Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Retention of subunits of the oligosaccharyltransferase complex in the endoplasmic reticulum.
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Ribophorin II (RII, RPN2) is one of three type I ER transmembrane proteins that, with DAD1, form the oligomeric complex carrying oligosaccharyltransferase activity.
"In this study, we have identified ER localization domains within the three type I transmembrane proteins, ribophorin I (RI), ribophorin II (RII), and OST48. Together with DAD1, these membrane proteins form an oligomeric complex that has oligosaccharyltransferase (OST) activity."
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RPN2 carries ER-retention information independently in its transmembrane and cytoplasmic domains, accounting for its steady-state ER-membrane residence.
"We have previously shown that ER retention information is independently contained within the transmembrane and the cytoplasmic domain of RII"
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The isolated lumenal domain of RPN2 is stabilized and retained in the ER when co-expressed with OST48, indicating direct RPN2-OST48 assembly within the OST complex.
"In the case of the Tac chimera containing only the luminal domain of RII, which by itself exits from the ER and is rapidly degraded, it is retained in the ER and becomes stabilized when coexpressed with OST48."
Proteomic analysis of mammalian oligosaccharyltransferase reveals multiple subcomplexes that contain Sec61, TRAP, and two potential new subunits.
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Ribophorin II is present in all mammalian OST subcomplexes isolated from actively translating ribosomes, establishing it as a constitutive OST subunit.
"All known mammalian OST subunits (STT3-A, ribophorin I, ribophorin II, OST48, and DAD1) were present in all complexes."
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The OST activity that RPN2 contributes to is the co-translational transfer of high-mannose sugars onto nascent polypeptides in the rough ER lumen.
"Oligosaccharyltransferase (OST) catalyzes the cotranslational transfer of high-mannose sugars to nascent polypeptides during N-linked glycosylation in the rough endoplasmic reticulum lumen."
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RPN2-containing OST complexes are heterogeneous and associate with Sec61 and, in the largest form, with the TRAP complex.
"Both remained stably associated with heterotrimeric Sec61alphabetagamma, while OSTC(III) also contained the tetrameric TRAP complex."
Defining the membrane proteome of NK cells.
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RPN2 was detected in a high-throughput membrane-proteome survey of the NK-like YTS cell line; the study assigns no function and only supports generic membrane association.
"Mass spectrometric analysis identified 1843 proteins with high confidence scores. On the basis of the presence of transmembrane regions or evidence of posttranslational modifications and prediction algorithms, approximately 40% of the identified proteins were predicted as plausible membrane proteins."
Host factors that interact with the pestivirus N-terminal protease, Npro, are components of the ribonucleoprotein complex.
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The RPN2 interaction reported here arises from a mass-spectrometry survey of host proteins bound to the pestivirus Npro protease, a viral-infection context that does not define an endogenous RPN2 molecular function.
"Here we used mass spectrometry to identify a new role for N(pro) through its interaction with over 55 associated proteins, mainly ribosomal proteins and ribonucleoproteins"
Armc5 deletion causes developmental defects and compromises T-cell immune responses.
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The RPN2-ARMC5 interaction derives from a yeast two-hybrid screen for ARMC5 partners; the study's functional conclusions concern ARMC5, not RPN2.
"Yeast 2-hybrid assays identify 16 ARMC5-binding partners."
Removal of RTF2 from Stalled Replisomes Promotes Maintenance of Genome Integrity.
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This study characterizes DDI1/DDI2 shuttle proteins in replication-fork restart; the RPN2-DDI2 interaction it reports is incidental to RPN2's ER glycosylation function.
"We further show that the proteasomal shuttle proteins DDI1 and DDI2 are required for RTF2 removal from stalled forks."
Cryo-electron microscopy structures of human oligosaccharyltransferase complexes OST-A and OST-B.
