OSTC (DC2) is a small (149 aa) multi-pass endoplasmic reticulum membrane protein that is a non-catalytic accessory subunit of the oligosaccharyltransferase (OST) complex. It is a defining, complex-specific subunit of the STT3A-containing OST-A complex, which carries out co-translational N-linked glycosylation, the en bloc transfer of the Glc3Man9GlcNAc2 glycan from dolichol-pyrophosphate onto asparagine residues within Asn-X-Ser/Thr sequons of nascent polypeptides in the ER. OSTC does not itself possess glycotransferase activity (the catalytic subunit is STT3A); instead it acts as an adapter/anchor that tethers the OST-A complex to the SEC61 protein-conducting channel of the ER translocon, positioning the catalytic machinery adjacent to emerging nascent chains and thereby supporting efficient co-translational glycosylation. Loss of OSTC produces a co-translational hypoglycosylation phenotype resembling loss of STT3A itself, while STT3A complexes lacking OSTC remain enzymatically active but fail to form stable associations with the SEC61 complex. OSTC has been resolved by cryo-EM as a component of human OST-A and of the SEC61-OST-A-TRAP translocon.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006487 protein N-linked glycosylation | IBA GO_REF:0000033 | ACCEPT | Summary: OSTC is a subunit of the OST-A complex that performs co-translational N-linked glycosylation; this is a correct core biological process. The phylogenetic (IBA) call agrees with direct experimental evidence (PMID:28860277). Supporting Evidence: file:human/OSTC/OSTC-uniprot.txt to an asparagine residue within an Asn-X-Ser/Thr PMID:28860277 loss of DC2 causes a defect in co-translational N-glycosylation of proteins that |
| GO:0030674 protein-macromolecule adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Captures OSTC's subunit-specific molecular function as an adapter/anchor that tethers the OST-A complex to the SEC61 translocon. This is the informative OSTC-specific MF (distinct from the complex-level catalytic activity) and is supported experimentally by PMID:28860277. Supporting Evidence: file:human/OSTC/OSTC-uniprot.txt acts as an adapter that PMID:28860277 do not form stable complexes with the Sec61 complex |
| GO:0008250 oligosaccharyltransferase complex | IBA GO_REF:0000033 | ACCEPT | Summary: OSTC is a bona fide subunit of the oligosaccharyltransferase complex. Correct core cellular component; the IBA agrees with direct proteomic and structural evidence. Supporting Evidence: PMID:28860277 DC2 (OSTC gene) and KCP2, two small membrane proteins, were initially detected as novel OST subunits in translocation channel |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | ACCEPT | Summary: OSTC is an ER membrane protein; ER is the correct (if broad) subcellular location. Consistent with experimental localization (PMID:21768116). The more precise term is endoplasmic reticulum membrane (GO:0005789). Supporting Evidence: file:human/OSTC/OSTC-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum |
| GO:0008250 oligosaccharyltransferase complex | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based electronic assignment of OST complex membership. Correct core cellular component, redundant with the experimental IDA/IBA annotations to the same term. Supporting Evidence: file:human/OSTC/OSTC-uniprot.txt Component of STT3A-containing oligosaccharyl transferase (OST- |
| GO:0009101 glycoprotein biosynthetic process | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: A broad parent process of the more precise protein N-linked glycosylation (GO:0006487) that OSTC participates in. Not incorrect, but subsumed by the specific term; keep as non-core. Supporting Evidence: file:human/OSTC/OSTC-uniprot.txt the first step in |
| GO:0016020 membrane | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: Uninformative high-level cellular component. OSTC is a membrane protein, but this is entirely subsumed by the specific endoplasmic reticulum membrane (GO:0005789) annotation. Over-annotation. Supporting Evidence: file:human/OSTC/OSTC-uniprot.txt Multi-pass |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from a high-throughput binary interactome map (interactor EDA, Q92838). Uninformative and not an established functional partner of OSTC; per policy an experimental IPI is not removed but is marked as over-annotated. The biologically meaningful OSTC interactions (STT3A/OST-A subunits, SEC61) are captured by the adaptor MF and complex-membership terms. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from a binary interactome reference map (interactor TUSC5, A5PKU2). Uninformative and not an established functional partner of OSTC; marked as over-annotated rather than removed (experimental IPI). |
