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  Domain Name: Sina
Seven in absentia (Sina) protein family, C-terminal substrate binding domain; composed of the Drosophila Sina protein, the mammalian Sina homolog (Siah), the plant protein SINAT5, and similar proteins. Sina, Siah and SINAT5 are RING-containing proteins that function as E3 ubiquitin ligases, acting either as single proteins or as a part of multiprotein complexes. Sina is expressed in many cells in the developing eye but is essential specifically for R7 photoreceptor cell development. Sina cooperates with Phyllopod (Phyl), Ebi and the E2 ubiquitin-conjugating enzyme Ubcd1 to catalyze the ubiquitination and subsequent degradation of Tramtrack (Ttk88); Ttk88 is a transcriptional repressor that blocks photoreceptor differentiation. Similarly, the mammalian homologue Siah1 cooperates with SIP (Siah-interacting protein), Ebi and the adaptor protein Skp1, to target beta-catenin for ubiquitination and degradation via a p53-dependent mechanism. SINAT5 targets NAC1 for ubiquitin-mediated degradation resulting in the downregulation of auxin, a hormone that controls many aspects of plant development. Other targets of Sina family proteins include c-Myb, synaptophysin, group 1 glutamate receptors, promyelocytic leukemia protein, alpha-synuclein, synphilin-1 and alpha-ketoglutarate dehydrogenase, among others. Sina proteins also bind proteins that are not targets for ubiquitination such as Phyl, adenomatous polyposis coli, VAV, BAG-1 and Dab-1. Siah binds to a consensus motif, PXAXVXP, which is present in Siah-binding proteins. Siah is a dimeric protein consisting of an N-terminal RING domain, two zinc finger motifs and a C-terminal substrate-binding domain (SBD); this SBD contains an eight-stranded antiparallel beta-sandwich fold similar to the MATH (meprin and TRAF-C homology) domain.
No pairwise interactions are available for this conserved domain.

Total Mutations Found: 0
Total Disease Mutations Found: 0
This domain occurred 3 times on human genes (6 proteins).

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 The histograms below the weblogo indicate mutations found on the domain. Red is for disease (OMIM) and blue is for SNPs.

 Functional Features are displayed as orange boxes under the histograms. You can choose which features are displayed in the box below.

Range on the Protein:  

   Protein ID            Protein Position

Domain Position:  

Feature Name:Total Found:
substrate binding site
dimer interface

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Please Cite: Peterson, T.A., Adadey, A., Santana-Cruz ,I., Sun, Y., Winder A, Kann, M.G., (2010) DMDM: Domain Mapping of Disease Mutations. Bioinformatics 26 (19), 2458-2459.

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