LMAN2

LMAN2 Full Name

lectin, mannose-binding 2

LMAN2 Introduction

LMAN2 encodes an evolutionarily conserved type I transmembrane lectin, also called vesicular integral membrane protein 36 (VIP36), that operates in the endoplasmic reticulum-Golgi intermediate compartment. The LMAN2 gene maps to chromosome 5q35.3 and is one of three human L-type lectins that share a legume-lectin-like fold, underscoring an ancient machinery for sugar-dependent protein sorting. Like its relative ERGIC-53, LMAN2 functions as a cargo receptor, binding glycoproteins that carry high-mannose N-glycans through a luminal carbohydrate-recognition domain. Structural and biochemical studies show that the receptor recognizes terminal alpha1,2-linked mannose residues and favors glycans in which the D1 mannosyl branch remains intact, with binding that is calcium-independent and optimal near acidic pH. This sugar specificity positions LMAN2 to discriminate between properly folded, early-processing glycoproteins and those that have been visited by downstream trimming enzymes, making it a sensor within the secretory quality-control network rather than a passive transporter.

Figure 1. N-glycans with high affinities for VIP36 on the biosynthetic pathway. (Source: Kamiya Y, et al. 2005)

LMAN2 cycles between the endoplasmic reticulum, the ER-Golgi intermediate compartment, and the cis-Golgi, and it can also reach the plasma membrane, where it shows an apical enrichment in polarized epithelial cells. Its itinerary is most consistent with a recycling carrier that captures selected glycan-tagged clients in the cis-Golgi and returns them to the ER, where the higher pH weakens binding and releases the cargo for further folding or degradation decisions. LMAN2 also associates with the molecular chaperone BiP, supporting a quality-control role in the maturation of secretory proteins, and it has been implicated in the trafficking of specific clients such as receptor guanylyl cyclase C. Alterations in LMAN2 localization have also been linked to defective protein glycosylation, connecting cargo-receptor fidelity to human disease. By coupling glycan structure to retrograde transport, LMAN2 helps maintain the fidelity of the secretory pathway and illustrates how lectin cargo receptors use sugar recognition to sort the proteome on its way out of the cell.

Alternate Names for LMAN2

LMAN2; lectin, mannose-binding 2; C5orf8, chromosome 5 open reading frame 8; vesicular integral-membrane protein VIP36; GP36B; VIP36; glycoprotein GP36b; vesicular integral protein of 36 kDa; vesicular integral-membrane protein 36; C5orf8;

• 1. Kamiya Y, et al. Sugar-binding properties of VIP36, an intracellular animal lectin operating as a cargo receptor. J Biol Chem. 2005 Nov 4;280(44):37178-82.
  2. Kamiya Y, et al. Molecular basis of sugar recognition by the human L-type lectins ERGIC-53, VIPL, and VIP36. J Biol Chem. 2008 Jan 25;283(4):1857-61.