| GO:0005789 endoplasmic reticulum membrane | NAS PMID:31831667 Cryo-electron microscopy structures of human oligosaccharylt... | ACCEPT | Summary: OSTC is an integral ER membrane protein and a subunit of the ER-membrane OST-A complex. Correct core cellular location; ComplexPortal NAS agrees with the experimental IDA (PMID:21768116) and cryo-EM structures. Supporting Evidence: file:human/OSTC/OSTC-uniprot.txt Multi-pass |
| GO:0006487 protein N-linked glycosylation | NAS PMID:31831667 Cryo-electron microscopy structures of human oligosaccharylt... | ACCEPT | Summary: Correct core biological process; OSTC is a subunit of the OST-A complex that catalyzes co-translational N-linked glycosylation. Redundant with the experimental IDA (PMID:28860277). Supporting Evidence: PMID:31831667 catalyzes the transfer of a high-mannose glycan onto secretory proteins in the endoplasmic reticulum |
| GO:0008250 oligosaccharyltransferase complex | NAS PMID:31831667 Cryo-electron microscopy structures of human oligosaccharylt... | ACCEPT | Summary: OST complex membership, supported by the cryo-EM structures of human OST-A and OST-B in which DC2/OSTC is resolved as a component of OST-A. Correct core cellular component. Supporting Evidence: PMID:31831667 distinct OST subunits, DC2 in OST-A and |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:21768116 DC2 and keratinocyte-associated protein 2 (KCP2), subunits o... | ACCEPT | Summary: Direct experimental localization of DC2/OSTC to the ER membrane. Correct core cellular location. Supporting Evidence: file:human/OSTC/OSTC-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum |
| GO:0005783 endoplasmic reticulum | EXP PMID:21768116 DC2 and keratinocyte-associated protein 2 (KCP2), subunits o... | ACCEPT | Summary: Experimental localization to the ER (broader parent of ER membrane). Correct; the more precise annotation is endoplasmic reticulum membrane (GO:0005789). Supporting Evidence: file:human/OSTC/OSTC-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-446209 | ACCEPT | Summary: Reactome traceable annotation placing the OST-catalyzed N-glycan transfer reaction at the ER membrane. Correct core cellular location for OSTC as an OST-A subunit. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9694793 | ACCEPT | Summary: Reactome annotation of ER membrane location via a specific substrate reaction (SARS-CoV-2 spike protein N-glycosylation). Same correct location as the general OST reaction; kept as non-core to avoid inflating substrate-specific reactions into core. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9816276 | ACCEPT | Summary: Reactome ER membrane location via a specific substrate reaction (CDH1 N-glycosylation). Correct location; kept as non-core (substrate-specific reaction). |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9918962 | ACCEPT | Summary: Reactome ER membrane location via a specific viral substrate reaction (flavivirus E protein N-glycosylation). Correct location; kept as non-core (substrate-specific reaction). |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9918988 | ACCEPT | Summary: Reactome ER membrane location via a specific viral substrate reaction (flavivirus pre-M N-glycosylation). Correct location; kept as non-core (substrate-specific reaction). |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9919011 | ACCEPT | Summary: Reactome ER membrane location via a specific viral substrate reaction (pre-NS1 N-glycosylation). Correct location; kept as non-core (substrate-specific reaction). |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9931286 | ACCEPT | Summary: Reactome ER membrane location via a specific substrate reaction (PD-L1/CD274 N-glycosylation). Correct location; kept as non-core (substrate-specific reaction). |
| GO:0160226 oligosaccharyltransferase complex A | IDA PMID:31831667 Cryo-electron microscopy structures of human oligosaccharylt... | ACCEPT | Summary: Cryo-EM directly resolves DC2/OSTC as a defining, complex-specific subunit of the STT3A-containing OST-A complex. This is the most precise and correct core cellular component for OSTC. Supporting Evidence: PMID:31831667 distinct OST subunits, DC2 in OST-A and |
