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2.A.31.2.12
Electrogenic sodium bicarbonate cotransporter 1, NBCe1 (Sodium bicarbonate cotransporter, NBC) (Na+/HCO3- cotransporter) (Solute carrier family 4 member 4) (kNBC1) of 1079 aas (Boron et al. 2009). Mutations cause proximal renal tubular acidosis and ocular pathology (Demirci et al. 2006). NBCe1, together with carbonic anhydrase II, CAII, provides an efficient mechanism of bicarbonate sensing in cortical astrocytes (Theparambil et al. 2017). NBCe1-B is widely expressed in many tissues, including the pancreas, submandibular gland, brain, heart, etc. It has very low activity under basal conditions due to auto-inhibition, but can be fully activated by interaction with IRBIT (TC# 8.A.151.1.1). IRBIT activates NBCe1-B by releasing the auto-inhibition module from the transmembrane domain (Su et al. 2020). NHE-3 (TC# 2.A.53.2.18) was markedly downregulated, while NBCe1 and the Na+-glucose transporter type-2 (SGLT2 or SGLT-2; TC#2.A.1.7.26) were upregulated after kidney transplantation (Velic et al. 2004). NBCe1 transports CO2 (Michenkova et al. 2021). R730 in hAE1 (TC# 2.A.31.1.1) is crucial for anion binding to both the entry and central sites, while in hNBCe1, a Na+ acts as an anchor for CO32- binding to the central site. Protonation of central acidic residues (E681 in hAE1 and D754 in hNBCe1) alters the ion dynamics in the permeation cavity and may contribute to the transport mode differences in SLC4 proteins (Zhekova et al. 2021).

Accession Number:Q9Y6R1
Protein Name:Electrogenic sodium bicarbonate cotransporter 1
Length:1079
Molecular Weight:121461.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:10
Location1 / Topology2 / Orientation3: Basolateral cell membrane1 / Multi-pass membrane protein2
Substrate Na+, bicarbonate

Cross database links:

DIP: DIP-59373N
Entrez Gene ID: 8671   
Pfam: PF07565    PF00955   
KEGG: hsa:8671   

Gene Ontology

GO:0016323 C:basolateral plasma membrane
GO:0005887 C:integral to plasma membrane
GO:0005452 F:inorganic anion exchanger activity
GO:0008510 F:sodium:bicarbonate symporter activity

References (23)

[1] “Cloning and functional expression of a human kidney Na+:HCO3-cotransporter.”  Burnham C.E.et.al.   9235899
[2] “Molecular cloning, chromosomal localization, tissue distribution, and functional expression of the human pancreatic sodium bicarbonate cotransporter.”  Abuladze N.et.al.   9651366
[3] “Cloning and characterization of a human electrogenic Na+-HCO-3 cotransporter isoform (hhNBC).”  Choi I.et.al.   10069984
[4] “Identification and cloning of the Na/HCO3- cotransporter (NBC) in human corneal endothelium.”  Sun X.C.et.al.   12907161
[5] “Generation and annotation of the DNA sequences of human chromosomes 2 and 4.”  Hillier L.W.et.al.   15815621
[6] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[7] “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.”  Gross E.et.al.   11744745
[8] “Expression of a sodium bicarbonate cotransporter in human parotid salivary glands.”  Park K.et.al.   11743927
[9] “Regulation of the sodium bicarbonate cotransporter kNBC1 function: role of Asp(986), Asp(988) and kNBC1-carbonic anhydrase II binding.”  Gross E.et.al.   12411514
[10] “Role of glycosylation in the renal electrogenic Na+-HCO3-cotransporter (NBCe1).”  Choi I.et.al.   12604466
[11] “Localization of NBC-1 variants in human kidney and renal cell carcinoma.”  Yamada H.et.al.   14559244
[12] “Identification of membrane topography of the electrogenic sodium bicarbonate cotransporter pNBC1 by in vitro transcription/translation.”  Tatishchev S.et.al.   12534288
[13] “Direct extracellular interaction between carbonic anhydrase IV and the human NBC1 sodium/bicarbonate co-transporter.”  Alvarez B.V.et.al.   14567693
[14] “Phosphorylation-induced modulation of pNBC1 function: distinct roles for the amino- and carboxy-termini.”  Gross E.et.al.   12730338
[15] “Expression of Na+/HCO3- co-transporter proteins (NBCs) in rat and human skeletal muscle.”  Kristensen J.M.et.al.   15329059
[16] “Identification of a carboxyl-terminal motif essential for the targeting of Na+-HCO-3 cotransporter NBC1 to the basolateral membrane.”  Li H.C.et.al.   15273250
[17] “Molecular mechanism of kNBC1-carbonic anhydrase II interaction in proximal tubule cells.”  Pushkin A.et.al.   15218065
[18] “Mutant carbonic anhydrase 4 impairs pH regulation and causes retinal photoreceptor degeneration.”  Yang Z.et.al.   15563508
[19] “Critical amino acid residues involved in the electrogenic sodium-bicarbonate cotransporter kNBC1-mediated transport.”  Abuladze N.et.al.   15817634
[20] “Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalities.”  Igarashi T.et.al.   10545938
[21] “A novel missense mutation in the sodium bicarbonate cotransporter (NBCe1/SLC4A4) causes proximal tubular acidosis and glaucoma through ion transport defects.”  Dinour D.et.al.   15471865
[22] “Missense mutations in Na+:HCO3- cotransporter NBC1 show abnormal trafficking in polarized kidney cells: a basis of proximal renal tubular acidosis.”  Li H.C.et.al.   15713912
[23] “Functional analysis of NBC1 mutants associated with proximal renal tubular acidosis and ocular abnormalities.”  Horita S.et.al.   15930088
Structure:
6CAA     

