UGGT1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0003980 UDP-glucose:glycoprotein glucosyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for the core enzymatic function of UGGT1. This is the defining molecular function of UGGT1: it transfers glucose from UDP-glucose to Man9GlcNAc2 N-glycans on misfolded glycoproteins. This activity has been experimentally demonstrated in PMID:10694380 (27-fold increase in glucose transfer from UDP-glucose to denatured substrates in HUGT1-transfected cells) and confirmed by reglucosylation assays in PMID:40267907. The IBA annotation is phylogenetically well-supported and represents the core function. Reason: This is the core molecular function of UGGT1, well-established experimentally (PMID:10694380, PMID:40267907) and phylogenetically (IBA). UGGT1 is a glycosyltransferase family 24 member (CAZy GT24) that catalyzes the reglucosylation of N-glycans on misfolded glycoproteins as part of the ER quality control cycle. Supporting Evidence: PMID:10694380 Extracts from HUGT1-transfected cells displayed a 27-fold increase in the transfer of [(14)C]glucose from UDP-[(14)C]glucose to denatured substrates. PMID:40267907 UGGT1 encodes UDP-glucose:glycoprotein glucosyltransferase 1, an enzyme critical for maintaining quality control of N-linked glycosylation.
GO:0005783 endoplasmic reticulum	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for ER localization. UGGT1 contains an N-terminal signal peptide and a C-terminal REEL ER-retrieval motif (UniProt). Arnold et al. (PMID:10694380) confirmed ER localization experimentally. This IBA is consistent with the more specific IEA annotation to ER lumen (GO:0005788). While GO:0005788 (ER lumen) is more precise, GO:0005783 (endoplasmic reticulum) is acceptable as a broader parent term and is correctly inferred phylogenetically. Reason: UGGT1 is an established ER-resident protein. It contains the REEL ER retrieval signal (UniProt), and experimental localization was confirmed in PMID:10694380. The IBA annotation at this level is appropriate and consistent with more specific ER lumen and ERGIC annotations. Supporting Evidence: PMID:10694380 HUGT1 encodes a 1555 amino acid polypeptide that, upon cleavage of an N-terminal signal peptide, is predicted to produce a soluble 173 kDa protein with the ER retrieval signal REEL.
GO:0051082 unfolded protein binding	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: UGGT1 does interact with unfolded/misfolded glycoproteins, but this interaction represents substrate recognition for its glucosyltransferase enzymatic activity (GO:0003980), not an independent binding function. The N-terminal non-catalytic domain recognizes glycoproteins with minor folding defects (UniProt FUNCTION annotation, PMID:10694380), and this recognition is prerequisite to the catalytic reglucosylation step. This is analogous to how a kinase recognizes its protein substrates -- we would not annotate a kinase with "substrate protein binding" simply because it must bind substrates to phosphorylate them. The term GO:0051082 is now formally obsolete (go-ontology#30962). The IBA was propagated from experimental annotations on UGGT1 orthologs, but the underlying experimental evidence reflects the same substrate-recognition mechanism. Reason: UGGT1 binding to unfolded proteins is incidental to its core enzymatic function as a UDP-glucose:glycoprotein glucosyltransferase. The protein recognizes misfolded glycoproteins as substrates for reglucosylation, not as an independent binding/chaperone function. As described in PMID:10694380, UGGT1 "operates as a gatekeeper for quality control by preventing transport of improperly folded glycoproteins out of the ER" through its glucosyltransferase activity -- the substrate recognition is integral to and subsumed by the enzymatic activity annotation GO:0003980. Additionally, GO:0051082 is now formally obsolete per go-ontology#30962. Supporting Evidence: PMID:10694380 UDP-glucose:glycoprotein glucosyltransferase (UGT) is a soluble protein of the endoplasmic reticulum (ER) that operates as a gatekeeper for quality control by preventing transport of improperly folded glycoproteins out of the ER.
