Phenylalanine:H⁺ symporter, PheP of 458 aas and 12 established TMSs (Pi and Pittard 1996; Pi et al. 2002).  Catalytic residues have been identified (Pi et al. 1993), and interhelical interactions have been proposed (Dogovski et al. 2003).

Bacteria

PheP of E. coli

Serine/Threonine transport protein, YifK of 461 aas and 12 TMSs in a probable 6 + 6 TMS arrangement (Khozov et al. 2023).

Bacteria

YifK of Escherichia coli

YdgF of Bacillus subtilis (P96704)

D-serine/L-alanine/D-alanine/glycine/D-cycloserine uptake porter of 556 aas, CycA.  Can be mutated to D-cycloserine (a seconary line antitubercular drug) resistance (Chen et al. 2012).

Actinobacteria

CycA of Mycobacterium bovis

The lysine specific transporter, LysP of 488 aas and 12 TMSs (Trip et al. 2013).

Firmicutes

LysP of Lactococcus lactis

Transporter of lysine, histidine and arginine, HisP or LysQ, of 477 aas and 12 TMSs (Trip et al. 2013).

Firmicutes

LysQ (HisP) of Lactococcus lactis

Lysine:H⁺ symporter. Forms a stable complex with CadC to allow lysine-dependent adaptation to acidic stress (Rauschmeier et al. 2013). The Salmonella orthologue is 95% identical to the E. coli protein and is highly specific for Lysine. Residues involved in lysine binding have been identified (Kaur et al. 2014).

Bacteria

LysP of E. coli

Serine transporter, SerP2 or YdgB, of 459 aas and 12 TMSs (Trip et al. 2013). Transports L-alanine (K_m = 20 μM), D-alanine (K_m = 38 μM), L-serine, D-serine (K_m = 356 μM) and glycine (Noens and Lolkema 2015). The encoding gene is adjacent to the one encoding SerP1 (TC# 2.A.3.1.21).

Firmicutes

SerP2 of Lactococcus lactis

Serine uptake transporter, SerP1, of 259 aas and 12 TMSs (Trip et al. 2013). L-serine is the highest affinity substrate (K_m = 18 μM), but SerP1 also transports L-threonine and L-cysteine (K_m values = 20 - 40 μM).  Does not transport D-serine (Noens and Lolkema 2015). The encoding gene is adjacent to a paralogue (serP2) with broad specificity for D- and L-small semipolar amino acids and glycine (see TC# 2.A.3.1.20).

Firmicutes

SerP1 of Lactococcus lactis

Transporter for phenylalainine, tyrosine and tryptophan of 449 aas and 12 TMSs, FywP or YsjA (Trip et al. 2013).

Firmicutes

FywP of Lactococcus lactis

ProY of 457 aas and 12 TMSs.  96% identical to ProY of Salmonella enterica, a cryptic proline transporter in this organism (Liao et al. 1997).

ProY of E. coli

Asparagine transporter of 499 aas and 12 TMSs, 91% identical to the orthologue in Salmonella enterica (2.A.3.1.8) (Jennings et al. 1995).

AnsP of E. coli

D-serine/D-alanine/glycine transporter, LysP or AnsP, of 453 aas and 11 TMSs (Xiao et al. 2020).

LysP of Corynebacterium glutamicum

Aromatic amino acid:H⁺ symporter, AroP of 457 aas and 12 TMSs (Cosgriff and Pittard 1997). Transports phenylalanine, tyrosine and tryptophan (Honoré and Cole 1990).

Bacteria

AroP of E. coli

γ-aminobutyrate:H⁺ symporter, GabP. It also transports a variety of pyridine carboxylates. Phosphatidylethanolamine is required for its proper topological organization(Zhang et al. 2005).

Bacteria

GabP of E. coli

β-alanine/γ-aminobutyrate/proline/3,4-dehydroproline:H⁺ symporter, GabP (Ferson et al. 1996; Zaprasis et al. 2014).  Also transports 3-aminobutyrate, 3-aminopropanoate, cis-4-aminobutenoate (Brechtel and King 1998).

Bacteria

GabP of Bacillus subtilis

D-Serine/D-alanine/glycine/D-cycloserine:H⁺ symporter (regulated by the small RNA, GcvB; Pulvermacher et al., 2009).  The system is active after growth in minimal medium but not after growth in complex medium (Baisa et al. 2013).

