SLC10A2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: The HuRI systematic binary interactome screen reports an interaction between SLC10A2 and UPK1B (UniProtKB:O75841) [PMID:32296183]. The annotation records only the generic term protein binding and says nothing about what SLC10A2 does. Reason: GO:0005515 protein binding is uninformative: it asserts that a binding event was seen without identifying a molecular function. The source is a proteome-scale yeast two-hybrid map [PMID:32296183] that assigns no function to either partner, and nothing in it supports a more specific molecular-function term for SLC10A2. Removal does not assert that the reported interaction is false; the informative molecular function of this protein is sodium-coupled bile acid symport [PMID:9458785, PMID:9856990]. Supporting Evidence: PMID:32296183 Here we present a human 'all-by-all' PMID:9458785 In transiently transfected COS cells, ileal Na(+)-bile acid cotransporter-mediated taurocholate uptake was strictly Na+ dependent and chloride independent.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: HuRI reports an interaction between SLC10A2 and EFNA5 (UniProtKB:P52803) [PMID:32296183], captured only as generic protein binding. Reason: Generic protein binding conveys no functional information about SLC10A2, and the cited proteome-scale two-hybrid screen provides no basis for a specific molecular-function term [PMID:32296183]. Removal concerns the uninformativeness of the term, not the validity of the interaction. Supporting Evidence: PMID:32296183 Here we present a human 'all-by-all'
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: HuRI reports an interaction between SLC10A2 and IFITM3 (UniProtKB:Q01628) [PMID:32296183], captured only as generic protein binding. Reason: Generic protein binding conveys no functional information about SLC10A2, and the cited proteome-scale two-hybrid screen provides no basis for a specific molecular-function term [PMID:32296183]. Removal concerns the uninformativeness of the term, not the validity of the interaction. Supporting Evidence: PMID:32296183 Here we present a human 'all-by-all'
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: HuRI reports an interaction between SLC10A2 and CTXN3 (UniProtKB:Q4LDR2) [PMID:32296183], captured only as generic protein binding. Reason: Generic protein binding conveys no functional information about SLC10A2, and the cited proteome-scale two-hybrid screen provides no basis for a specific molecular-function term [PMID:32296183]. Removal concerns the uninformativeness of the term, not the validity of the interaction. Supporting Evidence: PMID:32296183 Here we present a human 'all-by-all'
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: HuRI reports an interaction between SLC10A2 and TTMP (UniProtKB:Q5BVD1) [PMID:32296183], captured only as generic protein binding. Reason: Generic protein binding conveys no functional information about SLC10A2, and the cited proteome-scale two-hybrid screen provides no basis for a specific molecular-function term [PMID:32296183]. Removal concerns the uninformativeness of the term, not the validity of the interaction. Supporting Evidence: PMID:32296183 Here we present a human 'all-by-all'
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: HuRI reports an interaction between SLC10A2 and NRM (UniProtKB:Q8IXM6) [PMID:32296183], captured only as generic protein binding. Reason: Generic protein binding conveys no functional information about SLC10A2, and the cited proteome-scale two-hybrid screen provides no basis for a specific molecular-function term [PMID:32296183]. Removal concerns the uninformativeness of the term, not the validity of the interaction. Supporting Evidence: PMID:32296183 Here we present a human 'all-by-all'
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: HuRI reports an interaction between SLC10A2 and CCL4L2 (UniProtKB:Q8NHW4) [PMID:32296183], captured only as generic protein binding. Reason: Generic protein binding conveys no functional information about SLC10A2, and the cited proteome-scale two-hybrid screen provides no basis for a specific molecular-function term [PMID:32296183]. Removal concerns the uninformativeness of the term, not the validity of the interaction. Supporting Evidence: PMID:32296183 Here we present a human 'all-by-all'
