Property Summary

NCBI Gene PubMed Count 80
PubMed Score 359.36
PubTator Score 139.24

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (7)

Disease Target Count Z-score Confidence
Carcinoma 2147 0.0 1.0
Disease Target Count Z-score Confidence
Heart conduction disease 65 0.0 1.0
Disease Target Count Z-score Confidence
Retinitis pigmentosa 156 0.0 4.0

Expression

  Differential Expression (33)

Disease log2 FC p
nephrosclerosis -2.096 2.7e-02
malignant mesothelioma -6.800 1.4e-09
astrocytic glioma 2.900 4.5e-02
oligodendroglioma 3.500 1.2e-03
ependymoma -1.300 1.5e-02
group 3 medulloblastoma -3.000 2.4e-05
cystic fibrosis -1.246 1.0e-02
atypical teratoid/rhabdoid tumor -3.600 7.3e-07
glioblastoma 1.200 1.1e-02
medulloblastoma, large-cell -4.500 7.2e-06
primitive neuroectodermal tumor -2.500 1.6e-02
Crohn's disease -1.752 1.3e-02
ulcerative colitis -3.300 2.9e-06
tuberculosis 1.400 2.3e-04
primary pancreatic ductal adenocarcinoma -1.759 4.6e-02
non-small cell lung cancer -2.132 1.8e-13
intraductal papillary-mucinous adenoma (... -1.500 1.9e-03
intraductal papillary-mucinous carcinoma... -2.800 3.2e-02
intraductal papillary-mucinous neoplasm ... -2.100 1.9e-02
colon cancer -5.900 3.5e-07
lung cancer -4.800 1.1e-06
pancreatic cancer -1.900 5.6e-03
interstitial cystitis -1.300 6.3e-03
lung adenocarcinoma -1.400 3.3e-08
lung carcinoma -2.600 5.6e-24
Alzheimer's disease -1.800 4.4e-02
Pick disease -2.100 1.2e-04
progressive supranuclear palsy -1.500 3.8e-02
ductal carcinoma in situ -2.800 3.9e-04
invasive ductal carcinoma -2.800 7.8e-03
ovarian cancer -5.700 1.9e-22
pituitary cancer -3.000 7.2e-06
Down syndrome 1.100 9.4e-03

Gene RIF (54)

