LMAN1 (Protein ERGIC-53; also Gp58, MR60, lectin mannose-binding 1) is a 510-residue type I single-pass transmembrane L-type (leguminous-type) lectin of the early secretory pathway. Its luminal carbohydrate-recognition domain binds high-mannose N-glycans in a calcium-dependent manner, making it a mannose-specific lectin (identical to the myelomonocytic lectin MR60); it is not a glycosidase and has no catalytic activity. ERGIC-53 cycles between the endoplasmic reticulum, the ER-Golgi intermediate compartment (ERGIC) and the cis-Golgi, exiting the ER in COPII-coated vesicles and returning by COPI-dependent retrograde traffic via a C-terminal dilysine/diphenylalanine motif. Together with its soluble co-receptor MCFD2 it forms an oligomeric cargo receptor (the LMAN1-MCFD2 complex; full-length cryo-EM resolves a disulfide-linked homotetramer, revising older homohexamer models) that selectively captures glycoprotein cargo in the ER and transports it to the Golgi; its best characterized cargoes are coagulation factors V and VIII, and additional secretory glycoproteins (e.g. alpha-1-antitrypsin, cathepsins) have been proposed. As an abundant, rapidly cycling cargo receptor ERGIC-53 also contributes, together with Surf4 and p24 family members, to maintaining the architecture of the ERGIC and Golgi by controlling COPI recruitment. Loss-of-function mutations in LMAN1 cause autosomal recessive combined deficiency of factors V and VIII (F5F8D1).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005793 endoplasmic reticulum-Golgi intermediate compartment | IBA GO_REF:0000033 | ACCEPT | Summary: ERGIC is the defining site of action for ERGIC-53; the phylogenetic annotation matches the UniProt subcellular location and the protein's name. Reason: Correct core compartment; ERGIC-53 is the canonical ERGIC marker and acts there as a cycling cargo receptor. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum-Golgi intermediate |
| GO:0000139 Golgi membrane | IBA GO_REF:0000033 | ACCEPT | Summary: ERGIC-53 cycles through the Golgi apparatus membrane as part of its ER-ERGIC-Golgi itinerary; consistent with the UniProt Golgi apparatus membrane location. Reason: Correct compartment within the cycling itinerary, though the ERGIC is the primary steady-state location. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt Golgi apparatus membrane |
| GO:0005789 endoplasmic reticulum membrane | IBA GO_REF:0000033 | ACCEPT | Summary: ERGIC-53 captures cargo in the ER and exits via COPII vesicles; ER membrane is a bona fide part of its cycling itinerary. Reason: Correct compartment; matches the UniProt ER membrane location and the cargo-capture step in the ER. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt Endoplasmic reticulum |
| GO:0005537 D-mannose binding | IBA GO_REF:0000033 | ACCEPT | Summary: ERGIC-53/MR60 is a mannose-specific lectin; its CRD binds high-mannose N-glycans. The F5F8D1 variant W67S abolishes D-mannose binding, directly supporting this molecular function. Reason: Core molecular function; ERGIC-53 is identical to the mannose-specific lectin MR60 and recombinant WT (but not W67S) binds D-mannose. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt Mannose-specific lectin PMID:19787799 could bind to |
| GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport | IBA GO_REF:0000033 | ACCEPT | Summary: The defining biological process of ERGIC-53 is ER-to-Golgi transport of glycoprotein cargo as part of the LMAN1-MCFD2 cargo receptor. Reason: Core biological process; well supported across the family and by direct human studies of FV/FVIII transport. Supporting Evidence: PMID:12717434 forms a specific cargo receptor for the ER-to-Golgi transport of selected |
| GO:0030134 COPII-coated ER to Golgi transport vesicle | IBA GO_REF:0000033 | ACCEPT | Summary: ERGIC-53 is packaged into COPII vesicles at ER exit sites for anterograde transport; a C-terminal motif recruits COPII coat components. Reason: Correct; ERGIC-53 is a classic COPII cargo/cargo receptor exiting the ER in COPII vesicles. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt proper recognition of COPII coat components |
