Affinage

SLC4A7

Sodium bicarbonate cotransporter 3 · UniProt Q9Y6M7

Length
1214 aa
Mass
136.0 kDa
Annotated
2026-04-28
41 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC4A7 (NBCn1) is an electroneutral, Na⁺/HCO₃⁻ cotransporter that maintains intracellular pH homeostasis across a broad range of tissues—including vascular smooth muscle, neurons, sensory cells, epithelia, and macrophages—and couples bicarbonate import to biosynthetic and signaling processes. The transporter is stilbene (DIDS)-insensitive and EIPA-inhibitable, requires its C-terminal cytoplasmic domain for surface trafficking and transport activity, and is functionally enhanced by carbonic anhydrase II binding at residues D1135–D1136, while PKA independently reduces its activity (PMID:10347222, PMID:14736710, PMID:14578046). SLC4A7 knockout causes sensory degeneration (blindness and deafness), vascular pH dysregulation with altered blood pressure, impaired macrophage phagosome acidification, and delayed breast tumor growth, while mTORC1-driven translational upregulation of SLC4A7 channels intracellular HCO₃⁻ into de novo nucleotide synthesis to support cell proliferation (PMID:12808454, PMID:21947296, PMID:29779931, PMID:26212013, PMID:35772404). SLC4A7 also forms a membrane complex with Rhes in striatal neurons, facilitating tunneling nanotube formation and intercellular transfer of mutant Huntingtin independently of its transport activity (PMID:41861004).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1999 High

    Establishing the basic transport identity of SLC4A7 resolved what activity this orphan SLC4 family member encoded: it is an electroneutral, DIDS-insensitive, EIPA-inhibitable Na⁺/HCO₃⁻ cotransporter, and it physically associates with the vacuolar H⁺-ATPase at the apical membrane of renal intercalated cells.

    Evidence Functional reconstitution of mNBC3 cRNA in Xenopus oocytes; co-IP of NBC3 with V-ATPase subunit and immunolocalization in rabbit collecting duct

    PMID:10347222 PMID:10600945

    Open questions at the time
    • Stoichiometry of the Na⁺:HCO₃⁻ coupling not biochemically resolved
    • Functional significance of the NBC3–V-ATPase physical interaction not tested by disruption
  2. 2002 High

    Identification of the C-terminal PDZ motif as the molecular basis for NBC3's interaction with the V-ATPase (via NHERF-1 scaffolding) explained how the cotransporter is assembled into a macromolecular acid-base transport complex in native kidney.

    Evidence Peptide pull-down with mutagenesis (Leu→Gly abolishes binding) plus co-IP of a trimeric NBC3/56-kDa V-ATPase/NHERF-1 complex from rat kidney

    PMID:12444018

    Open questions at the time
    • Whether the trimeric complex is required for transport function in vivo was not tested
    • Other PDZ partners in non-renal tissues not yet surveyed
  3. 2003 High

    Knockout of SLC4A7 in mice revealed that the transporter is indispensable for sensory receptor survival, establishing an in vivo requirement for Na⁺/HCO₃⁻ cotransport in photoreceptor and auditory hair cell maintenance.

    Evidence Targeted KO mouse with histological degeneration of retinal photoreceptors and cochlear hair cells/spiral ganglion neurons; ERG and ABR electrophysiology

    PMID:12808454

    Open questions at the time
    • Molecular mechanism linking intracellular acidification to sensory cell death not delineated
    • Contribution of individual SLC4A7 splice variants to the sensory phenotype unknown
  4. 2004 High

    Defining carbonic anhydrase II as a direct binding partner at D1135–D1136 and showing that this interaction maximizes transport rate established a metabolon model in which CO₂ hydration is coupled to HCO₃⁻ import; PKA was shown to independently reduce transport activity.

