Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniPathway vocabulary mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs
Combined Automated Annotation using Multiple IEA Methods
Molecular cloning of a pancreatic islet-specific glucose-6-phosphatase catalytic subunit-related protein.
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IGRP is a 355-residue protein 50% identical to liver G6Pase with similar predicted transmembrane topology, conserved catalytic residues and an ER retention signal; it is translocated and glycosylated in a microsomal system.
"structurally related (50% overall identity) to the liver glucose-6-phosphatase and exhibited similar predicted transmembrane topology, conservation of catalytically important residues, and the presence of an endoplasmic reticulum retention signal."
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Expression is islet-specific and parallels insulin during development.
"During development, it was expressed in parallel with insulin mRNA."
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No phosphatase activity was detected in transfected cells in this first study, a result superseded by PMID:14722102.
"the IGRP failed to show glucose phosphotransferase or phosphatase activity with p-nitrophenol phosphate, inorganic pyrophosphate, or a range of sugar phosphates hydrolyzed by the liver enzyme."
Localization of the murine Niemann-Pick C1 protein to two distinct intracellular compartments.
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The abstract describes localisation of NPC1 only and does not mention G6pc2/IGRP.
"In this report, we use subcellular fractionation and microscopy to determine the localization of the murine Niemann-Pick C1 (NPC1) protein."
Enzymatic characterization of the pancreatic islet-specific glucose-6-phosphatase-related protein (IGRP).
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Recombinant IGRP hydrolyses glucose 6-phosphate with Km 0.29-0.45 mM.
"The K(m) and V(max) values determined using glucose-6-phosphate as the substrate were 0.45 mm and 32 nmol/mg/min by malachite green assay, and 0.29 mm and 77 nmol/mg/min by glucose oxidase/peroxidase coupling assay, respectively."
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A selective inhibitor distinguishes IGRP from liver G6Pase.
"Interestingly, this inhibitor did not affect LG-6-Pase activity, while conversely LG-6-Pase inhibitors did not affect IGRP activity."
G6PC2: a negative regulator of basal glucose-stimulated insulin secretion.
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Knockout islets have reduced glucose-6-phosphatase activity.
"Fig. 1A shows that glucose-6-phosphatase activity is reduced in islets isolated from G6pc2 KO mice."
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G6pc2 deletion shifts the glucose dose-response of GSIS to the left and lowers fasting glucose without changing fasting insulin.
"As a consequence, under fasting conditions in which plasma insulin levels were identical, blood glucose levels were reduced in G6pc2 KO mice, again consistent with human GWAS data."
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Deletion does not change the maximal rate of GSIS.
"This observation suggests that the absence of G6pc2 does not affect the Vmax of GSIS."
Identification of the beta cell antigen targeted by a prevalent population of pathogenic CD8+ T cells in autoimmune diabetes.
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IGRP is the target of a prevalent population of pathogenic CD8+ T cells in NOD mice.
"the autoantigen targeted by a prevalent population of pathogenic CD8+ T cells in nonobese diabetic mice is islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)"
Evidence for the expression of both the hydrolase and translocase components of hepatic glucose-6-phosphatase in murine pancreatic islets.
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Islets express the G6P transporter G6PT1 and IGRP; low IGRP expression was also seen in liver.
"the expression of islet-specific G6Pase-related protein (IGRP) in pancreatic islets was confirmed and its expression in liver was also observed"
The islet-specific glucose-6-phosphatase-related protein, implicated in diabetes, is a glycoprotein embedded in the endoplasmic reticulum membrane.
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Human IGRP is an ER glycoprotein with nine transmembrane domains, degraded mainly by the proteasome.
"IGRP is a glycoprotein, held in the endoplasmic reticulum by nine transmembrane domains"
Developmental control of CD8 T cell-avidity maturation in autoimmune diabetes.
Deletion of the gene encoding the islet-specific glucose-6-phosphatase catalytic subunit-related protein autoantigen results in a mild metabolic phenotype.
Glucose-6-phosphatase catalytic subunit gene family.