| GO:0000139 Golgi membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic transfer of the Golgi apparatus membrane location from the UniProt subcellular location vocabulary; consistent with the cycling itinerary. Reason: Correct compartment; redundant with the IBA Golgi membrane annotation. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt Golgi apparatus membrane |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic transfer of the ER membrane location from the UniProt subcellular location vocabulary. Reason: Correct compartment; redundant with the IBA ER membrane annotation. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt Endoplasmic reticulum |
| GO:0012505 endomembrane system | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Generic ARBA electronic assignment to the endomembrane system; far less informative than the specific ERGIC/ER/Golgi compartments already annotated. Reason: Overly general parent term; the specific ERGIC membrane, ER membrane and Golgi membrane annotations capture the localization precisely. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt Endoplasmic reticulum-Golgi intermediate |
| GO:0016020 membrane | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Bare "membrane" from InterPro; ERGIC-53 is a single-pass type I membrane protein, but the term is uninformative relative to the curated ER/ERGIC/Golgi membrane annotations. Reason: Uninformative generic term; the specific compartment-membrane annotations are preferable. ER/ERGIC membrane would be the appropriate refinement. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt Single-pass type I membrane protein |
| GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic transfer of the ERGIC membrane location; this is the precise core compartment for ERGIC-53. Reason: Correct and specific core compartment; redundant with the IDA ERGIC membrane annotation. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum-Golgi intermediate |
| GO:0005515 protein binding | IPI PMID:16304051 Combined deficiency of factor V and factor VIII is due to mu... | KEEP AS NON CORE | Summary: IntAct capture of the LMAN1-MCFD2 interaction (UniProtKB:Q8NI22). MCFD2 is the soluble co-receptor; the bare protein binding term is uninformative even though the interaction is biologically central. Reason: Records a real, important interaction (MCFD2) but bare GO:0005515 is uninformative; the cargo receptor complex (GO:0062137) and D-mannose binding capture the core function. Supporting Evidence: PMID:16304051 cargo receptor ferrying FV and FVIII from the |
| GO:0005515 protein binding | IPI PMID:17805346 Sequential steps and checkpoints in the early exocytic compa... | KEEP AS NON CORE | Summary: IntAct capture of the ERGIC-53/ERp44 interaction (UniProtKB:Q9BS26); ERp44 is a thiol-mediated retention protein localized to the ERGIC partly through binding ERGIC-53. Reason: Real interaction (ERp44) recorded, but bare protein binding is uninformative and peripheral to the lectin cargo-receptor core function. Supporting Evidence: PMID:17805346 interacts with ERGIC-53 |
| GO:0005515 protein binding | IPI PMID:17971482 Deletion of 3 residues from the C-terminus of MCFD2 affects ... | KEEP AS NON CORE | Summary: IntAct capture of the LMAN1-MCFD2 interaction (UniProtKB:Q8NI22); deletion of the MCFD2 C-terminus impairs binding to ERGIC-53 and causes F5F8D. Reason: Real MCFD2 interaction, but bare protein binding is uninformative; the cargo receptor complex term captures it more meaningfully. Supporting Evidence: PMID:17971482 ERGIC-53/MCFD2 protein complex functions as transport receptor of |
| GO:0005515 protein binding | IPI PMID:18287528 The cargo receptors Surf4, endoplasmic reticulum-Golgi inter... | KEEP AS NON CORE | Summary: IntAct capture of the ERGIC-53/Surf4 interaction (UniProtKB:O15260); Surf4 and ERGIC-53 are interacting cargo receptors. Reason: Real interaction (Surf4) recorded, but bare protein binding is uninformative; the functional role (Golgi/ERGIC architecture) is captured by GO:0007030. Supporting Evidence: PMID:18287528 Surf4 was found to interact with |