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: HuRI reports an interaction between SLC10A2 and TMEM222 (UniProtKB:Q9H0R3) [PMID:32296183], captured only as generic protein binding. Reason: Generic protein binding conveys no functional information about SLC10A2, and the cited proteome-scale two-hybrid screen provides no basis for a specific molecular-function term [PMID:32296183]. Removal concerns the uninformativeness of the term, not the validity of the interaction. Supporting Evidence: PMID:32296183 Here we present a human 'all-by-all'
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: HuRI reports an interaction between SLC10A2 and PSENEN (UniProtKB:Q9NZ42) [PMID:32296183], captured only as generic protein binding. Reason: Generic protein binding conveys no functional information about SLC10A2, and the cited proteome-scale two-hybrid screen provides no basis for a specific molecular-function term [PMID:32296183]. PSENEN is a gamma-secretase subunit, but a two-hybrid interaction with it does not place SLC10A2 in that complex or support any processing-related function, and no such role is reported for this transporter. Removal concerns the uninformativeness of the term, not the validity of the interaction. Supporting Evidence: PMID:32296183 Here we present a human 'all-by-all'
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: HuRI reports an interaction between SLC10A2 and TEX264 (UniProtKB:Q9Y6I9) [PMID:32296183], captured only as generic protein binding. Reason: Generic protein binding conveys no functional information about SLC10A2, and the cited proteome-scale two-hybrid screen provides no basis for a specific molecular-function term [PMID:32296183]. Removal concerns the uninformativeness of the term, not the validity of the interaction. Supporting Evidence: PMID:32296183 Here we present a human 'all-by-all'
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: The BioPlex 3.0 / HCT116 proteome-scale affinity-purification mass spectrometry survey reports co-purification of SLC10A2 with CLPTM1 (UniProtKB:O96005) [PMID:33961781]. The annotation records only generic protein binding. Reason: PMID:33961781 is the Huttlin et al. dual proteome-scale AP-MS interactome resource, not a focused study of SLC10A2 or CLPTM1: it created two cell-line-specific networks covering half the proteome and assigns no molecular function to individual pairs [PMID:33961781]. CLPTM1 is a putative lipid scramblase of internal membranes and a common companion of multi-pass membrane proteins in affinity proteomics, so the co-purification does not license an informative replacement term for SLC10A2, whose characterized molecular function is sodium-coupled bile acid symport [PMID:9856990]. Per repo policy the generic term is removed as uninformative rather than marked over-annotated; this does not dispute the interaction, which is reproduced independently in PMID:40355756 and is worth following up (see suggested_questions). Supporting Evidence: PMID:33961781 Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. PMID:9856990 These results indicate that the cotransport of bile acids and Na+ by human apical sodium-bile acid transporter is electrogenic and bidirectional and is best explained by a 2:1 Na+:bile acid coupling stoichiometry.
GO:0005515 protein binding	IPI PMID:40355756 The solute carrier superfamily interactome.	REMOVE	Summary: The solute carrier superfamily interactome survey independently reports the SLC10A2-CLPTM1 (UniProtKB:O96005) interaction [PMID:40355756], again as generic protein binding. Reason: As with the HuRI and BioPlex rows, GO:0005515 conveys no functional information. The cited study is an interaction-proteomics survey whose stated aim is a global map of SLC-protein interactions rather than functional assignment [PMID:40355756]. That the CLPTM1 interaction is reproduced by two independent methods makes it a credible interaction, but an interaction with a putative lipid scramblase does not by itself identify a molecular function for SLC10A2, and inventing one from interaction evidence alone is not permitted. Removal is a statement about the term, not about the interaction. Supporting Evidence: PMID:40355756 We aimed at obtaining a global survey of the SLC-protein interaction landscape and mapped the protein-protein interactions of 396 SLCs by interaction proteomics.