Effects of GCK, GCKR, G6PC2 and MTNR1B variants on glucose metabolism and insulin secretion.
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A G6PC2 SNP is associated with fasting glucose and insulin secretion indices in a Chinese population.
"We replicated the association between GCK rs1799884, G6PC2 rs16856187 and MTNR1B rs10830963 and fasting glucose in our samples"
Genetic and functional assessment of the role of the rs13431652-A and rs573225-A alleles in the G6PC2 promoter that are strongly associated with elevated fasting glucose levels.
Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels.
Novel stable isotope analyses demonstrate significant rates of glucose cycling in mouse pancreatic islets.
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Islets cycle about 16% of net glucose uptake at 5 mM glucose, and cycling is abolished in G6pc2 knockout islets.
"glucose cycling was abolished in G6pc2 KO mouse islets, confirming that G6pc2 opposes the action of the glucose sensor glucokinase by hydrolyzing G6P"
G6PC2 Modulates Fasting Blood Glucose In Male Mice in Response to Stress.
G6PC2 Modulates the Effects of Dexamethasone on Fasting Blood Glucose and Glucose Tolerance.
Effects of G6pc2 deletion on body weight and cholesterol in mice.
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Lower fasting glucose in knockout mice is robust across sex, background and diet.
"FBG was reduced in G6pc2 KO mice largely independent of gender, genetic background or diet"
Pancreatic islet beta cell-specific deletion of G6pc2 reduces fasting blood glucose.
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Beta-cell-specific deletion is sufficient to lower fasting glucose without changing fasting insulin.
"In adult mice, beta cell-specific deletion of G6pc2 was sufficient to reduce FBG without changing FPI."
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G6pc1 or G6pc3 dominate peripheral tissues; G6pc2 dominates islets, where G6pc1 is not detected.
"G6pc2 expression is much higher than G6pc3 in both pancreas and islets with G6pc1 expression not detected"
G6PC2 confers protection against hypoglycemia upon ketogenic diet feeding and prolonged fasting.
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G6pc2 knockout mice become hypoglycaemic on a ketogenic diet or a 24 h fast.
"blood glucose fell to 70 mg/dl or less in G6pc2 KO but not WT mice, suggesting that G6PC2 may have evolved, in part, to prevent hypoglycemia"
Nonsynonymous single-nucleotide polymorphisms in the G6PC2 gene affect protein expression, enzyme activity, and fasting blood glucose.
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G6PC1 has much higher G6Pase activity than G6PC2 at matched protein expression.
"G6PC1 exhibited much higher G6Pase activity than G6PC2 in these in vitro assays"
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Mouse G6PC2 has measurable microsomal G6Pase activity.
"Higher G6Pase activity was detected following transient expression of His tagged mouse G6PC2 compared with His-tagged human G6PC2"
Glucose-6-phosphatase catalytic subunit 2 negatively regulates glucose oxidation and insulin secretion in pancreatic beta-cells.
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G6pc2 deletion raises glycolytic and citric acid cycle flux by about 60% and doubles GSIS in a beta-cell line.
"deletion of G6pc2 led to ∼60% increases in glycolytic and citric acid cycle (CAC) fluxes at both 5 and 11 mM glucose concentrations"
G6PC1 and G6PC2 influence G6P flux but not HSD11B1 activity.
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Overexpression of G6PC1 or G6PC2 blunts glucose-stimulated fusion-gene expression in islet cells.
"While overexpression of G6PC1 and G6PC2 blunted glucose-stimulated fusion gene expression, it had minimal effect on glucocorticoid-stimulated fusion gene expression."
Biochemical and metabolic characterization of a G6PC2 inhibitor.
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Vmax for G6P hydrolysis is lower for G6PC2 than for G6PC1 and G6PC3.
"the observed Vmax for G6P hydrolysis by G6PC1 was considerably greater than that for G6PC2 and G6PC3"
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A human G6PC2 inhibitor does not inhibit mouse G6PC2.
"VU0945627 does not inhibit mouse G6PC2 despite its 84% sequence identity with human G6PC2."
