SPSB2: Human splA/ryanodine receptor domain and SOCS box containing 2 (SPSB2)
PDB Code: 3EMW
Human SPRY-domain-containing SOCS box protein 2 (SPSB2 or SSB-2) 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 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. Several human diseases arise from mutations in genes coding for SPRY domain containing proteins, for example mutations in the MEFV gene are associated with familial Mediterranean fever.
Knockout mice of SPSB2 have a reduced rate of platelet production, resulting in very mild thrombocytopenia and show low levels of blood urea nitrogen (BUN) pointing to a unique role of SPSB2 in regulating platelet production and BUN levels. The SPRY domain mediates interaction with the MET receptor tyrosine kinase and prostate apoptosis response protein 4. Here we determined the crystal structure of the SPSB2 SPRY domain in complex with a peptide derived from the RNA helicase VASA. Binding is dependent on four SPSB2 loops which hydrogen bond to an Asp-Ile-Asn-Asn-Asn motif in VASA.
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