An evolutionarily ancient Oatp: insights into conserved functional domains of these proteins.
Cellular uptake of organic solutes is mediated in large part by a gene family of membrane transporters called OATPs (SLC21A). To study the structural determinants and evolutionary development of the SLC21A family, we have cloned and functionally characterized a highly expressed evolutionarily primitive Oatp from the liver of the small skate, Raja erinacea. A full-length cDNA (2.3 kb) was obtained that encodes a protein of 689 amino acids. The characteristics of this novel skate Oatp, including tissue expression, subcellular localization, substrate selectivity, Na(+) dependence, and inhibitor selectivity were generally similar to liver-specific human OATP-C and rat Oatp4. However, sequence comparisons with other OATPs indicate that this skate Oatp shares only approximately 40-50% amino acid identity with the liver-specific OATPs/Oatps and with human OATP-F. Further computer analysis revealed that the highest amino acid identities reside in the first external (78%) and internal loops (75%) and transmembrane domains 2 (76%), 3 (62%), 4 (70%), and 11 (64%). We propose that the conserved regions of the SLC21A transporter family may be critical structural determinants of substrate specificity and function.
Cai
Shi-Ying
SY
Liver Center, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Wang
Wei
W
Soroka
Carol J
CJ
Ballatori
Nazzareno
N
Boyer
James L
JL
D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002462:Cell Membrane / Q000737:chemistry; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000737:chemistry / Q000302:isolation & purification; D004970:Estrone / Q000031:analogs & derivatives* / Q000378:metabolism; D019143:Evolution, Molecular; D006031:Glycosylation; D006801:Humans; D008099:Liver / Q000737:chemistry*; D008969:Molecular Sequence Data; D027361:Organic Anion Transporters / Q000032:analysis / Q000737:chemistry* / Q000235:genetics*; D010802:Phylogeny; D012313:RNA / Q000032:analysis; D051381:Rats; D016415:Sequence Alignment; D012860:Skates, Fish / Q000235:genetics*; D012964:Sodium / Q000494:pharmacology; D013656:Taurocholic Acid / Q000378:metabolism; D014018:Tissue Distribution; D014316:Tritium
D018076:DNA, Complementary; D027361:Organic Anion Transporters; D014316:Tritium; D004970:Estrone; D013656:Taurocholic Acid; D012313:RNA; D012964:Sodium; C017296:estrone sulfate