SLC19A3

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: Plasma-membrane localization is the correct and core cellular location for this transporter. As a cell-surface carrier that takes up extracellular thiamine, SLC19A3 acts at the plasma membrane; the phylogenetic (IBA) inference is consistent with Reactome (TAS) and the transport phenotype. This is a correct core CC, not to be treated as over-annotation despite being a propagated inference. Supporting Evidence: Reactome:R-HSA-199626 Two transport proteins, SLC19A2 (THTR1) and SLC19A3 (THTR2), associated with the plasma membrane, are each able to mediate the transport of extracellular thiamin into the cytosol.
GO:0015234 thiamine transmembrane transporter activity	IBA GO_REF:0000033	ACCEPT	Summary: This is the defining molecular function of SLC19A3. The phylogenetic inference across the SLC19 thiamine-transporter clade is fully consistent with direct experimental demonstration of thiamine uptake and with the UniProt catalytic reaction. Core MF; accept. Supporting Evidence: PMID:11731220 Uptake of [3H]thiamine, but not of methotrexate nor folic acid, was enhanced in SLC19A3 transfectants relative to vector control.
GO:0015234 thiamine transmembrane transporter activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assertion of the same core MF as the IBA/ISS/TAS annotations. Correct and experimentally supported; redundant with the manually curated records but represents the gene's own core function, so accept rather than flag as over-annotation.
GO:0015888 thiamine transport	IEA GO_REF:0000120	ACCEPT	Summary: Electronic BP assertion of thiamine transport, the core biological process for this transporter. Correct and redundant with the multiple experimental (IDA/IMP) records; accept.
GO:0016020 membrane	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Generic "membrane" is correct but far less informative than the plasma membrane annotation this protein also carries. It reflects only the multi-pass membrane-protein topology. Retain as non-core, superseded by the specific plasma membrane term.
GO:0051180 vitamin transport	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Correct but a high-level parent of the specific processes (thiamine transport, pyridoxine transport) already annotated with experimental evidence. Retain as non-core; the specific child terms are preferred.
GO:0090482 vitamin transmembrane transporter activity	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro2GO grouping term; it is the direct parent of thiamine transmembrane transporter activity (GO:0015234), which is annotated experimentally. Correct but too general to be the core MF; retain as non-core, superseded by GO:0015234.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" from the systematic high-throughput HuRI yeast-two- hybrid interactome (interactors ARLN, CYB561, CYP4F2, GET1, LAT, PLPPR2, THBD, TMEM14A, TMEM14B, TMEM242, ZFPL1). These are proteome-scale screen hits with no dedicated SLC19A3 functional follow-up and no specific adapter/ complex function established; the term is uninformative about molecular function. Marked as over-annotated rather than removed, since the IPI is an experimental record. Supporting Evidence: PMID:32296183 yeast two-hybrid (Y2H) represents the only binary PPI assay that can be operated at sufficient throughput to systematically screen the human proteome for binary PPIs
GO:0071934 thiamine transmembrane transport	IEA GO_REF:0000107	ACCEPT	Summary: Ensembl-Compara transfer (from mouse Slc19a3, UniProtKB:Q99PL8) of thiamine transmembrane transport, the core biological process. Correct and consistent with the experimental thiamine-transport annotations; accept.
GO:0042723 thiamine-containing compound metabolic process	TAS Reactome:R-HSA-196819	KEEP AS NON CORE	Summary: Reactome pathway-level placement of SLC19A3 within vitamin B1 metabolism. The transporter participates in thiamine homeostasis but does not itself metabolize (interconvert) thiamine-containing compounds; the specific thiamine-transport process terms capture its actual role more precisely. Retain as non-core context. Supporting Evidence: Reactome:R-HSA-196819 When pyrophosphorylated, thiamin is converted into the coenzyme thiamin pyrophosphate (ThPP, codecarboxylase) which plays an essential role in oxidative decarboxylation and group transfer reactions.
GO:0015888 thiamine transport	IDA PMID:33008889 pH-dependent pyridoxine transport by SLC19A2 and SLC19A3: Im...	ACCEPT	Summary: Direct assay: expression of SLC19A3 confers pH-dependent thiamine uptake (Km ~2.3 uM), and endogenous SLC19A3 knockdown in Caco-2 reduces carrier-mediated uptake. Core BP; accept. Supporting Evidence: PMID:33008889 transport the positively charged thiamine (vitamin B1) into cells to enable its efficient utilization
GO:0015888 thiamine transport	IDA PMID:35512554 Animal species differences in the pyridoxine transport funct...	ACCEPT	Summary: Direct demonstration that human SLC19A3 (and the rat/mouse orthologs) transport thiamine in transfected HEK293 cells. Core BP; accept. Supporting Evidence: PMID:35512554 all SLC19A2/3 orthologs were capable of thiamine transport
GO:0015888 thiamine transport	IMP PMID:35724964 Identification of the amino acid residues involved in the sp...	ACCEPT	Summary: Mutational analysis confirms thiamine transport by SLC19A3 (and orthologs) as the shared, conserved function against which the human-specific pyridoxine activity is contrasted. Core BP; accept. Supporting Evidence: PMID:35724964 rat and mouse orthologs of hSLC19A3 can transport thiamine but not pyridoxine