GO:0044322 endoplasmic reticulum quality control compartment	IEA GO_REF:0000108	ACCEPT	Summary: IEA annotation placing UGGT1 in the ER quality control compartment (ERQC). The ERQC is defined as "a subcompartment of the endoplasmic reticulum in which proteins with improper or incorrect folding accumulate." UGGT1 is a central enzyme in this compartment, acting as the folding sensor that reglucosylates misfolded glycoproteins for re-engagement with calnexin/calreticulin (PMID:10694380, PMID:40267907). The Reactome pathway R-HSA-901032 explicitly places UGGT1 in the ERQC. This is an appropriate and informative localization annotation. Reason: UGGT1 is a core component of the ERQC, functioning as the folding sensor that determines whether glycoproteins are retained for further folding attempts. Reactome R-HSA-901032 explicitly models UGGT1 in this compartment. The IEA annotation is well-supported by the known biology of UGGT1. Supporting Evidence: PMID:40267907 UGGT1 identifies and reglucosylates misfolded proteins, resulting in ER retention for re-binding to CNX/CRT to enable correct folding.
GO:0097359 UDP-glucosylation	IEA GO_REF:0000108	ACCEPT	Summary: IEA annotation for the biological process of UDP-glucosylation. GO:0097359 is defined as "the covalent attachment of a UDP-glucose residue to a substrate molecule." This accurately describes the process UGGT1 catalyzes: transferring glucose from UDP-glucose to Man9GlcNAc2 N-glycans on misfolded glycoproteins. The annotation is logically inferred from the MF annotation GO:0003980 and is correct. Reason: UDP-glucosylation is the direct process outcome of UGGT1's enzymatic activity. The annotation is correctly inferred from the molecular function GO:0003980 (UDP-glucose:glycoprotein glucosyltransferase activity). It accurately captures what UGGT1 does at the process level. Supporting Evidence: PMID:10694380 Extracts from HUGT1-transfected cells displayed a 27-fold increase in the transfer of [(14)C]glucose from UDP-[(14)C]glucose to denatured substrates.
GO:0003980 UDP-glucose:glycoprotein glucosyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation for UGGT1 glucosyltransferase activity from combined automated methods. This is a redundant annotation for the same GO term as the IBA and IDA annotations, but that is acceptable. The annotation correctly identifies UGGT1's core enzymatic function. Reason: Correct assignment of the core molecular function. While redundant with the IBA and IDA annotations to GO:0003980, duplicate annotations with different evidence codes are acceptable. Supporting Evidence: PMID:10694380 Extracts from HUGT1-transfected cells displayed a 27-fold increase in the transfer of [(14)C]glucose from UDP-[(14)C]glucose to denatured substrates.
GO:0005788 endoplasmic reticulum lumen	IEA GO_REF:0000044	ACCEPT	Summary: IEA annotation for ER lumen localization based on UniProt subcellular location mapping. UGGT1 is a soluble protein that resides in the ER lumen; it contains an N-terminal signal peptide (cleaved) and the C-terminal REEL ER retrieval signal (UniProt). Arnold et al. (PMID:10694380) confirmed ER localization. UniProt explicitly annotates SUBCELLULAR LOCATION as "Endoplasmic reticulum lumen." This is more specific than GO:0005783 and accurately captures where UGGT1 resides. Reason: UGGT1 is a soluble, luminal ER protein. UniProt annotation with experimental evidence (PMID:10694380) and PROSITE ER-targeting motif (PRU10138) confirm ER lumen localization. This is the most appropriate CC annotation for UGGT1. Supporting Evidence: PMID:10694380 HUGT1 encodes a 1555 amino acid polypeptide that, upon cleavage of an N-terminal signal peptide, is predicted to produce a soluble 173 kDa protein with the ER retrieval signal REEL.
