Slc5a1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0016324 apical plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation based on phylogenetic inference. SGLT1 apical localization is well-established across mammals. Direct experimental evidence in rat shows SGLT1 at apical membrane in MDCK cells (PMID:11831390), blood-brain barrier endothelial cells (PMID:14986005), and kidney proximal tubule S3 segments (PMID:16204409). Reason: Core localization for SGLT1 function. Phylogenetic inference is well-supported by multiple direct experimental studies in rat demonstrating apical membrane localization in intestinal epithelium, renal proximal tubules, and brain endothelial cells. The N-terminal domain determines apical targeting (PMID:11831390). Supporting Evidence: PMID:11831390 The products of N-terminal deletion clones up to the 19th amino acid were localized at the apical plasma membrane PMID:14986005 Immunostaining suggested that SGLT1 is located in the luminal membrane of the endothelial cells file:rat/Slc5a1/Slc5a1-deep-research-falcon.md Intestine: SGLT1 is localized to the brush‑border (apical) membrane of enterocytes, mediating dietary glucose/galactose absorption.
GO:0016324 apical plasma membrane	IEA GO_REF:0000044	ACCEPT	Summary: IEA annotation based on UniProtKB/Swiss-Prot subcellular location mapping. Redundant with IBA and IDA annotations for same term. Reason: While redundant with IBA annotation, this IEA represents valid automated inference from UniProt subcellular location annotation. Duplicates are acceptable in GO as they represent independent evidence paths. Core localization is correct. Supporting Evidence: UniProtKB:P53790 SUBCELLULAR LOCATION: Apical cell membrane
GO:0016324 apical plasma membrane	IDA PMID:14986005 Localization of the Na+-D-glucose cotransporter SGLT1 in the...	ACCEPT	Summary: Direct experimental evidence from immunohistochemistry in rat brain capillaries showing SGLT1 in luminal (apical) membrane of blood-brain barrier endothelial cells. Reason: High-quality experimental evidence demonstrating apical localization in brain endothelial cells. The study showed immunoreactivity in intracerebral capillaries with staining in the luminal membrane. Supporting Evidence: PMID:14986005 Immunostaining suggested that SGLT1 is located in the luminal membrane of the endothelial cells and in intracellular vesicles
GO:0016324 apical plasma membrane	IDA PMID:11831390 The apical localization of SGLT1 glucose transporter is dete...	ACCEPT	Summary: Direct experimental evidence from MDCK cell localization studies showing rat SGLT1 localizes to apical plasma membrane. N-terminal deletion analysis identified apical targeting signals. Reason: High-quality experimental evidence. Study used rat SGLT1 expressed in MDCK cells and demonstrated apical localization, with identification of the N-terminal targeting domain. Supporting Evidence: PMID:11831390 SGLT1, an isoform of Na+-dependent glucose cotransporters, is localized at the apical plasma membrane in the epithelial cells of the small intestine and the kidney
GO:0016324 apical plasma membrane	ISO GO_REF:0000121	ACCEPT	Summary: ISO annotation transferred from other mammalian species by RGD. Redundant with multiple direct experimental annotations (IDA) for rat SGLT1. Reason: Valid ortholog transfer that is consistent with direct rat experimental evidence. Duplicates are acceptable as independent evidence paths. Supporting Evidence: UniProtKB:P53790 SUBCELLULAR LOCATION: Apical cell membrane
GO:0005886 plasma membrane	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: IBA annotation for plasma membrane localization. This is a parent term of apical plasma membrane (GO:0016324) which is the more specific correct localization. Reason: While technically correct, this is less specific than apical plasma membrane. The more specific term GO:0016324 better captures SGLT1's polarized localization. Acceptable to retain as it captures the broader membrane context. Supporting Evidence: UniProtKB:P53790 FUNCTION: Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose or D-galactose at the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1.
GO:0005886 plasma membrane	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: ISO annotation transferred from mammalian orthologs. Less specific than apical plasma membrane annotations. Reason: Valid but less specific than apical plasma membrane. The more specific term GO:0016324 is preferred for capturing SGLT1's polarized epithelial localization. Supporting Evidence: UniProtKB:P53790 FUNCTION: Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose or D-galactose at the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1.
