NK2 homeobox 1
- OMIM: 600635
- MGI: 108067
The thyroidal transcription factor 1, abbreviated TTF1, is a protein as a transcription factor which controls, inter alia, the transcription of certain genes in the thyroid. TTF1 is the homeobox gene NK2 homeobox 1 NKX2 -1 abbreviated, coded and has been proven not only in humans but also in a variety of animal species.
Structure and Function
The human 371 amino acid long, located in the cell nucleus protein contains in its amino acid sequence, a 60 amino acid long homeodomain, can bind on the TTF1 to specific DNA sequence portions. This DNA binding is a prerequisite for the control of the transcription of other genes. TTF1 is essential for the expression of thyroglobulin and thyroid peroxidase in the adult thyroid in interaction with the transcription factor PAX8. In addition to controlling the expression of TTF1 surfactant proteins in the lung.
TTF1 plays an important role not only in the adult organism, but also during the organogenesis of the thyroid, lung and brain. In the embryo is TTF1 early in both the forebrain and in parts of the foregut detectable, even before the endodermal tissues in the foregut are morphologically recognizable as lung bud or as the thyroid system. TTF1 is thus one next to PAX8, and HHEX FOXE1 the earliest molecular markers for thyroid development.
Knockout mice in which TTF1 is inactive, die at birth and have neither thyroid nor lung parenchyma. Also in these mice lacking parts of the forebrain and the pituitary gland.
TTF1 was originally identified in mammals, but it is also been demonstrated in a number of species of chordates up to the lancelet. The expression of AmphiNk2 -1 in the lancelet Endostyl underlines that this structure to the thyroid of vertebrates is homologous.
The gene coding for TTF1 NKX2 -1 gene belongs to the subgroup of Nk2.1 Homöoboxgene. In mammals, there are in addition NKX2 -1 Another paralogous gene NKX2 -4, but which is not active in the thyroid nor in the lung but only in the forebrain. Namesake for the Nk2.1 group were originally NK2 Homöoboxgene from Drosophila melanogaster. The orthologous to Nk2.1 - group gene in Drosophila, scro, is also in the brain and in the anterior endoderm of the fly embryo active.
Importance in medicine
In human medicine the TTF1 protein is a useful marker for the identification of the primary tumor metastases. The immunohistochemical detection of TTF1 indicates a primary tumor in the lung.
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's patients could be correlated with reduced binding of the RET promoter and activation of RET by TTF1. Reduced RET activity is considered to be a significant cause that can lead to the manifestation of Hirschsprung's disease.