MIA3
Description
The MIA3 (MIA SH3 domain ER export factor 3) is a protein-coding gene located on chromosome 1.
MIA3, also known as TANGO1, is a protein that plays a vital role in the transport and organization of proteins within cells. It is found in many tissues and cell types. MIA3 localizes to the endoplasmic reticulum (ER) exit site, where it binds bulky cargo molecules, such as collagens, and creates specialized carriers for their export. This function suggests its involvement in the assembly of the extracellular matrix (ECM) and bone formation. MIA3 has been implicated in both tumor suppression and progression. The gene encoding MIA3 is linked to an increased risk of coronary artery disease. A related protein, TALI, is expressed in the liver and intestine and is essential for the export of very low-density lipoproteins (VLDL) and chylomicrons. TANGO1 and TALI form ring-like structures around COPII coats, crucial for the export of bulky cargoes. The discovery of TANGO1 revealed that cargo export from the ER is not always through vesicles, but can involve transient tunnels between the ER exit site and the next compartment of the secretory pathway. Mutations in TANGO1 can lead to a syndrome disease, and complete loss of TANGO1 results in defects in bone mineralization. These findings emphasize the critical role of TANGO1 in building and regulating the ER exit site, controlling the quantity and quality of exported cargo, which is essential for life.
MIA3 plays a crucial role in the transport of large cargo molecules, such as collagen VII (COL7A1) and lipoproteins, that cannot fit into standard COPII-coated vesicles. It facilitates their export from the endoplasmic reticulum (ER) by loading them into specialized transport carriers. MIA3 achieves this by binding to COPII coat subunits Sec23/24 at ER exit sites, guiding SH3-bound COL7A1 into growing carriers. While MIA3 does not influence global protein secretion, it is specifically involved in the secretion of COL7A1 and lipoproteins. Moreover, it contributes to the proper assembly of COPII coat components at ER exit sites (ERES) and the localization of SEC16A and membrane-bound ER-resident complexes consisting of MIA2 and PREB/SEC12 to ERES.
MIA3 is also known as ARNT, D320, ODCD2, TANGO, TANGO1, UNQ6077.
