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SPRY domain-containing SOCS box protein 3 (SPSB3)

Target: SPSB3
Molecular classification: Substrate recognition component (of E3 ubiquitin ligase complex), SPRY domain-containing protein, SOCS box protein, adaptor protein for ubiquitination machinery

Overview

SPRY domain-containing SOCS box protein 3 (SPSB3) is an adaptor protein in the CRL5 (Cullin-5-RING) E3 ubiquitin ligase complex[3][4]. SPSB3 contains a central SPRY domain and a C-terminal SOCS box; it recognizes specific substrate proteins for ubiquitination and proteasomal degradation, thus regulating their abundance in cells[3][4]. SPSB3 is involved in pathways such as the negative regulation of the cGAS/STING innate immune signaling axis, and it facilitates degradation of proteins like cGAS (cyclic GMP-AMP synthase) and SNAI1[4]. Although no drugs currently target SPSB3, its regulatory role in immune and cancer-related pathways makes it a protein of interest for basic research in protein turnover, immunity, and cell signaling[1][3][4].

Other names: SplA/ryanodine receptor domain and SOCS box containing 3SPSB3C16orf31SSB3SPRY domain-containing SOCS box protein SSB-3

Biological functions

Protein ubiquitination (substrate recognition for ubiquitin ligase complex; mediates K48-linked ubiquitination of targets such as CGAS and SNAI1)Negative regulation of innate immune pathways (notably cGAS/STING signaling)Regulation of epithelial-mesenchymal transition (via targeting and degrading SNAI1)protein-protein interactions in signaling and immune modulation

Disease associations

Cancer (implicated via regulation of SNAI1, a key epithelial-mesenchymal transition factor involved in metastasis; negative regulation of immune pathways relevant to tumor immunity)Other (general immune regulatory roles, e.g., innate and adaptive immune signaling via cGAS/STING)

Safety considerations

None specifically documented, as this is not currently a direct therapeutic target. Modulation of protein ubiquitination and innate immune suppression could be a concern if targeted experimentally.

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