Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

O88343 (S4A4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 105. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Electrogenic sodium bicarbonate cotransporter 1

Short name=Sodium bicarbonate cotransporter
Alternative name(s):
Na(+)/HCO3(-) cotransporter
Solute carrier family 4 member 4
Gene names
Name:Slc4a4
Synonyms:Nbc1, Nbce1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1079 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Electrogenic sodium/bicarbonate cotransporter with a Na+:HCO3- stoichiometry varying from 1:2 to 1:3. May regulate bicarbonate influx/efflux at the basolateral membrane of cells and regulate intracellular pH.

Enzyme regulation

Inhibited by stilbene derivatives and regulated by cyclic AMP.

Subunit structure

Interacts with CA2/carbonic anhydrase 2 and CA4/carbonic anhydrase 4 which may regulate transporter activity. Ref.9 Ref.10

Subcellular location

Basolateral cell membrane; Multi-pass membrane protein Ref.2.

Tissue specificity

Isoform 1 is specifically expressed in pancreatic ducts and acini. Also expressed in parotid acinar cells and in the colonic crypts. Ref.1 Ref.2 Ref.7 Ref.8

Post-translational modification

Phosphorylation of Ser-1026 by PKA increases the binding of CA2 and changes the Na+:HCO3- stoichiometry of the transporter from 3:1 to 2:1 By similarity.

N-glycosylated. May not be necessary for the transporter basic functions. Ref.6

Sequence similarities

Belongs to the anion exchanger (TC 2.A.31) family. [View classification]

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Ca4Q644442EBI-771342,EBI-6859308

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O88343-1)

Also known as: pNBC;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O88343-2)

Also known as: kNBC;

The sequence of this isoform differs from the canonical sequence as follows:
     1-44: Missing.
     45-85: HKRKAGHKEK...SSSSILKPLI → MSTENVEGKP...FNHSIFTSAV
Isoform 3 (identifier: O88343-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-44: Missing.
     45-85: HKRKAGHKEK...SSSSILKPLI → MSTENVEGKP...FNHSIFTSAV
     185-201: MIADHQIETGLLKPDLK → LLGESRKVIRPAGFIRP
     202-1079: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10791079Electrogenic sodium bicarbonate cotransporter 1
PRO_0000079228

Regions

Topological domain1 – 468468Cytoplasmic Potential
Transmembrane469 – 48820Helical; Potential
Topological domain489 – 50416Extracellular Potential
Transmembrane505 – 52622Helical; Potential
Topological domain527 – 55428Cytoplasmic Potential
Transmembrane555 – 58026Helical; Potential
Topological domain581 – 691111Extracellular Potential
Transmembrane692 – 71019Helical; Potential
Topological domain711 – 72515Cytoplasmic Potential
Transmembrane726 – 74823Helical; Potential
Topological domain749 – 77729Extracellular Potential
Transmembrane778 – 79720Helical; Potential
Topological domain798 – 82225Cytoplasmic Potential
Transmembrane823 – 84725Helical; Potential
Topological domain848 – 88134Extracellular Potential
Transmembrane882 – 90120Helical; Potential
Topological domain902 – 94948Cytoplasmic Potential
Transmembrane950 – 96718Helical; Potential
Topological domain968 – 9703Extracellular Potential
Transmembrane971 – 98616Helical; Potential
Topological domain987 – 107993Cytoplasmic Potential
Region748 – 77932Interaction with CA4 By similarity
Region1002 – 10043CA2-binding By similarity
Region1030 – 10334CA2-binding By similarity
Region1057 – 10593Required for basolateral targeting By similarity
Compositional bias1009 – 102416Lys-rich

Amino acid modifications

Modified residue301Phosphotyrosine Ref.12
Modified residue2541Phosphothreonine Ref.11
Modified residue2571Phosphoserine Ref.11
Modified residue2621Phosphoserine Ref.11
Modified residue10261Phosphoserine; by PKA By similarity
Modified residue10291Phosphoserine Ref.11
Modified residue10341Phosphoserine Ref.11
Glycosylation6411N-linked (GlcNAc...) By similarity
Glycosylation6611N-linked (GlcNAc...) By similarity