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Humans express two distinct OST complexes, the co-translational OST-A and the post-translocational OST-B, both resolved by cryo-EM; RPN2 (ribophorin-II) is a subunit of each.
"Mammals express two distinct OST complexes that act in a cotranslational (OST-A) or posttranslocational (OST-B) manner. Here, we present high-resolution cryo-electron microscopy structures of human OST-A and OST-B."
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OST-A and OST-B share an overall architecture and differ chiefly in the catalytic subunit (STT3A vs STT3B) and its complex-specific partner (DC2 vs MAGT1), while the ribophorins remain common core subunits.
"Although they have similar overall architectures, structural differences in the catalytic subunits STT3A and STT3B facilitate contacts to distinct OST subunits, DC2 in OST-A and MAGT1 in OST-B."
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The reaction catalyzed by the RPN2-containing complexes is transfer of a high-mannose glycan onto secretory proteins in the ER.
"Oligosaccharyltransferase (OST) catalyzes the transfer of a high-mannose glycan onto secretory proteins in the endoplasmic reticulum."
Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases.
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The RPN2-POMK interaction comes from a large-scale affinity-purification map of over 300 human kinases, a discovery-scale dataset that assigns no specific function to RPN2.
"Here, we present a comprehensive mass-spectrometry-based analysis of a human kinase interaction network covering more than 300 kinases."
Visualization of translation and protein biogenesis at the ER membrane.
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Cryo-electron tomography of native ER membranes resolves an atomic model of the most abundant translocon variant, comprising SEC61, TRAP and the RPN2-containing oligosaccharyltransferase complex A (OSTA).
"The near-complete atomic model of the most abundant ER translocon variant comprising the protein-conducting channel SEC61, TRAP and the oligosaccharyltransferase complex A (OSTA) reveals specific interactions of TRAP with other translocon components."
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The ribosome-translocon complex in which OST-A operates governs N-glycosylation of nascent proteins alongside their synthesis, translocation, membrane insertion and folding.
"It governs the synthesis, translocation, membrane insertion, N-glycosylation, folding and disulfide-bond formation of nascent proteins."
Positive selection CRISPR screens reveal a druggable pocket in an oligosaccharyltransferase required for inflammatory signaling to NF-κB.
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Genome-wide CRISPR screening identifies the RPN2-containing OST-A complex as specifically required for N-glycosylation and cell-surface delivery of TLR4, demonstrating substrate selectivity between the two OST complexes.
"we discovered that the LPS receptor Toll-like receptor 4 (TLR4) is specifically dependent on the oligosaccharyltransferase complex OST-A for N-glycosylation and cell-surface localization"
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Cryo-EM of the OST-A complex shows the inhibitor NGI-1 bound in the STT3A catalytic site trapping the dolichyl-PP-linked donor glycan, confirming that catalysis resides in STT3A rather than in accessory subunits such as RPN2.
"These variants, in conjunction with cryoelectron microscopy studies, revealed that NGI-1 binds the catalytic site of STT3A, where it traps a molecule of the donor substrate dolichyl-PP-GlcNAc2-Man9-Glc3, suggesting an uncompetitive inhibition mechanism."
Interleukin-2 induces N-glycosylation in T-cells: characterization of human lymphocyte oligosaccharyltransferase.
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Ribophorin II was identified by N-terminal sequencing among the four predominant proteins of an 85-fold purified human lymphocyte oligosaccharyltransferase preparation, giving direct biochemical evidence for RPN2 as an OST subunit.
"After solubilization and 85-fold purification from salt-washed microsomes, the enzyme preparation contained four predominant proteins. N-terminal sequence analysis identified the proteins as ribophorin I, ribophorin II (doublet), and a 50-kDa homologue of Wbp1, a yeast protein essential for N-glycosylation."
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The purified RPN2-containing enzyme accounts for the N-glycosylation activity of human lymphocytes, which rises about ten-fold upon mitogen activation.
"N-glycosylation activity increased 10-fold after mitogen activation of PBLs."
