NUS1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0009101 glycoprotein biosynthetic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic (PAN-GO) annotation to glycoprotein biosynthetic process. This is the downstream biological purpose of the dolichol-phosphate made by the cis-PT complex (Dol-P is the glycan carrier for N-glycosylation). It is correct but non-core: NUS1's direct/proximal process is dolichol/dolichyl-diphosphate biosynthesis, which feeds glycoprotein biosynthesis. Supporting Evidence: file:human/NUS1/NUS1-uniprot.txt phosphate which is utilized as a sugar carrier in protein glycosylation
GO:0043048 dolichyl monophosphate biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic annotation to dolichyl monophosphate biosynthetic process. This is a core biological process of NUS1: the DHDDS-NUS1 complex is an essential component of the Dol-P biosynthetic machinery. Well supported by UniProt and by experimental studies. Supporting Evidence: file:human/NUS1/NUS1-uniprot.txt an essential component of the dolichol monophosphate
GO:0005789 endoplasmic reticulum membrane	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic annotation placing NUS1 activity at the ER membrane. This is the correct, core subcellular location: NUS1 is a multi-pass ER membrane protein and the cis-PT complex acts at the ER membrane. Supporting Evidence: file:human/NUS1/NUS1-uniprot.txt Endoplasmic reticulum membrane
GO:1904423 dehydrodolichyl diphosphate synthase complex	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic annotation of NUS1 as part of the dehydrodolichyl diphosphate synthase complex. This is the defining core cellular component for NUS1 (the DHDDS-NUS1 heterotetramer; ComplexPortal CPX-6701). Supporting Evidence: file:human/NUS1/NUS1-uniprot.txt The active dehydrodolichyl diphosphate synthase complex is a
GO:0004659 prenyltransferase activity	IEA GO_REF:0000117	MODIFY	Summary: ARBA electronic annotation to the broad parent term prenyltransferase activity. NUS1 does not independently have prenyltransferase activity; it contributes to the complex-level cis-PT activity via its RXG motif. The specific cis-PT activity term GO:0045547, used with contributes_to, captures this more accurately. Modify to the specific term. Proposed replacements: ditrans,polycis-polyprenyl diphosphate synthase [(2E,6E)-farnesyl diphosphate specific] activity Supporting Evidence: file:human/NUS1/NUS1-uniprot.txt Contains the RXG motif, which is important for substrate
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: UniProt subcellular-location keyword mapping to ER membrane. Correct core location; consistent with experimental evidence. Accept (redundant with experimental ER-membrane annotations but the gene's own correct location). Supporting Evidence: file:human/NUS1/NUS1-uniprot.txt Endoplasmic reticulum membrane
GO:0009101 glycoprotein biosynthetic process	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ARBA electronic annotation to glycoprotein biosynthetic process. As with the IBA version, this is the correct downstream purpose of the pathway but non-core relative to NUS1's direct dolichol biosynthetic role. Supporting Evidence: file:human/NUS1/NUS1-uniprot.txt phosphate which is utilized as a sugar carrier in protein glycosylation
GO:0016020 membrane	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: ARBA electronic annotation to the very general term membrane. NUS1 is indeed a membrane protein, but this is uninformative given the specific ER-membrane annotations already present. Over-annotated (too general). Supporting Evidence: file:human/NUS1/NUS1-uniprot.txt Multi-pass
GO:0016765 transferase activity, transferring alkyl or aryl (other than methyl) groups	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: InterPro2GO electronic annotation from the UPP-synthase-like domain (IPR001441/IPR036424) to a broad transferase parent. NUS1 does not independently enable this activity (it is the non-catalytic subunit); catalysis is a property of the DHDDS-NUS1 complex, captured specifically by GO:0045547 (contributes_to). Broad and, for the isolated NUS1 subunit, misleading as an enables annotation. Over-annotated. Supporting Evidence: file:human/NUS1/NUS1-uniprot.txt Contains the RXG motif, which is important for substrate
