DAD1 (defender against cell death 1) is a small (113 aa), hydrophobic, multi-pass endoplasmic reticulum (ER) membrane protein that is a non-catalytic core subunit of the oligosaccharyltransferase (OST) complex. OST catalyzes the first committed step of protein N-linked glycosylation: the en-bloc transfer of the pre-assembled Glc3Man9GlcNAc2 oligosaccharide from the dolichyl-pyrophosphate lipid carrier onto asparagine residues within Asn-X-Ser/Thr sequons of nascent polypeptides. DAD1 is a common core subunit shared by both mammalian OST forms — the cotranslational STT3A complex (OST-A) and the post-translocational STT3B complex (OST-B) — and is required for the assembly and stability of both. It has no independent catalytic activity; rather, it contributes structurally to the integrity of the holo-enzyme, and its loss destabilizes OST and abolishes N-glycosylation. Because N-glycosylation is essential for the folding, quality control, and surface delivery of secretory and membrane proteins, depletion of DAD1 produces global hypoglycosylation and, historically, was first identified through the apoptotic phenotype that follows loss of the protein, which is the origin of its "defender against cell death" name.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006487 protein N-linked glycosylation | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) propagation of the core biological process. DAD1 is a subunit of the OST complex that performs the first step of N-linked glycosylation; this is the correct core BP for the gene. Accept. Supporting Evidence: file:human/DAD1/DAD1-uniprot.txt Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan |
| GO:0008250 oligosaccharyltransferase complex | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) propagation of OST complex membership. DAD1 is a conserved core subunit of the OST complex across eukaryotes; this is the correct core cellular component. Accept. Supporting Evidence: file:human/DAD1/DAD1-uniprot.txt Component of the oligosaccharyltransferase (OST) complex |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from the UniProt Subcellular Location mapping. This is the correct, specific subcellular location for DAD1 (a multi-pass ER membrane protein) and is the gene's core localization. A redundant-but-correct core CC; accept. Supporting Evidence: file:human/DAD1/DAD1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass |
| GO:0008250 oligosaccharyltransferase complex | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO (IEA) mapping of the DAD/Ost2 domain (IPR003038) to the OST complex. Correct core CC, redundant with experimental annotations; accept. Supporting Evidence: file:human/DAD1/DAD1-uniprot.txt Component of the oligosaccharyltransferase (OST) complex |
| GO:0016020 membrane | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro2GO (IEA) mapping to the generic parent term "membrane". This is subsumed by the specific and correct "endoplasmic reticulum membrane" annotation and adds no information. Not wrong, but over-general; mark as over-annotated. Supporting Evidence: file:human/DAD1/DAD1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass |
| GO:0005789 endoplasmic reticulum membrane | NAS PMID:31831667 Cryo-electron microscopy structures of human oligosaccharylt... | ACCEPT | Summary: NAS (ComplexPortal) localization to the ER membrane, consistent with the cryo-EM structures of human OST-A and OST-B and with the UniProt subcellular location. Correct core CC; accept. Supporting Evidence: file:human/DAD1/DAD1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass |
| GO:0006487 protein N-linked glycosylation | IDA PMID:31831667 Cryo-electron microscopy structures of human oligosaccharylt... | ACCEPT | Summary: IDA (ComplexPortal) for the OST complex, of which DAD1 is a subunit, performing N-linked glycosylation; supported by the cryo-EM structures of human OST-A and OST-B. This is the core biological process for DAD1; accept. 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 | NAS PMID:31831667 Cryo-electron microscopy structures of human oligosaccharylt... | ACCEPT | Summary: NAS (ComplexPortal) duplicate of the core N-linked glycosylation BP from the same OST structural paper. Correct but redundant with the IDA annotation above; accept. Supporting Evidence: PMID:31831667 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: IPI (ComplexPortal) placing DAD1 in the OST complex, based on the cryo-EM structures resolving DAD1 as a subunit of OST-A and OST-B. Correct core CC; accept. Supporting Evidence: file:human/DAD1/DAD1-uniprot.txt Component of the oligosaccharyltransferase (OST) complex |