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: PAINT places plasma-membrane activity at an ancestral SLC10 node (PANTHER:PTN000040759) spanning both the ileal ASBT and hepatic NTCP branches; SLC10A2 inherits it. Sodium-coupled uptake of luminal bile acids is by definition a plasma-membrane activity, and the human protein is directly shown to act in the apical membrane of the ileal epithelial cell [PMID:9856990]. Reason: The node placement is sound and the claim is unambiguously correct for this gene. Donor tracing resolves the sources as mouse Slc10a2 (MGI:MGI:1201406), rat Slc10a1 (RGD:3681), rat Slc10a2 (RGD:3682), human SLC10A1 (UniProtKB:Q14973) and human SLC10A4 (UniProtKB:Q96EP9), i.e. both branches of the family, which is exactly the breadth a family-level plasma-membrane node should have. Human-specific evidence is independent of the propagation: the two disease papers show that transport-null alleles still reach the plasma membrane [PMID:7592981, PMID:9109432], which is only interpretable if the wild-type protein resides there. GO:0016324 apical plasma membrane is the more precise location and is separately annotated, so this parent is appropriately retained alongside it. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000040759 SUPPORTS TRANSFER Ancestral SLC10 node covering both the apical ileal and basolateral hepatic branches; plasma-membrane residence is experimentally grounded in rodent and human descendants of both. Supporting Evidence: PMID:9856990 Intestinal absorption of bile acids depends on a sodium-bile acid cotransport protein in the apical membrane of the ileal epithelial cell. PMID:7592981 In transfected COS-1 cells, the single amino acid change abolished taurocholate transport activity but did not alter the transporter's synthesis or subcellular distribution.
GO:0005886 plasma membrane	TAS PMID:7592981 Identification of a mutation in the ileal sodium-dependent b...	ACCEPT	Summary: Curator statement from the paper that cloned the human ileal transporter and identified the P290S transport-null allele. The mutant protein was shown to be synthesized and distributed normally while losing transport, which presupposes plasma-membrane residence of the wild-type carrier [PMID:7592981]. Reason: The location is correct and the citation is apt. The study's central control was that the single amino acid change abolished taurocholate transport without altering the transporter's synthesis or subcellular distribution [PMID:7592981], a result that only has meaning for a plasma-membrane carrier. The cached record is abstract-only, but the abstract itself states the subcellular-distribution result, so the TAS row does not rest on text this review cannot see. Supporting Evidence: PMID:7592981 In transfected COS-1 cells, the single amino acid change abolished taurocholate transport activity but did not alter the transporter's synthesis or subcellular distribution. PMID:7592981 The ileal Na+/bile acid cotransporter plays a critical role in the reabsorption of bile acids from the small intestine.
GO:0005886 plasma membrane	TAS PMID:9109432 Primary bile acid malabsorption caused by mutations in the i...	ACCEPT	Summary: Curator statement from the PBAM disease-gene paper, in which the L243P and T262M alleles were shown to traffic normally to the plasma membrane while failing to transport bile acids [PMID:9109432]. Reason: This row is directly supported by the stated result: the disease alleles did not affect transporter protein expression or trafficking to the plasma membrane, yet abolished transport of taurocholate and other bile acids [PMID:9109432]. That experiment establishes plasma-membrane localization of the human protein in the course of showing the defect is catalytic rather than a trafficking failure. Duplicate GO ids from different references are acceptable, and this is an independent human-specific source for the same location. Supporting Evidence: PMID:9109432 In transfected COS cells, the L243P, T262M, and double mutant (L243P/T262M) did not affect transporter protein expression or trafficking to the plasma membrane; however, transport of taurocholate and other bile acids was abolished.