Family

Pituitary-specific positive transcription factor 1 (IPR015586)

Short name: Pit_1

Family relationships

None.

Description

POU proteins are eukaryotic transcription factors containing a bipartite DNA-binding domain referred to as the POU domain. The acronym POU (pronounced 'pow') is named after the pituitary-specific Pit-1, octamer-binding proteins Oct-1 and Oct-2, and the neural Unc-86 from Caenorhabditis elegans. The POU domain is a 70 to 75 amino-acid region found upstream of a homeobox domain in some transcription factors. POU domain genes have been described in organisms as divergent as C. elegans, Drosophila melanogaster (Fruit fly), Xenopus laevis (African clawed frog), Danio rerio (Zebrafish) (Brachydanio rerio) and Homo sapiens (Human) but have not been yet identified in plants and fungi. The various members of the POU family have a wide variety of functions, all of which are related to the development of an organism [PMID: 11159814].

The POU domain is a bipartite domain composed of two subunits separated by a non-conserved region of 15-55 amino acids. The N-terminal subunit is known as POU-specific (POUs) domain (IPR000327) and a C-terminal homeodomain. Both subdomains contain the structural motif 'helix-turn-helix', which directly associates with the two components of bipartite DNA-binding sites. The 3-D structure of the POU-domain has been determined by multidimensional NMR [PMID: 8462099] and X-ray crystallography to 3.0 A resolution [PMID: 8156594]. The subdomains are connected by a flexible linker [PMID: 11183772, PMID: 8156594, PMID: 9009203]. Despite of the lack of sequence homology, 3D structure of POUs is similar to 3D structure of bacteriophage lambda repressor and other members of HTH_3 family [PMID: 11183772, PMID: 8156594].

POU domain containing proteins bind to specific DNA sequences to cause temporal and spatial regulation of genes. Including genes: involved in the regulation of neuronal development in the central nervous system of mammals [PMID: 1967821]; immunoglobulin light and heavy chains (Oct-2) [PMID: 1967834]; and those for prolactin and growth hormone (Pit-1). Both elements of the POU-domain are required for high affinity sequence-specific DNA-binding. The domain may also be involved in protein-protein interactions [PMID: 1628619].

Pituitary-specific positive transcription factor 1 (PIT1) is required for the appearance of hormone specific cell types in the anterior pituitary, including: lactotrophs, which secrete prolactin (PRL); thyrotrophs, which secrete thyroid stimulating hormone (TSH); somatotrophs, which secrete growth hormone (GH), and corticotrophs, which secrete adrenocorticotropic hormone (ACTH) [PMID: 1977085]. PIT1-deficient Pit1dw mutant mouse shows that PIT1 autoregulation is not needed for initial activation or continued expression during critical phases of PIT1 target gene activation, but is necessary for subsequent maintenance of Pit1 gene expression after birth. Homozygous Pit1dw mice are about one-fourth to one-third normal size and are sterile. The small size is due to a defective anterior pituitary in which there is a great deficiency of GH-producing, PRL-producing, and TSH-producing cells. The human homologue POU1F1 gene has been shown to be mutated in some forms of human dwarfism caused by a lack of pituitary hormones [PMID: 1509263].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PANTHER