Bacteria

CycA of E. coli (P0AAE0)

Asparagine permease (AnsP) of 497 aas and 12 TMSs (Jennings et al. 1995).

Bacteria

AnsP of Salmonella typhimurium

Lysine permease of 611 aas and 13 putative TMSs, Lyp1.  Extracellular loops affect either the localization or activity of Lyp1. Half of the mutants are located in the extension of extracellular loop 3 or in a predicted alpha-helix in extracellular loop 4 (Van't Klooster et al. 2020). Phosphatidylserine and ergosterol are essential for Lyp1 function, and the transport activity displays a sigmoidal relationship with the concentration of these lipids. Lyp1 requires a relatively high fraction of lipids with one or more unsaturated acyl chains. Possibly a narrow band of lipids immediately surrounding the transmembrane stalk of a model protein allows conformational changes in the protein (Van't Klooster et al. 2020).

Yeast

Lyp1 of Saccharomyces cerevisiae (P32487)

S-adenosylmethionine uptake permease, SAM3 (also takes up polyamines, glutamate, lysine and the toxic S-adenosylmethionine analogue sinefungin) (Uemura et al., 2007; Zheng et al., 2007; Kashiwagi and Igarashi 2011).

Yeast

SAM3 or Agp3 (YPL274w) of Saccharomyces cerevisiae (Q08986)

The high affinity carnitine/polyamine (spermidine > putrescine)/carnitine), low affinity amino acid transporter, AGP2, of 596 aas and 12 TMSs (Aouida et al., 2005; Uemura et al., 2007).  Loss of the yeast transporter Agp2 upregulates the pleiotropic drug-resistant pump Pdr5 (TC# 3.A.1.205.1) and confers resistance to the protein synthesis inhibitor, cycloheximide (Manzoor et al. 2024).

Yeast

AGP2 of Saccharomyces cerevisiae (P38090)

General amino acid permease (all L-amino acids and some D-amino acids as well as β-alanine, polyamines and GABA). Systematic mutational analysis of the intracellular regions of yeast Gap1 permease revealed multiple intracellular regions involved in its secretion, transport activity, and down-regulation (Igarashi and Kashiwagi 2010; Merhi et al., 2011). GAP1 is a "transceptor", fuctioning in both transport and reception, necessary for cAMP-independent activation of the Protein Kinase A pathway under conditions of re-addition of amino acids to cells previously starved for amino acids (Diallinas 2017).

Yeast

Gap1 of Saccharomyces cerevisiae (P19145)

Amino acid permease, GAP1. Transports Arg, Met, Leu and Phe (Kraidlova et al., 2011).

Yeast

GAP1 of Candida albicans (Q5AG77)

General amino and permease and transceptor, GAP2. Transports all amino acids including citruline and eight tested toxic amino acid derivatives (Kraidlova et al., 2011).

Yeast

GAP2 of Candida albicans (Q59YT0)

Arginine transporter, GAP4 (Kraidlova et al., 2011)

Yeast

GAP4 of Candida albicans (Q59W33)

General amino acid porter, GAP6. Transports almost all amino acids tested except arginine and citruline (Kraidlova et al., 2011).

Yeast

GAP6 of Candida albicans (Q59NZ6)

Probable amino-acid permease Meu22 (Meiotic expression up-regulated protein 22)

Meu22 of Schizosaccharomyces pombe

Tryptophan permease, Tat2. Regulated via endocytosis by ATP-binding Cassette Transporters, Pdr5 (3.A.1.205.1) and Yor1 (3.A.208.3) as well as a seven-transmembrane protein, RSB1 (9.A.27.1.2) (Johnson et al., 2010).  Residues involved in binding and catalysis have been identified (Kanda and Abe 2013).  residues and regions important for proper folding and ER retention have been identified (Mochizuki et al. 2015). Tat2 may be a target of the anti-fungal agent, glabridine (Kalli et al. 2023).

Yeast

Tat2 of Saccharomyces cerevisiae (P38967)

The plasma membrane polyamine (putrescine, spermidine):H⁺ uptake symporter, LmPOT1 (inhibited by pentamidine and protonophores) (Hasne and Ullmann, 2005; Zhang et al. 2022).

