TCF7L2

From Wikipedia, the free encyclopedia


Transcription factor 7-like 2 (T-cell specific, HMG-box)
PDB rendering based on 1jdh.
Available structures: 1jdh, 1jpw, 2gl7, 2lef
Identifiers
Symbol(s) TCF7L2; TCF4; TCF-4
External IDs OMIM: 602228 MGI: 1202879 HomoloGene: 7564
RNA expression pattern

More reference expression data
Orthologs
Human Mouse
Entrez 6934 21416
Ensembl ENSG00000148737 ENSMUSG00000024985
Uniprot Q9NQB0 Q80WT9
Refseq NM_030756 (mRNA)
NP_110383 (protein)		 NM_009333 (mRNA)
NP_033359 (protein)
Location Chr 10: 114.7 - 114.92 Mb Chr 19: 55.8 - 55.99 Mb
Pubmed search [1] [2]

TCF7L2 also known as TCF4 is a protein acting as a transcription factor. A variant of the protein is linked to higher risk to develop type 2 diabetes.


Structure of complex between TCF7L2 (orange), β-catenin (red), BCL9 (brown); based on PDB 2GL7, see also PMID 17052462
Structure of complex between TCF7L2 (orange), β-catenin (red), BCL9 (brown); based on PDB 2GL7, see also PMID 17052462

Contents

[edit] Function

TCF7L2 is a transcription factor influencing the transcription of several genes thereby exerting a large variety of functions in the cell. It is a member of the Wnt signaling pathway. Stimulation of the pathway leads to the association of β-catenin with TCF7L2 and BCL9 in the nucleus, which in turn results in the activation of Wnt target genes.

[edit] Disease implications

TCF7L2 is implied in a large variety of diseases. Several single nucleotide polymorphisms are associated with type 2 diabetes. In European populations it was found to be a major determinant of type 2 risk.

A frameshift mutation of TCF7L2 is implied in colorectal cancer. Variants of the gene are most likely involved in many other cancer types. See PubMed GeneRIFs for more information [3].

[edit] Further reading

  • Segditsas S, Tomlinson I (2007). "Colorectal cancer and genetic alterations in the Wnt pathway.". Oncogene 25 (57): 7531–7. doi:10.1038/sj.onc.1210059. PMID 17143297. 
  • Florez JC (2007). "The new type 2 diabetes gene TCF7L2.". Current opinion in clinical nutrition and metabolic care 10 (4): 391–6. doi:10.1097/MCO.0b013e3281e2c9be. PMID 17563454. 
  • Castrop J, van Norren K, Clevers H (1992). "A gene family of HMG-box transcription factors with homology to TCF-1.". Nucleic Acids Res. 20 (3): 611. PMID 1741298. 
  • Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1-2): 171–4. PMID 8125298. 
  • Korinek V, Barker N, Morin PJ, et al. (1997). "Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma.". Science 275 (5307): 1784–7. PMID 9065401. 
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.". Gene 200 (1-2): 149–56. PMID 9373149. 
  • He TC, Sparks AB, Rago C, et al. (1998). "Identification of c-MYC as a target of the APC pathway.". Science 281 (5382): 1509–12. PMID 9727977. 
  • Barker N, Huls G, Korinek V, Clevers H (1999). "Restricted high level expression of Tcf-4 protein in intestinal and mammary gland epithelium.". Am. J. Pathol. 154 (1): 29–35. PMID 9916915. 
  • Omer CA, Miller PJ, Diehl RE, Kral AM (1999). "Identification of Tcf4 residues involved in high-affinity beta-catenin binding.". Biochem. Biophys. Res. Commun. 256 (3): 584–90. doi:10.1006/bbrc.1999.0379. PMID 10080941. 
  • Giannini AL, Vivanco MM, Kypta RM (2000). "Analysis of beta-catenin aggregation and localization using GFP fusion proteins: nuclear import of alpha-catenin by the beta-catenin/Tcf complex.". Exp. Cell Res. 255 (2): 207–20. doi:10.1006/excr.1999.4785. PMID 10694436. 
  • Duval A, Busson-Leconiat M, Berger R, Hamelin R (2000). "Assignment of the TCF-4 gene (TCF7L2) to human chromosome band 10q25.3.". Cytogenet. Cell Genet. 88 (3-4): 264–5. PMID 10828605. 
  • Duval A, Rolland S, Tubacher E, et al. (2000). "The human T-cell transcription factor-4 gene: structure, extensive characterization of alternative splicings, and mutational analysis in colorectal cancer cell lines.". Cancer Res. 60 (14): 3872–9. PMID 10919662. 
  • Brantjes H, Roose J, van De Wetering M, Clevers H (2001). "All Tcf HMG box transcription factors interact with Groucho-related co-repressors.". Nucleic Acids Res. 29 (7): 1410–9. PMID 11266540. 
  • Palacino JJ, Murphy MP, Murayama O, et al. (2001). "Presenilin 1 regulates beta-catenin-mediated transcription in a glycogen synthase kinase-3-independent fashion.". J. Biol. Chem. 276 (42): 38563–9. doi:10.1074/jbc.M105376200. PMID 11504726. 
  • Miravet S, Piedra J, Miró F, et al. (2002). "The transcriptional factor Tcf-4 contains different binding sites for beta-catenin and plakoglobin.". J. Biol. Chem. 277 (3): 1884–91. doi:10.1074/jbc.M110248200. PMID 11711551. 
  • Graham TA, Ferkey DM, Mao F, et al. (2002). "Tcf4 can specifically recognize beta-catenin using alternative conformations.". Nat. Struct. Biol. 8 (12): 1048–52. doi:10.1038/nsb718. PMID 11713475. 
  • Poy F, Lepourcelet M, Shivdasani RA, Eck MJ (2002). "Structure of a human Tcf4-beta-catenin complex.". Nat. Struct. Biol. 8 (12): 1053–7. doi:10.1038/nsb720. PMID 11713476. 
  • Thiele A, Wasner M, Müller C, et al. (2001). "Regulation and possible function of beta-catenin in human monocytes.". J. Immunol. 167 (12): 6786–93. PMID 11739494. 
  • Marchenko GN, Marchenko ND, Leng J, Strongin AY (2002). "Promoter characterization of the novel human matrix metalloproteinase-26 gene: regulation by the T-cell factor-4 implies specific expression of the gene in cancer cells of epithelial origin.". Biochem. J. 363 (Pt 2): 253–62. PMID 11931652. 
  • Leung JY, Kolligs FT, Wu R, et al. (2002). "Activation of AXIN2 expression by beta-catenin-T cell factor. A feedback repressor pathway regulating Wnt signaling.". J. Biol. Chem. 277 (24): 21657–65. doi:10.1074/jbc.M200139200. PMID 11940574. 