| GO:0008250 oligosaccharyltransferase complex | NAS PMID:31831667 Cryo-electron microscopy structures of human oligosaccharylt... | ACCEPT | Summary: NAS (ComplexPortal) duplicate of OST complex membership from the same structural paper. Correct but redundant with the IPI/IDA/IBA annotations; accept. Supporting Evidence: file:human/DAD1/DAD1-uniprot.txt Component of the oligosaccharyltransferase (OST) complex |
| GO:0160226 oligosaccharyltransferase complex A | IDA PMID:31831667 Cryo-electron microscopy structures of human oligosaccharylt... | ACCEPT | Summary: IDA placing DAD1 in the specific STT3A-containing OST-A complex, based on the cryo-EM structure of human OST-A (PDB 6S7O/6S7T, DAD1 = chain D). DAD1 is a shared core subunit present in both OST forms; this specific-form membership is correct and more informative than the generic GO:0008250. Accept. Supporting Evidence: file:human/DAD1/DAD1-uniprot.txt OST exists in two different complex forms which contain common core |
| GO:0160226 oligosaccharyltransferase complex A | IDA PMID:36697828 Visualization of translation and protein biogenesis at the E... | ACCEPT | Summary: IDA placing DAD1 in OST-A, from the cryo-ET study of the ribosome–translocon that resolved the SEC61-OSTA-TRAP translocon (PDB 8B6L includes DAD1 chain M per UniProt). The paper does not name DAD1 in the abstract/full text but structurally resolves the OST-A complex of which DAD1 is a subunit. Correct specific-form CC; accept. Supporting Evidence: PMID:36697828 OSTA, which is responsible for co-translational N-glycosylation of substrates, is observed in at least 50% of translocon particles in mammalian cells |
| GO:0160226 oligosaccharyltransferase complex A | IDA PMID:38670073 Positive selection CRISPR screens reveal a druggable pocket ... | ACCEPT | Summary: IDA placing DAD1 in OST-A, from the CRISPR/cryo-EM study of the STT3A-containing OST (PDB 8PN9, DAD1 = chain D per UniProt). Correct specific-form CC; accept. Supporting Evidence: PMID:38670073 the LPS receptor Toll-like receptor 4 (TLR4) is specifically dependent on the oligosaccharyltransferase complex OST-A for N-glycosylation |
| GO:0160227 oligosaccharyltransferase complex B | IDA PMID:31831667 Cryo-electron microscopy structures of human oligosaccharylt... | ACCEPT | Summary: IDA placing DAD1 in the specific STT3B-containing OST-B complex, based on the cryo-EM structure of human OST-B. DAD1 is a shared core subunit of both OST forms, so membership in OST-B is correct and informative alongside the OST-A annotation. Accept. Supporting Evidence: file:human/DAD1/DAD1-uniprot.txt OST exists in two different complex forms which contain common core |
| GO:0008250 oligosaccharyltransferase complex | IDA PMID:22467853 The oligosaccharyltransferase subunits OST48, DAD1 and KCP2 ... | ACCEPT | Summary: IDA (ARUK-UCL) for OST complex membership from the DAD1 knockdown study, which analyzed the stability and composition of STT3A- and STT3B-containing OST complexes. Correct core CC; accept. Supporting Evidence: PMID:22467853 DAD1 are required for the assembly of both STT3A- and STT3B-containing OST complexes |
| GO:0006487 protein N-linked glycosylation | IMP PMID:22467853 The oligosaccharyltransferase subunits OST48, DAD1 and KCP2 ... | ACCEPT | Summary: IMP: siRNA knockdown of DAD1 destabilizes OST and produces a pronounced hypoglycosylation phenotype, demonstrating a functional requirement of DAD1 for N-linked glycosylation. This is the core BP for the gene; accept. Supporting Evidence: PMID:22467853 underlie their pronounced hypoglycosylation phenotypes. Thus, OST48 and DAD1 are global modulators of OST stability and hence N-glycosylation |
| GO:0031647 regulation of protein stability | IMP PMID:22467853 The oligosaccharyltransferase subunits OST48, DAD1 and KCP2 ... | KEEP AS NON CORE | Summary: IMP: DAD1 depletion destabilizes both STT3A- and STT3B-containing OST complexes. This annotation captures DAD1's role in maintaining the stability/integrity of the OST complex (i.e., the stability of OST subunit proteins), which is a real and well-supported aspect of DAD1 biology but is ancillary to (a mechanism underlying) its core N-glycosylation role rather than a distinct core process. Keep as non-core. Supporting Evidence: PMID:22467853 DAD1 are required for the assembly of both STT3A- and STT3B-containing OST complexes |
