Figures & data
Figure 1. SOCS3 protein domain structure. SOCS3 can be divided into three domains: the N-terminal domain (N-term, residues 1–29), containing the kinase inhibitory region (K, KIR), the Src homology 2 (SH2) domain (residues 30–185, containing an N-terminal extension helix [ESS] and an interpolated PEST sequence), and the SOCS box (residues 186–225, containing a BC box and a Cul5 box).Citation9,Citation28
![Figure 1. SOCS3 protein domain structure. SOCS3 can be divided into three domains: the N-terminal domain (N-term, residues 1–29), containing the kinase inhibitory region (K, KIR), the Src homology 2 (SH2) domain (residues 30–185, containing an N-terminal extension helix [ESS] and an interpolated PEST sequence), and the SOCS box (residues 186–225, containing a BC box and a Cul5 box).Citation9,Citation28](/cms/asset/b669f7db-59f5-42b3-8e6a-3449418791eb/kjks_a_10925045_f0001.gif)
Figure 2. Diagram of the SOCS3 E3 ubiquitin ligase. Scaffold protein cullin-5 binds to Rbx2 and recruits the ubiquitin-conjugating E2 enzyme. By binding to the SOCS3/elonginBC complex, cullin-5 also recruits the SOCS3-associated substrate. The SOCS3 E3 ligase promotes transfer of ubiquitin (Ub) from the E2 subunit to a substrate lysine and subsequent proteasomal degradation of the substrate. Known substrates of the SOCS3 E3 ubiquitin ligase include IRS1/230, CD33,Citation31 Siglec7,Citation32 IDO,Citation33 FAK1,Citation34,Citation35 G-CSFR,Citation36,Citation37 and JAK1.Citation38
![Figure 2. Diagram of the SOCS3 E3 ubiquitin ligase. Scaffold protein cullin-5 binds to Rbx2 and recruits the ubiquitin-conjugating E2 enzyme. By binding to the SOCS3/elonginBC complex, cullin-5 also recruits the SOCS3-associated substrate. The SOCS3 E3 ligase promotes transfer of ubiquitin (Ub) from the E2 subunit to a substrate lysine and subsequent proteasomal degradation of the substrate. Known substrates of the SOCS3 E3 ubiquitin ligase include IRS1/230, CD33,Citation31 Siglec7,Citation32 IDO,Citation33 FAK1,Citation34,Citation35 G-CSFR,Citation36,Citation37 and JAK1.Citation38](/cms/asset/834d5da2-9e6f-4b7c-9d3b-16d24cc4a328/kjks_a_10925045_f0002.gif)
Figure 3. The physiological functions of SOCS3 are mediated via direct binding to gp130, G-CSFR, leptinR, and IL-12Rβ. By binding to these receptors, SOCS3 inhibits signaling by their cytokine ligands, thereby regulating a variety of biological processes.
![Figure 3. The physiological functions of SOCS3 are mediated via direct binding to gp130, G-CSFR, leptinR, and IL-12Rβ. By binding to these receptors, SOCS3 inhibits signaling by their cytokine ligands, thereby regulating a variety of biological processes.](/cms/asset/a88ed888-cbbc-427f-b3a6-b0f93b2d7d71/kjks_a_10925045_f0003.gif)