Paired box protein 8
| Paired box protein 8 | ||
|---|---|---|
|
||
| PAX-5 (yellow) with ETS-1 (green) on DNA (blue) according to PDB 1K78 | ||
| Properties of human protein | ||
| Mass / length primary structure | 450 amino acids; 48.1 kDa | |
| Isoforms | 5 | |
| Identifier | ||
| Gene name | PAX8 | |
| External IDs | ||
| Occurrence | ||
| Parent taxon | Bilateria (bilateral animals) | |
| Orthologue | ||
| human | mouse | |
| Entrez | 7849 | 18510 |
| Ensemble | ENSG00000125618 | ENSMUSG00000026976 |
| UniProt | Q06710 | Q6GU20 |
| Refseq (mRNA) | NM_003466 | NM_011040 |
| Refseq (protein) | NP_003457 | NP_035170 |
| Gene locus | Chr 2: 113.69 - 113.72 Mb | Chr 2: 24.24 - 24.3 Mb |
| PubMed search | 7849 |
18510
|
The paired box protein 8 , abbreviated to PAX8 , is a protein that, as a transcription factor , controls the transcription of certain genes in the thyroid gland , among other things . The gene encoding PAX8 belongs to the family of Pax genes . PAX8 has been found not only in humans, but also in a wide variety of animal species.
Structure and function
The protein, which is 450 amino acids long in humans and located in the cell nucleus , contains in its amino acid sequence a 127 amino acid long paired domain , via which PAX8 can bind to specific DNA sequence segments, and a partial homeodomain . In the thyroid gland, PAX8, in conjunction with TTF1, controls the transcription of thyroglobulin , thyroid peroxidase and the sodium iodide symporter .
PAX8 plays an important role not only in the adult organism, but also during the organogenesis of the thyroid and kidney . In the embryo, PAX8 is active in the developing thyroid gland, from the earliest anlage to the fully differentiated organ, in the various stages of development of the kidney, including the anterior kidney and the urinary kidney , and in the nervous system .
In knockout mice in which PAX8 is inactive, the thyroxine- producing follicular epithelial cells are missing in the thyroid gland ; the animals die soon after birth if they are not injected with thyroxine. A number of human genetic studies on a connection between congenital hypothyroidism and mutations in the PAX8 gene have so far only found isolated cases.
In knockout mice in which both PAX8 and the similar PAX2 are inactive, not only is the thyroid affected, the anterior kidney is also absent.
evolution
The PAX8 gene, which codes for the PAX8 protein, belongs to the Pax2 / 5/8 group within the family of Pax genes, which includes two other paralogous genes, PAX2 and PAX5 , in mammals . From this group, only PAX8 is active in the thyroid gland, while PAX2 and PAX8 are expressed together in the developing kidney and apparently have partly redundant functions there.
The Pax2 / 5/8 group was originally identified in the house mouse , but has now been found in a large number of animal species from bilateral animals to lancet fish and sea squirts . In the lancet fish, AmphiPax2 / 5/8 is also active in the endostyle , an organ that is homologous to the thyroid gland of vertebrates .
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
- ^ A. Mansouri, K. Chowdhury, P. Gruss: Follicular cells of the thyroid gland require Pax8 gene function. In: Nat Genet . 19 (1), May 1998, pp. 87-90. PMID 9590297
- ↑ SM Park, VK Chatterjee: Genetics of congenital hypothyroidism. In: J Med Genet. 42 (5), May 2005, pp. 379-389. PMID 15863666
- ↑ M. Bouchard, A. Souabni, M. Mandler, A. Neubüser, M. Busslinger: Nephric lineage specification by Pax2 and Pax8. In: Genes Dev. 16, 2002, pp. 2958-2970. PMID 12435636
- ↑ Z. Kozmik, ND Holland, A. Kalousova, J. Paces, M. Schubert, LZ Holland: Characterization of an amphioxus paired box gene, AmphiPax2 / 5/8: developmental expression patterns in optic support cells, nephridium, thyroid-like structures and pharyngeal gill slits, but not in the midbrain-hindbrain boundary region. In: Development. 126 (6), Mar 1999, pp. 1295-1304. PMID 10021347
- ↑ H. Wada, H. Saiga, N. Satoh, PW Holland: Tripartite organization of the ancestral chordate brain and the antiquity of placodes: insights from ascidian Pax-2/5/8, Hox and Otx genes. In: Development. 125 (6), Mar 1998, pp. 1113-1122. PMID 9463358