TODO: Add description for Uggt1
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0003980
UDP-glucose:glycoprotein glucosyltransferase activity
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Manual review: UDP-glucose:glycoprotein glucosyltransferase activity is consistent with known biology of Uggt1.
Reason: Retained as supported or plausible for this gene and evidence context.
|
|
GO:0005783
endoplasmic reticulum
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Manual review: endoplasmic reticulum is consistent with known biology of Uggt1.
Reason: Retained as supported or plausible for this gene and evidence context.
|
|
GO:0051082
unfolded protein binding
|
IBA
GO_REF:0000033 |
MARK AS OVER ANNOTATED |
Summary: Manual review: unfolded protein binding is too generic or over-extended for Uggt1.
Reason: Marked over-annotated because more specific terms capture the biology more accurately.
|
|
GO:0097359
UDP-glucosylation
|
IEA
GO_REF:0000108 |
ACCEPT |
Summary: Manual review: UDP-glucosylation is consistent with known biology of Uggt1.
Reason: Retained as supported or plausible for this gene and evidence context.
|
|
GO:0003980
UDP-glucose:glycoprotein glucosyltransferase activity
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: Manual review: UDP-glucose:glycoprotein glucosyltransferase activity is consistent with known biology of Uggt1.
Reason: Retained as supported or plausible for this gene and evidence context.
|
|
GO:0005788
endoplasmic reticulum lumen
|
IEA
GO_REF:0000044 |
ACCEPT |
Summary: Manual review: endoplasmic reticulum lumen is consistent with known biology of Uggt1.
Reason: Retained as supported or plausible for this gene and evidence context.
|
|
GO:0005793
endoplasmic reticulum-Golgi intermediate compartment
|
IEA
GO_REF:0000044 |
ACCEPT |
Summary: Manual review: endoplasmic reticulum-Golgi intermediate compartment is consistent with known biology of Uggt1.
Reason: Retained as supported or plausible for this gene and evidence context.
|
|
GO:0009101
glycoprotein biosynthetic process
|
IEA
GO_REF:0000002 |
KEEP AS NON CORE |
Summary: Manual review: glycoprotein biosynthetic process may be context-dependent or peripheral for Uggt1.
Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
|
|
GO:0016740
transferase activity
|
IEA
GO_REF:0000043 |
ACCEPT |
Summary: Manual review: transferase activity is consistent with known biology of Uggt1.
Reason: Retained as supported or plausible for this gene and evidence context.
|
|
GO:0016757
glycosyltransferase activity
|
IEA
GO_REF:0000043 |
ACCEPT |
Summary: Manual review: glycosyltransferase activity is consistent with known biology of Uggt1.
Reason: Retained as supported or plausible for this gene and evidence context.
|
|
GO:1901135
carbohydrate derivative metabolic process
|
IEA
GO_REF:0000117 |
KEEP AS NON CORE |
Summary: Manual review: carbohydrate derivative metabolic process may be context-dependent or peripheral for Uggt1.
Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
|
|
GO:0003980
UDP-glucose:glycoprotein glucosyltransferase activity
|
ISO
GO_REF:0000121 |
ACCEPT |
Summary: Manual review: UDP-glucose:glycoprotein glucosyltransferase activity is consistent with known biology of Uggt1.
Reason: Retained as supported or plausible for this gene and evidence context.
|
|
GO:0009306
protein secretion
|
ISO
GO_REF:0000121 |
KEEP AS NON CORE |
Summary: Manual review: protein secretion may be context-dependent or peripheral for Uggt1.
Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
|
|
GO:0032991
protein-containing complex
|
ISO
GO_REF:0000121 |
KEEP AS NON CORE |
Summary: Manual review: protein-containing complex may be context-dependent or peripheral for Uggt1.
Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
|
|
GO:0005515
protein binding
|
IPI
PMID:11278576 Association between the 15-kDa selenoprotein and UDP-glucose... |
MARK AS OVER ANNOTATED |
Summary: Manual review: protein binding is too generic or over-extended for Uggt1.
Reason: Marked over-annotated because more specific terms capture the biology more accurately.
|
|
GO:0005788
endoplasmic reticulum lumen
|
IDA
PMID:11535823 Immunolocalization of UDP-glucose:glycoprotein glucosyltrans... |
ACCEPT |
Summary: Manual review: endoplasmic reticulum lumen is consistent with known biology of Uggt1.
Reason: Retained as supported or plausible for this gene and evidence context.
|
|
GO:0005793
endoplasmic reticulum-Golgi intermediate compartment
|
IDA
PMID:11535823 Immunolocalization of UDP-glucose:glycoprotein glucosyltrans... |
ACCEPT |
Summary: Manual review: endoplasmic reticulum-Golgi intermediate compartment is consistent with known biology of Uggt1.