    Evidence In vitro Kd measurement (101 nM), D1135N/D1136N mutagenesis retaining only 29% activity, co-transfection rescue in HEK-293 cells, phosphorylation assays

    PMID:14736710

    Open questions at the time
    • PKA phosphorylation site on SLC4A7 not mapped
    • In vivo disruption of the CAII–NBC3 interaction not tested
  5. 2006 High

    siRNA knockdown in intact arteries demonstrated that SLC4A7 is the dominant Na⁺/HCO₃⁻ cotransporter setting steady-state pH in vascular smooth muscle, answering which SLC4 family member maintains pH in the vasculature.

    Evidence RT-PCR survey, siRNA knockdown (~43% mRNA reduction) in intact mouse mesenteric arteries with BCECF pH measurement showing 0.21 pH unit drop and 68% loss of Na⁺-dependent base influx

    PMID:16439691

    Open questions at the time
    • Compensatory upregulation of other acid-base transporters not assessed
    • Endothelial-specific contribution not isolated at this stage
  6. 2011 High

    Full KO vascular phenotyping resolved how SLC4A7 loss translates to blood pressure changes: intracellular acidification of both smooth muscle and endothelium reduces NO production and rho-kinase-dependent Ca²⁺ sensitivity, causing mild resting hypertension yet blunted angiotensin-II-induced hypertension.

    Evidence NBCn1 KO mice with myography, NO electrode, BCECF pH/Ca²⁺ imaging, MYPT1-Thr850 phosphorylation, and radiotelemetric blood pressure

    PMID:21947296

    Open questions at the time
    • Relative contribution of endothelial vs. smooth muscle SLC4A7 not resolved by cell-type-specific KO
    • Role in cardiac myocytes and potential cardiac phenotype not examined
  7. 2013 High

    Mapping the ErbB2→Akt/ERK/Src→KLF4 signaling axis to the SLC4A7 promoter explained how oncogenic HER2 signaling transcriptionally upregulates acid extrusion capacity in breast cancer cells.

    Evidence Multiple siRNA knockdowns of PI3K, Akt1, ERK1/2, Src, KLF4, Sp1 combined with luciferase promoter reporters and pH recovery assays

    PMID:24088818

    Open questions at the time
    • Direct KLF4 binding to the SLC4A7 promoter not confirmed by ChIP
    • Relevance to non-ErbB2 breast cancer subtypes not tested
  8. 2015 High

    Genetic ablation of SLC4A7 in a mammary tumor model proved that the transporter's pH-regulatory function is rate-limiting for breast cancer growth and proliferation in vivo, not merely correlative.

    Evidence NBCn1 KO mice: ~50% delayed tumor latency, ~65% reduced growth rate, ~60% lower Ki-67 index, shift to less aggressive histopathology

    PMID:26212013

    Open questions at the time
    • Whether tumor growth delay reflects pH-dependent proliferation or bicarbonate-dependent biosynthesis was unclear at this point
    • Human therapeutic targeting not demonstrated
  9. 2018 High

    Demonstrating that SLC4A7 maintains cytoplasmic pH during phagocytosis to enable phagosome acidification established a non-neoplastic immune defense role and showed that its transport and localization functions are both required for microbicidal activity.

    Evidence CRISPR/siRNA KO in human macrophages with phagosome acidification assays, microbicidal assays, and rescue by WT but not transport-dead or mislocalized mutants

    PMID:29779931

    Open questions at the time
    • Identity of the signal that upregulates SLC4A7 during macrophage differentiation not resolved
    • In vivo infection susceptibility of SLC4A7 KO mice not tested
  10. 2022 High

    Discovery that mTORC1 selectively upregulates SLC4A7 translation via S6K→eIF4B phosphorylation, and that the imported HCO₃⁻ feeds de novo nucleotide synthesis, uncoupled SLC4A7's growth-promoting role from simple pH regulation and identified a metabolic channeling mechanism.

    Evidence Rapamycin/S6K knockdown, eIF4B phosphorylation analysis, SLC4A7 siRNA/KO with ¹³C isotope tracing of purine/pyrimidine synthesis flux, xenograft tumor growth

    PMID:35772404

    Open questions at the time
    • Whether carbonic anhydrase II metabolon coupling contributes to the nucleotide synthesis flux unknown
    • Relative contribution of pH-independent HCO₃⁻ supply vs. pH-dependent mechanisms across cancer types not resolved
  11. 2024 High

    Functional blocking antibodies targeting extracellular SLC4A7 epitopes validated the transporter as a druggable therapeutic target in human breast cancer, reducing acid extrusion in primary organoids and tumor growth in xenografts.