GO:0005793 endoplasmic reticulum-Golgi intermediate compartment	IEA GO_REF:0000044	ACCEPT	Summary: IEA annotation for ERGIC localization based on UniProt subcellular location mapping. UniProt annotates UGGT1 SUBCELLULAR LOCATION as including "Endoplasmic reticulum-Golgi intermediate compartment" based on PROSITE and experimental evidence (PMID:10694380). UGGT1 cycles through the ERGIC as part of its ER retrieval mechanism, though its primary site of action is the ER lumen/ERQC. This is consistent with its ER retrieval signal (REEL) which would enable cycling through the ERGIC. Reason: UniProt annotates UGGT1 to ERGIC, and an ISS annotation also supports this localization. UGGT1 contains the REEL retrieval signal which mediates cycling through the secretory pathway, consistent with ERGIC presence. While the primary functional site is the ER lumen, ERGIC presence is expected for ER-retrieved proteins. Supporting Evidence: PMID:10694380 HUGT1 encodes a 1555 amino acid polypeptide that, upon cleavage of an N-terminal signal peptide, is predicted to produce a soluble 173 kDa protein with the ER retrieval signal REEL.
GO:0009101 glycoprotein biosynthetic process	IEA GO_REF:0000002	MODIFY	Summary: IEA annotation from InterPro mapping. GO:0009101 (glycoprotein biosynthetic process) is defined as "the chemical reactions and pathways resulting in the formation of glycoproteins." While UGGT1 does modify glycoproteins by adding glucose to their N-glycans, its role is in quality control and reglucosylation of already-formed glycoproteins, not in de novo glycoprotein biosynthesis. UGGT1 acts after the initial glycosylation and trimming steps, adding glucose back to N-glycans on misfolded proteins to retain them in the ER for refolding. This is better described as protein N-linked glycosylation (GO:0006487) or more specifically the ERQC pathway, rather than glycoprotein biosynthesis per se. Reason: UGGT1 does not participate in de novo glycoprotein biosynthesis. It acts downstream in the quality control cycle, reglucosylating N-glycans on misfolded glycoproteins that have already been synthesized and initially glycosylated. The IBA annotation to GO:0018279 (protein N-linked glycosylation via asparagine) is a more appropriate process term, and GO:0006487 (protein N-linked glycosylation) would also be suitable. GO:0009101 is misleading because UGGT1 does not contribute to glycoprotein biosynthesis in the usual sense. Proposed replacements: protein N-linked glycosylation
GO:0016740 transferase activity	IEA GO_REF:0000043	ACCEPT	Summary: IEA annotation from UniProt keyword mapping for the broad parent term "transferase activity." UGGT1 is indeed a transferase (it transfers glucose from UDP-glucose to glycoprotein substrates). However, the more specific term GO:0003980 (UDP-glucose:glycoprotein glucosyltransferase activity) is already annotated via IBA, IDA, and other IEA sources. GO:0016740 is a very broad ancestral term that adds no information beyond what GO:0003980 provides. Reason: While extremely broad, this IEA annotation is not incorrect. UGGT1 is a transferase. The more specific child term GO:0003980 is already captured by IBA and IDA annotations. It is acceptable for IEA annotations to be broader than what is determined by IBA or literature.
GO:0016757 glycosyltransferase activity	IEA GO_REF:0000043	ACCEPT	Summary: IEA annotation from UniProt keyword mapping for "glycosyltransferase activity." UGGT1 is a member of glycosyltransferase family 24 (CAZy GT24) and is classified as such in UniProt. This is a parent term of GO:0003980. While less specific than GO:0003980, it is correct and acceptable as an IEA annotation. Reason: Correct parent term annotation. UGGT1 belongs to CAZy GT24 and is a glycosyltransferase by classification (UniProt KW-0328). The more specific GO:0003980 is already annotated. Broader IEA annotations are acceptable.
