The lysosomal cystine transporter (LCT) family
TC# 2.A.43
is part of the

TOG Superfamily The transporter-opsin-G protein-coupled receptor (TOG) superfamily is a protein superfamily of integral membrane proteins, usually of 7 or 8 transmembrane alpha-helical segments (TMSs). It includes (1) ion-translocating microbial rhodopsins and (2) ...

and includes secondary transport proteins that are derived from animals, plants, fungi and other eukaryotes. They exhibit 7 putative transmembrane α-helical spanners ( TMSs) and vary in size between about 200 and 500 amino acyl residues, although most have between 300 and 400 residues. These proteins are found in intracellular organelles of eukaryotes, many in lysosomes. The few that have been characterized transport Cystine
TC# 2.A.43.1.1
, basic amino acids such as L-lysine and L-arginine
TC# 2.A.43.2.1
and drugs such as

fluconazole Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidiodomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and pityriasis versicolor. It is also used to pr ...

and caspofungin
TC# 2.A.43.2.7
.

Cystinosin

A protein mutated in the rare human genetic disease, nephropathic intermediate

cystinosis Cystinosis is a lysosomal storage disease characterized by the abnormal accumulation of cystine, the oxidized dimer of the amino acid cysteine. It is a genetic disorder that follows an autosomal recessive inheritance pattern. It is a rare autosom ...

, also called cystinosin
TC# 2.A.43.1.1
, is encoded by the CTNS gene. In cystinotic renal proximal tubules (RPTs), diminished cystinosin function appears to result in reduced reabsorption of solutes by other secondary transporters such as the Na⁺/Phosphate cotransporter, due to decreased expression of these other transport proteins.

Function

Evidence suggests that cystinosin transports cystine out of lysosomes in a pmf-dependent process. The proton motive force (pmf) across the lysosomal membrane is generated by a V-type ATPase which hydrolyzes cytoplasmic ATP to pump protons into the lysosomal lumen. Removal of the C-terminal GYDQL lysosomal sorting motif causes cystinosin to migrate to the plasma membrane with the intralysosomal face of cystinosin facing the extracellular medium. The cells then take up cystine in a pmf-dependent process.

Homologues

Distant homologues include the Lec15/Lec35 suppressor, SL15, of Chinese hamster ovary cells and ERS1, the ERD suppressor in ''S. cerevisiae''. Both of these suppressors, when overexpressed, have been reported to influence retention of lumenal endoplasmic reticular proteins as well as glycosylation in the Golgi apparatus. The Lec15 and Lec35 mutations are characterized by inefficient synthesis and utilization, respectively, of mannose-P-dolichol for glycolipid biosynthesis. All proteins in the LCT family are distantly related to the proteins of the microbial rhodopsin (MR) family
TC #3.E.1
, an established member of the

, which exhibit a 7 TMS topology.

Reaction

The reaction believed to be catalyzed by cystinosin is: ::Cystine (intralysosomal space) + H⁺ (intralysosomal space) → Cystine (cytoplasm) + H⁺ (cytoplasm)

References

{{Portal bar, Biology, border=no Integral membrane proteins