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
sponges and
eumetazoans, POU2 evolved in the
Bilatera, and POU5 appears to be unique to
vertebrates.[2]
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 positiveprokaryoteBacillus subtilis.[3] 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.
The POU domain is a bipartite domain composed of two subunits separated by a non-conserved region of 15-55 aa. The
N-terminal subunit is known as the POU-specific (POUs) domain (
InterPro: IPR000327), while the
C-terminal subunit is a homeobox domain (
InterPro: IPR007103). 3D structures of complexes including both POU subdomains bound to DNA are available. Both subdomains contain the structural motif '
helix-turn-helix', 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.[8] The subdomains are connected by a
flexible linker.[9][10][11] 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.[9][10]
Examples
Human genes encoding proteins containing the POU domain and related
pseudogenes include:
^Phillips K, Luisi B (Oct 2000). "The virtuoso of versatility: POU proteins that flex to fit". Journal of Molecular Biology. 302 (5): 1023–39.
doi:
10.1006/jmbi.2000.4107.
PMID11183772.
^Assa-Munt N, Mortishire-Smith RJ, Aurora R, Herr W, Wright PE (Apr 1993). "The solution structure of the Oct-1 POU-specific domain reveals a striking similarity to the bacteriophage lambda repressor DNA-binding domain". Cell. 73 (1): 193–205.
doi:
10.1016/0092-8674(93)90171-L.
PMID8462099.
S2CID24276357.
^Johnson WA, Hirsh J (Feb 1990). "Binding of a Drosophila POU-domain protein to a sequence element regulating gene expression in specific dopaminergic neurons". Nature. 343 (6257): 467–470.
doi:
10.1038/343467a0.
PMID1967821.
S2CID9315961.
^
abPhillips K, Luisi B (Oct 2000). "The virtuoso of versatility: POU proteins that flex to fit". Journal of Molecular Biology. 302 (5): 1023–1039.
doi:
10.1006/jmbi.2000.4107.
PMID11183772.
^
abKlemm JD, Rould MA, Aurora R, Herr W, Pabo CO (Apr 1994). "Crystal structure of the Oct-1 POU domain bound to an octamer site: DNA recognition with tethered DNA-binding modules". Cell. 77 (1): 21–32.
doi:
10.1016/0092-8674(94)90231-3.
PMID8156594.
S2CID36371069.