SLC26A1 (sulfate anion transporter 1, SAT1) is a member of the SLC26A/SulP anion transporter family: a 12-transmembrane, STAS-domain, sodium-independent and electroneutral anion exchanger that moves sulfate in exchange for oxalate, bicarbonate or thiosulfate, with chloride acting mainly as an allosteric activator. It is expressed most highly in kidney and liver and, in rodents, sits in the basolateral plasma membrane of renal proximal tubule, hepatocytes and intestinal epithelium. Its best-established physiological role is renal sulfate reabsorption: human and mouse loss of function causes urinary sulfate wasting and hyposulfatemia, and rare damaging variants lower plasma sulfate in the population. SLC26A1 also transports oxalate, and biallelic variants have been reported in calcium oxalate stone formers, but whether it contributes materially to whole-body oxalate homeostasis is unresolved, since a second knockout mouse line was not hyperoxaluric.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005452 solute:inorganic anion antiporter activity | IDA PMID:12713736 Characterization of the human sulfate anion transporter (hsa... | ACCEPT | Summary: SLC26A1 is an electroneutral, sodium-independent anion exchanger that exchanges sulfate for oxalate, bicarbonate or thiosulfate; solute:inorganic anion antiporter activity is an accurate description of this exchange. Reason: Human SLC26A1 expressed in Xenopus oocytes mediates sulfate, oxalate and bicarbonate exchange (PMID:12713736, PMID:27125215); this is the core transport activity. Supporting Evidence: PMID:27125215 electroneutral sodium-independent anion exchanger transporting sulfate, oxalate, PMID:12713736 induces sulfate, chloride, and oxalate transport in file:human/SLC26A1/SLC26A1-uniprot.txt Sodium-independent sulfate anion transporter |
| GO:0005452 solute:inorganic anion antiporter activity | IDA PMID:27125215 Extracellular Cl(-) regulates human SO4 (2-)/anion exchanger... | ACCEPT | Summary: SLC26A1 is an electroneutral, sodium-independent anion exchanger that exchanges sulfate for oxalate, bicarbonate or thiosulfate; solute:inorganic anion antiporter activity is an accurate description of this exchange. Reason: Human SLC26A1 expressed in Xenopus oocytes mediates sulfate, oxalate and bicarbonate exchange (PMID:12713736, PMID:27125215); this is the core transport activity. Supporting Evidence: PMID:27125215 electroneutral sodium-independent anion exchanger transporting sulfate, oxalate, PMID:12713736 induces sulfate, chloride, and oxalate transport in file:human/SLC26A1/SLC26A1-uniprot.txt Sodium-independent sulfate anion transporter |
| GO:0005452 solute:inorganic anion antiporter activity | IEA GO_REF:0000117 | ACCEPT | Summary: SLC26A1 is an electroneutral, sodium-independent anion exchanger that exchanges sulfate for oxalate, bicarbonate or thiosulfate; solute:inorganic anion antiporter activity is an accurate description of this exchange. Reason: Human SLC26A1 expressed in Xenopus oocytes mediates sulfate, oxalate and bicarbonate exchange (PMID:12713736, PMID:27125215); this is the core transport activity. Supporting Evidence: PMID:27125215 electroneutral sodium-independent anion exchanger transporting sulfate, oxalate, PMID:12713736 induces sulfate, chloride, and oxalate transport in file:human/SLC26A1/SLC26A1-uniprot.txt Sodium-independent sulfate anion transporter |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: SLC26A1 is a multi-pass plasma membrane anion exchanger. Reason: Consistent with its function as a cell-surface anion exchanger; surface expression of the human transporter was shown in oocytes and the rodent orthologue is at the basolateral plasma membrane. Supporting Evidence: file:human/SLC26A1/SLC26A1-uniprot.txt Multi-pass membrane protein file:human/SLC26A1/SLC26A1-uniprot.txt Sodium-independent sulfate anion transporter |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: SLC26A1 is a multi-pass plasma