| GO:0008047 enzyme activator activity | IMP PMID:22467853 The oligosaccharyltransferase subunits OST48, DAD1 and KCP2 ... | MARK AS OVER ANNOTATED | Summary: IMP-based molecular function asserting that DAD1 activates the OST enzyme. DAD1 is a non-catalytic structural subunit that is required for OST assembly/stability and hence for maximal enzyme activity; it does not act as a classical enzyme activator (allosteric or covalent stimulator) that binds and switches on a separate enzyme. The better model is a non-catalytic subunit contributing to the OST catalytic activity via complex integrity. This experimental annotation is not removed, but its MF is an over-interpretation; mark as over-annotated (the core MF contribution is modeled in core_functions via contributes_to_molecular_function). Supporting Evidence: PMID:22467853 global modulators of OST stability and hence N-glycosylation |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: HDA from a large-scale NK-cell membrane proteome; DAD1 was one of 1843 MS-identified proteins. Only supports the generic "membrane" term, which is subsumed by the specific and correct ER membrane annotation. Low-information; mark as over-annotated. Supporting Evidence: PMID:19946888 Mass spectrometric analysis identified 1843 proteins with high confidence scores |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-446209 | ACCEPT | Summary: TAS (Reactome) ER membrane localization from the "Transfer of N-glycan to the protein" reaction, in which DAD1 is listed as a component of the OST complex. Correct core CC; accept. Supporting Evidence: Reactome:R-HSA-446209 This reaction is catalyzed by the oligosaccharyltransferase (OST) complex, comprising at least seven proteins; DAD1 |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9694793 | ACCEPT | Summary: TAS (Reactome) ER membrane localization from an OST-catalyzed N-glycosylation reaction (viral spike protein). Correct core CC, redundant with the other ER membrane annotations; accept. Supporting Evidence: file:human/DAD1/DAD1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9816276 | ACCEPT | Summary: TAS (Reactome) ER membrane localization from the CDH1 (E-cadherin) N-glycosylation reaction catalyzed by OST. Correct core CC, redundant; accept. Supporting Evidence: file:human/DAD1/DAD1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9918962 | ACCEPT | Summary: TAS (Reactome) ER membrane localization from an OST-catalyzed N-glycosylation reaction. Correct core CC, redundant; accept. Supporting Evidence: file:human/DAD1/DAD1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9918988 | ACCEPT | Summary: TAS (Reactome) ER membrane localization from an OST-catalyzed N-glycosylation reaction. Correct core CC, redundant; accept. Supporting Evidence: file:human/DAD1/DAD1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9919011 | ACCEPT | Summary: TAS (Reactome) ER membrane localization from an OST-catalyzed N-glycosylation reaction. Correct core CC, redundant; accept. Supporting Evidence: file:human/DAD1/DAD1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9931286 | ACCEPT | Summary: TAS (Reactome) ER membrane localization from the PD-L1 (CD274) N-glycosylation reaction catalyzed by the OST complex in the ER lumen. Correct core CC, redundant; accept. Supporting Evidence: file:human/DAD1/DAD1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass |
| GO:0008250 oligosaccharyltransferase complex | ISS GO_REF:0000024 | ACCEPT | Summary: ISS (curator transfer from ortholog UniProtKB:E2R4X3) of OST complex membership. Correct core CC, redundant with experimental annotations; accept. Supporting Evidence: file:human/DAD1/DAD1-uniprot.txt Component of the oligosaccharyltransferase (OST) complex |
| GO:0009101 glycoprotein biosynthetic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation to the broad parent process "glycoprotein biosynthetic process". DAD1's role is specifically in protein N-linked glycosylation (GO:0006487), a descendant of this term, which is already annotated. This more general term is correct but subsumed; keep as non-core. Supporting Evidence: file:human/DAD1/DAD1-uniprot.txt the first step in protein N-glycosylation |
| GO:0043066 negative regulation of apoptotic process | TAS PMID:8413235 Molecular cloning of a human cDNA encoding a novel protein, ... | KEEP AS NON CORE | Summary: TAS from the original DAD1 cloning paper, where loss of DAD1 triggers apoptosis in the tsBN7 hamster mutant (hence "defender against cell death"). This anti-apoptotic phenotype is a downstream, indirect consequence of DAD1's essential OST / N-glycosylation role (loss of DAD1 destabilizes OST, abolishes N-glycosylation, and triggers apoptosis) rather than a distinct core molecular/biological function. Retain as non-core. Supporting Evidence: PMID:8413235 loss of the DAD1 protein triggers apoptosis |
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