    Evidence Anti-NBCn1 antibodies (KD ~0.14 nM) tested in primary breast carcinoma organoids, PDX tumor growth (~50% reduction), and flow cytometry for G2/M arrest and apoptosis

    PMID:38310186

    Open questions at the time
    • On-target toxicity to normal tissues expressing SLC4A7 (vasculature, sensory organs) not evaluated
    • Combinatorial efficacy with standard-of-care chemotherapy not tested
  12. 2026 High

    Unbiased proteomics identified Rhes as a direct membrane partner of SLC4A7 in striatal neurons, revealing a transport-activity-independent scaffolding role for SLC4A7 in tunneling nanotube formation and mutant Huntingtin intercellular transfer.

    Evidence LC-MS/MS of membrane Rhes complexes, domain interaction mapping, siRNA/pharmacological inhibition of SLC4A7 reducing TNT and mHTT transfer, SLC4A7 KO mice showing reduced mHTT transmission in vivo

    PMID:41861004

    Open questions at the time
    • Structural basis for the transport-independent SLC4A7–Rhes interaction not defined
    • Whether this mechanism extends to other neurodegenerative proteinopathies unknown
    • Rhes farnesylation-dependent membrane association mechanism with SLC4A7 not structurally resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • No high-resolution structure of SLC4A7 exists, and the mechanisms governing splice-variant-specific trafficking, the relative contributions of pH-dependent versus HCO₃⁻-supply-dependent functions across tissues, and the structural basis for transport-independent Rhes scaffolding remain open.
  • No cryo-EM or crystal structure of any SLC4A7 variant
  • Cell-type-specific conditional knockouts needed to disentangle vascular, neuronal, immune, and oncogenic phenotypes
  • PKA phosphorylation site on SLC4A7 still unmapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 10
Localization
GO:0005886 plasma membrane 7 GO:0005739 mitochondrion 1
Pathway
R-HSA-382551 Transport of small molecules 7 R-HSA-1643685 Disease 3 R-HSA-162582 Signal Transduction 2 R-HSA-1430728 Metabolism 1 R-HSA-168256 Immune System 1
Complex memberships
NBC3/NHERF-1/V-ATPase trimeric complexSLC4A7/Rhes membrane complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 NBC3 (SLC4A7) encodes a stilbene-insensitive, 5-(N-ethyl-N-isopropyl)-amiloride (EIPA)-inhibitable, electroneutral Na+/HCO3- cotransporter, as demonstrated by functional expression of mNBC3 cRNA in Xenopus laevis oocytes. Xenopus oocyte expression system, functional transport assay The Journal of biological chemistry High 10347222
1999 NBC3 (SLC4A7) protein localizes to the apical membrane of intercalated cells in rabbit cortical and outer medullary collecting ducts, where it co-immunoprecipitates with the vacuolar H+-ATPase 31-kDa subunit, and functional studies confirm apical Na+-dependent base transport that is EIPA-inhibitable and DIDS-insensitive in outer medullary collecting duct type A intercalated cells. Immunocytochemistry, co-immunoprecipitation, functional transport assay in isolated tubules The American journal of physiology High 10600945
2000 NBC3 (SLC4A7) localizes to the apical membrane of apical (narrow) cells in caput epididymidis and light (clear) cells in corpus and cauda epididymidis, co-localizing precisely with vacuolar H+-ATPase, suggesting a structural/functional interaction between the two transporters in cells with high vacuolar H+-ATPase expression. Immunolocalization (immunofluorescence and immunohistochemistry) Journal of andrology Medium 10975418
2002 The COOH terminus of NBC3 (SLC4A7) acts as a PDZ-interacting motif: an 18-amino-acid COOH-terminal peptide pulls down both the 56- and 70-kDa subunits of vacuolar H+-ATPase and NHERF-1 from kidney membrane proteins; truncation or Leu→Gly substitution of the C-terminal leucine abolishes binding to the proton pump subunits. A trimeric complex of NBC3, the 56-kDa H+-ATPase subunit, and NHERF-1 was identified in rat kidney. Sepharose bead pull-down with synthetic peptides, mutagenesis, co-immunoprecipitation from rat kidney lysates American journal of physiology. Cell physiology High 12444018
