SOCS1

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 (By similarity).

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:32499645, PubMed:33087723). Downregulates cytokine signaling by inhibiting the JAK/STAT signaling pathway. Acts by binding to JAK proteins and to IFNGR1 and inhibiting their kinase activity. In vitro, suppresses Tec protein-tyrosine activity (PubMed:9341160). Regulates IFN-gamma (IFNG)-mediated sensory neuron survival (By similarity). 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 (PubMed:11278610, PubMed:11313480).

Involvement in disease

Autoinflammatory syndrome, familial, with or without immunodeficiency

AISIMD

An autosomal dominant, autoinflammatory disorder with incomplete penetrance characterized by autoimmune cytopenia, hemolytic anemia, thrombocytopenia, and lymphadenopathy. Additional variable features may include autoimmune thyroiditis, psoriasis or eczema, nephritis, hepatitis, and symptoms of systemic lupus erythematosus. Immunodeficiency is present in some patients. Disease onset is usually in the first decades of life, although later onset has been reported.

None

The disease is caused by variants affecting the gene represented in this entry.

Pathway

Protein modification; protein ubiquitination.

Sequence similarities

Belongs to the SOCS1 family.

Tissue specificity

Expressed in all tissues with high expression in spleen, small intestine and peripheral blood leukocytes.

Cellular localization

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

Alternative names

• SSI1
• TIP3
• TIP3
• SSI1
• SOCS1
• Suppressor of cytokine signaling 1
• SOCS-1
• JAK-binding protein
• STAT-induced STAT inhibitor 1
• Tec-interacting protein 3
• JAB
• SSI-1
• TIP-3

Database links

• entrezGene:8651
• omim:603597
• swissprot:O15524

Target type

Proteins

Primary research area

Immunology & Infectious Disease

Other research areas

• Immuno-oncology

Molecular weight

23551Da