Reason: Retained as supported or plausible for this gene and evidence context.
|
|
GO:0051082
unfolded protein binding
|
ISO
GO_REF:0000121 |
MARK AS OVER ANNOTATED |
Summary: Manual review: unfolded protein binding is too generic or over-extended for Uggt1.
Reason: Marked over-annotated because more specific terms capture the biology more accurately.
|
|
GO:0051082
unfolded protein binding
|
IDA
PMID:10764828 Cloning and characterization of mammalian UDP-glucose glycop... |
MARK AS OVER ANNOTATED |
Summary: Manual review: unfolded protein binding is too generic or over-extended for Uggt1.
Reason: Marked over-annotated because more specific terms capture the biology more accurately.
|
|
GO:0005515
protein binding
|
IPI
PMID:10764828 Cloning and characterization of mammalian UDP-glucose glycop... |
MARK AS OVER ANNOTATED |
Summary: Manual review: protein binding is too generic or over-extended for Uggt1.
Reason: Marked over-annotated because more specific terms capture the biology more accurately.
|
|
GO:0005783
endoplasmic reticulum
|
ISO
GO_REF:0000121 |
ACCEPT |
Summary: Manual review: endoplasmic reticulum is consistent with known biology of Uggt1.
Reason: Retained as supported or plausible for this gene and evidence context.
|
|
GO:0003980
UDP-glucose:glycoprotein glucosyltransferase activity
|
IDA
PMID:10764828 Cloning and characterization of mammalian UDP-glucose glycop... |
ACCEPT |
Summary: Manual review: UDP-glucose:glycoprotein glucosyltransferase activity is consistent with known biology of Uggt1.
Reason: Retained as supported or plausible for this gene and evidence context.
|
|
GO:0051084
'de novo' post-translational protein folding
|
TAS
PMID:10764828 Cloning and characterization of mammalian UDP-glucose glycop... |
KEEP AS NON CORE |
Summary: Manual review: 'de novo' post-translational protein folding may be context-dependent or peripheral for Uggt1.
Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
|
|
GO:0003980
UDP-glucose:glycoprotein glucosyltransferase activity
|
TAS
PMID:10764828 Cloning and characterization of mammalian UDP-glucose glycop... |
ACCEPT |
Summary: Manual review: UDP-glucose:glycoprotein glucosyltransferase activity is consistent with known biology of Uggt1.
Reason: Retained as supported or plausible for this gene and evidence context.
|
|
GO:0003980
UDP-glucose:glycoprotein glucosyltransferase activity
|
IDA
PMID:12518055 UDP-Glc:glycoprotein glucosyltransferase recognizes structur... |
ACCEPT |
Summary: Manual review: UDP-glucose:glycoprotein glucosyltransferase activity is consistent with known biology of Uggt1.
Reason: Retained as supported or plausible for this gene and evidence context.
|
|
GO:0006457
protein folding
|
TAS
PMID:12518055 UDP-Glc:glycoprotein glucosyltransferase recognizes structur... |
KEEP AS NON CORE |
Summary: Manual review: protein folding may be context-dependent or peripheral for Uggt1.
Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
|
Exported on March 22, 2026 at 01:05 AM
Organism: Rattus norvegicus
Sequence:
