Reviewed,
UniProtKB/Swiss-Prot Q9Y6M7 (S4A7_HUMAN)
Last modified
June 16, 2009.
Version 57.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Sodium bicarbonate cotransporter 3 Alternative name(s): Sodium bicarbonate cotransporter 2 Sodium bicarbonate cotransporter 2b Short name=Bicarbonate transporter Solute carrier family 4 member 7 | ||||
| Gene names |
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| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 1214 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Electroneutral sodium- and bicarbonate-dependent cotransporter with a Na+:HCO3- 1:1 stoichiometry. Regulates intracellular pH and may play a role in bicarbonate salvage in secretory epithelia. May also have an associated sodium channel activity. Ref.2 Ref.7 |
| Enzyme regulation | Transporter activity is regulated by CA2/carbonic anhydrase 2, cAMP and PKA. Insensitive to stilbene derivatives. Ref.2 states it is inhibited by 5-(N-ethyl-N-isopropyl)-amiloride (EIPA). |
| Subunit structure | Interacts with CFTR through SLC9A3R1/EBP50. Interacts with USH1C. Forms a complex with ATP6V1B1 and SLC9A3R1/EBP50. Interacts in a pH dependent-manner with CA2/carbonic anhydrase 2. Ref.7 Ref.8 Ref.9 Ref.11 |
| Subcellular location | Basolateral cell membrane; Multi-pass membrane protein. Apical cell membrane; Multi-pass membrane protein By similarity. Cell projection › stereocilium By similarity. Note: Also described at the apical cell membrane. Localizes to the stereocilia of cochlear outer hair cells and to the lateral membrane of cochlear inner hair cells By similarity. |
| Tissue specificity | Highly expressed in testis and spleen. Also expressed in retina, colon, small intestine, ovary, thymus, prostate, muscle, heart and kidney. Isoform 1 is expressed in skeletal muscle and heart muscle. Ref.1 |
| Domain | The PDZ-binding motif mediates interaction with the CFTR, SLC9A3R1/EBP50 complex and probably with USH1C. Ref.7 |
| Post-translational modification | N-glycosylated By similarity. |
| Sequence similarities | Belongs to the anion exchanger (TC 2.A.31) family. [View classification] |
| biophysicochemical properties | Kinetic parameters: KM=24 mM for external sodium |
Ontologies
Alternative products
| This entry describes 5 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q9Y6M7-1) Also known as: mNBC3; NBCn1-A; 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: Q9Y6M7-2) The sequence of this isoform differs from the canonical sequence as follows: 251-374: Missing. | ||||||
| Isoform 3 (identifier: Q9Y6M7-3) The sequence of this isoform differs from the canonical sequence as follows: 1-90: Missing. 91-118: SQRVQFILGTEDDDEEHIPHDLFTEMDE → MAVTQFIHFREEIMGNMFFIIIFSTKDK 251-374: Missing. 1189-1214: PDKPVSVKISFEDEPRKKYVDAETSL → GDPSIGNISDEMAKTAQWKALSMNTENAKVTRSNMSPDKPVSVK | ||||||
| Isoform 4 (identifier: Q9Y6M7-4) The sequence of this isoform differs from the canonical sequence as follows: 1-90: Missing. 91-118: SQRVQFILGTEDDDEEHIPHDLFTEMDE → MAVTQFIHFREEIMGNMFFIIIFSTKDK 251-374: Missing. | ||||||
| Isoform 5 (identifier: Q9Y6M7-5) The sequence of this isoform differs from the canonical sequence as follows: 1-450: Missing. 451-465: PAVLLTGLTEVPVPT → MEVVEAEKIVLLTSA 1188-1188: S → SVDPSIVNISDEMAKTAQWKALSMNSENAKVTRSNMS | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1214 | 1214 | Sodium bicarbonate cotransporter 3 | PRO_0000079233 | |||||
Regions | |||||||||
| Topological domain | 1 – 608 | 608 | Extracellular Potential | ||||||
| Transmembrane | 609 – 629 | 21 | Potential | ||||||
| Topological domain | 630 – 637 | 8 | Cytoplasmic Potential | ||||||
| Transmembrane | 638 – 658 | 21 | Potential | ||||||
| Topological domain | 659 – 695 | 37 | Extracellular Potential | ||||||
| Transmembrane | 696 – 716 | 21 | Potential | ||||||
| Topological domain | 717 – 725 | 9 | Cytoplasmic Potential | ||||||
| Transmembrane | 726 – 746 | 21 | Potential | ||||||
| Topological domain | 747 – 817 | 71 | Extracellular Potential | ||||||
| Transmembrane | 818 – 838 | 21 | Potential | ||||||
| Topological domain | 839 – 861 | 23 | Cytoplasmic Potential | ||||||
| Transmembrane | 862 – 882 | 21 | Potential | ||||||
| Topological domain | 883 – 908 | 26 | Extracellular Potential | ||||||