PMID Text
26055330 miR-224 was significantly downregulated as ameloblasts differentiated, in parallel with upregulation of SLC4A4 and CFTR.
25866180 These results revealed that insulin can stimulate PT sodium transport even in type 2 diabetes with overt nephropathy.
25743102 The R298S is a temperature-sensitive mutation in NBCe1-A that results in instability of the colloidal system leading to abnormal aggregation.
25612232 our results indicate that SLC4A4 contributes to the HCO3(-) transport and tumor cell phenotype
25568315 Data indicate that a domain-like structure formed by extracellular loop 3 (EL-3) is present at the SLC4 Na+-coupled transporter NBCe1-A dimeric interface.
24489756 The cell membrane gene SLC4A4 and the trafficking regulator gene COPA, which also plays an important role in early endosome maturation, were identified for the cellular entry of poly-arginine peptide.
24453308 Our results demonstrate a surprisingly high apparent bicarbonate sensitivity mediated by NBCe1 in cortical astrocytes
24121512 A substrate access tunnel in the cytosolic domain is not an essential feature of the solute carrier 4 (SLC4) family of bicarbonate transporters.
23917030 a clear understanding of the structure-functional properties of NBCe1 is a prerequisite for elucidating the mechanisms of defective transepithelial bicarbonate transport--{REVIEW}
23636456 Suggest NBce1-A missense mutation as new pathogenic mechanism for generating human proximal tubular acidosis.
23362273 analysis of NBCe1 protein transmembrane segment 1 and structural effect of proximal renal tubular acidosis (pRTA) S427L mutation
23324180 features of NBCe1-like activity in renal preparations are influenced by yet-to-be-identified renal factors
23303189 novel role of STCH in the regulation of pHi through site-specific interactions with NBCe1-B and NHE1 and subsequent modulation of membrane transporter expression.
22479346 Data identified IGF1, SLC4A4, WWOX, and SFMBT1 as hypertension susceptibility genes by gene based association scan and gene expression analysis.
22415075 the regulation of anion fluxes in insulin-producing cells may involve both SLC4A4 and TMEM16A
22383045 Simultaneous switching of the putative transmembrane segment (TM6) and TM12 of NBCe1 for those from NBCn1 severely impairs the expression of the transporter at the plasma membrane.
22012331 study finds that NBCe1-B is equally stimulated by autoinhibitory domain removal and coexpression of IRBIT with full-length NBCe1-B.
21976511 Slc4a4/NBCe1 is a key element in a feedforward mechanism linking excitatory synaptic transmission to fast modulation of glycolysis in astrocytes.
21621518 the present results suggested that PTH stimulated intestinal HCO(3)(-) secretion, particularly in the ileum, by inducing the basolateral HCO(3)(-) uptake via NBCe1.
21317537 IRBIT opposes the effects of WNKs and SPAK by recruiting PP1 to the complex to dephosphorylate CFTR and NBCe1-B, restoring their cell surface expression, in addition to stimulating their activities
21234596 among four SNPs, only the K558R variant, which is predicted to lie in transmembrane segment 5, significantly reduces the NBCe1A activity without changing the trafficking behavior or the apparent extracellular Na(+) affinity.
21228764 Identify a novel homozygous nonsense mutation (W516X) in the kidney-type electrogenic sodium bicarbonate cotransporter 1 in a patient with isolated proximal renal tubular acidosis.
21224233 NBCe1 (SLC4A4) is electrogenic because it has an apparent Na+:HCO stoichiometry of 1:2 or 1:3, whereas NBCn1 (SLC4A7) is electroneutral because it has an apparent stoichiometry of 1:1.
20837482 C-terminal transmembrane region of NBCe1-A is tightly folded with unique structural and functional features.
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20197274 the pRTA residues in NBCe1-A are buried in the protein complex/lipid bilayer where they perform important structural roles.
19913121 Observational study of gene-disease association. (HuGE Navigator)
19662435 Observational study of gene-disease association. (HuGE Navigator)
19336397 Amino acid subsitution in this protein produces an increase in chloride transport.
