LMAN1L (ERGL; "Protein ERGIC-53-like", also "Lectin mannose-binding 1-like") is a testis- and prostate-enriched human paralog of LMAN1/ERGIC-53 and a member of the L-type lectin (legume lectin-like) family. It is a 526-aa single-pass type I membrane glycoprotein with a lumenal L-type lectin-like domain, a single transmembrane segment, and a short cytoplasmic tail, an architecture typical of ERGIC/ER-resident cargo receptors. By homology to ERGIC-53 it is predicted to be a calcium-dependent mannose-binding lectin that acts as a cargo receptor in the endoplasmic reticulum-Golgi intermediate compartment and in COPII-mediated ER-to-Golgi transport. Direct functional evidence is lacking, however; the protein is characterized only at the transcript level and essentially all of its functional roles are inferred by homology (phylogenetic and electronic annotation) rather than demonstrated for this paralog.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005793 endoplasmic reticulum-Golgi intermediate compartment | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic (IBA) assignment of ERGIC localization, propagated from the ERGIC-53/LMAN1 L-type lectin family. Consistent with the UniProt subcellular location, which is itself an inference by similarity (ECO:0000250); no direct experimental localization exists for this paralog. Reason: Plausible by homology to ERGIC-53 and consistent with the (similarity-based) UniProt ERGIC membrane location, but unverified experimentally for LMAN1L; kept as non-core given thin evidence. Supporting Evidence: file:human/LMAN1L/LMAN1L-uniprot.txt Endoplasmic reticulum-Golgi intermediate |
| GO:0000139 Golgi membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic (IBA) Golgi membrane localization propagated from the family. ERGIC-53-like cargo receptors cycle between ER, ERGIC and cis-Golgi, so this is plausible, but it is unverified for LMAN1L. Reason: Homology-plausible for an ERGIC-53-like cycling cargo receptor but without direct evidence for this paralog; retained as non-core. Supporting Evidence: file:human/LMAN1L/LMAN1L-uniprot.txt Single-pass type I membrane protein |
| GO:0005789 endoplasmic reticulum membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic (IBA) ER membrane localization propagated from the L-type lectin family. Consistent with the predicted single-pass type I membrane topology, but unverified for this paralog. Reason: Homology-plausible given the predicted membrane topology; no direct experimental support for LMAN1L, so kept as non-core. Supporting Evidence: file:human/LMAN1L/LMAN1L-uniprot.txt Single-pass type I membrane protein |
| GO:0005537 D-mannose binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic (IBA) assignment of D-mannose binding, propagated from the L-type lectin / vesicular mannose-binding lectin family. LMAN1L carries an L-type lectin-like domain consistent with this, but no direct carbohydrate-binding assay has been performed for this protein. Reason: The L-type lectin-like domain (and PANTHER "vesicular mannose-binding lectin" family placement) makes mannose binding the most defensible predicted molecular function, but it is purely homology/IBA-based with no experimental support; kept as non-core rather than core. It is a lectin, not a glycosidase, so no catalytic activity is assigned. Supporting Evidence: file:human/LMAN1L/LMAN1L-uniprot.txt L-type lectin-like |
| GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic (IBA) assignment of ER-to-Golgi transport, propagated from the ERGIC-53/LMAN1 cargo-receptor family. Plausible for an ERGIC-53-like protein but unverified for LMAN1L. Reason: Homology-plausible role for an ERGIC-53-like cargo receptor; no functional transport assay exists for this paralog, so retained as non-core. Supporting Evidence: file:human/LMAN1L/LMAN1L-uniprot.txt Endoplasmic reticulum-Golgi intermediate |
| GO:0030134 COPII-coated ER to Golgi transport vesicle | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic (IBA) localization to COPII transport vesicles, propagated from the cargo-receptor family. ERGIC-53 family members are packaged into COPII vesicles; plausible by homology but unverified for LMAN1L. Reason: Homology-plausible for an ERGIC-53-like cargo receptor but lacking direct evidence for this paralog; retained as non-core. Supporting Evidence: file:human/LMAN1L/LMAN1L-uniprot.txt Single-pass type I membrane protein |
| GO:0005793 endoplasmic reticulum-Golgi intermediate compartment | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Electronic (ARBA) ERGIC localization, redundant with the IBA ERGIC annotation and consistent with the similarity-based UniProt subcellular location. Reason: Correct compartment by homology to ERGIC-53 but unverified for this paralog; redundant with the IBA ERGIC annotation, kept as non-core. Supporting Evidence: file:human/LMAN1L/LMAN1L-uniprot.txt Endoplasmic reticulum-Golgi intermediate |
| GO:0012505 endomembrane system | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Electronic (ARBA) assignment to the very general "endomembrane system" term. This is an uninformative parent of the more specific ERGIC/ER localizations. Reason: Generic high-level compartment term superseded by the more specific ERGIC/ER membrane annotations; not informative on its own. Supporting Evidence: file:human/LMAN1L/LMAN1L-uniprot.txt Endoplasmic reticulum-Golgi intermediate |
| GO:0016020 membrane | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro-based electronic assignment of the generic "membrane" term. The protein is indeed a single-pass membrane protein, but the bare "membrane" term is uninformative relative to the specific ERGIC membrane localization. Reason: Uninformative generic parent; the specific ERGIC membrane term captures the localization better. Supporting Evidence: file:human/LMAN1L/LMAN1L-uniprot.txt Single-pass type I membrane protein |
| GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic transfer of the UniProt subcellular location ("Endoplasmic reticulum-Golgi intermediate compartment membrane", ECO:0000250) to the matching GO term. This is the most specific and best-supported localization, although the UniProt assignment is itself by similarity to ERGIC-53. Reason: Most specific localization, directly matching the UniProt (similarity-based) subcellular location; defensible by homology but unverified experimentally for this paralog, so kept as non-core. Supporting Evidence: file:human/LMAN1L/LMAN1L-uniprot.txt Endoplasmic reticulum-Golgi intermediate |
| GO:0031012 extracellular matrix | HDA PMID:28675934 Characterization of the Extracellular Matrix of Normal and D... | KEEP AS NON CORE | Summary: High-throughput MS detection of LMAN1L in the urea-insoluble pellet of a decellularized ECM proteomics preparation from TNBC-adjacent breast tissue. The authors explicitly note LMAN1L is a transmembrane protein, indicating it is a peripheral co-isolate of the ECM-enrichment protocol rather than a bona fide secreted ECM component. Reason: Genuine experimental detection but peripheral; LMAN1L is a transmembrane protein incidentally co-purifying in an ECM proteomics dataset, not a core extracellular matrix function. Supporting Evidence: PMID:28675934 LMAN1L, which is, in fact, a transmembrane protein |
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Download this section (compressed HTML)Q: Does LMAN1L actually bind high-mannose glycans in a calcium-dependent manner like ERGIC-53, and if so what is its cargo glycoprotein repertoire?
Q: Given its prostate/testis-enriched expression, does LMAN1L serve a tissue-specific cargo-receptor role distinct from the ubiquitous LMAN1, or is it a largely redundant/vestigial paralog?
Experiment: Express tagged LMAN1L in cultured cells and determine its subcellular localization by immunofluorescence colocalization with ERGIC-53/ERGIC, ER and cis-Golgi markers to test the predicted ERGIC residence.
Experiment: Perform glycan-array or carbohydrate-affinity (e.g. mannose-Sepharose, calcium-dependent) binding assays with purified recombinant LMAN1L lumenal domain to test the predicted D-mannose lectin activity directly.
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