2003 Loss of NBC3 (SLC4A7) in knockout mice causes blindness and auditory impairment due to degeneration of photoreceptors in the eye and hair cells/spiral ganglion neurons/fibrocytes in the inner ear, establishing a specific requirement for SLC4A7-mediated H+ disposal in sensory receptor maintenance. Targeted gene knockout mouse model, histology, electrophysiology (ERG, auditory brainstem responses) Nature genetics High 12808454
2003 The C-terminal cytoplasmic domain of NBC3 (NBC3Ct) is essential for cell surface trafficking and transport activity: deletion of NBC3Ct reduces transport activity to 12% of wild-type due to near-complete intracellular retention, as shown by immunoblot and confocal microscopy. NBC3Ct adopts an elongated prolate shape and does not change secondary structure over pH 6.2–7.8. C-terminal deletion mutagenesis, confocal microscopy, immunoblot, gel permeation chromatography, sedimentation velocity ultracentrifugation, circular dichroism Molecular membrane biology High 14578046
2004 Carbonic anhydrase II (CAII) binds the COOH-terminal domain of NBC3 (SLC4A7) with Kd = 101 nM, with stronger interaction at acid pH. The D1135-D1136 region is the essential CAII-binding site; D1135N/D1136N mutation retains only 29% of wild-type transport activity. CAII co-expression recruits CAII to the plasma membrane and enhances NBC3 transport. PKA reduces NBC3 transport activity independently of the NBC3/CAII interaction, without phosphorylating the NBC3 C-terminal domain. In vitro binding assay (Kd measurement), mutagenesis, co-transfection in HEK-293 cells, intracellular pH recovery assay, mass spectrometry, [γ-32P]ATP phosphorylation assay American journal of physiology. Cell physiology High 14736710
2006 NBCn1 (SLC4A7) is the only Na+-dependent HCO3- cotransporter of the SLC4 family detectable in mouse mesenteric, coronary, and cerebral small artery smooth muscle cells by RT-PCR. siRNA-mediated knockdown of NBCn1 in intact mesenteric arteries (~43% mRNA reduction) caused a 0.21 pH unit decrease in steady-state intracellular pH and a 68% decrease in Na+-dependent, amiloride-insensitive base influx after acid loading. RT-PCR, immunogold electron microscopy, siRNA knockdown in intact arteries, BCECF fluorescence pH measurement Circulation research High 16439691
2007 NBCn1 (SLC4A7) promoter is active in a broad range of tissues including vascular smooth muscle cells, endothelial cells, kidney thick ascending limb and medullary collecting duct, choroid plexus, hippocampus, retina, atrial cardiomyocytes, and non-vascular smooth muscle cells, as established by LacZ (β-galactosidase) knock-in reporter in mice. Gene disruption reduced amiloride-insensitive Na+-dependent HCO3- influx and lowered steady-state intracellular pH in bladder smooth muscle cells in the presence of CO2/HCO3-. LacZ knock-in reporter (antibody-independent), RT-PCR, BCECF fluorescence pH assay in knockout mice American journal of physiology. Cell physiology High 18077606
2008 In parotid acinar ParC5 cells, NBCn1 (SLC4A7) remains stably at the basolateral membrane and is not downregulated by cholinergic stimulation, PMA, or constitutive recycling inhibitors, in contrast to NBCe1, which undergoes PKC-dependent endocytosis. This stable membrane association supports constitutive HCO3- uptake. Confocal fluorescence microscopy, surface biotinylation, pharmacological treatments (carbachol, PMA, monensin, W-13, GF-109203X) American journal of physiology. Cell physiology Medium 18815229
2010 NBCn1 (SLC4A7) co-localizes with the postsynaptic density protein PSD-95 in hippocampal CA3 neuron dendrites; PSD-95 is pulled down from rat brain lysates with GST-NBCn1 fusion protein and co-immunoprecipitated with NBCn1. Chronic metabolic acidosis upregulates NBCn1 mRNA and protein in the hippocampus and enhances glutamate excitotoxicity. Double immunofluorescence, GST pull-down, co-immunoprecipitation from brain lysates, real-time PCR, immunoblot American journal of physiology. Cell physiology Medium 20147654
