SPSB4: Human SPRY domain-containing SOCS box protein SSB-4
PDB Code: 2V24
Human SPRY-domain-containing SOCS box protein 4 (SPSB4 or SSB-4) belongs to a family of four proteins containing an N-terminal SPRY (or B30.2) domain and a C-terminal SOCS box (SPSB1-4). The SOCS box functions as an adaptor domain that binds ElonginBC and potentially mediates further assembly with cullin ubiquitin ligases. The SPRY domain was first identified in the dual-specificity kinase splA and ryanodine receptors and is proposed to function as a protein-protein recognition domain.
The SPSB4 SPRY domain has been shown to bind prostate apoptosis response protein-4 (PARW or PAR-4) and the MET receptor tyrosine kinase. We determined the crystal structure of this domain at 2.2 Å resolution. The structure is highly conserved with the SPRY domain of the Drosophila homologue Gustavus which has been solved separately in the presence of ElonginBC and a high affinity peptide containing an Asp-Ile-Asn-Asn-Asn-Asn recognition motif from the RNA helicase VASA.
SPSB4 is expressed in the ovary in granulosa cells at all stages of follicular development and is therefore proposed to regulate granulosa cell physiology. Low level expression is also detected in the kidney as well as in eye and brain T-cells.

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