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-194187	ACCEPT	Summary: Reactome models the SLC10A2 reaction as occurring in the plasma membrane, specifically the apical surface of the enterocyte [Reactome:R-HSA-194187]. Reason: The Reactome reaction places ASBT in the plasma membrane on the apical surface of enterocytes and makes its transport step the first of intestinal bile salt reabsorption [Reactome:R-HSA-194187], which matches the experimental literature [PMID:9856990]. The row is kept as a broader parent of the apical term that is separately annotated. Supporting Evidence: Reactome:R-HSA-194187 A molecule of extracellular bile salt or bile acid (cholate, chenodeoxycholate, or their glycine or taurine conjugates) and a sodium ion are transported into the cytosol, mediated by ASBT (apical sodium-dependent bile acid transporter; SLC10A2) in the plasma membrane. Reactome:R-HSA-194187 In the body, ASBT is expressed on the apical surfaces of enterocytes, and this reaction is the first step in the process by which bile salts and acids are reaborbed from the intestinal lumen and returned to the liver
GO:0005902 microvillus	IEA GO_REF:0000107	ACCEPT	Summary: Ensembl Compara transfer of the mouse Slc10a2 (UniProtKB:P70172) microvillus annotation to the human orthologue. Mouse Slc10a2 carries GO:0005902 by IDA (QuickGO). The apical membrane of an ileal enterocyte is its microvillar brush-border membrane, so this is the sub-apical refinement of the localization established for the human protein [PMID:9856990, PMID:33222321]. Reason: The transfer is a clean one-to-one orthologue relationship (mouse Slc10a2 to human SLC10A2, not a paralogue), the donor annotation is experimental rather than itself inferred, and the asserted location is the structural form taken by the compartment the human protein is independently placed in: intestinal bile acid absorption depends on a cotransport protein in the apical membrane of the ileal epithelial cell [PMID:9856990], and conjugated bile salts cross into terminal ileal enterocytes through this transporter [PMID:33222321]. No human-specific immunolocalization paper is cached, so the microvillar precision rests on the mouse IDA, whose full text this review cannot inspect; deferring to that curator is the correct action rather than downgrading a sound orthologue transfer. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P70172 · Slc10a2 SUPPORTS TRANSFER Mouse one-to-one orthologue; carries GO:0005902 microvillus by IDA, so the donor annotation is experimental and not itself a propagation. ensembl:ENSMUSP00000023835 SUPPORTS TRANSFER Ensembl protein identifier for the same mouse Slc10a2 donor used by the Compara orthology call. Supporting Evidence: PMID:9856990 Intestinal absorption of bile acids depends on a sodium-bile acid cotransport protein in the apical membrane of the ileal epithelial cell. PMID:33222321 conjugated bile salts cross the otherwise impermeable lipid bilayer of (primarily terminal ileal) enterocytes through the apical sodium-dependent bile acid transporter (gene SLC10A2)
GO:0008508 bile acid:sodium symporter activity	IBA GO_REF:0000033	ACCEPT	Summary: Bile acid sodium symporter activity propagated from the ancestral SLC10 bile-acid transporter node (PANTHER:PTN000040761), seeded by the experimentally characterized rat Ntcp (RGD:3681) and Asbt (RGD:3682). This is the core molecular function of SLC10A2 and is independently established for the human protein [PMID:9458785, PMID:9856990]. Reason: The node placement is correct: both rodent donors are bona fide Na+/bile acid cotransporters, the function is ancestral to the whole NTCP/ASBT clade, and SLC10A2 sits squarely inside it with no evidence of loss or divergence. Quite the opposite, the human protein is strictly Na+-dependent and chloride-independent [PMID:9458785] and its 2:1 Na+ to bile acid coupling and electrogenicity were measured directly in voltage-clamped cells [PMID:9856990]. The term is at the right granularity: it names both the substrate and the coupling ion, and the more general GO:0015125 bile acid transmembrane transporter activity would be an ancestor of it. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000040761 SUPPORTS TRANSFER Ancestral NTCP/ASBT node for Na+-coupled bile acid symport; the function is shared by both branches of the family and is experimentally established in the human descendant too. Supporting Evidence: PMID:9458785 In transiently transfected COS cells, ileal Na(+)-bile acid cotransporter-mediated taurocholate uptake was strictly Na+ dependent and chloride independent. PMID:9458785 Analysis of the substrate specificity in transfected COS or CHO cells showed that both conjugated and unconjugated bile acids are efficiently transported. PMID:9856990 These results indicate that the cotransport of bile acids and Na+ by human apical sodium-bile acid transporter is electrogenic and bidirectional and is best explained by a 2:1 Na+:bile acid coupling stoichiometry.
