Affinage

SLC15A4

Solute carrier family 15 member 4 · UniProt Q8N697

Length
577 aa
Mass
62.0 kDa
Annotated
2026-04-28
79 papers in source corpus 17 papers cited in narrative 17 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC15A4 (PHT1) is an endolysosomal proton-coupled transporter of histidine, di/tripeptides, and bacterially derived peptides that functions as a central signaling hub coupling endosomal innate immune sensing to type I interferon production and metabolic reprogramming in immune cells. Its transporter activity maintains endolysosomal pH and supports mTORC1 activation, AMPK signaling, and the mTORC1-TFEB axis that controls secretory granule homeostasis and metabolic fitness in macrophages, mast cells, and plasmacytoid dendritic cells (PMID:25238095, PMID:29155995, PMID:34385317). A conformational switch from outward-facing to inward-facing state creates a cytoplasmic cavity into which the N-terminal helix of the adaptor TASL inserts, enabling TASL-mediated IRF5 activation downstream of TLR7/8/9 without affecting NF-κB or MAPK branches (PMID:32433612, PMID:37863913, PMID:40781080). SLC15A4 traffics to LAMP1+/LAMP2+ endolysosomes via an AP-3-dependent pathway and is required for proper colocalization of nucleic acid-sensing TLRs with their ligands, and also transports muramyl dipeptide to facilitate NOD-dependent innate responses (PMID:35349343, PMID:29784761).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2010 High

    A forward genetic screen established that SLC15A4 is selectively required for TLR7/9-mediated IFN-I production in pDCs but not conventional DCs, and linked it genetically to the AP-3/BLOC trafficking pathway — resolving whether this transporter has a non-redundant immune function.

    Evidence ENU mutagenesis (feeble mutant), positional cloning, cell-type-specific cytokine assays, epistasis with AP-3/BLOC mutants in mouse

    PMID:21045126

    Open questions at the time
    • Mechanism by which SLC15A4 supports IFN-I was unknown
    • Whether transporter activity per se is required was untested
    • Downstream signaling pathway not delineated
  2. 2014 High

    Demonstrating that SLC15A4's transport activity — not merely its physical presence — is required for TLR-triggered cytokine production resolved a key mechanistic question: transporter-dead mutants failed to restore pH regulation, v-ATPase integrity, and mTOR/IRF7 signaling.

    Evidence Transporter activity assays, endolysosomal pH measurements, transporter-dead mutant rescue experiments in B cells and pDCs, mouse lupus model

    PMID:25238095

    Open questions at the time
    • How transport activity couples to mTOR activation was unclear
    • Identity of direct signaling interactors remained unknown
    • Role in non-pDC immune cells unexplored
  3. 2017 High

    Extension of SLC15A4 function beyond pDCs revealed that it governs the mTORC1-TFEB axis in mast cells, controlling secretory granule homeostasis and limiting FcεRI/IL-33-driven inflammatory responses.

    Evidence Slc15a4 KO mast cells, mTORC1 activity assays, TFEB nuclear translocation imaging, degranulation assays in vitro and in vivo

    PMID:29155995

    Open questions at the time
    • How SLC15A4 transporter activity feeds into mTORC1 regulation mechanistically
    • Whether SLC15A4 physically associates with mTORC1 machinery
  4. 2018 High

    Localization of SLC15A4 to endosomal membranes of macrophages and demonstration that it transports bacterially derived muramyl dipeptide established a role in NOD-dependent innate sensing beyond TLR pathways.

    Evidence Fluorescent MDP-rhodamine imaging, Pht1 KO mice cytokine assays, subcellular fractionation

    PMID:29784761

    Open questions at the time
    • Whether NOD and TLR functions of SLC15A4 are mechanistically separable
    • Structural basis of peptide recognition unknown
  5. 2020 High

    Identification of TASL as a direct lysosomal binding partner of SLC15A4 answered the long-standing question of how SLC15A4 specifically activates the IRF pathway: TASL's pLxIS motif recruits and activates IRF5, decoupling IFN-I signaling from NF-κB/MAPK.

