TF7L2_HUMAN
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 03-AUG-2022, entry version 215.
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 NIDDM.
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 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 [26]
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 [27]
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 [28]
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 [29]
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 [30]
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 [31]
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 [32]
RP INVOLVEMENT IN NIDDM.
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 [33]
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 [34]
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 [35]
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 [36]
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 [37]
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 [38]
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 [39]
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 [40]
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 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). {ECO:0000250|UniProtKB:Q924A0,
CC ECO:0000269|PubMed:10080941, ECO:0000269|PubMed:11266540,
CC ECO:0000269|PubMed:12446687, ECO:0000269|PubMed:12556497,
CC ECO:0000269|PubMed:12727872, ECO:0000269|PubMed:16434966,
CC ECO:0000269|PubMed:16714285, ECO:0000269|PubMed:17052462,
CC ECO:0000269|PubMed:17873903, 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; Q93009: USP7; NbExp=2; IntAct=EBI-924724, EBI-302474;
CC Q9NQB0; P12956: XRCC6; NbExp=10; IntAct=EBI-924724, EBI-353208;
CC Q9NQB0-10; Q9NP55: BPIFA1; NbExp=3; IntAct=EBI-11746252, EBI-953896;
CC Q9NQB0-10; Q5BKX5-3: C19orf54; NbExp=3; IntAct=EBI-11746252, EBI-11976299;
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}. Note=Diffuse
CC pattern. Colocalizes with SUMO1 and PIAS4 in a subset of PML
CC (promyelocytic leukemia) nuclear 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: Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]:
CC A multifactorial disorder of glucose homeostasis caused by a lack of
CC sensitivity to the body's own insulin. Affected individuals usually
CC have an obese body habitus and manifestations of a metabolic syndrome
CC characterized by diabetes, insulin resistance, hypertension and
CC hypertriglyceridemia. The disease results in long-term complications
CC that affect the eyes, kidneys, nerves, and blood vessels.
CC {ECO:0000269|PubMed:16415884, ECO:0000269|PubMed:24390345}.
CC Note=Disease susceptibility is associated with variants affecting the
CC 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 ---------------------------------------------------------------------------
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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 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; 266.
DR CORUM; Q9NQB0; -.
DR DIP; DIP-36236N; -.
DR IntAct; Q9NQB0; 186.
DR MINT; Q9NQB0; -.
DR STRING; 9606.ENSP00000358404; -.
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; Q9NQB0; -.
DR PeptideAtlas; Q9NQB0; -.
DR PRIDE; 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 Antibodypedia; 31824; 477 antibodies from 34 providers.
DR DNASU; 6934; -.
DR Ensembl; ENST00000352065.10; ENSP00000344823.5; ENSG00000148737.17. [Q9NQB0-12]
DR Ensembl; ENST00000355717.9; ENSP00000347949.4; ENSG00000148737.17. [Q9NQB0-11]
DR Ensembl; ENST00000355995.8; ENSP00000348274.4; ENSG00000148737.17. [Q9NQB0-1]
DR Ensembl; ENST00000369397.8; ENSP00000358404.4; ENSG00000148737.17. [Q9NQB0-8]
DR Ensembl; ENST00000538897.5; ENSP00000446172.1; ENSG00000148737.17. [Q9NQB0-6]
DR Ensembl; ENST00000627217.3; ENSP00000486891.1; ENSG00000148737.17. [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 CTD; 6934; -.
DR DisGeNET; 6934; -.
DR GeneCards; TCF7L2; -.
DR HGNC; HGNC:11641; TCF7L2.
DR HPA; ENSG00000148737; Tissue enriched (brain).
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; WCVESNK; -.
DR OrthoDB; 807716at2759; -.
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 SignaLink; Q9NQB0; -.
DR SIGNOR; Q9NQB0; -.
DR BioGRID-ORCS; 6934; 71 hits in 1096 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 196 other tissues.
DR ExpressionAtlas; Q9NQB0; baseline and differential.
DR Genevisible; Q9NQB0; HS.
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: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; IBA:GO_Central.
DR GO; GO:0044334; P:canonical Wnt signaling pathway involved in positive regulation of epithelial to mesenchymal transition; 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:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; ISS:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; 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: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:0032092; P:positive regulation of protein binding; IDA:BHF-UCL.
DR GO; GO:0046827; P:positive regulation of protein export from nucleus; IMP:BHF-UCL.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; 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 DisProt; DP00175; -.
DR Gene3D; 1.10.30.10; -; 1.
DR Gene3D; 4.10.900.10; -; 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; PTHR10373; 1.
DR Pfam; PF08347; CTNNB1_binding; 1.
DR Pfam; PF00505; HMG_box; 1.
DR SMART; SM00398; HMG; 1.
DR SUPFAM; SSF47095; SSF47095; 1.
DR PROSITE; PS50118; HMG_BOX_2; 1.
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
