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2.A.31.2.2
Electrogenic Na+:HCO3- cotransporter, rkNBC (NBCI, NBCe1, SLC4A4). The human orthologue, NBCe1/SLC4A4;Q9Y6R1, is stimulated by carbonic anhydrase II and IX which together form a transport metabolon (Becker and Deitmer, 2007; Orlowski et al., 2012). The bicarbonate channel in the C-terminal two-thirds of the protein is regulated by the N-terminal hydrophilic domain (Chang et al., 2008) which may actually form part of the channel (Zhu et al. 2013). The topological location and structural importance of the NBCe1-A residues mutated in proximal renal tubular acidosis have been identified (Zhu et al., 2010). Defective membrane expression of the Na+/HCO3- cotransporter NBCe1 is associated with familial migraines (Suzuki et al., 2010). This transporter plays a role in pH regulation and bicarbonate transport in the kideny proximal tubule (Yamazaki et al., 2011; Zhu et al. 2013). The three lysyl residues in the KKMIK motif in TMS5 plays a role in DIDS inhibition (Lu and Boron 2007). Electrogenicity of NBCe1 probably depends on interactions between TM1-5 and TM6-13 (Choi et al. 2007). A I551F variant of NBCe1-A shows reduced cell surface expression, resulting in diminished transport activity (Yamazaki et al. 2021). Carbonic anhydrase IX is a marker of disease severity in obstructive sleep apnea (Geçkil et al. 2022).  NBCe1-A uses an elevator-type transport mechanism with a small vertical ∼5 Å shift of the ion coordination site (Pushkin et al. 2024).

Accession Number:Q9JI66
Protein Name:Electrogenic sodium bicarbonate cotransporter 1
Length:1079
Molecular Weight:121343.00
Species: [10116]
Number of TMSs:10
Location1 / Topology2 / Orientation3: Basolateral cell membrane1 / Multi-pass membrane protein2
Substrate

Cross database links:

RefSeq: NP_445876.1   
Entrez Gene ID: 84484   
Pfam: PF07565    PF00955   
KEGG: rno:84484   

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
GO:0006820 P:anion transport
GO:0006885 P:regulation of pH
GO:0006814 P:sodium ion transport

References (10)

[1] “Cloning and functional expression of rNBC, an electrogenic Na(+)-HCO3-cotransporter from rat kidney.”  Romero M.F.et.al.   9486238
[2] “Cloning, renal distribution, and regulation of the rat Na+-HCO3-cotransporter.”  Burnham C.E.et.al.   9841505
[3] “An electrogenic Na(+)-HCO3(-) cotransporter (NBC) with a novel COOH-terminus, cloned from rat brain.”  Bevensee M.O.et.al.   10837348
[4] “The electrogenic sodium bicarbonate cotransporter: developmental expression in rat brain and possible role in acid vulnerability.”  Giffard R.G.et.al.   10648705
[5] “Immunolocalization of electrogenic sodium-bicarbonate cotransporters pNBC1 and kNBC1 in the rat eye.”  Bok D.et.al.   11592950
[6] “Coordinated down-regulation of NBC-1 and NHE-3 in sodium and bicarbonate loading.”  Amlal H.et.al.   11703600
[7] “Localization of Na+-HCO-3 cotransporter (NBC-1) variants in rat and human pancreas.”  Satoh H.et.al.   12444017
[8] “Role of glycosylation in the renal electrogenic Na+-HCO3-cotransporter (NBCe1).”  Choi I.et.al.   12604466
[9] “Expression of Na+/HCO3- co-transporter proteins (NBCs) in rat and human skeletal muscle.”  Kristensen J.M.et.al.   15329059
[10] “Inhibition of renal Na+/H+ exchange in cadmium-intoxicated rats.”  Ahn D.-W.et.al.   15781297

External Searches:

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence 
1:	MEDEAVLDRG ASFLKHVCDE EEVEGHHTIY IGVHVPKSYR RRRRHKRKAG HKEKKEKERI 
61:	SENYSDKSDV ENADESSSSI LKPLISPAAE RIRFILGEED DSPAPPQLFT ELDELLAVDG 
121:	QEMEWKETAR WIKFEEKVEQ GGERWSKPHV ATLSLHSLFE LRTCMEKGSI MLDREASSLP 
181:	QLVEMIADHQ IETGLLKPDL KDKVTYTLLR KHRHQTKKSN LRSLADIGKT VSSASRMFSN 
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:	NFSKDHSFDY LEFRLWIGLW SAFMCLILVA TDASFLVQYF TRFTEEGFSS LISFIFIYDA 
601:	FKKMIKLADY YPINSDFRVG YNTHFSCACL PPDPVNLSVS NDTTLAPEDL PTVSSTDMYH 
661:	NATFDWAYLS KKECVKFGGK LVGNNCDFVP DITLMSFILF LGTYTSSMAM KKFKTSRYFP 
721:	TTARKLISDF AIILSILIFC VIDALVGVDT PKLIVPSEFK PTSPHRGWFV PPFGGNPWWV 
781:	CLAAAIPALL VTILIFMDQQ ITAVIVNRKE HKLKKGAGYH LDLFWVAILM VVCSFMALPW 
841:	YVAATVISIA HIDSLKMETE TSAPGEQPKF LGVREQRVTG TLVFILTGLS VFMAPILKFI 
901:	PMPVLYGVFL YMGVASLNGV QFMDRLKLLL MPLKHQPDFI YLRHVPLRRV HLFTSLQVLC 
961:	LALLWILKST VAAIIFPVMI LALVAVRKGM DYLFSQHDLS FLDDVIPEKD KKKKEDEKKK 
1021:	KKKKGSLDSD NDDSDCPYSE KVPSIKIPMD ITEQQPFLSD NKPLDRERSS TFLERHTSC