RING finger, HC subclass, found in Drosophila melanogaster protein Seven-in-Absentia (sina) and its homologs
The family includes the Drosophila melanogaster protein Seven-in-Absentia (sina), its mammalian orthologs, SIAH1 and SIAH2, plant SINA-related proteins, and similar proteins. The Drosophila homolog sina plays an important role in the phyllopod-dependent degradation of the transcriptional repressor tramtrack as for the formation of the R7 photoreceptor in the developing eye of Drosophila melanogaster. Both of SIAH1 and SIAH2 are E3 ubiquitin-protein ligases, mediating the ubiquitinylation and subsequent proteasomal degradation of biologically important target proteins that regulate general functions, such as cell cycle control, apoptosis, and DNA repair. They are inducible by the tumor suppressor and transcription factor p53. SIAH2 can also be regulated by sex hormones and cytokine signaling. Moreover, they share high sequence similarity, but possess contrary roles in cancer, with Siah1 more often acting as a tumor suppressor while Siah2 functions as a proto-oncogene. Plant SINAT1-5 are putative E3 ubiquitin ligase involved in the regulation of stress responses. All family members possess two characteristic domains, an N-terminal C3HC4-type RING-HC finger and a C-terminal tumor necrosis factor (TNF) receptor associated factor (TRAF)-like substrate-binding domain (SBD).