GO:0031526 brush border membrane	IDA PMID:14986005 Localization of the Na+-D-glucose cotransporter SGLT1 in the...	ACCEPT	Summary: Brush border membrane localization is the canonical site of intestinal and renal SGLT1. The cached abstract of PMID:14986005 describes brain capillary endothelium, but the curator read the full text and the localization is correct for the gene. Reason: Accepted in deference to the curator, who had the full text; brush border membrane localization of rat SGLT1 is independently supported by intestinal apical membrane preparations (PMID:17272350) and by UniProt. Supporting Evidence: PMID:17272350 Western blotting showed that in each case there was a significant decrease in apical GLUT2 level, but no change in SGLT1 level. UniProtKB:P53790 Responsible for the absorption of D-glucose or D-galactose across the apical brush-border membrane of enterocytes, whereas basolateral exit is provided by GLUT2.
GO:0031526 brush border membrane	IDA PMID:17272350 Apical GLUT2 and Cav1.3: regulation of rat intestinal glucos...	ACCEPT	Summary: Direct experimental evidence showing SGLT1 at intestinal brush border membrane in rat jejunum. Western blotting confirmed SGLT1 presence in apical membrane preparations. Reason: High-quality experimental evidence demonstrating SGLT1 at brush border membrane of rat intestinal epithelium. This is a core localization for intestinal glucose absorption. Supporting Evidence: PMID:17272350 Western blotting showed that in each case there was a significant decrease in apical GLUT2 level, but no change in SGLT1 level
GO:0005903 brush border	ISO GO_REF:0000121	MODIFY	Summary: ISO annotation for brush border localization. Brush border (GO:0005903) is the parent of brush border membrane (GO:0031526). The more specific membrane term is more accurate for a transmembrane transporter. Reason: For a transmembrane transporter, the more specific term brush border membrane (GO:0031526) is more appropriate than the general brush border term. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:107678 · mouse Slc5a1 SUPPORTS SOURCE BUT NOT TARGET Mouse donor localization evidence is genuine, but for this apical transporter the brush border membrane (GO:0031526) is the appropriate compartment; the issue is term granularity, not the donor. Proposed replacements: brush border membrane Supporting Evidence: UniProtKB:P53790 Responsible for the absorption of D-glucose or D-galactose across the apical brush-border membrane of enterocytes, whereas basolateral exit is provided by GLUT2.
GO:0016020 membrane	IEA GO_REF:0000002	MODIFY	Summary: Very general IEA annotation based on InterPro record mapping. SGLT1 has many more specific membrane annotations (apical plasma membrane, brush border membrane). Reason: This is too general to be informative. SGLT1 has specific annotations to apical plasma membrane and brush border membrane that are much more informative. The term is correct but uninformative, so it is replaced by the specific location rather than flagged as overreaching. Proposed replacements: apical plasma membrane Supporting Evidence: UniProtKB:P53790 SUBCELLULAR LOCATION: Apical cell membrane
GO:0043226 organelle	IDA PMID:14986005 Localization of the Na+-D-glucose cotransporter SGLT1 in the...	MODIFY	Summary: The paper mentions intracellular vesicles containing SGLT1 in brain endothelial cells. However, 'organelle' is extremely vague and should be more specific. Reason: The paper specifically mentions intracellular vesicles, not generic organelles. A more specific term would be appropriate if we want to capture this localization. Proposed replacements: cytoplasmic vesicle Supporting Evidence: PMID:14986005 Immunostaining suggested that SGLT1 is located in the luminal membrane of the endothelial cells and in intracellular vesicles
GO:0016323 basolateral plasma membrane	TAS PMID:14986005 Localization of the Na+-D-glucose cotransporter SGLT1 in the...	UNDECIDED	Summary: Questionable annotation. PMID:14986005 specifically shows SGLT1 in the LUMINAL (apical) membrane of brain endothelial cells, not basolateral. This appears to be an error in annotation. Reason: The cited paper explicitly states SGLT1 is in the luminal membrane, which is the apical/blood-facing side of brain capillary endothelium, not basolateral. SGLT1 is canonically an apical transporter; basolateral glucose exit is mediated by GLUT2. However, this is a TAS row and only the abstract is cached; the author statement the curator relied on may concern another cell type or context in the full text. Changed from REMOVE to UNDECIDED at the 2026 re-review pending a check of the full text. Supporting Evidence: PMID:14986005 Immunostaining suggested that SGLT1 is located in the luminal membrane of the endothelial cells
GO:0005911 cell-cell junction	IDA PMID:17090404 Asymmetric subcellular distribution of glucose transporters ...	KEEP AS NON CORE	Summary: Direct experimental evidence showing SGLT1 clusters at cell-cell junctions in arterial endothelium. High-density clusters found in proximity to cell-to-cell junctions. Reason: Valid experimental finding in endothelial cells showing SGLT1 clustering near cell-cell junctions. This represents a secondary localization pattern in vascular endothelium, not the primary physiological localization in intestine/kidney. Supporting Evidence: PMID:17090404 Clusters of the glucose transporter isoforms were found at a high density in proximity to the cell-to-cell junctions
GO:0005769 early endosome	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: ISO annotation from mammalian orthologs. SGLT1 trafficking through endosomal compartments is plausible for membrane protein recycling. Reason: Likely reflects trafficking/recycling rather than steady-state functional localization. Not a core localization but may be valid for protein turnover. Supporting Evidence: PMID:12773314 Thereby it was found that the major amount of SGLT1 resided in intracellular compartments and only a minor amount in apical plasma membranes.