| GO:0005515 protein binding | IPI PMID:19787799 A novel missense mutation causing abnormal LMAN1 in a Japane... | KEEP AS NON CORE | Summary: IntAct capture of the LMAN1-MCFD2 interaction (UniProtKB:Q8NI22); the F5F8D1 W67S variant abolishes MCFD2 interaction (and D-mannose binding). Reason: Real MCFD2 interaction, but bare protein binding is uninformative; this paper better supports the D-mannose binding annotation. Supporting Evidence: PMID:19787799 did not co-immunoprecipitate the mutant LMAN1 with MCFD2 |
| GO:0005515 protein binding | IPI PMID:20138881 Crystal structure of the LMAN1-CRD/MCFD2 transport receptor ... | KEEP AS NON CORE | Summary: IntAct capture from the LMAN1-CRD/MCFD2 crystal structure (UniProtKB:Q8NI22); defines the LMAN1-MCFD2 binding interface. Reason: Real, structurally defined MCFD2 interaction, but bare protein binding is uninformative; the cargo receptor complex term captures it. Supporting Evidence: PMID:20138881 LMAN1 is a glycoprotein receptor, mediating transfer from the ER to the ER-Golgi |
| GO:0005515 protein binding | IPI PMID:20142513 Structural basis for the cooperative interplay between the t... | KEEP AS NON CORE | Summary: IntAct capture from the ERGIC-53-CRD/MCFD2 structural study (UniProtKB:Q8NI22); MCFD2 binds a surface remote from the sugar-binding site. Reason: Real MCFD2 interaction with structural detail, but bare protein binding is uninformative as a standalone function. Supporting Evidence: PMID:20142513 ERGIC-53-CRD binds MCFD2 through its molecular surface remote from the |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: High-throughput BioPlex interactome capture of the LMAN1-MCFD2 interaction (UniProtKB:Q8NI22). Reason: High-throughput interaction (MCFD2); bare protein binding is uninformative and not elevated to core. Supporting Evidence: PMID:33961781 cell-specific remodeling of the human |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | KEEP AS NON CORE | Summary: OpenCell endogenous-tagging interactome capture of the LMAN1-MCFD2 interaction (UniProtKB:Q8NI22). Reason: High-throughput interaction (MCFD2); bare protein binding is uninformative and not elevated to core. Supporting Evidence: PMID:35271311 cartography of human cellular organization |
| GO:0005793 endoplasmic reticulum-Golgi intermediate compartment | IEA GO_REF:0000120 | ACCEPT | Summary: Combined-method electronic assignment to the ERGIC, the core compartment for ERGIC-53. Reason: Correct core compartment; redundant with IDA/IBA ERGIC annotations. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt Endoplasmic reticulum-Golgi intermediate |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog-based electronic assignment to the Golgi apparatus; consistent with the cycling itinerary through the Golgi. Reason: Correct compartment within the cycling itinerary; ERGIC remains the primary steady-state location. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt Golgi apparatus membrane |
| GO:0030017 sarcomere | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ortholog-based electronic assignment to the sarcomere; there is no biological support for ERGIC-53 acting at the sarcomere and it conflicts with its early-secretory-pathway localization. Reason: Implausible compartment for an ER/ERGIC/Golgi cargo receptor; likely spurious electronic transfer. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt Single-pass type I membrane protein |
| GO:0030134 COPII-coated ER to Golgi transport vesicle | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog-based electronic assignment to the COPII vesicle; ERGIC-53 is a COPII cargo receptor. Reason: Correct; redundant with the IBA COPII vesicle annotation. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt proper recognition of COPII coat components |