2010 SLC4A7 localizes to mitochondria of rat coronary endothelial cells and suppresses ischemia-induced mitochondrial apoptosis: selective inhibition (S0859) or siRNA knockdown of SLC4A7 increases caspase-3/caspase-9 activity and Bax-mitochondria binding without activating caspase-8 or caspase-12 pathways. siRNA knockdown, pharmacological inhibition (S0859), caspase activity assays, subcellular fractionation/mitochondrial localization, Western blot Cardiovascular research Medium 20962104
2011 Knockout of NBCn1 (SLC4A7) in mice eliminates Na+/HCO3- cotransport in mesenteric artery smooth muscle and endothelial cells, causing intracellular acidification. This acidification reduces NO-mediated vasorelaxation (by lowering NOS activity/NO production rather than eNOS expression or endothelial Ca2+ responses), reduces rho-kinase-dependent smooth muscle Ca2+ sensitivity (via reduced MYPT1-Thr850 phosphorylation), and causes mild resting hypertension with resistance to angiotensin-II-induced hypertension. NBCn1 knockout mice, fluorescence microscopy (BCECF pH, Ca2+ imaging), myography, NO electrode, radioisotope L-arginine conversion, Western blot, radiotelemetry, in vitro rho-kinase activity assay at defined pH Circulation High 21947296
2012 In human primary breast carcinomas, Na+/HCO3- cotransport mediated predominantly by NBCn1 (SLC4A7) is the main mechanism of acid extrusion at pHi >6.6, accounting for >90% of net acid extrusion in the presence of CO2/HCO3-. NBCn1 plasma membrane density is 20–30% higher in breast carcinomas and metastases compared with matched normal breast tissue. pH-sensitive fluorophore (BCECF) intracellular pH measurements in primary tumor tissue, DIDS inhibition, Western blot International journal of cancer Medium 22907202
2013 ErbB2 (HER2) receptor signaling upregulates NBCn1 (SLC4A7) expression and acid extrusion capacity via downstream kinases Akt1, ERK1/2, and Src, and the transcription factor KLF4 (positive regulator), while Sp1 acts as a negative regulator. The minimal ΔNErbB2-responsive SLC4A7 promoter region was identified. siRNA knockdown (PI3K, Akt1, ERK1/2, Src, KLF4, Sp1), dominant-negative Sp1 transfection, luciferase promoter reporter assay, intracellular pH measurement (acid extrusion capacity), Western blot FASEB journal High 24088818
2013 Optional structural elements (OSEs) of NBCn1 (SLC4A7) alter both surface abundance and intrinsic transport activity when expressed in Xenopus oocytes: the MEAD N-terminus increases surface abundance; novel cassette IV reduces surface abundance; cassettes II, III, and novel cassette IV increase intrinsic HCO3- transport activity per molecule. Electrophysiology (two-electrode voltage clamp) and cell surface biotinylation in Xenopus oocytes The Journal of physiology Medium 23959679
2014 NBCn1 (SLC4A7) C-terminal domain binds 13 PDZ-domain proteins including NHERF-1, NHERF-2, PSD-95, syntrophins, and others. Syntrophin γ2 directly binds NBCn1 (reciprocal GST pull-downs) and functionally increases both intracellular pH recovery rate (Na/HCO3 cotransport activity) and an NBCn1-associated ionic conductance in Xenopus oocytes. PDZ protein array screen, reciprocal GST pull-down, Xenopus oocyte functional assay (pH recovery, electrophysiology) Physiological reports Medium 24844638
2015 NBCn1 (SLC4A7) is responsible for the elevated net acid extrusion and alkaline intracellular pH of breast cancer compared to normal breast tissue: NBCn1 protein increases ~2.5-fold during breast carcinogenesis and its genetic knockout delays tumor latency by ~50%, reduces tumor growth rate by ~65%, lowers Ki-67-measured cancer cell proliferation by ~60%, and shifts histopathology toward less aggressive tumor types in a mouse mammary tumor model. NBCn1 knockout mice, intracellular pH measurement, tumor growth kinetics, Ki-67/phospho-histone H3 staining, microdialysis for interstitial metabolites, histopathology Oncogene High 26212013