[edit] Extgernal links

  • TCF7L2 here called TCF4 features on this Wnt pathway web site: Wnt signalling molecules TCFs
  • Structure determination of TCF7L2: PDB entry 2GL7 and related publication on PubMed
  • PubMed GeneRIFs (summaries of related scientific publications) - [4]
  • Weizmann Institute GeneCard for TCF7L2


v • d • e
Transcription factors and intracellular receptors
(1) Basic domains
(1.1) Basic leucine zipper (bZIP)
Activating transcription factor (AATF, 1, 2, 3, 4, 5, 6, 7) • AP-1 (c-Fos, FOSB, FOSL1, FOSL2, c-Jun, JUNB, JUND) • BACH (1, 2) • BATF • BLZF1 • C/EBP (α, β, γ, δ, ε, ζ) • CREB (1, 3, L1) • CREM • DBP • DDIT3 • GABPA • HLF • MAF (B, F, G, K) • NFE (2, L1, L2) • NRL • NRF1 • XBP1
(1.2) Basic helix-loop-helix (bHLH)
ATOH1 • AhR • AHRR • ARNT • ASCL1 • BHLHB2 • BMAL (ARNTL, ARNTL2) • CLOCK • EPAS1 • HAND (1, 2) • HES (5, 6) • HEY (1, 2, L) • HES1 • HIF (1A, 3A) • ID (1, 2, 3, 4) • LYL1 • MXD4 • MYCL1 • MYCN • Myogenic regulatory factors (MyoD, Myogenin, MYF5, MYF6) • Neurogenins • NeuroD (1, 2) • NPAS (1, 2, 3) • OLIG (1, 2) • Scleraxis • TAL1 • Twist • USF1
(1.3) bHLH-ZIP
MAX • MITF • MNT • MLX • MXI1 • Myc • SREBP (1, 2)
(1.6) Basic helix-span-helix (bHSH)
(2) Zinc finger
DNA-binding domains
(2.1) Nuclear receptor (Cys4)
subfamily 1 (Thyroid hormone (α, β), CAR, FXR, LXR (α, β), PPAR (α, β/δ, γ), PXR, RAR (α, β, γ), ROR (α, β, γ), Rev-ErbA (α, β), VDR) • subfamily 2 (COUP-TF (I, II), Ear-2, HNF4 (α, γ), PNR, RXR (α, β, γ), Testicular receptor (2, 4), TLX) • subfamily 3 (Steroid hormone (Estrogen (α, β), Estrogen related (α, β, γ), Androgen, Glucocorticoid, Mineralocorticoid, Progesterone)) • subfamily 4 NUR (NGFIB, NOR1, NURR1) • subfamily 5 (LRH-1, SF1) • subfamily 6 (GCNF) • subfamily 0 (DAX1, SHP)
(2.2) Other Cys4
GATA (1, 2, 3, 4, 5, 6) • MTA (1, 2, 3)
(2.3) Cys2His2