Protozoans

POT1 of Leishmania major (AAW52506)

The putriscene-cadaverine polyamine uptake porter, POT1.1 (613aas; 12-13 TMSs) Also called PAT12; transports paraquot as well as polyamines (Soysa et al. 2013; Fujita and Shinozaki 2014)

Euglenozoa

POT1.1 of Trypansosoma cruzi

Plasma membrane polyamine/paraquot uptake transporter of 490 aas, RMV1. Also called PUT3 and LAT1. Mutations give rise to partial paraquot (a toxic common herbicide that generates superoxide and reactive oxygen species (ROS)) (Fujita and Shinozaki 2014).

Plants

RMV1 of Arabidopsis thaliana

Golgi polyamine/paraquot uptake transporter of 478 aas, LAT4. Also called PUT2 and PAR1.  Mutations give rise to paraquot resistance (Par1) both in A. thaliana and in rice.  Probably present in the chloroplast membrane (Fujita and Shinozaki 2014).

Plants

LAT4 of Arabidopsis thaliana

Spermidine-preferring polyamine transporter, PUT1 of 531 aas.  Also transports paraquot (Fujita and Shinozaki 2014).

Plants

PUT1 of Oryza sativa

The hydrophobic amino acid efflux transporter, YjeH (exports L-methionine and other neutral, hydrophobic amino acids such as Leu, Ile and Val; R. Figge, personal communication; Liu et al. 2015).

Bacteria

YjeH of E. coli (P39277)

The Ceftriaxone resistance porter, YjeH (Hu et al. 2007).

Proteobacteria

YjeH of Salmonella enterica (serovar Typhimurium) (Q8ZKC0)

L-Leucine uptake porter, YjeH, of 426 aas and 11 or 12 TMSs (Deutschbauer et al. 2011).

YjeH of Shewanella oneidensis

APC family member; Ala/Val/Leu-rich protein encoded within an operon that also encodes a 23S rRNA methyl transferase, RumA. Two half sized TrkA proteins are encoded within an operon that is divergently transcribed. Possibly, they regulate transport.

Bacteria

AVL-rich protein of Salinispora tropica (A4X503)

Uncharacterized transporter

Actinobacteria

Uncharacterized porter of Streptomyces coelicolor

APC protein with 610 aas and 12 TMSs.  77% identical to an orthologue in Weissella viridescens that serves as a receptor or uptake transporter for the two peptide bacteriocin, plantaricin JK (1.C.30.1.1) (Oppegård et al. 2016; Ekblad et al. 2017).

APC uptake porter of Weissella confusa

Hypothetical transporter  (H.T.) (442 aas; 13 TMSs)

Archaea

H.T. of Picrophilus torridus (Q6L0Y3) 

Cationic amino acid transporter, CAAT (462 aas; 12 TMSs) 

Archaea

CAAT of Thermoplasma acidophilum (Q9HJ13)

Amino acid permease (AAP) (417 aas; 12 TMSs) 

Archaea

AAP of Sulfolobus solfataricus (Q97YX9)

Hypothetical protein (H.P.) 

Eukaryotes

H.P. of Dictyostelium discoideum (Q54KK4)

Uncharacterized transporter

Actinobacteria

Uncharacterized porter of Streptomyces coelicolor

Putrescine:ornithine antiporter for putrescine export; putrescine:H⁺ symporter for uptake (Igarashi and Kashiwagi 1996). Modeling tools have been used to gain information about the structures and functions of CadB and PotE in E. coli (Tomitori et al., 2012).

Bacteria

PotE of E. coli (P0AAF1)

Arginine/Ornithine antiporter of 497 aas and 13 TMSs, ArcD2 (Trip et al. 2013).

Firmicutes

ArcD2 of Lactococcus lactis

Arginine/Ornithine antiporter of 526 aas and 14 TMSs (Trip et al. 2013).

Firmicutes

ArcD1 of Lactococcus lactis

Cadaverine:lysine antiporter [Catalyzes cadaverine uptake via H⁺ symport (Km=21μM) and cadaverine export (Km=300 μM) via cadaverine:lysine antiport.] (Soksawatmaekhin et al., 2004). Modeling tools have been used to gain information about the structures and functions of CadB and PotE in E. coli (Tomitori et al., 2012).