GO:0032383 regulation of intracellular cholesterol transport	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ARBA electronic annotation to regulation of intracellular cholesterol transport, reflecting NUS1's reported role in stabilizing NPC2 and regulating LDL-derived cholesterol trafficking. This is a genuine accessory function (see the experimental IGI from PMID:19723497) but is not the conserved core molecular/biological function of NUS1 and is partly downstream of the cis-PTase/glycosylation defect. Keep as non-core. Supporting Evidence: file:human/NUS1/NUS1-uniprot.txt Regulates the glycosylation and stability of nascent
GO:0043048 dolichyl monophosphate biosynthetic process	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO electronic annotation (Nus1/NgBR family, IPR038887) to dolichyl monophosphate biosynthetic process. This is a core process for NUS1 and is consistent with experimental and phylogenetic evidence. Supporting Evidence: file:human/NUS1/NUS1-uniprot.txt an essential component of the dolichol monophosphate
GO:0045547 ditrans,polycis-polyprenyl diphosphate synthase [(2E,6E)-farnesyl diphosphate specific] activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation (RHEA/EC 2.5.1.87 mapping) to the specific cis-PT activity. This is the correct catalytic reaction of the complex. For NUS1 as an isolated subunit the biologically precise relation is contributes_to rather than enables, since NUS1 lacks activity on its own; this is modeled in core_functions via contributes_to. The term itself is correct. Accept. Supporting Evidence: file:human/NUS1/NUS1-uniprot.txt Both subunits
GO:1904423 dehydrodolichyl diphosphate synthase complex	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO electronic annotation (Nus1/NgBR family) placing NUS1 in the dehydrodolichyl diphosphate synthase complex. Correct core complex membership. Supporting Evidence: file:human/NUS1/NUS1-uniprot.txt The active dehydrodolichyl diphosphate synthase complex is a
GO:0005515 protein binding	IPI PMID:21572394 Nogo-B receptor is necessary for cellular dolichol biosynthe...	MARK AS OVER ANNOTATED	Summary: IPI protein-binding annotation from an IntAct interaction with UniProtKB:Q9H7T3 (C10orf95). Bare protein binding is uninformative and does not describe NUS1's molecular function. Per policy, retain but mark as over-annotated rather than remove.
GO:0005515 protein binding	IPI PMID:32817466 Structural elucidation of the cis-prenyltransferase NgBR/DHD...	MARK AS OVER ANNOTATED	Summary: IPI protein-binding annotation from an IntAct interaction with UniProtKB:Q86SQ9 (DHDDS). DHDDS is the obligate catalytic partner of NUS1, so this interaction is biologically central, but bare "protein binding" is uninformative; the specific and informative capture is complex membership (GO:1904423, separately annotated) and the contributes_to cis-PT activity. Retain but mark as over-annotated per policy.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: IPI protein-binding annotation from the BioPlex (Huttlin et al. 2021) high-throughput AP-MS interactome, again capturing the DHDDS interaction (UniProtKB:Q86SQ9). Bare protein binding is uninformative. Retain but mark as over-annotated per policy.
GO:0005789 endoplasmic reticulum membrane	NAS PMID:32817466 Structural elucidation of the cis-prenyltransferase NgBR/DHD...	ACCEPT	Summary: ComplexPortal NAS annotation locating NUS1 at the ER membrane. Correct core location, consistent with experimental and structural evidence. Supporting Evidence: file:human/NUS1/NUS1-uniprot.txt Endoplasmic reticulum membrane
GO:0006489 dolichyl diphosphate biosynthetic process	IDA PMID:32817466 Structural elucidation of the cis-prenyltransferase NgBR/DHD...	ACCEPT	Summary: ComplexPortal IDA annotation to dolichyl diphosphate (dehydrodolichyl diphosphate) biosynthetic process, the direct product of the cis-PT reaction. This is the core biological process of the DHDDS-NUS1 complex and is directly supported by the structural/biochemical characterization of the NgBR/DHDDS complex. Supporting Evidence: file:human/NUS1/NUS1-uniprot.txt produce dehydrodolichyl diphosphate (Dedol-PP), a precursor of dolichol
