MAN1B1 (ER alpha-1,2-mannosidase I, ERManI, ERMan1) is a calcium-dependent, type II single-pass endoplasmic reticulum membrane glycosidase of glycoside hydrolase family 47 (GH47, EC 3.2.1.113) that trims terminal alpha-1,2-linked mannose residues from N-linked oligosaccharides. At low enzyme concentration it removes a single mannose from Man9GlcNAc2 to generate Man8GlcNAc2 isomer B, the first committed mannose-trimming step of N-glycan maturation; at the high local concentrations found in the ER-derived quality control compartment (ERQC) it excises additional alpha-1,2-mannoses to yield Man5-6GlcNAc2. This trimming removes misfolded glycoproteins from the calnexin/reglucosylation folding cycle and generates the demannosylated signal that commits them to ER-associated degradation (ERAD), where the trimmed glycan is recognized by downstream lectins (e.g. OS-9/XTP3-B) and delivered to the HRD1 ubiquitin-ligase machinery. ERManI thus functions as a key "mannose timer" in glycoprotein quality control. It is widely expressed, resides in the ER membrane and concentrates in mobile ER-like quality control vesicles that converge on the pericentriolar ERQC. Biallelic loss-of-function variants cause an autosomal-recessive congenital disorder of glycosylation with intellectual disability (Rafiq syndrome / MAN1B1-CDG).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0016020 membrane | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Generic membrane localization inferred phylogenetically. MAN1B1 is a single-pass type II ER membrane protein, but the more specific endoplasmic reticulum membrane term captures the location informatively. Reason: Bare "membrane" is uninformative relative to the specific ER membrane annotation; MAN1B1 is anchored in the ER membrane, not membranes generally. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: MAN1B1 is an ER-resident enzyme; phylogenetic assignment of ER localization is consistent with experimental evidence. Reason: Correct site of action; MAN1B1 acts in the endoplasmic reticulum on nascent and misfolded glycoproteins. Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0004571 mannosyl-oligosaccharide 1,2-alpha-mannosidase activity | IBA GO_REF:0000033 | ACCEPT | Summary: The defining molecular function of MAN1B1; phylogenetic assignment of GH47 alpha-1,2-mannosidase activity is well supported. Reason: Core molecular function; corroborated by direct enzymatic assays, crystal structures, EC 3.2.1.113, and CAZy GH47 membership. Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase |
| GO:0036503 ERAD pathway | IBA GO_REF:0000033 | ACCEPT | Summary: MAN1B1 generates the trimmed-mannose ERAD signal that commits misfolded glycoproteins to degradation; phylogenetic assignment is well supported. Reason: Core biological process; mannose trimming by ERManI is required for ERAD of misfolded glycoproteins. Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation |
| GO:0004571 mannosyl-oligosaccharide 1,2-alpha-mannosidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic assignment of the core GH47 alpha-1,2-mannosidase activity, consistent with experimental evidence. Reason: Correct core molecular function; redundant with IDA/EXP evidence. Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt EC=3.2.1.113 |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: GH47 mannosidases require a Ca2+ ion in the active site for catalysis; MAN1B1 binds calcium as a structural/catalytic cofactor. This is a real attribute but subsidiary to the mannosidase activity, not an independent calcium-signaling function. Reason: Accurate structural cofactor requirement of the GH47 fold but not a standalone core function; the catalytic mannosidase activity is the informative function. Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt Name=Ca(2+) PMID:10409699 The mannose cleavage reaction required divalent cations as indicated by inhibition with EDTA or EGTA and reversal of the inhibition by the addition of Ca(2+) |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic transfer of ER membrane localization from the UniProt subcellular location; MAN1B1 is a single-pass type II ER membrane protein. Reason: Correct compartment; redundant with experimental IDA/EXP ER membrane annotations. Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt Single-pass type II membrane protein |
