|PROSITE documentation PDOC51081|
SINA/Siah family proteins represent mammalian homologs of the Drosophila SINA (seven in absentia) protein. SINA is required for R7 photoreceptor cell differentiation within the sevenless pathway . Members of this family are E3 ubiquitin ligases that regulate ubiquitination and protein degradation. Siahs are known to recognize several target proteins including Deleted in Colorectal Cancer (DCC), synaptophysin and Numb and promote their degradation [2,3].
SINA/Siah sequences are highly conserved from plants to mammals. Whereas the N terminus and RING domain of Siah bind E2 proteins, the C terminus can be considered as a substrate- and cofactor-interaction domain (substrate-binding domain, SBD) that interacts with a number of proteins, some of which are degraded . The SBD domain displays some sequence similarities with the C-terminal region of TRAF proteins. It contains a cysteine-rich region, the SIAH-type zinc finger, with eight totally conserved Cys and His residues that coordinate two zinc atoms .
The profile we developed covers the entire SIAH-type zinc finger.Last update:
February 2005 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Carthew R.W. Rubin G.M.|
|Title||seven in absentia, a gene required for specification of R7 cell fate in the Drosophila eye.|
|2||Authors||Hu G. Zhang S. Vidal M. Baer J.L. Xu T. Fearon E.R.|
|Title||Mammalian homologs of seven in absentia regulate DCC via the ubiquitin-proteasome pathway.|
|Source||Genes Dev. 11:2701-2714(1997).|
|3||Authors||Susini L. Passer B.J. Amzallag-Elbaz N. Juven-Gershon T. Prieur S. Privat N. Tuynder M. Gendron M.C. Israel A. Amson R. Oren M. Telerman A.|
|Title||Siah-1 binds and regulates the function of Numb.|
|Source||Proc. Natl. Acad. Sci. U.S.A. 98:15067-15072(2001).|
|4||Authors||Hu G. Fearon E.R.|
|Title||Siah-1 N-terminal RING domain is required for proteolysis function, and C-terminal sequences regulate oligomerization and binding to target proteins.|
|Source||Mol. Cell. Biol. 19:724-732(1999).|
|5||Authors||Polekhina G. House C.M. Traficante N. Mackay J.P. Relaix F. Sassoon D.A. Parker M.W. Bowtell D.D.|
|Title||Siah ubiquitin ligase is structurally related to TRAF and modulates TNF-alpha signaling.|
|Source||Nat. Struct. Biol. 9:68-75(2002).|