GO:1904380 endoplasmic reticulum mannose trimming	IEA GO_REF:0000117	REMOVE	Summary: IEA annotation from ARBA machine learning. GO:1904380 is defined as "any protein alpha-1,2-demannosylation that takes place in the endoplasmic reticulum quality control compartment (ERQC)." UGGT1 is NOT a mannosidase and does NOT trim mannose residues. UGGT1 is a glucosyltransferase that adds glucose to N-glycans. Mannose trimming in the ERQC is carried out by ER mannosidase I (MAN1B1) and EDEM family members (PMID:40267907). This annotation is incorrect and was likely mis-assigned by the ARBA model. Reason: UGGT1 does not perform mannose trimming. It is a glucosyltransferase that adds glucose to Man9GlcNAc2 N-glycans on misfolded glycoproteins. Mannose trimming is carried out by distinct enzymes (ERManI/MAN1B1, EDEM1/2/3) that act in the ERQC pathway. While UGGT1 operates in the same pathway as the mannose trimming enzymes, it performs an entirely different enzymatic reaction (glucosylation, not demannosylation). This is an incorrect ARBA prediction. Supporting Evidence: PMID:40267907 A molecular marking system involving multiple ER-resident exo-mannosidases, including ER mannosidase I (ERManI) and EDEM family members, operates in tandem with this cyclical process by progressively trimming mannose residues from glycoproteins.
GO:0005515 protein binding	IPI PMID:17353931 Large-scale mapping of human protein-protein interactions by...	REMOVE	Summary: IPI annotation for "protein binding" from a large-scale IP-MS study (PMID:17353931, Ewing et al. 2007). This study mapped protein-protein interactions for 338 bait proteins using immunoprecipitation followed by mass spectrometry. UGGT1 was identified as a prey in this screen, but the study does not provide specific information about the biological significance of the interaction. The term "protein binding" (GO:0005515) is uninformative and does not tell us anything about UGGT1's actual function. Reason: Per curation guidelines, "protein binding" (GO:0005515) should be avoided as it provides no information about the actual molecular function. This annotation comes from a large-scale proteomics screen (PMID:17353931) that does not provide insight into the specific nature of the interaction. UGGT1 is known to interact with SELENOF (PMID:24415556) and METTL23 (PMID:23349634), but these are better captured by specific interaction annotations rather than the uninformative "protein binding" term.
GO:0003980 UDP-glucose:glycoprotein glucosyltransferase activity	IDA PMID:40267907 Bi-allelic UGGT1 variants cause a congenital disorder of gly...	ACCEPT	Summary: IDA annotation for UGGT1 glucosyltransferase activity from Dardas et al. 2025 (PMID:40267907). This study identified bi-allelic UGGT1 variants causing a congenital disorder of glycosylation (UGGT1-CDG). The authors performed both cellular reglucosylation assays and in vitro catalytic activity assays using HPLC-based quantification of glucose transfer. Pathogenic UGGT1 variants were shown to impair glucosylation and catalytic activity, providing direct evidence for UGGT1 as a UDP-glucose:glycoprotein glucosyltransferase. Reason: Strong experimental evidence from direct enzymatic assays. Dardas et al. (PMID:40267907) used both cellular reglucosylation assays (calreticulin pull-down) and in vitro catalytic activity assays (HPLC-based glucose transfer quantification) to demonstrate UGGT1 glucosyltransferase activity. Pathogenic variants showed impaired activity, confirming the enzymatic function. Supporting Evidence: PMID:40267907 Molecular studies showed that pathogenic UGGT1 variants impair UGGT1 glucosylation and catalytic activity, disrupt mRNA splicing, or inhibit endoplasmic reticulum (ER) retention.