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MEDEAVLDRG ASFLKHVCDE EEVEGHHTIY IGVHVPKSYR RRRRHKRKTG HKEKKEKERI 
61:	SENYSDKSDI ENADESSSSI LKPLISPAAE RIRFILGEED DSPAPPQLFT ELDELLAVDG 
121:	QEMEWKETAR WIKFEEKVEQ GGERWSKPHV ATLSLHSLFE LRTCMEKGSI MLDREASSLP 
181:	QLVEMIVDHQ IETGLLKPEL KDKVTYTLLR KHRHQTKKSN LRSLADIGKT VSSASRMFTN 
241:	PDNGSPAMTH RNLTSSSLND ISDKPEKDQL KNKFMKKLPR DAEASNVLVG EVDFLDTPFI 
301:	AFVRLQQAVM LGALTEVPVP TRFLFILLGP KGKAKSYHEI GRAIATLMSD EVFHDIAYKA 
361:	KDRHDLIAGI DEFLDEVIVL PPGEWDPAIR IEPPKSLPSS DKRKNMYSGG ENVQMNGDTP 
421:	HDGGHGGGGH GDCEELQRTG RFCGGLIKDI KRKAPFFASD FYDALNIQAL SAILFIYLAT 
481:	VTNAITFGGL LGDATDNMQG VLESFLGTAV SGAIFCLFAG QPLTILSSTG PVLVFERLLF 
541:	NFSKDNNFDY LEFRLWIGLW SAFLCLILVA TDASFLVQYF TRFTEEGFSS LISFIFIYDA 
601:	FKKMIKLADY YPINSNFKVG YNTLFSCTCV PPDPANISIS NDTTLAPEYL PTMSSTDMYH 
661:	NTTFDWAFLS KKECSKYGGN LVGNNCNFVP DITLMSFILF LGTYTSSMAL KKFKTSPYFP 
721:	TTARKLISDF AIILSILIFC VIDALVGVDT PKLIVPSEFK PTSPNRGWFV PPFGENPWWV 
781:	CLAAAIPALL VTILIFMDQQ ITAVIVNRKE HKLKKGAGYH LDLFWVAILM VICSLMALPW 
841:	YVAATVISIA HIDSLKMETE TSAPGEQPKF LGVREQRVTG TLVFILTGLS VFMAPILKFI 
901:	PMPVLYGVFL YMGVASLNGV QFMDRLKLLL MPLKHQPDFI YLRHVPLRRV HLFTFLQVLC 
961:	LALLWILKST VAAIIFPVMI LALVAVRKGM DYLFSQHDLS FLDDVIPEKD KKKKEDEKKK 
1021:	KKKKGSLDSD NDDSDCPYSE KVPSIKIPMD IMEQQPFLSD SKPSDRERSP TFLERHTSC