MAGT1 is an endoplasmic-reticulum membrane, thioredoxin-like oxidoreductase and an accessory subunit of the STT3B-containing (post-translocational) oligosaccharyltransferase complex (OST-B). It carries a lumenal thioredoxin fold with a redox-active CXXC (CVVC) motif and is one of two mutually exclusive STT3B-specific accessory subunits (MAGT1 or its paralog TUSC3). Within OST-B, MAGT1 promotes N-linked glycosylation of a subset of acceptor sequons that are near cysteine residues or bracketed by disulfides: in its predominantly oxidized state it forms transient mixed disulfides with the free thiols of nascent glycoprotein substrates, delaying disulfide-bond formation so that the catalytic STT3B subunit can access and glycosylate the unmodified asparagine. It also has oxidoreductase-independent roles in substrate recognition by OST-B. Although historically named "magnesium transporter 1" and reported to support cellular Mg2+ uptake, its principal, best-supported molecular function is the OST-B oxidoreductase role; any contribution to Mg2+ homeostasis appears to be secondary and at least partly a downstream consequence of altered glycosylation. Loss of MAGT1 function causes X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia (XMEN) and a congenital disorder of glycosylation (MAGT1-CDG).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006487 protein N-linked glycosylation | IBA GO_REF:0000033 | ACCEPT | Summary: Core biological process. As an accessory subunit of the STT3B OST complex, MAGT1 is required for N-linked glycosylation of a subset of acceptor sites. The phylogenetic (IBA) inference is consistent with strong experimental evidence and with the OST3/OST6 family membership. Supporting Evidence: file:human/MAGT1/MAGT1-uniprot.txt Involved in N- |
| GO:0008250 oligosaccharyltransferase complex | IBA GO_REF:0000033 | ACCEPT | Summary: Core cellular component. MAGT1 is a subunit of the OST (specifically the STT3B/OST-B complex). The IBA inference agrees with experimental co-IP and cryo-EM data. The more specific child term oligosaccharyltransferase complex B (GO:0160227) is also annotated. Supporting Evidence: PMID:25135935 MagT1, an ER-localized thioredoxin homologue, is a subunit of the STT3B |
| GO:1903830 magnesium ion transmembrane transport | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Over-annotation of the core function. This IBA is propagated from the historical "magnesium transporter" characterization and a Drosophila ortholog (FB:FBgn0032015). The best-supported function of human MAGT1 is the OST-B oxidoreductase role; UniProt now frames the Mg2+ role as indirect/probable, and the leading interpretation is that Mg2+ phenotypes are largely downstream of a glycosylation defect. Not core. Supporting Evidence: file:human/MAGT1/MAGT1-uniprot.txt Could indirectly play a role in Mg(2+) |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | ACCEPT | Summary: Correct core localization. MAGT1 is an ER-resident protein (colocalizes with calreticulin). This IEA (from the UniProt subcellular-location mapping) is redundant with the experimental IDA (PMID:25135935) but is correct; accept. Supporting Evidence: PMID:25135935 Colocalization of MagT1-V5 and calreticulin confirmed that MagT1 is an ER resident protein |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Correct core localization. MAGT1 is a multi-pass ER membrane protein; the ER membrane is where the OST-B complex acts. This IEA is redundant with experimental and Reactome annotations to the same term; accept. Supporting Evidence: file:human/MAGT1/MAGT1-uniprot.txt Endoplasmic reticulum membrane |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Non-core localization derived from the historical Mg2+-transporter model, in which MAGT1 was proposed to be a plasma-membrane channel. Surface-biotinylation shows MAGT1 has very low cell-surface reactivity and it colocalizes with the ER marker calreticulin, so the functionally important pool is the ER. UniProt still lists Cell membrane, so keep but as non-core. Supporting Evidence: file:human/MAGT1/MAGT1-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0006487 protein N-linked glycosylation | IEA GO_REF:0000117 | ACCEPT | Summary: Correct core process, redundant with the experimental IMP annotations and the IBA. The ARBA electronic model assigns the correct N-linked glycosylation role for an OST-B subunit; accept. Supporting Evidence: file:human/MAGT1/MAGT1-uniprot.txt Involved in N- |