GO:0048471 perinuclear region of cytoplasm	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: ISO annotation from orthologs. May reflect biosynthetic pathway localization (ER/Golgi) rather than functional localization. Reason: Likely reflects biosynthetic pathway (ER/Golgi in perinuclear region) rather than functional localization. Not a core localization for SGLT1 function. Supporting Evidence: PMID:12773314 Thereby it was found that the major amount of SGLT1 resided in intracellular compartments and only a minor amount in apical plasma membranes.
GO:0005412 D-glucose:sodium symporter activity	IBA GO_REF:0000033	ACCEPT	Summary: Core molecular function of SGLT1 - IBA based on phylogenetic inference. This is the defining activity of the SGLT1 transporter family. Reason: This is THE core molecular function of SGLT1. The transporter catalyzes 2 Na+ : 1 D-glucose cotransport as established across all species. UniProt confirms this catalytic activity with Rhea reaction annotation. Supporting Evidence: PMID:15829715 the renal brush-border membrane Na+/glucose co-transporter-1 (SGLT1) is a molecular target for Cd2+ toxicity
GO:0005412 D-glucose:sodium symporter activity	ISO GO_REF:0000121	ACCEPT	Summary: ISO annotation from mammalian orthologs. Consistent with direct rat evidence. Reason: Core molecular function, well-supported by direct rat experimental evidence and consistent phylogenetic conservation. Supporting Evidence: UniProtKB:P53790 Reaction=D-glucose(out) + 2 Na(+)(out) = D-glucose(in) + 2 Na(+)(in)
GO:0005412 D-glucose:sodium symporter activity	IDA PMID:15829715 The endogenous CXXC motif governs the cadmium sensitivity of...	ACCEPT	Summary: Direct experimental evidence showing rat SGLT1 Na+/glucose cotransport activity. Study used methyl-D-glucopyranoside uptake assays in SGLT1-expressing cells. Reason: High-quality direct experimental evidence demonstrating the core molecular function in rat SGLT1. Supporting Evidence: PMID:15829715 Cd2+ acted as a noncompetitive, partial inhibitor of methyl-D-glucopyranoside uptake in vesicles from COS-7 cells transiently expressing SGLT1
GO:0005412 D-glucose:sodium symporter activity	TAS PMID:11831390 The apical localization of SGLT1 glucose transporter is dete...	ACCEPT	Summary: TAS annotation from paper on SGLT1 apical localization. Paper discusses SGLT1 as glucose transporter but main focus is localization not transport activity. Reason: The paper refers to SGLT1's known function as Na+-dependent glucose cotransporter. While the experimental focus is localization, the stated function is accurate. Supporting Evidence: PMID:11831390 SGLT1, an isoform of Na+-dependent glucose cotransporters, is localized at the apical plasma membrane
GO:0015371 galactose:sodium symporter activity	ISO GO_REF:0000121	ACCEPT	Summary: ISO annotation for galactose transport. SGLT1 transports both D-glucose and D-galactose with similar affinity - this is well-established in the literature. Reason: Core molecular function. SGLT1 transports D-galactose as well as D-glucose, both with high affinity. UniProt catalytic activity annotation confirms this. PMID:16204409 used galactose uptake to measure SGLT1 activity. Supporting Evidence: PMID:16204409 The phlorizin-sensitive uptake of d-[(3)H]galactose in BBM vesicles
GO:0015371 galactose:sodium symporter activity	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation based on sequence similarity. Consistent with ISO annotation and UniProt functional annotation. Reason: Core molecular function. Galactose transport by SGLT1 is well-established and conserved across species. Supporting Evidence: UniProtKB:P53790 Reaction=D-galactose(out) + 2 Na(+)(out) = D-galactose(in) + 2 Na(+)(in)
GO:0005372 water transmembrane transporter activity	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation for water transport. SGLT1 functions as a water channel with high water conductivity comparable to aquaporins, enabling passive water transport. Reason: Core molecular function. UniProt describes SGLT1 as having high water conductivity comparable to aquaporins, enabling passive water transport in response to osmotic gradients created during sugar/Na+ uptake. Supporting Evidence: UniProtKB:P53790 Acts as a water channel enabling passive water transport in response to the osmotic gradient created upon sugar and Na(+) uptake. PMID:26945065 Calculation of the unitary water channel permeability, pf, yielded similar values for cell and proteoliposome experiments.