    Evidence Co-immunoprecipitation, extensive TASL mutagenesis, SLC15A4/TASL deletion with pathway-specific readouts, primary and transformed human immune cells

    PMID:32433612

    Open questions at the time
    • Structural basis of SLC15A4-TASL interaction unknown
    • Whether SLC15A4 conformational state governs TASL recruitment
    • How transporter function relates to adaptor recruitment
  6. 2021 High

    BioID and fluxome analyses revealed that SLC15A4 constitutively associates with Raptor and LAMTOR components, and that its loss rewires macrophage metabolism (reduced pyruvate-to-TCA flux, increased glutaminolysis), establishing SLC15A4 as a metabolic sensor coupling lysosomal transport to mTORC1/AMPK signaling.

    Evidence Proximity-dependent biotin identification (BioID), metabolic flux analysis, macrophage KO, AMPK/mTOR activity assays; co-IP with Raptor/LAMTORs in CAL-1 human pDC line

    PMID:33560415 PMID:34385317

    Open questions at the time
    • Direct versus indirect nature of SLC15A4-mTORC1 association not resolved
    • Whether metabolic reprogramming and TASL/IRF5 signaling are independent outputs
  7. 2022 High

    Live-cell imaging established that SLC15A4 is required for formation of the LAMP2+VAMP3+ hybrid compartment where IFN-I production initiates, and confirmed AP-3-dependent trafficking; functional divergence from paralog SLC15A3 was demonstrated genetically.

    Evidence Live-cell fluorescence imaging/colocalization, SLC15A3 vs SLC15A4 mutant comparison, AP-3 genetic epistasis in mouse models

    PMID:35349343

    Open questions at the time
    • Molecular determinants of AP-3 recognition on SLC15A4 not identified
    • Whether SLC15A3 and SLC15A4 have overlapping substrates in immune contexts
  8. 2023 High

    Cryo-EM structures resolved the conformational cycle of SLC15A4 and the unprecedented mechanism of TASL recruitment: TASL's N-terminal helix inserts into the inward-facing cavity, while a cholesterol-stabilized dimer represents the outward-facing apo state. The inhibitor feeblin locks SLC15A4 in the outward-open conformation incompatible with TASL binding, causing TASL degradation and blocking TLR-IRF5 signaling.

    Evidence Multiple independent cryo-EM structures (apo monomeric/dimeric, TASL-bound, feeblin-bound), biochemical binding assays, TLR pathway assays including SLE patient cells

    PMID:37709742 PMID:37863876 PMID:37863913

    Open questions at the time
    • How lysosomal luminal conditions trigger the outward-to-inward conformational switch in vivo
    • Whether transport and TASL recruitment are simultaneous or sequential
    • Substrate-bound inward-facing structure not yet captured
  9. 2024 High

    Substrate-bound cryo-EM structures defined the dipeptide recognition mechanism in the outward-facing state, and covalent inhibitors identified by chemoproteomics validated SLC15A4 as a druggable target suppressing both TLR and NOD signaling in vivo.

    Evidence Cryo-EM of SLC15A4+dipeptide and SLC15A4-TASL complex; activity-based protein profiling with functional inhibitor validation in human/mouse immune cells and in vivo models

    PMID:38191941 PMID:39719710

    Open questions at the time
    • Full transport cycle structures (inward-open with substrate) not available
    • In vivo pharmacokinetics and selectivity of covalent inhibitors in disease models
  10. 2025 High

    Conformation-selective antibodies that distinguish the luminal-open (TASL-incompetent) from cytoplasmic-open (TASL-competent) states provided direct evidence that TASL recruitment is gated by a conformational switch, validating the structural model.