Bacteria

CadB of E. coli (P0AAE8)

Homodimeric electrogenic arginine (Km=80μM):agmatine antiporter, AdiC, involved in extreme acid resistance (Fang et al., 2007; Gong et al., 2003; Iyer et al., 2003). A projection structure at 6.5 Å resolution has been published (Casagrande et al., 2008), and the 3.2 Å resolution X-ray structure was determined by Fang et al., 2009 and Gao et al., 2009. Protonation of glutamate 208 induces release of agmatine in the outward-facing conformation (Zomot and Bahar, 2011). The 3.0 Å structure of an Arg-bound form in an open-to-out conformation completed the picture of the major states of the porter during the transport cycle (Kowalczyk et al., 2011). Aromatic residues may regulate access to both the outward- and inward-facing states (Krammer et al. 2016). Both the glutamate- and arginine (AdiC; TC# 2.A.3.2.5)-dependent acid resistance systems increase the internal pH and reverse the transmembrane potential (Richard and Foster 2004).

Bacteria

YjdE (AdiC) of E. coli (P39269)

The histidine/histamine antiporter, HdcP of 490 aas and 13 TMSs (Trip et al. 2013).

Firmictues

HdcP of Streptococcus thermophilus

Cationic amino acid transporter 3 (CAT-3) (CAT3) (Cationic amino acid transporter y+) (Solute carrier family 7 member 3). Mutations in CAT3 are potential causes of childhood epilepsy (Sourbron et al. 2021).

Animals

SLC7A3 of Homo sapiens

Bacteria

Uncharacterized amino acid transporter

Actinobacteria

Uncharacterized permease of Streptomyces coelicolor

Uncharacterized APC-3 family member

Actinobacteria

U-APC3a of Streptomyces coelicolor

Uncharacterized transporter

Proteobacteria

Uncharacterized transporter of Myxococcus xanthus

Histamine uptake transporter; involved in the utilization of histamine as a nitrogen source.  In an operon with two histamine catabilic enzymes, and all are induced by hsitamine (Johnson et al. 2008).

Proteobacteria

Histamine uptake transporter of Pseudomonas aeruginosa

APC family member of 663 aas and 12 TMSs.

Fungi

APC porter of Phytophthora infestans

Uncharacterized protein of 490 aas and 12 TMSs

Firmicutes

UP of Alicyclobacillus acidoterrestris

Amino acid transporter, PotE, of 475 aas.

Firmicutes

PotE of Caldanaerobacter subterraneus subsp. tengcongensis (Thermoanaerobacter tengcongensis)

Branched chain amino acid (Leucine/isoleucine/valine) uptake transporter of 469 aas and 12 TMSs, BcaP or CitA (den Hengst et al. 2006).

Firmicutes

BcaP (CitA) of Lactococcus lactis

Plastidic cationic amino acid transporter, CAT, of 582 aas and 14 TMSs.  Exports phenylalanine, tyrosine and tryptophan our of chloroplasts into the cytoplasm (Widhalm et al. 2015).

CAT of Petunia hybrida

Amino acid transporter, AAT1 or CAT1, of 594 aas and 14 TMSs. It is a high-affinity permease involved in the transport of the cationic amino acids (e.g., arginine, lysine, histidine, citrulline, valine, and glutamate). It transports mostly basic amino acids, and, to a lesser extent, neutral and acidic amino acids. It probably functions as a proton symporter. It transports histidine with a Km of 35 μM at Ph 4.5, the optimal pH for this system (Frommer et al. 1995).  Amino acid transporter (AAT) genes regulate seed protein content in chickpea (Cicer arietinum L.) (Kalwan et al. 2023).

Plants

AAT1 of Arabidopsis thaliana

solute carrier family 7 (orphan transporter), member 14, SLC7A14 of 771 aas and 15 or 16 TMSs. SLC7A14 mutations occur in patients with inherited retinal dystrophy (autosomal recessive retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) (Guo et al. 2019). It is a pH-dependent, trans-stimulated, low affinity cationic amino acid (e.g., arg and lys) system that is inhibited by α-trimethyl-L-lysine, properties assigned to lysosomal transport system c in human skin fibroblasts (Jaenecke et al. 2012).

Animals

SLC7A14 of Homo sapiens

Low affinity cationic amino acid transporter 2 (CAT-2) (CAT2) (Solute carrier family 7 member 2) (Closs 1996). Elevated SLC7A2 expression is associated with an abnormal neuroinflammatory response and nitrosative stress in Huntington's disease (Gaudet et al. 2024).