GO:0008508 bile acid:sodium symporter activity	TAS PMID:9109432 Primary bile acid malabsorption caused by mutations in the i...	ACCEPT	Summary: Curator statement of the symporter activity from the PBAM disease-gene paper, in which disease alleles abolished transport of taurocholate and other bile acids in transfected cells [PMID:9109432]. Reason: The citation supports the activity directly through loss of function in a heterologous system, and the paper's conclusion names the gene's role in intestinal reclamation of bile acids [PMID:9109432]. The sodium dependence of that transport is established in the companion characterization [PMID:9458785], so the full symporter term is warranted rather than a plain bile acid transporter term. Supporting Evidence: PMID:9109432 In transfected COS cells, the L243P, T262M, and double mutant (L243P/T262M) did not affect transporter protein expression or trafficking to the plasma membrane; however, transport of taurocholate and other bile acids was abolished. PMID:9109432 These findings establish that SLC10A2 mutations can cause PBAM and underscore the ileal Na+/bile acid cotransporter's role in intestinal reclamation of bile acids.
GO:0008508 bile acid:sodium symporter activity	TAS Reactome:R-HSA-194187	ACCEPT	Summary: Reactome's SLC10A2 reaction is the cotransport of a bile salt or bile acid together with sodium from the extracellular region into the cytosol [Reactome:R-HSA-194187], which is exactly what GO:0008508 describes. Reason: The term matches the modelled reaction and the experimental literature. One discrepancy worth recording that does not affect the term choice: Reactome writes the reaction with a single sodium ion, whereas the human protein was measured at 2:1 Na+ to bile acid [PMID:9856990] and UniProt's curated RHEA reactions use two Na+. GO:0008508 does not fix the stoichiometry, so the annotation is correct either way. Supporting Evidence: Reactome:R-HSA-194187 A molecule of extracellular bile salt or bile acid (cholate, chenodeoxycholate, or their glycine or taurine conjugates) and a sodium ion are transported into the cytosol, mediated by ASBT (apical sodium-dependent bile acid transporter; SLC10A2) in the plasma membrane. PMID:9856990 A 3-fold reduction in extracellular Na+ produced a negative 52 mV shift of the flux-voltage relationship, consistent with a 2:1 Na+:bile acid coupling stoichiometry.
GO:0015721 bile acid and bile salt transport	IBA GO_REF:0000033	ACCEPT	Summary: The process counterpart of the symporter activity, propagated from the same ancestral NTCP/ASBT node (PANTHER:PTN000040761). SLC10A2 performs the apical uptake step by which bile acids are reclaimed from the intestinal lumen [PMID:19498215, Reactome:R-HSA-159418]. Reason: SLC10A2 passes the participation test unambiguously: it is the entity that translocates the bile acid across the membrane, not something consumed by or merely required for the process. The node placement is the same sound one as for GO:0008508, and human-specific evidence is direct, since bile acids are almost quantitatively reclaimed in the ileum by this transporter [PMID:19498215] and loss of function interrupts the enterohepatic circulation [PMID:9109432]. The term is at the right level; GO has no enterohepatic circulation process term (checked via OLS), so nothing more specific is available. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000040761 SUPPORTS TRANSFER Same ancestral NTCP/ASBT node as the symporter activity; bile acid transport is the defining process of the clade and is experimentally established for the human descendant. Supporting Evidence: PMID:19498215 Following their movement with bile into the lumen of the small intestine, bile acids are almost quantitatively reclaimed in the ileum by the apical sodium-dependent bile acid transporter. PMID:9109432 Primary bile acid malabsorption (PBAM) is an idiopathic intestinal disorder associated with congenital diarrhea, steatorrhea, interruption of the enterohepatic circulation of bile acids, and reduced plasma cholesterol levels.
GO:0015721 bile acid and bile salt transport	TAS Reactome:R-HSA-159418	ACCEPT	Summary: Reactome's bile acid recycling pathway begins with ASBT (SLC10A2)-mediated uptake by enterocytes, followed by FABP6-mediated transcellular movement and basolateral efflux [Reactome:R-HSA-159418]. Reason: The pathway places SLC10A2 as the apical uptake step of the enterohepatic cycle, which is the correct role and the correct process term. The cited pathway and the review literature agree that this step recovers the great majority of the bile salt pool [Reactome:R-HSA-159418, PMID:19498215]. Duplicate GO ids from different evidence sources are acceptable. Supporting Evidence: Reactome:R-HSA-159418 This recycling involves a series of transport processes: uptake by enterocytes mediated by ASBT (SLC10A2), traversal of the enterocyte cytosol mediated by ileal bile acid binding protein (I-BABP - FABP6), efflux from enterocytes mediated by MRP3 (ABCC3) PMID:19498215 Following their movement with bile into the lumen of the small intestine, bile acids are almost quantitatively reclaimed in the ileum by the apical sodium-dependent bile acid transporter.
