{PDOC00035} {PS00035; POU_1} {PS00465; POU_2} {PS51179; POU_3} {PS51936; POU_4} {BEGIN} ************************************************************************************** * POU-specific (POUs) domain signatures and profile and POUs atypical domain profile * ************************************************************************************** The POU (pronounced 'pow') domain [1 to 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 ) 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 alpha helices packed to enclose an extensive hydrophobic core (see ). The POUs domain contains an unusual HTH structure, which differs from the canonical HTH motif in the length of the first alpha 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. HNF1alpha (MODY3 gene product, the most commonly mutated MODY protein) and HNF1beta (hepatocyte nuclear factor 1beta; 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 alpha-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 ). 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. -Consensus pattern: [RKQ]-R-[LIM]-x-[LF]-G-[LIVMFY]-x-Q-x-[DNQ]-V-G -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Consensus pattern: S-Q-[STK]-[TA]-I-[SC]-R-[FH]-[ET]-x-[LSQ]-x(0,1)-[LIR]- [ST] -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: August 2020 / Text revised; profile added. [ 1] Robertson M. "Homoeo boxes, POU proteins and the limits to promiscuity." Nature 336:522-524(1988). PubMed=2904652; DOI=10.1038/336522a0 [ 2] Sturm R.A., Herr W. "The POU domain is a bipartite DNA-binding structure." Nature 336:601-604(1988). PubMed=2904656; DOI=10.1038/336601a0 [ 3] Herr 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. "The POU domain: a large conserved region in the mammalian pit-1, oct-1, oct-2, and Caenorhabditis elegans unc-86 gene products." Genes Dev. 2:1513-1516(1988). PubMed=3215510 [ 4] Levine M., Hoey T. "Homeobox proteins as sequence-specific transcription factors." Cell 55:537-540(1988). PubMed=2902929 [ 5] Rosenfeld M.G. "POU-domain transcription factors: pou-er-ful developmental regulators." Genes Dev. 5:897-907(1991). PubMed=2044958 [ 6] Schoeler H.R. Trends Genet. 7:323-329(1991). [ 7] Verrijzer C.P., Van der Vliet P.C. "POU domain transcription factors." Biochim. Biophys. Acta 1173:1-21(1993). PubMed=8485147 [ 8] Assa-Munt N., Mortishire-Smith R.J., Aurora R., Herr W., Wright P.E. "The solution structure of the Oct-1 POU-specific domain reveals a striking similarity to the bacteriophage lambda repressor DNA-binding domain." Cell 73:193-205(1993). PubMed=8462099 [ 9] Lu P., Rha G.B., Chi Y.-I. "Structural basis of disease-causing mutations in hepatocyte nuclear factor 1beta." Biochemistry 46:12071-12080(2007). PubMed=17924661; DOI=10.1021/bi7010527 [10] Chi Y.-I., Frantz J.D., Oh B.-C., Hansen L., Dhe-Paganon S., Shoelson S.E. "Diabetes mutations delineate an atypical POU domain in HNF-1alpha." Mol. Cell. 10:1129-1137(2002). PubMed=12453420; DOI=10.1016/s1097-2765(02)00704-9 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}