19294449 it is proposed that specific orientation & precise location of the FL motif in the primary sequence of NBC1 are strict requirements for the alpha-helical structure of the C-terminal cytoplasmic domain & for targeting of NBC1 to the basolateral membrane
19158093 NBCe1-A Transmembrane Segment 1 Lines the Ion Translocation Pathway.
19102757 NBC1 expressed in Hek293 is inhibited by cAMP but not by cholinergic stimulation, as opposed to the findings in native intestinal tissue.
18614622 NBCe1-A-Q29X mutation that causes proximal renal tubular acidosis treated in a targeted and specific manner
18441326 analysis of the SLC4A4 human mutation and structural model
18223262 Autosomal recessive pRTA with ocular abnormalities' is, for instance, attributable to homozygous mutations in the gene for kNBC-1
17881426 No mutation was found in the coding regions and intron-exon boundaries of the genes for CA II, CA IV, CA XIV, kNCB1, NHE3, NHE8, NHRF1, NHRF2 and SLC26A6 amplified from genomic DNA of family members with pRTA.
17661077 Of the NBC1 mutations, G486R, like T485S, is a partial loss of function mutation without major trafficking abnormalities, while L522P causes the clinical phenotypes mainly through its inability to reach the plasma membranes.
17182531 We propose that the phenylalanine-leucine motif in the COOH-terminal tail of NBC1 is essential for the targeting of NBC1 to the basolateral membrane but is distinct from the membrane-targeting di-leucine motif identified in other membrane proteins.
16857349 Existence of an electrogenic sodium bicarbonate cotransporter in the basolateral membrane of respiratory epithelial cells that mediates bicarbonate entry from the interstitium.
16707554 Pathophysiology of proximal renal tubular acidosis(pRTA0 caused by R881C mutation is likely due to deficit of NBCe1-A at proximal tubule basolateral membrane, rather than defect in transport activity of individual molecules.
16687407 CA II does not enhance NBCe1-A activity
16622177 NBC1 targets to the basolateral membrane of OK cells by a default mechanism and the COOH terminus plays a role on NBC1 stability in the basolateral membrane.
16159892 PMA inhibition of hkNBCe1 is mediated by Ca-dependent PKC and PMA does not induce downregulation of cotransporter surface expression. ANG II inhibition of hkNBCe1 is mediated by both PKCepsilon and downregulation of cotransporter surface expression.
15930088 NBC1 may have a role in proximal renal tubular acidosis and ocular abnormalities
15817634 asymmetry of distribution of kNBC1 charged amino acids involved in ion recognition in putative outward-facing and inward-facing conformations
15713912 The expression of two missense mutations of NBC1 in MDCK cells and X. laevis oocytes to determine the distribution of the mutant proteins in polarized cells is reported.
15366422 Early activation of NBC1 activity by 10% CO2 was mediated by NBC1 phosphorylation.
15273250 a carboxyl-terminal motif with the sequence QQPFLS, which spans amino acid residues 1010-1015, and specifically the amino acid residue Phe (position 1013) are essential for the exclusive targeting of NBC1 to the basolateral membrane
15218065 First direct evidence that a complex of an electrogenic sodium bicarbonate cotransporter (human kNBC1) with carbonic anhydrase II functions as a transport metabolon.
15123668 the electrogenic NBCe1 renders the cell membrane potential an effective regulator of intracellular H(+) buffering and acid/base-coupled metabolite transport
14567693 carbonic anhydrase IV binds EC4 of NBC1, and this interaction is essential for full NBC1 activity
14559244 expression of kNBC-1 but not of pNBC-1 was detected in both normal human kidney and renal cell carcinoma tissues
12730338 phosphorylation of Ser1026 mediates the cAMP-dependent shift in the stoichiometry of pNBC1, whereas Thr49 plays an essential role in the cAMP-induced increase in basolateral membrane conductance
12534288 An in vitro transcription/translation analysis in the presence of canine pancreatic microsomal membranes shows that pNBC1 contains 10 transmembrane domains with cytoplasmic localization of the N- and C-termini.

