Q2Y0W8 (S4A8_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 73.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Electroneutral sodium bicarbonate exchanger 1 Alternative name(s): Electroneutral Na(+)-driven Cl-HCO3 exchanger Solute carrier family 4 member 8 k-NBC3 | ||||
| Gene names |
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| Organism | Homo sapiens (Human) [Reference proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo![]() |
Protein attributes
| Sequence length | 1093 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Mediates electroneutral sodium- and carbonate-dependent chloride-HCO3- exchange with a Na+:HCO3- stoichiometry of 2:1. Plays a major role in pH regulation in neurons. May be involved in cell pH regulation by transporting HCO3- from blood to cell. Enhanced expression in severe acid stress could be important for cell survival by mediating the influx of HCO3- into the cells. Also mediates lithium-dependent HCO3- cotransport. May be regulated by osmolarity. Ref.1 Ref.7 UniProtKB Q8JZR6 |
| 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 | |
| Tissue specificity | Expressed in the pyramidal cells of the hippocampus (at protein level). Highly expressed in all major regions of the brain, spinal column and in testis, and moderate levels in trachea, thyroid and medulla region of kidney. Low expression levels observed in pancreas and kidney cortex. Ref.1 Ref.7 Ref.9 |
| Sequence similarities | Belongs to the anion exchanger (TC 2.A.31) family. [View classification] |
| Sequence caution | The sequence BAA34459.1 differs from that shown. Reason: Erroneous initiation. The sequence CAD38576.2 differs from that shown. Reason: Erroneous initiation. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Anion exchange Antiport Ion transport Sodium transport Transport |
| Cellular component | Membrane |
| Coding sequence diversity | Alternative splicing Polymorphism |
| Domain | Coiled coil Transmembrane Transmembrane helix |
| Ligand | Sodium |
| Technical term | Complete proteome Reference proteome |
| Gene Ontology (GO) | |
| Biological_process | bicarbonate transport Traceable author statement. Source: Reactome sodium ion transportInferred from electronic annotation. Source: UniProtKB-KW transmembrane transportTraceable author statement. Source: Reactome |
| Cellular_component | integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membraneTraceable author statement. Source: Reactome |
| Molecular_function | inorganic anion exchanger activity Inferred from electronic annotation. Source: InterPro |
| Complete GO annotation... | |
Alternative products
| This entry describes 7 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 Ref.2 (identifier: Q2Y0W8-1) 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.3 (identifier: Q2Y0W8-2) The sequence of this isoform differs from the canonical sequence as follows: 1-16: MPAAGSNEPDGVLSYQ → MFNKNNSNKLRSTPRYRRGDPGYLNFTELGPLKPEQKDQWSQH 1028-1093: EAEKMLEIGG...GNAKEKSLFN → VIVLAPTVYLGASNYRT | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 3 Ref.1 (identifier: Q2Y0W8-3) The sequence of this isoform differs from the canonical sequence as follows: 1028-1093: EAEKMLEIGG...GNAKEKSLFN → VIVLAPTVYLGASNYRT | ||||||
| Note: May be due to an intron retention. | ||||||
| Isoform 4 Ref.2 (identifier: Q2Y0W8-4) The sequence of this isoform differs from the canonical sequence as follows: 1-53: Missing. 1028-1093: EAEKMLEIGG...GNAKEKSLFN → VIVLAPTVYLGASNYRT | ||||||
| Note: May be due to an intron retention. | ||||||
| Isoform 5 Ref.2 (identifier: Q2Y0W8-5) The sequence of this isoform differs from the canonical sequence as follows: 1-53: Missing. | ||||||
| Isoform 6 Ref.5 Ref.6 (identifier: Q2Y0W8-6) The sequence of this isoform differs from the canonical sequence as follows: 671-691: ECQEMHGEFMGSACGHHGPYT → VSLGAARCPSIVTTGLGGTSK 692-1093: Missing. | ||||||
| Isoform 7 Ref.4 (identifier: Q2Y0W8-7) The sequence of this isoform differs from the canonical sequence as follows: 1-53: Missing. 725-800: VRSMVSDFAV...LLCTILIFMD → MESCSVAWLE...RPPKMLGLQA 801-1093: Missing. | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1093 | 1093 | Electroneutral sodium bicarbonate exchanger 1 | PRO_0000328922 | |||||
Regions | |||||||||
| Topological domain | 1 – 478 | 478 | Extracellular Potential | ||||||
| Transmembrane | 479 – 499 | 21 | Helical; Potential | ||||||
| Topological domain | 500 – 523 | 24 | Cytoplasmic Potential | ||||||
| Transmembrane | 524 – 544 | 21 | Helical; Potential | ||||||
| Topological domain | 545 – 565 | 21 | Extracellular Potential | ||||||
| Transmembrane | 566 – 586 | 21 | Helical; Potential | ||||||
| Topological domain | 587 – 595 | 9 | Cytoplasmic Potential | ||||||
| Transmembrane | 596 – 616 | 21 | Helical; Potential | ||||||
| Topological domain | 617 – 687 | 71 | Extracellular Potential | ||||||
| Transmembrane | 688 – 708 | 21 | Helical; Potential | ||||||
| Topological domain | 709 – 731 | 23 | Cytoplasmic Potential | ||||||
| Transmembrane | 732 – 752 | 21 | Helical; Potential | ||||||
| Topological domain | 753 – 778 | 26 | Extracellular Potential | ||||||
| Transmembrane | 779 – 799 | 21 | Helical; Potential | ||||||
| Topological domain | 800 – 824 | 25 | Cytoplasmic Potential | ||||||
| Transmembrane | 825 – 845 | 21 | Helical; Potential | ||||||
| Topological domain | 846 – 881 | 36 | Extracellular Potential | ||||||
| Transmembrane | 882 – 902 | 21 | Helical; Potential | ||||||
| Topological domain | 903 – 904 | 2 | Cytoplasmic Potential | ||||||
| Transmembrane | 905 – 925 | 21 | Helical; Potential | ||||||
| Topological domain | 926 – 962 | 37 | Extracellular Potential | ||||||
| Transmembrane | 963 – 983 | 21 | Helical; Potential | ||||||
| Topological domain | 984 – 1093 | 110 | Cytoplasmic Potential | ||||||
| Coiled coil | 1010 – 1036 | 27 | Potential | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 53 | 53 | Missing in isoform 4, isoform 5 and isoform 7. Ref.2 Ref.4 | VSP_052759 | |||||
| Alternative sequence | 1 – 16 | 16 | MPAAG…VLSYQ → MFNKNNSNKLRSTPRYRRGD PGYLNFTELGPLKPEQKDQW SQH in isoform 2. Ref.3 | VSP_052760 | |||||
| Alternative sequence | 671 – 691 | 21 | ECQEM…HGPYT → VSLGAARCPSIVTTGLGGTS K in isoform 6. Ref.5 Ref.6 | VSP_052761 | |||||
| Alternative sequence | 692 – 1093 | 402 | Missing in isoform 6. Ref.5 Ref.6 | VSP_052762 | |||||
| Alternative sequence | 725 – 800 | 76 | VRSMV…LIFMD → MESCSVAWLECGGVILAHCN LRLLPSSWDYRHAPPRPANF CIFSGDGVSPCWPGWSQSLD LVICLPRPPKMLGLQA in isoform 7. Ref.4 | VSP_052763 | |||||
| Alternative sequence | 801 – 1093 | 293 | Missing in isoform 7. Ref.4 | VSP_052764 | |||||
| Alternative sequence | 1028 – 1093 | 66 | EAEKM…KSLFN → VIVLAPTVYLGASNYRT in isoform 2, isoform 3 and isoform 4. Ref.1 Ref.2 Ref.3 | VSP_052765 | |||||
| Natural variant | 312 | 1 | D → A. Corresponds to variant rs35966334 [ dbSNP | Ensembl ]. | VAR_048351 | |||||
| Natural variant | 898 | 1 | I → V. Corresponds to variant rs12318785 [ dbSNP | Ensembl ]. | VAR_048352 | |||||
Experimental info | |||||||||
| Sequence conflict | 1008 | 1 | M → T in AAC82380. Ref.1 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Cloning, characterization, and chromosomal mapping of a human electroneutral Na(+)-driven Cl-HCO3 exchanger." Grichtchenko I.I., Choi I., Zhong X., Bray-Ward P., Russell J.M., Boron W.F. J. Biol. Chem. 276:8358-8363(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, TISSUE SPECIFICITY, INHIBITION. Tissue: Frontal cortex. |
| [2] | "An electroneutral Na+-driven Cl-HCO3 exchanger (NDCBE1) with a novel COOH-terminus cloned from human brain." Bouyer P., Parker M.D., Boron W.F. Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 4 AND 5). Tissue: Brain and Heart. |
| [3] | "Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:277-286(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain. |
| [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., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7). Tissue: Amygdala. |
