Q9BY07 (S4A5_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 29, 2013.
Version 87.
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: Electrogenic sodium bicarbonate cotransporter 4 Alternative name(s): NBCe2 Solute carrier family 4 member 5 | ||||
| Gene names |
| ||||
| 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 | 1137 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence 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. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Anion exchange Ion transport Sodium transport Transport |
| Cellular component | Cell membrane Membrane |
| Coding sequence diversity | Alternative splicing Polymorphism |
| Domain | Transmembrane Transmembrane helix |
| Ligand | Sodium |
| Technical term | Complete proteome Reference proteome |
| Gene Ontology (GO) | |
| Cellular_component | apical plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membraneNon-traceable author statement Ref.1. Source: UniProtKB plasma membraneTraceable author statement. Source: Reactome |
| Molecular_function | inorganic anion exchanger activity Inferred from electronic annotation. Source: InterPro sodium:bicarbonate symporter activityNon-traceable author statement Ref.1. Source: UniProtKB |
| Complete GO annotation... | |
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 key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1137 | 1137 | Electrogenic sodium bicarbonate cotransporter 4 | PRO_0000328920 | |||||
Regions | |||||||||
| Topological domain | 1 – 523 | 523 | Cytoplasmic Potential | ||||||
| Transmembrane | 524 – 544 | 21 | Helical; Potential | ||||||
| Topological domain | 545 – 566 | 22 | Extracellular Potential | ||||||
| Transmembrane | 567 – 587 | 21 | Helical; Potential | ||||||
| Topological domain | 588 – 608 | 21 | Cytoplasmic Potential | ||||||
| Transmembrane | 609 – 629 | 21 | Helical; Potential | ||||||
| Topological domain | 630 – 639 | 10 | Extracellular Potential | ||||||
| Transmembrane | 640 – 660 | 21 | Helical; Potential | ||||||
| Topological domain | 661 – 738 | 78 | Cytoplasmic Potential | ||||||
| Transmembrane | 739 – 759 | 21 | Helical; Potential | ||||||
| Topological domain | 760 – 776 | 17 | Extracellular Potential | ||||||
| Transmembrane | 777 – 797 | 21 | Helical; Potential | ||||||
| Topological domain | 798 – 827 | 30 | Cytoplasmic Potential | ||||||
| Transmembrane | 828 – 848 | 21 | Helical; Potential | ||||||
| Topological domain | 849 – 873 | 25 | Extracellular Potential | ||||||
| Transmembrane | 874 – 894 | 21 | Helical; Potential | ||||||
| Topological domain | 895 – 930 | 36 | Cytoplasmic Potential | ||||||
| Transmembrane | 931 – 951 | 21 | Helical; Potential | ||||||
| Topological domain | 952 | 1 | Extracellular Potential | ||||||
| Transmembrane | 953 – 973 | 21 | Helical; Potential | ||||||
| Topological domain | 974 – 1011 | 38 | Cytoplasmic Potential | ||||||
| Transmembrane | 1012 – 1032 | 21 | Helical; Potential | ||||||
| Transmembrane | 1033 – 1053 | 21 | Helical; Potential | ||||||
| Topological domain | 1054 – 1137 | 84 | Extracellular Potential | ||||||
| Compositional bias | 433 – 497 | 65 | Gly-rich | ||||||
Natural variations | |||||||||
| Alternative sequence | 27 – 91 | 65 | ECPPI…ISRTR → G in isoform 7. Ref.8 | VSP_052770 | |||||
| Alternative sequence | 88 – 91 | 4 | SRTR → EHKG in isoform 5. Ref.9 | VSP_052771 | |||||
| Alternative sequence | 774 – 811 | 38 | Missing in isoform 6 and isoform 7. Ref.6 Ref.8 | VSP_052772 | |||||
| Alternative sequence | 866 – 993 | 128 | KAAGY…FWERC → GTESNRHHRLHPDGNLCLPG SHPKVYPPAGAVRSLPLHGR GLPEWHPVLGTLQALPDASQ APAGPCLPAARAAAPDPPLH PGADPLPGGALDPQIHGGCH HLPGHDPGPHHRSKASGFHL FPARPGLD in isoform 5. Ref.9 | VSP_052773 | |||||
| Alternative sequence | 866 – 924 | 59 | Missing in isoform 6. Ref.6 | VSP_052774 | |||||