| Transmembrane | 909 – 929 | 21 | Potential | ||||||
| Topological domain | 930 – 954 | 25 | Cytoplasmic Potential | ||||||
| Transmembrane | 955 – 975 | 21 | Potential | ||||||
| Topological domain | 976 – 1011 | 36 | Extracellular Potential | ||||||
| Transmembrane | 1012 – 1032 | 21 | Potential | ||||||
| Topological domain | 1033 – 1034 | 2 | Cytoplasmic Potential | ||||||
| Transmembrane | 1035 – 1055 | 21 | Potential | ||||||
| Topological domain | 1056 – 1092 | 37 | Extracellular Potential | ||||||
| Transmembrane | 1093 – 1113 | 21 | Potential | ||||||
| Topological domain | 1114 – 1214 | 101 | Cytoplasmic Potential | ||||||
| Region | 1134 – 1136 | 3 | CA2-binding | ||||||
| Motif | 1211 – 1214 | 4 | PDZ-binding | ||||||
Amino acid modifications | |||||||||
| Modified residue | 233 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 379 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 382 | 1 | Phosphoserine Ref.13 | ||||||
| Modified residue | 403 | 1 | Phosphoserine Ref.13 | ||||||
| Modified residue | 407 | 1 | Phosphoserine Ref.13 | ||||||
| Modified residue | 1167 | 1 | Phosphothreonine Ref.13 Ref.12 | ||||||
| Modified residue | 1176 | 1 | Phosphoserine Ref.13 Ref.12 | ||||||
| Modified residue | 1188 | 1 | Phosphoserine Ref.13 | ||||||
| Modified residue | 1194 | 1 | Phosphoserine Ref.13 | ||||||
| Modified residue | 1213 | 1 | Phosphoserine Ref.13 Ref.10 | ||||||
| Glycosylation | 171 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 269 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 398 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 406 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 786 | 1 | N-linked (GlcNAc...) Potential | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 450 | 450 | Missing in isoform 5. | VSP_017159 | |||||
| Alternative sequence | 1 – 90 | 90 | Missing in isoform 3 and isoform 4. | VSP_017160 | |||||
| Alternative sequence | 91 – 118 | 28 | SQRVQ…TEMDE → MAVTQFIHFREEIMGNMFFI IIFSTKDK in isoform 3 and isoform 4. | VSP_017161 | |||||
| Alternative sequence | 251 – 374 | 124 | Missing in isoform 2, isoform 3 and isoform 4. | VSP_017162 | |||||
| Alternative sequence | 451 – 465 | 15 | PAVLL…VPVPT → MEVVEAEKIVLLTSA in isoform 5. | VSP_017163 | |||||
| Alternative sequence | 1188 | 1 | S → SVDPSIVNISDEMAKTAQWK ALSMNSENAKVTRSNMS in isoform 5. | VSP_017164 | |||||
| Alternative sequence | 1189 – 1214 | 26 | PDKPV…AETSL → GDPSIGNISDEMAKTAQWKA LSMNTENAKVTRSNMSPDKP VSVK in isoform 3. | VSP_017165 | |||||
| Natural variant | 326 | 1 | E → K: dbSNP rs3755652. | VAR_055317 | |||||
Experimental info | |||||||||
| Mutagenesis | 1135 – 1136 | 2 | DD → NN: Loss of interaction with CA2. Loss of regulation by CA2. | ||||||
| Mutagenesis | 1163 – 1165 | 3 | DDD → NNN: No effect on interaction with CA2. No effect on regulation by CA2. Ref.9 | ||||||
| Mutagenesis | 1214 | 1 | L → G: Loss of interaction with ATP6V1B1. Ref.8 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Molecular cloning of a new sodium bicarbonate cotransporter cDNA from human retina." Ishibashi K., Sasaki S., Marumo F. Biochem. Biophys. Res. Commun. 246:535-538(1998) [PubMed: 9610397] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY. Tissue: Retina. |
| [2] | "Cloning, tissue distribution, genomic organization, and functional characterization of NBC3, a new member of the sodium bicarbonate cotransporter family." Pushkin A., Abuladze N., Lee I., Newman D., Hwang J., Kurtz I. J. Biol. Chem. 274:16569-16575(1999) [PubMed: 10347222] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, REGULATION, VARIANT LYS-326. Tissue: Kidney and Skeletal muscle. |
| [3] | "Cloning of a HCO3 transporter, NT2-NBC, from human brain, similar to both the Anion exchangers (AEs) and the Na/Bicarbonate Cotransporters (NBCs)." Romero M.F. Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4). Tissue: Neuroepithelium. |
| [4] | "The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Blocker H., Heubner D., Hoerlein A., Michel G., Wedler H., Kohrer K., Ottenwalder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). Tissue: Cervix. |