MCSRGDANAAGAAAARRVTGLCYNMGLLIALALLCLFSLAEANSKAITTSLTTKWFSAPLLLEASEFLAEDSQEKFWSFVEASQNIGSSDQHDTDRSYYDAILEAAFRFLSPLQQNLLKFCLSLRSYSASIQAFQQIAVDEPPPEGCKSFLSVHGKQTCDLGTLESLLLTAPDRPKPLLFKGDHRYPSSNPESPVVIFYSEIGHEEFSNIHHQLISKSNEGKINYVFRHYISNPRKEPVHLSGYGVELAIKSTEYKAKDDTQVKGTEVNTTVIGENDPIDEVQGFLFGKLRELYPSLEGQLKEFRKHLVESTNEMAPLKVWQLQDLSFQTAARILAAPVELALVVMKDISQNFPTKARAITKTAVSAQLRAEVEENQKYFKGTIGLQPGDSALFINGLHIDLDTQDIFSLFDTLRNEARVMEGLHRLGIEGLSLHNILKLNIQPSETDYAVDIRSPAISWVNNLEVDSRYNSWPSSLQELLRPTFPGVIRQIRKNLHNMVFIVDPVHETTAELVSIAEMFLSNHIPLRIGFIFVVNDSEDVDGMQDAGVAVLRAYNYVGQEVDGYHAFQTLTQIYNKVRTGEKVKVEHVVSVLEKKYPYVEVNSILGIDSAYDQNRKEARGYYEQTGVGPLPVVLFNGMPFEKEQLDPDELETITMHKILETTTFFQRAVYLGELSHDQDVVEYIMNQPNVVPRINSRILTAKREYLDLTASNNFYVDDFARFSALDSRGKTAAIANSMNYLTKKGMSSKEIYDDSFIRPVTFWIVGDFDSPSGRQLLYDAIKHQKTSNNVRISMINNPSREISDSSTPVSRAIWAALQTQTSNSAKNFITKMVKEETAEALAAGVDIGEFSVGGMDVSLFKEVFESSRMDFILSHALYCRDVLKLKKGQRVVISNGRIIGPLEDSELFNQDDFHLLENIILKTSGQKIKSHIQQLRVEEDVASDLVMKVDALLSAQPKGEARIEYQFFEDKHSAIKLKPKEGETYYDVVAVVDPVTREAQRLAPLLLVLAQLINMSLRVFMNCQSKLSDMPLKSFYRYVLEPEISFTADNSFAKGPIAKFLDMPQSPLFTLNLNTPESWMVESVRTPYDLDNIYLEEVDSIVAAEYELEYLLLEGHCYDITTGQPPRGLQFTLGTSANPTTVDTIVMANLGYFQLKANPGAWILRLRKGRSDDIYRIYSHDGTDSPPDANDVVVILNNFKSKIIKVKVQKKADMANEDLLSDGTNENESGFWDSFKWGFSGQKTEEVKQDKDDIINIFSVASGHLYERFLRIMMLSVLKNTKTPVKFWFLKNYLSPTFKEFIPYMAKKYNFQYELVQYKWPRWLHQQTEKQRIIWGYKILFLDVLFPLVVDKFLFVDADQIVRTDLKELRDFNLDGAPYGYTPFCDSRREMDGYRFWKSGYWASHLAGRKYHISALYVVDLKKFRKIAAGDRLRGQYQGLSQDPNSLSNLDQDLPNNMIHQVPIKSLPQEWLWCETWCDDASKKRAKTIDLCNNPMTKEPKLEAAVRIVPEWQDYDQEIKQLQTLFQEEKELGTLHEEETQEGSQKHEEL
I begin with the InterPro architecture. A broad family signature, IPR009448 (UDP-glucose:Glycoprotein Glucosyltransferase family, residues 34–1541), blankets almost the entire polypeptide, establishing identity as a UDP-glucose-dependent glucosyltransferase specialized for glycoprotein quality control. The N-terminal two-thirds are partitioned into three thioredoxin-like folds: IPR040693 (UGGT, thioredoxin-like domain 1, residues 58–236), IPR040694 (thioredoxin-like domain 2, residues 312–443), and IPR040692 (thioredoxin-like domain 3, residues 451–699). A fourth thioredoxin-like module follows: IPR040525 (UDP-glucose:glycoprotein glucosyltransferase, thioredoxin-like domain 4, residues 723–955). These repeated thioredoxin-like domains form a modular recognition platform rather than a redox enzyme; in UGGTs they create a multi-surface scaffold that samples and clamps unfolded or non-native glycoprotein conformers. This modular recognition causes selective binding of denatured substrates and positions them for catalysis.
The C-terminal third houses the catalytic engine: IPR029044 (Nucleotide-diphospho-sugar transferases homologous superfamily, residues 1256–1519) and IPR040497 (Glucosyltransferase 24, catalytic domain, residues 1256–1523). This GT-B–type nucleotide-sugar transferase core binds UDP-glucose and executes glycosyl transfer to exposed hydroxyls on misfolded glycoproteins. The ordered layout—three thioredoxin-like recognition modules leading into a UDP-sugar catalytic domain—explains how the enzyme binds and assesses unfolded substrates and then reglucosylates them.
From these domains, the molecular function resolves as glycosyltransferase chemistry that uses UDP-glucose to add a glucose moiety to glycoprotein substrates, matching GO:0016740 glycosyltransferase activity. The thioredoxin-like array dictates specificity toward non-native conformers, while the GT24 catalytic core performs the sugar transfer that tags glycoproteins for further folding cycles.
This activity feeds directly into biological quality control of secretory-pathway proteins. By reglucosylating non-native glycoproteins, the enzyme sustains the calnexin/calreticulin cycle and thereby enforces ER protein maturation, which is a core facet of GO:0006458 protein folding and, more specifically, glycoprotein quality control in the secretory pathway. The repeated thioredoxin-like modules function as conformational sentinels; their occupancy correlates with folding state, ensuring that only properly folded clients exit the cycle.
