ERGIC-53 and ERGL type 1 transmembrane proteins, N-terminal lectin domain
ERGIC-53 and ERGL, N-terminal carbohydrate recognition domain. ERGIC-53 and ERGL are eukaryotic mannose-binding type 1 transmembrane proteins of the early secretory pathway that transport newly synthesized glycoproteins from the endoplasmic reticulum (ER) to the ER-Golgi intermediate compartment (ERGIC). ERGIC-53 and ERGL have an N-terminal lectin-like carbohydrate recognition domain (represented by this alignment model) as well as a C-terminal transmembrane domain. ERGIC-53 functions as a 'cargo receptor' to facilitate the export of glycoproteins with different characteristics from the ER, while the ERGIC-53-like protein (ERGL) which may act as a regulator of ERGIC-53. In mammals, ERGIC-53 forms a complex with MCFD2 (multi-coagulation factor deficiency 2) which then recruits blood coagulation factors V and VIII. Mutations in either MCFD2 or ERGIC-53 cause a mild form of inherited hemophilia known as combined deficiency of factors V and VIII (F5F8D). In addition to the lectin and transmembrane domains, ERGIC-53 and ERGL have a short N-terminal cytoplasmic region of about 12 amino acids. ERGIC-53 forms disulphide-linked homodimers and homohexamers. ERGIC-53 and ERGL are sequence-similar to the lectins of leguminous plants. L-type lectins have a dome-shaped beta-barrel carbohydrate recognition domain with a curved seven-stranded beta-sheet referred to as the "front face" and a flat six-stranded beta-sheet referred to as the "back face". This domain homodimerizes so that adjacent back sheets form a contiguous 12-stranded sheet and homotetramers occur by a back-to-back association of these homodimers. Though L-type lectins exhibit both sequence and structural similarity to one another, their carbohydrate binding specificities differ widely.
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