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POU (pronounced 'pow') is a
family Family (from ) is a Social group, group of people related either by consanguinity (by recognized birth) or Affinity (law), affinity (by marriage or other relationship). It forms the basis for social order. Ideally, families offer predictabili ...
of
eukaryotic The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...
transcription factors In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fun ...
that have well-conserved
homeodomain A homeobox is a Nucleic acid sequence, DNA sequence, around 180 base pairs long, that regulates large-scale anatomical features in the early stages of embryonic development. Mutations in a homeobox may change large-scale anatomical features of ...
s. The Pou domain is a bipartite DNA binding domain found in these proteins.


Etymology

The acronym POU is derived from the names of three transcription factors: * the Pituitary-specific Pit-1 * the Octamer transcription factor proteins Oct-1 and Oct-2 (octamer sequence is ATGCAAAT) * the neural Unc-86 transcription factor from ''
Caenorhabditis elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a Hybrid word, blend of the Greek ''caeno-'' (recent), ''r ...
''.


Diversity

POU domain
genes In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
have been described in organisms as divergent as ''
Caenorhabditis elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a Hybrid word, blend of the Greek ''caeno-'' (recent), ''r ...
'', ''
Drosophila ''Drosophila'' (), from Ancient Greek δρόσος (''drósos''), meaning "dew", and φίλος (''phílos''), meaning "loving", is a genus of fly, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or p ...
'', ''
Xenopus ''Xenopus'' () (Gk., ξενος, ''xenos'' = strange, πους, ''pous'' = foot, commonly known as the clawed frog) is a genus of highly aquatic frogs native to sub-Saharan Africa. Twenty species are currently described with ...
'',
zebrafish The zebrafish (''Danio rerio'') is a species of freshwater ray-finned fish belonging to the family Danionidae of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (an ...
and human but have not been yet identified in
plants Plants are the eukaryotes that form the kingdom Plantae; they are predominantly photosynthetic. This means that they obtain their energy from sunlight, using chloroplasts derived from endosymbiosis with cyanobacteria to produce sugars f ...
and
fungi A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and mold (fungus), molds, as well as the more familiar mushrooms. These organisms are classified as one ...
. Comparisons of POU domain genes across the animals suggests that the family can be divided into six major classes (POU1-POU6). Pit-1 is part of the POU1 class, Oct-1 and Oct-2 are members of POU2, while Unc-86 is a member of POU4. The six classes diverged early in animal evolution: POU1, POU3, POU4, and POU6 classes evolved before the last common ancestor of
sponge Sponges or sea sponges are primarily marine invertebrates of the animal phylum Porifera (; meaning 'pore bearer'), a basal clade and a sister taxon of the diploblasts. They are sessile filter feeders that are bound to the seabed, and a ...
s and
eumetazoa Eumetazoa (), also known as Epitheliozoa or Histozoa, is a proposed basal animal subkingdom as a sister group of Porifera (sponges). The basal eumetazoan clades are the Ctenophora and the ParaHoxozoa. Placozoa is now also seen as a eumetazoan ...
ns, POU2 evolved in the Bilatera, and POU5 appears to be unique to
vertebrate Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...
s. There is a surprisingly high degree of amino acid sequence conservation (37%-42%) of POU homeodomains to the transcriptional regulator comS, the competence protein from the
gram positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. The Gram stain i ...
prokaryote A prokaryote (; less commonly spelled procaryote) is a unicellular organism, single-celled organism whose cell (biology), cell lacks a cell nucleus, nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Ancient Gree ...
''
Bacillus subtilis ''Bacillus subtilis'' (), known also as the hay bacillus or grass bacillus, is a gram-positive, catalase-positive bacterium, found in soil and the gastrointestinal tract of ruminants, humans and marine sponges. As a member of the genus ''Bacill ...
''. Akin to the way that POU homeodomain regulators lead to tissue differentiation in metazoans, this transcription factor is critical for differentiation of a subpopulation of ''B. subtilis'' into a state of genetic competence.


Function

POU proteins are eukaryotic
transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...
s containing a bipartite DNA binding domain referred to as the POU domain. The various members of the POU family have a wide variety of functions, all of which are related to the function of the neuroendocrine system and the development of an organism. Some other genes are also regulated, including those for immunoglobulin light and heavy chains (Oct-2), and trophic hormone genes, such as those for
prolactin Prolactin (PRL), also known as lactotropin and mammotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secr ...
and
growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in ...
(Pit-1).


Structure

The POU domain is a bipartite domain composed of two subunits separated by a non-conserved region of 15-55 aa. The
N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...
subunit is known as the POU-specific (POUs) domain (), while the
C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When t ...
subunit is a homeobox domain (). 3D structures of complexes including both POU subdomains bound to DNA are available. Both subdomains contain the structural motif '
helix-turn-helix Helix-turn-helix is a DNA-binding domain (DBD). The helix-turn-helix (HTH) is a major structural motif capable of binding DNA. Each monomer incorporates two alpha helix, α helices, joined by a short strand of amino acids, that bind to the majo ...
', which directly associates with the two components of bipartite DNA binding sites, and both are required for high affinity sequence-specific DNA-binding. The domain may also be involved in protein-protein interactions. The subdomains are connected by a flexible linker. In proteins a POU-specific domain is always accompanied by a homeodomain. Despite 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.


Examples

Human genes encoding proteins containing the POU domain and related
pseudogene Pseudogenes are nonfunctional segments of DNA that resemble functional genes. Pseudogenes can be formed from both protein-coding genes and non-coding genes. In the case of protein-coding genes, most pseudogenes arise as superfluous copies of fun ...
s include: * HDX; * POU1F1; * POU2F1; POU2F2; POU2F3; *
POU3F1 POU domain, class 3, transcription factor 1 (also known as Oct-6) is a protein that in humans is encoded by the ''POU3F1'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene i ...
; POU3F2; POU3F3; POU3F4; * POU4F1; POU4F2; POU4F3; * POU5F1; POU5F1B; POU5F1P2; POU5F1P3; POU5F1P4; POU5F1P5; POU5F1P6; POU5F1P7; * POU5F2; * POU6F1; POU6F2


References

{{Transcription factors, g3