SLC3A1
Function
Acts as a chaperone that facilitates biogenesis and trafficking of functional transporter heteromers to the plasma membrane (By similarity) (PubMed:10588648, PubMed:11318953, PubMed:16609684, PubMed:16825196, PubMed:32494597, PubMed:32817565, PubMed:7686906, PubMed:8486766, PubMed:8663184, PubMed:8663357). Associates with SLC7A9 to form a functional transporter complex that mediates the electrogenic exchange between cationic amino acids and neutral amino acids, with a stoichiometry of 1:1. SLC7A9-SLC3A1 transporter has system b(0,+)-like activity with high affinity for extracellular cationic amino acids and L-cystine and lower affinity for intracellular neutral amino acids. Substrate exchange is driven by high concentration of intracellular neutral amino acids and the intracellular reduction of L-cystine to L-cysteine. SLC7A9-SLC3A1 acts as a major transporter for reabsorption of L-cystine and dibasic amino acids across the brush border membrane in early proximal tubules (PubMed:10588648, PubMed:11318953, PubMed:16609684, PubMed:16825196, PubMed:32494597, PubMed:32817565, PubMed:7686906, PubMed:8486766, PubMed:8663184, PubMed:8663357). Associates with SLC7A13 to form a functional complex that transports anionic and neutral amino acids via exchange or facilitated diffusion. SLC7A13-SLC3A1 may act as a major transporter for L-cystine in late proximal tubules, ensuring its reabsorption from the luminal fluid in exchange for cytosolic L-glutamate or L-aspartate (By similarity).
Involvement in disease
Cystinuria
CSNU
An autosomal disorder characterized by impaired epithelial cell transport of cystine and dibasic amino acids (lysine, ornithine, and arginine) in the proximal renal tubule and gastrointestinal tract. The impaired renal reabsorption of cystine and its low solubility causes the formation of calculi in the urinary tract, resulting in obstructive uropathy, pyelonephritis, and, rarely, renal failure.
None
The disease is caused by variants affecting the gene represented in this entry.
Hypotonia-cystinuria syndrome
HCS
Characterized generalized hypotonia at birth, nephrolithiasis, growth hormone deficiency, minor facial dysmorphism, failure to thrive, followed by hyperphagia and rapid weight gain in late childhood.
None
The disease is caused by variants affecting the gene represented in this entry. Hypotonia-cystinuria syndrome is a contiguous gene syndrome caused by a homozygous deletion on chromosome 2p21 that disrupts the gene represented in this entry and PREPL (PubMed:16385448, PubMed:21686663). A homozygous 77.4-kb deletion that disrupts the gene represented in this entry, PREPL, and CAMKMT, causes atypical hypotonia-cystinuria syndrome, characterized by mild to moderate intellectual disability and respiratory chain complex IV deficiency (PubMed:21686663).
Tissue Specificity
Expressed in the brush border membrane in the kidney (at protein level). Predominantly expressed in the kidney, small intestine and pancreas. Weakly expressed in liver.
Cellular localization
- Cell membrane
- Single-pass type II membrane protein
- Apical cell membrane
- Single-pass type II membrane protein
Alternative names
NBAT, SLC3A1, Amino acid transporter heavy chain SLC3A1, D2h, Neutral and basic amino acid transport protein, Solute carrier family 3 member 1, rBAT