| GO:0005783 endoplasmic reticulum | IDA GO_REF:0000052 | ACCEPT | Summary: Direct immunofluorescence (HPA) evidence for ER localization, consistent with ERGIC-53 capturing cargo in the ER. Reason: Correct compartment within the cycling itinerary; supported by direct imaging. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt Endoplasmic reticulum |
| GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport | NAS PMID:36490287 Separate roles of LMAN1 and MCFD2 in ER-to-Golgi trafficking... | ACCEPT | Summary: ComplexPortal NAS annotation; LMAN1 and MCFD2 form a complex that transports FV and FVIII from the ER to the Golgi, with MCFD2 carrying the cargo-binding role and LMAN1 acting as a shuttling carrier. Reason: Core biological process; directly asserted by the cited functional study of the LMAN1/MCFD2-dependent FV/FVIII secretion pathway. Supporting Evidence: PMID:36490287 cargo binding and transport are carried out by MCFD2 and that LMAN1 PMID:36490287 transports FV and FVIII from the endoplasmic reticulum (ER) to the Golgi |
| GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane | IDA PMID:12717434 Bleeding due to disruption of a cargo-specific ER-to-Golgi t... | ACCEPT | Summary: Direct evidence (ComplexPortal) for ERGIC membrane localization; LMAN1 is a mannose-binding type 1 transmembrane protein localized to the ERGIC. Reason: Correct, specific core compartment with direct support. Supporting Evidence: PMID:12717434 localized to the endoplasmic |
| GO:0062137 cargo receptor complex | IPI PMID:12717434 Bleeding due to disruption of a cargo-specific ER-to-Golgi t... | ACCEPT | Summary: The LMAN1-MCFD2 complex (ComplexPortal CPX-8001) is a cargo receptor for ER-to-Golgi transport of FV/FVIII; MCFD2 is localized to the ERGIC through a Ca2+-dependent interaction with LMAN1. Reason: Core cellular component; LMAN1 is a defining subunit of the LMAN1-MCFD2 cargo receptor complex. Supporting Evidence: PMID:12717434 forms a specific cargo receptor for the ER-to-Golgi transport of selected |
| GO:0005515 protein binding | IPI PMID:34779586 BET1 variants establish impaired vesicular transport as a ca... | KEEP AS NON CORE | Summary: IntAct capture of the ERGIC-53/BET1 interaction (UniProtKB:O15155); ERGIC-53 was identified as a novel interaction partner of the ER-to-Golgi SNARE BET1. Reason: Real interaction (BET1) recorded, but bare protein binding is uninformative; peripheral to the lectin cargo-receptor core function. Supporting Evidence: PMID:34779586 ERGICβ53 as a novel interaction partner of BET1 |
| GO:0046872 metal ion binding | EXP PMID:24498414 Structural basis for disparate sugar-binding specificities i... | KEEP AS NON CORE | Summary: The CRD coordinates Ca2+, which is required for the lectin's high-mannose carbohydrate recognition; structural studies resolve Ca2+ in the sugar-binding pocket. Reason: Ca2+ is a structural cofactor of the carbohydrate-recognition domain, supporting (not equivalent to) the core D-mannose binding function. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt ligand="Ca(2+)" PMID:24498414 carbohydrate recognition domains (CRDs) |
| GO:0005515 protein binding | IPI PMID:31142615 The E3 ubiquitin ligase MARCH2 regulates ERGIC3-dependent tr... | KEEP AS NON CORE | Summary: IntAct capture of the ERGIC-53/SERPINA1 (alpha-1-antitrypsin) interaction (UniProtKB:P01009); alpha-1-antitrypsin is a candidate secretory glycoprotein cargo. Reason: Real interaction (SERPINA1) recorded; bare protein binding is uninformative, though it hints at a broader cargo repertoire. Supporting Evidence: PMID:31142615 Ξ±1-antitrypsin and haptoglobin specifically bind to ERGIC3 |
| GO:0005783 endoplasmic reticulum | IDA PMID:19401338 Role of syntaxin 18 in the organization of endoplasmic retic... | ACCEPT | Summary: Direct evidence for ER localization from a study of ER subdomain organization (syntaxin 18), consistent with ERGIC-53's cycling itinerary. Reason: Correct compartment within the cycling itinerary; supported by direct imaging. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt Endoplasmic reticulum |