    Evidence Antibody screening, cryo-EM conformational trapping, functional TASL binding and TLR pathway readouts

    PMID:40781080

    Open questions at the time
    • Physiological signals that bias SLC15A4 toward the inward-facing, TASL-competent conformation remain unidentified
    • Whether conformational equilibrium differs across immune cell types

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include how luminal substrate sensing triggers the conformational switch that enables TASL recruitment, whether transport and TASL-mediated signaling are temporally coupled or independent outputs, and how SLC15A4's metabolic (mTORC1/AMPK) and signaling (IRF5) functions are coordinated in different immune cell types.
  • Conformational trigger mechanism in vivo unknown
  • Temporal relationship between transport and signaling unresolved
  • Cell-type-specific regulation of dual functions not systematically addressed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 5 GO:0060090 molecular adaptor activity 3
Localization
GO:0005764 lysosome 5 GO:0005768 endosome 3
Pathway
R-HSA-168256 Immune System 7 R-HSA-162582 Signal Transduction 4 R-HSA-382551 Transport of small molecules 4
Partners
IRF5LAMTOR1LAMTOR2PRKAA1RPTORTASL
Complex memberships
SLC15A4-TASL signaling complex

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2020 SLC15A4 physically interacts with TASL (encoded by CXorf21) on the lysosomal membrane; TASL localization and function depend on this interaction. TASL contains a conserved pLxIS motif that recruits and activates IRF5, linking endolysosomal TLR7/8/9 sensing specifically to the IRF pathway without affecting NF-κB or MAPK signaling. Co-immunoprecipitation, extensive mutagenesis of TASL, deletion of SLC15A4 or TASL with pathway-specific readouts (IRF vs NF-κB/MAPK), primary and transformed human immune cells Nature High 32433612
2010 Slc15a4 (PHT1) is required for TLR7- and TLR9-mediated type I IFN and proinflammatory cytokine production specifically in plasmacytoid dendritic cells (pDCs), but not in conventional DCs; AP-3, BLOC-1, and BLOC-2 Hermansky-Pudlak syndrome proteins form a membrane trafficking pathway also uniquely required for endosomal TLR signaling in pDCs. Forward genetic screen (feeble ENU mutant), positional cloning, cell-type-specific cytokine assays, genetic epistasis with AP-3/BLOC complex mutants Proceedings of the National Academy of Sciences of the United States of America High 21045126
2014 SLC15A4 is a lysosome-resident proton-coupled amino-acid transporter that moves histidine and oligopeptides from the lysosomal lumen to the cytosol; its transporter activity (not merely its structural presence) is necessary for TLR7/9-triggered cytokine production. SLC15A4 loss disrupts endolysosomal pH regulation and v-ATPase integrity, leading to impaired mTOR pathway activation and failure of the IRF7-IFN-I regulatory circuit. Transporter activity assays, pH measurement, mTOR pathway analysis, transporter-dead mutant rescue experiments in B cells and pDCs, mouse lupus model Immunity High 25238095
2022 SLC15A4 is required for trafficking and colocalization of nucleic acid-sensing TLRs and their ligands to endolysosomes, and for formation of the LAMP2+VAMP3+ hybrid compartment in which IFN-I production is initiated. SLC15A4 trafficking to endolysosomes depends on the AP-3 complex. A function-impairing mutation in SLC15A3 does not impair type I IFN production by pDCs, indicating functional divergence within the SLC15 family. Live-cell fluorescence imaging/colocalization, genetic comparison of SLC15A4 vs SLC15A3 mutant mice, AP-3 complex genetic epistasis, feeble mutant and genomic deletion models Proceedings of the National Academy of Sciences of the United States of America High 35349343
