Homeobox protein TGIF1

Homeobox protein TGIF1 is a protein that in humans is encoded by the TGIF1 gene.[5][6][7] Alternative splicing has been observed at this locus and eight variants, encoding four distinct isoforms, are described.

TGIF1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2LK2
Identifiers
Aliases	TGIF1, HPE4, TGIF, TGFB induced factor homeobox 1
External IDs	OMIM: 602630 MGI: 1194497 HomoloGene: 7574 GeneCards: TGIF1
Gene location (Human) Chr. Chromosome 18 (human)[1] Band 18p11.31 Start 3,411,608 bp[1] End 3,459,978 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17|17 E1.3 Start 70,844,205 bp[2] End 70,853,546 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • DNA binding • GO:0001948 protein binding • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding • GO:0001078, GO:0001214, GO:0001206 DNA-binding transcription repressor activity, RNA polymerase II-specific • GO:0001106 transcription corepressor activity • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific • co-SMAD binding Cellular component • cell nucleus • nucleoplasm Biological process • regulation of transcription, DNA-templated • negative regulation of gene expression • multicellular organism development • response to drug • cellular response to growth factor stimulus • negative regulation of transcription from RNA polymerase II promoter • transcription, DNA-templated Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	7050	21815
Ensembl	ENSG00000177426	ENSMUSG00000047407
UniProt	Q15583	P70284
RefSeq (mRNA)	NM_001278682 NM_001278684 NM_001278686 NM_003244 NM_170695 NM_173207 NM_173208 NM_173209 NM_173210 NM_173211 NM_174886 NM_001374396 NM_001374397	NM_001164074 NM_001164075 NM_001164076 NM_001164077 NM_009372
RefSeq (protein)	NP_001265611 NP_001265613 NP_001265615 NP_003235 NP_733796 NP_775299 NP_775300 NP_775301 NP_775302 NP_775303 NP_777480 NP_001361325 NP_001361326	NP_001157546 NP_001157547 NP_001157548 NP_001157549 NP_033398
Location (UCSC)	Chr 18: 3.41 – 3.46 Mb	Chr 17: 70.84 – 70.85 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

The protein encoded by this gene is a member of the three-amino acid loop extension (TALE) superclass of atypical homeodomains. TALE homeobox proteins are highly conserved transcription regulators. This particular homeodomain binds to a previously characterized retinoid X receptor responsive element from the cellular retinol-binding protein II promoter. In addition to its role in inhibiting 9-cis-retinoic acid-dependent RXR alpha transcription activation of the retinoic acid responsive element, the protein is an active transcriptional co-repressor of SMAD2 and may participate in the transmission of nuclear signals during development and in the adult.

Clinical significance

Mutations in this gene are associated with holoprosencephaly type 4, which is a structural anomaly of the brain.[7] It has also been associated with risk of otitis media (inflammation of the middle ear)

Interactions

Homeobox protein TGIF1 has been shown to interact with:

• C-jun,[8]
• CTBP1,[9]
• HDAC1,[9][10] and
• Mothers against decapentaplegic homolog 2.[8][11]

References

1. GRCh38: Ensembl release 89: ENSG00000177426 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000047407 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Bertolino E, Reimund B, Wildt-Perinic D, Clerc RG (February 1996). "A novel homeobox protein which recognizes a TGT core and functionally interferes with a retinoid-responsive motif". J Biol Chem. 270 (52): 31178–88. doi:10.1074/jbc.270.52.31178. PMID 8537382.
6. Gripp KW, Wotton D, Edwards MC, Roessler E, Ades L, Meinecke P, Richieri-Costa A, Zackai EH, Massagué J, Muenke M, Elledge SJ (June 2000). "Mutations in TGIF cause holoprosencephaly and link NODAL signalling to human neural axis determination". Nat Genet. 25 (2): 205–8. doi:10.1038/76074. PMID 10835638.
7. "Entrez Gene: TGIF1 TGFB-induced factor homeobox 1".
8. Pessah M, Prunier C, Marais J, Ferrand N, Mazars A, Lallemand F, Gauthier JM, Atfi A (May 2001). "c-Jun interacts with the corepressor TG-interacting factor (TGIF) to suppress Smad2 transcriptional activity". Proc. Natl. Acad. Sci. U.S.A. 98 (11): 6198–203. doi:10.1073/pnas.101579798. PMC 33445. PMID 11371641.
9. Melhuish TA, Wotton D (December 2000). "The interaction of the carboxyl terminus-binding protein with the Smad corepressor TGIF is disrupted by a holoprosencephaly mutation in TGIF". J. Biol. Chem. 275 (50): 39762–6. doi:10.1074/jbc.C000416200. PMID 10995736.
10. Melhuish TA, Gallo CM, Wotton D (August 2001). "TGIF2 interacts with histone deacetylase 1 and represses transcription". J. Biol. Chem. 276 (34): 32109–14. doi:10.1074/jbc.M103377200. PMID 11427533.
11. Wotton D, Lo RS, Lee S, Massagué J (April 1999). "A Smad transcriptional corepressor". Cell. 97 (1): 29–39. doi:10.1016/s0092-8674(00)80712-6. PMID 10199400.