Natural variations

Alternative sequence1 – 4444Missing in isoform 2 and isoform 3.
VSP_016709
Alternative sequence45 – 8541HKRKA…LKPLI → MSTENVEGKPNNLGERGRAR SSTFLRVFQPMFNHSIFTSA V in isoform 2 and isoform 3.
VSP_016710
Alternative sequence185 – 20117MIADH…KPDLK → LLGESRKVIRPAGFIRP in isoform 3.
VSP_016711
Alternative sequence202 – 1079878Missing in isoform 3.
VSP_016712

Experimental info

Sequence conflict3881T → A in AAC40160. Ref.1
Sequence conflict5461H → N in AAC40160. Ref.1
Sequence conflict5601W → R in AAC40160. Ref.1
Sequence conflict5641M → L in AAC40160. Ref.1
Sequence conflict5671V → I in AAC40160. Ref.1
Sequence conflict5891S → P in AAC40160. Ref.1
Sequence conflict7401C → G in AAC40160. Ref.1
Sequence conflict7751G → E in AAC40160. Ref.1
Sequence conflict8141K → Q in AAC40160. Ref.1
Sequence conflict8321V → I in AAC40160. Ref.1
Sequence conflict8351F → L in AAC40160. Ref.1
Sequence conflict8481S → F in AAD31036. Ref.2
Sequence conflict8761Q → P in AAD31036. Ref.2
Sequence conflict8841F → L in AAC40160. Ref.1
Sequence conflict9011P → R in AAD31036. Ref.2
Sequence conflict909 – 9102FL → SW in AAD31036. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (pNBC) [UniParc].

Last modified December 20, 2005. Version 2.
Checksum: DBC7C3DEBE10BE97

FASTA1,079121,484
        10         20         30         40         50         60 
MEDEAVLDRG ASFLKHVCDE EEVEGHHTIY IGVHVPKSYR RRRRHKRKAG HKEKKEKERI 

        70         80         90        100        110        120 
SENYSDKSDV ENADESSSSI LKPLISPAAE RIRFILGEED DSPAPPQLFT ELDELLAVDG 

       130        140        150        160        170        180 
QEMEWKETAR WIKFEEKVEQ GGERWSKPHV ATLSLHSLFE LRTCMEKGSI MLDREASSLP 

       190        200        210        220        230        240 
QLVEMIADHQ IETGLLKPDL KDKVTYTLLR KHRHQTKKSN LRSLADIGKT VSSASRMFSN 

       250        260        270        280        290        300 
PDNGSPAMTH RNLTSSSLND ISDKPEKDQL KNKFMKKLPR DAEASNVLVG EVDFLDTPFI 

       310        320        330        340        350        360 
AFVRLQQAVM LGALTEVPVP TRFLFILLGP KGKAKSYHEI GRAIATLMSD EVFHDIAYKA 

       370        380        390        400        410        420 
KDRHDLIAGI DEFLDEVIVL PPGEWDPTIR IEPPKSLPSS DKRKNMYSGG ENVQMNGDTP 

       430        440        450        460        470        480 
HDGGHGGGGH GDCEELQRTG RFCGGLIKDI KRKAPFFASD FYDALNIQAL SAILFIYLAT 

       490        500        510        520        530        540 
VTNAITFGGL LGDATDNMQG VLESFLGTAV SGAIFCLFAG QPLTILSSTG PVLVFERLLF 

       550        560        570        580        590        600 
NFSKDHNFDY LEFRLWIGLW SAFMCLVLVA TDASFLVQYF TRFTEEGFSS LISFIFIYDA 

       610        620        630        640        650        660 
FKKMIKLADY YPINSDFKVG YNTHFSCACL PPDPVNLSVS NDTTLAPEDL PTISSTDMYH 