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The RPN2-containing oligosaccharyltransferase activity localizes predominantly to the microsomal (ER) fraction of lymphocytes.
"The enzyme mediating N-glycosylation in lymphocytes was localized predominantly but not entirely to a microsomal organelle by subcellular fractionation."
Transfer of N-glycan to the protein
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Reactome names RPN2 (ribophorin 2) as one of the subunits of the ER-membrane OST complex that transfers the 14-sugar lipid-linked oligosaccharide en bloc onto nascent protein, and notes that an RPN2 mutation causes a congenital disorder of glycosylation.
"This reaction is catalyzed by the oligosaccharyltransferase (OST) complex, comprising at least seven proteins; DAD1 (Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1), DDOST (OST48 in yeast), RPN1 (ribophorin 1), RPN2 (ribophorin 2), OST4, TUSC3 (N33), MAGT1 (magnesium transporter protein 1) and either STT3A or STT3B"
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The acceptor specificity of the RPN2-containing OST complex is the Asn-X-Thr/Ser sequon, and not all such sites are used in vivo.
"The signal for glycosylation is the consensus sequence Asn - X - Thr/Ser, where the first amino acid is always Asn, the second can be any amino acid except for Pro, and the third position may be Thr, Ser or Cys, with a preference for the first"
Spike protein gets N-glycosylated
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RPN2 is listed as an OST-complex participant in the ER N-glycosylation of the SARS-CoV-2 spike protein; this is a substrate-specific reaction record rather than evidence for a distinct RPN2 function.
"Glycosyltransferases in the endoplasmatic reticulum are responsible for the attachment of numerous high-mannose N-glycans on the SARS-CoV-2 spike protein."
CDH1 is N-glycosylated on asparagine residues in endoplasmic reticulum
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RPN2 participates as an OST subunit in ER N-glycosylation of E-cadherin, a substrate-level reaction record that supports the generic ER-membrane localization rather than a CDH1-specific RPN2 role.
"All four glycosylated asparagines in CDH1 conform with the glycosylation sequon Asn-X-Thr/Ser which is glycosylated in the endoplasmic reticulum (ER) through transfer of the preassembled, high-mannose oligosaccharide"
E is N-glycosylated
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RPN2 appears as an OST-complex participant in the ER N-glycosylation of the dengue virus E glycoprotein; a host-pathway reaction record, not evidence of a virus-specific RPN2 function.
"DENV-2 E protein is known to be N-glycosylated at Asn-67 and Asn-153 (Asn-347 and Asn-433 of the polyprotein, respectively), a process requiring, among others, the oligosaccharyl transferase activity of the host OST complex"
pre-M is N-glycosylated
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RPN2 appears as an OST-complex participant in ER N-glycosylation of the dengue virus prM protein; a substrate-level reaction record supporting only ER-membrane localization.
"Dengue virus pre-prM is N-glycosylated at Asn-7, Asn-31, Asn-52, and Asn-69 (Asn-121, Asn-145, Asn-166 and Asn-183 of the polyprotein), requiring, among others, the oligosaccharyl transferase activity of the OST complex"
Pre-NS1 folds and is N-glycosylated
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RPN2 appears as an OST-complex participant in the co-folding N-glycosylation of dengue virus NS1; a substrate-level record supporting ER-membrane localization only.
"Pre-NS1 protein, while being folded, is glycosylated at Asn-130 and Asn-207 (Asn-905 and Asn-982 in the polyprotein, respectively)."
CD274 N-linked glycosylation in ER
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RPN2 appears as an OST-complex participant in the ER N-glycosylation of PD-L1 (CD274); the catalytic role in the record is attributed to STT3A/STT3B, consistent with RPN2 being a non-catalytic subunit.
"PD-L1 is N-glycosylated at N192, N200 and N219 by the OST complex (STT3A and STT3A) in the ER lumen."