=EBI-924724, EBI-353208; CC Q9NQB0-10; Q5BKX5-3: ACTMAP; NbExp=3; IntAct=EBI-11746252, EBI-11976299; CC Q9NQB0-10; Q9NP55: BPIFA1; NbExp=3; IntAct=EBI-11746252, EBI-953896; CC Q9NQB0-10; Q9BYD5: CNFN; NbExp=3; IntAct=EBI-11746252, EBI-12819063; CC Q9NQB0-10; O43186: CRX; NbExp=3; IntAct=EBI-11746252, EBI-748171; CC Q9NQB0-10; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-11746252, EBI-3867333; CC Q9NQB0-10; A1KXE4-2: FAM168B; NbExp=3; IntAct=EBI-11746252, EBI-12193763; CC Q9NQB0-10; Q08379: GOLGA2; NbExp=3; IntAct=EBI-11746252, EBI-618309; CC Q9NQB0-10; Q5TA45: INTS11; NbExp=3; IntAct=EBI-11746252, EBI-748258; CC Q9NQB0-10; P14923: JUP; NbExp=3; IntAct=EBI-11746252, EBI-702484; CC Q9NQB0-10; Q3LI72: KRTAP19-5; NbExp=3; IntAct=EBI-11746252, EBI-1048945; CC Q9NQB0-10; Q3SYF9: KRTAP19-7; NbExp=3; IntAct=EBI-11746252, EBI-10241353; CC Q9NQB0-10; Q3LI59: KRTAP21-2; NbExp=3; IntAct=EBI-11746252, EBI-18395721; CC Q9NQB0-10; Q3LI64: KRTAP6-1; NbExp=3; IntAct=EBI-11746252, EBI-12111050; CC Q9NQB0-10; Q3LI66: KRTAP6-2; NbExp=5; IntAct=EBI-11746252, EBI-11962084; CC Q9NQB0-10; Q8IUC3: KRTAP7-1; NbExp=3; IntAct=EBI-11746252, EBI-18394498; CC Q9NQB0-10; P35548: MSX2; NbExp=3; IntAct=EBI-11746252, EBI-6447480; CC Q9NQB0-10; Q9UF11-2: PLEKHB1; NbExp=3; IntAct=EBI-11746252, EBI-12832742; CC Q9NQB0-10; O43741: PRKAB2; NbExp=3; IntAct=EBI-11746252, EBI-1053424; CC Q9NQB0-10; P86480: PRR20D; NbExp=3; IntAct=EBI-11746252, EBI-12754095; CC Q9NQB0-10; Q53HV7-2: SMUG1; NbExp=3; IntAct=EBI-11746252, EBI-12275818; CC Q9NQB0-10; Q08117-2: TLE5; NbExp=3; IntAct=EBI-11746252, EBI-11741437; CC Q9NQB0-10; Q13077: TRAF1; NbExp=3; IntAct=EBI-11746252, EBI-359224; CC Q9NQB0-10; Q86WV8: TSC1; NbExp=3; IntAct=EBI-11746252, EBI-12806590; CC Q9NQB0-10; Q6NVU6: UFSP1; NbExp=3; IntAct=EBI-11746252, EBI-12068150; CC -!- SUBCELLULAR LOCATION: Nucleus, PML body {ECO:0000269|PubMed:12727872, CC ECO:0000269|PubMed:22699938, ECO:0000269|PubMed:9916915}. Nucleus CC {ECO:0000269|PubMed:19304756}. Note=Diffuse pattern. Colocalizes with CC SUMO1 and PIAS4 in a subset of PML (promyelocytic leukemia) nuclear CC bodies. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=17; CC Name=1; Synonyms=TCF-4M; CC IsoId=Q9NQB0-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9NQB0-2; Sequence=VSP_006970, VSP_006972; CC Name=3; CC IsoId=Q9NQB0-3; Sequence=VSP_006966; CC Name=4; CC IsoId=Q9NQB0-4; Sequence=VSP_006964, VSP_006970, VSP_006972; CC Name=5; CC IsoId=Q9NQB0-5; Sequence=VSP_006964; CC Name=6; Synonyms=TCF-4I; CC IsoId=Q9NQB0-6; Sequence=VSP_006967; CC Name=7; CC IsoId=Q9NQB0-7; Sequence=VSP_006964, VSP_006966; CC Name=8; CC IsoId=Q9NQB0-8; Sequence=VSP_006962; CC Name=9; Synonyms=TCF-4G; CC IsoId=Q9NQB0-9; Sequence=VSP_006965, VSP_006969; CC Name=10; CC IsoId=Q9NQB0-10; Sequence=VSP_006962, VSP_006963, VSP_006968, CC VSP_006971; CC Name=11; CC IsoId=Q9NQB0-11; Sequence=VSP_006962, VSP_045821, VSP_006965, CC VSP_006969; CC Name=12; CC IsoId=Q9NQB0-12; Sequence=VSP_006962, VSP_045822; CC Name=13; Synonyms=TCF-4J; CC IsoId=Q9NQB0-13; Sequence=VSP_006962, VSP_006964, VSP_006966; CC Name=14; Synonyms=TCF-4B, short; CC IsoId=Q9NQB0-14; Sequence=VSP_006962, VSP_006965, VSP_006969; CC Name=15; Synonyms=TCF-4A; CC IsoId=Q9NQB0-15; Sequence=VSP_006962, VSP_053750, VSP_006965, CC VSP_006969; CC Name=16; Synonyms=TCF-4K; CC IsoId=Q9NQB0-16; Sequence=VSP_006962, VSP_053750, VSP_006964; CC Name=17; Synonyms=TCF-4X2; CC IsoId=Q9NQB0-17; Sequence=VSP_053748, VSP_053749; CC -!