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Q9BY07 (S4A5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 96. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Electrogenic sodium bicarbonate cotransporter 4
Alternative name(s):
NBCe2
Solute carrier family 4 member 5
Gene names
Name:SLC4A5
Synonyms:NBC4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1137 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

Mediates sodium- and bicarbonate-dependent electrogenic sodium bicarbonate cotransport, with a Na+:HCO3- stoichiometry of 2:1. May have a housekeeping function in regulating the pH of tissues in which it is expressed. May play a role in mediating Na+:HCO3- cotransport in hepatocytes and intrahepatic cholangiocytes. Also may be important in protecting the renal paranchyma from alterations in urine pH. Ref.4 Ref.5 Ref.6 UniProtKB Q6RI88

Enzyme regulation

Activity is inhibited by 4,4'-di-isothiocyanatostilbene-2,2'-disulfonic acid (DIDS - an inhibitor of several anion channels and transporters).

Subcellular location

Apical cell membrane; Multi-pass membrane protein. Note: Expressed in the apical plasma membrane domain of a subset of collecting ducts in the renal medulla. Ref.10

Tissue specificity

Highest expression observed in liver, spleen and testis; moderate expression in the choroid plexus, hippocampus, cerebrum and cerebellum of brain, and in kidney cortex and kidney medulla. Also observed in heart, pancreas, muscle, lung, placenta, stomach and small intestine. Weakest expression seen in peripheral blood lymphocytes, colon, duodenum, jejunum, ileum and skeletal muscle. Ref.1 Ref.2 Ref.4 Ref.10

Sequence similarities

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

Sequence caution

The sequence AAG18492.1 differs from that shown. Reason: Frameshift at position 1047.

The sequence AAL50802.1 differs from that shown. Reason: Frameshift at positions 760, 925 and 1047.

The sequence EAW99691.1 differs from that shown. Reason: Frameshift at position 1047.

Alternative products

This entry describes 8 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 Ref.2 (identifier: Q9BY07-1)

Also known as: NBC4a;

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 Ref.1 Ref.2 Ref.7 (identifier: Q9BY07-2)

Also known as: NBC4b;

The sequence of this isoform differs from the canonical sequence as follows:
     1046-1046: M → MSLSTTD
Isoform 3 Ref.4 Ref.7 (identifier: Q9BY07-3)

Also known as: NBC4c;

The sequence of this isoform differs from the canonical sequence as follows:
     973-988: Missing.
Isoform 4 Ref.3 Ref.7 (identifier: Q9BY07-4)

Also known as: NBC4d;

The sequence of this isoform differs from the canonical sequence as follows:
     950-1046: Missing.
Isoform 5 Ref.9 (identifier: Q9BY07-5)

Also known as: isoform d variant;

The sequence of this isoform differs from the canonical sequence as follows:
     88-91: SRTR → EHKG
     866-993: KAAGYHLDLF...KKLTPFWERC → GTESNRHHRL...HLFPARPGLD
     994-1137: Missing.
Note: No experimental confirmation available. Incomplete sequence.
Isoform 6 Ref.6 (identifier: Q9BY07-6)

Also known as: NBC4f;

The sequence of this isoform differs from the canonical sequence as follows:
     774-811: Missing.
     866-924: Missing.
     973-988: Missing.
     1046-1046: M → MSLSTTD
     1071-1075: NILPE → KIEFP
     1076-1137: Missing.
Isoform 7 Ref.8 (identifier: Q9BY07-7)

The sequence of this isoform differs from the canonical sequence as follows:
     27-91: ECPPIHIGLPVPTYPQRKTDQKGHLSGLQKVHWGLRPDQPQQELTGPGSGASSQDSSMDLISRTR → G
     774-811: Missing.
     973-988: Missing.
Note: No experimental confirmation available.
Isoform 8 Ref.6 (identifier: Q9BY07-8)

Also known as: NBC4e;

The sequence of this isoform differs from the canonical sequence as follows:
     1068-1137: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11371137Electrogenic sodium bicarbonate cotransporter 4
PRO_0000328920