2023 Cryo-EM structures of human SLC15A4 reveal apo monomeric and dimeric outward-facing conformations (dimeric form stabilized by four cholesterol molecules at the interface), and a TASL-bound complex in which SLC15A4 adopts an inward-facing conformation that forms a binding pocket into which the N-terminal helix of TASL inserts — a previously undescribed interaction mode for solute carriers. Cryo-EM structure determination at high resolution, structural comparison of apo vs TASL-bound states Nature communications High 37863913
2023 Cryo-EM structure of SLC15A4 (PHT1) in the outward-open conformation combined with biochemical and structural modeling defines the inward-open cavity as the TASL-binding site; the first 16 N-terminal residues of TASL fold into a helix that inserts into this cavity. Cryo-EM, biochemical binding assays, structural modeling of PHT1-TASL complex Nature communications High 37709742
2023 Feeblin, a small-molecule inhibitor, binds SLC15A4 in a lysosomal outward-open conformation that is incompatible with TASL binding on the cytoplasmic side; this conformation-locking mechanism prevents TASL recruitment and leads to TASL proteostatic degradation, thereby blocking TLR7/8-IRF5 signaling. Cryo-EM structure of feeblin-SLC15A4 complex, phenotypic assay for TASL degradation, TLR pathway activity assays in human immune cells including SLE patient cells Nature communications High 37863876
2024 Cryo-EM structures of SLC15A3 (apo) and SLC15A4 (apo and dipeptide-bound) define the specific dipeptide recognition mechanism; each protomer adopts an outward-facing conformation, and the N-terminal helix of TASL inserts deeply into the inward-facing cavity of SLC15A4 in the complex structure. Cryo-EM structure determination of SLC15A3 apo, SLC15A4 apo, SLC15A4+substrate, and SLC15A4-TASL complex Structure High 39719710
2021 SLC15A4 loss in macrophages causes insufficient pyruvate biotransformation to the TCA cycle while increasing glutaminolysis; SLC15A4 is required for M1-prone metabolic shift and inflammatory IL-12 production after TLR9 stimulation. SLC15A4 was found in close proximity to AMPK and mTOR, and its deficiency impaired TLR-mediated AMPK activation. SLC15A4-intact macrophages resist nutrient fluctuations by limiting glutamine use, protecting respiratory homeostasis. Proximity-dependent biotin identification (BioID), fluxome analysis (metabolic flux), macrophage KO, AMPK/mTOR activity assays Proceedings of the National Academy of Sciences of the United States of America High 34385317
2021 Human SLC15A4 exhibits pH- and temperature-dependent transport activity for dipeptides and tripeptides; it localizes to LAMP1+ compartments and constitutively associates with Raptor and LAMTORs (mTORC1 regulatory complex components). Knockdown in human pDC line CAL-1 impairs TLR7/8/9-triggered IFN-I production and mTORC1 activity, and impairs autophagy sustainability and mitochondrial membrane potential under starvation. Transport activity assays in human cells, LAMP1 co-localization, co-immunoprecipitation with Raptor/LAMTORs, SLC15A4 KD in CAL-1 cells with IFN-I/mTORC1/autophagy/mitochondrial readouts International immunology High 33560415