membrane anion exchanger. Reason: Consistent with its function as a cell-surface anion exchanger; surface expression of the human transporter was shown in oocytes and the rodent orthologue is at the basolateral plasma membrane. Supporting Evidence: file:human/SLC26A1/SLC26A1-uniprot.txt Multi-pass membrane protein file:human/SLC26A1/SLC26A1-uniprot.txt Sodium-independent sulfate anion transporter |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: SLC26A1 is a multi-pass plasma membrane anion exchanger. Reason: Consistent with its function as a cell-surface anion exchanger; surface expression of the human transporter was shown in oocytes and the rodent orthologue is at the basolateral plasma membrane. Supporting Evidence: file:human/SLC26A1/SLC26A1-uniprot.txt Multi-pass membrane protein file:human/SLC26A1/SLC26A1-uniprot.txt Sodium-independent sulfate anion transporter |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-427555 | ACCEPT | Summary: SLC26A1 is a multi-pass plasma membrane anion exchanger. Reason: Consistent with its function as a cell-surface anion exchanger; surface expression of the human transporter was shown in oocytes and the rodent orthologue is at the basolateral plasma membrane. Supporting Evidence: file:human/SLC26A1/SLC26A1-uniprot.txt Multi-pass membrane protein file:human/SLC26A1/SLC26A1-uniprot.txt Sodium-independent sulfate anion transporter |
| GO:0006821 chloride transport | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Chloride transport by SLC26A1 is real but atypical: in human SLC26A1 extracellular chloride acts mainly as an allosteric activator of sulfate/oxalate exchange, and SLC26A1-associated chloride flux has divergent properties from its sulfate transport. Reason: Chloride movement is a minor, divergent property of the human transporter rather than its physiological role, which is sulfate (and possibly oxalate) exchange (PMID:27125215). Supporting Evidence: PMID:27125215 bicarbonate, thiosulfate, and (with divergent properties) chloride. |
| GO:0008271 secondary active sulfate transmembrane transporter activity | IEA GO_REF:0000002 | ACCEPT | Summary: Anion exchange driven by counter-anion gradients is secondary active sulfate transport; the InterPro-based term is correct. Reason: SLC26A1 transports sulfate by exchange with other anions (secondary active), as shown for the human protein (PMID:27125215). Supporting Evidence: PMID:27125215 electroneutral sodium-independent anion exchanger transporting sulfate, oxalate, file:human/SLC26A1/SLC26A1-uniprot.txt Sodium-independent sulfate anion transporter |
| GO:0015108 chloride transmembrane transporter activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Chloride transport by SLC26A1 is real but atypical: in human SLC26A1 extracellular chloride acts mainly as an allosteric activator of sulfate/oxalate exchange, and SLC26A1-associated chloride flux has divergent properties from its sulfate transport. Reason: Chloride movement is a minor, divergent property of the human transporter rather than its physiological role, which is sulfate (and possibly oxalate) exchange (PMID:27125215). Supporting Evidence: PMID:27125215 bicarbonate, thiosulfate, and (with divergent properties) chloride. |
| GO:0015108 chloride transmembrane transporter activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Chloride transport by SLC26A1 is real but atypical: in human SLC26A1 extracellular chloride acts mainly as an allosteric activator of sulfate/oxalate exchange, and SLC26A1-associated chloride flux has divergent properties from its sulfate transport. Reason: Chloride movement is a minor, divergent property of the human transporter rather than its physiological role, which is sulfate (and possibly oxalate) exchange (PMID:27125215). Supporting Evidence: PMID:27125215 bicarbonate, thiosulfate, and (with divergent properties) chloride. |