Animals

SLC7A2 of Homo sapiens

High affinity cationic amino acid transporter 1 (CAT-1) (CAT1, CTR1) (Ecotropic retroviral leukemia receptor homologue) (ERR), (SLC7a1) (System Y+ basic amino acid transporter) (Closs 1996). It takes up Arginine, Lysine and Ornithine. Its gene shows increased expression in various cancers such as colorectal cancer (CRC) (Okita et al. 2020). Treatment of a blood-brain barrier (BBB) mimetic with CAT-1 substrates as well as knockdown of CAT-1 expression yielded increases in leptin transport.Thus, an amino acid transporter is a regulator of leptin BBB transport in the iPSC-derived BBB model. These results provide insight into regulation of hormone transport across the BBB (Shi et al. 2022).  It is a possible drug target for pheochromocytomas and paragangliomas (PPGLs), rare neuroendocrine tumors (Vit et al. 2023).

Animals

SLC7A1 of Homo sapiens

The single high affinity plasma membrane choline transporter of 563 aas and 12 TMSs. Expression of the CTR/HNM1 gene in wild-type cells is regulated by phospholipid precursors, inositol and choline, but no such effect is seen in cells bearing mutations in the phospholipid regulatory genes INO2, INO4 and OPI1. There is no regulation by INO2 and OPI1 in the absence of a conserved decamer motif. However constructs lacking this sequence are still controlled by INO4. Other substrates of the choline permease, i.e., ethanolamine, nitrogen mustard and nitrogen half mustard do not regulate expression of CTR/HNM1 (Li and Brendel 1993). Exposing cells to increasing levels of choline results in two different regulatory mechanisms. Initial exposure to choline results in a rapid decrease in Hnm1-mediated transport activity, whereas chronic exposure results in Hnm1 degradation through an endocytic mechanism that depends on the ubiquitin ligase Rsp5 and the casein kinase 1 redundant pair Yck1/Yck2 (Fernández-Murray et al. 2013).

Yeast

Ctr (Hnm1) of Saccharomyces cerevisiae

γ-aminobutyric acid (GABA) permease, Uga4 (also transports the polyamine, putrescine) (Uemura et al., 2007; Kashiwagi and Igarashi 2011).

Yeast

Uga4 of Saccharomyces cerevisiae (NP_010071)

The 7-keto-8-aminopelargonic acid (KAPA) transporter, Bio5 (Phalip et al., 1999).

The polyamine (putrescine > spermidine > spermine) exporter, Tpo5p (Ykl174c) [found in the Golgi or post-Golgi secretory vesicles; induction:spermine > spermidine > putrescine] (Igarashi and Kashiwagi 2010).

Yeast

Tpo5 of Saccharomyces cerevisiae

The thiamine (vitamin B₁) transporter, Thi9 (SPAC9.10). Uptake is inhibited by pyrithiamine, oxythiamine, amprolium, and the thiazole part of thiamine indicating that these compounds are substrates of Thi9 (Vogl et al., 2008).

Yeast

Thi9 of Schizosaccharomyces pombe (Q9UT18)

Uncharacterized amino acid transporter

Actinobacteria

Uncharacterized permease of Streptomyces coelicolor

SwnT of 501 aas and 12 TMSs in a 6 + 6 TMS arrangement. Slafractonia leguminicola infects red clover and other legumes, causing black patch disease. This fungus produces two mycotoxins, slaframine and swainsonine, that are toxic to livestock grazing on clover hay or pasture infested with S. leguminicola. Swainsonine toxicosis causes locoism, while slaframine causes slobbers syndrome. SwnT may play a role in pathogenesis in addition to mycotoxin transport (Das et al. 2023).

SwnT of Slafractonia leguminicola

Archaea

MtbP of Methanoscarina acetivorans (Q8TN67).

ApcT, a proton coupled broad specificity amino acid transporter.  3-d structure available at 2.3Å resolution (3GIA_A; Shaffer et al., 2009).

Archaea

ApcT of Methanocaldococcus jannaschii (Q58026)

YbaT of Escherichia coli

Bacteria

Glutamate:γ-aminobutyrate antiporter of 477 aas and 12 TMSs, GadC.  Expression of gadCB in L. lactis in the presence of chloride is increased when the culture pH decreases to low levels, while glutamate stimulated gadCB expression (Sanders et al. 1998). These genes encode a glutamate-dependent acid resistance mechanism that is optimally active when needed for acid neutralization.