| GO:0008250 oligosaccharyltransferase complex | IEA GO_REF:0000117 | ACCEPT | Summary: Correct core complex membership, redundant with the experimental IDA/IPI and IBA annotations to the same term. Accept. Supporting Evidence: file:human/MAGT1/MAGT1-uniprot.txt Accessory component of the STT3B-containing form of the |
| GO:0015095 magnesium ion transmembrane transporter activity | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Over-annotation. This ARBA electronic annotation assigns a direct Mg2+ transporter activity based on the historical name/family, but the best-supported molecular function of MAGT1 is the thioredoxin-like OST-B oxidoreductase activity. UniProt downgrades the Mg2+ role to indirect/probable and no longer uses "magnesium transporter" as the primary name. There is no robust evidence that MAGT1 itself is a Mg2+ channel/transporter; mark as over-annotated. Supporting Evidence: file:human/MAGT1/MAGT1-uniprot.txt Could indirectly play a role in Mg(2+) |
| GO:0055085 transmembrane transport | TAS Reactome:R-HSA-5223345 | MARK AS OVER ANNOTATED | Summary: Generic transmembrane-transport annotation propagated from the Reactome "Miscellaneous transport and binding events" pathway, itself based on the contested Mg2+-transporter model. Not the core function; mark as over-annotated. Supporting Evidence: file:human/MAGT1/MAGT1-uniprot.txt Could indirectly play a role in Mg(2+) |
| GO:0005789 endoplasmic reticulum membrane | NAS PMID:31831667 Cryo-electron microscopy structures of human oligosaccharylt... | ACCEPT | Summary: Correct core localization from the OST-A/OST-B cryo-EM study (ComplexPortal assertion). MAGT1 is a membrane subunit of OST-B at the ER membrane. Accept. Supporting Evidence: PMID:31831667 DC2 in OST-A and |
| GO:0008250 oligosaccharyltransferase complex | IPI PMID:31831667 Cryo-electron microscopy structures of human oligosaccharylt... | ACCEPT | Summary: Core complex membership supported by cryo-EM structural identification of MAGT1 as a subunit of OST-B (ComplexPortal IPI). Accept. Supporting Evidence: PMID:31831667 facilitate contacts to distinct OST subunits, DC2 in OST-A and |
| GO:0005789 endoplasmic reticulum membrane | IMP PMID:31337704 Magnesium transporter 1 (MAGT1) deficiency causes selective ... | ACCEPT | Summary: Correct core localization. Experimental annotation (MAGT1-deficiency study). MAGT1 is a multi-pass ER membrane protein; accept. (Assigned by FlyBase against the human JBC paper.) Supporting Evidence: file:human/MAGT1/MAGT1-uniprot.txt Endoplasmic reticulum membrane |
| GO:0005886 plasma membrane | IDA PMID:19717468 Mammalian MagT1 and TUSC3 are required for cellular magnesiu... | KEEP AS NON CORE | Summary: Experimental (IDA) plasma-membrane localization from the Zhou & Clapham Mg2+-uptake study, which modeled MAGT1 as a plasma-membrane Mg2+ transporter. Subsequent work localizes the functionally relevant pool to the ER (colocalization with calreticulin; low surface biotinylation). Per policy, an experimental annotation is not removed; retain as non-core. Supporting Evidence: PMID:19717468 MagT1 and TUSC3 are indispensable members of the vertebrate plasma membrane Mg(2+) transport system |
| GO:0006487 protein N-linked glycosylation | IMP PMID:31337704 Magnesium transporter 1 (MAGT1) deficiency causes selective ... | ACCEPT | Summary: Core process. Experimental (IMP) evidence: MAGT1-deficient cells show selective defects in N-linked glycosylation. Accept. Supporting Evidence: PMID:31337704 humans lacking functional MAGT1 have a selective deficiency in both immune |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-446209 | ACCEPT | Summary: Correct core localization (Reactome "Transfer of N-glycan to the protein"). Redundant with experimental and IEA annotations; accept. Supporting Evidence: file:human/MAGT1/MAGT1-uniprot.txt Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9694793 | ACCEPT | Summary: Correct core localization, propagated via a Reactome viral-spike-glycosylation pathway (OST-B acts at the ER membrane). Redundant but correct; accept. Supporting Evidence: file:human/MAGT1/MAGT1-uniprot.txt Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9918962 | ACCEPT | Summary: Correct core localization, propagated via a Reactome flavivirus-glycosylation pathway. Redundant with other ER-membrane annotations; accept. Supporting Evidence: file:human/MAGT1/MAGT1-uniprot.txt Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9918988 | ACCEPT | Summary: Correct core localization, propagated via a Reactome