| GO:0031012 extracellular matrix | HDA PMID:28675934 Characterization of the Extracellular Matrix of Normal and D... | MARK AS OVER ANNOTATED | Summary: High-throughput ECM proteomics detection; ERGIC-53 is an intracellular early-secretory-pathway membrane protein and not a genuine ECM component. Reason: Proteomic over-detection inconsistent with the established ER/ERGIC/Golgi localization; not a true ECM protein. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt Endoplasmic reticulum-Golgi intermediate |
| GO:0031012 extracellular matrix | HDA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | MARK AS OVER ANNOTATED | Summary: High-throughput ECM proteomics detection in colon cancer tissue; not a genuine ECM localization for this intracellular cargo receptor. Reason: Proteomic over-detection inconsistent with the established intracellular localization. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt Endoplasmic reticulum-Golgi intermediate |
| GO:1903748 negative regulation of protein localization to mitochondrion | HMP PMID:24270810 High-content genome-wide RNAi screens identify regulators of... | KEEP AS NON CORE | Summary: LMAN1 was a hit in a genome-wide RNAi screen for regulators of parkin translocation to damaged mitochondria; a high-throughput phenotype far removed from its characterized cargo-receptor function. Reason: High-throughput screen hit only; peripheral and not mechanistically connected to the core ER-to-Golgi lectin function. Retained but not elevated. Supporting Evidence: PMID:24270810 regulators that have an impact on parkin |
| GO:0005793 endoplasmic reticulum-Golgi intermediate compartment | IDA PMID:21525244 C4orf41 and TTC-15 are mammalian TRAPP components with a rol... | ACCEPT | Summary: Direct evidence for ERGIC localization from a study of mammalian TRAPP components in early ER-to-Golgi trafficking. Reason: Correct core compartment with direct support. Supporting Evidence: PMID:21525244 ER-to-Golgi trafficking at a very early stage |
| GO:0005515 protein binding | IPI PMID:22337587 Protein interaction profiling of the p97 adaptor UBXD1 point... | KEEP AS NON CORE | Summary: IPI capture of ERGIC-53 interactions with RAB3GAP1/RAB3GAP2 (Q15042/Q9H2M9) and UBXN6 (Q9BZV1) via its C-terminal cytoplasmic tail; the p97-UBXD1 complex modulates ERGIC-53 trafficking. Reason: Real interactions (RAB3GAP1/2, UBXN6) recorded, but bare protein binding is uninformative; these modulate ERGIC-53 trafficking and are peripheral to the lectin core function. Supporting Evidence: PMID:22337587 Rab3GAP1/2 complex involved in the fusion of vesicles |
| GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane | TAS Reactome:R-HSA-5694446 | ACCEPT | Summary: Reactome curation of ERGIC membrane localization in the COPII transport pathway. Reason: Correct core compartment; redundant with experimental ERGIC annotations. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum-Golgi intermediate |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-203973 | ACCEPT | Summary: Reactome curation of ER membrane localization during vesicle budding. Reason: Correct compartment; redundant with curated ER membrane annotations. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt Endoplasmic reticulum |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-204008 | ACCEPT | Summary: Reactome curation of ER membrane localization during COPII coat recruitment. Reason: Correct compartment; redundant. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt Endoplasmic reticulum |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-5694417 | ACCEPT | Summary: Reactome curation of ER membrane localization during COPII inner-coat assembly. Reason: Correct compartment; redundant. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt Endoplasmic reticulum |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-5694428 | ACCEPT | Summary: Reactome curation (LMAN family proteins bind glycosylated cargo) placing ERGIC-53 at the ER membrane. Reason: Correct compartment; this reaction directly reflects the lectin cargo-binding role. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt Endoplasmic reticulum |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-5694431 | ACCEPT | Summary: Reactome curation (hexameric LMAN1:MCFD2 bind glycosylated Factor V and VIII precursors) placing ERGIC-53 at the ER membrane. Reason: Correct compartment; this reaction directly reflects the FV/FVIII cargo-receptor role. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt Endoplasmic reticulum |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-5694522 | ACCEPT | Summary: Reactome curation of ER membrane localization during inner coat assembly and cargo binding. Reason: Correct compartment; redundant. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt Endoplasmic reticulum |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-5694527 | ACCEPT | Summary: Reactome curation of ER membrane localization during COPII budding (loss of SAR1B GTPase). Reason: Correct compartment; redundant. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt Endoplasmic reticulum |
| GO:0005515 protein binding | IPI PMID:24806965 TMEM115 is an integral membrane protein of the Golgi complex... | KEEP AS NON CORE | Summary: IPI capture of the ERGIC-53/TMEM115 interaction (UniProtKB:Q12893); TMEM115 is a Golgi protein involved in retrograde transport. Reason: Real interaction (TMEM115) recorded, but bare protein binding is uninformative and peripheral to the lectin core function. Supporting Evidence: PMID:24806965 interacts with the COG complex |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: High-throughput NK-cell membrane proteome detection; bare "membrane" is uninformative relative to the curated ER/ERGIC/Golgi membrane annotations. Reason: Uninformative generic term from a proteomics survey; superseded by specific compartment-membrane annotations. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt Single-pass type I membrane protein |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | MARK AS OVER ANNOTATED | Summary: High-throughput exosome proteomics detection (parotid gland exosomes); not a site of action for this early-secretory-pathway cargo receptor. Reason: Proteomic over-detection; not biologically meaningful for ERGIC-53 function. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt Endoplasmic reticulum-Golgi intermediate |
| GO:0012507 ER to Golgi transport vesicle membrane | TAS Reactome:R-HSA-203973 | ACCEPT | Summary: Reactome curation placing ERGIC-53 in the ER-to-Golgi transport vesicle membrane during vesicle budding. Reason: Correct compartment for a COPII cargo receptor; redundant with COPII vesicle annotations. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt proper recognition of COPII coat components |
| GO:0012507 ER to Golgi transport vesicle membrane | TAS Reactome:R-HSA-5694409 | ACCEPT | Summary: Reactome curation placing ERGIC-53 in the ER-to-Golgi transport vesicle membrane (nucleotide exchange on RAB1). Reason: Correct compartment; redundant. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt proper recognition of COPII coat components |
| GO:0012507 ER to Golgi transport vesicle membrane | TAS Reactome:R-HSA-5694418 | ACCEPT | Summary: Reactome curation placing ERGIC-53 in the ER-to-Golgi transport vesicle membrane (RAB1 tethering). Reason: Correct compartment; redundant. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt proper recognition of COPII coat components |
| GO:0012507 ER to Golgi transport vesicle membrane | TAS Reactome:R-HSA-5694439 | ACCEPT | Summary: Reactome curation placing ERGIC-53 in the ER-to-Golgi transport vesicle membrane (COPII binds TRAPPCII and RAB1). Reason: Correct compartment; redundant. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt proper recognition of COPII coat components |
| GO:0012507 ER to Golgi transport vesicle membrane | TAS Reactome:R-HSA-5694441 | ACCEPT | Summary: Reactome curation placing ERGIC-53 in the ER-to-Golgi transport vesicle membrane (CSNK1D phosphorylates SEC23). Reason: Correct compartment; redundant. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt proper recognition of COPII coat components |
