POU (pronounced 'pow') is a family of

proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that have well-conserved

homeodomain A homeobox is a DNA sequence, around 180 base pairs long, that regulates large-scale anatomical features in the early stages of embryonic development. For instance, mutations in a homeobox may change large-scale anatomical features of the full-g ...

Etymology

The acronym POU is derived from the names of three transcription factors: * the Pituitary-specific

Pit-1 POU domain, class 1, transcription factor 1 (Pit1, growth hormone factor 1), also known as POU1F1, is a transcription factor for growth hormone. Function PIT1 is a pituitary-specific transcription factor responsible for pituitary development a ...

* the Octamer transcription factor proteins

Oct-1 POU domain, class 2, transcription factor 1 is a protein that in humans is encoded by the ''POU2F1'' gene. Interactions POU2F1 has been shown to interact with: * EPRS, * Glucocorticoid receptor, * Glyceraldehyde 3-phosphate dehydrogenase, ...

and

Oct-2 Oct-2 (octamer-binding protein 2) also known as POU domain, class 2, transcription factor 2 is a protein that in humans is encoded by the POU2F2 gene. Oct-2 is an octamer transcription factor which is a member of the POU family POU or pou may r ...

(octamer sequence is ATGCAAAT) * the

neural In Biology, biology, the nervous system is the Complex system, highly complex part of an animal that coordinates its Behavior, actions and Sense, sensory information by transmitting action potential, signals to and from different parts of its ...

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 blend of the Greek ''caeno-'' (recent), ''rhabditis'' (ro ...

''.

Diversity

POU domain

genes In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

have been described in organisms as divergent as ''

'', ''

Drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...

'', ''

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 within it. The two best-known ...

'',

zebrafish The zebrafish (''Danio rerio'') is a freshwater fish belonging to the minnow family ( Cyprinidae) of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (and thus often ...

and human but have not been yet identified in

plants Plants are predominantly Photosynthesis, photosynthetic eukaryotes of the Kingdom (biology), kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all curr ...

and

fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...

. Comparisons of POU domain genes across the animals suggests that the family can be divided into six major classes (POU1-POU6).

is part of the POU1 class,

and

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, the members of the phylum Porifera (; meaning 'pore bearer'), are a basal animal clade as a sister of the diploblasts. They are multicellular organisms that have bodies full of pores and channels allowing water to circulate through t ...

s and

eumetazoa Eumetazoa (), also known as diploblasts, Epitheliozoa, or Histozoa, are a proposed basal animal clade as a sister group of the Porifera (sponges). The basal eumetazoan clades are the Ctenophora and the ParaHoxozoa. Placozoa is now also seen as a ...

ns, POU2 evolved in the

Bilatera The Bilateria or bilaterians are animals with bilateral symmetry as an embryo, i.e. having a left and a right side that are mirror images of each other. This also means they have a head and a tail (anterior-posterior axis) as well as a belly and ...

, and POU5 appears to be unique to

vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, ...

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. Gram-positive bact ...

prokaryote A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Connec ...

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 ''Bacillu ...

''. Akin to the way that POU homeodomain regulators lead to tissue differentiation in

metazoans Animals are multicellular, eukaryotic organisms in the biological kingdom Animalia. With few exceptions, animals consume organic material, breathe oxygen, are able to move, can reproduce sexually, and go through an ontogenetic stage in ...

, this transcription factor is critical for differentiation of a subpopulation of ''B. subtilis'' into a state of

genetic competence In microbiology, genetics, cell biology, and molecular biology, competence is the ability of a cell to alter its genetics by taking up extracellular ("naked") DNA from its environment in the process called transformation. Competence may be diff ...

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 of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...

s containing a bipartite

DNA binding domain A DNA-binding domain (DBD) is an independently folded protein domain that contains at least one structural motif that recognizes double- or single-stranded DNA. A DBD can recognize a specific DNA sequence (a recognition sequence) or have a genera ...