2017 SLC15A4 is required for mast cell secretory-granule (lysosome-derived) homeostasis; its loss diminishes mTORC1 activity, increasing nuclear translocation of TFEB, which causes hyperdegranulation. SLC15A4 controls the mTORC1-TFEB signaling axis to limit FcεRI-mediated and IL-33-triggered inflammatory responses both in vitro and in vivo. Slc15a4 KO mast cells, mTORC1 activity assays, TFEB localization imaging, degranulation assays, FcεRI and IL-33 stimulation in vitro and in vivo International immunology High 29155995
2018 SLC15A4 (PHT1) is expressed on endosomal membranes of macrophages (whereas PEPT2 is on the plasma membrane); both transporters transport bacterially derived di/tripeptides (including muramyl dipeptide) to facilitate NOD-dependent cytokine production. Pht1 KO mice show reduced proinflammatory cytokine responses to bacterial peptide ligands. Fluorescent MDP-rhodamine imaging, Pht1 KO mice cytokine assays, subcellular fractionation/localization Journal of immunology High 29784761
2024 Chemoproteomic (activity-based protein profiling) approach identified first-in-class covalent inhibitors of SLC15A4 that suppress SLC15A4-mediated endolysosomal TLR and NOD signaling in human and mouse immune cells and suppress inflammation in vivo; mechanistically the inhibitors target SLC15A4 transporter function to block downstream immune signaling. Chemical proteomics/ABPP, functional inhibitor characterization in multiple human/mouse immune cell types, in vivo inflammation models, clinical ex vivo validation Nature chemical biology High 38191941
2016 PHT1 (SLC15A4) plays an important role in histidine transport in brain parenchyma; ablation of Pht1 reduces L-histidine uptake in brain slices by ~50% and reduces brain parenchyma L-histidine levels in vivo, with compensatory upregulation of PEPT2 (~2-fold) in Pht1 null mice. In vitro brain slice uptake assays, in vivo pharmacokinetics, biodistribution studies, PCR and immunoblot in Pht1 null vs wildtype mice Biochemical pharmacology Medium 27845049
2019 PHT1 (SLC15A4) mediates carnosine uptake in glioblastoma cells; siRNA-mediated knockdown of PHT1 significantly reduces carnosine uptake, and competitive inhibition with L-histidine (PHT1/2 inhibitor) blocks carnosine entry. siRNA knockdown, HPLC-MS carnosine uptake assay, competitive inhibition with substrate analogs Amino acids Medium 31073693
2022 miR-31-5p directly targets the 3'UTR of SLC15A4 and negatively regulates SLC15A4 expression; inhibition of miR-31-5p in pDC-like cells increases IRF5 phosphorylation and IFN-stimulated gene induction upon TLR stimulation, while overexpression of miR-31-5p reverses this effect. Luciferase reporter assay (miRNA-target validation), miR-31-5p mimic/inhibitor transfection, IRF5 phosphorylation immunofluorescence, ISG expression by RT-qPCR Journal of inflammation research Medium 36510495
2025 Conformation-selective antibodies against SLC15A4 reveal two functional states: clone 107 binds the TASL-binding-incompetent luminal-open (outward-facing) state, while clone 235 stabilizes the TASL-binding-competent cytoplasmic-open (inward-facing) state, demonstrating that TASL recruitment depends on a conformational switch in SLC15A4. Antibody screening, cryo-EM validation of conformational states, functional assays for TASL binding competence, TLR pathway activity readouts Nature communications High 40781080