Cellular placement follows from function and architecture. The absence of transmembrane domains and the reliance on soluble thioredoxin-like scaffolding indicate a soluble luminal enzyme that operates within the endoplasmic reticulum. This aligns with a residency in the endoplasmic reticulum and supports the GO:0005783 endoplasmic reticulum. A soluble luminal orientation allows continuous surveillance of nascent glycoproteins emerging from ER translocons.
Mechanistically, I hypothesize that the thioredoxin-like domains (residues 58–955) act as a multivalent clamp that captures unfolded glycoproteins and presents them to the C-terminal GT24 catalytic core (residues 1256–1523). Upon binding UDP-glucose, the catalytic domain transfers glucose to specific acceptor hydroxyls on the substrate, re-establishing a recognition epitope that recruits lectin chaperones. This reglucosylation likely occurs adjacent to the calnexin/calreticulin system and transiently couples to ER-resident chaperones and oxidoreductases. Expected partners include calnexin and calreticulin for lectin-mediated retention, ERp57 and other protein disulfide isomerases for oxidative folding, BiP/HSPA5 for general chaperoning, and UDP-glucose–supply pathways that feed the GT-B catalytic module. Together, these interactions create a luminal decision hub that triages folding states and cycles non-native glycoproteins through reglucosylation until they achieve native conformation.
An endoplasmic reticulum–resident glucosyltransferase that recognizes non-native glycoproteins via a multi-thioredoxin-like recognition platform and uses UDP-glucose to reglucosylate them, thereby feeding substrates back into lectin-assisted folding cycles. By tagging incompletely folded glycoproteins, it sustains quality control and promotes productive maturation within the ER lumen, operating as a soluble luminal catalyst that coordinates with calnexin/calreticulin pathways and associated chaperone systems.
Mediates the glucose-dependent regulation of protein folding in the endoplasmic reticulum. It catalyzes the transfer of a glucose moiety from UDP-glucose to non-native glycoproteins thereby assisting their proper folding; similar activity can be exhibited by UGGT2.
IPR009448, family) — residues 34-1541IPR040693, domain) — residues 58-236IPR040694, domain) — residues 312-443IPR040692, domain) — residues 451-699IPR040525, domain) — residues 723-955IPR029044, homologous_superfamily) — residues 1256-1519IPR040497, domain) — residues 1256-1523Molecular Function: molecular_function (GO:0003674), binding (GO:0005488), catalytic activity (GO:0003824), glycosyltransferase activity (GO:0016740), protein binding (GO:0005515), glycosyltransferase activity (GO:0016757), unfolded protein binding (GO:0051082), hexosyltransferase activity (GO:0016758), UDP-glycosyltransferase activity (GO:0008194), glucosyltransferase activity (GO:0046527), UDP-glucosyltransferase activity (GO:0035251)
Biological Process: biological_process (GO:0008150), cellular process (GO:0009987), protein folding (GO:0006457), protein folding (GO:0006458), 'de novo' post-translational protein folding (GO:0051084)
Cellular Component: cellular_component (GO:0005575), cellular anatomical entity (GO:0110165), intracellular anatomical structure (GO:0005622), organelle (GO:0043226), membrane-enclosed lumen (GO:0031974), cytoplasm (GO:0005737), endomembrane system (GO:0012505), organelle lumen (GO:0043233), endoplasmic reticulum (GO:0005783), intracellular organelle (GO:0043229), membrane-bounded organelle (GO:0043227), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), endoplasmic reticulum lumen (GO:0005788), intracellular membrane-bounded organelle (GO:0043231), intracellular organelle lumen (GO:0070013)
