Reaction participants Show >> << Hide
- Name help_outline L-aspartate Identifier CHEBI:29991 Charge -1 Formula C4H6NO4 InChIKeyhelp_outline CKLJMWTZIZZHCS-REOHCLBHSA-M SMILEShelp_outline [NH3+][C@@H](CC([O-])=O)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 76 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline L-glutamate Identifier CHEBI:29985 (CAS: 11070-68-1) help_outline Charge -1 Formula C5H8NO4 InChIKeyhelp_outline WHUUTDBJXJRKMK-VKHMYHEASA-M SMILEShelp_outline [NH3+][C@@H](CCC([O-])=O)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 249 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:76307 | RHEA:76308 | RHEA:76309 | RHEA:76310 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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Publications
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Novel cystine transporter in renal proximal tubule identified as a missing partner of cystinuria-related plasma membrane protein rBAT/SLC3A1.
Nagamori S., Wiriyasermkul P., Guarch M.E., Okuyama H., Nakagomi S., Tadagaki K., Nishinaka Y., Bodoy S., Takafuji K., Okuda S., Kurokawa J., Ohgaki R., Nunes V., Palacin M., Kanai Y.
Heterodimeric amino acid transporters play crucial roles in epithelial transport, as well as in cellular nutrition. Among them, the heterodimer of a membrane protein b(0,+)AT/SLC7A9 and its auxiliary subunit rBAT/SLC3A1 is responsible for cystine reabsorption in renal proximal tubules. The mutatio ... >> More
Heterodimeric amino acid transporters play crucial roles in epithelial transport, as well as in cellular nutrition. Among them, the heterodimer of a membrane protein b(0,+)AT/SLC7A9 and its auxiliary subunit rBAT/SLC3A1 is responsible for cystine reabsorption in renal proximal tubules. The mutations in either subunit cause cystinuria, an inherited amino aciduria with impaired renal reabsorption of cystine and dibasic amino acids. However, an unsolved paradox is that rBAT is highly expressed in the S3 segment, the late proximal tubules, whereas b(0,+)AT expression is highest in the S1 segment, the early proximal tubules, so that the presence of an unknown partner of rBAT in the S3 segment has been proposed. In this study, by means of coimmunoprecipitation followed by mass spectrometry, we have found that a membrane protein AGT1/SLC7A13 is the second partner of rBAT. AGT1 is localized in the apical membrane of the S3 segment, where it forms a heterodimer with rBAT. Depletion of rBAT in mice eliminates the expression of AGT1 in the renal apical membrane. We have reconstituted the purified AGT1-rBAT heterodimer into proteoliposomes and showed that AGT1 transports cystine, aspartate, and glutamate. In the apical membrane of the S3 segment, AGT1 is suggested to locate itself in close proximity to sodium-dependent acidic amino acid transporter EAAC1 for efficient functional coupling. EAAC1 is proposed to take up aspartate and glutamate released into luminal fluid by AGT1 due to its countertransport so that preventing the urinary loss of aspartate and glutamate. Taken all together, AGT1 is the long-postulated second cystine transporter in the S3 segment of proximal tubules and a possible candidate to be involved in isolated cystinuria. << Less
Proc. Natl. Acad. Sci. U.S.A. 113:775-780(2016) [PubMed] [EuropePMC]
This publication is cited by 9 other entries.