GO:1904423 dehydrodolichyl diphosphate synthase complex	IPI PMID:32817466 Structural elucidation of the cis-prenyltransferase NgBR/DHD...	ACCEPT	Summary: ComplexPortal IPI annotation of NUS1 as part of the dehydrodolichyl diphosphate synthase complex, supported by the crystal structure of the NgBR/DHDDS heterodimer. Core complex membership. Supporting Evidence: file:human/NUS1/NUS1-uniprot.txt The active dehydrodolichyl diphosphate synthase complex is a
GO:0038084 vascular endothelial growth factor signaling pathway	IMP PMID:28602162 Endothelial miR-26a regulates VEGF-Nogo-B receptor-mediated ...	KEEP AS NON CORE	Summary: IMP annotation (BHF-UCL) to VEGF signaling from a study showing miR-26a regulates VEGF-NgBR-mediated angiogenesis, with NgBR knockdown reducing VEGF-induced eNOS phosphorylation and EC migration. This is a tissue-specific (endothelial) accessory signaling role, distinct from NUS1's conserved cis-PT/dolichol function, reflecting the historical "Nogo-B receptor" identity of the protein. Biologically supported but non-core; keep as non-core. Supporting Evidence: PMID:28602162 NgBR is necessary for VEGF-induced angiogenesis in ECs
GO:0090050 positive regulation of cell migration involved in sprouting angiogenesis	IMP PMID:28602162 Endothelial miR-26a regulates VEGF-Nogo-B receptor-mediated ...	KEEP AS NON CORE	Summary: IMP annotation (BHF-UCL) reflecting that NgBR knockdown abrogates VEGF-induced endothelial cell migration. A tissue-specific angiogenesis role tied to the Nogo-B-receptor function, not the conserved molecular function. Keep as non-core. Supporting Evidence: PMID:28602162 VEGF significantly induced HUVEC migration, an effect that was completely abrogated when NgBR was knocked down
GO:1903589 positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis	IMP PMID:28602162 Endothelial miR-26a regulates VEGF-Nogo-B receptor-mediated ...	KEEP AS NON CORE	Summary: IMP annotation (BHF-UCL) to positive regulation of endothelial cell proliferation in sprouting angiogenesis, from the VEGF-NgBR angiogenesis study. Same tissue-specific accessory angiogenic role as the other PMID:28602162 annotations; non-core. Supporting Evidence: PMID:28602162 the overexpression of miR-26a significantly reduced VEGF-induced HUVEC proliferation, migration, and tube formation
GO:0005789 endoplasmic reticulum membrane	EXP PMID:21572394 Nogo-B receptor is necessary for cellular dolichol biosynthe...	ACCEPT	Summary: Experimental (EXP) annotation locating NUS1 at the ER membrane, from the study establishing NgBR as a component of the Dol-P biosynthetic machinery. Correct core location. Supporting Evidence: file:human/NUS1/NUS1-uniprot.txt Endoplasmic reticulum membrane
GO:0045547 ditrans,polycis-polyprenyl diphosphate synthase [(2E,6E)-farnesyl diphosphate specific] activity	EXP PMID:25066056 Mutation of Nogo-B receptor, a subunit of cis-prenyltransfer...	ACCEPT	Summary: Experimental annotation to the specific cis-PT activity, from Park et al. 2014 showing NgBR is a subunit required for cis-PTase activity and dolichol synthesis in yeast, mice and man. This is the core catalytic activity of the complex. For NUS1 as a subunit the biologically precise relation is contributes_to (NUS1 does not catalyze alone; DHDDS carries the catalytic residues), as modeled in core_functions. Accept the term. Supporting Evidence: PMID:25066056 Nogo-B receptor (NgBR) is a subunit required for dolichol synthesis in yeast, mice, and man
GO:0045547 ditrans,polycis-polyprenyl diphosphate synthase [(2E,6E)-farnesyl diphosphate specific] activity	EXP PMID:32817466 Structural elucidation of the cis-prenyltransferase NgBR/DHD...	ACCEPT	Summary: Experimental annotation to the specific cis-PT activity, from the structural study of the NgBR/DHDDS complex, which shows NgBR participates in the enzyme's active site through its C-terminal RXG motif. Core catalytic activity; modeled as contributes_to in core_functions. Supporting Evidence: PMID:32817466 participates in the enzyme's active site through its C-terminal -RXG- motif
GO:0006489 dolichyl diphosphate biosynthetic process	IDA PMID:28842490 A conserved C-terminal RXG motif in the NgBR subunit of cis-...	ACCEPT	Summary: IDA annotation to dolichyl (dehydrodolichyl) diphosphate biosynthetic process, from the study establishing the first purification system for heteromeric cis-PT and demonstrating both NgBR and hCIT function in catalysis and substrate binding. Core biological process. Supporting Evidence: PMID:28842490 both NgBR and hCIT subunits function in catalysis and substrate binding