| GO:0005975 carbohydrate metabolic process | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Generic carbohydrate metabolic process from InterPro; far less informative than the specific N-glycan/mannose trimming and ERAD processes MAN1B1 participates in. Reason: Over-general; the specific ER mannose trimming (GO:1904380) and ER N-glycan trimming (GO:0140277) terms better capture the biology. Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase |
| GO:0009100 glycoprotein metabolic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Generic glycoprotein metabolic process from ARBA; correct in essence but far less informative than the specific N-glycan trimming and ERAD annotations. Reason: Over-general parent process; the specific glycan-trimming/ERAD terms are preferred. Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation |
| GO:0016020 membrane | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Generic membrane localization from InterPro, superseded by the specific ER membrane annotation. Reason: Uninformative parent; MAN1B1 is specifically an ER membrane protein. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0036503 ERAD pathway | IEA GO_REF:0000117 | ACCEPT | Summary: Electronic (ARBA) assignment of the ERAD pathway, consistent with experimental evidence that ERManI mannose trimming is required for ERAD. Reason: Correct core biological process; redundant with IMP/IDA evidence. Supporting Evidence: PMID:18003979 required for trimming to Man 5β6 GlcNAc 2 and for ERAD in cells in vivo |
| GO:0004571 mannosyl-oligosaccharide 1,2-alpha-mannosidase activity | TAS Reactome:R-HSA-4793949 | ACCEPT | Summary: Reactome curation of MAN1B1 mannosidase activity (defective-MAN1B1 reaction context). Reason: Correct core molecular function; redundant with experimental evidence. Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt EC=3.2.1.113 |
| GO:0004571 mannosyl-oligosaccharide 1,2-alpha-mannosidase activity | TAS Reactome:R-HSA-901024 | ACCEPT | Summary: Reactome curation of MAN1B1 hydrolysis of a 1,2-linked mannose (a branch). Reason: Correct core molecular function; redundant with experimental evidence. Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt EC=3.2.1.113 |
| GO:0004571 mannosyl-oligosaccharide 1,2-alpha-mannosidase activity | TAS Reactome:R-HSA-901036 | ACCEPT | Summary: Reactome curation of MAN1B1 hydrolysis of a second 1,2-linked mannose (a branch). Reason: Correct core molecular function; redundant with experimental evidence. Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt EC=3.2.1.113 |
| GO:0004571 mannosyl-oligosaccharide 1,2-alpha-mannosidase activity | TAS Reactome:R-HSA-901039 | ACCEPT | Summary: Reactome curation of MAN1B1 hydrolysis of a 1,2-linked mannose (c branch). Reason: Correct core molecular function; redundant with experimental evidence. Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt EC=3.2.1.113 |
| GO:0004571 mannosyl-oligosaccharide 1,2-alpha-mannosidase activity | TAS Reactome:R-HSA-901074 | ACCEPT | Summary: Reactome curation of MAN1B1/EDEM2 hydrolysis of a 1,2-linked mannose (b branch). Reason: Correct core molecular function; redundant with experimental evidence. Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt EC=3.2.1.113 |
| GO:0004571 mannosyl-oligosaccharide 1,2-alpha-mannosidase activity | TAS Reactome:R-HSA-9036008 | ACCEPT | Summary: Reactome curation of MAN1B1 mannosidase activity (defective-MAN1B1 reaction context). Reason: Correct core molecular function; redundant with experimental evidence. Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt EC=3.2.1.113 |
| GO:0004571 mannosyl-oligosaccharide 1,2-alpha-mannosidase activity | TAS Reactome:R-HSA-9036011 | ACCEPT | Summary: Reactome curation of MAN1B1 mannosidase activity (defective-MAN1B1 reaction context). Reason: Correct core molecular function; redundant with experimental evidence. Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt EC=3.2.1.113 |
| GO:0004571 mannosyl-oligosaccharide 1,2-alpha-mannosidase activity | TAS Reactome:R-HSA-9036012 | ACCEPT | Summary: Reactome curation of MAN1B1 mannosidase activity (defective-MAN1B1 reaction context). Reason: Correct core molecular function; redundant with experimental evidence. Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt EC=3.2.1.113 |
| GO:0004571 mannosyl-oligosaccharide 1,2-alpha-mannosidase activity | TAS Reactome:R-HSA-9696807 | ACCEPT | Summary: Reactome curation of MAN1B1 mannosidase activity in the context of N-glycan mannose trimming of viral (SARS-CoV-2) spike. Reason: Correct core molecular function acting on a viral glycoprotein substrate; redundant with experimental evidence. Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt EC=3.2.1.113 |
| GO:0140277 endoplasmic reticulum N-glycan trimming | IMP PMID:18003979 Endoplasmic reticulum (ER) mannosidase I is compartmentalize... | ACCEPT | Summary: Knockdown/inhibition of ERManI blocks N-glycan trimming in the ER, directly demonstrating its role in ER N-glycan trimming. Reason: Core biological process with direct experimental (IMP) support. Supporting Evidence: PMID:18003979 required for trimming to Man 5β6 GlcNAc 2 and for ERAD in cells in vivo |
| GO:0036503 ERAD pathway | IDA PMID:10521544 Cloning and expression of a specific human alpha 1,2-mannosi... | ACCEPT | Summary: MAN1B1 generates the trimmed Man8B glycan that initiates the ERAD-targeting signal during N-glycan maturation. Reason: Core biological process; ERManI mannose trimming commits misfolded glycoproteins to ERAD. Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation |
| GO:1904380 endoplasmic reticulum mannose trimming | IDA PMID:10521544 Cloning and expression of a specific human alpha 1,2-mannosi... | ACCEPT | Summary: The recombinant enzyme directly removes a single alpha-1,2-mannose from Man9GlcNAc to produce Man8GlcNAc isomer B, the first ER mannose-trimming step. Reason: Core biological process with direct enzymatic (IDA) demonstration of ER mannose trimming. Supporting Evidence: PMID:10409699 the enzyme that catalyzes the first mannose trimming step in mammalian Asn-linked oligosaccharide biosynthesis |
| GO:1904380 endoplasmic reticulum mannose trimming | IMP PMID:18003979 Endoplasmic reticulum (ER) mannosidase I is compartmentalize... | ACCEPT | Summary: ERManI knockdown impairs ER mannose trimming to Man5-6GlcNAc2 in cells, confirming its role in ER mannose trimming. Reason: Core biological process with direct experimental (IMP) support. Supporting Evidence: PMID:18003979 required for trimming to Man 5β6 GlcNAc 2 and for ERAD in cells in vivo |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:18003979 Endoplasmic reticulum (ER) mannosidase I is compartmentalize... | ACCEPT | Summary: ERManI is localized to the ER membrane and concentrates in the ER-derived quality control compartment. Reason: Correct compartment with direct experimental support. Supporting Evidence: PMID:18003979 ERManI is strikingly concentrated together with the ERAD substrate in the pericentriolar ER-derived quality control compartment |
| GO:1904380 endoplasmic reticulum mannose trimming | TAS Reactome:R-HSA-901032 | ACCEPT | Summary: Reactome curation of ER mannose trimming in the ER Quality Control Compartment pathway. Reason: Correct core biological process; redundant with experimental evidence. Supporting Evidence: PMID:18003979 required for trimming to Man 5β6 GlcNAc 2 and for ERAD in cells in vivo |
| GO:0004571 mannosyl-oligosaccharide 1,2-alpha-mannosidase activity | EXP PMID:15713668 Mechanism of class 1 (glycosylhydrolase family 47) alpha-man... | ACCEPT | Summary: Structural and kinetic study of the GH47 catalytic mechanism with active-site mutagenesis directly demonstrating the alpha-1,2-mannosidase activity. Reason: Core molecular function with direct experimental (EXP) and structural support. Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt EC=3.2.1.113 |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:10409699 Identification, expression, and characterization of a cDNA e... | ACCEPT | Summary: Epitope-tagged ERManI displays an ER pattern of localization in cells, supporting ER membrane localization. Reason: Correct compartment with experimental support. Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0004571 mannosyl-oligosaccharide 1,2-alpha-mannosidase activity | IMP PMID:18003979 Endoplasmic reticulum (ER) mannosidase I is compartmentalize... | ACCEPT | Summary: Functional knockdown/inhibition experiments tie loss of mannosidase activity to impaired N-glycan trimming, supporting the enables annotation. Reason: Core molecular function consistent with direct enzymatic assays. Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt EC=3.2.1.113 |
| GO:0036503 ERAD pathway | IMP PMID:18003979 Endoplasmic reticulum (ER) mannosidase I is compartmentalize... | ACCEPT | Summary: ERManI is required for ERAD of a model misfolded glycoprotein in cells; loss leads to accumulation of untrimmed glycans. Reason: Core biological process with direct experimental (IMP) support. Supporting Evidence: PMID:18003979 required for trimming to Man 5β6 GlcNAc 2 and for ERAD in cells in vivo |