Source papers

Stage 0 corpus · 79 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Phosphate transport in Arabidopsis: Pht1;1 and Pht1;4 play a major role in phosphate acquisition from both low- and high-phosphate environments. The Plant journal : for cell and molecular biology 509 15272879
2002 Expression analysis suggests novel roles for members of the Pht1 family of phosphate transporters in Arabidopsis. The Plant journal : for cell and molecular biology 330 12164813
2020 TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9. Nature 173 32433612
2007 A mutant of the Arabidopsis phosphate transporter PHT1;1 displays enhanced arsenic accumulation. The Plant cell 169 17400898
2004 Transcriptional regulation and functional properties of Arabidopsis Pht1;4, a high affinity transporter contributing greatly to phosphate uptake in phosphate deprived plants. Plant molecular biology 168 15604713
2010 Slc15a4, AP-3, and Hermansky-Pudlak syndrome proteins are required for Toll-like receptor signaling in plasmacytoid dendritic cells. Proceedings of the National Academy of Sciences of the United States of America 166 21045126
2012 The Pht1;9 and Pht1;8 transporters mediate inorganic phosphate acquisition by the Arabidopsis thaliana root during phosphorus starvation. The New phytologist 164 22578268
2014 The histidine transporter SLC15A4 coordinates mTOR-dependent inflammatory responses and pathogenic antibody production. Immunity 133 25238095
2006 Differential regulation of five Pht1 phosphate transporters from maize (Zea mays L.). Plant biology (Stuttgart, Germany) 117 16547863
2003 Characterization of two phosphate transporters from barley; evidence for diverse function and kinetic properties among members of the Pht1 family. Plant molecular biology 111 14756304
2013 Essential requirement for IRF8 and SLC15A4 implicates plasmacytoid dendritic cells in the pathogenesis of lupus. Proceedings of the National Academy of Sciences of the United States of America 110 23382217
2015 A member of the Phosphate transporter 1 (Pht1) family from the arsenic-hyperaccumulating fern Pteris vittata is a high-affinity arsenate transporter. The New phytologist 101 26010225
2016 Systematic Identification, Evolution and Expression Analysis of the Zea mays PHT1 Gene Family Reveals Several New Members Involved in Root Colonization by Arbuscular Mycorrhizal Fungi. International journal of molecular sciences 98 27304955
2004 Promoter analysis of the barley Pht1;1 phosphate transporter gene identifies regions controlling root expression and responsiveness to phosphate deprivation. Plant physiology 90 15542491
2004 Characterization of promoter expression patterns derived from the Pht1 phosphate transporter genes of barley (Hordeum vulgare L.). Journal of experimental botany 84 15020637
2015 Plant phosphorus acquisition in a common mycorrhizal network: regulation of phosphate transporter genes of the Pht1 family in sorghum and flax. The New phytologist 83 25615409
2014 Genome-wide investigation and expression analysis suggest diverse roles and genetic redundancy of Pht1 family genes in response to Pi deficiency in tomato. BMC plant biology 81 24618087
2013 Functional analysis of the novel mycorrhiza-specific phosphate transporter AsPT1 and PHT1 family from Astragalus sinicus during the arbuscular mycorrhizal symbiosis. The New phytologist 80 23442117
2014 Arabidopsis PHOSPHATE TRANSPORTER1 genes PHT1;8 and PHT1;9 are involved in root-to-shoot translocation of orthophosphate. BMC plant biology 78 25428623
1988 Legless, a novel mutation found in PHT1-1 transgenic mice. Science (New York, N.Y.) 73 3406741
2008 Closely related members of the Medicago truncatula PHT1 phosphate transporter gene family encode phosphate transporters with distinct biochemical activities. The Journal of biological chemistry 67 18596039
2012 Functional characterization of 14 Pht1 family genes in yeast and their expressions in response to nutrient starvation in soybean. PloS one 63 23133521
2014 Phosphate concentration and arbuscular mycorrhizal colonisation influence the growth, yield and expression of twelve PHT1 family phosphate transporters in foxtail millet (Setaria italica). PloS one 57 25251671
2017 Genome-wide Identification, Characterization, and Expression Analysis of PHT1 Phosphate Transporters in Wheat. Frontiers in plant science 49 28443126
2018 SLC15A2 and SLC15A4 Mediate the Transport of Bacterially Derived Di/Tripeptides To Enhance the Nucleotide-Binding Oligomerization Domain-Dependent Immune Response in Mouse Bone Marrow-Derived Macrophages. Journal of immunology (Baltimore, Md. : 1950) 47 29784761