GO:1904380 endoplasmic reticulum mannose trimming	TAS Reactome:R-HSA-901032	REMOVE	Summary: TAS annotation from Reactome pathway R-HSA-901032 (ER Quality Control Compartment). UGGT1 is correctly placed in the ERQC pathway by Reactome, but GO:1904380 (ER mannose trimming) specifically describes alpha-1,2-demannosylation. UGGT1 does not trim mannose; it adds glucose. UGGT1 operates in the same quality control pathway as the mannose-trimming enzymes but performs a distinct reaction (reglucosylation). This annotation is incorrect -- UGGT1 was likely erroneously associated with this process term because it is part of the broader ERQC pathway that includes mannose trimming steps. Reason: UGGT1 does not perform mannose trimming. GO:1904380 is defined as "any protein alpha-1,2-demannosylation that takes place in the ERQC." UGGT1 is a glucosyltransferase, not a mannosidase. While UGGT1 participates in the ERQC pathway alongside mannose-trimming enzymes, it catalyzes the opposite modification: adding glucose rather than removing mannose. This annotation appears to be a mis-mapping from the Reactome ERQC pathway. Supporting Evidence: PMID:40267907 A molecular marking system involving multiple ER-resident exo-mannosidases, including ER mannosidase I (ERManI) and EDEM family members, operates in tandem with this cyclical process by progressively trimming mannose residues from glycoproteins. This stepwise de-mannosylation eventually reduces the affinity of UGGT1 for its substrate, preventing further reglucosylation and facilitating the extraction of misfolded proteins from the CNX cycle
GO:0003980 UDP-glucose:glycoprotein glucosyltransferase activity	TAS Reactome:R-HSA-548884	ACCEPT	Summary: TAS annotation from Reactome reaction R-HSA-548884 which models UGGT1/2 transferring glucose from dolichyl beta-D-glucosyl phosphate to unfolded protein glycans. The Reactome entry states that "UGGT1 and 2 are able to distinguish proteins with minor folding defects in the ERQC and reglucosylate them." This correctly captures the core enzymatic function of UGGT1. Reason: Correctly annotated from a well-curated Reactome reaction that specifically models the UGGT1 glucosyltransferase reaction. Consistent with all other evidence for GO:0003980. Supporting Evidence: Reactome:R-HSA-548884 The UDP-glucose:glycoprotein glucosyltransferases 1 and 2 (UGGT1 and 2) are able to distinguish proteins with minor folding defects in the ERQC and reglucosylate them, by transferring a glucose (from dolichyl beta-D-glucosyl phosphate, DbGP) onto the alpha 1,3 mannose of the b (or c, not shown here) branch
GO:0005515 protein binding	IPI PMID:23349634 A newly uncovered group of distantly related lysine methyltr...	REMOVE	Summary: IPI annotation for protein binding from Cloutier et al. 2013 (PMID:23349634). This study identified UGGT1 as an interactor of METTL23, a lysine methyltransferase, by affinity purification coupled to mass spectrometry. UniProt confirms "Interacts with METTL23" (PMID:23349634). The interaction was identified in the context of a study showing METTL23 preferentially associates with molecular chaperones. While the interaction is real, the term "protein binding" is uninformative. Reason: Per curation guidelines, "protein binding" (GO:0005515) is uninformative and should be avoided. The underlying data shows UGGT1 interacts with METTL23 (a lysine methyltransferase) but this does not inform us about UGGT1's molecular function. The interaction may reflect METTL23's role in regulating chaperone/quality-control machinery rather than a core function of UGGT1. Supporting Evidence: PMID:23349634 A common theme for most of these putative methyltransferases' interactors was chaperones, be they of the Hsp70 or Hsp90 variety (see METTL18, CAMKMT, METTL21C, METTL22, METTL23, METTL21A, and METTL21B)
GO:0032991 protein-containing complex	IDA PMID:23349634 A newly uncovered group of distantly related lysine methyltr...	KEEP AS NON CORE	Summary: IDA annotation for "protein-containing complex" from Cloutier et al. 2013 (PMID:23349634). This study showed UGGT1 interacts with METTL23 by AP-MS. Additionally, UniProt notes that UGGT1 forms a tight complex with SELENOF (PMID:24415556) and is part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, and UGGT1 (by similarity from UniProtKB:Q9JLA3). The term GO:0032991 is very generic -- it simply indicates the protein is found in some complex. While technically correct, it is not very informative. Reason: UGGT1 is part of protein complexes (with SELENOF, with METTL23, and as part of a larger ER chaperone complex), so the annotation is not wrong. However, GO:0032991 is a very generic CC term. Participation in protein complexes is not a core defining feature of UGGT1 -- its core function is its glucosyltransferase enzymatic activity. The SELENOF complex enhances UGGT1 activity (PMID:24415556) but this is regulatory, not a core localization. Supporting Evidence: PMID:23349634 A common theme for most of these putative methyltransferases' interactors was chaperones, be they of the Hsp70 or Hsp90 variety (see METTL18, CAMKMT, METTL21C, METTL22, METTL23, METTL21A, and METTL21B)
