Thyroid transcription factor 1
| Thyroid transcription factor 1 | ||
|---|---|---|
| Properties of human protein | ||
| Mass / length primary structure | 371 amino acids; 38.6 kDa | |
| Secondary to quaternary structure | Home box (161-220) | |
| Isoforms | 2 | |
| Identifier | ||
| Gene names | NKX2-1 ; TTF1; TITF1 | |
| External IDs | ||
| Occurrence | ||
| Parent taxon | Chordates | |
| Orthologue | ||
| human | mouse | |
| Entrez | 7080 | 21869 |
| Ensemble | ENSG00000136352 | ENSMUSG00000001496 |
| UniProt | P43699 | Q6PFE0 |
| Refseq (mRNA) | NM_001079668 | NM_009385 |
| Refseq (protein) | NP_001073136 | NP_033411 |
| Gene locus | Chr 14: 36.06 - 36.06 Mb | Chr 12: 57.45 - 57.45 Mb |
| PubMed search | 7080 |
21869
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The thyroidal transcription factor 1 , abbreviated TTF1 , is a protein that, as a transcription factor , controls, among other things, the transcription of certain genes in the thyroid . TTF1 is the homeobox - Gen NK2 homeobox 1 abbreviated, NKX2-1 , coded and has not been shown only in humans but also in a variety of animal species.
Structure and function
The protein, which is 371 amino acids long in humans and located in the cell nucleus , contains in its amino acid sequence a 60 amino acid long homeodomain through which TTF1 can bind to specific DNA sequence segments. This DNA binding is a prerequisite for the control of the transcription of other genes. TTF1, in conjunction with the transcription factor PAX8, is essential for the expression of thyroglobulin and thyroid peroxidase in the adult thyroid. In addition, TTF1 should control the expression of surfactant proteins in the lungs.
TTF1 plays an important role not only in the adult organism, but also during the organogenesis of the thyroid gland, the lungs and the brain . In the embryo, TTF1 can be detected at an early stage both in the forebrain and in parts of the foregut , namely before the endodermal tissue in the foregut is morphologically recognizable as a lung bud or as a thyroid anlage. TTF1 is one of the earliest molecular markers for thyroid development alongside PAX8, FOXE1 and HHEX.
Knockout mice in which TTF1 is inactive die at birth and have neither thyroid nor lung parenchyma. In addition, parts of the forebrain and pituitary gland are missing in these mice .
evolution
TTF1 was originally identified in mammals , but it has also been found in a number of species from chordates to lancetfish . The expression of AmphiNk2-1 in the endostyle of the lancet fish underlines that this structure is homologous to the thyroid gland of vertebrates .
The NKX2-1 gene coding for TTF1 belongs to the Nk2.1 subgroup of homeobox genes. In mammals there are in addition to NKX2-1. Another, paralogous gene, NKX2-4 , which is active neither in the thyroid gland nor in the lungs, but only in the forebrain. The namesake for the Nk2.1 group were originally NK2 homeobox genes from Drosophila melanogaster . The gene orthologous to the Nk2.1 group in Drosophila , scro , is also active in the brain and in the anterior endoderm of the fly embryo .
Importance in medicine
In human medicine, the TTF1 protein is a useful marker for identifying the primary tumor from metastases . The immunohistochemical detection of TTF1 indicates a primary tumor in the lung area.
From human genetics there is evidence of a connection between TTF1 and Hirschsprung's disease . Both single nucleotide polymorphisms (SNPs) in the promoter of the RET gene and SNPs in the NKX2-1 gene in Hirschsprung patients could be correlated with reduced binding of the RET promoter and activation of RET by TTF1. Decreased RET activity is considered to be a major cause that can lead to the manifestation of Hirschsprung's disease.
Mutations in this gene underlie benign hereditary chorea .
Individual evidence
- ↑ D. Christophe: The control of thyroid-specific gene expression: what exactly have we learned as yet? In: Mol Cell Endocrinol. 223 (1-2), Aug 31, 2004, pp. 1-4. PMID 15358049
- ↑ M. De Felice, R. Di Lauro: Thyroid development and its disorders: genetics and molecular mechanisms. In: Endocr Rev . 25 (5), Oct 2004, pp. 722-746. PMID 15466939
- ↑ S. Kimura, Y. Hara, T. Pineau, P. Fernandez-Salguero, CH Fox, JM Ward, FJ Gonzalez: The T / ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid , lung, ventral forebrain, and pituitary. In: Genes Dev. 10 (1), Jan 1, 1996, pp. 60-69. PMID 8557195
- ^ TV Venkatesh, ND Holland, LZ Holland, MT Su, R. Bodmer: Sequence and developmental expression of amphioxus AmphiNk2-1: insights into the evolutionary origin of the vertebrate thyroid gland and forebrain. In: Dev Genes Evol. 209 (4), Apr 1999, pp. 254-249. PMID 10079369
- ↑ PWH Holland, AF Booth, EA Bruford: Classification and nomenclature of all human homeobox genes In: BMC Biology. 5, 2007, p. 47. PMID 17963489
- ↑ S. Zaffran, G. Das, M. Frasch: The NK-2 homeobox gene scarecrow (scro) is expressed in pharynx, ventral nerve cord and brain of Drosophila embryos. In: Mech Dev. 94 (1-2), Jun 2000, pp. 237-241. PMID 10842079
- ↑ SY Park, BH Kim, JH Kim, S. Lee, GH Kang: Panels of immunohistochemical markers help determine primary sites of metastatic adenocarcinoma. In: Arch Pathol Lab Med . 131 (10), Oct 2007, pp. 1561-1567. PMID 17922593
- ↑ MM Garcia-Barceló, DK Lau, ES Ngan, TY Leon, T. Liu, M. So, X. Miao, VC Lui, KK Wong, RW Ganster, DT Cass, GD Croaker, PK Tam: Evaluation of the NK2 homeobox 1 gene (NKX2-1) as a Hirschsprung's disease locus. In: Ann Hum Genet. 72 (Pt 2), Mar 2008, pp 170-177. PMID 18081917 .
- ^ Chorea, hereditary benign. In: Online Mendelian Inheritance in Man . (English)