Homeobox protein TGIF1

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)
End	3,459,978 bp
Gene location (Mouse)
Chr.	Chromosome 17 (mouse)
End	71,160,541 bp
RNA expression pattern
	Top expressed in
	stromal cell of endometrium; ; gallbladder; ; corpus epididymis; ; rectum; ; gastric mucosa; ; right uterine tube; ; left uterine tube; ; skin of abdomen; ; caput epididymis; ; minor salivary gland;
	Top expressed in
	saccule; ; ectoderm; ; otic placode; ; lip; ; primitive streak; ; corneal stroma; ; spermatocyte; ; cumulus cell; ; abdominal wall; ; maxillary prominence;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	DNA binding ; protein binding ; DNA-binding transcription factor activity ; RNA polymerase II cis-regulatory region sequence-specific DNA binding ; DNA-binding transcription repressor activity, RNA polymerase II-specific ; transcription corepressor activity ; DNA-binding transcription factor activity, RNA polymerase II-specific ; co-SMAD binding ;
Cellular component	nucleus ; nucleoplasm ;
Biological process	regulation of transcription, DNA-templated ; negative regulation of gene expression ; multicellular organism development ; cellular response to growth factor stimulus ; negative regulation of transcription by RNA polymerase II ; transcription, DNA-templated ;
	Sources:Amigo / QuickGO
Orthologs
	7050
	21815
	ENSG00000177426
	ENSMUSG00000047407
	Q15583
	P70284
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 Contents Function ; Clinical significance ; Interactions ; References ; Further reading ;
	NM_001164074 ; NM_001164075 ; NM_001164076 ; NM_001164077 ; NM_009372
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
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated December 24, 2023

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.

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]

Related Research Articles

Histone acetyltransferase p300 also known as p300 HAT or E1A-associated protein p300 also known as EP300 or p300 is an enzyme that, in humans, is encoded by the EP300 gene. It functions as histone acetyltransferase that regulates transcription of genes via chromatin remodeling by allowing histone proteins to wrap DNA less tightly. This enzyme plays an essential role in regulating cell growth and division, prompting cells to mature and assume specialized functions (differentiate), and preventing the growth of cancerous tumors. The p300 protein appears to be critical for normal development before and after birth.

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Mothers against decapentaplegic homolog 2 also known as SMAD family member 2 or SMAD2 is a protein that in humans is encoded by the SMAD2 gene. MAD homolog 2 belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways.

SMAD family member 6, also known as SMAD6, is a protein that in humans is encoded by the SMAD6 gene.

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Activin receptor type-1B is a protein that in humans is encoded by the ACVR1B gene.

Zinc finger E-box-binding homeobox 2 is a protein that in humans is encoded by the ZEB2 gene. The ZEB2 protein is a transcription factor that plays a role in the transforming growth factor β (TGFβ) signaling pathways that are essential during early fetal development.

<span class="mw-page-title-main">CTBP1</span> Protein-coding gene in the species Homo sapiens

C-terminal-binding protein 1 also known as CtBP1 is a protein that in humans is encoded by the CTBP1 gene. CtBP1 is one of two CtBP proteins, the other protein being CtBP2.

Scaffold attachment factor B, also known as SAFB, is a gene with homologs that have been studied in humans and mice.

LIM/homeobox protein Lhx3 is a protein that in humans is encoded by the LHX3 gene.

Homeobox protein Hox-C8 is a protein that in humans is encoded by the HOXC8 gene.

Prospero homeobox protein 1 is a protein that in humans is encoded by the PROX1 gene. The Prox1 gene is critical for the development of multiple tissues. Prox1 activity is necessary and sufficient to specify a lymphatic endothelial cell fate in endothelial progenitors located in the embryonic veins.

Paired mesoderm homeobox protein 2A is a protein that in humans is encoded by the PHOX2A gene.

Homeobox protein Hox-C4 is a protein that in humans is encoded by the HOXC4 gene.

Forkhead box protein G1 is a protein that in humans is encoded by the FOXG1 gene.

Homeobox protein SIX3 is a protein that in humans is encoded by the SIX3 gene.

Forkhead box protein H1 is a protein that in humans is encoded by the FOXH1 gene.

Zinc finger protein ZIC2 is a protein that in humans is encoded by the ZIC2 gene. ZIC2 is a member of the Zinc finger of the cerebellum (ZIC) protein family.

Homeobox protein TGIF2 is a protein that in humans is encoded by the TGIF2 gene.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000177426 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000047407 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ 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.
↑ 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. S2CID 24723063.
1 2 "Entrez Gene: TGIF1 TGFB-induced factor homeobox 1".
1 2 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. Bibcode:2001PNAS...98.6198P. doi: 10.1073/pnas.101579798 . PMC 33445 . PMID 11371641.
1 2 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.
↑ 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.
↑ 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. S2CID 6907878.

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. S2CID 15442879.
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. S2CID 6907878.
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. Bibcode:2001PNAS...98.6198P. 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/mend.15.11.0732 . 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 . hdl: 10261/112516 . 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. S2CID 8297098.
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. S2CID 2238304.
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. S2CID 34076824.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000177426 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 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.

[pmid8537382-5] 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.

[pmid10835638-6] 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. S2CID 24723063.

[entrez-7] 1 2 "Entrez Gene: TGIF1 TGFB-induced factor homeobox 1".

[pmid11371641-8] 1 2 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. Bibcode:2001PNAS...98.6198P. doi: 10.1073/pnas.101579798 . PMC 33445 . PMID 11371641.

[pmid10995736-9] 1 2 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.

[pmid11427533-10] 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.

[pmid10199400-11] 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. S2CID 6907878.

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