AA Sequence

MEDEAVLDRGASFLKHVCDEEEVEGHHTIYIGVHVPKSYRRRRRHKRKTGHKEKKEKERISENYSDKSDI      1 - 70
ENADESSSSILKPLISPAAERIRFILGEEDDSPAPPQLFTELDELLAVDGQEMEWKETARWIKFEEKVEQ     71 - 140
GGERWSKPHVATLSLHSLFELRTCMEKGSIMLDREASSLPQLVEMIVDHQIETGLLKPELKDKVTYTLLR    141 - 210
KHRHQTKKSNLRSLADIGKTVSSASRMFTNPDNGSPAMTHRNLTSSSLNDISDKPEKDQLKNKFMKKLPR    211 - 280
DAEASNVLVGEVDFLDTPFIAFVRLQQAVMLGALTEVPVPTRFLFILLGPKGKAKSYHEIGRAIATLMSD    281 - 350
EVFHDIAYKAKDRHDLIAGIDEFLDEVIVLPPGEWDPAIRIEPPKSLPSSDKRKNMYSGGENVQMNGDTP    351 - 420
HDGGHGGGGHGDCEELQRTGRFCGGLIKDIKRKAPFFASDFYDALNIQALSAILFIYLATVTNAITFGGL    421 - 490
LGDATDNMQGVLESFLGTAVSGAIFCLFAGQPLTILSSTGPVLVFERLLFNFSKDNNFDYLEFRLWIGLW    491 - 560
SAFLCLILVATDASFLVQYFTRFTEEGFSSLISFIFIYDAFKKMIKLADYYPINSNFKVGYNTLFSCTCV    561 - 630
PPDPANISISNDTTLAPEYLPTMSSTDMYHNTTFDWAFLSKKECSKYGGNLVGNNCNFVPDITLMSFILF    631 - 700
LGTYTSSMALKKFKTSPYFPTTARKLISDFAIILSILIFCVIDALVGVDTPKLIVPSEFKPTSPNRGWFV    701 - 770
PPFGENPWWVCLAAAIPALLVTILIFMDQQITAVIVNRKEHKLKKGAGYHLDLFWVAILMVICSLMALPW    771 - 840
YVAATVISIAHIDSLKMETETSAPGEQPKFLGVREQRVTGTLVFILTGLSVFMAPILKFIPMPVLYGVFL    841 - 910
YMGVASLNGVQFMDRLKLLLMPLKHQPDFIYLRHVPLRRVHLFTFLQVLCLALLWILKSTVAAIIFPVMI    911 - 980
LALVAVRKGMDYLFSQHDLSFLDDVIPEKDKKKKEDEKKKKKKKGSLDSDNDDSDCPYSEKVPSIKIPMD    981 - 1050
IMEQQPFLSDSKPSDRERSPTFLERHTSC                                            1051 - 1079
//

Text Mined References (84)