GO:0031923 pyridoxine transport	IDA PMID:33008889 pH-dependent pyridoxine transport by SLC19A2 and SLC19A3: Im...	KEEP AS NON CORE	Summary: Directly demonstrated: expression of SLC19A3 induces saturable, pH-dependent pyridoxine (vitamin B6) uptake (Km 18.5 uM), and endogenous SLC19A3 knockdown in Caco-2 reduces pyridoxine uptake. This is a genuine, experimentally solid secondary substrate of the human transporter, so keep as a real (non-core) function; thiamine remains the physiologically named, disease-relevant substrate. Supporting Evidence: PMID:33008889 silencing the endogenous SLC19A3, but not SLC19A2, of Caco-2 cells with gene-specific siRNAs lead to a significant reduction in carrier-mediated pyridoxine uptake
GO:0031923 pyridoxine transport	IDA PMID:35512554 Animal species differences in the pyridoxine transport funct...	KEEP AS NON CORE	Summary: Human SLC19A3 transports pyridoxine, whereas the rat/mouse orthologs do not (species-restricted secondary activity). Experimentally supported non-core function. Supporting Evidence: PMID:35512554 both rat and mouse Slc19a2 can transport pyridoxine, but rat or mouse Slc19a3 cannot
GO:0031923 pyridoxine transport	IMP PMID:35724964 Identification of the amino acid residues involved in the sp...	KEEP AS NON CORE	Summary: Mutagenesis (residues Gln86, Gly87, Ile91, Thr93, Trp94, Ser168, Asn173) identifies the determinants specifically required for human SLC19A3 pyridoxine transport but dispensable for thiamine transport, confirming pyridoxine as a bona fide substrate. Experimentally supported non-core function. Supporting Evidence: PMID:35724964 the hSLC19A3-specific amino acid residues of Gln86, Gly87, Ile91, Thr93, Trp94, Ser168, and Asn173 are critical for pyridoxine transport
GO:0031923 pyridoxine transport	IDA PMID:36456177 Disrupted in renal carcinoma 2 (DIRC2/SLC49A4) is an H(+)-dr...	KEEP AS NON CORE	Summary: In the DIRC2 study, SLC19A3 was used as a plasma-membrane pyridoxine-transport positive control that drives cellular pyridoxine accumulation. Consistent with the other pyridoxine-transport records; experimentally supported non-core function. Supporting Evidence: PMID:36456177 SLC19A2 and SLC19A3, known as thiamine transporter 1 (THTR1) and THTR2, respectively, also transport pyridoxine
GO:0015888 thiamine transport	IDA PMID:11731220 SLC19A3 encodes a second thiamine transporter ThTr2.	ACCEPT	Summary: Original functional characterization: SLC19A3 transfectants take up [3H]thiamine but not folate/methotrexate, with high specificity for vitamin B1 and pH optimum ~7.5, establishing ThTr2. Foundational evidence for the core BP; accept. Supporting Evidence: PMID:11731220 Uptake of [3H]thiamine, but not of methotrexate nor folic acid, was enhanced in SLC19A3 transfectants relative to vector control.
GO:0015234 thiamine transmembrane transporter activity	TAS Reactome:R-HSA-199626	ACCEPT	Summary: Reactome traceable assertion of the core molecular function: SLC19A3 mediates transport of extracellular thiamine into the cytosol at the plasma membrane. Core MF; accept. Supporting Evidence: Reactome:R-HSA-199626 SLC19A2 (THTR1) and SLC19A3 (THTR2), associated with the plasma membrane, are each able to mediate the transport of extracellular thiamin into the cytosol
GO:0071934 thiamine transmembrane transport	ISS GO_REF:0000024	ACCEPT	Summary: Curator sequence-similarity transfer (from mouse Slc19a3, UniProtKB:Q99PL8) of thiamine transmembrane transport. Consistent with the human experimental evidence; core BP, accept.
GO:0042723 thiamine-containing compound metabolic process	TAS Reactome:R-HSA-196819	KEEP AS NON CORE	Summary: Duplicate of the earlier Reactome pathway-level thiamine-metabolism placement (also appears with TAS from R-HSA-196819). As above, the transporter participates in thiamine homeostasis but is not a metabolic (interconverting) enzyme; retain as non-core context.
GO:0005886 plasma membrane	TAS Reactome:R-HSA-199626	ACCEPT	Summary: Reactome traceable assertion of plasma-membrane localization, the core cellular location where SLC19A3 mediates thiamine uptake. Accept. Supporting Evidence: Reactome:R-HSA-199626 Two transport proteins, SLC19A2 (THTR1) and SLC19A3 (THTR2), associated with the plasma membrane
GO:0015234 thiamine transmembrane transporter activity	ISS GO_REF:0000024	ACCEPT	Summary: Curator sequence-similarity transfer of the core thiamine transmembrane transporter activity from mouse Slc19a3. Consistent with human experimental data; core MF, accept.
GO:0016020 membrane	NAS PMID:11136550 Identification and characterization of the human and mouse S...	KEEP AS NON CORE	Summary: Non-traceable author statement from the original cloning paper, reflecting the predicted 12-transmembrane topology. Correct but generic and less informative than the plasma membrane annotation; retain as non-core. Supporting Evidence: PMID:11136550 Like the SLC19A1 and SLC19A2 proteins, SLC19A3 contains 12 putative transmembrane domains.

Gene Description

Existing Annotations Review

Core Functions

High-affinity thiamine (vitamin B1) uptake across the plasma membrane, coupled to proton antiport (thiamine-in / H+-out), enabling cellular thiamine utilization; specific for vitamin B1 and does not transport folate.

References

📚 Additional Documentation

Notes

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