Generated by BioReason
Exported on March 22, 2026 at 01:05 AM
Organism: Rattus norvegicus
Sequence:
MCSRGDANAAGAAAARRVTGLCYNMGLLIALALLCLFSLAEANSKAITTSLTTKWFSAPLLLEASEFLAEDSQEKFWSFVEASQNIGSSDQHDTDRSYYDAILEAAFRFLSPLQQNLLKFCLSLRSYSASIQAFQQIAVDEPPPEGCKSFLSVHGKQTCDLGTLESLLLTAPDRPKPLLFKGDHRYPSSNPESPVVIFYSEIGHEEFSNIHHQLISKSNEGKINYVFRHYISNPRKEPVHLSGYGVELAIKSTEYKAKDDTQVKGTEVNTTVIGENDPIDEVQGFLFGKLRELYPSLEGQLKEFRKHLVESTNEMAPLKVWQLQDLSFQTAARILAAPVELALVVMKDISQNFPTKARAITKTAVSAQLRAEVEENQKYFKGTIGLQPGDSALFINGLHIDLDTQDIFSLFDTLRNEARVMEGLHRLGIEGLSLHNILKLNIQPSETDYAVDIRSPAISWVNNLEVDSRYNSWPSSLQELLRPTFPGVIRQIRKNLHNMVFIVDPVHETTAELVSIAEMFLSNHIPLRIGFIFVVNDSEDVDGMQDAGVAVLRAYNYVGQEVDGYHAFQTLTQIYNKVRTGEKVKVEHVVSVLEKKYPYVEVNSILGIDSAYDQNRKEARGYYEQTGVGPLPVVLFNGMPFEKEQLDPDELETITMHKILETTTFFQRAVYLGELSHDQDVVEYIMNQPNVVPRINSRILTAKREYLDLTASNNFYVDDFARFSALDSRGKTAAIANSMNYLTKKGMSSKEIYDDSFIRPVTFWIVGDFDSPSGRQLLYDAIKHQKTSNNVRISMINNPSREISDSSTPVSRAIWAALQTQTSNSAKNFITKMVKEETAEALAAGVDIGEFSVGGMDVSLFKEVFESSRMDFILSHALYCRDVLKLKKGQRVVISNGRIIGPLEDSELFNQDDFHLLENIILKTSGQKIKSHIQQLRVEEDVASDLVMKVDALLSAQPKGEARIEYQFFEDKHSAIKLKPKEGETYYDVVAVVDPVTREAQRLAPLLLVLAQLINMSLRVFMNCQSKLSDMPLKSFYRYVLEPEISFTADNSFAKGPIAKFLDMPQSPLFTLNLNTPESWMVESVRTPYDLDNIYLEEVDSIVAAEYELEYLLLEGHCYDITTGQPPRGLQFTLGTSANPTTVDTIVMANLGYFQLKANPGAWILRLRKGRSDDIYRIYSHDGTDSPPDANDVVVILNNFKSKIIKVKVQKKADMANEDLLSDGTNENESGFWDSFKWGFSGQKTEEVKQDKDDIINIFSVASGHLYERFLRIMMLSVLKNTKTPVKFWFLKNYLSPTFKEFIPYMAKKYNFQYELVQYKWPRWLHQQTEKQRIIWGYKILFLDVLFPLVVDKFLFVDADQIVRTDLKELRDFNLDGAPYGYTPFCDSRREMDGYRFWKSGYWASHLAGRKYHISALYVVDLKKFRKIAAGDRLRGQYQGLSQDPNSLSNLDQDLPNNMIHQVPIKSLPQEWLWCETWCDDASKKRAKTIDLCNNPMTKEPKLEAAVRIVPEWQDYDQEIKQLQTLFQEEKELGTLHEEETQEGSQKHEEL
I begin with the InterPro architecture. A broad family signature, IPR009448 (UDP-glucose:Glycoprotein Glucosyltransferase family, residues 34–1541), blankets almost the entire polypeptide, establishing identity as a UDP-glucose-dependent glucosyltransferase specialized for glycoprotein quality control. The N-terminal two-thirds are partitioned into three thioredoxin-like folds: IPR040693 (UGGT, thioredoxin-like domain 1, residues 58–236), IPR040694 (thioredoxin-like domain 2, residues 312–443), and IPR040692 (thioredoxin-like domain 3, residues 451–699). A fourth thioredoxin-like module follows: IPR040525 (UDP-glucose:glycoprotein glucosyltransferase, thioredoxin-like domain 4, residues 723–955). These repeated thioredoxin-like domains form a modular recognition platform rather than a redox enzyme; in UGGTs they create a multi-surface scaffold that samples and clamps unfolded or non-native glycoprotein conformers. This modular recognition causes selective binding of denatured substrates and positions them for catalysis.
The C-terminal third houses the catalytic engine: IPR029044 (Nucleotide-diphospho-sugar transferases homologous superfamily, residues 1256–1519) and IPR040497 (Glucosyltransferase 24, catalytic domain, residues 1256–1523). This GT-B–type nucleotide-sugar transferase core binds UDP-glucose and executes glycosyl transfer to exposed hydroxyls on misfolded glycoproteins. The ordered layout—three thioredoxin-like recognition modules leading into a UDP-sugar catalytic domain—explains how the enzyme binds and assesses unfolded substrates and then reglucosylates them.
From these domains, the molecular function resolves as glycosyltransferase chemistry that uses UDP-glucose to add a glucose moiety to glycoprotein substrates, matching GO:0016740 glycosyltransferase activity. The thioredoxin-like array dictates specificity toward non-native conformers, while the GT24 catalytic core performs the sugar transfer that tags glycoproteins for further folding cycles.
