Fig. 2.

Function of TANGO1 in procollagen packaging and transport at ERES. Newly synthesized proteins exit the ER via coat protein complex II (COPII) vesicles, but procollagens form prefibrils that are too large to fit into typical COPII vesicles.^{( 8} , ²² , ^{23 )} cTAGE5 first binds the ER‐membrane protein Sec12 and concentrates it to the ERES. Procollagen is subsequently guided to ERES when TANGO1 binds HSP47 through its ER SH3‐like luminal domain. TANGO1 and cTAGE5 bind to the COPII inner coat components Sec23 and Sec24 and recruit the NRZ tethering complex (NBAS/RINT1/ZW10), which in turn recruits ERGIC membranes to the ERES. TANGO1/cTAGE5 finally assembles the fusion machinery SLY1 and syntaxin18 that drives incorporation of ERGIC membranes into ERES. The transmembrane helices of TANGO1 prevent the miscibility of ERGIC and ERES membranes while allowing the transfer of collagen from the lumen of the ER to the ERGIC membranes via a tunnel.^{( 5} , ⁸ , ^{22 )} Proteins are shown by symbols as defined in the figure legend, all different domains of TANGO1 are shown and the SH3‐like collagen interacting site is highlighted with a dotted line.