Regions

Topological domain1 – 523523Cytoplasmic Potential
Transmembrane524 – 54421Helical; Potential
Topological domain545 – 56622Extracellular Potential
Transmembrane567 – 58721Helical; Potential
Topological domain588 – 60821Cytoplasmic Potential
Transmembrane609 – 62921Helical; Potential
Topological domain630 – 63910Extracellular Potential
Transmembrane640 – 66021Helical; Potential
Topological domain661 – 73878Cytoplasmic Potential
Transmembrane739 – 75921Helical; Potential
Topological domain760 – 77617Extracellular Potential
Transmembrane777 – 79721Helical; Potential
Topological domain798 – 82730Cytoplasmic Potential
Transmembrane828 – 84821Helical; Potential
Topological domain849 – 87325Extracellular Potential
Transmembrane874 – 89421Helical; Potential
Topological domain895 – 93036Cytoplasmic Potential
Transmembrane931 – 95121Helical; Potential
Topological domain9521Extracellular Potential
Transmembrane953 – 97321Helical; Potential
Topological domain974 – 101138Cytoplasmic Potential
Transmembrane1012 – 103221Helical; Potential
Transmembrane1033 – 105321Helical; Potential
Topological domain1054 – 113784Extracellular Potential
Compositional bias433 – 49765Gly-rich

Natural variations

Alternative sequence27 – 9165ECPPI…ISRTR → G in isoform 7. Ref.8
VSP_052770
Alternative sequence88 – 914SRTR → EHKG in isoform 5. Ref.9
VSP_052771
Alternative sequence774 – 81138Missing in isoform 6 and isoform 7. Ref.6 Ref.8
VSP_052772
Alternative sequence866 – 993128KAAGY…FWERC → GTESNRHHRLHPDGNLCLPG SHPKVYPPAGAVRSLPLHGR GLPEWHPVLGTLQALPDASQ APAGPCLPAARAAAPDPPLH PGADPLPGGALDPQIHGGCH HLPGHDPGPHHRSKASGFHL FPARPGLD in isoform 5. Ref.9
VSP_052773
Alternative sequence866 – 92459Missing in isoform 6. Ref.6
VSP_052774
Alternative sequence950 – 104697Missing in isoform 4. Ref.3
VSP_052775
Alternative sequence973 – 98816Missing in isoform 3, isoform 6 and isoform 7. Ref.5 Ref.6 Ref.8
VSP_052776
Alternative sequence994 – 1137144Missing in isoform 5. Ref.9
VSP_052777
Alternative sequence10461M → MSLSTTD in isoform 2 and isoform 6. Ref.1 Ref.2 Ref.6
VSP_052778
Alternative sequence1068 – 113770Missing in isoform 8. Ref.6
VSP_052779
Alternative sequence1071 – 10755NILPE → KIEFP in isoform 6. Ref.6
VSP_052780
Alternative sequence1076 – 113762Missing in isoform 6. Ref.6
VSP_052781
Natural variant2511S → N.
Corresponds to variant rs17009792 [ dbSNP | Ensembl ].
VAR_048350
Natural variant2531H → Y. Ref.9
Corresponds to variant rs55651232 [ dbSNP | Ensembl ].
VAR_061032

Experimental info

Sequence conflict6121H → Y in AAL48291. Ref.6
Sequence conflict6121H → Y in AAL50802. Ref.6
Sequence conflict6991A → T in AAL48291. Ref.6
Sequence conflict7591L → R in AAL50802. Ref.6
Sequence conflict8131T → P in AAK26741. Ref.2
Sequence conflict8961T → M in AAL48291. Ref.6
Sequence conflict9231G → R in AAL48291. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (NBC4a) [UniParc].

Last modified April 8, 2008. Version 2.
Checksum: ED4E4A4DC2CA17F1

FASTA1,137126,255
        10         20         30         40         50         60 
MKVKEEKAGV GKLDHTNHRR RFPDQKECPP IHIGLPVPTY PQRKTDQKGH LSGLQKVHWG 

        70         80         90        100        110        120 
LRPDQPQQEL TGPGSGASSQ DSSMDLISRT RSPAAEQLQD ILGEEDEAPN PTLFTEMDTL 

       130        140        150        160        170        180 
QHDGDQMEWK ESARWIKFEE KVEEGGERWS KPHVSTLSLH SLFELRTCLQ TGTVLLDLDS 

       190        200        210        220        230        240 
GSLPQIIDDV IEKQIEDGLL RPELRERVSY VLLRRHRHQT KKPIHRSLAD IGKSVSTTNR 

       250        260        270        280        290        300 
SPARSPGAGP SLHHSTEDLR MRQSANYGRL CHAQSRSMND ISLTPNTDQR KNKFMKKIPK 

       310        320        330        340        350        360 
DSEASNVLVG EVDFLDQPFI AFVRLIQSAM LGGVTEVPVP TRFLFILLGP SGRAKSYNEI 