| GO:0160226 oligosaccharyltransferase complex A | IDA PMID:36697828 Visualization of translation and protein biogenesis at the E... | ACCEPT | Summary: Cryo-EM/ET of the ER translocon resolves OSTC within the SEC61-OST-A-TRAP translocon, confirming OST-A membership at the SEC61 interface. Correct core cellular component. Supporting Evidence: PMID:36697828 the luminal OSTC Ξ²-hairpin |
| GO:0160226 oligosaccharyltransferase complex A | IDA PMID:38670073 Positive selection CRISPR screens reveal a druggable pocket ... | ACCEPT | Summary: Cryo-EM of the STT3A-containing OST complex resolves OSTC as an OST-A subunit (PDB 8PN9). Correct core cellular component. Supporting Evidence: PMID:38670073 the oligosaccharyltransferase complex OST-A |
| GO:0006487 protein N-linked glycosylation | IDA PMID:28860277 DC2 and KCP2 mediate the interaction between the oligosaccha... | ACCEPT | Summary: Direct experimental evidence that loss of DC2/OSTC causes a co-translational N-glycosylation defect phenocopying loss of STT3A. Strongly supports involvement in protein N-linked glycosylation. Core biological process. Supporting Evidence: PMID:28860277 loss of DC2 causes a defect in co-translational N-glycosylation of proteins that |
| GO:0008250 oligosaccharyltransferase complex | IDA PMID:28860277 DC2 and KCP2 mediate the interaction between the oligosaccha... | ACCEPT | Summary: Direct experimental evidence that DC2/OSTC is an exclusive accessory subunit of the STT3A OST complex. Correct core cellular component. Supporting Evidence: PMID:28860277 DC2 (OSTC gene) and KCP2, two small membrane proteins, were initially detected as novel OST subunits in translocation channel |
| GO:0030674 protein-macromolecule adaptor activity | IDA PMID:28860277 DC2 and KCP2 mediate the interaction between the oligosaccha... | ACCEPT | Summary: Direct experimental evidence that DC2/OSTC (with KCP2) mediates the interaction between the OST-A complex and the SEC61 translocon; STT3A complexes lacking OSTC remain catalytically active but fail to associate stably with SEC61. This defines OSTC's subunit-specific adapter/anchor molecular function. Core MF. Supporting Evidence: PMID:28860277 STT3A complexes that lack DC2 or KCP2 are enzymatically active when assayed using a synthetic peptide acceptor but do not form stable complexes with the Sec61 complex file:human/OSTC/OSTC-uniprot.txt acts as an adapter that |
| GO:0004579 dolichyl-diphosphooligosaccharide-protein glycotransferase activity | IC PMID:15835887 Proteomic analysis of mammalian oligosaccharyltransferase re... | ACCEPT | Summary: Curator inference (from OST complex membership) that OSTC contributes to the complex-level glycotransferase activity. Correctly uses the contributes_to qualifier - OSTC is a non-catalytic subunit and does not itself enable this activity (the catalyst is STT3A), but it is part of the complex that carries it out. Core MF, modeled via contributes_to_molecular_function. Supporting Evidence: PMID:15835887 Our results identify two potential new subunits of mammalian OST file:human/OSTC/OSTC-uniprot.txt the first step in |
| GO:0008250 oligosaccharyltransferase complex | IDA PMID:15835887 Proteomic analysis of mammalian oligosaccharyltransferase re... | ACCEPT | Summary: Original proteomic identification of DC2/OSTC as a subunit of mammalian OST. Correct core cellular component. Supporting Evidence: PMID:15835887 identified a 17 kDa protein as DC2 which is weakly homologous to the C-terminal |
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Download this section (compressed HTML)Q: Is the adapter/anchor role of OSTC required only for stable OST-A-SEC61 association, or does OSTC also modulate substrate selection or scanning efficiency of the STT3A active site?
Q: Does the substrate-specific effect of OSTC/DC2 on APP processing and gamma-secretase (PMID:21768116) reflect a direct role of OSTC beyond bulk co-translational glycosylation?
Experiment: Structure-guided mutagenesis of the OSTC luminal loop and C-terminal motif to dissect OST-A assembly versus SEC61 anchoring, quantifying co-translational glycosylation efficiency of endogenous STT3A substrates.
Experiment: Proximity labeling or crosslinking-MS in OSTC-deficient versus wild-type cells to map the OST-A-translocon interactome and identify substrates most sensitive to loss of the OSTC anchor.
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