GO:0005372 water transmembrane transporter activity	ISO GO_REF:0000121	ACCEPT	Summary: ISO annotation from orthologs for water transport activity. Reason: Core molecular function. Water transport by SGLT1 is well-documented and important for transepithelial water permeability in intestine. Supporting Evidence: UniProtKB:P53790 Acts as a water channel enabling passive water transport in response to the osmotic gradient created upon sugar and Na(+) uptake. PMID:26945065 Calculation of the unitary water channel permeability, pf, yielded similar values for cell and proteoliposome experiments.
GO:0055056 D-glucose transmembrane transporter activity	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: ISO annotation for general glucose transporter activity. This is less specific than D-glucose:sodium symporter activity which captures the coupling mechanism. Reason: While correct, this is less informative than D-glucose:sodium symporter activity (GO:0005412) which specifies the sodium-coupling mechanism that defines SGLT1. Supporting Evidence: UniProtKB:P53790 Reaction=D-glucose(out) + 2 Na(+)(out) = D-glucose(in) + 2 Na(+)(in)
GO:0015151 alpha-glucoside transmembrane transporter activity	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Alpha-glucoside transmembrane transporter activity transferred from human SGLT1 (UniProtKB:P13866). SGLT1 transports the alpha-glucoside methyl-alpha-D-glucopyranoside (AMG), the standard non-metabolizable SGLT substrate, so the term is correct, but the physiological substrates are D-glucose and D-galactose. Reason: The GO definition covers glycosides with an alpha-linked glucose residue, which includes methyl-alpha-D-glucopyranoside used in SGLT1 uptake assays (human donor IDA, PMID:20980548). The activity is real but reflects a model substrate, so it is kept as non-core rather than flagged as over-annotation (changed from MARK_AS_OVER_ANNOTATED at the 2026 re-review). Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P13866 · human SLC5A1 SUPPORTS TRANSFER Human SGLT1 transports methyl-alpha-D-glucopyranoside (IDA, PMID:20980548); the transfer to rat is sound, but the substrate is a non-physiological model compound. Supporting Evidence: PMID:20980548 In these experiments the sugar used was nonmetabolizable and SGLT-specific, αMDG.
GO:0015293 symporter activity	IEA GO_REF:0000043	MODIFY	Summary: IEA annotation from UniProtKB keyword mapping. Very general term. Reason: Too general. The specific term D-glucose:sodium symporter activity (GO:0005412) is much more informative and captures the actual substrate specificity. The term is correct but uninformative, so it is replaced with the specific term (changed from MARK_AS_OVER_ANNOTATED at review follow-up, for consistency with the GO:0022857 row). GOA no longer carries this row. Proposed replacements: D-glucose:sodium symporter activity Supporting Evidence: UniProtKB:P53790 FUNCTION: Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose or D-galactose at the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1.
GO:0022857 transmembrane transporter activity	IEA GO_REF:0000002	MODIFY	Summary: Very general IEA annotation from InterPro mapping. Reason: Far too general to be informative. Specific molecular function annotations (D-glucose:sodium symporter activity) provide the relevant information. The term is correct but uninformative, so it is replaced with the specific term (changed from MARK_AS_OVER_ANNOTATED at the 2026 re-review). Proposed replacements: D-glucose:sodium symporter activity Supporting Evidence: UniProtKB:P53790 FUNCTION: Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose or D-galactose at the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1.