| GO:0012507 ER to Golgi transport vesicle membrane | TAS Reactome:R-HSA-5694446 | ACCEPT | Summary: Reactome curation placing ERGIC-53 in the ER-to-Golgi transport vesicle membrane (v-SNARE binding on tethered vesicle). Reason: Correct compartment; redundant. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt proper recognition of COPII coat components |
| GO:0012507 ER to Golgi transport vesicle membrane | TAS Reactome:R-HSA-947991 | ACCEPT | Summary: Reactome curation (Transport of glycoproteins with Man8/Man9 N-glycans to the Golgi) placing ERGIC-53 in the transport vesicle membrane; directly reflects its high-mannose lectin cargo function. Reason: Correct compartment; this reaction directly reflects the high-mannose-glycoprotein transport role of ERGIC-53. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt proper recognition of COPII coat components |
| GO:0007030 Golgi organization | IMP PMID:18287528 The cargo receptors Surf4, endoplasmic reticulum-Golgi inter... | KEEP AS NON CORE | Summary: Silencing Surf4 together with ERGIC-53 reduces ERGIC clusters and fragments the Golgi by impairing COPI recruitment; cargo receptors including ERGIC-53 are required to maintain ERGIC/Golgi architecture. Reason: Experimentally supported (IMP), but this is an emergent structural role of an abundant cycling cargo receptor rather than its primary, defining cargo-transport function. Retained as a valid non-core process. Supporting Evidence: PMID:18287528 cargo receptors are essential for maintaining the architecture of ERGIC and Golgi by controlling COP I recruitment |
| GO:0034498 early endosome to Golgi transport | IMP NOT PMID:18287528 The cargo receptors Surf4, endoplasmic reticulum-Golgi inter... | ACCEPT | Summary: ERGIC-53 functions in the ER-ERGIC-Golgi early secretory pathway and COPI-dependent retrograde recycling; the study shows its role is in maintaining ERGIC/Golgi architecture via COPI, with no role in early endosome to Golgi transport. The NOT qualifier correctly records that ERGIC-53 does NOT act in this endosomal pathway. Reason: The negation is appropriate because ERGIC-53 operates in ER/ERGIC/Golgi cargo transport and COPI retrograde traffic rather than in endosome-to-Golgi transport. Supporting Evidence: PMID:18287528 cargo receptors are essential for maintaining the architecture of ERGIC and Golgi by controlling COP I recruitment |
| GO:0005793 endoplasmic reticulum-Golgi intermediate compartment | IDA PMID:15308636 Proteomics of endoplasmic reticulum-Golgi intermediate compa... | ACCEPT | Summary: ERGIC proteomics enriched ERGIC-53 ~110-fold in purified ERGIC membranes, providing direct biochemical evidence for ERGIC localization. Reason: Correct core compartment with direct biochemical support. Supporting Evidence: PMID:15308636 enriched 110-fold over the homogenate for ERGIC-53 |
| GO:0005515 protein binding | IPI PMID:9774442 Molecular cloning of the oncofetal isoform of the human panc... | KEEP AS NON CORE | Summary: IPI capture of an interaction with the oncofetal bile salt-dependent lipase (UniProtKB:O75612) from a cloning study; a candidate glycoprotein cargo/partner. Reason: Real interaction recorded, but bare protein binding is uninformative and the partner is peripheral to the established function. Supporting Evidence: PMID:9774442 oncofetal isoform of the human pancreatic bile |
| GO:0005537 D-mannose binding | TAS PMID:7876089 ERGIC-53, a membrane protein of the endoplasmic reticulum-Go... | ACCEPT | Summary: ERGIC-53 is identical to MR60, an intracellular mannose-specific lectin; the TAS annotation records the foundational identification of its D-mannose binding activity. (PMID:7876089 not cached; supported via the UniProt record documenting ERGIC-53 = MR60.) Reason: Core molecular function; ERGIC-53/MR60 is a mannose-specific lectin, corroborated by the W67S loss-of-D-mannose-binding variant. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt is identical to MR60, an intracellular mannose- |
