STT3B is the catalytic subunit of the STT3B-containing oligosaccharyltransferase (OST) complex (OST-B), one of two human OST isoforms (the other carries STT3A). OST is a multi-subunit, multi-pass endoplasmic reticulum membrane enzyme that catalyzes the central reaction of N-linked glycosylation: the en bloc transfer of the preassembled high-mannose glycan Glc3Man9GlcNAc2 from the lipid donor dolichyl-diphosphate onto the asparagine of N-X-Ser/Thr (X not Pro) sequons in acceptor proteins in the ER lumen (EC 2.4.99.18). STT3B provides the active site and the acceptor-peptide and lipid-linked-oligosaccharide binding pockets, and catalysis requires a divalent metal ion cofactor (Mg2+/Mn2+). Whereas the STT3A complex is stably associated with the Sec61 translocon and performs the bulk of cotranslational glycosylation of nascent chains, the STT3B complex is not translocon-associated and acts as a proofreading second pass, glycosylating sequons that STT3A skipped, including C-terminal sequons, sequons close to the signal-sequence cleavage site, cysteine-proximal sequons, and sites in short loops of multi-spanning membrane proteins. This post-translational/post-translocational activity, which depends on the OST-B oxidoreductase subunits MAGT1 or TUSC3, also functions as a surveillance system that glycosylates cryptic sequons exposed in unfolded secretory proteins, marking them for N-glycan-dependent ER-associated degradation. Loss-of-function variants cause STT3B-CDG, a congenital disorder of glycosylation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004579 dolichyl-diphosphooligosaccharide-protein glycotransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Core molecular function of STT3B: the catalytic subunit of the OST complex that transfers the dolichol-linked oligosaccharide onto acceptor asparagines. Well supported by experiment for the human protein and correctly propagated by the phylogenetic (IBA) inference. Supporting Evidence: file:human/STT3B/STT3B-uniprot.txt Catalytic subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan |
| GO:0006487 protein N-linked glycosylation | IBA GO_REF:0000033 | ACCEPT | Summary: Core biological process; STT3B mediates N-linked glycosylation as the OST catalytic subunit. Correctly inferred by phylogeny and strongly supported experimentally for the human protein. Supporting Evidence: PMID:19167329 we show that the OST isoforms cooperate and act sequentially to mediate protein N-glycosylation |
| GO:0008250 oligosaccharyltransferase complex | IBA GO_REF:0000033 | ACCEPT | Summary: STT3B is the catalytic subunit of the OST complex. Correct core cellular-component/complex membership (the more specific term is GO:0160227, oligosaccharyltransferase complex B). Supporting Evidence: file:human/STT3B/STT3B-uniprot.txt Component of the oligosaccharyltransferase (OST) complex |
| GO:0043687 post-translational protein modification | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: True but high-level parent term. STT3B's distinctive post-translational role is captured more precisely by GO:0180057 (protein post-translational transfer of dolichol-linked oligosaccharide). Retained as non-core. |
| GO:0004576 oligosaccharyl transferase activity | IEA GO_REF:0000002 | MODIFY | Summary: Correct direction but less informative than the specific dolichol-dependent activity actually catalyzed by STT3B. Should use the more precise child term GO:0004579 (dolichyl-diphosphooligosaccharide-protein glycotransferase activity), which is independently annotated with experimental evidence. Proposed replacements: dolichyl-diphosphooligosaccharide-protein glycotransferase activity Supporting Evidence: file:human/STT3B/STT3B-uniprot.txt catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue |
| GO:0004579 dolichyl-diphosphooligosaccharide-protein glycotransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Correct core molecular function, derived electronically from the EC/Rhea mapping (EC 2.4.99.18; RHEA:22980), consistent with the experimental annotations. Redundant but correct. Supporting Evidence: file:human/STT3B/STT3B-uniprot.txt catalyzes the initial transfer of a defined glycan |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | ACCEPT | Summary: Correct compartment. STT3B is an ER protein; the more precise term is GO:0005789 (ER membrane). Redundant with experimental ER annotations. Supporting Evidence: file:human/STT3B/STT3B-uniprot.txt Endoplasmic reticulum membrane; Multi-pass membrane protein |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Correct core localization: STT3B is a multi-pass ER membrane protein. Consistent with the UniProt subcellular location and the OST-B cryo-EM structure. Supporting Evidence: file:human/STT3B/STT3B-uniprot.txt Endoplasmic reticulum membrane; Multi-pass membrane protein |