GO:0008324 monoatomic cation transmembrane transporter activity	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: IEA from ARBA machine learning. SGLT1 uses Na+ gradient to drive glucose transport but is not primarily a cation transporter - it is a sugar transporter. Reason: Misleading annotation. While SGLT1 translocates Na+ ions, it is primarily a sugar transporter that uses the Na+ gradient as driving force. The sodium transport is coupled to/incidental to the primary glucose transport function. GOA no longer carries this row. Supporting Evidence: UniProtKB:P53790 FUNCTION: Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose or D-galactose at the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1.
GO:0001951 intestinal D-glucose absorption	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation for intestinal glucose absorption - THE core biological process for SGLT1 in the gut. Reason: Core biological process. SGLT1 is the primary transporter for dietary glucose absorption across enterocyte brush border membrane. Supporting Evidence: PMID:17272350 We have proposed a model of intestinal glucose absorption in which transport by SGLT1 induces rapid insertion and activation of GLUT2
GO:0001951 intestinal D-glucose absorption	ISO GO_REF:0000121	ACCEPT	Summary: ISO annotation from orthologs. Consistent with direct rat evidence. Reason: Core biological process, well-supported by rat experimental evidence. Supporting Evidence: UniProtKB:P53790 Has a primary role in the transport of dietary monosaccharides from enterocytes to blood.
GO:0001951 intestinal D-glucose absorption	TAS PMID:15829715 The endogenous CXXC motif governs the cadmium sensitivity of...	ACCEPT	Summary: TAS annotation. The cited paper (abstract-only in cache) is about cadmium inhibition of renal brush-border SGLT1 D-glucose transport; its abstract does not mention the intestine, so the intestinal context is not supported by this reference as cached. Reason: Core biological process, accepted on independent grounds rather than on the cited abstract. PMID:15829715 supports SGLT1 Na+-coupled D-glucose transport only (renal context); intestinal D-glucose absorption by SGLT1 is supported by PMID:17272350 and the same term is carried by the ISS and ISO rows. The curator's TAS (full text not cached) is not overruled. Supporting Evidence: PMID:15829715 Cd2+ binding to the CXXC motif induces conformational changes that cause a partial inhibition of d-glucose transport PMID:17272350 We have proposed a model of intestinal glucose absorption in which transport by SGLT1 induces rapid insertion and activation of GLUT2
GO:0035623 renal D-glucose absorption	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for renal glucose reabsorption. SGLT1 handles glucose reabsorption in S3 segment of proximal tubule (minor fraction, ~3% of total). Reason: Core biological process. PMID:16204409 directly demonstrates SGLT1 in rat kidney S3 proximal tubule segments with functional glucose transport activity. Supporting Evidence: PMID:16204409 SGLT1 (SLC5A1) mediates a part of glucose and galactose reabsorption in the mammalian proximal tubule PMID:16204409 the expression of SGLT1 is represented by a 75-kDa protein localized largely in the PT S3 segments
GO:0035623 renal D-glucose absorption	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation from sequence similarity. Consistent with direct rat evidence. Reason: Core biological process, well-supported by direct rat experimental evidence. Supporting Evidence: UniProtKB:P53790 Together with SGLT2, functions in reabsorption of D-glucose from glomerular filtrate, playing a nonredundant role in the S3 segment of the proximal tubules (By similarity).
GO:0035623 renal D-glucose absorption	ISO GO_REF:0000121	ACCEPT	Summary: ISO annotation from orthologs. Consistent with IBA and direct rat evidence. Reason: Core biological process with strong experimental support in rat. Supporting Evidence: UniProtKB:P53790 Together with SGLT2, functions in reabsorption of D-glucose from glomerular filtrate, playing a nonredundant role in the S3 segment of the proximal tubules (By similarity).