       370        380        390        400        410        420 
GRAIATLMVD DLFSDVAYKA RNREDLIAGI DEFLDEVIVL PPGEWDPNIR IEPPKKVPSA 

       430        440        450        460        470        480 
DKRKSVFSLA ELGQMNGSVG GGGGAPGGGN GGGGGGGSGG GAGSGGAGGT SSGDDGEMPA 

       490        500        510        520        530        540 
MHEIGEELIW TGRFFGGLCL DIKRKLPWFP SDFYDGFHIQ SISAILFIYL GCITNAITFG 

       550        560        570        580        590        600 
GLLGDATDNY QGVMESFLGT AMAGSLFCLF SGQPLIILSS TGPILIFEKL LFDFSKGNGL 

       610        620        630        640        650        660 
DYMEFRLWIG LHSAVQCLIL VATDASFIIK YITRFTEEGF STLISFIFIY DAIKKMIGAF 

       670        680        690        700        710        720 
KYYPINMDFK PNFITTYKCE CVAPDTVNTT VFNASAPLAP DTNASLYNLL NLTALDWSLL 

       730        740        750        760        770        780 
SKKECLSYGG RLLGNSCKFI PDLALMSFIL FFGTYSMTLT LKKFKFSRYF PTKVRALVAD 

       790        800        810        820        830        840 
FSIVFSILMF CGIDACFGLE TPKLHVPSVI KPTRPDRGWF VAPFGKNPWW VYPASILPAL 

       850        860        870        880        890        900 
LVTILIFMDQ QITAVIVNRK ENKLKKAAGY HLDLFWVGIL MALCSFMGLP WYVAATVISI 

       910        920        930        940        950        960 
AHIDSLKMET ETSAPGEQPQ FLGVREQRVT GIIVFILTGI SVFLAPILKC IPLPVLYGVF 

       970        980        990       1000       1010       1020 
LYMGVASLNG IQMGTGGSEF KIQKKLTPFW ERCKLFLMPA KHQPDHAFLR HVPLRRIHLF 

      1030       1040       1050       1060       1070       1080 
TLVQILCLAV LWILKSTVAA IIFPVMILGL IIVRRLLDFI FSQHDLAWID NILPEKEKKE 

      1090       1100       1110       1120       1130 
TDKKRKRKKG AHEDCDEEPQ FPPPSVIKIP MESVQSDPQN GIHCIARKRS SSWSYSL 

« Hide

Isoform 2 (NBC4b) [UniParc].

Checksum: 3C32B411955873FD
Show »

FASTA1,143126,860
Isoform 3 (NBC4c) [UniParc].

Checksum: DC17DB7C69ABD27D
Show »

FASTA1,121124,551
Isoform 4 (NBC4d) [UniParc].

Checksum: FEE31CEF13F4F57B
Show »

FASTA1,040115,240
Isoform 5 (isoform d variant) [UniParc].

Checksum: 9C45DA4AC127035F
Show »

FASTA993108,663
Isoform 6 (NBC4f) [UniParc].

Checksum: 61243CD7DF614154
Show »

FASTA968107,526
Isoform 7 [UniParc].

Checksum: 93AAC3C3E0649931
Show »

FASTA1,019113,390
Isoform 8 (NBC4e) [UniParc].

Checksum: 7D1BA0C19F65AC3F
Show »