Multiple promoter and enhancer differences likely contribute to augmented G6PC2 expression in human versus mouse pancreatic islet alpha cells.
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Mouse G6pc2 is about 20-fold beta-cell biased, against about 5-fold in human.
"In mice, RNA-Seq analyses have demonstrated that G6pc2 is expressed at approximately 20-fold higher levels in pancreatic islet β-cells versus α-cells"
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The authors predicted an alpha-cell role for G6PC2 from the futile-cycle model.
"Based on the established function of the glucokinase/G6PC2 futile cycle in β-cells we predict that G6PC2 is highly likely to modulate the sensitivity of glucagon secretion to glucose in α-cells."
G6PC2 controls glucagon secretion by defining the set point for glucose in pancreatic α cells.
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Inducible alpha-cell-specific deletion of G6pc2 shifts the glucose set point for suppression of amino-acid-stimulated glucagon secretion leftward, so mutant islets secrete less glucagon at 0.5-5 mM glucose although secretion at zero glucose is unchanged.
"when incubated in the presence of 0.5mM, 1mM, 3mM, or 5mM glucose, α-G6PC2KO islets secreted significantly (P < 0.0001) less glucagon relative to control islets, confirming a left shift in the glucose response curve for glucagon release"
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Fasting and glucose-suppressed plasma glucagon are lower in alpha-cell-specific knockouts of both sexes, with insulin unchanged.
"revealed lower glucagon concentrations in both male and female α-G6PC2KO mice relative to controls"
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Islet composition, alpha and beta cell proportions and proliferation are unaffected by alpha-cell deletion.
"We observed no changes in proliferation of α or β cells, nor in their relative proportions in islets of 12-week-old α-G6PC2KO versus age-matched control mice"
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The same effect on glucose suppression of glucagon secretion was reproduced by shRNA knockdown in sorted primary human alpha cells.
"we normalized the results to the KCl response, and found the shG6PC2-exressing α cell pseudoislets to be significantly (P < 0.05 at 1mM glucose, P < 0.01 at 3, 5 and 9 mM glucose) more sensitive to glucose"
Cloning and characterization of the human and rat islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) genes.
mouse/G6pc2/G6pc2-uniprot.txt
OpenScientist blinded function-assignment report on G6pc2 and gluconeogenesis (GO:0006094)
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Without this review's decision or the Bgee report, OpenScientist judged gluconeogenesis refuted as a biological process for G6pc2 while retaining glucose-6-phosphatase activity as its molecular function.
"The gluconeogenesis BP should be removed or flagged as a non-core, paralog-driven IBA carry-over."
mouse/G6pc2/G6pc2-bioinformatics/chicken_paralogs.md
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Chicken G6PC1 is the liver and kidney paralog; chicken G6PC2 is low in every sampled tissue, and no chicken paralog has a pancreas or islet call.
"Present calls in pancreas or islet for any chicken paralog: none."
A variant in the G6PC2/ABCB11 locus is associated with increased fasting plasma glucose, increased basal hepatic glucose production and increased insulin release after oral and intravenous glucose loads.
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In elderly Danish twins, carriers of the fasting-glucose raising rs560887 G allele had nominally higher basal hepatic glucose production during a hyperinsulinaemic-euglycaemic clamp.
"Among elderly twins, G allele carriers had higher basal hepatic glucose production (p = 0.04)."
Effects of sex and fasting/refeeding on hepatic AMPK signaling in chickens (Gallus gallus).
Expression of glucose-6-phosphatase system genes in murine cortex and hypothalamus.
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Mouse G6pc2 transcript is detectable in hypothalamus only at increased template input, and not in cortex.
"was detectable only in hypothalamus tissue at increased template inputs"
mouse/G6pc2/G6pc2-bioinformatics/RESULTS.md
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G6pc2 is islet- and pancreas-dominant; G6pc1 dominates liver, kidney and intestine.
"islet of Langerhans (100); pancreas (90)"
mouse/G6pc2/G6pc2-deep-research-claude-code.md