LMAN2 (VIP36) — Gene Review Notes

UniProt: Q12907 (LMAN2_HUMAN). Gene symbol: LMAN2 (HGNC:16986), synonym C5orf8.
Protein name: Vesicular integral-membrane protein VIP36 (also Glycoprotein GP36b, Lectin
mannose-binding 2). 356 aa precursor; signal peptide 1-44; mature chain 45-356; single-pass
type I membrane protein (lumenal 45-322, TM 323-345, cytoplasmic 346-356).

What VIP36 is

VIP36/LMAN2 is a type I transmembrane leguminous-type (L-type) lectin of the early
secretory pathway. Its lumenal L-type lectin-like domain (52-276) binds carbohydrate in a
Ca2+-dependent manner [file:human/LMAN2/LMAN2-uniprot.txt "L-type lectin-like"; UniProt COFACTOR
"Binds 2 calcium ions per subunit"]. UniProt FUNCTION: "Plays a role as an intracellular lectin
in the early secretory pathway. Interacts with N-acetyl-D-galactosamine and high-mannose type
glycans and may also bind to O-linked glycans. Involved in the transport and sorting of
glycoproteins carrying high mannose-type glycans" [file:human/LMAN2/LMAN2-uniprot.txt].

It is a member of the same L-type lectin family as LMAN1/ERGIC-53 (P49257; PANTHER
PTN000259611). It is NOT a glycosidase / mannosidase — it has no catalytic activity; it is a
carbohydrate-binding cargo/sorting receptor. The CDD/InterPro signatures are lectin signatures
(cd06901 lectin_VIP36_VIPL; IPR035664 VIP36_lectin; PF03388 Lectin_leg-like).

Localization (core CC = ERGIC/Golgi/ER membrane of the early secretory pathway)

UniProt SUBCELLULAR LOCATION (from PubMed:10444376, Fullekrug et al. "VIP36 localisation to the
early secretory pathway"): "Endoplasmic reticulum-Golgi intermediate compartment membrane ...
Golgi apparatus membrane ... Endoplasmic reticulum membrane" [file:human/LMAN2/LMAN2-uniprot.txt].
It cycles early in the secretory pathway between ER/ERGIC and Golgi.

Carbohydrate / D-mannose binding (core MF)

Transport / sorting / quality control (core BP)

VIP36 functions in post-ER quality control and ER<->Golgi cycling of high-mannose glycoproteins:
- Silencing VIP36 accelerated cargo transport, arguing against a pure anterograde role and
consistent with a quality-control / retrograde recycling role: PMID:20477988.
- Retrograde Golgi-to-ER recycling (basis for GO:0006890 IMP): PMID:20477988.
- VIP36 is "postulated as a cargo receptor for Golgi-to-endoplasmic reticulum transport"
PMID:22016386.
- Reactome: COPII-mediated vesicle transport (R-HSA-204005); Cargo concentration in the ER
(R-HSA-5694530); consistent with COPII vesicle (GO:0030134) and ER-to-Golgi transport
(GO:0006888) IBA annotations.

Interactions

Secondary / cell-surface role (ectodomain shedding, macrophages)

A minor pool of Endo-H-resistant (late-Golgi / cell-surface) VIP36 reaches the plasma membrane
and is shed; the shed/cell-surface VIP36 regulates phagocytosis in macrophages:
- PMID:22016386
- PMID:22016386
- PMID:22016386
This is the basis for the extracellular region / plasma membrane / cell surface IDA and the
positive regulation of phagocytosis IMP/IEA. These are genuine but secondary to the core
ER-Golgi lectin/sorting function, which dominates the protein's biology. Notably the lectin
activity is dispensable for phagocytosis enhancement PMID:22016386, underscoring that this is a separate moonlighting
role rather than the core function.

Proteomics-only localizations (non-core / over-annotation)

Cofactor / metal

Lectin domain binds 2 Ca2+ per subunit as a structural cofactor required for carbohydrate
binding [file:human/LMAN2/LMAN2-uniprot.txt COFACTOR "Binds 2 calcium ions per subunit"]; multiple
Ca2+-binding residues (162, 164, 166, 193). UniProt keyword "Metal-binding" / GO:0046872 metal ion
binding (IEA) is a structural attribute, not the core function. (No metal/calcium binding row is
present in the GOA TSV stub, so no annotation is reviewed for it.)

Summary of review decisions

Falcon deep-research findings (incorporated 2026-06)