GO:0016020 membrane	IEA GO_REF:0000120	ACCEPT	Summary: Automatic annotation combining the InterPro bile acid sodium symporter signature (IPR002657) with the UniProt subcellular-location vocabulary term SL-0162 (membrane). SLC10A2 is a multi-pass membrane protein with seven transmembrane helices [PMID:15350125]. Reason: The mapping is correct though uninformative on its own. GO:0016020 is a broad parent of the more specific plasma-membrane, apical-plasma-membrane and microvillus terms that are separately annotated, and the signature-to-term mapping is sound: the seven-transmembrane topology of the protein was confirmed experimentally by glycosylation-scanning mutagenesis [PMID:15350125]. Retaining a correct broad IEA parent alongside its correctly annotated children is acceptable practice. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: InterPro:IPR002657 SUPPORTS TRANSFER Bile acid sodium symporter family signature; membership entails a polytopic membrane protein, so the mapping to GO:0016020 is safe, if less specific than the curated locations. UniProtKB-SubCell:SL-0162 SUPPORTS TRANSFER UniProt subcellular-location vocabulary term for membrane, matching the UniProt subcellular location recorded for Q12908 (membrane, multi-pass membrane protein). Supporting Evidence: PMID:15350125 Membrane topology was further evaluated and confirmed by N-glycosylation-scanning mutagenesis, as reporter sites inserted in the putative extracellular loops 1 and 3 were glycosylated.
GO:0016324 apical plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: Apical plasma membrane activity propagated from an ASBT-specific sub-node (PANTHER:PTN002570923) whose donors are exclusively Slc10a2 orthologues, mouse (MGI:MGI:1201406) and rat (RGD:3682). This is the most informative and biologically correct location for SLC10A2, and it is directly supported for the human protein [PMID:9856990, PMID:33222321]. Reason: This row is the single most important annotation for distinguishing SLC10A2 from its sister gene, and the phylogeny carries the distinction explicitly. Donor tracing shows that the apical node PANTHER:PTN002570923 is seeded only by ASBT orthologues (mouse and rat Slc10a2), whereas the basolateral term GO:0016323 on human SLC10A1 comes from a separate sub-node (PANTHER:PTN002570905) seeded by NTCP orthologues, and the shared ancestral node PANTHER:PTN000040759 carries only the unqualified plasma-membrane term. So PAINT resolved the apical versus basolateral split of the SLC10 family at the node level rather than over-propagating either location across it, and the node placement is exactly right. Human-specific evidence agrees: intestinal bile acid absorption depends on a cotransport protein in the apical membrane of the ileal epithelial cell [PMID:9856990], and conjugated bile salts enter terminal ileal enterocytes through this transporter [PMID:33222321]. The apical location is also what makes the gene's role mechanistically coherent, since the substrate is in the intestinal lumen. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002570923 SUPPORTS TRANSFER ASBT-specific sub-node; apical localization is the experimentally supported location for this branch, in contrast to the basolateral localization placed on the NTCP sub-node PANTHER:PTN002570905. Supporting Evidence: PMID:9856990 Intestinal absorption of bile acids depends on a sodium-bile acid cotransport protein in the apical membrane of the ileal epithelial cell. PMID:33222321 conjugated bile salts cross the otherwise impermeable lipid bilayer of (primarily terminal ileal) enterocytes through the apical sodium-dependent bile acid transporter (gene SLC10A2) Reactome:R-HSA-194187 In the body, ASBT is expressed on the apical surfaces of enterocytes, and this reaction is the first step in the process by which bile salts and acids are reaborbed from the intestinal lumen and returned to the liver
