SLC7 family members may be divided into two major groups: cationic amino acid transporters (CATs) and glycoprotein-associated amino acid transporters (gpaATs).

Cationic amino acid transporters are 14 TM proteins, which mediate pH- and sodium-independent transport of cationic amino acids (system y⁺), apparently as an exchange mechanism. These transporters are sensitive to inhibition by N-ethylmaleimide.

CAT4 appears to be non-functional in heterologous expression [3], while SLC7A14 has yet to be characterized.

Glycoprotein-associated amino acid transporters are 12 TM proteins, which heterodimerize with members of the SLC3 family to act as cell-surface amino acid exchangers.

Heterodimers between 4F2hc and LAT1 or LAT2 generate sodium-independent system L transporters. LAT1 transports large neutral amino acids including branched-chain and aromatic amino acids as well as miglustat, whereas LAT2 transports most of the neutral amino acids.

Heterodimers between 4F2hc and y⁺LAT1 or y⁺LAT2 generate transporters similar to the system y⁺L , which transport cationic (L-arginine, L-lysine, L-ornithine) amino acids independent of sodium and neutral (L-leucine, L-isoleucine, L-methionine, L-glutamine) amino acids in a partially sodium-dependent manner. These transporters are N-ethylmaleimide-insensitive. Heterodimers between rBAT and b^0,+AT appear to mediate sodium-independent system b^0,+ transport of most of the neutral amino acids and cationic amino acids (L-arginine, L-lysine and L-ornithine).

Asc-1 appears to heterodimerize with 4F2hc to allow the transport of small neutral amino acids (such as L-alanine, L-serine, L-threonine, L-glutamine and glycine), as well as D-serine, in a sodium-independent manner.

xCT generates a heterodimer with 4F2hc for a system x^-_e-c transporter that mediates the sodium-independent exchange of L-cystine and L-glutamic acid.

AGT has been conjugated with SLC3 members as fusion proteins to generate functional transporters, but the identity of a native heterodimer has yet to be ascertained.

* Key recommended reading is highlighted with an asterisk

* Colas C. (2020) Toward a Systematic Structural and Functional Annotation of Solute Carriers Transporters-Example of the SLC6 and SLC7 Families. Front Pharmacol, 11: 1229. [PMID:32973497]

* Kanai Y. (2021) Amino acid transporter LAT1 (SLC7A5) as a molecular target for cancer diagnosis and therapeutics. Pharmacol Ther,: 107964 [Epub ahead of print]. [PMID:34390745]

* Koppula P, Zhuang L, Gan B. (2020) Cystine transporter SLC7A11/xCT in cancer: ferroptosis, nutrient dependency, and cancer therapy. Protein Cell, [Epub ahead of print]. [PMID:33000412]

* Lin W, Wang C, Liu G, Bi C, Wang X, Zhou Q, Jin H. (2020) SLC7A11/xCT in cancer: biological functions and therapeutic implications. Am J Cancer Res, 10 (10): 3106-3126. [PMID:33163260]

1. Etoga JL, Ahmed SK, Patel S, Bridges RJ, Thompson CM. (2010) Conformationally-restricted amino acid analogues bearing a distal sulfonic acid show selective inhibition of system x(c)(-) over the vesicular glutamate transporter. Bioorg Med Chem Lett, 20 (8): 2680-3. [PMID:20303751]

2. Oda K, Hosoda N, Endo H, Saito K, Tsujihara K, Yamamura M, Sakata T, Anzai N, Wempe MF, Kanai Y et al.. (2010) L-type amino acid transporter 1 inhibitors inhibit tumor cell growth. Cancer Sci, 101 (1): 173-9. [PMID:19900191]

3. Wolf S, Janzen A, Vékony N, Martiné U, Strand D, Closs EI. (2002) Expression of solute carrier 7A4 (SLC7A4) in the plasma membrane is not sufficient to mediate amino acid transport activity. Biochem J, 364 (Pt 3): 767-75. [PMID:12049641]