id: Q9HAT1 gene_symbol: LMAN1L product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: 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. alternative_products: - name: '1' id: Q9HAT1-1 - name: '2' id: Q9HAT1-2 sequence_note: Not described - name: '3' id: Q9HAT1-3 sequence_note: VSP_013143 existing_annotations: - term: id: GO:0005793 label: endoplasmic reticulum-Golgi intermediate compartment evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in review: 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. action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/LMAN1L/LMAN1L-uniprot.txt supporting_text: Endoplasmic reticulum-Golgi intermediate - term: id: GO:0000139 label: Golgi membrane evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in review: 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. action: KEEP_AS_NON_CORE reason: Homology-plausible for an ERGIC-53-like cycling cargo receptor but without direct evidence for this paralog; retained as non-core. supported_by: - reference_id: file:human/LMAN1L/LMAN1L-uniprot.txt supporting_text: Single-pass type I membrane protein - term: id: GO:0005789 label: endoplasmic reticulum membrane evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in review: 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. action: KEEP_AS_NON_CORE reason: Homology-plausible given the predicted membrane topology; no direct experimental support for LMAN1L, so kept as non-core. supported_by: - reference_id: file:human/LMAN1L/LMAN1L-uniprot.txt supporting_text: Single-pass type I membrane protein - term: id: GO:0005537 label: D-mannose binding evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables review: 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. action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/LMAN1L/LMAN1L-uniprot.txt supporting_text: L-type lectin-like - term: id: GO:0006888 label: endoplasmic reticulum to Golgi vesicle-mediated transport evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: 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. action: KEEP_AS_NON_CORE reason: Homology-plausible role for an ERGIC-53-like cargo receptor; no functional transport assay exists for this paralog, so retained as non-core. supported_by: - reference_id: file:human/LMAN1L/LMAN1L-uniprot.txt supporting_text: Endoplasmic reticulum-Golgi intermediate - term: id: GO:0030134 label: COPII-coated ER to Golgi transport vesicle evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in review: 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. action: KEEP_AS_NON_CORE reason: Homology-plausible for an ERGIC-53-like cargo receptor but lacking direct evidence for this paralog; retained as non-core. supported_by: - reference_id: file:human/LMAN1L/LMAN1L-uniprot.txt supporting_text: Single-pass type I membrane protein - term: id: GO:0005793 label: endoplasmic reticulum-Golgi intermediate compartment evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: Electronic (ARBA) ERGIC localization, redundant with the IBA ERGIC annotation and consistent with the similarity-based UniProt subcellular location. action: KEEP_AS_NON_CORE reason: Correct compartment by homology to ERGIC-53 but unverified for this paralog; redundant with the IBA ERGIC annotation, kept as non-core. supported_by: - reference_id: file:human/LMAN1L/LMAN1L-uniprot.txt supporting_text: Endoplasmic reticulum-Golgi intermediate - term: id: GO:0012505 label: endomembrane system evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: Electronic (ARBA) assignment to the very general "endomembrane system" term. This is an uninformative parent of the more specific ERGIC/ER localizations. action: MARK_AS_OVER_ANNOTATED reason: Generic high-level compartment term superseded by the more specific ERGIC/ER membrane annotations; not informative on its own. supported_by: - reference_id: file:human/LMAN1L/LMAN1L-uniprot.txt supporting_text: Endoplasmic reticulum-Golgi intermediate - term: id: GO:0016020 label: membrane evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: located_in review: 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. action: MARK_AS_OVER_ANNOTATED reason: Uninformative generic parent; the specific ERGIC membrane term captures the localization better. supported_by: - reference_id: file:human/LMAN1L/LMAN1L-uniprot.txt supporting_text: Single-pass type I membrane protein - term: id: GO:0033116 label: endoplasmic reticulum-Golgi intermediate compartment membrane evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: 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. action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/LMAN1L/LMAN1L-uniprot.txt supporting_text: Endoplasmic reticulum-Golgi intermediate - term: id: GO:0031012 label: extracellular matrix evidence_type: HDA original_reference_id: PMID:28675934 qualifier: located_in review: 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. action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: PMID:28675934 supporting_text: LMAN1L, which is, in fact, a transmembrane protein references: - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms findings: [] - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: GO_REF:0000044 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt findings: [] - id: GO_REF:0000117 title: Electronic Gene Ontology annotations created by ARBA machine learning models findings: [] - id: PMID:28675934 title: Characterization of the Extracellular Matrix of Normal and Diseased Tissues Using Proteomics. findings: - statement: LMAN1L was detected solely in the urea-insoluble pellet of a decellularized ECM proteomics preparation from TNBC-adjacent breast tissue, and the authors note it is in fact a transmembrane protein (i.e. a peripheral co-isolate, not a core ECM component). reference_section_type: RESULTS reference_review: relevance: LOW correctness: VERIFIED review_notes: PMC-verified ECM proteomics methods paper; sole source of the extracellular matrix HDA annotation. The text explicitly flags LMAN1L as a transmembrane protein detected only in the insoluble pellet, so this is a peripheral/contaminant detection, not evidence of an extracellular function. - id: file:human/LMAN1L/LMAN1L-uniprot.txt title: UniProt entry Q9HAT1 (LMA1L_HUMAN), Protein ERGIC-53-like (LMAN1L/ERGL) findings: - statement: Single-pass type I membrane glycoprotein with a lumenal L-type lectin-like domain (31-252); member of the ERGIC-53/LMAN1 L-type lectin family (PANTHER "vesicular mannose-binding lectin"). SUBCELLULAR LOCATION (by similarity, ECO:0000250) is the endoplasmic reticulum-Golgi intermediate compartment membrane. reference_section_type: OTHER - statement: Tissue specificity (PubMed:11255007) - highly expressed in normal and neoplastic prostate, also in cardiac atrium, salivary gland, spleen and selective CNS cells. Evidence level is transcript only (PE 2). reference_section_type: OTHER reference_review: relevance: HIGH correctness: VERIFIED review_notes: Primary source for LMAN1L domain architecture, membrane topology, family/lectin assignment, similarity-based ERGIC localization, and tissue specificity. Underscores that functional roles are homology-inferred (PE 2, ECO:0000250) rather than experimentally demonstrated. core_functions: - description: Predicted (by homology to ERGIC-53/LMAN1, not experimentally demonstrated) mannose-binding L-type lectin functioning as a type I membrane cargo receptor in the endoplasmic reticulum-Golgi intermediate compartment, likely participating in COPII-mediated ER-to-Golgi cargo transport. All functional roles are inferred from family membership and domain architecture; direct evidence for this paralog is lacking. molecular_function: id: GO:0005537 label: D-mannose binding locations: - id: GO:0033116 label: endoplasmic reticulum-Golgi intermediate compartment membrane supported_by: - reference_id: file:human/LMAN1L/LMAN1L-uniprot.txt supporting_text: L-type lectin-like - reference_id: file:human/LMAN1L/LMAN1L-uniprot.txt supporting_text: Endoplasmic reticulum-Golgi intermediate directly_involved_in: - id: GO:0006888 label: endoplasmic reticulum to Golgi vesicle-mediated transport proposed_new_terms: [] suggested_questions: - question: Does LMAN1L actually bind high-mannose glycans in a calcium-dependent manner like ERGIC-53, and if so what is its cargo glycoprotein repertoire? - question: 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? suggested_experiments: - description: 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. - description: 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.