       670        680        690        700        710        720 
NVTFDWAYLS KKECVKYGGK LVGNNCDFVP DITLMSFILF LGTYTSSMAM KKFKTSRYFP 

       730        740        750        760        770        780 
TTARKLISDF AIILSILIFC VIDALVGVDT PKLIVPSEFK PTSPNRGWFV PPFGGNPWWV 

       790        800        810        820        830        840 
CLAAAIPALL VTILIFMDQQ ITAVIVNRKE HKLKKGAGYH LDLFWVAILM VVCSFMALPW 

       850        860        870        880        890        900 
YVAATVISIA HIDSLKMETE TSAPGEQPKF LGVREQRVTG TLVFILTGLS VFMAPILKFI 

       910        920        930        940        950        960 
PMPVLYGVFL YMGVASLNGV QFMDRLKLLL MPLKHQPDFI YLRHVPLRRV HLFTFLQVLC 

       970        980        990       1000       1010       1020 
LALLWILKST VAAIIFPVMI LALVAVRKGM DYLFSQHDLS FLDDVIPEKD KKKKEDEKKK 

      1030       1040       1050       1060       1070 
KKKKGSLDSD NDDSDCPYSE KVPSIKIPMD IMEQQPFLSD NKPLDRERSS TFLERHTSC 

« Hide

Isoform 2 (kNBC) [UniParc].

Checksum: 75CD2F7008D52ADE
Show »

FASTA1,035116,182
Isoform 3 [UniParc].

Checksum: 95E7EA3165687E5D
Show »

FASTA15717,829

References

« Hide 'large scale' references
[1]"Molecular cloning, chromosomal localization, tissue distribution, and functional expression of the human pancreatic sodium bicarbonate cotransporter."
Abuladze N., Lee I., Newman D., Hwang J., Boorer K., Pushkin A., Kurtz I.
J. Biol. Chem. 273:17689-17695(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Pancreas.
[2]"Molecular and functional evidence for electrogenic and electroneutral Na(+)-HCO(3)(-) cotransporters in murine duodenum."
Praetorius J., Hager H., Nielsen S., Aalkjaer C., Friis U.G., Ainsworth M.A., Johansen T.
Am. J. Physiol. 280:G332-G343(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
Strain: C57BL/6.
Tissue: Duodenum.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-400 (ISOFORM 1).
Strain: C57BL/6J.
Tissue: Kidney and Medulla oblongata.
[4]Lubec G., Kang S.U.
Submitted (APR-2007) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 1-9; 60-67; 168-174; 323-331; 343-359; 607-618; 753-766; 857-869 AND 935-943, IDENTIFICATION BY MASS SPECTROMETRY.
Strain: C57BL/6.
Tissue: Brain.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 382-1079.
Strain: FVB/N.
Tissue: Kidney.
[6]"Role of glycosylation in the renal electrogenic Na+-HCO3-cotransporter (NBCe1)."
Choi I., Hu L., Rojas J.D., Schmitt B.M., Boron W.F.
Am. J. Physiol. 284:F1199-F1206(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION.
[7]"cAMP-mediated regulation of murine intestinal/pancreatic Na+/HCO3-cotransporter subtype pNBC1."
Bachmann O., Rossmann H., Berger U.V., Colledge W.H., Ratcliff R., Evans M.J., Gregor M., Seidler U.
Am. J. Physiol. 284:G37-G45(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: REGULATION BY CAMP, TISSUE SPECIFICITY.
[8]"Expression of Na+/HCO3- cotransporter and its role in pH regulation in mouse parotid acinar cells."
Kim Y.-B., Yang B.H., Piao Z.G., Oh S.B., Kim J.S., Park K.
Biochem. Biophys. Res. Commun. 304:593-598(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[9]"Direct extracellular interaction between carbonic anhydrase IV and the human NBC1 sodium/bicarbonate co-transporter."
Alvarez B.V., Loiselle F.B., Supuran C.T., Schwartz G.J., Casey J.R.
Biochemistry 42:12321-12329(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CA4.
[10]"Molecular mechanism of kNBC1-carbonic anhydrase II interaction in proximal tubule cells."
Pushkin A., Abuladze N., Gross E., Newman D., Tatishchev S., Lee I., Fedotoff O., Bondar G., Azimov R., Ngyuen M., Kurtz I.
J. Physiol. (Lond.) 559:55-65(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CA2.
[11]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-254; SER-257; SER-262; SER-1029 AND SER-1034, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[12]"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain."
Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.
J. Proteome Res. 7:311-318(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-30, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Brain.
[13]"Specific phosphopeptide enrichment with immobilized titanium ion affinity chromatography adsorbent for phosphoproteome analysis."
Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H.
J. Proteome Res. 7:3957-3967(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF020195 mRNA. Translation: AAC40160.1.
AF141934 mRNA. Translation: AAD31036.3.
AK085387 mRNA. Translation: BAC39437.1.
AK140443 mRNA. Translation: BAE24389.1.
BC026592 mRNA. Translation: AAH26592.1.
PIRT14031.
RefSeqNP_001129732.1. NM_001136260.1.
NP_061230.2. NM_018760.2.
UniGeneMm.41044.