2020 Spatial Divergence of PHR-PHT1 Modules Maintains Phosphorus Homeostasis in Soybean Nodules. Plant physiology 44 32680974
2013 Expression of the peptide transporters PepT1, PepT2, and PHT1 in the embryonic and posthatch chick. Poultry science 44 23571341
2021 SLC15A4 mediates M1-prone metabolic shifts in macrophages and guards immune cells from metabolic stress. Proceedings of the National Academy of Sciences of the United States of America 37 34385317
2015 Increased phosphate transport of Arabidopsis thaliana Pht1;1 by site-directed mutagenesis of tyrosine 312 may be attributed to the disruption of homomeric interactions. Plant, cell & environment 37 25754174
2012 Slc15a4, a gene required for pDC sensing of TLR ligands, is required to control persistent viral infection. PLoS pathogens 37 23028315
2021 Human SLC15A4 is crucial for TLR-mediated type I interferon production and mitochondrial integrity. International immunology 35 33560415
2017 Functional characterization of the PHT1 family transporters of foxtail millet with development of a novel Agrobacterium-mediated transformation procedure. Scientific reports 33 29070807
2014 A Brassica napus PHT1 phosphate transporter, BnPht1;4, promotes phosphate uptake and affects roots architecture of transgenic Arabidopsis. Plant molecular biology 33 25194430
2013 Variants in TNFSF4, TNFAIP3, TNIP1, BLK, SLC15A4 and UBE2L3 interact to confer risk of systemic lupus erythematosus in Chinese population. Rheumatology international 32 24091983
2022 The solute carrier SLC15A4 is required for optimal trafficking of nucleic acid-sensing TLRs and ligands to endolysosomes. Proceedings of the National Academy of Sciences of the United States of America 30 35349343
2017 Lysosome biogenesis regulated by the amino-acid transporter SLC15A4 is critical for functional integrity of mast cells. International immunology 30 29155995
2023 A conformation-locking inhibitor of SLC15A4 with TASL proteostatic anti-inflammatory activity. Nature communications 28 37863876
2019 The proton-coupled oligopeptide transporters PEPT2, PHT1 and PHT2 mediate the uptake of carnosine in glioblastoma cells. Amino acids 28 31073693
2011 Molecular cloning, characterization and expression analysis of two members of the Pht1 family of phosphate transporters in Glycine max. PloS one 27 21698287
2022 Phosphate transporter PHT1;1 is a key determinant of phosphorus acquisition in Arabidopsis natural accessions. Plant physiology 26 35639954
2024 Chemoproteomic development of SLC15A4 inhibitors with anti-inflammatory activity. Nature chemical biology 25 38191941
2023 Structural basis for recruitment of TASL by SLC15A4 in human endolysosomal TLR signaling. Nature communications 25 37863913
2021 The peptide symporter SLC15a4 is essential for the development of systemic lupus erythematosus in murine models. PloS one 24 33444326
2019 Integrative Analysis of the Wheat PHT1 Gene Family Reveals A Novel Member Involved in Arbuscular Mycorrhizal Phosphate Transport and Immunity. Cells 24 31121904
2014 Divergent developmental expression and function of the proton-coupled oligopeptide transporters PepT2 and PhT1 in regional brain slices of mouse and rat. Journal of neurochemistry 24 24548120
2023 Wheat PHT1;9 acts as one candidate arsenate absorption transporter for phytoremediation. Journal of hazardous materials 23 36940527
2017 Identification and expression profiling of Pht1 phosphate transporters in wheat in controlled environments and in the field. Plant biology (Stuttgart, Germany) 22 29148171
2017 Identification of SLC20A1 and SLC15A4 among other genes as potential risk factors for combined pituitary hormone deficiency. Genetics in medicine : official journal of the American College of Medical Genetics 20 29261175
2022 miR-31-5p Regulates Type I Interferon by Targeting SLC15A4 in Plasmacytoid Dendritic Cells of Systemic Lupus Erythematosus. Journal of inflammation research 18 36510495
2020 Expression of PHT1 family transporter genes contributes for low phosphate stress tolerance in foxtail millet (Setaria italica) genotypes. Planta 17 33159589
2019 Phosphate supply influenced the growth, yield and expression of PHT1 family phosphate transporters in seven millets. Planta 17 31300887
2014 Slc15a4 function is required for intact class switch recombination to IgG2c in response to TLR9 stimulation. Immunology and cell biology 17 25310967