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 Neuroendocrinology is the branch of biology (specifically of physiology) which studies the interaction between the nervous system and the endocrine system; i.e. how the brain regulates the hormonal activity in the body. The nervous and endocrine ...

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 Trophic hormones are hormones of the anterior lobe of the pituitary. These hormones affect growth, function, or nutrition of other endocrine cells. Trophic hormones can be found in body systems including the endocrine, gastrointestinal, urinary, a ...

genes, such as those for

prolactin Prolactin (PRL), also known as lactotropin, 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 secreted from the pit ...

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 h ...

(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 ami ...

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, 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 the protein is ...

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 protein (DBP). The helix-turn-helix (HTH) is a major structural motif capable of binding DNA. Each monomer incorporates two α helices, joined by a short strand of amino acids, that bind to the major groove of D ...

', 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 molecular biology, an intrinsically disordered protein (IDP) is a protein that lacks a fixed or ordered three-dimensional structure, typically in the absence of its macromolecular interaction partners, such as other proteins or RNA. IDPs rang ...

. 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. Most arise as superfluous copies of functional genes, either directly by DNA duplication or indirectly by Reverse transcriptase, reverse transcription of an mRNA trans ...

s include: * HDX; * POU1F1; *

POU2F1 POU domain, class 2, transcription factor 1 is a protein that in humans is encoded by the ''POU2F1'' gene. Interactions POU2F1 has been shown to interact with: * EPRS, * Glucocorticoid receptor, * Glyceraldehyde 3-phosphate dehydrogenase, ...

;

POU2F2 POU or pou may refer to: People * Pou (surname), a surname * Chu Pou (303–350), Chinese general and politician * Pou Temara (born 1948), New Zealand Māori academic Codes * POU, IATA airport code and FAA location identifier for Hudson Valley Re ...

;

POU2F3 POU domain, class 2, transcription factor 3 is a protein that in humans is encoded by the ''POU2F3'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meani ...

; *

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. See also * Octamer transcription factor Octamer transcription factors are a protein family, family of transcriptio ...

;

POU3F2 POU domain, class 3, transcription factor 2 is a protein that in humans is encoded by the ''POU3F2'' gene. Function N-Oct-3 is a protein belonging to a large family of transcription factors that bind to the octameric DNA sequence ATGCAAAT. Mos ...

;

POU3F3 POU class 3 homeobox 3 is a protein that in humans is encoded by the POU3F3 gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''bi ...

;

POU3F4 POU domain, class 3, transcription factor 4 is a protein that in humans is encoded by the ''POU3F4'' gene found on the X chromosome. POU3F4 is involved in the patterning of the neural tube and both the paraventricular and supraoptic nuclei of t ...

; *

POU4F1 POU domain, class 4, transcription factor 1 (POU4F1) also known as brain-specific homeobox/POU domain protein 3A (BRN3A), homeobox/POU domain protein RDC-1 or Oct-T1 is a protein that in humans is encoded by the ''POU4F1'' gene. BRN3A (POU4F1) is ...

;

POU4F2 POU domain, class 4, transcription factor 2 is a protein that in humans is encoded by the ''POU4F2'' gene. Function POU4F2 is a member of the POU-domain family of transcription factors. POU-domain proteins have been observed to play important ...

;

POU4F3 POU domain, class 4, transcription factor 3 is a protein that in humans is encoded by the ''POU4F3'' gene. It's a member of BRN-3 group, also known as POU family class 4. Nomenclature DFNA15 refers to a type of nonsyndromic deafness Nonsyndrom ...

; *

POU5F1 Oct-4 (octamer-binding transcription factor 4), also known as POU5F1 (POU domain, class 5, transcription factor 1), is a protein that in humans is encoded by the ''POU5F1'' gene. Oct-4 is a homeodomain transcription factor of the POU family. I ...

; POU5F1B; POU5F1P2; POU5F1P3; POU5F1P4; POU5F1P5; POU5F1P6; POU5F1P7; * POU5F2; * POU6F1; POU6F2

References

{{Transcription factors, g3