The POU (pronounced 'pow') domain [1,2,3,4,5,6,7] is a highly charged 155-162-amino
acid region of sequence similarity which has been identified in the three
mammalian transcription factors Pit-1, Oct-1, and Oct-2 and in the product of
the nematode gene unc-86. The POU domain is a bipartite DNA binding protein
module that binds selectively to the DNA octamer motif ATGCAAAT and a subset
of derivatives. It consists of two subdomains, a C-terminal homeodomain (POUh)
(see <PDOC00027>) and an N-terminal 75- to 82-residue POU-specific (POUs)
region separated by a short non-conserved linker. The POU-specific region or
'box' can be subdivided further into two highly conserved regions, A and B,
separated by a less highly conserved segment. The POUs domain is always found
in association with a POUh domain, and both are required for high affinity and
sequence-specific DNA binding.
The POUs domain consists of four α helices packed to enclose an extensive
hydrophobic core (see <PDB:1POU>). The POUs domain contains an unusual HTH
structure, which differs from the canonical HTH motif in the length of the
first α helix and the turn. The region of hypervariability located between
subdomains A and B lies within the sequence corresponding to the C-terminal
end of helix 2 and the linker between helices 2 and 3. In the model of the
POUs-DNA complex, the C-terminus of helix 2 and the turn of the HTH motif
project away from the DNA such that sequence variability in this region can be
accomodated without adversely affecting DNA binding .
Some proteins currently known to contain a POUs domain are listed below:
- Oct-1 (or OTF-1, NF-A1) (gene POU2F1), a transcription factor for small
nuclear RNA and histone H2B genes.
- Oct-2 (or OTF-2, NF-A2) (gene POU2F2), a transcription factor that
specifically binds to the immunoglobulin promoters octamer motif and
activates these genes.
- Oct-3 (or Oct-4, NF-A3) (gene POU5F1), a transcription factor that also
binds to the octamer motif.
- Oct-6 (or OTF-6, SCIP) (gene POU3F1), an octamer-binding transcription
factor thought to be involved in early embryogenesis and neurogenesis.
- Oct-7 (or N-Oct 3, OTF-7, Brn-2) (gene POU3F2), a nervous-system specific
octamer-binding transcription factor.
- Oct-11 (or OTF-11) (gene POU2F3), an octamer-binding transcription factor.
- Pit-1 (or GHF-1) (gene POU1F1), a transcription factor that activates
growth hormone and prolactin genes.
- Brn-1 (or OTF-8) (gene POU3F3).
- Brn-3A (or RDC-1) (gene POU4F1), a probable transcription factor that may
play a role in neuronal tissue differentiation.
- Brn-3B (gene POU4F2), a probable transcription factor that may play a role
in determining or maintaining the identities of a small subset of visual
- Brn-3C (gene POU4F3).
- Brn-4 (or OTF-9) (gene POU3F4), a probable transcription factor which
exerts its primary action widely during early neural development and in a
very limited set of neurons in the mature brain.
- Mpou (or Brn-5, Emb) (gene POU6F1), a transcription factor that binds
preferentially to a variant of the octamer motif.
- Skn, that activates cytokeratin 10 (k10) gene expression.
- Sprm-1, a transcription factor that binds preferentially to the octamer
motif and that may exert a regulatory function in meiotic events that are
required for terminal differentiation of male germ cell.
- Unc-86, a Caenorhabditis elegans transcription factor involved in cell
lineage and differentiation.
- Cf1-a, a Drosophila neuron-specific transcription factor necessary for the
expression of the dopa decarboxylase gene (dcc).
- I-POU, a Drosophila protein that forms a stable heterodimeric complex with
Cf1-a and inhibits its action.
- Drosophila protein nubbin/twain (PDM-1 or DPou-19).
- Drosophila protein didymous (PDM-2 or DPou-28) that may play multiple roles
- Bombyx mori silk gland factor 3 (SGF-3).
- Xenopus proteins Pou1, Pou2, and Pou3.
- Zebrafish proteins Pou1, Pou2, Pou[C], ZP-12, ZP-23, ZP-47 and ZP-50.
- Caenorhabditis elegans protein ceh-6.
- Caenorhabditis elegans protein ceh-18.
HNF1α (MODY3 gene product, the most commonly mutated MODY protein) and
HNF1β (hepatocyte nuclear factor 1β; also known as vHNF1 or TCF2) (MODY5
gene product) are atypical members of the POU transcription factors. Their
atypical POUs domains have at least one additional α-helix at the N-terminus, and the second helix and adjacent loop of their POUh domains are
much longer, creating a more extensive interface between the POUs and POUh
domains (see <PDB:2H8R>). This extended interface fixes the relative
orientations of the two domains and provides rigidity for DNA recognition as
opposed to the flexibility seen in another POU transcription factor, Pit-1
We have derived two signature patterns for the 'POU' domain. The first one
spans positions 15 to 27 of the domain, the second positions 42 to 55. We have
also developed a profile which covers the entire POUs domain and another that
covers the entire atypical POUs domain.
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