| Alternative sequence | 950 – 1046 | 97 | Missing in isoform 4. Ref.3 | VSP_052775 | |||||
| Alternative sequence | 973 – 988 | 16 | Missing in isoform 3, isoform 6 and isoform 7. Ref.5 Ref.6 Ref.8 | VSP_052776 | |||||
| Alternative sequence | 994 – 1137 | 144 | Missing in isoform 5. Ref.9 | VSP_052777 | |||||
| Alternative sequence | 1046 | 1 | M → MSLSTTD in isoform 2 and isoform 6. Ref.1 Ref.2 Ref.6 | VSP_052778 | |||||
| Alternative sequence | 1068 – 1137 | 70 | Missing in isoform 8. Ref.6 | VSP_052779 | |||||
| Alternative sequence | 1071 – 1075 | 5 | NILPE → KIEFP in isoform 6. Ref.6 | VSP_052780 | |||||
| Alternative sequence | 1076 – 1137 | 62 | Missing in isoform 6. Ref.6 | VSP_052781 | |||||
| Natural variant | 251 | 1 | S → N. Corresponds to variant rs17009792 [ dbSNP | Ensembl ]. | VAR_048350 | |||||
| Natural variant | 253 | 1 | H → Y. Ref.9 Corresponds to variant rs55651232 [ dbSNP | Ensembl ]. | VAR_061032 | |||||
Experimental info | |||||||||
| Sequence conflict | 612 | 1 | H → Y in AAL48291. Ref.6 | ||||||
| Sequence conflict | 612 | 1 | H → Y in AAL50802. Ref.6 | ||||||
| Sequence conflict | 699 | 1 | A → T in AAL48291. Ref.6 | ||||||
| Sequence conflict | 759 | 1 | L → R in AAL50802. Ref.6 | ||||||
| Sequence conflict | 813 | 1 | T → P in AAK26741. Ref.2 | ||||||
| Sequence conflict | 896 | 1 | T → M in AAL48291. Ref.6 | ||||||
| Sequence conflict | 923 | 1 | G → R in AAL48291. Ref.6 | ||||||
Sequences
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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. 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. |
| IPI | IPI00061148. IPI00107529. IPI00218089. IPI00655610. IPI00889641. IPI00889661. IPI00889759. IPI00889761. |
| RefSeq | NP_067019.3. NM_021196.3. NP_597812.1. NM_133478.2. |
| UniGene | Hs.744095. |
3D structure databases | |
| ProteinModelPortal | Q9BY07. |
| SMR | Q9BY07. Positions 111-428, 505-546. |
| ModBase | Search... |
Protein-protein interaction databases | |
| MINT | MINT-6489517. |
| STRING | 9606.ENSP00000350475. |
Protein family/group databases | |
| TCDB | 2.A.31.2.8. anion exchanger (AE) family. |
PTM databases | |
| PhosphoSite | Q9BY07. |
Polymorphism databases | |
| DMDM | 182691595. |
Proteomic databases | |
| PaxDb | Q9BY07. |
| PRIDE | Q9BY07. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000346834; ENSP00000251768; ENSG00000188687. ENST00000357822; ENSP00000350475; ENSG00000188687. ENST00000358683; ENSP00000351513; ENSG00000188687. ENST00000359484; ENSP00000352461; ENSG00000188687. ENST00000377632; ENSP00000366859; ENSG00000188687. ENST00000377634; ENSP00000366861; ENSG00000188687. ENST00000394019; ENSP00000377587; ENSG00000188687. |
| GeneID | 57835. |
| KEGG | hsa:57835. |
| UCSC | uc002skn.3. human. uc002sko.1. human. uc002skp.1. human. uc010ffc.1. human. |
Organism-specific databases | |
| CTD | 57835. |
| GeneCards | GC02M074443. |
| HGNC | HGNC:18168. SLC4A5. |
| HPA | HPA036621. |
| MIM | 606757. gene. |
| neXtProt | NX_Q9BY07. |
| PharmGKB | PA164742397. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | NOG318437. |
| HOVERGEN | HBG004326. |
| InParanoid | Q9BY07. |
| KO | K13857. |
Enzyme and pathway databases | |
| Reactome | REACT_15518. Transmembrane transport of small molecules. |
Gene expression databases | |
| ArrayExpress | Q9BY07. |
| Bgee | Q9BY07. |
| CleanEx | HS_SLC4A5. |
| Genevestigator | Q9BY07. |
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 | SLC4A5. human. |
| GenomeRNAi | 57835. |
| NextBio | 64831. |
| SOURCE | Search... |
Entry information
| Entry name | S4A5_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q9BY07 Secondary accession number(s): Q32MA7 Q9HBU5 | ||||||||
| 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 2 Human chromosome 2: 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