GO:0098708 D-glucose import across plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for glucose import. Accurate description of SGLT1's transport direction (import into cell). Reason: Core biological process. SGLT1 imports glucose from lumen into epithelial cells. This is a fundamental aspect of its transport function. Supporting Evidence: UniProtKB:P53790 Reaction=D-glucose(out) + 2 Na(+)(out) = D-glucose(in) + 2 Na(+)(in)
GO:0098708 D-glucose import across plasma membrane	ISO GO_REF:0000121	ACCEPT	Summary: ISO annotation from orthologs. Consistent with IBA annotation. Reason: Core biological process describing the import direction of SGLT1-mediated glucose transport. Supporting Evidence: UniProtKB:P53790 Reaction=D-glucose(out) + 2 Na(+)(out) = D-glucose(in) + 2 Na(+)(in)
GO:1904659 D-glucose transmembrane transport	ISO GO_REF:0000121	ACCEPT	Summary: ISO annotation for glucose transmembrane transport. Reason: Core biological process. This is the primary transport function of SGLT1. Supporting Evidence: UniProtKB:P53790 Reaction=D-glucose(out) + 2 Na(+)(out) = D-glucose(in) + 2 Na(+)(in)
GO:1904659 D-glucose transmembrane transport	TAS PMID:11831390 The apical localization of SGLT1 glucose transporter is dete...	ACCEPT	Summary: TAS annotation. Paper focuses on localization but references SGLT1's glucose transport function. Reason: Core biological process. While paper's experimental focus is localization, SGLT1's glucose transport function is accurately referenced. Supporting Evidence: PMID:11831390 SGLT1 glucose transporter...plays a pivotal role in the absorption and reabsorption of sugars
GO:0015757 galactose transmembrane transport	IEA GO_REF:0000108	ACCEPT	Summary: IEA annotation based on logical inference. SGLT1 transports galactose with similar affinity to glucose - this is experimentally demonstrated in rat. Reason: Core biological process. Galactose transport by SGLT1 is well-established. PMID:16204409 used galactose uptake assays to measure rat SGLT1 activity. Supporting Evidence: PMID:16204409 SGLT1 (SLC5A1) mediates a part of glucose and galactose reabsorption in the mammalian proximal tubule
GO:0050892 intestinal absorption	TAS PMID:16204409 Rat renal glucose transporter SGLT1 exhibits zonal distribut...	ACCEPT	Summary: TAS annotation. The paper primarily focuses on kidney, though it mentions intestinal absorption as SGLT1 function. Reason: Core biological process. SGLT1's role in intestinal absorption is well-established. Supporting Evidence: PMID:16204409 SGLT1 (SLC5A1) mediates a part of glucose and galactose reabsorption in the mammalian proximal tubule
GO:0050892 intestinal absorption	ISO GO_REF:0000121	ACCEPT	Summary: ISO annotation from orthologs. Consistent with known SGLT1 function. Reason: Core biological process for SGLT1 in the gut. Supporting Evidence: UniProtKB:P53790 Has a primary role in the transport of dietary monosaccharides from enterocytes to blood.
GO:0035377 transepithelial water transport	ISO GO_REF:0000121	ACCEPT	Summary: ISO annotation for water transport function. SGLT1 acts as a water channel with high conductivity comparable to aquaporins. Reason: Core biological process. SGLT1's water transport activity is important for intestinal water absorption coupled to glucose/Na+ uptake. Supporting Evidence: UniProtKB:P53790 Acts as a water channel enabling passive water transport in response to the osmotic gradient created upon sugar and Na(+) uptake. PMID:26945065 Calculation of the unitary water channel permeability, pf, yielded similar values for cell and proteoliposome experiments.
GO:0098719 sodium ion import across plasma membrane	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: ISO annotation for sodium import. SGLT1 couples 2 Na+ import per glucose. Reason: While technically accurate (SGLT1 imports 2 Na+ per glucose), sodium transport is secondary to the primary function of glucose transport. The Na+ gradient drives glucose uptake rather than being the primary transported substrate. Supporting Evidence: UniProtKB:P53790 FUNCTION: Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose or D-galactose at the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1.
GO:0006814 sodium ion transport	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: IEA annotation from UniProtKB keyword mapping. Reason: While Na+ is cotransported with glucose, this annotation may give the misleading impression that SGLT1 is primarily a sodium transporter. The primary function is glucose transport using the Na+ gradient. GOA no longer carries this row. Supporting Evidence: UniProtKB:P53790 FUNCTION: Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose or D-galactose at the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1.
GO:0006811 monoatomic ion transport	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: Very general IEA annotation for ion transport. Reason: Too general and misleading. SGLT1 is a sugar transporter that cotransports sodium, not primarily an ion transporter. GOA no longer carries this row. Supporting Evidence: UniProtKB:P53790 FUNCTION: Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose or D-galactose at the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1.
GO:0055085 transmembrane transport	IEA GO_REF:0000002	MODIFY	Summary: Very general IEA annotation from InterPro mapping. Reason: Far too general to be informative. Specific process annotations provide the relevant information about SGLT1 function. The term is correct but uninformative, so it is replaced with the specific term (changed from MARK_AS_OVER_ANNOTATED at the 2026 re-review). Proposed replacements: D-glucose transmembrane transport Supporting Evidence: UniProtKB:P53790 FUNCTION: Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose or D-galactose at the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1.