Further reading

• El-Jaick KB, Powers SE, Bartholin L, Myers KR, Hahn J, Orioli IM, Ouspenskaia M, Lacbawan F, Roessler E, Wotton D, Muenke M (2007). "Functional analysis of mutations in TGIF associated with holoprosencephaly". Mol. Genet. Metab. 90 (1): 97–111. doi:10.1016/j.ymgme.2006.07.011. PMC 1820763. PMID 16962354.
• Münke M, Page DC, Brown LG, Armson BA, Zackai EH, Mennuti MT, Emanuel BS (1989). "Molecular detection of a Yp/18 translocation in a 45,X holoprosencephalic male". Hum. Genet. 80 (3): 219–23. doi:10.1007/BF01790089. PMID 3192211.
• Overhauser J, Mitchell HF, Zackai EH, Tick DB, Rojas K, Muenke M (1995). "Physical mapping of the holoprosencephaly critical region in 18p11.3". Am. J. Hum. Genet. 57 (5): 1080–5. PMC 1801375. PMID 7485158.
• Wotton D, Lo RS, Lee S, Massagué J (1999). "A Smad transcriptional corepressor". Cell. 97 (1): 29–39. doi:10.1016/S0092-8674(00)80712-6. PMID 10199400.
• Yang Y, Hwang CK, D'Souza UM, Lee SH, Junn E, Mouradian MM (2000). "Three-amino acid extension loop homeodomain proteins Meis2 and TGIF differentially regulate transcription". J. Biol. Chem. 275 (27): 20734–41. doi:10.1074/jbc.M908382199. PMID 10764806.
• Melhuish TA, Wotton D (2001). "The interaction of the carboxyl terminus-binding protein with the Smad corepressor TGIF is disrupted by a holoprosencephaly mutation in TGIF". J. Biol. Chem. 275 (50): 39762–6. doi:10.1074/jbc.C000416200. PMID 10995736.
• Lo RS, Wotton D, Massagué J (2001). "Epidermal growth factor signaling via Ras controls the Smad transcriptional co-repressor TGIF". EMBO J. 20 (1–2): 128–36. doi:10.1093/emboj/20.1.128. PMC 140192. PMID 11226163.
• Pessah M, Prunier C, Marais J, Ferrand N, Mazars A, Lallemand F, Gauthier JM, Atfi A (2001). "c-Jun interacts with the corepressor TG-interacting factor (TGIF) to suppress Smad2 transcriptional activity". Proc. Natl. Acad. Sci. U.S.A. 98 (11): 6198–203. doi:10.1073/pnas.101579798. PMC 33445. PMID 11371641.
• Yu X, Li P, Roeder RG, Wang Z (2001). "Inhibition of androgen receptor-mediated transcription by amino-terminal enhancer of split". Mol. Cell. Biol. 21 (14): 4614–25. doi:10.1128/MCB.21.14.4614-4625.2001. PMC 87125. PMID 11416139.
• Wotton D, Knoepfler PS, Laherty CD, Eisenman RN, Massagué J (2001). "The Smad transcriptional corepressor TGIF recruits mSin3". Cell Growth Differ. 12 (9): 457–63. PMID 11571228.
• Sharma M, Sun Z (2002). "5'TG3' interacting factor interacts with Sin3A and represses AR-mediated transcription". Mol. Endocrinol. 15 (11): 1918–28. doi:10.1210/me.15.11.1918. PMID 11682623.
• Dintilhac A, Bernués J (2002). "HMGB1 interacts with many apparently unrelated proteins by recognizing short amino acid sequences". J. Biol. Chem. 277 (9): 7021–8. doi:10.1074/jbc.M108417200. PMID 11748221.
• Chen CP, Chern SR, Du SH, Wang W (2002). "Molecular diagnosis of a novel heterozygous 268C-->T (R90C) mutation in TGIF gene in a fetus with holoprosencephaly and premaxillary agenesis". Prenat. Diagn. 22 (1): 5–7. doi:10.1002/pd.202. PMID 11810641.
• Aguilella C, Dubourg C, Attia-Sobol J, Vigneron J, Blayau M, Pasquier L, Lazaro L, Odent S, David V (2003). "Molecular screening of the TGIF gene in holoprosencephaly: identification of two novel mutations". Hum. Genet. 112 (2): 131–4. doi:10.1007/s00439-002-0862-8. PMID 12522553.
• Chen F, Ogawa K, Nagarajan RP, Zhang M, Kuang C, Chen Y (2003). "Regulation of TG-interacting factor by transforming growth factor-beta". Biochem. J. 371 (Pt 2): 257–63. doi:10.1042/BJ20030095. PMC 1223316. PMID 12593671.
• Lam DS, Lee WS, Leung YF, Tam PO, Fan DS, Fan BJ, Pang CP (2003). "TGFbeta-induced factor: a candidate gene for high myopia". Invest. Ophthalmol. Vis. Sci. 44 (3): 1012–5. doi:10.1167/iovs.02-0058. PMID 12601022.
• Dubourg C, Lazaro L, Pasquier L, Bendavid C, Blayau M, Le Duff F, Durou MR, Odent S, David V (2004). "Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients with features of holoprosencephaly spectrum: Mutation review and genotype-phenotype correlations". Hum. Mutat. 24 (1): 43–51. doi:10.1002/humu.20056. PMID 15221788.