PROSITE documentation PDOC00035
POU-specific (POUs) domain signatures and profile and POUs atypical domain profile


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 [8].

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 system neurons.
  • 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 during development.
  • 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 [9,10].

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.

Last update:

August 2020 / Text revised; profile added.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

POU_3, PS51179; POU-specific (POUs) domain profile  (MATRIX)

POU_4, PS51936; POU-specific (POUs) atypical domain profile  (MATRIX)

POU_1, PS00035; POU-specific (POUs) domain signature 1  (PATTERN)

POU_2, PS00465; POU-specific (POUs) domain signature 2  (PATTERN)


1AuthorsRobertson M.
TitleHomoeo boxes, POU proteins and the limits to promiscuity.
SourceNature 336:522-524(1988).
PubMed ID2904652

2AuthorsSturm R.A. Herr W.
TitleThe POU domain is a bipartite DNA-binding structure.
SourceNature 336:601-604(1988).
PubMed ID2904656

3AuthorsHerr W. Sturm R.A. Clerc R.G. Corcoran L.M. Baltimore D. Sharp P.A. Ingraham H.A. Rosenfeld M.G. Finney M. Ruvkun G. Horvitz H.R.
TitleThe POU domain: a large conserved region in the mammalian pit-1, oct-1, oct-2, and Caenorhabditis elegans unc-86 gene products.
SourceGenes Dev. 2:1513-1516(1988).
PubMed ID3215510

4AuthorsLevine M. Hoey T.
TitleHomeobox proteins as sequence-specific transcription factors.
SourceCell 55:537-540(1988).
PubMed ID2902929

5AuthorsRosenfeld M.G.
TitlePOU-domain transcription factors: pou-er-ful developmental regulators.
SourceGenes Dev. 5:897-907(1991).
PubMed ID2044958

6AuthorsSchoeler H.R.
SourceTrends Genet. 7:323-329(1991).

7AuthorsVerrijzer C.P. Van der Vliet P.C.
TitlePOU domain transcription factors.
SourceBiochim. Biophys. Acta 1173:1-21(1993).
PubMed ID8485147

8AuthorsAssa-Munt N. Mortishire-Smith R.J. Aurora R. Herr W. Wright P.E.
TitleThe solution structure of the Oct-1 POU-specific domain reveals a striking similarity to the bacteriophage lambda repressor DNA-binding domain.
SourceCell 73:193-205(1993).
PubMed ID8462099

9AuthorsLu P. Rha G.B. Chi Y.-I.
TitleStructural basis of disease-causing mutations in hepatocyte nuclear factor 1beta.
SourceBiochemistry 46:12071-12080(2007).
PubMed ID17924661

10AuthorsChi Y.-I. Frantz J.D. Oh B.-C. Hansen L. Dhe-Paganon S. Shoelson S.E.
TitleDiabetes mutations delineate an atypical POU domain in HNF-1alpha.
SourceMol. Cell. 10:1129-1137(2002).
PubMed ID12453420

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