Sushi domain-containing protein 6 (SUSD6)

Sushi domain-containing protein 6 (SUSD6) is a transmembrane protein characterized by the presence of Sushi or complement control protein (CCP) domains. SUSD6 is mainly implicated in the negative regulation of major histocompatibility complex class I (MHC-I) antigen presentation by forming a membrane-associated complex with TMEM127 and recruiting the E3 ubiquitin ligase WWP2, which promotes ubiquitination and lysosomal degradation of MHC-I molecules. This leads to decreased surface expression of MHC-I and allows cancer cells, especially in acute myeloid leukemia and several solid tumors, to evade immune detection by CD8+ T cells. High expression of SUSD6 is associated with poor prognosis in AML. Genetic ablation of SUSD6 increases tumor immunogenicity and suppresses tumor growth in a CD8+ T cell-dependent manner, defining it as a potential novel therapeutic target at the interface of tumor immunology and antigen presentation. SUSD6 has also been linked more broadly to DNA damage responses, cell death, and tumor suppression[1][2][4][6].

Other names

Sushi domain-containing protein 6SUSD6DRAGOKIAA0247Drug-activated gene overexpressed protein

(For future drugs) Inhibition of SUSD6 could enhance MHC-I antigen presentation, promote T cell recognition, and reduce tumor immune evasion by blocking the SUSD6/TMEM127/WWP2 axis that targets MHC-I complexes for lysosomal degradation