3D structure databases

ProteinModelPortalO88343.
SMRO88343. Positions 107-382, 453-493, 920-952.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActO88343. 6 interactions.
MINTMINT-4130871.
STRING10090.ENSMUSP00000121744.

PTM databases

PhosphoSiteO88343.

Proteomic databases

PaxDbO88343.
PRIDEO88343.

Protocols and materials databases

DNASU54403.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000113216; ENSMUSP00000108842; ENSMUSG00000060961. [O88343-3]
ENSMUST00000130041; ENSMUSP00000118413; ENSMUSG00000060961. [O88343-2]
ENSMUST00000148750; ENSMUSP00000119325; ENSMUSG00000060961. [O88343-1]
GeneID54403.
KEGGmmu:54403.
UCSCuc008yak.1. mouse. [O88343-1]

Organism-specific databases

CTD8671.
MGIMGI:1927555. Slc4a4.

Phylogenomic databases

eggNOGNOG251607.
GeneTreeENSGT00560000076851.
HOGENOMHOG000280684.
HOVERGENHBG004326.
InParanoidO88343.
KOK13575.
OrthoDBEOG7TMZR0.
PhylomeDBO88343.

Gene expression databases

ArrayExpressO88343.
BgeeO88343.
GenevestigatorO88343.

Family and domain databases

Gene3D3.40.1100.10. 1 hit.
InterProIPR013769. Band3_cytoplasmic_dom.
IPR011531. HCO3_transpt_C.
IPR003020. HCO3_transpt_euk.
IPR003024. Na/HCO3_transpt.
IPR016152. PTrfase/Anion_transptr.
[Graphical view]
PANTHERPTHR11453. PTHR11453. 1 hit.
PfamPF07565. Band_3_cyto. 1 hit.
PF00955. HCO3_cotransp. 1 hit.
[Graphical view]
PRINTSPR01231. HCO3TRNSPORT.
PR01232. NAHCO3TRSPRT.
SUPFAMSSF55804. SSF55804. 1 hit.
TIGRFAMsTIGR00834. ae. 1 hit.
ProtoNetSearch...

Other

ChiTaRSSLC4A4. mouse.
NextBio311268.
PROO88343.
SOURCESearch...

Entry information

Entry nameS4A4_MOUSE
AccessionPrimary (citable) accession number: O88343
Secondary accession number(s): Q3USE4 expand/collapse secondary AC list , Q8BUG0, Q8QZR9, Q9R1C4
Entry history
Integrated into UniProtKB/Swiss-Prot: December 20, 2005
Last sequence update: December 20, 2005
Last modified: April 16, 2014
This is version 105 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot