An evolutionarily ancient Oatp: insights into conserved functional domains of these proteins

• Published in: American journal of physiology: Gastrointestinal and liver physiology Vol. 282; no. 4; pp. G702 - G710
• Main Authors: Cai, Shi-Ying, Wang, Wei, Soroka, Carol J, Ballatori, Nazzareno, Boyer, James L
• Format: Journal Article
• Language: English
• Published: United States 01.04.2002
• Subjects: Algorithms; Amino Acid Sequence; Animals; Blotting, Northern; Blotting, Western; Cell Membrane - chemistry; Conserved Sequence; DNA, Complementary - chemistry; DNA, Complementary - isolation & purification; Estrone - analogs & derivatives; Estrone - metabolism; Evolution, Molecular; Glycosylation; Humans; Liver - chemistry; Molecular Sequence Data; Organic Anion Transporters - analysis; Organic Anion Transporters - chemistry; Organic Anion Transporters - genetics; Phylogeny; Rats; RNA - analysis; Sequence Alignment; Skates (Fish) - genetics; Sodium - pharmacology; Taurocholic Acid - metabolism; Tissue Distribution; Tritium
• ISSN: 0193-1857; 1522-1547
• DOI: 10.1152/ajpgi.00458.2001

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.