PMID Year Title
26055330 2015 MicroRNA 224 Regulates Ion Transporter Expression in Ameloblasts To Coordinate Enamel Mineralization.
25866180 2015 Stimulatory effect of insulin on renal proximal tubule sodium transport is preserved in type 2 diabetes with nephropathy.
25743102 2015 Rescue of the temperature-sensitive, autosomal-recessive mutation R298S in the sodium-bicarbonate cotransporter NBCe1-A characterized by a weakened dimer and abnormal aggregation.
25612232 2015 The Na(+)/HCO3(-) Co-Transporter SLC4A4 Plays a Role in Growth and Migration of Colon and Breast Cancer Cells.
25568315 2015 Interplay between disulfide bonding and N-glycosylation defines SLC4 Na+-coupled transporter extracellular topography.
24952745 2014 Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.
24951543 2014 Meta-analysis of genome-wide association studies in multiethnic Asians identifies two loci for age-related nuclear cataract.
24489756 2014 COPA and SLC4A4 are required for cellular entry of arginine-rich peptides.
24453308 2014 The electrogenic sodium bicarbonate cotransporter NBCe1 is a high-affinity bicarbonate carrier in cortical astrocytes.
24315451 2014 Fraction of exhaled nitric oxide values in childhood are associated with 17q11.2-q12 and 17q12-q21 variants.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24121512 2013 A substrate access tunnel in the cytosolic domain is not an essential feature of the solute carrier 4 (SLC4) family of bicarbonate transporters.
23917030 2013 Structure, function, and regulation of the SLC4 NBCe1 transporter and its role in causing proximal renal tubular acidosis.
23636456 2013 Missense mutation T485S alters NBCe1-A electrogenicity causing proximal renal tubular acidosis.
23376485 2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine.
23362273 2013 Topology of NBCe1 protein transmembrane segment 1 and structural effect of proximal renal tubular acidosis (pRTA) S427L mutation.
23324180 2013 Substrate specificity of the electrogenic sodium/bicarbonate cotransporter NBCe1-A (SLC4A4, variant A) from humans and rabbits.
23303189 2013 Chaperone stress 70 protein (STCH) binds and regulates two acid/base transporters NBCe1-B and NHE1.
23166209 2012 Impact of ancestry and common genetic variants on QT interval in African Americans.
22479346 2012 Identification of IGF1, SLC4A4, WWOX, and SFMBT1 as hypertension susceptibility genes in Han Chinese with a genome-wide gene-based association study.
22415075 2012 Expression of TMEM16A and SLC4A4 in human pancreatic islets.
22383045 2012 Effect of simultaneously replacing putative TM6 and TM12 of human NBCe1-A with those from NBCn1 on surface abundance in Xenopus oocytes.
22012331 2012 Relief of autoinhibition of the electrogenic Na-HCO(3) [corrected] cotransporter NBCe1-B: role of IRBIT vs.amino-terminal truncation.
21976511 2011 NBCe1 mediates the acute stimulation of astrocytic glycolysis by extracellular K+.
21621518 2011 Electrogenic Na?/HCO?? co-transporter-1 is essential for the parathyroid hormone-stimulated intestinal HCO?? secretion.
21317537 2011 IRBIT governs epithelial secretion in mice by antagonizing the WNK/SPAK kinase pathway.
21234596 2011 Functional characterization of nonsynonymous single nucleotide polymorphisms in the electrogenic Na+-HCO3- cotransporter NBCe1A.
21228764 2011 Severe metabolic acidosis causes early lethality in NBC1 W516X knock-in mice as a model of human isolated proximal renal tubular acidosis.
21224233 2011 Role of an extracellular loop in determining the stoichiometry of Na+-HCO?? cotransporters.
20837482 2010 Structural and functional characterization of the C-terminal transmembrane region of NBCe1-A.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
20197274 2010 Topological location and structural importance of the NBCe1-A residues mutated in proximal renal tubular acidosis.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19662435 2009 Modifier gene study of meconium ileus in cystic fibrosis: statistical considerations and gene mapping results.
19336397 2009 Mutation of Aspartate 555 of the Sodium/Bicarbonate Transporter SLC4A4/NBCe1 Induces Chloride Transport.
19294449 2009 Sequence- or position-specific mutations in the carboxyl-terminal FL motif of the kidney sodium bicarbonate cotransporter (NBC1) disrupt its basolateral targeting and alpha-helical structure.
19158093 2009 NBCe1-A Transmembrane Segment 1 Lines the Ion Translocation Pathway.
19102757 2008 cAMP-dependent and cholinergic regulation of the electrogenic intestinal/pancreatic Na+/HCO3- cotransporter pNBC1 in human embryonic kidney (HEK293) cells.
19056867 2009 Large-scale proteomics and phosphoproteomics of urinary exosomes.
18614622 2008 G418-mediated ribosomal read-through of a nonsense mutation causing autosomal recessive proximal renal tubular acidosis.
18441326 2008 Entry to "formula tunnel" revealed by SLC4A4 human mutation and structural model.