| GO:0000139 Golgi membrane | TAS PMID:7876089 ERGIC-53, a membrane protein of the endoplasmic reticulum-Go... | ACCEPT | Summary: TAS annotation of Golgi membrane localization for ERGIC-53; consistent with its cycling itinerary through the Golgi. (PMID:7876089 not cached; supported via the UniProt record.) Reason: Correct compartment within the cycling itinerary; redundant with curated Golgi membrane annotations. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt Golgi apparatus membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS PMID:7876089 ERGIC-53, a membrane protein of the endoplasmic reticulum-Go... | ACCEPT | Summary: TAS annotation of ER membrane localization for ERGIC-53. (PMID:7876089 not cached; supported via the UniProt record documenting the ER membrane location.) Reason: Correct compartment; redundant with curated ER membrane annotations. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt Endoplasmic reticulum |
| GO:0006457 protein folding | TAS PMID:9546392 Mutations in the ER-Golgi intermediate compartment protein E... | KEEP AS NON CORE | Summary: The original F5F8D paper proposed ERGIC-53 may function as a "molecular chaperone" for ER-to-Golgi transport of a subset of secreted proteins. ERGIC-53 is a transport receptor, not a folding enzyme; the protein folding term reflects the historical chaperone framing of its transport role. Reason: ERGIC-53 is a cargo receptor/lectin, not a folding catalyst; protein folding is at best an indirect, downstream consequence of efficient cargo transport. Retained as non-core. Supporting Evidence: PMID:9546392 ERGIC-53 may function as a molecular |
| GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport | TAS PMID:9546392 Mutations in the ER-Golgi intermediate compartment protein E... | ACCEPT | Summary: The foundational F5F8D paper implicates ERGIC-53 in ER-to-Golgi transport of a specific subset of secreted proteins including FV and FVIII. Reason: Core biological process with strong genetic/biochemical support. Supporting Evidence: PMID:9546392 transport from ER to Golgi of a specific subset of secreted proteins |
| GO:0007596 blood coagulation | TAS PMID:9546392 Mutations in the ER-Golgi intermediate compartment protein E... | KEEP AS NON CORE | Summary: LMAN1 mutations cause combined deficiency of coagulation factors V and VIII; blood coagulation is a physiological consequence of its role in secreting FV/FVIII, not a direct molecular activity of ERGIC-53. Reason: Downstream physiological process resulting from cargo transport of FV/FVIII; ERGIC-53 itself has no coagulation activity. Retained as non-core. Supporting Evidence: PMID:9546392 combined deficiency of coagulation factors V and VIII |
| GO:0016020 membrane | TAS PMID:7876089 ERGIC-53, a membrane protein of the endoplasmic reticulum-Go... | MARK AS OVER ANNOTATED | Summary: Legacy TAS "membrane" annotation; bare term is uninformative relative to the curated ER/ERGIC/Golgi membrane annotations. (PMID:7876089 not cached; supported via the UniProt record.) Reason: Uninformative generic term; superseded by specific compartment-membrane annotations. ER/ERGIC membrane is the appropriate refinement. Supporting Evidence: file:human/LMAN1/LMAN1-uniprot.txt Single-pass type I membrane protein |
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Download this section (compressed HTML)Q: Given that LMAN1 N-glycan binding is dispensable for FV/FVIII transport (MCFD2 carries cargo binding), what is the full repertoire of cargoes that depend on LMAN1's own lectin activity versus those routed primarily through MCFD2?
Q: Beyond FV/FVIII, which endogenous high-mannose glycoproteins (e.g. cathepsins, alpha-1-antitrypsin) are bona fide LMAN1 cargoes in vivo?
Experiment: Compare FV/FVIII and broader secretome trafficking in LMAN1-null cells reconstituted with wild-type LMAN1 versus the carbohydrate-binding-dead and W67S variants to separate the lectin-dependent from MCFD2-shuttling contributions.
Experiment: Perform proximity labeling (BioID/APEX) from endogenously tagged LMAN1 across cell types to define the cargo and machinery interactome and test the proposed cargoes (SERPINA1, cathepsins) as genuine clients.
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