2016 The conservation of phosphate-binding residues among PHT1 transporters suggests that distinct transport affinities are unlikely to result from differences in the phosphate-binding site. Biochemical Society transactions 14 27911737
2023 Molecular basis of TASL recruitment by the peptide/histidine transporter 1, PHT1. Nature communications 13 37709742
2021 The Caenorhabditis elegans Patched domain protein PTR-4 is required for proper organization of the precuticular apical extracellular matrix. Genetics 13 34740248
2016 Association Study Between SLC15A4 Polymorphisms and Haplotypes and Systemic Lupus Erythematosus in a Han Chinese Population. Genetic testing and molecular biomarkers 13 27362648
2016 A novel role for PHT1 in the disposition of l-histidine in brain: In vitro slice and in vivo pharmacokinetic studies in wildtype and Pht1 null mice. Biochemical pharmacology 12 27845049
2021 GTPase ROP6 negatively modulates phosphate deficiency through inhibition of PHT1;1 and PHT1;4 in Arabidopsis thaliana. Journal of integrative plant biology 11 34288396
2018 A requirement for slc15a4 in imiquimod-induced systemic inflammation and psoriasiform inflammation in mice. Scientific reports 11 30262916
2021 The enhanced phosphorus use efficiency in phosphate-deficient and mycorrhiza-inoculated barley seedlings involves activation of different sets of PHT1 transporters in roots. Planta 10 34312721
2011 Arabidopsis Pht1;5 plays an integral role in phosphate homeostasis. Plant signaling & behavior 9 22057342
2019 Expression analysis and functional characterization of two PHT1 family phosphate transporters in ryegrass. Planta 8 31776735
2022 Identification of SLC15A4/PHT1 Gene Products Upregulation Marking the Intestinal Epithelial Monolayer of Ulcerative Colitis Patients. International journal of molecular sciences 7 36361959
2024 PHT1;5 Repressed by ANT Mediates Pi Acquisition and Distribution under Low Pi and Salinity in Salt Cress. Plant & cell physiology 6 37758243
2023 Isolation and Characterization of Erianthus arundinaceus Phosphate Transporter 1 (PHT1) Gene Promoter and 5' Deletion Analysis of Transcriptional Regulation Regions under Phosphate Stress in Transgenic Tobacco. Plants (Basel, Switzerland) 6 37960116
2011 THE EVALUATION OF PEPTIDE/HISTIDINE TRANSPORTER 1 (PHT1) FUNCTION: UPTAKE KINETICS UTILIZING A COS-7 STABLY TRANSFECTED CELL LINE. Revista mexicana de ciencias farmaceutica 6 23888104
2022 A Eucalyptus Pht1 Family Gene EgPT8 Is Essential for Arbuscule Elongation of Rhizophagus irregularis. Microbiology spectrum 5 36227088
2020 Expression dynamics of solute carrier family 15 member 4 (SLC15A4) and its potential regulatory role in ovarian development of the Indian white shrimp, Penaeus indicus. Molecular biology reports 5 32363413
2023 A Non-Coding Variant in SLC15A4 Modulates Enhancer Activity and Lysosomal Deacidification Linked to Lupus Susceptibility. Frontiers in lupus 4 38317862
2022 Whole exome sequencing identifies novel germline variants of SLC15A4 gene as potentially cancer predisposing in familial colorectal cancer. Molecular genetics and genomics : MGG 4 35562597
2024 Genome-Wide Identification and Characterization of the PHT1 Gene Family and Its Response to Mycorrhizal Symbiosis in Salvia miltiorrhiza under Phosphate Stress. Genes 3 38790218
2024 Identification and expression analysis of Phosphate Transporter 1 (PHT1) genes in the highly phosphorus-use-efficient Hakea prostrata (Proteaceae). Plant, cell & environment 2 39136390
2022 Systematic Identification and Expression Analysis of the Sorghum Pht1 Gene Family Reveals Several New Members Encoding High-Affinity Phosphate Transporters. International journal of molecular sciences 2 36430345
2020 Function and application of the Eutrema salsugineum PHT1;1 gene in phosphate deficiency stress. Plant biology (Stuttgart, Germany) 2 32779343
2025 Crucial role of the Pht1;4 Gene in Sb(V) tolerance and uptake in Arabidopsis thaliana. Ecotoxicology and environmental safety 1 40367618
2023 A Non-Coding Variant in SLC15A4 Modulates Enhancer Activity and Lysosomal Deacidification Linked to Lupus Susceptibility. bioRxiv : the preprint server for biology 1 37546883
2025 Functional Characterization of Acer Truncatum PHT1 Family Phosphate Transporter Genes and Their Involvement in Arbuscular Mycorrhizal Symbiosis. Physiologia plantarum 0 40556045
2025 Development of conformation-selective antibodies targeting human SLC15A4. Nature communications 0 40781080
2024 The structures of the peptide transporters SLC15A3 and SLC15A4 reveal the recognition mechanisms for substrate and TASL. Structure (London, England : 1993) 0 39719710