| GO:0036503 ERAD pathway | IMP PMID:21062743 Mannose trimming is required for delivery of a glycoprotein ... | ACCEPT | Summary: Mannose trimming by ERManI is required for handoff of a substrate glycoprotein from EDEM1 to the late ERAD lectin XTP3-B and the downstream HRD1/SCF(Fbs2) ligases. Reason: Core biological process; experimentally links ERManI trimming to downstream ERAD steps. Supporting Evidence: PMID:21062743 Mannose trimming is required for delivery of a glycoprotein from EDEM1 to XTP3-B |
| GO:0019082 viral protein processing | TAS Reactome:R-HSA-9694548 | KEEP AS NON CORE | Summary: Reactome annotation of MAN1B1 in N-glycan mannose trimming of the SARS-CoV-2 spike glycoprotein. This is the generic mannosidase activity acting on a viral glycoprotein substrate, not a distinct viral function. Reason: Real but peripheral; reflects the core mannosidase activity applied to a viral substrate rather than a dedicated viral-processing role. Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt EC=3.2.1.113 |
| GO:0036510 trimming of terminal mannose on C branch | TAS Reactome:R-HSA-901039 | ACCEPT | Summary: Reactome curation of the specific sub-step in which ERManI trims the terminal C-branch mannose; an accurate refinement of its trimming activity. Reason: Correct specific sub-process of N-glycan mannose trimming. Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase |
| GO:0031410 cytoplasmic vesicle | IDA PMID:25411339 Mammalian ER mannosidase I resides in quality control vesicl... | ACCEPT | Summary: At steady state ERManI resides in mobile ER-like quality control vesicles (QCVs) to which ERAD substrates are delivered, supporting a cytoplasmic vesicle localization. Reason: Genuine localization with direct experimental support (QCVs). Supporting Evidence: PMID:25411339 quality control vesicles (QCVs) with ER-like density, to which ERAD substrates are delivered |
| GO:0004571 mannosyl-oligosaccharide 1,2-alpha-mannosidase activity | IDA PMID:10521544 Cloning and expression of a specific human alpha 1,2-mannosi... | ACCEPT | Summary: The recombinant human enzyme directly removes a single alpha-1,2-mannose from Man9GlcNAc to give Man8GlcNAc isomer B, directly demonstrating its mannosidase activity. Reason: Core molecular function with direct enzymatic (IDA) support. Supporting Evidence: PMID:10409699 the enzyme that catalyzes the first mannose trimming step in mammalian Asn-linked oligosaccharide biosynthesis |
| GO:0044322 endoplasmic reticulum quality control compartment | IDA PMID:18003979 Endoplasmic reticulum (ER) mannosidase I is compartmentalize... | ACCEPT | Summary: ERManI is strikingly concentrated with ERAD substrate in the pericentriolar ER-derived quality control compartment (ERQC), where its high local concentration enables extensive trimming. Reason: Genuine, functionally important localization with direct experimental support. Supporting Evidence: PMID:18003979 ERManI is strikingly concentrated together with the ERAD substrate in the pericentriolar ER-derived quality control compartment |
| GO:0044322 endoplasmic reticulum quality control compartment | TAS PMID:21062743 Mannose trimming is required for delivery of a glycoprotein ... | ACCEPT | Summary: ERQC localization asserted in the context of ERManI-dependent ERAD substrate delivery. Reason: Consistent with direct IDA evidence for ERQC localization. Supporting Evidence: PMID:18003979 pericentriolar ER-derived quality control compartment |
| GO:0004571 mannosyl-oligosaccharide 1,2-alpha-mannosidase activity | IDA PMID:22160784 In vitro mannose trimming property of human ER alpha-1,2 man... | ACCEPT | Summary: In vitro assays show recombinant hERManI generates Man6GlcNAc2 and Man5GlcNAc2 and preferentially trims misfolded glycoproteins, directly demonstrating its mannosidase activity and conformational selectivity. Reason: Core molecular function with direct in vitro enzymatic (IDA) support. Supporting Evidence: PMID:22160784 generated Man(6)GlcNAc(2)-PA and Man(5)GlcNAc(2)-PA from 100 ΞΌM |
| GO:0005783 endoplasmic reticulum | TAS PMID:22160784 In vitro mannose trimming property of human ER alpha-1,2 man... | ACCEPT | Summary: ER localization asserted in an in vitro mannose-trimming study; consistent with the established ER residence of ERManI. Reason: Correct compartment; redundant with experimental ER membrane annotations. Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0005794 Golgi apparatus | TAS PMID:22160784 In vitro mannose trimming property of human ER alpha-1,2 man... | KEEP AS NON CORE | Summary: A Golgi localization has been reported for ERManI, but later work attributes the apparent Golgi pattern to membrane disturbance during immunofluorescence; ERManI functions in the ER/ERQC, not the Golgi. Reason: Disputed/likely fixation artifact; not a genuine site of action. Retained as non-core rather than removed because a TAS source asserts it. Supporting Evidence: PMID:25411339 Golgi pattern |
