TRAPPC2

TRAPPC2 is a human gene encoding for a protein that is a subunit of the TRAPP (Transport Protein Particle) complex. TRAPP complexes are multisubunit protein complexes involved in vesicle trafficking, specifically in the early secretory pathway.

Function:

The TRAPP complex functions as a guanine nucleotide exchange factor (GEF) for Rab1 and possibly other Rab GTPases. Rab GTPases are small GTP-binding proteins that are essential regulators of vesicular transport. By acting as a GEF, TRAPP activates Rab proteins by promoting the exchange of GDP (guanosine diphosphate) for GTP (guanosine triphosphate). This activation is crucial for vesicle docking and fusion at the endoplasmic reticulum (ER) and Golgi apparatus. TRAPPC2 specifically contributes to the structural integrity and function of the TRAPP complex. It is thought to be involved in tethering vesicles to the Golgi.

Structure:

TRAPPC2 is a relatively small protein. The precise structure and interactions within the TRAPP complex are complex and continue to be investigated.

Clinical Significance:

Mutations in the TRAPPC2 gene have been linked to X-linked spondyloepiphyseal dysplasia tarda (SEDT). SEDT is a skeletal dysplasia characterized by short stature, abnormal epiphyses (the ends of long bones), and spinal deformities. The exact mechanism by which mutations in TRAPPC2 lead to SEDT is not fully understood but likely involves disruptions in cartilage development and bone growth due to impaired protein trafficking processes. The X-linked inheritance pattern means that males are more likely to be affected, as they only have one X chromosome. Carrier females may exhibit milder symptoms or be asymptomatic. Genetic testing can be used to diagnose SEDT caused by TRAPPC2 mutations.

Interactions:

TRAPPC2 interacts with other subunits of the TRAPP complex, including TRAPPC1, TRAPPC3, and others. These interactions are crucial for the assembly and stability of the entire complex. Further research is ongoing to fully elucidate the complex interplay of the TRAPP subunits and their respective roles in vesicle trafficking and cellular function.