GO:0005515 protein binding	IPI PMID:26808496 Comparative Proteomics Reveals Important Viral-Host Interact...	REMOVE	Summary: IPI annotation for protein binding from Liu et al. 2016 (PMID:26808496). This study used affinity purification of HCV E2 protein complexes from HCV-infected human hepatoma cells and identified UGGT1 (referred to as UGT1) as a novel E2 binding partner. The interaction was validated and shown to be functionally relevant: "gene silencing of UGT1 in human hepatoma cell line Huh7.5.1 markedly decreased the production of infectious HCV, indicating a regulatory role of UGT1 in viral lifecycle." While this is an interesting finding about UGGT1's role in the HCV lifecycle, the "protein binding" term is uninformative and this interaction reflects UGGT1's normal ER quality control function on the viral glycoprotein E2. Reason: Per curation guidelines, "protein binding" (GO:0005515) is uninformative. The interaction between UGGT1 and HCV E2 likely reflects UGGT1's normal role in glycoprotein quality control -- HCV E2 is a heavily glycosylated ER protein that would be subject to UGGT1's quality control function. This is not a novel molecular function of UGGT1 but rather evidence that UGGT1's normal glucosyltransferase activity acts on viral glycoproteins as substrates. Supporting Evidence: PMID:26808496 85 cellular proteins and three viral proteins were successfully identified in three independent trials, among which alphafetoprotein (AFP), UDP-glucose: glycoprotein glucosyltransferase 1 (UGT1) and HCV NS4B were further validated as novel E2 binding partners.
GO:0070062 extracellular exosome	HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid...	MARK AS OVER ANNOTATED	Summary: HDA annotation for extracellular exosome localization from a proteomic analysis of human parotid gland exosomes (PMID:19199708). UGGT1 (referred to as "UDP-glucose ceramide glucosyltransferase-like 1 isoform 1") was identified among 491 proteins in the exosome fraction of parotid saliva by MudPIT mass spectrometry. However, the authors note that parotid exosomes "lacked endoplasmic reticulum or nuclear resident proteins," suggesting ER-resident proteins should not normally be present in exosomes. UGGT1 is an ER-resident protein with a strong ER retention signal (REEL), making its presence in exosomes likely a contaminant or artifact of the proteomics approach. Reason: UGGT1 is an established ER-resident protein with a strong ER retrieval signal (REEL). Its detection in exosomes from parotid gland saliva (PMID:19199708) most likely represents contamination or low-level leakage rather than true exosomal localization. The authors themselves note that ER-resident proteins should not be present in true exosomes. High-throughput proteomics of exosome fractions frequently identify ER contaminants. Extracellular exosome is not a meaningful localization for UGGT1. Supporting Evidence: PMID:19199708 we found that parotid exosomes lacked endoplasmic reticulum or nuclear resident proteins, distinguishing them from apoptotic bodies or shed membranes 19 , 22 , 31
GO:0005788 endoplasmic reticulum lumen	TAS Reactome:R-HSA-548884	ACCEPT	Summary: TAS annotation for ER lumen localization from Reactome reaction R-HSA-548884. UGGT1 is modeled in Reactome as a soluble ER lumen protein that catalyzes the reglucosylation of misfolded glycoproteins. This is consistent with UniProt's annotation of SUBCELLULAR LOCATION as "Endoplasmic reticulum lumen" and with the experimental evidence from PMID:10694380 showing ER localization and the presence of an ER retrieval signal (REEL). Reason: UGGT1 is a well-established ER lumen protein. Reactome correctly places it in the ER lumen for its reglucosylation reaction. Consistent with the IEA annotation from UniProt and experimental evidence (PMID:10694380). Supporting Evidence: PMID:10694380 HUGT1 encodes a 1555 amino acid polypeptide that, upon cleavage of an N-terminal signal peptide, is predicted to produce a soluble 173 kDa protein with the ER retrieval signal REEL.