| [5] | 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]. |
| [6] | "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 6). Tissue: Testis. |
| [7] | "Characterization of Na+/HCO-3 cotransporter isoform NBC-3." Amlal H., Burnham C.E., Soleimani M. Am. J. Physiol. 276:F903-F913(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-670 (ISOFORMS 1/3/6), FUNCTION, TISSUE SPECIFICITY, INHIBITION. Tissue: Testis carcinoma. |
| [8] | Erratum Amlal H., Burnham C.E., Soleimani M. Am. J. Physiol. 277:F477-F477(1999) |
| [9] | "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. |
| [10] | "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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AF069512 mRNA. Translation: AAC82380.1. DQ063579 mRNA. Translation: AAY79176.1. DQ975204 mRNA. Translation: ABJ09587.1. DQ996537 mRNA. Translation: ABJ91576.1. DQ996398 mRNA. Translation: ABJ91577.1. AB018282 mRNA. Translation: BAA34459.1. Different initiation. AL831915 mRNA. Translation: CAD38576.2. Different initiation. CH471111 Genomic DNA. Translation: EAW58192.1. BC025994 mRNA. Translation: AAH25994.1. AF107099 mRNA. Translation: AAD52981.1. |
| IPI | IPI00097856. IPI00184876. IPI00737057. IPI00792986. IPI00794077. IPI00889606. IPI00889627. |
| RefSeq | NP_001035049.1. NM_001039960.2. NP_001245330.1. NM_001258401.2. NP_001245331.1. NM_001258402.1. NP_001245332.1. NM_001258403.1. NP_001254544.1. NM_001267615.1. |
| UniGene | Hs.4749. |
3D structure databases | |
| ProteinModelPortal | Q2Y0W8. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q2Y0W8. 1 interaction. |
| STRING | 9606.ENSP00000405812. |
Protein family/group databases | |
| TCDB | 2.A.31.2.4. anion exchanger (AE) family. |
PTM databases | |
| PhosphoSite | Q2Y0W8. |
Polymorphism databases | |
| DMDM | 121942008. |
Proteomic databases | |
| PaxDb | Q2Y0W8. |
| PRIDE | Q2Y0W8. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000358657; ENSP00000351483; ENSG00000050438. ENST00000453097; ENSP00000405812; ENSG00000050438. ENST00000599597; ENSP00000472774; ENSG00000050438. |
| GeneID | 9498. |
| KEGG | hsa:9498. |
| UCSC | uc001rym.3. human. uc001ryo.2. human. uc001ryq.4. human. uc001ryr.3. human. uc010snj.2. human. |
Organism-specific databases | |
| CTD | 9498. |
| GeneCards | GC12P051807. |
| HGNC | HGNC:11034. SLC4A8. |
| HPA | HPA046665. |
| MIM | 605024. gene. |
| neXtProt | NX_Q2Y0W8. |
| PharmGKB | PA35900. |
| HUGE | Search... |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | NOG268067. |
| HOVERGEN | HBG004326. |
| KO | K13859. |
| OMA | VLNIHYE. |
Enzyme and pathway databases | |
| Reactome | REACT_15518. Transmembrane transport of small molecules. |
Gene expression databases | |
| ArrayExpress | Q2Y0W8. |
| Bgee | Q2Y0W8. |
| CleanEx | HS_SLC4A8. |
| Genevestigator | Q2Y0W8. |
Family and domain databases | |
| Gene3D | 3.40.1100.10. 1 hit. |
| InterPro | IPR013769. Band3_cytoplasmic_dom. IPR011531. HCO3_transpt_C. IPR003020. HCO3_transpt_euk. IPR003024. Na/HCO3_transpt. IPR016152. PTrfase/Anion_transptr. [Graphical view] |
| PANTHER | PTHR11453. PTHR11453. 1 hit. |
| Pfam | PF07565. Band_3_cyto. 1 hit. PF00955. HCO3_cotransp. 1 hit. [Graphical view] |
| PRINTS | PR01231. HCO3TRNSPORT. PR01232. NAHCO3TRSPRT. |
| SUPFAM | SSF55804. PTrfase/Anion_transptr. 1 hit. |
| TIGRFAMs | TIGR00834. ae. 1 hit. |
| PROSITE | PS00219. ANION_EXCHANGER_1. False negative. PS00220. ANION_EXCHANGER_2. False negative. [Graphical view] |
| ProtoNet | Search... |
Other | |
| ChiTaRS | SLC4A8. human. |
| GenomeRNAi | 9498. |
| NextBio | 35584. |
| SOURCE | Search... |
Entry information
| Entry name | S4A8_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q2Y0W8 Secondary accession number(s): A0MMZ1 Q9UKX8 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any 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
| Human chromosome 12 Human chromosome 12: 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