ATBF1 • BCL(6, 11A, 11B) • CTCF • E4F1 • EGR (2, 3) • ERV3 • General transcription factors (TFIIA, TFIIB, TFIID, TFIIE, TFIIF: 1, 2, TFIIH: 1, 2, 4, 2I, 3A, 3C1, 3C2) • GFI1 • GLI-Krüppel family (1, 2, 3, YY1) • HIC (1, 2) • HIVEP (1, 2, 3) • IKZF (1, 2, 3) • ILF (2, 3) • KLF (2, 4, 5, 6, 9, 10, 11, 12, 13) • MTF1 • MYT1 • OSR1 • Sp1 • zinc finger ((3, 7, 9, 10, 19, 22, 24, 33B, 34, 35, 41, 43, 44, 51, 74, 143, 146, 148, 165, 202, 217, 219, 238, 239, 259, 267, 268, 281, 295, 318, 330, 346, 350, 365, 366, 384, 451, 452, 471, 593, 638, 649, 655) • Zbtb7 (7A) • ZBT (16, 17, 33)
(2.4) Cys6
(2.5) Alternating composition
AIRE • DIDO1 • GRLF1 • ING (1, 2, 4) • JARID (1A, 1B, 1C, 1D, 2) • JMJD1B
(3) Helix-turn-helix
domains
ARX • CDX (1, 2) • CRX • CUTL1 • DLX (3, 4, 5) • EMX2 • EN (1, 2) • FHL (1, 2, 3) • HESX1 • HHEX • HLX • Homeobox (A1, A3, A4, A5, A7, A9, A10, A11, A13, B1, B2, B3, B4, B5, B6, B7, B8, B9, B13, C4, C5, C6, C8, C9, C10, C11, C13, D1, D3, D4, D8, D9, D10, D11, D12, D13) • HOPX • MEIS (1, 2) • MEOX2 • MNX1 • MSX (1, 2) • NANOG • NKX (2-1, 2-5, 3-1) • PHF (3, 6, 10, 17) • POU domain (PIT-1, BRN-3: 1, 2, Octamer transcription factor: 1, 2, 3/4, 6, 7) • OTX (1, 2) • PDX1
(3.2) Paired box
PAX (1, 2, 3, 4, 5, 6, 7, 8, 9)
E2F (1, 2, 3, 4, 5) • FOX proteins (C1, C2, E1, G1, H1, K2, L2, M1, N3, O1A, , O3A, O4, P1, P2, P3)
HSF (1, 2, 4)
(3.5) Tryptophan clusters
ELF (4, 5) • EGF • ELK (1, 3, 4) • ERF • ERG • ETS (1, 2) • ETV (1, 4, 5, 6) • FLI1 • Interferon regulatory factors (1, 2, 3, 4, 5, 6, 7, 8) • MYB • MYBL2
(3.6) TEA domain
transcriptional enhancer factor 1, 2
(4) β-Scaffold factors with
minor groove contacts
(4.1) Rel homology region
NF-κB (NFKB1, NFKB2, REL, RELA, RELB) • NFAT (C1, C2, C3, C4, 5)
(4.2) STAT
STAT (1, 2, 3, 4, 5, 6)
(4.3) p53
(4.4) MADS box
Mef2 (A, B, C, D) • SRF
HNF (1A, 1B) • LEF1 • SOX (2, 3, 4, 5, 6, 8, 9, 10, 11, 13, 15, 18) • SRY • SSRP1
(4.10) Cold-shock domain
(4.11) Runt
(0) Other
transcription factors
(0.2) HMGI(Y)
HMGA (1, 2) • HBP1
Rb • RBL1 • RBL2
(0.5) AP-2/EREBP-related factors
Apetala 2 • EREBP • B3
(0.6) Miscellaneous
ARID (1A, 1B, 2, 3A, 3B, 4A) • CAP • IFI (16, 35) • MLL (2, 3, T1) • MNDA • NFI (A, B, C, X) • NFY (A, B, C) • Rho/Sigma • R-SMAD
v • d • e
Animal intercellular signaling peptides and proteins
Growth factors
Other