GO:0005793 endoplasmic reticulum-Golgi intermediate compartment	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation for ERGIC localization transferred from experimentally-verified orthologs by curator judgment. UniProt annotates UGGT1 to the ERGIC based on both PROSITE ER-targeting rules and experimental evidence (PMID:10694380). The ISS annotation is consistent with the IEA annotation to the same term and with the known biology of UGGT1 as a protein that cycles through the early secretory pathway via its REEL retrieval signal. Reason: Consistent with the IEA annotation and UniProt subcellular location data. UGGT1 contains the REEL retrieval signal enabling cycling through the ERGIC. The ISS transfer from orthologs is well-supported. Supporting Evidence: PMID:10694380 HUGT1 encodes a 1555 amino acid polypeptide that, upon cleavage of an N-terminal signal peptide, is predicted to produce a soluble 173 kDa protein with the ER retrieval signal REEL.
GO:0051082 unfolded protein binding	IDA PMID:10694380 Two homologues encoding human UDP-glucose:glycoprotein gluco...	MARK AS OVER ANNOTATED	Summary: The IDA annotation to GO:0051082 from PMID:10694380 reflects the experimental observation that UGGT1 selectively recognizes and acts upon misfolded/unfolded glycoproteins. Arnold et al. (2000) demonstrated that HUGT1 (UGGT1) extracts show a 27-fold increase in transfer of [14C]glucose from UDP-[14C]glucose to denatured substrates. The assay measured glucosyltransferase activity toward denatured substrates, not an independent binding activity. UGGT1's interaction with unfolded glycoproteins is substrate recognition intrinsic to its glucosyltransferase catalytic cycle: the N-terminal domain senses folding defects, and the C-terminal catalytic domain then reglucosylates the substrate. UniProt describes the FUNCTION as "Recognizes glycoproteins with minor folding defects. Reglucosylates single N-glycans near the misfolded part of the protein." This is an enzymatic activity, not a standalone binding function. The term GO:0051082 is now formally obsolete (go-ontology#30962). Reason: The experimental evidence in PMID:10694380 demonstrates glucosyltransferase activity (glucose transfer to denatured substrates), which inherently requires substrate recognition/binding. Annotating this as "unfolded protein binding" separately from the glucosyltransferase activity is an over-annotation -- it conflates enzymatic substrate recognition with an independent molecular function. UGGT1 is not a chaperone that simply binds and holds unfolded proteins; it is an enzyme that recognizes misfolded glycoprotein substrates and catalytically reglucosylates them. The core molecular function is fully captured by GO:0003980 (UDP-glucose:glycoprotein glucosyltransferase activity). Furthermore, GO:0051082 is now formally obsolete per go-ontology#30962. Supporting Evidence: PMID:10694380 UDP-glucose:glycoprotein glucosyltransferase (UGT) is a soluble protein of the endoplasmic reticulum (ER) that operates as a gatekeeper for quality control by preventing transport of improperly folded glycoproteins out of the ER. PMID:10694380 Extracts from HUGT1-transfected cells displayed a 27-fold increase in the transfer of [(14)C]glucose from UDP-[(14)C]glucose to denatured substrates.
