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UniProtKB/Swiss-Prot Q9Y6M7 (S4A7_HUMAN)
Last modified
July 22, 2008.
Version 50.
History...
Clusters with 100%,
90%,
50% identity |
Documents (4) |
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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 |
| ||||
| 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. |
| 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. |
| Subcellular location | Basolateral cell membrane; Multi-pass membrane protein. Apical cell membrane; Multi-pass membrane proteinBy similarity. Cell projection › stereociliumBy 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. |
| Domain | The PDZ-binding motif mediates interaction with the CFTR, SLC9A3R1/EBP50 complex and probably with USH1C. |
| 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
Keywords | |
|---|---|
| Biological process | Ion transport Sodium transport Symport Transport |
| Cellular component | Cell membrane Cell projection Membrane |
| Coding sequence diversity | Alternative splicing |
| Domain | Transmembrane |
| Ligand | Sodium |
| PTM | Glycoprotein Phosphoprotein |
Gene Ontology (GO) | |
| Biological process | bicarbonate transport Ref.2 Non-traceable author statement. Source: UniProtKB |
| Cellular component | integral to membrane Ref.2 Non-traceable author statement. Source: UniProtKB |
| Molecular function | protein binding Inferred from physical interaction. Source: IntAct sodium:bicarbonate symporter activity Ref.2Non-traceable author statement. Source: UniProtKB |
| Complete GO annotation... | |
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 | ||||||
| Notes: 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 | 407 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 1167 | 1 | Phosphothreonine | ||||||
| Modified residue | 1176 | 1 | Phosphoserine | ||||||
| Modified residue | 1213 | 1 | Phosphoserine | ||||||
| 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 | |||||
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 | ||||||
| Mutagenesis | 1214 | 1 | L → G: Loss of interaction with ATP6V1B1 | ||||||
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. 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 German cDNA consortium Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). Tissue: Cervix. |
| [5] | "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. |
| [6] | "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. |
| [7] | "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. |
| [8] | "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. |
| [9] | "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. |
| [10] | "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. |
| + | Additional computationally mapped references. |

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