{PDOC51081}
{PS51081; ZF_SIAH}
{BEGIN}
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* Zinc finger SIAH-type profile *
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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 [1]. 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  [4].  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 [5].

The   crystal  structure  of  SIAH-type  zinc  finger  has  been  solved  (see
<PDB:1K2F>)  [5].  It folds  in two subdomains, each one binding one zinc atom
and consisting of two beta-strands and an alpha helice.

The profile we developed covers the entire SIAH-type zinc finger.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: February 2005 / First entry.

[ 1] Carthew R.W., Rubin G.M.
     "seven in absentia, a gene required for specification of R7 cell fate
     in the Drosophila eye."
     Cell 63:561-577(1990).
     PubMed=2146028
[ 2] Hu G., Zhang S., Vidal M., Baer J.L., Xu T., Fearon E.R.
     "Mammalian homologs of seven in absentia regulate DCC via the
     ubiquitin-proteasome pathway."
     Genes Dev. 11:2701-2714(1997).
     PubMed=9334332
[ 3] 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.
     "Siah-1 binds and regulates the function of Numb."
     Proc. Natl. Acad. Sci. U.S.A. 98:15067-15072(2001).
     PubMed=11752454; DOI=10.1073/pnas.261571998
[ 4] Hu G., Fearon E.R.
     "Siah-1 N-terminal RING domain is required for proteolysis function,
     and C-terminal sequences regulate oligomerization and binding to
     target proteins."
     Mol. Cell. Biol. 19:724-732(1999).
     PubMed=9858595
[ 5] Polekhina G., House C.M., Traficante N., Mackay J.P., Relaix F.,
     Sassoon D.A., Parker M.W., Bowtell D.D.
     "Siah ubiquitin ligase is structurally related to TRAF and modulates
     TNF-alpha signaling."
     Nat. Struct. Biol. 9:68-75(2002).
     PubMed=11742346; DOI=10.1038/nsb743

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