Bacteria

GadC of Lactococcus lactis

The GadC homologue

Bacteria

YcaM of E.coli (P75835)

Glutamate:GABA antiporter, GadC (YcaM). GadC, transports GABA/Glu only under acidic conditions, with no detectable activity at pH  values higher than 6.5 (Ma et al., 2012). Ma et al. (2012) determined the crystal structure of GadC at 3.1 Å resolution under basic conditions. GadC, comprising 12 TMSs, exists in a closed state, with its carboxy-terminal domain serving as a plug to block an otherwise inward-open conformation. Structural and biochemical analyses revealed the essential transport residues, identified the transport path and suggested a transport mechanism involving the rigid-body rotation of a helical bundle for GadC and other amino acid antiporters.  Both this glutamate- and the arginine (AdiC; TC#2.A.3.2.5)-dependent acid resistance systems increase the internal pH and reverse the transmembrane potential (Richard and Foster 2004).

Bacteria

GadC of E. coli (C8U8G2)

Inner membrane transporter, YgjI or GadC. Catalyzes L-glutamate:γ-amino butyrate (GABA) antiport (De Biase and Pennacchietti 2012).

Bacteria

YgjI of E. coli

Inner membrane transporter, YjeM of 500 aas and 12 TMSs. Probably an amino acid transporter, possibly an amino acid:organic amine antiporter.

Bacteria

YjeM of E. coli

Aspartate/Glutamate transporter of 488 aas and 12 TMSs, AcaP (Trip et al. 2013).

Firmicutes

AcaP of Lactococcus lactis

Putriscine/agmatine transporter of 466 aas and 12 TMSs, AguD or YrfD (Trip et al. 2013).

Firmicutes

AguD of Lactococcus lactis

L-type neutral amino acid transporter, LAT1 (Na⁺-independent) (prefers amino acids with branched or aromatic side chains: Phe, Ile, Leu, Val, Trp, His; catalyzes obligatory exchange with μM affinities on the outside and mM affinities on the inside [1000x difference]). Both LAT1 and LAT2 (2.A.3.8.6) catalyze uptake of S-nitroso-L-cysteine. These and other LAT family members are specifically inhibited by 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid (Li and Whorton, 2005). Mediates tryptophan:kynurenine exchange (Kaper et al., 2007). Also transports thyroid hormones and their derivatives (Kinne et al., 2011; Krause and Hinz 2017; Krause and Hinz 2019).  The chicken orthologue transports thyrold hormones, especially T2, with low affinity (Nele Bourgeois et al. 2016). Lat1 transports 26 biologically active ultrashort peptides (USPs) into cells as is also true of LAT2 and PEPT1 (Khavinson et al. 2023). The sizes and structures of ligand-binding sites of the amino acid transporters LAT1, LAT2, and of the peptide transporter PEPT1 are sufficient for the transport of the 26 biologically active di-, tri-, and tetra-peptides. Comparative analyses of the binding of all possible di- and tri-peptides (8400 compounds) at the binding sites of the LAT and PEPT family transporters was considered (Khavinson et al. 2023). The 26 biologically active USPs systematically showed higher binding scores to LAT1, LAT2, and PEPT1, as compared with di- and tri-peptides. Most of the 26 studied USPs were found to bind to the LAT1, LAT2, and PEPT1 transporters more efficiently than the previously known substrates or inhibitors of these transporters. Peptides ED, DS, DR, EDR, EDG, AEDR, AEDL, KEDP, and KEDG, and peptoids DS7 and KE17 with negatively charged Asp^- or Glu^- amino acid residues at the N-terminus and neutral or positively charged residues at the C-terminus of the peptide were found to be the most effective ligands of the transporters under investigation. It can be assumed that the antitumor effect of the KE, EW, EDG, and AEDG peptides could be associated with their ability to inhibit the LAT1, LAT2, and PEPT1 amino acid transporters (Khavinson et al. 2023). LAT1 enables T cell activation under inflammatory conditions in mice (Ogbechi et al. 2023).

Animals

LAT1 of Rattus norvegicus (Q63016)

Aromatic amino acid exchanger, AAT-9 (Veljkovic et al., 2004b)

Animals

AAT-9 of Caenorhabditis elegans (Q9NA91)

The aromatic-preferring amino acid transporter (ArpAT or Slc7a15). Functions with rBAT or 4F2hc (8.A.9) and transports preferentially tyr and 3,4-dihydroxyphenylalanine (L-DOPA), but also ala, glu, ser, cys and arg by a Na⁺-independent mechanism (present in mouse, rat, dog and chicken, but silenced in humans and chimps)(Fernández et al., 2005; Sato et al., 2005).  It is expressed in the CNS (Sreedharan et al. 2011).