This activity feeds directly into biological quality control of secretory-pathway proteins. By reglucosylating non-native glycoproteins, the enzyme sustains the calnexin/calreticulin cycle and thereby enforces ER protein maturation, which is a core facet of GO:0006458 protein folding and, more specifically, glycoprotein quality control in the secretory pathway. The repeated thioredoxin-like modules function as conformational sentinels; their occupancy correlates with folding state, ensuring that only properly folded clients exit the cycle.
Cellular placement follows from function and architecture. The absence of transmembrane domains and the reliance on soluble thioredoxin-like scaffolding indicate a soluble luminal enzyme that operates within the endoplasmic reticulum. This aligns with a residency in the endoplasmic reticulum and supports the GO:0005783 endoplasmic reticulum. A soluble luminal orientation allows continuous surveillance of nascent glycoproteins emerging from ER translocons.
Mechanistically, I hypothesize that the thioredoxin-like domains (residues 58–955) act as a multivalent clamp that captures unfolded glycoproteins and presents them to the C-terminal GT24 catalytic core (residues 1256–1523). Upon binding UDP-glucose, the catalytic domain transfers glucose to specific acceptor hydroxyls on the substrate, re-establishing a recognition epitope that recruits lectin chaperones. This reglucosylation likely occurs adjacent to the calnexin/calreticulin system and transiently couples to ER-resident chaperones and oxidoreductases. Expected partners include calnexin and calreticulin for lectin-mediated retention, ERp57 and other protein disulfide isomerases for oxidative folding, BiP/HSPA5 for general chaperoning, and UDP-glucose–supply pathways that feed the GT-B catalytic module. Together, these interactions create a luminal decision hub that triages folding states and cycles non-native glycoproteins through reglucosylation until they achieve native conformation.
An endoplasmic reticulum–resident glucosyltransferase that recognizes non-native glycoproteins via a multi-thioredoxin-like recognition platform and uses UDP-glucose to reglucosylate them, thereby feeding substrates back into lectin-assisted folding cycles. By tagging incompletely folded glycoproteins, it sustains quality control and promotes productive maturation within the ER lumen, operating as a soluble luminal catalyst that coordinates with calnexin/calreticulin pathways and associated chaperone systems.
Mediates the glucose-dependent regulation of protein folding in the endoplasmic reticulum. It catalyzes the transfer of a glucose moiety from UDP-glucose to non-native glycoproteins thereby assisting their proper folding; similar activity can be exhibited by UGGT2.
IPR009448, family) — residues 34-1541IPR040693, domain) — residues 58-236IPR040694, domain) — residues 312-443IPR040692, domain) — residues 451-699IPR040525, domain) — residues 723-955IPR029044, homologous_superfamily) — residues 1256-1519IPR040497, domain) — residues 1256-1523Molecular Function: molecular_function (GO:0003674), binding (GO:0005488), catalytic activity (GO:0003824), glycosyltransferase activity (GO:0016740), protein binding (GO:0005515), glycosyltransferase activity (GO:0016757), unfolded protein binding (GO:0051082), hexosyltransferase activity (GO:0016758), UDP-glycosyltransferase activity (GO:0008194), glucosyltransferase activity (GO:0046527), UDP-glucosyltransferase activity (GO:0035251)
Biological Process: biological_process (GO:0008150), cellular process (GO:0009987), protein folding (GO:0006457), protein folding (GO:0006458), 'de novo' post-translational protein folding (GO:0051084)
Cellular Component: cellular_component (GO:0005575), cellular anatomical entity (GO:0110165), intracellular anatomical structure (GO:0005622), organelle (GO:0043226), membrane-enclosed lumen (GO:0031974), cytoplasm (GO:0005737), endomembrane system (GO:0012505), organelle lumen (GO:0043233), endoplasmic reticulum (GO:0005783), intracellular organelle (GO:0043229), membrane-bounded organelle (GO:0043227), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), endoplasmic reticulum lumen (GO:0005788), intracellular membrane-bounded organelle (GO:0043231), intracellular organelle lumen (GO:0070013)
Generated by BioReason
Source: Uggt1-deep-research-bioreason-rl.md
The functional summary states:
An endoplasmic reticulum-resident glucosyltransferase that recognizes non-native glycoproteins via a multi-thioredoxin-like recognition platform and uses UDP-glucose to reglucosylate them, thereby feeding substrates back into lectin-assisted folding cycles. By tagging incompletely folded glycoproteins, it sustains quality control and promotes productive maturation within the ER lumen, operating as a soluble luminal catalyst that coordinates with calnexin/calreticulin pathways and associated chaperone systems.