| GO:1903561 extracellular vesicle | HDA PMID:24769233 Proteomic analysis of cerebrospinal fluid extracellular vesi... | KEEP AS NON CORE | Summary: High-throughput proteomic detection of MAN1B1 in cerebrospinal fluid extracellular vesicles; a real but peripheral detection unrelated to its ER catalytic function. Reason: Large-scale proteomics detection; not a functional site of action. Supporting Evidence: PMID:24769233 cerebrospinal fluid |
| GO:0044322 endoplasmic reticulum quality control compartment | TAS Reactome:R-HSA-4793949 | ACCEPT | Summary: Reactome curation of ERQC localization (defective-MAN1B1 reaction context). Reason: Correct compartment; redundant with IDA ERQC evidence. Supporting Evidence: PMID:18003979 pericentriolar ER-derived quality control compartment |
| GO:0044322 endoplasmic reticulum quality control compartment | TAS Reactome:R-HSA-9036008 | ACCEPT | Summary: Reactome curation of ERQC localization (defective-MAN1B1 reaction context). Reason: Correct compartment; redundant with IDA ERQC evidence. Supporting Evidence: PMID:18003979 pericentriolar ER-derived quality control compartment |
| GO:0044322 endoplasmic reticulum quality control compartment | TAS Reactome:R-HSA-9036011 | ACCEPT | Summary: Reactome curation of ERQC localization (defective-MAN1B1 reaction context). Reason: Correct compartment; redundant with IDA ERQC evidence. Supporting Evidence: PMID:18003979 pericentriolar ER-derived quality control compartment |
| GO:0044322 endoplasmic reticulum quality control compartment | TAS Reactome:R-HSA-9036012 | ACCEPT | Summary: Reactome curation of ERQC localization (defective-MAN1B1 reaction context). Reason: Correct compartment; redundant with IDA ERQC evidence. Supporting Evidence: PMID:18003979 pericentriolar ER-derived quality control compartment |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: High-throughput membrane proteome detection of MAN1B1; consistent with its membrane anchoring but uninformative relative to the specific ER membrane term. Reason: Generic membrane term from proteomics; MAN1B1 is specifically an ER membrane protein. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: PMID:19946888 membrane proteome |
| GO:0044322 endoplasmic reticulum quality control compartment | TAS Reactome:R-HSA-901024 | ACCEPT | Summary: Reactome curation of ERQC localization. Reason: Correct compartment; redundant with IDA ERQC evidence. Supporting Evidence: PMID:18003979 pericentriolar ER-derived quality control compartment |
| GO:0044322 endoplasmic reticulum quality control compartment | TAS Reactome:R-HSA-901036 | ACCEPT | Summary: Reactome curation of ERQC localization. Reason: Correct compartment; redundant with IDA ERQC evidence. Supporting Evidence: PMID:18003979 pericentriolar ER-derived quality control compartment |
| GO:0044322 endoplasmic reticulum quality control compartment | TAS Reactome:R-HSA-901039 | ACCEPT | Summary: Reactome curation of ERQC localization. Reason: Correct compartment; redundant with IDA ERQC evidence. Supporting Evidence: PMID:18003979 pericentriolar ER-derived quality control compartment |
| GO:0044322 endoplasmic reticulum quality control compartment | TAS Reactome:R-HSA-901074 | ACCEPT | Summary: Reactome curation of ERQC localization. Reason: Correct compartment; redundant with IDA ERQC evidence. Supporting Evidence: PMID:18003979 pericentriolar ER-derived quality control compartment |
| GO:0044322 endoplasmic reticulum quality control compartment | TAS Reactome:R-HSA-9696807 | ACCEPT | Summary: Reactome curation of ERQC localization in the spike N-glycan trimming pathway. Reason: Correct compartment; redundant with IDA ERQC evidence. Supporting Evidence: PMID:18003979 pericentriolar ER-derived quality control compartment |
| GO:0004571 mannosyl-oligosaccharide 1,2-alpha-mannosidase activity | IDA PMID:12090241 The specificity of the yeast and human class I ER alpha 1,2-... | ACCEPT | Summary: Demonstrates that the human class I ER alpha-1,2-mannosidase can trim beyond a single mannose, refining the specificity of the mannosidase activity. Reason: Core molecular function with direct experimental support; informs the broader-than-single-residue specificity underlying the mannose timer. Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt at high enzyme concentrations, as found in the ER |