2018 SLC4A7, strongly induced upon macrophage differentiation, is required for phagosome acidification: loss of SLC4A7 reduces phagosomal acidification and intracellular microbicidal capacity. The phenotype is rescued by wild-type SLC4A7 but not by transport-deficient or mislocalized mutants. Loss of SLC4A7 causes cytoplasmic acidification during phagocytosis, indicating that SLC4A7 maintains cytoplasmic pH homeostasis to enable phagosome acidification. siRNA/CRISPR loss-of-function in human macrophage cell lines, phagosome acidification assay (fluorescent beads/bacteria), microbicidal assay, rescue with wild-type and mutant SLC4A7 Cell host & microbe High 29779931
2018 NBCn1 (SLC4A7) protein increases ~2-fold in ErbB2-induced breast cancer tissue (despite decreased mRNA), mediates net acid extrusion and maintains alkaline intracellular pH in cancer tissue. Its knockout delays ErbB2-induced carcinogenesis (median tumor-free survival 9.5 vs 12 months), reduces tumor growth rate by ~1/3, and inhibits cancer cell proliferation particularly in central glycolysis-high tumor areas. NBCn1 knockout mice crossed with ErbB2 transgenic mice, intracellular pH measurement, tumor growth kinetics, Ki-67 staining, microdialysis, Western blot, mRNA quantification Oncogene High 29907770
2022 mTORC1 stimulates SLC4A7 expression through S6K-dependent phosphorylation of translation factor eIF4B, selectively increasing SLC4A7 mRNA translation. SLC4A7-mediated intracellular HCO3- import promotes de novo purine and pyrimidine synthesis (nucleotide synthesis flux) and cell/tumor growth without altering intracellular pH in mTORC1-driven cells. mTORC1 inhibition (rapamycin), S6K knockdown, eIF4B phosphorylation analysis, SLC4A7 loss-of-function (siRNA/KO) with isotope tracing of nucleotide synthesis flux, tumor xenograft growth assay Molecular cell High 35772404
2024 In colonic Caco2BBe cells, NBCn1 (SLC4A7) knockdown lowers intracellular pH proportionally to knockdown extent, reduces proliferation, decreases migration speed, and disrupts cell adhesion. NBCn1 localizes to the leading edge of migrating cells and co-localizes with focal adhesion markers vinculin and paxillin, suggesting involvement in cell-matrix adhesion establishment. siRNA knockdown, BCECF intracellular pH measurement, Ki-67 proliferation assay, wound healing/migration assay, co-localization with focal adhesion markers by immunofluorescence, murine Nbcn1-/- colonoid proliferation assay American journal of physiology. Cell physiology Medium 38646790
2024 Extracellularly-targeted anti-NBCn1 antibodies (KD ≈ 0.14 nM) that block human SLC4A7-mediated Na+/HCO3- cotransport reduce net acid extrusion in primary human breast carcinoma organoids, decelerate triple-negative breast cancer xenograft tumor growth by ~50%, and pH-dependently induce G2/M arrest and apoptosis of metastatic breast cancer cells. Functional antibody blocking assay, pH measurement in primary organoids, patient-derived xenograft tumor growth, flow cytometry (cell cycle/apoptosis) British journal of cancer High 38310186
2026 Slc4a7 is a top membrane-binding partner of Rhes (identified by unbiased LC-MS/MS of membrane-associated Rhes complexes). Rhes directly interacts with Slc4a7 through both its amino- and carboxyl-terminal domains. siRNA depletion or pharmacological inhibition of Slc4a7 substantially reduces Rhes-induced tunneling nanotube (TNT) formation and mutant Huntingtin intercellular transfer. Rhes modulates intracellular pH via Slc4a7 to facilitate TNT formation, but this interaction does not require Slc4a7 transporter activity. Rhes farnesylation is required for its membrane association with Slc4a7 and TNT formation. Slc4a7 knockout mice show reduced mHTT cell-to-cell transmission in the striatum in vivo. LC-MS/MS proteomics, siRNA knockdown, pharmacological inhibition, domain interaction assays (N- and C-terminal domain binding), intracellular pH measurement, TNT formation assay, mHTT transfer assay, Slc4a7 knockout mice with in vivo mHTT transmission Science advances High 41861004

