SPSB1 is encoded by the SPSB1 gene located on chromosome 1p36.22 and belongs to the SOCS (Suppressor of Cytokine Signaling) box protein family . It contains two critical domains:
SPRY domain: Mediates substrate recognition and protein-protein interactions.
SOCS box: Recruits E3 ubiquitin ligase complexes for proteasomal degradation of target proteins .
SPSB1 acts as an adaptor in ubiquitination pathways, fine-tuning signaling cascades such as TGF-β, NF-κB, and c-MET .
The SPSB1 protein comprises 231–273 amino acids, depending on isoform and recombinant production systems . Key structural features include:
Domain | Function | Interacting Partners |
---|---|---|
SPRY domain | Binds substrates (e.g., TβRII, iNOS) | TGF-β receptor II, c-MET |
SOCS box | Recruits Elongin B/C-CUL5 E3 ligase complexes for ubiquitination | CUL5, ELOC |
Recombinant SPSB1 (e.g., His-tagged variants) is produced in E. coli for research applications, with purity >85–90% .
SPSB1 directly binds TGF-β type II receptor (TβRII) via its SPRY domain, promoting its ubiquitination and degradation. This inhibits Smad2/3 phosphorylation and downstream signaling, impacting cell proliferation and differentiation .
In breast cancer, SPSB1 enhances hepatocyte growth factor (HGF)-induced c-MET signaling, promoting tumor cell survival and chemotherapy resistance. Silencing SPSB1 reduces metastasis and relapse risk .
SPSB1 suppresses NF-κB activation by targeting unknown substrates, reducing pro-inflammatory cytokines (e.g., IL-6, IFN-β) during viral infections or cytokine stimulation .
Overexpression of SPSB1 in critically ill patients inhibits TGF-β-mediated myogenesis, contributing to ICU-acquired muscle weakness (ICUAW) .
Recombinant SPSB1 is available for in vitro studies:
Applications: Ubiquitination assays, protein interaction studies, signaling pathway analysis.
SPRY Domain-Containing SOCS Cox Protein 1, also known as SPSB1, is a human recombinant protein that plays a crucial role in various cellular processes. This protein is part of the SOCS (Suppressor of Cytokine Signaling) family, which is involved in the negative regulation of cytokine signaling pathways. The SPRY domain is a conserved protein domain that is involved in protein-protein interactions.
The human recombinant SPRY Domain-Containing SOCS Cox Protein 1 is typically produced in Escherichia coli (E. coli) and is a single, non-glycosylated polypeptide chain. It contains 231 amino acids, specifically from the 24th to the 223rd amino acid of the native protein . The molecular mass of this recombinant protein is approximately 26 kDa .
SPRY Domain-Containing SOCS Cox Protein 1 functions as a substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex . This complex is involved in the ubiquitination and subsequent proteasomal degradation of target proteins. By regulating the degradation of specific proteins, SPSB1 plays a critical role in controlling various cellular processes, including signal transduction, cell cycle progression, and immune responses.
The SOCS family proteins, including SPSB1, are essential for maintaining cellular homeostasis. They act as negative regulators of cytokine signaling, preventing excessive inflammatory responses and ensuring that signaling pathways are tightly controlled. Dysregulation of SOCS proteins can lead to various diseases, including autoimmune disorders, chronic inflammation, and cancer.
Human recombinant SPRY Domain-Containing SOCS Cox Protein 1 is widely used in research to study its role in cytokine signaling and its potential therapeutic applications. It is also used in the development of assays to screen for modulators of SOCS protein activity, which could lead to new treatments for diseases associated with cytokine signaling dysregulation.