| GO:0015116 sulfate transmembrane transporter activity | IBA GO_REF:0000033 | ACCEPT | Summary: Sulfate transport is the best-established activity and physiological role of SLC26A1: the human protein transports sulfate in oocytes, and human and mouse loss of function cause renal sulfate wasting and hyposulfatemia. Reason: Direct human functional and genetic evidence (PMID:12713736, PMID:27125215, PMID:36719378). Supporting Evidence: file:human/SLC26A1/SLC26A1-uniprot.txt Sodium-independent sulfate anion transporter PMID:27125215 electroneutral sodium-independent anion exchanger transporting sulfate, oxalate, PMID:36719378 we identify SLC26A1 as a sulfate transporter in humans and experimentally validate several loss-of-function alleles |
| GO:0015116 sulfate transmembrane transporter activity | IEA GO_REF:0000107 | ACCEPT | Summary: Sulfate transport is the best-established activity and physiological role of SLC26A1: the human protein transports sulfate in oocytes, and human and mouse loss of function cause renal sulfate wasting and hyposulfatemia. Reason: Direct human functional and genetic evidence (PMID:12713736, PMID:27125215, PMID:36719378). Supporting Evidence: file:human/SLC26A1/SLC26A1-uniprot.txt Sodium-independent sulfate anion transporter PMID:27125215 electroneutral sodium-independent anion exchanger transporting sulfate, oxalate, PMID:36719378 we identify SLC26A1 as a sulfate transporter in humans and experimentally validate several loss-of-function alleles |
| GO:0015116 sulfate transmembrane transporter activity | ISS GO_REF:0000024 | ACCEPT | Summary: Sulfate transport is the best-established activity and physiological role of SLC26A1: the human protein transports sulfate in oocytes, and human and mouse loss of function cause renal sulfate wasting and hyposulfatemia. Reason: Direct human functional and genetic evidence (PMID:12713736, PMID:27125215, PMID:36719378). Supporting Evidence: file:human/SLC26A1/SLC26A1-uniprot.txt Sodium-independent sulfate anion transporter PMID:27125215 electroneutral sodium-independent anion exchanger transporting sulfate, oxalate, PMID:36719378 we identify SLC26A1 as a sulfate transporter in humans and experimentally validate several loss-of-function alleles |
| GO:0015116 sulfate transmembrane transporter activity | TAS Reactome:R-HSA-427555 | ACCEPT | Summary: Sulfate transport is the best-established activity and physiological role of SLC26A1: the human protein transports sulfate in oocytes, and human and mouse loss of function cause renal sulfate wasting and hyposulfatemia. Reason: Direct human functional and genetic evidence (PMID:12713736, PMID:27125215, PMID:36719378). Supporting Evidence: file:human/SLC26A1/SLC26A1-uniprot.txt Sodium-independent sulfate anion transporter PMID:27125215 electroneutral sodium-independent anion exchanger transporting sulfate, oxalate, PMID:36719378 we identify SLC26A1 as a sulfate transporter in humans and experimentally validate several loss-of-function alleles |
| GO:0015383 sulfate:bicarbonate antiporter activity | IEA GO_REF:0000107 | ACCEPT | Summary: UniProt records sulfate/hydrogencarbonate exchange for human SLC26A1 (RHEA:72387) from oocyte studies. Reason: Experimentally supported specific exchange mode of the human transporter (PMID:27125215). Supporting Evidence: PMID:27125215 electroneutral sodium-independent anion exchanger transporting sulfate, oxalate, file:human/SLC26A1/SLC26A1-uniprot.txt sulfate-hydrogencarbonate |
| GO:0015383 sulfate:bicarbonate antiporter activity | ISS GO_REF:0000024 | ACCEPT | Summary: UniProt records sulfate/hydrogencarbonate exchange for human SLC26A1 (RHEA:72387) from oocyte studies. Reason: Experimentally supported specific exchange mode of the human transporter (PMID:27125215). Supporting Evidence: PMID:27125215 electroneutral sodium-independent anion exchanger transporting sulfate, oxalate, file:human/SLC26A1/SLC26A1-uniprot.txt sulfate-hydrogencarbonate |
| GO:0015701 bicarbonate transport | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Bicarbonate is one of the counter-anions moved by SLC26A1 during sulfate exchange. Reason: Bicarbonate movement is the coupled counter-flux of sulfate exchange rather than a distinct physiological role. Supporting Evidence: PMID:27125215 electroneutral sodium-independent anion exchanger transporting sulfate, oxalate, |
| GO:0016020 membrane | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Generic membrane localization; correct but uninformative relative to plasma membrane and basolateral plasma membrane. Reason: True but less specific than the plasma-membrane annotations already present. Supporting Evidence: file:human/SLC26A1/SLC26A1-uniprot.txt Multi-pass membrane protein |
| GO:0016020 membrane | TAS PMID:11087667 Mapping of five new putative anion transporter genes in huma... | KEEP AS NON CORE | Summary: TAS from a paper that maps SLC26A1 to 4p16.3 but functionally characterizes SLC26A6; membrane localization of SLC26A1 is not assayed there, though it is true. Reason: Localization is correct (plasma membrane transporter) but generic and only weakly supported by this reference. Supporting Evidence: PMID:11087667 mapping of SLC26A1 to 4p16.3 file:human/SLC26A1/SLC26A1-uniprot.txt Multi-pass membrane protein |
| GO:0016323 basolateral plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: In rodent kidney proximal tubule, liver and intestine, Sat1 localizes to the basolateral plasma membrane, where it mediates basolateral sulfate and oxalate exchange. Reason: Basolateral localization is established for the rat and mouse orthologues and is consistent with the human renal sulfate-reabsorption defect (PMID:36719378). Supporting Evidence: file:human/SLC26A1/SLC26A1-uniprot.txt Basolateral cell membrane |
| GO:0016323 basolateral plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: In rodent kidney proximal tubule, liver and intestine, Sat1 localizes to the basolateral plasma membrane, where it mediates basolateral sulfate and oxalate exchange. Reason: Basolateral localization is established for the rat and mouse orthologues and is consistent with the human renal sulfate-reabsorption defect (PMID:36719378). Supporting Evidence: file:human/SLC26A1/SLC26A1-uniprot.txt Basolateral cell membrane |
| GO:0019531 oxalate transmembrane transporter activity | IBA GO_REF:0000033 | ACCEPT | Summary: Human SLC26A1 transports oxalate in oocytes (sulfate/oxalate exchange). The in vivo importance of this activity for oxalate homeostasis is contested: a second Slc26a1-knockout mouse line was not hyperoxaluric and a human loss-of-function patient lacked reproducible hyperoxaluria. Reason: The molecular activity is experimentally supported for the human protein (PMID:12713736, PMID:27125215); the contested point is its physiological weight, not the activity. Supporting Evidence: PMID:12713736 induces sulfate, chloride, and oxalate transport in PMID:27125215 electroneutral sodium-independent anion exchanger transporting sulfate, oxalate, PMID:36719378 Thus, the role of SLC26A1 may be predominantly related to sulfate homeostasis, whereas its role in oxalate homeostasis requires further study. |
| GO:0019531 oxalate transmembrane transporter activity | IEA GO_REF:0000107 | ACCEPT | Summary: Human SLC26A1 transports oxalate in oocytes (sulfate/oxalate exchange). The in vivo importance of this activity for oxalate homeostasis is contested: a second Slc26a1-knockout mouse line was not hyperoxaluric and a human loss-of-function patient lacked reproducible hyperoxaluria. Reason: The molecular activity is experimentally supported for the human protein (PMID:12713736, PMID:27125215); the contested point is its physiological weight, not the activity. Supporting Evidence: PMID:12713736 induces sulfate, chloride, and oxalate transport in PMID:27125215 electroneutral sodium-independent anion exchanger transporting sulfate, oxalate, PMID:36719378 Thus, the role of SLC26A1 may be predominantly related to sulfate homeostasis, whereas its role in oxalate homeostasis requires further study. |
| GO:0019531 oxalate transmembrane transporter activity | ISS GO_REF:0000024 | ACCEPT | Summary: Human SLC26A1 transports oxalate in oocytes (sulfate/oxalate exchange). The in vivo importance of this activity for oxalate homeostasis is contested: a second Slc26a1-knockout mouse line was not hyperoxaluric and a human loss-of-function patient lacked reproducible hyperoxaluria. Reason: The molecular activity is experimentally supported for the human protein (PMID:12713736, PMID:27125215); the contested point is its physiological weight, not the activity. Supporting Evidence: PMID:12713736 induces sulfate, chloride, and oxalate transport in PMID:27125215 electroneutral sodium-independent anion exchanger transporting sulfate, oxalate, PMID:36719378 Thus, the role of SLC26A1 may be predominantly related to sulfate homeostasis, whereas its role in oxalate homeostasis requires further study. |
| GO:0019532 oxalate transport | ISS GO_REF:0000024 | ACCEPT | Summary: Oxalate transport by SLC26A1 is supported in heterologous expression; its physiological contribution to whole-body oxalate handling is unresolved. Reason: Correct process for the experimentally shown oxalate exchange activity (PMID:12713736, PMID:27125215); in vivo weight disputed (PMID:30383413, PMID:36719378). Supporting Evidence: PMID:12713736 induces sulfate, chloride, and oxalate transport in PMID:36719378 Thus, the role of SLC26A1 may be predominantly related to sulfate homeostasis, whereas its role in oxalate homeostasis requires further study. |
| GO:0055085 transmembrane transport | IEA GO_REF:0000002 | MODIFY | Summary: Very general parent process. Reason: The specific transmembrane transport process supported for SLC26A1 is sulfate transmembrane transport. Proposed replacements: sulfate transmembrane transport Supporting Evidence: file:human/SLC26A1/SLC26A1-uniprot.txt Sodium-independent sulfate anion transporter PMID:27125215 electroneutral sodium-independent anion exchanger transporting sulfate, oxalate, |
| GO:0140900 chloride:bicarbonate antiporter activity | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Chloride:bicarbonate exchange is the canonical activity of several SLC26 paralogs (SLC26A3, SLC26A6), propagated here by phylogeny. Human SLC26A1 differs: chloride mainly activates sulfate exchange allosterically, and SLC26A1-associated chloride transport has divergent, partly DIDS-insensitive and cation-dependent properties; direct Cl-/HCO3- exchange has not been shown for SLC26A1. Reason: Target-specific functional data (PMID:27125215) indicate SLC26A1 diverged from the Cl-/HCO3- exchanger clade activity; its supported exchange modes are sulfate/oxalate, sulfate/bicarbonate and sulfate/thiosulfate. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN008330351 SUPPORTS SOURCE BUT NOT TARGET Ancestral node carrying the Cl-/HCO3- exchange IBD. Node placement not re-examined here; the target-specific oocyte data (PMID:27125215) show divergent chloride handling and no demonstrated Cl-/HCO3- exchange by SLC26A1. UniProtKB:Q9BXS9 SUPPORTS SOURCE BUT NOT TARGET SLC26A6 is a bona fide Cl-/HCO3- exchanger; its activity does not transfer to SLC26A1. UniProtKB:O43511 SUPPORTS SOURCE BUT NOT TARGET Pendrin (SLC26A4) Cl-/HCO3- exchange; paralog activity. Supporting Evidence: PMID:27125215 bicarbonate, thiosulfate, and (with divergent properties) chloride. PMID:27125215 electroneutral sodium-independent anion exchanger transporting sulfate, oxalate, |
| GO:1902358 sulfate transmembrane transport | IBA GO_REF:0000033 | ACCEPT | Summary: Sulfate transport is the best-established activity and physiological role of SLC26A1: the human protein transports sulfate in oocytes, and human and mouse loss of function cause renal sulfate wasting and hyposulfatemia. Reason: Direct human functional and genetic evidence (PMID:12713736, PMID:27125215, PMID:36719378). Supporting Evidence: file:human/SLC26A1/SLC26A1-uniprot.txt Sodium-independent sulfate anion transporter PMID:27125215 electroneutral sodium-independent anion exchanger transporting sulfate, oxalate, PMID:36719378 we identify SLC26A1 as a sulfate transporter in humans and experimentally validate several loss-of-function alleles |
| GO:1902358 sulfate transmembrane transport | IEA GO_REF:0000002 | ACCEPT | Summary: Sulfate transport is the best-established activity and physiological role of SLC26A1: the human protein transports sulfate in oocytes, and human and mouse loss of function cause renal sulfate wasting and hyposulfatemia. Reason: Direct human functional and genetic evidence (PMID:12713736, PMID:27125215, PMID:36719378). Supporting Evidence: file:human/SLC26A1/SLC26A1-uniprot.txt Sodium-independent sulfate anion transporter PMID:27125215 electroneutral sodium-independent anion exchanger transporting sulfate, oxalate, PMID:36719378 we identify SLC26A1 as a sulfate transporter in humans and experimentally validate several loss-of-function alleles |
| GO:1902358 sulfate transmembrane transport | ISS GO_REF:0000024 | ACCEPT | Summary: Sulfate transport is the best-established activity and physiological role of SLC26A1: the human protein transports sulfate in oocytes, and human and mouse loss of function cause renal sulfate wasting and hyposulfatemia. Reason: Direct human functional and genetic evidence (PMID:12713736, PMID:27125215, PMID:36719378). Supporting Evidence: file:human/SLC26A1/SLC26A1-uniprot.txt Sodium-independent sulfate anion transporter PMID:27125215 electroneutral sodium-independent anion exchanger transporting sulfate, oxalate, PMID:36719378 we identify SLC26A1 as a sulfate transporter in humans and experimentally validate several loss-of-function alleles |
| GO:1902358 sulfate transmembrane transport | TAS Reactome:R-HSA-427555 | ACCEPT | Summary: Sulfate transport is the best-established activity and physiological role of SLC26A1: the human protein transports sulfate in oocytes, and human and mouse loss of function cause renal sulfate wasting and hyposulfatemia. Reason: Direct human functional and genetic evidence (PMID:12713736, PMID:27125215, PMID:36719378). Supporting Evidence: file:human/SLC26A1/SLC26A1-uniprot.txt Sodium-independent sulfate anion transporter PMID:27125215 electroneutral sodium-independent anion exchanger transporting sulfate, oxalate, PMID:36719378 we identify SLC26A1 as a sulfate transporter in humans and experimentally validate several loss-of-function alleles |
| GO:1902476 chloride transmembrane transport | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Chloride transport by SLC26A1 is real but atypical: in human SLC26A1 extracellular chloride acts mainly as an allosteric activator of sulfate/oxalate exchange, and SLC26A1-associated chloride flux has divergent properties from its sulfate transport. Reason: Chloride movement is a minor, divergent property of the human transporter rather than its physiological role, which is sulfate (and possibly oxalate) exchange (PMID:27125215). Supporting Evidence: PMID:27125215 bicarbonate, thiosulfate, and (with divergent properties) chloride. |
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Download this section (compressed HTML)Q: Does SLC26A1 loss cause calcium oxalate nephrolithiasis in humans through altered oxalate handling, through urinary sulfate wasting, or not at all?
Q: What explains the discordant oxalate phenotypes of the two Slc26a1-knockout mouse lines (hyperoxaluria in one, reduced urinary oxalate in the other)?
Experiment: Measure plasma/urinary sulfate and oxalate, and stone composition, in the reported biallelic SLC26A1 stone formers and in additional biallelic carriers.
Experiment: Hepatocyte- and kidney-specific Slc26a1 deletion in mice with controlled diet and microbiota to separate hepatic oxalate efflux from renal sulfate reabsorption.
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