GO:0003980 UDP-glucose:glycoprotein glucosyltransferase activity	IDA PMID:10694380 Two homologues encoding human UDP-glucose:glycoprotein gluco...	ACCEPT	Summary: IDA annotation for the core enzymatic activity from the foundational characterization paper by Arnold et al. 2000 (PMID:10694380). This study cloned HUGT1 (UGGT1), expressed it in COS-1 cells, and demonstrated a 27-fold increase in glucose transfer from UDP-glucose to denatured glycoprotein substrates. Site-directed mutagenesis of highly conserved residues (D1452A, Q1453A, D1454A, L1455A, P1456A, N1457A) in the catalytic domain identified four residues essential for catalytic function. This is the primary experimental evidence establishing UGGT1 as a UDP-glucose:glycoprotein glucosyltransferase. Reason: Foundational direct assay evidence for UGGT1's core molecular function. Arnold et al. (PMID:10694380) performed definitive enzymatic assays (radiolabeled glucose transfer) and site-directed mutagenesis confirming the glucosyltransferase activity. This is the gold-standard IDA evidence. Supporting Evidence: PMID:10694380 Extracts from HUGT1-transfected cells displayed a 27-fold increase in the transfer of [(14)C]glucose from UDP-[(14)C]glucose to denatured substrates. PMID:10694380 Site-directed alanine mutagenesis within a highly conserved region of HUGT1 identified four residues that are essential for catalytic function.
GO:0005783 endoplasmic reticulum	IDA PMID:10694380 Two homologues encoding human UDP-glucose:glycoprotein gluco...	ACCEPT	Summary: IDA annotation for ER localization from Arnold et al. 2000 (PMID:10694380). The study showed that UGGT1 (HUGT1) is localized to the ER, consistent with its signal peptide, ER retrieval signal (REEL), and function as an ER-resident quality control enzyme. The study expressed HUGT1 in COS-1 cells and obtained protein localized to the ER for enzymatic activity assays. Reason: Direct experimental evidence of ER localization from the characterization study (PMID:10694380). The more specific GO:0005788 (ER lumen) is also annotated, but GO:0005783 is acceptable as the parent term confirmed by this IDA. Supporting Evidence: PMID:10694380 HUGT1 encodes a 1555 amino acid polypeptide that, upon cleavage of an N-terminal signal peptide, is predicted to produce a soluble 173 kDa protein with the ER retrieval signal REEL.
GO:0051084 'de novo' post-translational protein folding	TAS PMID:10694380 Two homologues encoding human UDP-glucose:glycoprotein gluco...	MODIFY	Summary: TAS annotation for "de novo post-translational protein folding" (GO:0051084), defined as "the process of assisting in the correct noncovalent folding of newly formed polypeptides or folding intermediates." UGGT1 does participate in the protein folding quality control cycle by reglucosylating misfolded glycoproteins so they can re-engage with calnexin/calreticulin for further folding attempts (PMID:10694380, PMID:40267907). However, UGGT1 itself is not a chaperone that directly assists in protein folding. It is an enzyme that tags misfolded proteins for re-entry into the calnexin/calreticulin chaperone cycle. The term implies direct folding assistance, which is misleading for UGGT1. A more accurate process annotation would be one reflecting its role in protein quality control in the ER or N-linked glycosylation. Reason: UGGT1 does not directly fold proteins. It is an enzyme (glucosyltransferase) that acts as a folding sensor, recognizing misfolded glycoproteins and reglucosylating them so they can re-bind calnexin/calreticulin for another round of folding. The actual folding is performed by the calnexin/calreticulin chaperone system. "De novo post-translational protein folding" implies direct chaperone activity, which is inaccurate for UGGT1. A better process term would be GO:0006487 (protein N-linked glycosylation) or GO:0097359 (UDP-glucosylation), which more accurately reflect UGGT1's enzymatic role in the quality control cycle. Proposed replacements: protein N-linked glycosylation Supporting Evidence: PMID:40267907 UGGT1 identifies and reglucosylates misfolded proteins, resulting in ER retention for re-binding to CNX/CRT to enable correct folding. PMID:10694380 UDP-glucose:glycoprotein glucosyltransferase (UGT) is a soluble protein of the endoplasmic reticulum (ER) that operates as a gatekeeper for quality control by preventing transport of improperly folded glycoproteins out of the ER.

Gene Description

Existing Annotations Review

Core Functions

References

Deep Research

Falcon

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