viral-glycosylation pathway. Redundant with other ER-membrane annotations; accept. Supporting Evidence: file:human/MAGT1/MAGT1-uniprot.txt Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9919011 | ACCEPT | Summary: Correct core localization, propagated via a Reactome viral-protein-glycosylation pathway. Redundant with other ER-membrane annotations; accept. Supporting Evidence: file:human/MAGT1/MAGT1-uniprot.txt Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9931286 | ACCEPT | Summary: Correct core localization, propagated via the Reactome "CD274 N-linked glycosylation in ER" pathway. Redundant with other ER-membrane annotations; accept. Supporting Evidence: file:human/MAGT1/MAGT1-uniprot.txt Endoplasmic reticulum membrane |
| GO:0160227 oligosaccharyltransferase complex B | IDA PMID:31831667 Cryo-electron microscopy structures of human oligosaccharylt... | ACCEPT | Summary: Best (most specific) core complex annotation. Cryo-EM directly identifies MAGT1 as a subunit of the STT3B-containing OST-B complex. Accept as the representative complex-membership term. Supporting Evidence: PMID:31831667 facilitate contacts to distinct OST subunits, DC2 in OST-A and |
| GO:0015693 magnesium ion transport | IMP PMID:19717468 Mammalian MagT1 and TUSC3 are required for cellular magnesiu... | KEEP AS NON CORE | Summary: Experimental (IMP) evidence that MAGT1 knockdown lowers intracellular Mg2+ and arrests zebrafish development (Zhou & Clapham). This is a real phenotype, but is now interpreted as an indirect/downstream role rather than a direct core molecular function; the acts_upstream_of_or_within qualifier is appropriate for an indirect effect. Per policy an experimental annotation is not removed; retain as non-core. Supporting Evidence: PMID:19717468 its expression level is up-regulated in low extracellular |
| GO:0015095 magnesium ion transmembrane transporter activity | TAS Reactome:R-HSA-5339538 | MARK AS OVER ANNOTATED | Summary: Over-annotation. Reactome ("MAGT1 transports Mg2+ from extracellular region to cytosol") encodes the historical direct-transporter model. The best-supported MF is the OST-B oxidoreductase activity; the direct Mg2+-transporter activity is contested and likely indirect. Mark as over-annotated. Supporting Evidence: file:human/MAGT1/MAGT1-uniprot.txt Could indirectly play a role in Mg(2+) |
| GO:0006487 protein N-linked glycosylation | IMP PMID:31036665 Mutations in MAGT1 lead to a glycosylation disorder with a v... | ACCEPT | Summary: Core process. Experimental (IMP) evidence from MAGT1-CDG patients: STT3B-dependent post-translational glycosylation of substrates (GLUT1, SHBG, transferrin) is dysfunctional. Accept. Supporting Evidence: PMID:31036665 different substrates, such as GLUT1 and SHBG, demonstrating that the |
| GO:0005783 endoplasmic reticulum | IDA PMID:25135935 Oxidoreductase activity is necessary for N-glycosylation of ... | ACCEPT | Summary: Core localization, directly demonstrated (IDA): endogenous MAGT1 colocalizes with the ER lumenal lectin calreticulin and does not colocalize with the plasma-membrane Na+K+-ATPase. Accept. Supporting Evidence: PMID:25135935 MagT1 colocalizes with calreticulin, a lumenal lectin in the RER |
| GO:0006487 protein N-linked glycosylation | IMP PMID:25135935 Oxidoreductase activity is necessary for N-glycosylation of ... | ACCEPT | Summary: Core process, strongly supported. siRNA depletion of MAGT1 reduces glycan occupancy on STT3B-dependent acceptor sites; the active-site CVVC motif is required. This is the key experimental annotation for the N-glycosylation role. Accept. Supporting Evidence: PMID:25135935 is required for glycosylation of STT3B-dependent |
| GO:0008250 oligosaccharyltransferase complex | IDA PMID:25135935 Oxidoreductase activity is necessary for N-glycosylation of ... | ACCEPT | Summary: Core complex membership, directly demonstrated (IDA) by native co-immunoprecipitation: MAGT1 is a subunit of the STT3B complex. Accept. Supporting Evidence: PMID:25135935 MagT1, an ER-localized thioredoxin homologue, is a subunit of the STT3B |
| GO:0035577 azurophil granule membrane | TAS Reactome:R-HSA-6798739 | KEEP AS NON CORE | Summary: Non-core localization propagated from a Reactome neutrophil-degranulation pathway ("Exocytosis of azurophil granule membrane proteins"). MAGT1 was detected in neutrophil granule/membrane proteomics, but its characterized function is at the ER membrane as an OST-B subunit. Keep as non-core. Supporting Evidence: file:human/MAGT1/MAGT1-uniprot.txt Multi-pass membrane protein |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | KEEP AS NON CORE | Summary: Generic membrane localization from high-throughput NK-cell membrane proteomics. Correct but uninformative (parent of the specific ER-membrane term); keep as non-core. Supporting Evidence: file:human/MAGT1/MAGT1-uniprot.txt Multi-pass membrane protein |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5339538 | KEEP AS NON CORE | Summary: Non-core localization from the Reactome Mg2+-transport reaction, encoding the historical plasma-membrane transporter model. The functionally relevant pool is the ER; keep as non-core. Supporting Evidence: file:human/MAGT1/MAGT1-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6798739 | KEEP AS NON CORE | Summary: Non-core plasma-membrane localization propagated from the Reactome neutrophil-degranulation pathway. Not the ER core; keep as non-core. Supporting Evidence: file:human/MAGT1/MAGT1-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0006487 protein N-linked glycosylation | NAS PMID:18455129 Oligosaccharyltransferase-subunit mutations in nonsyndromic ... | ACCEPT | Summary: Correct core process (non-core-evidence NAS). Molinari et al. describe MAGT1/IAP as a paralog of the OTase subunit TUSC3 and implicate OTase activity in cognition; the general N-glycosylation involvement is sound and consistent with later experimental work. Accept. Supporting Evidence: PMID:18455129 the key step of N-glycosylation |
| GO:0050890 cognition | IMP PMID:18455129 Oligosaccharyltransferase-subunit mutations in nonsyndromic ... | KEEP AS NON CORE | Summary: Rests on the MAGT1 V311G missense variant proposed to cause non-syndromic X-linked intellectual disability. UniProt flags this pathological role as questionable (CAUTION, citing PubMed:23871722, which found the variant not to segregate with disease). This is not a core molecular function and the underlying variant is contested; retain but strictly as non-core. Supporting Evidence: file:human/MAGT1/MAGT1-uniprot.txt its pathological role is |
| GO:0008250 oligosaccharyltransferase complex | IDA PMID:15835887 Proteomic analysis of mammalian oligosaccharyltransferase re... | ACCEPT | Summary: Core complex membership. Proteomic analysis of mammalian OST identified new OST-associated subunits; MAGT1/IAP is one of the OST3/OST6-family accessory proteins later confirmed as a bona fide STT3B/OST-B subunit. Accept. Supporting Evidence: PMID:15835887 two potential new subunits of mammalian OST |
| GO:0015036 disulfide oxidoreductase activity | IDA PMID:25135935 Oxidoreductase activity is necessary for N-glycosylation of ... | NEW | Summary: Proposed new annotation capturing MAGT1's core molecular function, which is currently missing from GOA. MAGT1 is a lumenal ER thioredoxin-like protein whose redox-active CXXC (CVVC) motif is required for glycosylation of STT3B-dependent acceptor sites; the protein is predominantly oxidized in vivo and forms transient mixed disulfides with glycoprotein substrates. Mutagenesis of the active-site cysteines (C87/C90) abolishes activity. This is the thioredoxin-like protein-disulfide oxidoreductase activity that underlies the OST-B proofreading role. Supporting Evidence: PMID:25135935 the CXXC motif is necessary for MagT1 and TUSC3 activity PMID:25135935 The predominant form of MagT1 in vivo is oxidized, which is |
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Download this section (compressed HTML)Q: Is MAGT1's contribution to cellular Mg2+ homeostasis entirely a downstream consequence of hypoglycosylation of Mg2+-handling/immune glycoproteins, or does MAGT1 retain any direct role in Mg2+ flux across a membrane?
Q: What distinguishes the substrate/acceptor-site preferences of MAGT1- versus TUSC3-containing OST-B complexes in tissues where both are expressed, given their apparent redundancy?
Experiment: Global, site-resolved N-glycoproteomics comparing MAGT1-null, TUSC3-null, and MAGT1/TUSC3-double-null cells to define the full set of cysteine-proximal / disulfide-bracketed acceptor sites that specifically require the MAGT1 oxidoreductase.
Experiment: Reconstitute purified OST-B with wild-type versus CVVC-motif-mutant MAGT1 and directly assay both mixed-disulfide formation with a model glycoprotein substrate and glycotransferase activity on cysteine-proximal sequons, decoupling oxidoreductase-dependent from oxidoreductase-independent (substrate-recognition) roles.
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