ID:TF7L2_HUMAN DESCRIPTION: RecName: Full=Transcription factor 7-like 2; AltName: Full=HMG box transcription factor 4; AltName: Full=T-cell-specific transcription factor 4; Short=T-cell factor 4; Short=TCF-4; Short=hTCF-4; FUNCTION: Participates in the Wnt signaling pathway and modulates MYC expression by binding to its promoter in a sequence-specific manner. Acts as repressor in the absence of CTNNB1, and as activator in its presence. Activates transcription from promoters with several copies of the Tcf motif 5'-CCTTTGATC-3' in the presence of CTNNB1. TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by TCF7L2/TCF4 and CTNNB1. Expression of dominant-negative mutants results in cell-cycle arrest in G1. Necessary for the maintenance of the epithelial stem-cell compartment of the small intestine. SUBUNIT: Interacts with TGFB1I1 (By similarity). Interacts with CTNNB1 (via the armadillo repeat); forms stable transcription complex. Interacts with EP300. Interacts with NLK. Interacts with CCDC85B (probably through the HMG box); prevents interaction with CTNNB1. Interacts with TNIK. Interacts with MAD2L2; prevents TCF7L2/TCF4 binding to promZIPK/DAPK3oters, negatively modulating its transcriptional activity. Interacts with ZIPK/DAPK3. Interacts with XIAP/BIRC4 and TLE3. Interacts with DDIT3/CHOP. INTERACTION: P35222:CTNNB1; NbExp=27; IntAct=EBI-924724, EBI-491549; Q9UER7:DAXX; NbExp=5; IntAct=EBI-924724, EBI-77321; P14923:JUP; NbExp=13; IntAct=EBI-924724, EBI-702484; Q13761:RUNX3; NbExp=14; IntAct=EBI-924724, EBI-925990; P12956:XRCC6; NbExp=9; IntAct=EBI-924724, EBI-353208; SUBCELLULAR LOCATION: Nucleus, PML body. Note=Diffuse pattern. Colocalizes with SUMO1 and PIAS4 in a subset of PML (promyelocytic leukemia) nuclear bodies. TISSUE SPECIFICITY: Detected in epithelium from small intestine, with the highest expression at the top of the crypts and a gradient of expression from crypt to villus. Detected in colon epithelium and colon cancer, and in epithelium from mammary gland and carcinomas derived therefrom. DEVELOPMENTAL STAGE: Highly expressed in crypt regions and barely detectable in villi in epithelium from fetal small intestine at week 16. At week 22 expression in villi had increased strongly. DOMAIN: The promoter-specific activation domain interacts with the transcriptional coactivator EP300. PTM: In vitro, phosphorylated by TNIK. PTM: Phosphorylated at Thr-201 and/or Thr-212 by NLK. Phosphorylation by NLK at these sites inhibits DNA-binding by TCF7L2/TCF4, thereby preventing transcriptional activation of target genes of the canonical Wnt/beta-catenin signaling pathway. PTM: Polysumoylated. Sumoylation is enhanced by PIAS family members and desumoylation is enhanced by SENP2. Sumoylation/desumoylation regulates TCF7L2/TCF4 transcription activity in the Wnt/beta-catenin signaling pathway without altering interaction with CTNNB1 nor binding to DNA. DISEASE: Note=Constitutive activation and subsequent transactivation of target genes may lead to the maintenance of stem-cell characteristics (cycling and longevity) in cells that should normally undergo terminal differentiation and constitute the primary transforming event in colorectal cancer (CRC). DISEASE: Genetic variations in TCF7L2 are associated with susceptibility to non-insulin-dependent diabetes mellitus (NIDDM) [MIM:125853]. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and insulin resistance. SIMILARITY: Belongs to the TCF/LEF family. SIMILARITY: Contains 1 HMG box DNA-binding domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9NQB0
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0001103 RNA polymerase II repressing transcription factor binding GO:0003677 DNA binding GO:0003700 transcription factor activity, sequence-specific DNA binding GO:0005515 protein binding GO:0008013 beta-catenin binding GO:0008134 transcription factor binding GO:0019901 protein kinase binding GO:0035257 nuclear hormone receptor binding GO:0043565 sequence-specific DNA binding GO:0044212 transcription regulatory region DNA binding GO:0045295 gamma-catenin binding GO:0070016 armadillo repeat domain binding
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0001568 blood vessel development GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006357 regulation of transcription from RNA polymerase II promoter GO:0007050 cell cycle arrest GO:0007223 Wnt signaling pathway, calcium modulating pathway GO:0008283 cell proliferation GO:0009749 response to glucose GO:0010909 positive regulation of heparan sulfate proteoglycan biosynthetic process GO:0016055 Wnt signaling pathway GO:0031016 pancreas development GO:0032024 positive regulation of insulin secretion GO:0032092 positive regulation of protein binding GO:0032350 regulation of hormone metabolic process GO:0042593 glucose homeostasis GO:0043433 negative regulation of sequence-specific DNA binding transcription factor activity GO:0043570 maintenance of DNA repeat elements GO:0044334 canonical Wnt signaling pathway involved in positive regulation of epithelial to mesenchymal transition GO:0045444 fat cell differentiation GO:0045892 negative regulation of transcription, DNA-templated GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0046827 positive regulation of protein export from nucleus GO:0048625 myoblast fate commitment GO:0048660 regulation of smooth muscle cell proliferation GO:0051897 positive regulation of protein kinase B signaling GO:0060070 canonical Wnt signaling pathway GO:0090090 negative regulation of canonical Wnt signaling pathway GO:1904837 beta-catenin-TCF complex assembly GO:2000675 negative regulation of type B pancreatic cell apoptotic process GO:2001237 negative regulation of extrinsic apoptotic signaling pathway
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Common Gene Haplotype Alleles 
