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Two C‐Terminal Variants of NBC4, a New Member of the Sodium Bicarbonate Cotransporter Family: Cloning, Characterization, and Localization
Author(s) -
Pushkin Alexander,
Abuladze Natalia,
Newman Debra,
Lee Ivan,
Xu Gouping,
Kurtz Ira
Publication year - 2000
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/15216540050176539
Subject(s) - amino acid , cotransporter , peptide sequence , gene , biochemistry , positional cloning , solute carrier family , coding region , genetics , symporter , nucleic acid sequence , microbiology and biotechnology , biology , chemistry , transporter , sodium , locus (genetics) , organic chemistry
We report the cloning, characterization, and chromosomal assignment of a new member of the sodium bicarbonate cotransporter (NBC) family, NBC4. The NBC4 gene was mapped to chromosome 2p13 and is a new candidate gene for Alstrom syndrome. Two variants of the transporter have been isolated from human testis and heart, which differ in their C termini. NBC4a encodes a 1137‐residue polypeptide and is widely expressed in various tissues, including liver, testis, and spleen. NBC4b is identical to NBC4a except that it has a 16‐nucleotide insert, creating a C‐terminal frame shift. NBC4b encodes a 1074‐residue polypeptide and is highly expressed in heart. Amino acids 1‐1046 are common to both NBC4 variants. NBC4a has two protein‐interacting domains that are lacking in NBC4b: a proline‐rich sequence, PPPSVIKIP (amino acids 1102‐1110), and a consensus PDZ‐interacting domain, SYSL (1134‐1137). NBC4b lacks the stretch of charged residues present in the C terminus of NBC4a and other members of the NBC family.Unlike other members of the NBC family, both NBC4a and NBC4b have a unique glycine‐rich region (amino acids 440‐ 469). In comparison with other members of the bicarbonate transport superfamily, NBC4a and NBC4b are most similar structurally to the electrogenic sodium bicarbonate cotransporters (NBC1).