Source papers

Stage 0 corpus · 41 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Cloning, tissue distribution, genomic organization, and functional characterization of NBC3, a new member of the sodium bicarbonate cotransporter family. The Journal of biological chemistry 160 10347222
2011 Disruption of Na+,HCO₃⁻ cotransporter NBCn1 (slc4a7) inhibits NO-mediated vasorelaxation, smooth muscle Ca²⁺ sensitivity, and hypertension development in mice. Circulation 120 21947296
2012 Contribution of Na+,HCO3(-)-cotransport to cellular pH control in human breast cancer: a role for the breast cancer susceptibility locus NBCn1 (SLC4A7). International journal of cancer 99 22907202
2003 Blindness and auditory impairment caused by loss of the sodium bicarbonate cotransporter NBC3. Nature genetics 95 12808454
2015 Disrupting Na⁺, HCO₃⁻-cotransporter NBCn1 (Slc4a7) delays murine breast cancer development. Oncogene 77 26212013
2006 NBCn1 (slc4a7) mediates the Na+-dependent bicarbonate transport important for regulation of intracellular pH in mouse vascular smooth muscle cells. Circulation research 75 16439691
2007 Antibody-independent localization of the electroneutral Na+-HCO3- cotransporter NBCn1 (slc4a7) in mice. American journal of physiology. Cell physiology 71 18077606
2004 Regulation of the human NBC3 Na+/HCO3- cotransporter by carbonic anhydrase II and PKA. American journal of physiology. Cell physiology 68 14736710
2018 The Bicarbonate Transporter SLC4A7 Plays a Key Role in Macrophage Phagosome Acidification. Cell host & microbe 66 29779931
2018 Na+,HCO3--cotransporter NBCn1 (Slc4a7) accelerates ErbB2-induced breast cancer development and tumor growth in mice. Oncogene 48 29907770
1999 Characterization of Na+/HCO-3 cotransporter isoform NBC-3. The American journal of physiology 46 10362779
2000 Immunolocalization of NBC3 and NHE3 in the rat epididymis: colocalization of NBC3 and the vacuolar H+-ATPase. Journal of andrology 44 10975418
2010 Neuronal expression of sodium/bicarbonate cotransporter NBCn1 (SLC4A7) and its response to chronic metabolic acidosis. American journal of physiology. Cell physiology 39 20147654
2013 ErbB2 upregulates the Na+,HCO3(-)-cotransporter NBCn1/SLC4A7 in human breast cancer cells via Akt, ERK, Src, and Kruppel-like factor 4. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 38 24088818
2002 The COOH termini of NBC3 and the 56-kDa H+-ATPase subunit are PDZ motifs involved in their interaction. American journal of physiology. Cell physiology 34 12444018
2022 The mTORC1-SLC4A7 axis stimulates bicarbonate import to enhance de novo nucleotide synthesis. Molecular cell 31 35772404
1999 NBC3 expression in rabbit collecting duct: colocalization with vacuolar H+-ATPase. The American journal of physiology 31 10600945
2008 Sodium/bicarbonate cotransporter NBCn1/slc4a7 increases cytotoxicity in magnesium depletion in primary cultures of hippocampal neurons. The European journal of neuroscience 28 19170751
2010 SLC4A7 sodium bicarbonate co-transporter controls mitochondrial apoptosis in ischaemic coronary endothelial cells. Cardiovascular research 27 20962104
2001 Mouse Na+: HCO3- cotransporter isoform NBC-3 (kNBC-3): cloning, expression, and renal distribution. Kidney international 25 11260402
2007 Chronic continuous hypoxia decreases the expression of SLC4A7 (NBCn1) and SLC4A10 (NCBE) in mouse brain. American journal of physiology. Regulatory, integrative and comparative physiology 24 17928512
