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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-8-21
pubmed:databankReference
pubmed:abstractText
Several electrogenic sodium bicarbonate cotransporters have been cloned from different human organs. In the renal proximal tubule, the electrogenic sodium bicarbonate cotransporter kNBC1 (1035aa) mediates the majority of basolateral sodium bicarbonate absorption. In pancreatic ducts, the electrogenic sodium bicarbonate cotransporter pNBC1 (1079aa) mediates basolateral sodium bicarbonate influx. hNBC1 (hhNBC), cloned from human heart, is identical to pNBC1 at the amino acid level. We have demonstrated that kNBC1 and pNBC1 are highly homologous proteins that have different N-termini. In kNBC1, 41 amino acids replace the initial 85 amino acids of pNBC1. Whether these proteins are coded by one or more genes is unknown. In order to determine the genetic basis for these transcripts, we first characterized the genomic organization of the NBC1 gene (SLC4A4). NBC1 spans approximately 450 kilobases containing 26 exons that are flanked by typical splice donor and acceptor sequences at the intron-exon boundaries. Exon 1 is specific for the pNBC1 transcript. The first alternative exon of the hNBC1 transcript, containing the 5'-untranslated region, is derived from the last 43 nucleotides of intron 1 in the NBC1 gene coupled to exon 2. kNBC1 is transcribed from an alternative promoter in intron 3. In the first alternative exon of kNBC1, the last 313 nucleotides of intron 3 are coupled to exon 4, which is common to pNBC1 and hNBC1. The major transcription initiation site in kNBC1 is located 192 nucleotides upstream from the translation initiation codon. A minor start site is located 182 nucleotides upstream from the translation initiation codon. Structural analysis of the proximal kNBC1 promoter revealed an atypical TATA sequence (-33) and several potentially important transcription factor binding sites. Functional studies showed that the 5'-flanking region of the alternative kNBC1 promoter (-159 to+43) is sufficient for promoter activity. This work is the first demonstration that the three N-terminal transcripts of the human electrogenic sodium bicarbonate cotransporter NBC1 are encoded by the SLC4A4 gene. Furthermore, knowledge of the genomic organization and alternative promoter usage in the NBC1 gene provides a molecular basis for understanding disorders involving electrogenic sodium bicarbonate cotransporters and facilitates the elucidation of transcriptional control of NBC1 expression.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0378-1119
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
251
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
109-22
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10876088-Amino Acid Sequence, pubmed-meshheading:10876088-Animals, pubmed-meshheading:10876088-Base Sequence, pubmed-meshheading:10876088-Carrier Proteins, pubmed-meshheading:10876088-Cell Line, Transformed, pubmed-meshheading:10876088-DNA, pubmed-meshheading:10876088-Exons, pubmed-meshheading:10876088-Gene Expression, pubmed-meshheading:10876088-Genes, pubmed-meshheading:10876088-Humans, pubmed-meshheading:10876088-Introns, pubmed-meshheading:10876088-Luciferases, pubmed-meshheading:10876088-Molecular Sequence Data, pubmed-meshheading:10876088-Promoter Regions, Genetic, pubmed-meshheading:10876088-Recombinant Fusion Proteins, pubmed-meshheading:10876088-Sequence Alignment, pubmed-meshheading:10876088-Sequence Analysis, DNA, pubmed-meshheading:10876088-Sequence Homology, Amino Acid, pubmed-meshheading:10876088-Sodium-Bicarbonate Symporters, pubmed-meshheading:10876088-Transcription, Genetic, pubmed-meshheading:10876088-Transfection
pubmed:year
2000
pubmed:articleTitle
Structural organization of the human NBC1 gene: kNBC1 is transcribed from an alternative promoter in intron 3.
pubmed:affiliation
Division of Nephrology, UCLA School of Medicine, 10833 Le Conte Avenue, Rm 7-155 Factor Building, Los Angeles, CA 90095-1689, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't