GO:0045547 ditrans,polycis-polyprenyl diphosphate synthase [(2E,6E)-farnesyl diphosphate specific] activity	IDA PMID:28842490 A conserved C-terminal RXG motif in the NgBR subunit of cis-...	ACCEPT	Summary: IDA annotation to the specific cis-PT activity from the reconstituted, purified heteromeric enzyme; the C-terminal RXG motif of NgBR is essential for enzyme activity. Core catalytic activity; modeled as contributes_to in core_functions given NUS1 is the non-catalytic subunit. Supporting Evidence: PMID:28842490 a critical RXG sequence in the C-terminal tail of NgBR that is conserved and essential for enzyme activity
GO:1904423 dehydrodolichyl diphosphate synthase complex	IDA PMID:28842490 A conserved C-terminal RXG motif in the NgBR subunit of cis-...	ACCEPT	Summary: IDA annotation of NUS1 as part of the dehydrodolichyl diphosphate synthase complex, from the purification of the heteromeric NgBR/hCIT enzyme. Core complex membership. Supporting Evidence: PMID:28842490 eukaryotic cis-PT is composed of the NgBR and hCIT subunits
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-4419978	ACCEPT	Summary: Reactome TAS annotation locating the DHDDS:NUS1 elongation reaction at the ER membrane. Correct core location. Supporting Evidence: Reactome:R-HSA-4419978 The ER membrane-associated enzyme dehydrodolichyl diphosphate synthase
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-4755545	ACCEPT	Summary: Reactome TAS annotation (defective-DHDDS reaction context) locating the enzyme at the ER membrane. Correct core location. Supporting Evidence: Reactome:R-HSA-4755545 The ER membrane-associated enzyme dehydrodolichyl diphosphate synthase
GO:0004659 prenyltransferase activity	IDA PMID:25066056 Mutation of Nogo-B receptor, a subunit of cis-prenyltransfer...	MODIFY	Summary: IDA annotation with the contributes_to qualifier to prenyltransferase activity. This correctly captures that NUS1 contributes to, but does not independently possess, the cis-PT catalytic activity of the complex. The term is broad; the more specific cis-PT activity (GO:0045547) is preferable and is used with contributes_to in core_functions. Modify to the specific term. Proposed replacements: ditrans,polycis-polyprenyl diphosphate synthase [(2E,6E)-farnesyl diphosphate specific] activity Supporting Evidence: PMID:25066056 Nogo-B receptor (NgBR) is a subunit required for dolichol synthesis in yeast, mice, and man
GO:0032383 regulation of intracellular cholesterol transport	IGI PMID:19723497 Nogo-B receptor stabilizes Niemann-Pick type C2 protein and ...	KEEP AS NON CORE	Summary: IGI annotation (MGI, with NPC2 UniProtKB:P61916) to regulation of intracellular cholesterol transport. Experimentally supported: NgBR binds and stabilizes NPC2, and loss of NgBR causes free-cholesterol accumulation and defective sterol sensing (Harrison et al. 2009). This is a genuine accessory function of NUS1 but not its conserved core molecular/biological function (and is partly downstream of reduced cis-PTase activity affecting NPC2 glycosylation). Keep as non-core. Do not remove (experimental). Supporting Evidence: PMID:19723497 NgBR enhances NPC2 protein stability
GO:0043048 dolichyl monophosphate biosynthetic process	IMP PMID:25066056 Mutation of Nogo-B receptor, a subunit of cis-prenyltransfer...	ACCEPT	Summary: IMP annotation to dolichyl monophosphate biosynthetic process, from the demonstration that NgBR is required for dolichol synthesis (loss-of-function R290H reduces dolichol levels and cis-PTase activity). Core biological process for NUS1. Supporting Evidence: PMID:25066056 Nogo-B receptor (NgBR) is a subunit required for dolichol synthesis in yeast, mice, and man
GO:0005789 endoplasmic reticulum membrane	IDA PMID:19723497 Nogo-B receptor stabilizes Niemann-Pick type C2 protein and ...	ACCEPT	Summary: IDA annotation locating NgBR at the ER membrane (Harrison et al. 2009 showed NgBR localizes primarily to the ER and colocalizes with ER markers PDI and calnexin). Correct core location. Supporting Evidence: PMID:19723497 NgBR localizes primarily to the endoplasmic reticulum (ER)

Gene Description

Existing Annotations Review

Core Functions

References

📚 Additional Documentation

Notes

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