2005 Time course of auditory impairment in mice lacking the electroneutral sodium bicarbonate cotransporter NBC3 (slc4a7). Brain research. Developmental brain research 22 16181686
2003 Structural and functional characterization of the human NBC3 sodium/bicarbonate co-transporter carboxyl-terminal cytoplasmic domain. Molecular membrane biology 18 14578046
2013 Effects of optional structural elements, including two alternative amino termini and a new splicing cassette IV, on the function of the sodium-bicarbonate cotransporter NBCn1 (SLC4A7). The Journal of physiology 17 23959679
2008 Electrogenic NBCe1 (SLC4A4), but not electroneutral NBCn1 (SLC4A7), cotransporter undergoes cholinergic-stimulated endocytosis in salivary ParC5 cells. American journal of physiology. Cell physiology 17 18815229
2023 Bicarbonate transporter SLC4A7 promotes EMT and metastasis of HNSCC by activating the PI3K/AKT/mTOR signaling pathway. Molecular carcinogenesis 15 36727616
2016 The Hypertension Risk Variant Rs820430 Functions as an Enhancer of SLC4A7. American journal of hypertension 15 27784683
2014 Systematic family-wide analysis of sodium bicarbonate cotransporter NBCn1/SLC4A7 interactions with PDZ scaffold proteins. Physiological reports 14 24844638
2007 Variation in a bicarbonate co-transporter gene family member SLC4A7 is associated with propensity to addictions: a study using fine-mapping and three samples. Addiction (Abingdon, England) 11 17624982
2024 Antibodies toward Na+,HCO3--cotransporter NBCn1/SLC4A7 block net acid extrusion and cause pH-dependent growth inhibition and apoptosis in breast cancer. British journal of cancer 9 38310186
2020 Sodium bicarbonate cotransporter NBCn1/Slc4a7 affects locomotor activity and hearing in mice. Behavioural brain research 9 33321164
2025 SLC4A7 suppresses lung adenocarcinoma oncogenesis by reducing lactate transport and protein lactylation. International journal of oncology 7 40084702
2020 Novel mutation in SLC4A7 gene causing autosomal recessive progressive rod-cone dystrophy. Ophthalmic genetics 7 32594822
2017 Alternative transcription of sodium/bicarbonate transporter SLC4A7 gene enhanced by single nucleotide polymorphisms. Physiological genomics 7 28087757
2024 The electroneutral Na+-HCO3- cotransporter NBCn1 (SLC4A7) modulates colonic enterocyte pHi, proliferation, and migration. American journal of physiology. Cell physiology 6 38646790
2023 Update on the relationship between the SLC4A7 variant rs4973768 and breast cancer risk: a systematic review and meta-analysis. The Journal of international medical research 4 37128157
2022 SLC4A7 and mTORC1 raise nucleotide synthesis with bicarbonate. Molecular cell 4 36055205
2019 The apical Na+ -HCO3 - cotransporter Slc4a7 (NBCn1) does not contribute to bicarbonate transport by mouse salivary gland ducts. Journal of cellular physiology 4 30767201
2024 Slc4a7 Regulates Retina Development in Zebrafish. International journal of molecular sciences 1 39273559
2026 Membrane-associated Rhes-Slc4a7 complex orchestrates tunneling nanotube formation and mutant Huntingtin spread. Science advances 0 41861004
2025 Sulforaphane inhibits gastric cancer progression by regulating the YY1/PSMB8-AS1/miR-888-5p/SLC4A7 axis. Biochemical and biophysical research communications 0 41056875