18223262 2008 Proximal RTA: Are all the charts completed yet?
17881426 2008 Familial pure proximal renal tubular acidosis--a clinical and genetic study.
17661077 2008 Functional analysis of a novel missense NBC1 mutation and of other mutations causing proximal renal tubular acidosis.
17182531 2007 Identification of a novel signal in the cytoplasmic tail of the Na+:HCO3- cotransporter NBC1 that mediates basolateral targeting.
16857349 2006 Identification and membrane localization of electrogenic sodium bicarbonate cotransporters in Calu-3 cells.
16769890 2006 IRBIT, an inositol 1,4,5-trisphosphate receptor-binding protein, specifically binds to and activates pancreas-type Na+/HCO3- cotransporter 1 (pNBC1).
16707554 2006 The human NBCe1-A mutant R881C, associated with proximal renal tubular acidosis, retains function but is mistargeted in polarized renal epithelia.
16687407 2006 Effect of human carbonic anhydrase II on the activity of the human electrogenic Na/HCO3 cotransporter NBCe1-A in Xenopus oocytes.
16636648 2006 Proximal renal tubular acidosis and ocular pathology: a novel missense mutation in the gene (SLC4A4) for sodium bicarbonate cotransporter protein (NBCe1).
16622177 2006 Role of NH(2) and COOH termini in targeting, stability, and activity of sodium bicarbonate cotransporter 1.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16159892 2006 PMA- and ANG II-induced PKC regulation of the renal Na+-HCO3- cotransporter (hkNBCe1).
15930088 2005 Functional analysis of NBC1 mutants associated with proximal renal tubular acidosis and ocular abnormalities.
15817634 2005 Critical amino acid residues involved in the electrogenic sodium-bicarbonate cotransporter kNBC1-mediated transport.
15815621 2005 Generation and annotation of the DNA sequences of human chromosomes 2 and 4.
15713912 2005 Missense mutations in Na+:HCO3- cotransporter NBC1 show abnormal trafficking in polarized kidney cells: a basis of proximal renal tubular acidosis.
15563508 2005 Mutant carbonic anhydrase 4 impairs pH regulation and causes retinal photoreceptor degeneration.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15471865 2004 A novel missense mutation in the sodium bicarbonate cotransporter (NBCe1/SLC4A4) causes proximal tubular acidosis and glaucoma through ion transport defects.
15366422 2004 Regulation of renal Na+/HCO3- cotransporter stimulation by CO2: role of phosphorylation, exocytosis and protein synthesis.
15329059 2004 Expression of Na+/HCO3- co-transporter proteins (NBCs) in rat and human skeletal muscle.
15273250 2004 Identification of a carboxyl-terminal motif essential for the targeting of Na+-HCO-3 cotransporter NBC1 to the basolateral membrane.
15218065 2004 Molecular mechanism of kNBC1-carbonic anhydrase II interaction in proximal tubule cells.
15123668 2004 Voltage dependence of H+ buffering mediated by sodium bicarbonate cotransport expressed in Xenopus oocytes.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14567693 2003 Direct extracellular interaction between carbonic anhydrase IV and the human NBC1 sodium/bicarbonate co-transporter.
14559244 2003 Localization of NBC-1 variants in human kidney and renal cell carcinoma.
12907161 2003 Identification and cloning of the Na/HCO(3-) cotransporter (NBC) in human corneal endothelium.
12730338 2003 Phosphorylation-induced modulation of pNBC1 function: distinct roles for the amino- and carboxy-termini.
12604466 2003 Role of glycosylation in the renal electrogenic Na+-HCO3- cotransporter (NBCe1).
12534288 2003 Identification of membrane topography of the electrogenic sodium bicarbonate cotransporter pNBC1 by in vitro transcription/translation.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12411514 2002 Regulation of the sodium bicarbonate cotransporter kNBC1 function: role of Asp(986), Asp(988) and kNBC1-carbonic anhydrase II binding.
11744745 2001 Phosphorylation of Ser(982) in the sodium bicarbonate cotransporter kNBC1 shifts the HCO(3)(-) : Na(+) stoichiometry from 3 : 1 to 2 : 1 in murine proximal tubule cells.
11743927 2002 Expression of a sodium bicarbonate cotransporter in human parotid salivary glands.
10652014 2000 Physiologic and molecular aspects of the Na+:HCO3- cotransporter in health and disease processes.
10600945 1999 NBC3 expression in rabbit collecting duct: colocalization with vacuolar H+-ATPase.
10545938 1999 Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalities.
10099707 1999 Electrogenic Na+/HCO3- cotransporters: cloning and physiology.
10069984 1999 Cloning and characterization of a human electrogenic Na+-HCO-3 cotransporter isoform (hhNBC).
9651366 1998 Molecular cloning, chromosomal localization, tissue distribution, and functional expression of the human pancreatic sodium bicarbonate cotransporter.
9235899 1997 Cloning and functional expression of a human kidney Na+:HCO3- cotransporter.
8358434 1993 3,400 new expressed sequence tags identify diversity of transcripts in human brain.