GO:0150104 transport across blood-brain barrier	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: ISO annotation for BBB transport. Rat experimental evidence shows SGLT1 in brain capillary endothelium with upregulation after ischemia. Reason: Valid annotation supported by rat experimental evidence (PMID:14986005). Not a core function (intestine/kidney are primary sites) but represents an established secondary physiological role. Supporting Evidence: PMID:14986005 The data suggest that SGLT1 participates in transport of D-glucose across the blood-brain barrier
GO:1902476 chloride transmembrane transport	ISO NOT GO_REF:0000121	ACCEPT	Summary: NOT annotation - SGLT1 does not transport chloride. Transferred from human SGLT1 (UniProtKB:P13866), where tracer flux showed that Cl- modulates SGLT1 kinetics but is not itself transported (PMID:10973981). Reason: The negated annotation is correct and informative; it distinguishes SGLT1 from Na+/Cl--coupled transporters such as GAT1. Earlier reviews treated this row as a positive chloride-transport claim; it is a NOT annotation and is accepted (changed from UNDECIDED at the 2026 re-review). Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P13866 · human SLC5A1 SUPPORTS TRANSFER Human SGLT1 NOT chloride transmembrane transport (IDA, PMID:10973981); the negative finding transfers to the rat ortholog. Supporting Evidence: PMID:10973981 In contrast, Cl(-) was not transported by SGLT1.
GO:0000017 alpha-glucoside transport	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Alpha-glucoside transport transferred from human SGLT1 (UniProtKB:P13866). SGLT1 transports methyl-alpha-D-glucopyranoside, an alpha-glucoside model substrate; the physiological substrates are D-glucose and D-galactose. Reason: Correct per the GO definition (glycosides with an alpha-linked glucose residue), based on human SGLT1 uptake of methyl-alpha-D-glucopyranoside (PMID:20980548), but not a physiological core process. Changed from MARK_AS_OVER_ANNOTATED at the 2026 re-review. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P13866 · human SLC5A1 SUPPORTS TRANSFER Human SGLT1 alpha-methyl-D-glucoside transport (PMID:20980548) transfers soundly to rat; the substrate is a model compound, hence non-core. Supporting Evidence: PMID:20980548 In these experiments the sugar used was nonmetabolizable and SGLT-specific, αMDG.
GO:0009758 carbohydrate utilization	IDA PMID:25592016 Induction of histone H3K4 methylation at the promoter, enhan...	MODIFY	Summary: IDA annotation from study on dietary regulation of Sglt1 gene expression. The paper shows epigenetic regulation (H3K4 methylation) of Sglt1 in response to high-starch diet, not direct SGLT1 involvement in carbohydrate utilization. Reason: The paper demonstrates transcriptional regulation of Sglt1 by diet, not a direct role for SGLT1 protein in carbohydrate utilization. The appropriate process would be related to glucose absorption/transport, not utilization. Proposed replacements: intestinal D-glucose absorption Supporting Evidence: PMID:25592016 Feeding rats the high-starch/low-fat diet induced mono-, di-, and trimethylation of histone H3K4 on the promoter and transcribed regions of the Si and Sglt1 genes
GO:0001656 metanephros development	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Metanephros development (acts upstream of or within) transferred from mouse Slc5a1 (MGI:MGI:107678). The donor evidence is an antisense experiment in embryonic kidney explants in which SGLT1 knockdown reduced tubule formation (PMID:10997927). Reason: SGLT1 transports glucose in developing tubules; the explant data indicate that this uptake is needed for tubulogenesis, which fits the acts_upstream_of_or_within qualifier but is an indirect, non-core role of a glucose transporter. The source is now traced, so the row is changed from UNDECIDED to KEEP_AS_NON_CORE. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: MGI:MGI:107678 · mouse Slc5a1 SUPPORTS TRANSFER Mouse IMP (PMID:10997927, antisense in metanephric explants) supports an upstream requirement of SGLT1 for tubulogenesis; transfer to rat is reasonable but the role is indirect. Supporting Evidence: PMID:10997927 Treatment with SGLT-1 antisense selectively decreased the population of tubules in the metanephric explants.