Animals

ArpAT of Mus musculus (Q50E62)

The Ser/Thr exchange transporter (SteT) (also transports aromatic amino acids with lower efficiency) (Reig et al., 2007). The substrate-bound state of SteT shows increased conformational flexibility and kinetic stability, enabling transport of substrate across the cell membrane (Bippes et al. 2009). TMS8 sculpts the substrate-binding site and undergoes conformational changes during the transport cycle of SteT (Bartoccioni et al., 2010). Mutations allow substrate binding but not translocation. Other mutations stabilize the protein and result in higher production levels (Rodríguez-Banqueri et al. 2016).

Bacteria

SteT of Bacillus subtilis (O34739)

Low-affinity methionine permease, MUP3

Bacteria

FrlA of Escherichia coli

Cystine/glutamate antiporter (Amino acid transport system xCT; Asc1; CD98hc) (Calcium channel blocker resistance protein CCBR1) (Solute carrier family 7 member 11; SLC7A11).  The pathology and development of non-competive diaryl-isoxazole inhibitors have been presented (Newell et al. 2013).  In Lama paco (alpaca), the Slc7a11 porter of 503 aas and 12 TMSs probably functions in melanogenesis and coat color regulation (Tian et al. 2015).  It interacts with mucin-1 (MUC1-C; P15941) which forms a complex with xCT. It also forms a complex with SLC3A2 heavy chain (CD98hc, 4F2hc or MDU1 (TC# 8.A.9.2.2). Together they maintain glutathione levels and redox balance and influence cancer development (Hasegawa et al. 2016). xCT is the receptor for Kaposi's sarcoma-associated herpesvirus (KSHV, human herpesvirus 8), the causative agent of Kaposi's sarcoma and other lymphoproliferative syndromes often associated with HIV/AIDS (Kaleeba and Berger 2006). Sulfasalazine is an inhibitor of xCT that is known to increase cellular oxidative stress, giving it anti-tumor potential, but it seems to have many side effects (Nagane et al. 2018). xCT is a cancer stem cell-related target and can be used to develop preclinical therapeutic approaches, able to hamper tumor growth and dissemination (Ruiu et al. 2019). Residues involved in substrate binding have been proposed based on in silico approaches (Sharma and Anirudh 2019). The tissue distribution of xCT in chickens has been determined (Choi et al. 2020). xCT supports tumor cell growth through glutathione-based oxidative stress resistance, and mutations can enhance its stability (Oda et al. 2020). Signals of pseudo-starvation unveiled that SLC7A11 is key determinant in the control of Treg (T) cell proliferative potential (Procaccini et al. 2021). xCT antiporter function inhibits HIV-1 infection (Rabinowitz et al. 2021). SLC7A11 providess a gateway of metabolic perturbation and ferroptosis vulnerability in cancer (Lee and Roh 2022). CEBPG (CCAAT Enhancer Binding Protein Gamma) suppresses ferroptosis through transcriptional control of SLC7A11 in ovarian cancer (Zhang et al. 2023). xCT protects cancer cells from oxidative stress and is overexpressed in many cancers. Yan et al. 2023 reported that, whereas moderate overexpression of SLC7A11 is beneficial for cancer cells treated with H₂O₂, a common oxidative stress inducer, its high overexpression dramatically increases H₂O₂-induced cell death. Mechanistically, high cystine uptake in cancer cells with high overexpression of SLC7A11 in combination with H₂O₂ treatment results in toxic buildup of intracellular cystine and other disulfide molecules, NADPH depletion, redox system collapse, and rapid cell death (likely disulfidptosis). Additionally, high overexpression of SLC7A11 promotes tumor growth but suppresses tumor metastasis, likely because metastasizing cancer cells with high expression of SLC7A11 are particularly susceptible to oxidative stress. Our findings reveal that xCT expression level dictates cancer cells' sensitivity to oxidative stress and suggests a context-dependent role for SLC7A11 in tumor biology (Yan et al. 2023).  By inhibiting the xCT transporter or AMPA receptors in vivo, brain swelling and peritumoral alterations can be mitigated (Yakubov et al. 2023). Butyrate enhances erastin-induced ferroptosis of osteosarcoma cells by regulating the ATF3/SLC7A11 pathway(Nie et al. 2023).  