PROSITE documentation PDOC50917SPOC domain profile
Split end (spen) proteins have been identified in worms, flies and vertebrates and appear to play a similar role in each organism: they regulate expression of key transcriptional effectors in diverse signaling pathways. Spen proteins vary widely in size (90-600 kDa), but are nevertheless characterized by three repeated N-terminal RNA recognition motifs (RRMs) (see <PDOC00030>) and a highly conserved C-terminal SPOC domain (Spen Paralog and Ortholog C-terminal domain), of ~165 amino acids [1]. It has been suggested that Spen proteins play an essential role in regulating transcriptional repression, and that the conserved function of the SPOC domain is to mediate interaction with corepressors [2].
The SPOC domain is folded into a single compact domain consisting of a β-barrel with seven strands framed by six α helices (see <PDB:1OW1>). It appears to be ideally suited to mediate interaction with other proteins through a number of deep grooves and clefts in the surface as well as two nonpolar loops. Most significantly, the structure reveals a highly basic patch on the surface, which is absolutely conserved throughout the Spen protein family. This basic patch has been shown to mediate the tight and specific interaction of the SPOC domain of the human transcriptional corepressor SHARP with the conserved acidic C-terminal LSD motif from the SMRT/NCoR corepressors. Of the residues conserved across the whole family, most lie on the molecular surface rather than in the core [2].
Some proteins known to contain a SPOC domain are listed below:
- Drosophila split ends (spen). It promotes sclerite development in the head region and represses head-like sclerite development in the thorax.
- Mouse MINT (Msx2 intercating nuclear target). It is involved in skeletal and neuronal development by mediating repression by the homeodomain transcriptional repressor Msx2.
- Human SHARP (SMRT/HDAC1-associated repressor protein), the homolog of MINT.
The profile we developed covers the entire SPOC domain.
Last update:August 2003 / First entry.
-------------------------------------------------------------------------------
PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Wiellette E.L. Harding K.W. Mace K.A. Ronshaugen M.R. Wang F.Y. McGinnis W. |
| Title | spen encodes an RNP motif protein that interacts with Hox pathways to repress the development of head-like sclerites in the Drosophila trunk. | |
| Source | Development 126:5373-5385(1999). | |
| PubMed ID | 10556062 |
| 2 | Authors | Ariyoshi M. Schwabe J.W.R. |
| Title | A conserved structural motif reveals the essential transcriptional repression function of Spen proteins and their role in developmental signaling. | |
| Source | Genes Dev. 17:1909-1920(2003). | |
| PubMed ID | 12897056 | |
| DOI | 10.1101/gad.266203 |
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 prosite_license.html.
View entry in original PROSITE document format
View entry in raw text format (no links)