Translocation associated membrane protein 2 (TRAM2)

Translocation associated membrane protein 2 (TRAM2) is a critical component of the endoplasmic reticulum (ER) translocon complex, a gated channel responsible for the translocation and proper processing of secretory and membrane proteins. TRAM2 is essential for type I collagen biosynthesis, particularly in cells transitioning to active collagen production, such as hepatic stellate cells and fibroblasts. Its C-terminal domain interacts with the ER Ca²⁺ pump SERCA2b, elevating local ER calcium concentration needed for collagen folding and assembly. TRAM2 also functions as a ceramide-binding protein, influencing the topology and translocation of specific proteins. Overexpression of TRAM2 is observed in several cancers, such as glioma and oral squamous cell carcinoma, where it promotes proliferation, invasion, metastasis, and poor clinical prognosis—often through activation of pathways like PI3K/AKT/mTOR and matrix metalloproteinases (MMPs). TRAM2 is thus implicated as a potential therapeutic target in cancer and fibrosis, while abnormal modulation may present risks for ER function, protein folding, and tissue homeostasis.

Other names

Translocating chain-associated membrane protein 2KIAA0057TRAM-like proteinTRAM2