| GO:0006487 protein N-linked glycosylation | IEA GO_REF:0000117 | ACCEPT | Summary: Correct core biological process, electronically inferred (ARBA). Redundant with the experimental IDA/IMP annotations to the same term. Supporting Evidence: PMID:31296534 The STT3B complex is not associated with the translocon, yet glycosylates certain acceptor sites that have been skipped by the STT3A complex |
| GO:0008250 oligosaccharyltransferase complex | IEA GO_REF:0000117 | ACCEPT | Summary: Correct core complex membership, electronically inferred (ARBA). Redundant with experimental complex annotations. Supporting Evidence: file:human/STT3B/STT3B-uniprot.txt Component of the oligosaccharyltransferase (OST) complex |
| GO:0009101 glycoprotein biosynthetic process | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: True but a less-informative parent of protein N-linked glycosylation, which is the specific process STT3B carries out. Retained as non-core. |
| GO:0016020 membrane | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Correct but uninformative high-level location. The specific compartment is the ER membrane (GO:0005789). Retained as non-core. |
| GO:0005515 protein binding | IPI PMID:19167329 Cotranslational and posttranslational N-glycosylation of pol... | MARK AS OVER ANNOTATED | Summary: Bare protein-binding IPI (partner RPN1/P04843, a bona fide OST subunit). Not informative as a molecular function; the meaningful function is captured by OST complex membership (GO:0008250/GO:0160227) and the catalytic activity. Flagged as an over-annotation per curation policy (not removed). |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | MARK AS OVER ANNOTATED | Summary: Bare protein-binding IPI from a histone crosslinking-MS screen. Not informative about STT3B function. Flagged as over-annotated per policy. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Bare protein-binding IPI from the HuRI binary interactome (partner INCA1/Q0VD86). Not informative about STT3B function. Flagged as over-annotated per policy. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MARK AS OVER ANNOTATED | Summary: Bare protein-binding IPI from the OpenCell resource (partner RPN1/P04843, an OST subunit). Uninformative as a molecular function. Flagged as over-annotated per policy. |
| GO:0005789 endoplasmic reticulum membrane | NAS PMID:31831667 Cryo-electron microscopy structures of human oligosaccharylt... | ACCEPT | Summary: Correct core ER-membrane localization, from the OST-B cryo-EM structure paper (ComplexPortal NAS). Consistent with the multiple other ER-membrane annotations. Supporting Evidence: PMID:31831667 catalyzes the transfer of a high-mannose glycan onto secretory proteins in the endoplasmic reticulum |
| GO:0006487 protein N-linked glycosylation | IDA PMID:31831667 Cryo-electron microscopy structures of human oligosaccharylt... | ACCEPT | Summary: Core biological process supported by direct structural and functional characterization of the OST-B complex (ComplexPortal IDA). Supporting Evidence: PMID:31831667 Oligosaccharyltransferase (OST) catalyzes the transfer of a high-mannose glycan onto secretory proteins in the endoplasmic reticulum |
| GO:0008250 oligosaccharyltransferase complex | IPI PMID:31831667 Cryo-electron microscopy structures of human oligosaccharylt... | ACCEPT | Summary: Core complex membership, established by the cryo-EM structure of OST-B in which STT3B is the catalytic subunit. The most specific term is GO:0160227 (oligosaccharyltransferase complex B), which is separately annotated. Supporting Evidence: PMID:31831667 structural differences in the catalytic subunits STT3A and STT3B facilitate contacts to distinct OST subunits, DC2 in OST-A and MAGT1 in OST-B |
| GO:0005783 endoplasmic reticulum | IDA GO_REF:0000052 | ACCEPT | Summary: Direct (immunofluorescence, HPA) evidence for ER localization. Correct; the more precise term is ER membrane (GO:0005789). Supporting Evidence: file:human/STT3B/STT3B-uniprot.txt Endoplasmic reticulum membrane; Multi-pass membrane protein |