GO:0005412 D-glucose:sodium symporter activity	ISO GO_REF:0000121	ACCEPT	Summary: D-glucose:sodium symporter activity transferred by orthology from human SGLT1 (UniProtKB:P13866); this is the defining activity of SGLT1. Reason: Donor-split duplicate of the mouse-sourced (MGI:MGI:107678) ISO row; here the donor is human SGLT1 (P13866), which has extensive IDA support for Na+-coupled glucose transport. Consistent with rat experimental evidence. Supporting Evidence: UniProtKB:P53790 Reaction=D-glucose(out) + 2 Na(+)(out) = D-glucose(in) + 2 Na(+)(in)
GO:0006812 monoatomic cation transport	IEA GO_REF:0000117	MODIFY	Summary: Monoatomic cation transport from an ARBA rule. SGLT1 does move Na+ (2 Na+ per sugar), but the generic cation-transport term says nothing about the coupled sugar transport that defines the protein. Reason: The claim is not wrong, but it is far less informative than the specific sodium ion import term, consistent with the treatment of the retired generic ion-transport rows. Replace with sodium ion import across plasma membrane. Proposed replacements: sodium ion import across plasma membrane Supporting Evidence: UniProtKB:P53790 FUNCTION: Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose or D-galactose at the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1.
GO:0016324 apical plasma membrane	ISO GO_REF:0000121	ACCEPT	Summary: Apical plasma membrane transferred by orthology from human SGLT1 (UniProtKB:P13866); the canonical location of SGLT1 in enterocytes and proximal tubule. Reason: Donor-split duplicate of the mouse-sourced ISO row; here the donor is human SGLT1 (P13866), which has IDA/EXP support for apical localization. Consistent with rat IDA rows (PMID:14986005, PMID:11831390). Supporting Evidence: UniProtKB:P53790 SUBCELLULAR LOCATION: Apical cell membrane
GO:0016324 apical plasma membrane	ISS GO_REF:0000024	ACCEPT	Summary: Apical plasma membrane by sequence similarity to mouse SGLT1 (UniProtKB:Q8C3K6), the source of the UniProt subcellular-location statement for the rat entry. Reason: Mouse Slc5a1 apical localization is experimentally established and conserved; consistent with direct rat evidence for apical/brush-border membrane localization. Supporting Evidence: UniProtKB:P53790 SUBCELLULAR LOCATION: Apical cell membrane
GO:0055056 D-glucose transmembrane transporter activity	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: D-glucose transmembrane transporter activity transferred by orthology from human SGLT1 (UniProtKB:P13866); correct but less specific than D-glucose:sodium symporter activity. Reason: Donor-split duplicate of the mouse-sourced ISO row, here with human SGLT1 (P13866) as donor; reviewed consistently with that row. The Na+-coupled symporter term is the informative core activity. Supporting Evidence: UniProtKB:P53790 Reaction=D-glucose(out) + 2 Na(+)(out) = D-glucose(in) + 2 Na(+)(in)
GO:1904659 D-glucose transmembrane transport	ISO GO_REF:0000121	ACCEPT	Summary: D-glucose transmembrane transport (acts upstream of or within) transferred from human SGLT1 (UniProtKB:P13866); SGLT1 directly transports D-glucose. Reason: Donor-split duplicate of the mouse-sourced ISO row with the same qualifier; here the donor is human SGLT1 (P13866). Core transport process. Supporting Evidence: UniProtKB:P53790 Reaction=D-glucose(out) + 2 Na(+)(out) = D-glucose(in) + 2 Na(+)(in)
GO:1904659 D-glucose transmembrane transport	ISO GO_REF:0000121	ACCEPT	Summary: D-glucose transmembrane transport (involved in) transferred from human SGLT1 (UniProtKB:P13866); SGLT1 directly transports D-glucose across the plasma membrane. Reason: Same donor and term as the acts_upstream_of_or_within row but asserting direct involvement, which is correct for the transporter itself. Core transport process. Supporting Evidence: UniProtKB:P53790 Reaction=D-glucose(out) + 2 Na(+)(out) = D-glucose(in) + 2 Na(+)(in)

Gene Description

Existing Annotations Review

Core Functions

Primary molecular function - electrogenic Na+-coupled D-glucose symporter with 2:1 Na+:glucose stoichiometry

Co-transports D-galactose with sodium using same mechanism as glucose transport

Acts as water channel with high conductivity comparable to aquaporins

References

Deep Research

Falcon

📚 Additional Documentation

Notes

Bioreason Rl Predictions

Bioreason Rl Review

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