| [5] | "The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. Gibbs R.A.Nature 440:1194-1198(2006) [PubMed: 16641997] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [6] | 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. Venter J.C.Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [7] | "The cystic fibrosis transmembrane conductance regulator interacts with and regulates the activity of the HCO3- salvage transporter human Na+-HCO3-cotransport isoform 3." Park M., Ko S.B.H., Choi J.Y., Muallem G., Thomas P.J., Pushkin A., Lee M.-S., Kim J.Y., Lee M.G., Muallem S., Kurtz I. J. Biol. Chem. 277:50503-50509(2002) [PubMed: 12403779] [Abstract] Cited for: FUNCTION, INTERACTION WITH CFTR AND SLC9A3R1, DOMAIN. |
| [8] | "The COOH termini of NBC3 and the 56-kDa H+-ATPase subunit are PDZ motifs involved in their interaction." Pushkin A., Abuladze N., Newman D., Muronets V., Sassani P., Tatishchev S., Kurtz I. Am. J. Physiol. 284:C667-C673(2003) [PubMed: 12444018] [Abstract] Cited for: INTERACTION WITH ATP6V1B1 AND SLC9A3R1, MUTAGENESIS OF LEU-1214. |
| [9] | "Regulation of the human NBC3 Na+/HCO3- cotransporter by carbonic anhydrase II and PKA." Loiselle F.B., Morgan P.E., Alvarez B.V., Casey J.R. Am. J. Physiol. 286:C1423-C1433(2004) [PubMed: 14736710] [Abstract] Cited for: INTERACTION WITH CA2, REGULATION, MUTAGENESIS OF 1135-ASP-ASP-1136 AND 1163-ASP--ASP-1165. |
| [10] | "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry." Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C. Anal. Chem. 76:2763-2772(2004) [PubMed: 15144186] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1213, MASS SPECTROMETRY. Tissue: T-cell. |
| [11] | "Scaffold protein harmonin (USH1C) provides molecular links between Usher syndrome type 1 and type 2." Reiners J., van Wijk E., Maerker T., Zimmermann U., Juergens K., te Brinke H., Overlack N., Roepman R., Knipper M., Kremer H., Wolfrum U. Hum. Mol. Genet. 14:3933-3943(2005) [PubMed: 16301216] [Abstract] Cited for: INTERACTION WITH USH1C. |
| [12] | "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1167 AND SER-1176, MASS SPECTROMETRY. |
| [13] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-382; SER-403; SER-407; THR-1167; SER-1176; SER-1188; SER-1194 AND SER-1213, MASS SPECTROMETRY. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| AB012130 mRNA. Translation: BAA25898.1. AF047033 mRNA. Translation: AAD38322.1. AF089726 mRNA. Translation: AAG16773.1. AF053755 mRNA. Translation: AAF21720.1. CR627428 mRNA. Translation: CAH10515.1. AC099535 Genomic DNA. No translation available. CH471055 Genomic DNA. Translation: EAW64382.1. | |
| IPI | IPI00021058. IPI00328342. IPI00387156. IPI00719704. IPI00719757. |
| PIR | JE0160. |
| RefSeq | NP_003606.3. |
| UniGene | Hs.250072 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1BZK based on UniProtKB P02730. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q9Y6M7. 1 interaction. |
PTM databases | |
| PhosphoSite | Q9Y6M7. |
Proteomic databases | |
| PRIDE | Q9Y6M7. |
Genome annotation databases | |
| Ensembl | ENSG00000033867. Homo sapiens. [Contig view] |
| GeneID | 9497. |
Organism-specific databases | |
| GeneCards | GC03M027389. |
| H-InvDB | HIX0003134. |
| HGNC | HGNC:11033. SLC4A7. |
| MIM | 603353. gene. |
| PharmGKB | PA35899. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOVERGEN | Q9Y6M7. |
Gene expression databases | |
| ArrayExpress | Q9Y6M7. |
| Bgee | Q9Y6M7. |
| CleanEx | HS_SLC4A7. |
| GermOnline | ENSG00000033867. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR018241. Anion_exchange_CS. IPR011531. HCO3_transpt_C. IPR013769. HCO3_transpt_cyt. IPR003020. HCO3_transpt_euk. [Graphical view] |
| Gene3D | G3DSA:3.40.1100.10. HCO3_transpt_cyt. 1 hit. |
| PANTHER | PTHR11453. HCO3_transpt_euk. 1 hit. |
| Pfam | PF07565. Band_3_cyto. 1 hit. PF00955. HCO3_cotransp. 1 hit. [Graphical view] |
| PRINTS | PR01231. HCO3TRNSPORT. |
| TIGRFAMs | TIGR00834. ae. 1 hit. |
| PROSITE | PS00219. ANION_EXCHANGER_1. False negative. PS00220. ANION_EXCHANGER_2. False negative. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| SOURCE | Search... |
Entry information
| Entry name | S4A7_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q9Y6M7 Secondary accession number(s): A6NIA8 Q9UIB9 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 3 Human chromosome 3: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