| GO:0005783 endoplasmic reticulum | EXP PMID:12887896 Oligosaccharyltransferase isoforms that contain different ca... | ACCEPT | Summary: Experimental evidence (Kelleher et al. 2003) for ER localization of the STT3B-containing OST. Correct core compartment (specific term GO:0005789). Supporting Evidence: PMID:12887896 N-linked glycosylation of nascent proteins in the lumen of the endoplasmic reticulum |
| GO:0180057 protein post-translational transfer of dolichol-linked oligosaccharide | IMP PMID:19167329 Cotranslational and posttranslational N-glycosylation of pol... | ACCEPT | Summary: Captures STT3B's most distinctive mechanistic role: post-translational (post-translocational) transfer of the dolichol-linked oligosaccharide onto sequons skipped during cotranslational glycosylation. Directly supported by the Factor VII N360 experiments. Supporting Evidence: PMID:19167329 The STT3B isoform is responsible for posttranslational glycosylation of FVII on N360 |
| GO:0180058 protein co-translational transfer of dolichol-linked oligosaccharide | IMP PMID:19167329 Cotranslational and posttranslational N-glycosylation of pol... | KEEP AS NON CORE | Summary: STT3B can also glycosylate certain sites cotranslationally (e.g. the sequon adjacent to the signal sequence, and sites skipped by STT3A in a cotranslational mode). Genuine but a secondary role relative to the post-translational activity; the bulk of cotranslational glycosylation is STT3A. Retained as non-core. Supporting Evidence: PMID:19167329 The STT3B isoform is required for efficient cotranslational glycosylation of an acceptor site adjacent to the N-terminal signal sequence of a secreted protein |
| GO:0160227 oligosaccharyltransferase complex B | IDA PMID:31831667 Cryo-electron microscopy structures of human oligosaccharylt... | ACCEPT | Summary: Most precise and correct complex membership: STT3B is the defining catalytic subunit of the OST-B complex, resolved by cryo-EM (PDB 6S7T). Core cellular component. Supporting Evidence: PMID:31831667 structural differences in the catalytic subunits STT3A and STT3B facilitate contacts to distinct OST subunits, DC2 in OST-A and MAGT1 in OST-B |
| GO:0004579 dolichyl-diphosphooligosaccharide-protein glycotransferase activity | IDA PMID:31296534 Quantitative glycoproteomics reveals new classes of STT3A- a... | ACCEPT | Summary: Core catalytic activity, directly demonstrated by quantitative glycoproteomics in STT3B-knockout cells showing loss of glycosylation at STT3B-dependent sites. Supporting Evidence: PMID:31296534 The STT3B complex is not associated with the translocon, yet glycosylates certain acceptor sites that have been skipped by the STT3A complex |
| GO:0004579 dolichyl-diphosphooligosaccharide-protein glycotransferase activity | IDA PMID:39509507 Regulated N-glycosylation controls chaperone function and re... | ACCEPT | Summary: Core catalytic activity, supported by the regulated-N-glycosylation study characterizing OST-A/OST-B activity on chaperone substrates. Supporting Evidence: PMID:39509507 N-glycosylated in the endoplasmic reticulum (ER) |
| GO:0006487 protein N-linked glycosylation | IDA PMID:31296534 Quantitative glycoproteomics reveals new classes of STT3A- a... | ACCEPT | Summary: Core biological process, directly demonstrated by SILAC glycoproteomics of STT3B-dependent acceptor sites. Supporting Evidence: PMID:31296534 Acceptor sites located in short loops of multi-spanning |
| GO:0043687 post-translational protein modification | IDA PMID:31296534 Quantitative glycoproteomics reveals new classes of STT3A- a... | KEEP AS NON CORE | Summary: High-level parent term. STT3B's post-translational role is more precisely GO:0180057. Retained as non-core. |
| GO:0008250 oligosaccharyltransferase complex | IDA PMID:22467853 The oligosaccharyltransferase subunits OST48, DAD1 and KCP2 ... | ACCEPT | Summary: Core complex membership; the OST-subunit study demonstrates STT3B in the OST complex whose assembly depends on OST48/DAD1. Correct. Supporting Evidence: PMID:22467853 OST48 and DAD1 are required for the assembly of both STT3A- and STT3B-containing OST complexes |
| GO:0004579 dolichyl-diphosphooligosaccharide-protein glycotransferase activity | IMP PMID:22467853 The oligosaccharyltransferase subunits OST48, DAD1 and KCP2 ... | ACCEPT | Summary: Core catalytic activity, supported by subunit-depletion hypoglycosylation phenotypes of STT3B-containing complexes. Supporting Evidence: PMID:22467853 OST48 and DAD1 are global modulators of OST stability and hence N-glycosylation |
| GO:0006487 protein N-linked glycosylation | IMP PMID:22467853 The oligosaccharyltransferase subunits OST48, DAD1 and KCP2 ... | ACCEPT | Summary: Core biological process; supported by hypoglycosylation phenotypes on depletion of OST subunits that assemble STT3B-containing complexes. Supporting Evidence: PMID:22467853 OST48 and DAD1 are required for the assembly of both STT3A- and STT3B-containing OST complexes |
| GO:0004579 dolichyl-diphosphooligosaccharide-protein glycotransferase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Core catalytic activity transferred by sequence similarity from an ortholog. Consistent with the experimental annotations of the same term. Supporting Evidence: file:human/STT3B/STT3B-uniprot.txt This subunit contains the active site and the acceptor peptide and donor lipid-linked oligosaccharide (LLO) binding pockets |
| GO:0032991 protein-containing complex | IDA PMID:28246125 ZMPSTE24 defends against influenza and other pathogenic viru... | MARK AS OVER ANNOTATED | Summary: Uninformative high-level complex term (from a ZMPSTE24 antiviral co-purification study). The meaningful, specific complex is the OST complex (GO:0008250 / GO:0160227). Over-annotation relative to those. |
| GO:0008250 oligosaccharyltransferase complex | ISS GO_REF:0000024 | ACCEPT | Summary: Core complex membership transferred by sequence similarity from an ortholog. Correct and consistent with experimental annotations. Supporting Evidence: file:human/STT3B/STT3B-uniprot.txt Component of the oligosaccharyltransferase (OST) complex |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-446209 | ACCEPT | Summary: Correct core ER-membrane localization (Reactome, N-glycan transfer reaction). Consistent with all other ER-membrane annotations. Supporting Evidence: file:human/STT3B/STT3B-uniprot.txt Endoplasmic reticulum membrane; Multi-pass membrane protein |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9694793 | ACCEPT | Summary: Correct core ER-membrane localization (Reactome, viral spike protein N-glycosylation pathway). Redundant but correct. Supporting Evidence: file:human/STT3B/STT3B-uniprot.txt Endoplasmic reticulum membrane; Multi-pass membrane protein |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9918962 | ACCEPT | Summary: Correct core ER-membrane localization (Reactome). Redundant but correct. Supporting Evidence: file:human/STT3B/STT3B-uniprot.txt Endoplasmic reticulum membrane; Multi-pass membrane protein |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9918988 | ACCEPT | Summary: Correct core ER-membrane localization (Reactome). Redundant but correct. Supporting Evidence: file:human/STT3B/STT3B-uniprot.txt Endoplasmic reticulum membrane; Multi-pass membrane protein |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9919011 | ACCEPT | Summary: Correct core ER-membrane localization (Reactome). Redundant but correct. Supporting Evidence: file:human/STT3B/STT3B-uniprot.txt Endoplasmic reticulum membrane; Multi-pass membrane protein |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9926534 | ACCEPT | Summary: Correct core ER-membrane localization (Reactome). Redundant but correct. Supporting Evidence: file:human/STT3B/STT3B-uniprot.txt Endoplasmic reticulum membrane; Multi-pass membrane protein |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9931286 | ACCEPT | Summary: Correct core ER-membrane localization (Reactome, CD274/PD-L1 N-linked glycosylation). Redundant but correct. Supporting Evidence: file:human/STT3B/STT3B-uniprot.txt Endoplasmic reticulum membrane; Multi-pass membrane protein |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | KEEP AS NON CORE | Summary: Correct but uninformative high-level location, from a high-throughput membrane-proteome dataset. The specific compartment is the ER membrane (GO:0005789). Retained as non-core. |
| GO:0004579 dolichyl-diphosphooligosaccharide-protein glycotransferase activity | IMP PMID:19167329 Cotranslational and posttranslational N-glycosylation of pol... | ACCEPT | Summary: Core catalytic activity, demonstrated by isoform-specific siRNA knockdown causing hypoglycosylation of STT3B-dependent sites. Supporting Evidence: PMID:19167329 we show that the OST isoforms cooperate and act sequentially to mediate protein N-glycosylation |
| GO:0004579 dolichyl-diphosphooligosaccharide-protein glycotransferase activity | IMP PMID:22607976 STT3B-dependent posttranslational N-glycosylation as a surve... | ACCEPT | Summary: Core catalytic activity, supported by STT3B-dependent post-translational glycosylation of TTR in the surveillance study. Supporting Evidence: PMID:22607976 triggers STT3B-dependent posttranslational N-glycosylation |
| GO:0006487 protein N-linked glycosylation | IMP PMID:19167329 Cotranslational and posttranslational N-glycosylation of pol... | ACCEPT | Summary: Core biological process, demonstrated by isoform-specific knockdown hypoglycosylation phenotypes. Supporting Evidence: PMID:19167329 we show that the OST isoforms cooperate and act sequentially to mediate protein N-glycosylation |
| GO:0006487 protein N-linked glycosylation | IMP PMID:22607976 STT3B-dependent posttranslational N-glycosylation as a surve... | ACCEPT | Summary: Core biological process; STT3B-dependent N-glycosylation of cryptic sequons in unfolded secretory proteins. Supporting Evidence: PMID:22607976 triggers STT3B-dependent posttranslational N-glycosylation |
| GO:0006516 glycoprotein catabolic process | IMP PMID:22607976 STT3B-dependent posttranslational N-glycosylation as a surve... | KEEP AS NON CORE | Summary: Supported by the TTR study: STT3B-dependent glycosylation of unfolded substrates routes them to N-glycan-dependent ERAD/degradation. STT3B contributes indirectly (glycan-tagging), so retained as non-core rather than a core catabolic function. Supporting Evidence: PMID:22607976 this modification provides an alternative pathway for degradation, which is EDEM3-mediated N-glycan-dependent ERAD |
| GO:0006986 response to unfolded protein | IMP PMID:19167329 Cotranslational and posttranslational N-glycosylation of pol... | KEEP AS NON CORE | Summary: STT3B participates in ER protein-homeostasis surveillance of unfolded proteins, but in Ruiz-Canada et al. the unfolded-protein-response induction is specifically caused by loss of STT3A, not STT3B. Kept as non-core; this is a peripheral, indirect involvement rather than a core STT3B function. Supporting Evidence: PMID:19167329 Depletion of STT3A, but not STT3B, causes an induction of the unfolded protein response (UPR) pathway |
| GO:0006986 response to unfolded protein | IMP PMID:22607976 STT3B-dependent posttranslational N-glycosylation as a surve... | KEEP AS NON CORE | Summary: Supported by STT3B-dependent recognition/glycosylation of cryptic sequons exposed in unfolded (e.g. TTR) proteins as part of the ER surveillance system. Peripheral/indirect; retained as non-core. Supporting Evidence: PMID:22607976 prolonged TTR unfolding induces externalization of cryptic N-glycosylation site |
| GO:0008250 oligosaccharyltransferase complex | TAS PMID:19167329 Cotranslational and posttranslational N-glycosylation of pol... | ACCEPT | Summary: Core complex membership (STT3B as OST catalytic subunit), asserted from the literature. The most specific term is GO:0160227. Supporting Evidence: PMID:19167329 STT3 proteins are the active site subunits of the eukaryotic OST |
| GO:0008250 oligosaccharyltransferase complex | TAS PMID:22607976 STT3B-dependent posttranslational N-glycosylation as a surve... | ACCEPT | Summary: Core complex membership asserted from the literature. Redundant with other OST-complex annotations. Supporting Evidence: file:human/STT3B/STT3B-uniprot.txt Component of the oligosaccharyltransferase (OST) complex |
| GO:0036503 ERAD pathway | IMP PMID:22607976 STT3B-dependent posttranslational N-glycosylation as a surve... | KEEP AS NON CORE | Summary: STT3B-dependent post-translational glycosylation of unfolded secretory proteins targets them for N-glycan-dependent ERAD. STT3B contributes to this pathway indirectly (its glycan modification is the recognition signal), so retained as non-core; the core molecular activity remains N-glycosyl transfer. Supporting Evidence: PMID:22607976 this modification provides an alternative pathway for degradation, which is EDEM3-mediated N-glycan-dependent ERAD |
| GO:0043687 post-translational protein modification | IMP PMID:19167329 Cotranslational and posttranslational N-glycosylation of pol... | KEEP AS NON CORE | Summary: High-level parent term; STT3B's specific post-translational role is GO:0180057. Retained as non-core. |
| GO:0043687 post-translational protein modification | IMP PMID:22607976 STT3B-dependent posttranslational N-glycosylation as a surve... | KEEP AS NON CORE | Summary: High-level parent term; the specific STT3B post-translational activity is GO:0180057. Retained as non-core. |
| GO:0006487 protein N-linked glycosylation | ISS GO_REF:0000024 | ACCEPT | Summary: Core biological process transferred by sequence similarity from an ortholog. Consistent with the experimental annotations. Supporting Evidence: file:human/STT3B/STT3B-uniprot.txt the first step in protein N-glycosylation |
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