- TISSUE SPECIFICITY: Detected in epithelium from small intestine, with CC the highest expression at the top of the crypts and a gradient of CC expression from crypt to villus. Detected in colon epithelium and colon CC cancer, and in epithelium from mammary gland and carcinomas derived CC therefrom. {ECO:0000269|PubMed:9916915}. CC -!- DEVELOPMENTAL STAGE: Highly expressed in crypt regions and barely CC detectable in villi in epithelium from fetal small intestine at week CC 16. At week 22 expression in villi had increased strongly. CC -!- DOMAIN: The promoter-specific activation domain interacts with the CC transcriptional coactivator EP300. CC -!- PTM: In vitro, phosphorylated by TNIK. {ECO:0000269|PubMed:12556497}. CC -!- PTM: Phosphorylated at Thr-201 and/or Thr-212 by NLK. Phosphorylation CC by NLK at these sites inhibits DNA-binding by TCF7L2/TCF4, thereby CC preventing transcriptional activation of target genes of the canonical CC Wnt/beta-catenin signaling pathway. {ECO:0000269|PubMed:12556497}. CC -!- PTM: Polysumoylated. Sumoylation is enhanced by PIAS family members and CC desumoylation is enhanced by SENP2. Sumoylation/desumoylation regulates CC TCF7L2/TCF4 transcription activity in the Wnt/beta-catenin signaling CC pathway without altering interaction with CTNNB1 nor binding to DNA. CC {ECO:0000269|PubMed:12727872}. CC -!- DISEASE: Note=Constitutive activation and subsequent transactivation of CC target genes may lead to the maintenance of stem-cell characteristics CC (cycling and longevity) in cells that should normally undergo terminal CC differentiation and constitute the primary transforming event in CC colorectal cancer (CRC). CC -!- DISEASE: Type 2 diabetes mellitus (T2D) [MIM:125853]: A multifactorial CC disorder of glucose homeostasis caused by a lack of sensitivity to the CC body's own insulin. Affected individuals usually have an obese body CC habitus and manifestations of a metabolic syndrome characterized by CC diabetes, insulin resistance, hypertension and hypertriglyceridemia. CC The disease results in long-term complications that affect the eyes, CC kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:16415884, CC ECO:0000269|PubMed:24390345}. Note=Disease susceptibility is associated CC with variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 12]: Low expression in pancreas and colon. CC {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 13]: Common splicing form, lowest expression in CC skeletal muscle. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 14]: High transcriptional activity. Major CC isoform in liver. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the TCF/LEF family. {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; Y11306; CAA72166.2; -; mRNA. DR EMBL; AJ270770; CAB97212.1; -; Genomic_DNA. DR EMBL; AJ270771; CAB97212.1; JOINED; Genomic_DNA. DR EMBL; AJ270772; CAB97212.1; JOINED; Genomic_DNA. DR EMBL; AJ270773; CAB97212.1; JOINED; Genomic_DNA. DR EMBL; AJ270774; CAB97212.1; JOINED; Genomic_DNA. DR EMBL; AJ270775; CAB97212.1; JOINED; Genomic_DNA. DR EMBL; AJ270776; CAB97212.1; JOINED; Genomic_DNA. DR EMBL; AJ270778; CAB97212.1; JOINED; Genomic_DNA. DR EMBL; AJ270770; CAB97213.1; -; Genomic_DNA. DR EMBL; AJ270771; CAB97213.1; JOINED; Genomic_DNA. DR EMBL; AJ270772; CAB97213.1; JOINED; Genomic_DNA. DR EMBL; AJ270773; CAB97213.1; JOINED; Genomic_DNA. DR EMBL; AJ270774; CAB97213.1; JOINED; Genomic_DNA. DR EMBL; AJ270775; CAB97213.1; JOINED; Genomic_DNA. DR EMBL; AJ270776; CAB97213.1; JOINED; Genomic_DNA. DR EMBL; AJ270778; CAB97213.1; JOINED; Genomic_DNA. DR EMBL; AJ270770; CAB97214.1; -; Genomic_DNA. DR EMBL; AJ270771; CAB97214.1; JOINED; Genomic_DNA. DR EMBL; AJ270772; CAB97214.1; JOINED; Genomic_DNA. DR EMBL; AJ270773; CAB97214.1; JOINED; Genomic_DNA. DR EMBL; AJ270774; CAB97214.1; JOINED; Genomic_DNA. DR EMBL; AJ270775; CAB97214.1; JOINED; Genomic_DNA. DR EMBL; AJ270777; CAB97214.1; JOINED; Genomic_DNA. DR EMBL; AJ270778; CAB97214.1; JOINED; Genomic_DNA. DR EMBL; AJ270770; CAB97215.1; -; Genomic_DNA. DR EMBL; AJ270771; CAB97215.1; JOINED; Genomic_DNA. DR EMBL; AJ270772; CAB97215.1; JOINED; Genomic_DNA. DR EMBL; AJ270773; CAB97215.1; JOINED; Genomic_DNA. DR EMBL; AJ270774; CAB97215.1; JOINED; Genomic_DNA. DR EMBL; AJ270775; CAB97215.1; JOINED; Genomic_DNA. DR EMBL; AJ270777; CAB97215.1; JOINED; Genomic_DNA. DR EMBL; AJ270778; CAB97215.1; JOINED; Genomic_DNA. DR EMBL; AJ270770; CAB97216.1; -; Genomic_DNA. DR EMBL; AJ270771; CAB97216.1; JOINED; Genomic_DNA. DR EMBL; AJ270772; CAB97216.1; JOINED; Genomic_DNA. DR EMBL; AJ270773; CAB97216.1; JOINED; Genomic_DNA. DR EMBL; AJ270774; CAB97216.1; JOINED; Genomic_DNA. DR EMBL; AJ270775; CAB97216.1; JOINED; Genomic_DNA. DR EMBL; AJ270778; CAB97216.1; JOINED; Genomic_DNA. DR EMBL; AJ270770; CAB97217.1; -; Genomic_DNA. DR EMBL; AJ270771; CAB97217.1; JOINED; Genomic_DNA. DR EMBL; AJ270772; CAB97217.1; JOINED; Genomic_DNA. DR EMBL; AJ270773; CAB97217.1; JOINED; Genomic_DNA. DR EMBL; AJ270774; CAB97217.1; JOINED; Genomic_DNA. DR EMBL; AJ270775; CAB97217.1; JOINED; Genomic_DNA. DR EMBL; AJ270778; CAB97217.1; JOINED; Genomic_DNA. DR EMBL; AJ270770; CAB97218.1; -; Genomic_DNA. DR EMBL; AJ270771; CAB97218.1; JOINED; Genomic_DNA. DR EMBL; AJ270772; CAB97218.1; JOINED; Genomic_DNA. DR EMBL; AJ270773; CAB97218.1; JOINED; Genomic_DNA. DR EMBL; AJ270774; CAB97218.1; JOINED; Genomic_DNA. DR EMBL; AJ270775; CAB97218.1; JOINED; Genomic_DNA. DR EMBL; AJ270776; CAB97218.1; JOINED; Genomic_DNA. DR EMBL; AJ270777; CAB97218.1; JOINED; Genomic_DNA. DR EMBL; AJ270770; CAB97219.1; -; Genomic_DNA. DR EMBL; AJ270771; CAB97219.1; JOINED; Genomic_DNA. DR EMBL; AJ270772; CAB97219.1; JOINED; Genomic_DNA. DR EMBL; AJ270773; CAB97219.1; JOINED; Genomic_DNA. DR EMBL; AJ270774; CAB97219.1; JOINED; Genomic_DNA. DR EMBL; AJ270775; CAB97219.1; JOINED; Genomic_DNA. DR EMBL; AJ270776; CAB97219.1; JOINED; Genomic_DNA. DR EMBL; AJ270777; CAB97219.1; JOINED; Genomic_DNA. DR EMBL; FJ010167; ACI28525.1; -; mRNA. DR EMBL; FJ010169; ACI28527.1; -; mRNA. DR EMBL; FJ010172; ACI28530.1; -; mRNA. DR EMBL; HM352839; ADK35175.1; -; mRNA. DR EMBL; HM352842; ADK35178.1; -; mRNA. DR EMBL; HM352844; ADK35180.1; -; mRNA. DR EMBL; HM352845; ADK35187.1; -; mRNA. DR EMBL; HM352846; ADK35181.1; -; mRNA. DR EMBL; HM352847; ADK35182.1; -; mRNA. DR EMBL; HM352849; ADK35184.1; -; mRNA. DR EMBL; HM352850; ADK35185.1; -; mRNA. DR EMBL; AB440195; BAH24004.1; -; mRNA. DR EMBL; AK299295; BAG61310.1; -; mRNA. DR EMBL; AL135792; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL158212; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL445486; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL451084; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471066; EAW49513.1; -; Genomic_DNA. DR EMBL; CH471066; EAW49515.1; -; Genomic_DNA. DR EMBL; CH471066; EAW49516.1; -; Genomic_DNA. DR EMBL; BC032656; AAH32656.1; -; mRNA. DR EMBL; AB034691; BAA86225.1; -; mRNA. DR CCDS; CCDS53577.1; -. [Q9NQB0-7] DR CCDS; CCDS53578.1; -. [Q9NQB0-11] DR CCDS; CCDS55729.1; -. [Q9NQB0-12] DR CCDS; CCDS7576.1; -. [Q9NQB0-8] DR CCDS; CCDS86148.1; -. [Q9NQB0-6] DR CCDS; CCDS91348.1; -. [Q9NQB0-1] DR PIR; S22807; S22807. DR RefSeq; NP_001139746.1; NM_001146274.1. [Q9NQB0-7] DR RefSeq; NP_001139755.1; NM_001146283.1. [Q9NQB0-11] DR RefSeq; NP_001139756.1; NM_001146284.1. [Q9NQB0-10] DR RefSeq; NP_001139758.1; NM_001146286.1. [Q9NQB0-14] DR RefSeq; NP_001185455.1; NM_001198526.1. [Q9NQB0-13] DR RefSeq; NP_001185457.1; NM_001198528.1. [Q9NQB0-12] DR RefSeq; NP_001185460.1; NM_001198531.1. [Q9NQB0-9] DR RefSeq; XP_005270141.1; XM_005270084.1. DR RefSeq; XP_005270146.1; XM_005270089.1. DR RefSeq; XP_005270153.1; XM_005270096.2. DR RefSeq; XP_005270160.1; XM_005270103.1. DR RefSeq; XP_016872081.1; XM_017016592.1. DR RefSeq; XP_016872082.1; XM_017016593.1. DR PDB; 1JDH; X-ray; 1.90 A; B=12-49. DR PDB; 1JPW; X-ray; 2.50 A; D/E/F=6-54. DR PDB; 2GL7; X-ray; 2.60 A; B/E=1-53. DR PDBsum; 1JDH; -. DR PDBsum; 1JPW; -. DR PDBsum; 2GL7; -. DR AlphaFoldDB; Q9NQB0; -. DR SMR; Q9NQB0; -. DR BioGRID; 112795; 272. DR CORUM; Q9NQB0; -. DR DIP; DIP-36236N; -. DR IntAct; Q9NQB0; 188. DR MINT; Q9NQB0; -. DR STRING; 9606.ENSP00000486891; -. DR BindingDB; Q9NQB0; -. DR ChEMBL; CHEMBL3038511; -. DR iPTMnet; Q9NQB0; -. DR PhosphoSitePlus; Q9NQB0; -. DR BioMuta; TCF7L2; -. DR DMDM; 29337146; -. DR EPD; Q9NQB0; -. DR jPOST; Q9NQB0; -. DR MassIVE; Q9NQB0; -. DR MaxQB; Q9NQB0; -. DR PaxDb; 9606-ENSP00000358404; -. DR PeptideAtlas; Q9NQB0; -. DR ProteomicsDB; 15216; -. DR ProteomicsDB; 29884; -. DR ProteomicsDB; 30005; -. DR ProteomicsDB; 82120; -. [Q9NQB0-1] DR ProteomicsDB; 82121; -. [Q9NQB0-10] DR ProteomicsDB; 82122; -. [Q9NQB0-2] DR ProteomicsDB; 82123; -. [Q9NQB0-3] DR ProteomicsDB; 82124; -. [Q9NQB0-4] DR ProteomicsDB; 82125; -. [Q9NQB0-5] DR ProteomicsDB; 82126; -. [Q9NQB0-6] DR ProteomicsDB; 82127; -. [Q9NQB0-7] DR ProteomicsDB; 82128; -. [Q9NQB0-8] DR ProteomicsDB; 82129; -. [Q9NQB0-9] DR Pumba; Q9NQB0; -. DR Antibodypedia; 31824; 520 antibodies from 35 providers. DR DNASU; 6934; -. DR Ensembl; ENST00000352065.10; ENSP00000344823.5; ENSG00000148737.18. [Q9NQB0-12] DR Ensembl; ENST00000355717.9; ENSP00000347949.4; ENSG00000148737.18. [Q9NQB0-11] DR Ensembl; ENST00000355995.9; ENSP00000348274.4; ENSG00000148737.18. [Q9NQB0-1] DR Ensembl; ENST00000369397.8; ENSP00000358404.4; ENSG00000148737.18. [Q9NQB0-8] DR Ensembl; ENST00000538897.5; ENSP00000446172.1; ENSG00000148737.18. [Q9NQB0-6] DR Ensembl; ENST00000627217.3; ENSP00000486891.1; ENSG00000148737.18. [Q9NQB0-7] DR GeneID; 6934; -. DR KEGG; hsa:6934; -. DR MANE-Select; ENST00000355995.9; ENSP00000348274.4; NM_001367943.1; NP_001354872.1. DR UCSC; uc001lac.5; human. [Q9NQB0-1] DR AGR; HGNC:11641; -. DR CTD; 6934; -. DR DisGeNET; 6934; -. DR GeneCards; TCF7L2; -. DR HGNC; HGNC:11641; TCF7L2. DR HPA; ENSG00000148737; Low tissue specificity. DR MalaCards; TCF7L2; -. DR MIM; 125853; phenotype. DR MIM; 602228; gene. DR neXtProt; NX_Q9NQB0; -. DR OpenTargets; ENSG00000148737; -. DR Orphanet; 528084; Non-specific syndromic intellectual disability. DR PharmGKB; PA36394; -. DR VEuPathDB; HostDB:ENSG00000148737; -. DR eggNOG; KOG3248; Eukaryota. DR GeneTree; ENSGT00940000155535; -. DR HOGENOM; CLU_013229_5_0_1; -. DR InParanoid; Q9NQB0; -. DR OMA; SLPPITX; -. DR OrthoDB; 5351131at2759; -. DR PhylomeDB; Q9NQB0; -. DR TreeFam; TF318448; -. DR PathwayCommons; Q9NQB0; -. DR Reactome; R-HSA-201722; Formation of the beta-catenin:TCF transactivating complex. DR Reactome; R-HSA-3769402; Deactivation of the beta-catenin transactivating complex. DR Reactome; R-HSA-381771; Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1). DR Reactome; R-HSA-4086398; Ca2+ pathway. DR Reactome; R-HSA-4411364; Binding of TCF/LEF:CTNNB1 to target gene promoters. DR Reactome; R-HSA-4641265; Repression of WNT target genes. DR Reactome; R-HSA-5339700; Signaling by TCF7L2 mutants. DR Reactome; R-HSA-8853884; Transcriptional Regulation by VENTX. DR Reactome; R-HSA-8951430; RUNX3 regulates WNT signaling. DR Reactome; R-HSA-9823730; Formation of definitive endoderm. DR SignaLink; Q9NQB0; -. DR SIGNOR; Q9NQB0; -. DR BioGRID-ORCS; 6934; 73 hits in 1176 CRISPR screens. DR ChiTaRS; TCF7L2; human. DR EvolutionaryTrace; Q9NQB0; -. DR GeneWiki; TCF7L2; -. DR GenomeRNAi; 6934; -. DR Pharos; Q9NQB0; Tbio. DR PRO; PR:Q9NQB0; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; Q9NQB0; Protein. DR Bgee; ENSG00000148737; Expressed in lateral nuclear group of thalamus and 198 other cell types or tissues. DR ExpressionAtlas; Q9NQB0; baseline and differential. DR GO; GO:1990907; C:beta-catenin-TCF complex; IBA:GO_Central. DR GO; GO:0070369; C:beta-catenin-TCF7L2 complex; IDA:BHF-UCL. DR GO; GO:0071664; C:catenin-TCF7L2 complex; IBA:GO_Central. DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL. DR GO; GO:0005654; C:nucleoplasm; IDA:BHF-UCL. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell. DR GO; GO:0032993; C:protein-DNA complex; IDA:BHF-UCL. DR GO; GO:0070016; F:armadillo repeat domain binding; IPI:BHF-UCL. DR GO; GO:0008013; F:beta-catenin binding; IDA:BHF-UCL. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:BHF-UCL. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central. DR GO; GO:0045295; F:gamma-catenin binding; IPI:BHF-UCL. DR GO; GO:0016922; F:nuclear receptor binding; IPI:BHF-UCL. DR GO; GO:1990841; F:promoter-specific chromatin binding; IEA:Ensembl. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:BHF-UCL. DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB. DR GO; GO:0001568; P:blood vessel development; IMP:BHF-UCL. DR GO; GO:0060070; P:canonical Wnt signaling pathway; IMP:BHF-UCL. DR GO; GO:0045444; P:fat cell differentiation; IDA:BHF-UCL. DR GO; GO:0042593; P:glucose homeostasis; IDA:BHF-UCL. DR GO; GO:0043570; P:maintenance of DNA repeat elements; IMP:BHF-UCL. DR GO; GO:0048625; P:myoblast fate commitment; IDA:BHF-UCL. DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:UniProtKB. DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:BHF-UCL. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:BHF-UCL. DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; ISS:BHF-UCL. DR GO; GO:0045721; P:negative regulation of gluconeogenesis; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:2000675; P:negative regulation of type B pancreatic cell apoptotic process; ISS:BHF-UCL. DR GO; GO:0031016; P:pancreas development; TAS:BHF-UCL. DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:BHF-UCL. DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IMP:BHF-UCL. DR GO; GO:0010909; P:positive regulation of heparan sulfate proteoglycan biosynthetic process; IMP:BHF-UCL. DR GO; GO:0032024; P:positive regulation of insulin secretion; IMP:BHF-UCL. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:BHF-UCL. DR GO; GO:0032092; P:positive regulation of protein binding; IDA:BHF-UCL. DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IMP:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0032350; P:regulation of hormone metabolic process; IDA:BHF-UCL. DR GO; GO:0048660; P:regulation of smooth muscle cell proliferation; IMP:BHF-UCL. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0009749; P:response to glucose; ISS:BHF-UCL. DR CDD; cd21996; HMG-box_TCF7-like; 1. DR DisProt; DP00175; -. DR Gene3D; 1.10.30.10; High mobility group box domain; 1. DR Gene3D; 4.10.900.10; TCF3-CBD (Catenin binding domain); 1. DR IDEAL; IID00100; -. DR InterPro; IPR027397; Catenin-bd_sf. DR InterPro; IPR013558; CTNNB1-bd_N. DR InterPro; IPR009071; HMG_box_dom. DR InterPro; IPR036910; HMG_box_dom_sf. DR InterPro; IPR024940; TCF/LEF. DR PANTHER; PTHR10373; TRANSCRIPTION FACTOR 7 FAMILY MEMBER; 1. DR PANTHER; PTHR10373:SF32; TRANSCRIPTION FACTOR 7-LIKE 2; 1. DR Pfam; PF08347; CTNNB1_binding; 1. DR Pfam; PF00505; HMG_box; 1. DR SMART; SM01366; c-clamp; 1. DR SMART; SM00398; HMG; 1. DR SUPFAM; SSF47095; HMG-box; 1. DR PROSITE; PS50118; HMG_BOX_2; 1. DR Genevisible; Q9NQB0; HS. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Diabetes mellitus; KW DNA-binding; Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome; KW Repressor; Transcription; Transcription regulation; Ubl conjugation; KW Wnt signaling pathway. FT CHAIN 1..619 FT /note="Transcription factor 7-like 2" FT /id="PRO_0000048623" FT DNA_BIND 350..418 FT /note="HMG box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267" FT REGION 1..96 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1..53 FT /note="CTNNB1-binding" FT /evidence="ECO:0000250" FT REGION 201..395 FT /note="Mediates interaction with MAD2L2" FT /evidence="ECO:0000269|PubMed:19443654" FT REGION 318..350 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 420..441 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 459..505 FT /note="Promoter-specific activation domain" FT REGION 496..547 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 574..619 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 425..430 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255" FT COMPBIAS 16..46 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 47..63 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 64..91 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 318..332 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 333..350 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 520..537 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 584..619 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 201 FT /note="Phosphothreonine; by NLK" FT /evidence="ECO:0000305|PubMed:12556497" FT MOD_RES 212 FT /note="Phosphothreonine; by NLK" FT /evidence="ECO:0000305|PubMed:12556497" FT CROSSLNK 22 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 320 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000269|PubMed:12727872" FT CROSSLNK 539 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 1..6 FT /note="MPQLNG -> MSSFLS (in isoform 17)" FT /evidence="ECO:0000303|PubMed:21256126" FT /id="VSP_053748" FT VAR_SEQ 7..290 FT /note="Missing (in isoform 17)" FT /evidence="ECO:0000303|PubMed:21256126" FT /id="VSP_053749" FT VAR_SEQ 128..150 FT /note="Missing (in isoform 8, isoform 10, isoform 11, FT isoform 12, isoform 13, isoform 14, isoform 15 and isoform FT 16)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:19602480, FT ECO:0000303|PubMed:21256126, ECO:0000303|PubMed:9065401" FT /id="VSP_006962" FT VAR_SEQ 184 FT /note="V -> VSPLPCCTQGHDCQHFYPPSDFTVSTQVFRDMKRSHSLQKVGEPWCI FT E (in isoform 11)" FT /evidence="ECO:0000305" FT /id="VSP_045821" FT VAR_SEQ 260..263 FT /note="Missing (in isoform 10)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_006963" FT VAR_SEQ 290 FT /note="M -> MSSFLS (in isoform 15 and isoform 16)" FT /evidence="ECO:0000303|PubMed:21256126" FT /id="VSP_053750" FT VAR_SEQ 440..465 FT /note="EHSECFLNPCLSLPPITDLSAPKKCR -> GEKKSAFATYKVKAAASAHPLQ FT MEAY (in isoform 9, isoform 11, isoform 14 and isoform 15)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:19602480, ECO:0000303|PubMed:21256126, FT ECO:0000303|PubMed:9065401, ECO:0000303|Ref.5" FT /id="VSP_006965" FT VAR_SEQ 440..456 FT /note="Missing (in isoform 4, isoform 5, isoform 7, isoform FT 13 and isoform 16)" FT /evidence="ECO:0000303|PubMed:19602480, FT ECO:0000303|PubMed:21256126" FT /id="VSP_006964" FT VAR_SEQ 457..619 FT /note="DLSAPKKCRARFGLDQQNNWCGPCRRKKKCVRYIQGEGSCLSPPSSDGSLLD FT SPPPSPNLLGSPPRDAKSQTEQTQPLSLSLKPDPLAHLSMMPPPPALLLAEATHKASAL FT CPNGALDLPPAALQPAAPSSSIAQPSTSSLHSHSSLAGTQPQPLSLVTKSLE -> GEK FT KSAFATYKVKAAASAHPLQMEAY (in isoform 6)" FT /evidence="ECO:0000303|PubMed:21256126" FT /id="VSP_006967" FT VAR_SEQ 457..482 FT /note="DLSAPKKCRARFGLDQQNNWCGPCRR -> GEKKSAFATYKVKAAASAHPLQ FT MEAY (in isoform 10)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_006968" FT VAR_SEQ 457..478 FT /note="DLSAPKKCRARFGLDQQNNWCG -> DANTPKKCRALFGLDRQTLWCK (in FT isoform 3, isoform 7 and isoform 13)" FT /evidence="ECO:0000303|PubMed:19602480, FT ECO:0000303|PubMed:21256126" FT /id="VSP_006966" FT VAR_SEQ 466..619 FT /note="Missing (in isoform 9, isoform 11, isoform 14 and FT isoform 15)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:19602480, ECO:0000303|PubMed:21256126, FT ECO:0000303|PubMed:9065401, ECO:0000303|Ref.5" FT /id="VSP_006969" FT VAR_SEQ 481..619 FT /note="RRKKKCVRYIQGEGSCLSPPSSDGSLLDSPPPSPNLLGSPPRDAKSQTEQTQ FT PLSLSLKPDPLAHLSMMPPPPALLLAEATHKASALCPNGALDLPPAALQPAAPSSSIAQ FT PSTSSLHSHSSLAGTQPQPLSLVTKSLE -> SL (in isoform 12)" FT /evidence="ECO:0000303|PubMed:19602480" FT /id="VSP_045822" FT VAR_SEQ 482..494 FT /note="RKKKCVRYIQGEG -> CKYSKEVSGTVRA (in isoform 2 and FT isoform 4)" FT /evidence="ECO:0000305" FT /id="VSP_006970" FT VAR_SEQ 483..619 FT /note="Missing (in isoform 10)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_006971" FT VAR_SEQ 495..619 FT /note="Missing (in isoform 2 and isoform 4)" FT /evidence="ECO:0000305" FT /id="VSP_006972" FT VARIANT 346 FT /note="K -> N (in dbSNP:rs2757884)" FT /evidence="ECO:0000269|PubMed:10919662" FT /id="VAR_047126" FT VARIANT 465 FT /note="R -> C (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035939" FT MUTAGEN 10..11 FT /note="DD->AA: Reduces CTNNB1 binding." FT /evidence="ECO:0000269|PubMed:10080941" FT MUTAGEN 16 FT /note="D->A: Abolishes CTNNB1 binding." FT /evidence="ECO:0000269|PubMed:10080941" FT MUTAGEN 17 FT /note="E->A: Reduces CTNNB1 binding." FT /evidence="ECO:0000269|PubMed:10080941" FT MUTAGEN 19 FT /note="I->A: Reduces transcription activation." FT /evidence="ECO:0000269|PubMed:11713476" FT MUTAGEN 21 FT /note="F->A: Reduces transcription activation." FT /evidence="ECO:0000269|PubMed:11713476" FT MUTAGEN 23..24 FT /note="DE->AA: Reduces CTNNB1 binding." FT /evidence="ECO:0000269|PubMed:10080941" FT MUTAGEN 24 FT /note="E->A: Reduces CTNNB1 binding, and abolishes CTNNB1 FT binding; when associated with A-26; A-28 and A-29." FT /evidence="ECO:0000269|PubMed:11713475" FT MUTAGEN 26 FT /note="E->A: Abolishes CTNNB1 binding; when associated with FT A-24; A-28 and A-29." FT /evidence="ECO:0000269|PubMed:11713475" FT MUTAGEN 28 FT /note="E->A: Abolishes CTNNB1 binding; when associated with FT A-24; A-26 and A-29." FT /evidence="ECO:0000269|PubMed:11713475" FT MUTAGEN 29 FT /note="E->A: Reduces CTNNB1 binding, and abolishes CTNNB1 FT binding; when associated with A-24; A-26 and A-28." FT /evidence="ECO:0000269|PubMed:11713475" FT MUTAGEN 48 FT /note="L->A: Abolishes CTNNB1 binding." FT /evidence="ECO:0000269|PubMed:10080941" FT MUTAGEN 201 FT /note="T->V: Reduced phosphorylation by NLK and enhanced FT DNA-binding; when associated with V-212." FT /evidence="ECO:0000269|PubMed:12556497" FT MUTAGEN 212 FT /note="T->V: Reduced phosphorylation by NLK and enhanced FT DNA-binding; when associated with V-201." FT /evidence="ECO:0000269|PubMed:12556497" FT MUTAGEN 320 FT /note="K->R: Loss of sumoylation. No effect on localization FT to nuclear bodies." FT /evidence="ECO:0000269|PubMed:12727872" FT MUTAGEN 322 FT /note="E->A: Loss of sumoylation." FT /evidence="ECO:0000269|PubMed:12727872" FT CONFLICT 118..121 FT /note="NGSL -> KRSV (in Ref. 2; CAB97212/CAB97213)" FT /evidence="ECO:0000305" FT CONFLICT 167 FT /note="Q -> R (in Ref. 4; ADK35180)" FT /evidence="ECO:0000305" FT CONFLICT 226 FT /note="P -> L (in Ref. 4; ADK35180)" FT /evidence="ECO:0000305" FT CONFLICT 290 FT /note="M -> V (in Ref. 1; CAA72166)" FT /evidence="ECO:0000305" FT CONFLICT 331 FT /note="L -> H (in Ref. 3; ACI28527)" FT /evidence="ECO:0000305" FT CONFLICT 596 FT /note="S -> W (in Ref. 1; CAA72166)" FT /evidence="ECO:0000305" FT HELIX 22..31 FT /evidence="ECO:0007829|PDB:1JDH" FT HELIX 38..48 FT /evidence="ECO:0007829|PDB:1JDH" SQ SEQUENCE 619 AA; 67919 MW; 4DD2D3CC814AE16E CRC64; MPQLNGGGGD DLGANDELIS FKDEGEQEEK SSENSSAERD LADVKSSLVN ESETNQNSSS DSEAERRPPP RSESFRDKSR ESLEEAAKRQ DGGLFKGPPY PGYPFIMIPD LTSPYLPNGS LSPTARTLHF QSGSTHYSAY KTIEHQIAVQ YLQMKWPLLD VQAGSLQSRQ ALKDARSPSP AHIVSNKVPV VQHPHHVHPL TPLITYSNEH FTPGNPPPHL PADVDPKTGI PRPPHPPDIS PYYPLSPGTV GQIPHPLGWL VPQQGQPVYP ITTGGFRHPY PTALTVNASM SRFPPHMVPP HHTLHTTGIP HPAIVTPTVK QESSQSDVGS LHSSKHQDSK KEEEKKKPHI KKPLNAFMLY MKEMRAKVVA ECTLKESAAI NQILGRRWHA LSREEQAKYY ELARKERQLH MQLYPGWSAR DNYGKKKKRK RDKQPGETNE HSECFLNPCL SLPPITDLSA PKKCRARFGL DQQNNWCGPC RRKKKCVRYI QGEGSCLSPP SSDGSLLDSP PPSPNLLGSP PRDAKSQTEQ TQPLSLSLKP DPLAHLSMMP PPPALLLAEA THKASALCPN GALDLPPAAL QPAAPSSSIA QPSTSSLHSH SSLAGTQPQP LSLVTKSLE //