FASTA1,067118,125

References

« Hide 'large scale' references
[1]"Cloning, characterization and chromosomal assignment of NBC4, a new member of the sodium bicarbonate cotransporter family."
Pushkin A., Abuladze N., Newman D., Lee I., Xu G., Kurtz I.
Biochim. Biophys. Acta 1493:215-218(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY.
Tissue: Heart.
[2]"Two C-terminal variants of NBC4, a new member of the sodium bicarbonate cotransporter family: cloning, characterization, and localization."
Pushkin A., Abuladze N., Newman D., Lee I., Xu G., Kurtz I.
IUBMB Life 50:13-19(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY.
Tissue: Heart and Testis.
[3]"Genomic organization of the DCTN1-SLC4A5 locus encoding both NBC4 and p150(Glued)."
Pushkin A., Abuladze N., Newman D., Tatishchev S., Kurtz I.
Cytogenet. Cell Genet. 95:163-168(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
Tissue: Testis.
[4]"Functional characterization of NBC4: a new electrogenic sodium-bicarbonate cotransporter."
Sassani P., Pushkin A., Gross E., Gomer A., Abuladze N., Dukkipati R., Carpenito G., Kurtz I.
Am. J. Physiol. 282:C408-C416(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, TISSUE SPECIFICITY, INHIBITION.
Tissue: Testis.
[5]"Functional characterization of human NBC4 as an electrogenic Na+-HCO cotransporter (NBCe2)."
Virkki L.V., Wilson D.A., Vaughan-Jones R.D., Boron W.F.
Am. J. Physiol. 282:C1278-C1289(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, INHIBITION.
[6]"Expression of the Na+-HCO-3 cotransporter NBC4 in rat kidney and characterization of a novel NBC4 variant."
Xu J., Wang Z., Barone S., Petrovic M., Amlal H., Conforti L., Petrovic S., Soleimani M.
Am. J. Physiol. 284:F41-F50(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 8), FUNCTION, INHIBITION.
Tissue: Liver.
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"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] (ISOFORM 7).
[9]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 88-993 (ISOFORM 5), VARIANT TYR-253.
Tissue: Brain.
[10]"Molecular expression of SLC4-derived Na+-dependent anion transporters in selected human tissues."
Damkier H.H., Nielsen S., Praetorius J.
Am. J. Physiol. 293:R2136-R2146(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF207661 mRNA. Translation: AAG18492.1. Frameshift.
AF243499 mRNA. Translation: AAK26741.1.
AF293338 mRNA. Translation: AAK97073.1.
AF293337 mRNA. Translation: AAK97072.1.
AF452248 mRNA. Translation: AAL48291.1.
AF453528 mRNA. Translation: AAL50802.1. Frameshift.
CH471053 Genomic DNA. Translation: EAW99690.1.
CH471053 Genomic DNA. Translation: EAW99691.1. Frameshift.
CH471053 Genomic DNA. Translation: EAW99693.1.
BC109221 mRNA. Translation: AAI09222.1.
AB209752 mRNA. Translation: BAD92989.1.
RefSeqNP_067019.3. NM_021196.3.
NP_597812.1. NM_133478.2.
UniGeneHs.594099.

3D structure databases

ProteinModelPortalQ9BY07.
SMRQ9BY07. Positions 113-402, 505-546.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ9BY07. 1 interaction.
MINTMINT-6489517.
STRING9606.ENSP00000350475.

Protein family/group databases

TCDB2.A.31.2.8. the anion exchanger (ae) family.

PTM databases

PhosphoSiteQ9BY07.

Polymorphism databases

DMDM182691595.

Proteomic databases

PaxDbQ9BY07.
PRIDEQ9BY07.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000346834; ENSP00000251768; ENSG00000188687. [Q9BY07-4]
ENST00000357822; ENSP00000350475; ENSG00000188687. [Q9BY07-1]
ENST00000358683; ENSP00000351513; ENSG00000188687. [Q9BY07-7]
ENST00000359484; ENSP00000352461; ENSG00000188687. [Q9BY07-7]
ENST00000377632; ENSP00000366859; ENSG00000188687. [Q9BY07-4]
ENST00000377634; ENSP00000366861; ENSG00000188687. [Q9BY07-1]
ENST00000394019; ENSP00000377587; ENSG00000188687. [Q9BY07-3]
GeneID57835.
KEGGhsa:57835.
UCSCuc002skn.3. human. [Q9BY07-3]
uc002sko.1. human. [Q9BY07-1]
uc002skp.1. human. [Q9BY07-7]
uc010ffc.1. human. [Q9BY07-4]

Organism-specific databases

CTD57835.
GeneCardsGC02M074443.
HGNCHGNC:18168. SLC4A5.
HPAHPA036621.
MIM606757. gene.
neXtProtNX_Q9BY07.
PharmGKBPA164742397.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG318437.
HOVERGENHBG004326.
InParanoidQ9BY07.
KOK13857.
OMAELIWTGR.
OrthoDBEOG7TMZR0.
PhylomeDBQ9BY07.
TreeFamTF313630.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

BgeeQ9BY07.
CleanExHS_SLC4A5.
GenevestigatorQ9BY07.

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

ChiTaRSSLC4A5. human.
GeneWikiSLC4A5.
GenomeRNAi57835.
NextBio64831.
PROQ9BY07.
SOURCESearch...

Entry information

Entry nameS4A5_HUMAN
AccessionPrimary (citable) accession number: Q9BY07
Secondary accession number(s): Q32MA7 expand/collapse secondary AC list , Q59EQ9, Q8WXD3, Q8WXD7, Q96DS7, Q96DS8, Q9HBU5
Entry history
Integrated into UniProtKB/Swiss-Prot: April 8, 2008
Last sequence update: April 8, 2008
Last modified: April 16, 2014
This is version 96 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM