InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: TCF7L2

Summary

InnateDB Protein

IDBP-600852.3

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

TCF7L2

Protein Name

transcription factor 7-like 2 (T-cell specific, HMG-box)

Synonyms

TCF-4; TCF4;

Species

Homo sapiens

Ensembl Protein

ENSP00000443626

InnateDB Gene

IDBG-89861 (TCF7L2)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:12408868, ECO:0000269PubMed:12727872, ECO:0000269PubMed:19443654, ECO:0000269PubMed:22699938, ECO:0000269PubMed:9727977}.

Subcellular Localization

Nucleus, PML body {ECO:0000269PubMed:12727872, ECO:0000269PubMed:22699938, ECO:0000269PubMed:9916915}. Note=Diffuse pattern. Colocalizes with SUMO1 and PIAS4 in a subset of PML (promyelocytic leukemia) nuclear bodies.

Disease Associations

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).Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269PubMed:16415884, ECO:0000269PubMed:24390345}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

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. {ECO:0000269PubMed:9916915}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 58 experimentally validated interaction(s) in this database.
They are also associated with 6 interaction(s) predicted by orthology.

Experimentally validated
Total	58 [view]
Protein-Protein	44 [view]
Protein-DNA	7 [view]
Protein-RNA	1 [view]
DNA-DNA	6 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	6 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000978	RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0001103	RNA polymerase II repressing transcription factor binding
GO:0003682	chromatin binding
GO:0003700	sequence-specific DNA binding transcription factor activity
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:0006357	regulation of transcription from RNA polymerase II promoter
GO:0007050	cell cycle arrest
GO:0007420	brain development
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:0048699	generation of neurons
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:2000675	negative regulation of type B pancreatic cell apoptotic process
GO:2001237	negative regulation of extrinsic apoptotic signaling pathway

Cellular Component

GO:0000790	nuclear chromatin
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005667	transcription factor complex
GO:0005737	cytoplasm
GO:0016605	PML body
GO:0032993	protein-DNA complex
GO:0070369	beta-catenin-TCF7L2 complex