GO:0016324 apical plasma membrane	IEA GO_REF:0000107	ACCEPT	Summary: Ensembl Compara transfer of the mouse Slc10a2 apical plasma membrane annotation (UniProtKB:P70172, GO:0016324 by IDA per QuickGO) to the human orthologue, duplicating by a second route the location also reached by PAINT. Reason: The orthology call is one-to-one between mouse Slc10a2 and human SLC10A2, the donor annotation is experimental rather than inferred, and the conclusion matches independent human-specific statements of apical localization [PMID:9856990, PMID:33222321]. A duplicate GO id arrived at by two different inference methods is acceptable, and here it is a useful cross-check: an Ensembl orthologue transfer and a PAINT node placement agree. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P70172 · Slc10a2 SUPPORTS TRANSFER Mouse one-to-one orthologue with GO:0016324 by IDA; donor evidence is experimental, so the transfer is not a chain of inferences. ensembl:ENSMUSP00000023835 SUPPORTS TRANSFER Ensembl protein identifier for the same mouse Slc10a2 donor. Supporting Evidence: PMID:9856990 Intestinal absorption of bile acids depends on a sodium-bile acid cotransport protein in the apical membrane of the ileal epithelial cell. PMID:33222321 conjugated bile salts cross the otherwise impermeable lipid bilayer of (primarily terminal ileal) enterocytes through the apical sodium-dependent bile acid transporter (gene SLC10A2)
GO:0098719 sodium ion import across plasma membrane	IDA PMID:9856990 Bile acid uptake via the human apical sodium-bile acid cotra...	NEW	Summary: SLC10A2 carries sodium into the enterocyte as the coupling ion of bile acid symport. Voltage-clamp measurements on the human protein expressed in CHO cells lacking other bile acid transporters showed that transport is electrogenic and that lowering extracellular Na+ three-fold shifted the flux-voltage relationship by -52 mV, indicating two Na+ translocated per bile acid [PMID:9856990]. No sodium-transport term is currently annotated to the gene. Reason: Participation test. The sodium leg of the symport is work the protein itself performs, because the same transport cycle moves the Na+ ions and the bile acid, and the ion movement was measured directly as current carried by the human transporter with non-transfected cells as the negative control [PMID:9856990]. This is not a necessity or substrate argument, since the protein is the entity that translocates the ion. Direction and location match the term definition (the directed movement of sodium ions from outside of a cell, across the plasma membrane and into the cytosol, per OLS), since uptake is from the intestinal lumen across the apical membrane into the enterocyte. Comparator check (QuickGO, 2026-10-04). Sodium-coupled symporters conventionally carry a sodium-transport process term alongside their solute term. SLC5A1/SGLT1 (UniProtKB:P13866) carries GO:0098719 by IDA, SLC34A1/NaPi-IIa (UniProtKB:Q06495) carries GO:0098719, and SLC5A5/NIS (UniProtKB:Q92911) carries GO:0006814 sodium ion transport by IBA and GO:0035725 by IEA. The term is therefore conventionally applied to exactly this role. Within SLC10 it is absent from SLC10A2, from SLC10A1 and from mouse Slc10a2 alike, i.e. a family-level gap rather than a cross-family convention that would argue against the term. Non-redundancy and scope. GO:0098719 is neither an ancestor nor a descendant of GO:0015721 bile acid and bile salt transport, and the plasma-membrane-specific import term was chosen over the broader GO:0035725 because both direction and compartment are experimentally established. gocams/index.tsv contains no model for SLC10A2 or Q12908, so no curator has already placed this gene in the pathway with a different term. Supporting Evidence: PMID:9856990 These results indicate that the cotransport of bile acids and Na+ by human apical sodium-bile acid transporter is electrogenic and bidirectional and is best explained by a 2:1 Na+:bile acid coupling stoichiometry. PMID:9856990 A 3-fold reduction in extracellular Na+ produced a negative 52 mV shift of the flux-voltage relationship, consistent with a 2:1 Na+:bile acid coupling stoichiometry. PMID:9458785 In transiently transfected COS cells, ileal Na(+)-bile acid cotransporter-mediated taurocholate uptake was strictly Na+ dependent and chloride independent.

Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

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