Socs1

Developmental stage

In the developing brain, expressed at low levels from 10 dpc stages to young adulthood (P25) with peak levels from 14 dpc to P8. In the cortex, expression first observed at 14 dpc uniformly in all cells. Also expressed in the innermost layers of the developing retina. Levels of expression remain unchanged from P8 until adulthood. In the peripheral nervous system, high levels found in virtually all neurons of the dorsal root ganglion.

Domain

The ESS and SH2 domains are required for JAK phosphotyrosine binding. Further interaction with the KIR domain is necessary for signal and kinase inhibition.

The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes. The Elongin BC complex binding domain is also known as BC-box with the consensus [APST]-L-x(3)-C-x(3)-[AILV] and is part of the SOCS box.

Function

Essential negative regulator of type I and type II interferon (IFN) signaling, as well as that of other cytokines, including IL2, IL4, IL6 and leukemia inhibitory factor (LIF) (PubMed:10064597, PubMed:15169905, PubMed:15522878, PubMed:9202125). Downregulates cytokine signaling by inhibiting the JAK/STAT signaling pathway. Acts by binding to JAK proteins and to IFNGR1 and inhibiting their kinase activity (PubMed:10064597, PubMed:15522878, PubMed:9202125). In vitro, suppresses Tec protein-tyrosine activity (By similarity). Regulates IFN-gamma (IFNG)-mediated sensory neuron survival. Probable substrate recognition component of an ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity).

Pathway

Protein modification; protein ubiquitination.

Sequence Similarities

Belongs to the SOCS1 family.

Tissue Specificity

High expression in thymus. Lower expression in lung and spleen (PubMed:9202125). Expressed in both Th1 and Th2 cells.

Cellular localization

• Nucleus
• Cytoplasmic vesicle
• Detected in perinuclear cytoplasmic vesicles upon interaction with FGFR3.

Alternative names

Cish1, Ssi1, Socs1, Suppressor of cytokine signaling 1, SOCS-1, JAK-binding protein, STAT-induced STAT inhibitor 1, JAB, SSI-1

Database links

swissprot:O35716 entrezGene:12703

Other research areas

• Immuno-oncology