This is an excellent and comprehensive summary. The curated review confirms UDP-glucose:glycoprotein glucosyltransferase activity (GO:0003980), unfolded protein binding (GO:0051082, though marked as over-annotated in favor of more specific terms), endoplasmic reticulum (GO:0005783), ER lumen (GO:0005788), ERGIC (GO:0005793), UDP-glucosylation (GO:0097359), glycosyltransferase activity (GO:0016757), and protein folding (GO:0006457).
BioReason accurately describes the four thioredoxin-like recognition domains as "conformational sentinels" that assess folding state -- this is a correct and informative interpretation of the domain architecture. The GT24 catalytic domain description and UDP-glucose utilization are accurate.
The mechanistic description of the calnexin/calreticulin cycle, the reglucosylation-based quality control loop, and the coordination with ERp57/PDI and BiP/HSPA5 is all well-supported by established ER biology. The summary captures both the molecular mechanism and its biological context comprehensively.
Notably, the curated review marks unfolded protein binding (GO:0051082) as over-annotated, preferring more specific terms. BioReason's thinking trace describes the thioredoxin-like domains as recognizing "non-native conformers" -- which aligns with the biology without over-committing to the generic GO term.
Comparison with interpro2go:
The interpro2go annotation for Uggt1 is glycoprotein biosynthetic process (GO:0009101), which the curated review keeps as non-core. BioReason does not recapitulate this annotation directly but instead correctly focuses on the quality control / reglucosylation role rather than biosynthesis per se. This is a more accurate representation -- Uggt1 is not involved in de novo glycoprotein synthesis but rather in folding quality control via the calnexin/calreticulin cycle. BioReason provides significantly more insight than interpro2go here.
The trace is among the best in this set. The domain-by-domain walkthrough is thorough, and the functional interpretation is precise. The distinction between the thioredoxin-like domains serving as recognition platforms (not redox enzymes) is explicitly stated and correct. The hypothesized interaction with BiP/HSPA5, calnexin/calreticulin, ERp57, and UDP-glucose supply pathways is well-supported. The characterization of the enzyme as a "luminal decision hub" is an apt description.
id: Q9JLA3
gene_symbol: Uggt1
product_type: PROTEIN
status: DRAFT
taxon:
id: NCBITaxon:10116
label: Rattus norvegicus
description: 'TODO: Add description for Uggt1'
existing_annotations:
- term:
id: GO:0003980
label: UDP-glucose:glycoprotein glucosyltransferase activity
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: 'Manual review: UDP-glucose:glycoprotein glucosyltransferase activity is consistent with known biology of Uggt1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0005783
label: endoplasmic reticulum
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: 'Manual review: endoplasmic reticulum is consistent with known biology of Uggt1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0051082
label: unfolded protein binding
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: 'Manual review: unfolded protein binding is too generic or over-extended for Uggt1.'
action: MARK_AS_OVER_ANNOTATED
reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
id: GO:0097359
label: UDP-glucosylation
evidence_type: IEA
original_reference_id: GO_REF:0000108
review:
summary: 'Manual review: UDP-glucosylation is consistent with known biology of Uggt1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0003980
label: UDP-glucose:glycoprotein glucosyltransferase activity
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: 'Manual review: UDP-glucose:glycoprotein glucosyltransferase activity is consistent with known biology of Uggt1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0005788
label: endoplasmic reticulum lumen
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
summary: 'Manual review: endoplasmic reticulum lumen is consistent with known biology of Uggt1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0005793
label: endoplasmic reticulum-Golgi intermediate compartment
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
summary: 'Manual review: endoplasmic reticulum-Golgi intermediate compartment is consistent with known biology of Uggt1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0009101
label: glycoprotein biosynthetic process
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
summary: 'Manual review: glycoprotein biosynthetic process may be context-dependent or peripheral for Uggt1.'
action: KEEP_AS_NON_CORE
reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
id: GO:0016740
label: transferase activity
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: 'Manual review: transferase activity is consistent with known biology of Uggt1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0016757
label: glycosyltransferase activity
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: 'Manual review: glycosyltransferase activity is consistent with known biology of Uggt1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:1901135
label: carbohydrate derivative metabolic process
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: 'Manual review: carbohydrate derivative metabolic process may be context-dependent or peripheral for Uggt1.'
action: KEEP_AS_NON_CORE
reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
id: GO:0003980
label: UDP-glucose:glycoprotein glucosyltransferase activity
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: 'Manual review: UDP-glucose:glycoprotein glucosyltransferase activity is consistent with known biology of Uggt1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0009306
label: protein secretion
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: 'Manual review: protein secretion may be context-dependent or peripheral for Uggt1.'
