PROSITE documentation PDOC51818Homeo-Prospero (HPD) domain profile
The prospero-related homeoproteins Prox1 and Prox2 are the vertebrate homologs of the Drosophila melanogaster homeodomain-containing protein Prospero, the founder member of a family of transcription factors which have been shown to play critical roles in many developmental events. The only common feature of this family of proteins is the 160-residue C-terminal Homeo-Prospero domain (HPD), which consists of a highly divergent homeodomain (HD) and an associated Prospero domain (PD) that are essential for sequence-specific DNA binding and the transcriptional activation function of Prospero. The structure of these two regions consists of a single structural unit (HPD), in which the Prospero domain region is in position to contribute to DNA binding and also to mask a defined nuclear export signal that is within the homeodomain region. The HPD domain coordinately regulates Prospero nuclear localization and DNA binding specificity. The HPD domain is required for nearly all the known functions of Prospero, including regulation of nuclear/ cytoplasmic localization, sequence-specific DNA binding, and transcriptional activation [1,2,3,4,5,6].
The HD region does assume an overall fold very similar to homeodomains but with one striking difference. In the homeodomain structure, the so-called DNA recognition helix is either at the extreme C-terminus of the protein or leads into a flexible linker of variable length that connects to another essentially independent domain. In the HPD domain the recognition helix (α3) connects the HD region and the PD region as a single structural unit (see <PDB:1MIJ>). The PD region can be described as a four-helix bundle (α3-α6). At the extreme C terminus of the HPD domain, a short helix is masked by the PD. When this helix is unmasked, Prospero is exported from the nucleus [2,3].
The profile we developed covers the entire HPD domain.
Last update:October 2016 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Tomarev S.I. Sundin O. Banerjee-Basu S. Duncan M.K. Yang J.-M. Piatigorsky J. |
| Title | Chicken homeobox gene Prox 1 related to Drosophila prospero is expressed in the developing lens and retina. | |
| Source | Dev. Dyn. 206:354-367(1996). | |
| PubMed ID | 8853985 | |
| DOI | 10.1002/(SICI)1097-0177(199608)206:4<354::AID-AJA2>3.0.CO;2-H |
| 2 | Authors | Ryter J.M. Doe C.Q. Matthews B.W. |
| Title | Structure of the DNA binding region of prospero reveals a novel homeo-prospero domain. | |
| Source | Structure 10:1541-1549(2002). | |
| PubMed ID | 12429095 |
| 3 | Authors | Yousef M.S. Matthews B.W. |
| Title | Structural basis of Prospero-DNA interaction: implications for transcription regulation in developing cells. | |
| Source | Structure 13:601-607(2005). | |
| PubMed ID | 15837198 | |
| DOI | 10.1016/j.str.2005.01.023 |
| 4 | Authors | Chen X. Patel T.P. Simirskii V.I. Duncan M.K. |
| Title | PCNA interacts with Prox1 and represses its transcriptional activity. | |
| Source | Mol. Vis. 14:2076-2086(2008). | |
| PubMed ID | 19023449 |
| 5 | Authors | Nishijima I. Ohtoshi A. |
| Title | Characterization of a novel prospero-related homeobox gene, Prox2. | |
| Source | Mol. Genet. Genomics 275:471-478(2006). | |
| PubMed ID | 16470382 | |
| DOI | 10.1007/s00438-006-0105-0 |
| 6 | Authors | Pistocchi A. Bartesaghi S. Cotelli F. Del Giacco L. |
| Title | Identification and expression pattern of zebrafish prox2 during embryonic development. | |
| Source | Dev. Dyn. 237:3916-3920(2008). | |
| PubMed ID | 19035352 | |
| DOI | 10.1002/dvdy.21798 |
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