| GO:0005783 endoplasmic reticulum | IDA PMID:18003979 Endoplasmic reticulum (ER) mannosidase I is compartmentalize... | ACCEPT | Summary: Direct evidence for ER localization of ERManI. Reason: Correct site of action with direct experimental support. Supporting Evidence: PMID:18003979 pericentriolar ER-derived quality control compartment |
| GO:0016020 membrane | IDA PMID:18003979 Endoplasmic reticulum (ER) mannosidase I is compartmentalize... | MARK AS OVER ANNOTATED | Summary: Generic membrane localization; superseded by the specific ER membrane annotation from the same evidence. Reason: Uninformative parent of the specific ER membrane localization. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0004571 mannosyl-oligosaccharide 1,2-alpha-mannosidase activity | TAS PMID:10409699 Identification, expression, and characterization of a cDNA e... | ACCEPT | Summary: Identification and characterization of human ER mannosidase I as the enzyme catalyzing the first mannose-trimming step. Reason: Core molecular function with strong experimental basis. Supporting Evidence: PMID:10409699 the enzyme that catalyzes the first mannose trimming step in mammalian Asn-linked oligosaccharide biosynthesis |
| GO:0005783 endoplasmic reticulum | TAS PMID:10409699 Identification, expression, and characterization of a cDNA e... | ACCEPT | Summary: ER localization asserted from the original characterization of ER mannosidase I. Reason: Correct site of action; consistent with experimental ER membrane evidence. Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0009311 oligosaccharide metabolic process | TAS PMID:10409699 Identification, expression, and characterization of a cDNA e... | MARK AS OVER ANNOTATED | Summary: Generic oligosaccharide metabolic process; correct but far less informative than the specific N-glycan/mannose trimming terms. Reason: Over-general parent process; the specific ER mannose trimming term is preferred. Supporting Evidence: PMID:10409699 Asn-linked oligosaccharide biosynthesis |
| GO:0004571 mannosyl-oligosaccharide 1,2-alpha-mannosidase activity | TAS PMID:10521544 Cloning and expression of a specific human alpha 1,2-mannosi... | ACCEPT | Summary: Original cloning/characterization establishing the specific human alpha-1,2-mannosidase activity producing Man8GlcNAc2 isomer B. Reason: Core molecular function with strong experimental basis. Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase |
| GO:0005509 calcium ion binding | TAS PMID:10521544 Cloning and expression of a specific human alpha 1,2-mannosi... | KEEP AS NON CORE | Summary: Calcium is required for ERManI activity; this is a structural/catalytic cofactor requirement of the GH47 fold rather than an independent calcium-signaling function. Reason: Real cofactor requirement but subsidiary to the catalytic mannosidase activity. Supporting Evidence: PMID:10521544 Calcium is required for enzyme activity |
| GO:0016020 membrane | TAS PMID:10521544 Cloning and expression of a specific human alpha 1,2-mannosi... | MARK AS OVER ANNOTATED | Summary: Generic membrane localization; superseded by the specific ER membrane annotation. Reason: Uninformative parent; MAN1B1 is specifically an ER membrane protein. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: file:human/MAN1B1/MAN1B1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
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Download this section (compressed HTML)Q: What determines the conformational selectivity by which ERManI preferentially trims mannoses from misfolded versus correctly folded glycoproteins, and is this intrinsic to the enzyme or dependent on ERQC cofactors?
Q: How is the high local concentration of ERManI in quality control vesicles/ERQC regulated to tune the kinetics of the mannose timer?
Experiment: Reconstitute ERManI trimming on defined folded versus misfolded glycoprotein substrates at controlled enzyme concentrations to quantify how local concentration and substrate conformation set the rate of progression from Man9 to Man5-6.
Experiment: Live-cell imaging of QCV/ERQC dynamics in cells expressing wild-type versus Rafiq-syndrome (R334C, E397K) MAN1B1 variants to test how disease mutations affect localization, vesicle trafficking, and ERAD substrate clearance.
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