LIG_SPRY_1

The SPRY domain was first identified in a Dictyostelium discoideum non-receptor tyrosine kinase spore lysis A (splA) and in Mammalia calcium-release channels ryanodine receptors (Ponting,1997). The SPRY domain was subsequently detected in a total of 10 distinct protein families, including the human sequences DDX1, hnRNPs, HERC1 and RanBPM (Ponting,1997). There are currently 2053 eukaryotic proteins listed in the SMART Database (release 6.0) that contain a SPRY domain, including more than 80 proteins encoded in the human genome. Many of these proteins have a conserved N-terminal extension, the PRY domain (50–60 residues) which together with the SPRY domain creates the B30.2 domain (approximately 170 amino acids). It has been shown that the B30.2 domain has evolved recently from the more ancient SPRY domain by incorporating PRY sequences (Rhodes,2005). The B30.2 domain is only found in Vertebrata and it may have been selected as a component of immune defense.
The SPRY domain is present in many protein families covering a wide range of functions in different biological processes: the RyR receptors, which regulate intracellular calcium release (Tae,2009); the TRIM5alpha, a host restriction factor acting in the innate immune defense against retroviral infection, including human immunodeficiency virus type-1 (HIV-1) (Zhang,2010); and the SSB family, which is involved in the negative regulation of cytokine signaling (Masters,2005). The SSB-2 is a component of the E3 ubiquitin-protein ligase complex that mediates the proteasomal degradation of target proteins (Kuang,2010). The ~140 amino acid residue domain adopts a novel fold consisting of a β-sandwich structure formed by two four-stranded anti-parallel β-sheets with a unique topology. In combination with the B30.2 domain, these two domains are predicted to adopt a structure resembling the immunoglobulin fold, consisting predominantly of layered anti-parallel β sheets (Seto,1999).