action: KEEP_AS_NON_CORE
reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
id: GO:0032991
label: protein-containing complex
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: 'Manual review: protein-containing complex may be context-dependent or peripheral for Uggt1.'
action: KEEP_AS_NON_CORE
reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:11278576
review:
summary: 'Manual review: protein binding is too generic or over-extended for Uggt1.'
action: MARK_AS_OVER_ANNOTATED
reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
id: GO:0005788
label: endoplasmic reticulum lumen
evidence_type: IDA
original_reference_id: PMID:11535823
review:
summary: 'Manual review: endoplasmic reticulum lumen is consistent with known biology of Uggt1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0005793
label: endoplasmic reticulum-Golgi intermediate compartment
evidence_type: IDA
original_reference_id: PMID:11535823
review:
summary: 'Manual review: endoplasmic reticulum-Golgi intermediate compartment is consistent with known biology of Uggt1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0051082
label: unfolded protein binding
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: 'Manual review: unfolded protein binding is too generic or over-extended for Uggt1.'
action: MARK_AS_OVER_ANNOTATED
reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
id: GO:0051082
label: unfolded protein binding
evidence_type: IDA
original_reference_id: PMID:10764828
review:
summary: 'Manual review: unfolded protein binding is too generic or over-extended for Uggt1.'
action: MARK_AS_OVER_ANNOTATED
reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:10764828
review:
summary: 'Manual review: protein binding is too generic or over-extended for Uggt1.'
action: MARK_AS_OVER_ANNOTATED
reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
id: GO:0005783
label: endoplasmic reticulum
evidence_type: ISO
original_reference_id: GO_REF:0000121
review:
summary: 'Manual review: endoplasmic reticulum is consistent with known biology of Uggt1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0003980
label: UDP-glucose:glycoprotein glucosyltransferase activity
evidence_type: IDA
original_reference_id: PMID:10764828
review:
summary: 'Manual review: UDP-glucose:glycoprotein glucosyltransferase activity is consistent with known biology of Uggt1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0051084
label: '''de novo'' post-translational protein folding'
evidence_type: TAS
original_reference_id: PMID:10764828
review:
summary: 'Manual review: ''de novo'' post-translational protein folding may be context-dependent or peripheral for Uggt1.'
action: KEEP_AS_NON_CORE
reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
id: GO:0003980
label: UDP-glucose:glycoprotein glucosyltransferase activity
evidence_type: TAS
original_reference_id: PMID:10764828
review:
summary: 'Manual review: UDP-glucose:glycoprotein glucosyltransferase activity is consistent with known biology of Uggt1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0003980
label: UDP-glucose:glycoprotein glucosyltransferase activity
evidence_type: IDA
original_reference_id: PMID:12518055
review:
summary: 'Manual review: UDP-glucose:glycoprotein glucosyltransferase activity is consistent with known biology of Uggt1.'
action: ACCEPT
reason: Retained as supported or plausible for this gene and evidence context.
- term:
id: GO:0006457
label: protein folding
evidence_type: TAS
original_reference_id: PMID:12518055
review:
summary: 'Manual review: protein folding may be context-dependent or peripheral for Uggt1.'
action: KEEP_AS_NON_CORE
reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
references:
- id: GO_REF:0000002
title: Gene Ontology annotation through association of InterPro records with GO terms
findings: []
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
- id: GO_REF:0000043
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
findings: []
- id: GO_REF:0000044
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
findings: []
- id: GO_REF:0000108
title: Automatic assignment of GO terms using logical inference, based on on inter-ontology links
findings: []
- id: GO_REF:0000117
title: Electronic Gene Ontology annotations created by ARBA machine learning models
findings: []
- id: GO_REF:0000120
title: Combined Automated Annotation using Multiple IEA Methods
findings: []
- id: GO_REF:0000121
title: RGD ISO annotations to rat from other mammalian species
findings: []
- id: PMID:10764828
title: 'Cloning and characterization of mammalian UDP-glucose glycoprotein: glucosyltransferase and the development of a specific substrate for this enzyme.'
findings: []
- id: PMID:11278576
title: Association between the 15-kDa selenoprotein and UDP-glucose:glycoprotein glucosyltransferase in the endoplasmic reticulum of mammalian cells.
findings: []
- id: PMID:11535823
title: Immunolocalization of UDP-glucose:glycoprotein glucosyltransferase indicates involvement of pre-Golgi intermediates in protein quality control.
findings: []
- id: PMID:12518055
title: UDP-Glc:glycoprotein glucosyltransferase recognizes structured and solvent accessible hydrophobic patches in molten globule-like folding intermediates.
findings: []