It shows increased activity in ovarian cancer and may be a theraputic target (Fantone et al. 2024; Han et al. 2024). The non-natriuretic-dependent Xc- is composed of two protein subunits, SLC7A11 and SLC3A2, with SLC7A11 being responsible for cystine uptake and glutathione biosynthesis. SLC7A11 is implicated in tumor development through its regulation of redox homeostasis, amino acid metabolism, modulation of immune function, and induction of programmed cell death. Jiang and Sun 2024 summarized the structure and biological functions of SLC7A11. It depends on SLC3A2 (4F2, 4F2HC, CD98, MDU1, NACAE) listed in TCDB under TC# 8.A.9.2.2. Luteolin attenuates CCl4-induced hepatic injury by inhibiting ferroptosis via SLC7A11 (Han et al. 2024). Targeting sirtuiin-3 (SIRT3) sensitizes glioblastoma to ferroptosis by promoting mitophagy and inhibiting SLC7A11 (Li et al. 2024). An inhibitor of SLC7A11 (xCT) has been identified (Yue et al. 2024).  It acts as a chaperone that facilitates biogenesis and trafficking of functional transporters heterodimers to the plasma membrane. It forms heterodimers with SLC7 family transporters (SLC7A5, SLC7A6, SLC7A7, SLC7A8, SLC7A10 and SLC7A11), a group of amino-acid antiporters (Rossier et al. 1999).  Heterodimers function as amino acids exchangers, the specificity of the substrate depending on the SLC7A subunit. Heterodimers SLC3A2/SLC7A6 or SLC3A2/SLC7A7 mediate the uptake of dibasic amino acids (Bröer et al. 2000.  LAPTM4B (see TC# 2.A.74.1.3) counteracts ferroptosis by suppressing the ubiquitin-proteasome degradation of SLC7A11 in non-small cell lung cancer (Yan et al. 2024).  STEAP3 (TC# 5.B.6.1.1) affects ovarian cancer progression by regulating ferroptosis through the p53/SLC7A11 pathway (Han et al. 2024).  The E3 ligase TRIM7 suppresses the tumorigenesis of gastric cancer by targeting SLC7A11 (Chen et al. 2024). Sevoflurane-induced neurotoxicity occurs through SLC7A11-associated ferroptosis (Hu et al. 2024). Human USP38 (ubiquitin-specific peptidase 38) exacerbates myocardial injury and malignant ventricular arrhythmias after ischemia/reperfusion by promoting ferroptosis through the P53/SLC7A11 pathway (Gong et al. 2025).  Dicoumarol sensitizes hepatocellular carcinoma cells to ferroptosis induced by imidazole ketone erastin (IKE) (Yang et al. 2025).  Ferroptosis, an iron-dependent form of regulated cell death, is characterized by the lethal accumulation of lipid peroxides on cellular membranes. It not only inhibits tumor growth but also enhances immunotherapy responses and overcomes drug resistance in cancer therapy. The inhibition of the cystine-glutamate antiporter, system Xc-, induces ferroptosis. Imidazole ketone erastin (IKE), an inhibitor of the system Xc- functional subunit solute carrier family 7 member 11 (SLC7A11), is an effective and metabolically stable inducer of ferroptosis (Yang et al. 2025).

Animals

SLC7A11 (xCT) of Homo sapiens

B(0,+)-type amino acid transporter 1 (B(0,+)AT) (Glycoprotein-associated amino acid transporter b0,+AT1) (Solute carrier family 7 member 9).  The cryo-EM structure of the human heteromeric amino acid transporter b(0,+)AT-rBAT complex has been solved (Yan et al. 2020). The two subunits, a heavy chain and a light chain are linked by a disulfide bridge. The light chain forms a heterodimer with rBAT, a heavy chain which mediates the membrane trafficking of b(0,+)AT. The b(0,+)AT-rBAT complex is an obligatory exchanger, which mediates the influx of cystine and cationic amino acids and the efflux of neutral amino acids in the kidney and small intestine. Yan et al. 2020 reported the cryo-EM structure of the human b(0,+)AT-rBAT complex alone and in complex with an arginine substrate at resolutions of 2.7 and 2.3 Å, respectively. The overall structure is a dimer of heterodimers. Arg is bound to the substrate binding site in an occluded pocket. The cryoEM structure reveals a heterotetrameric protein assembly composed of two heavy and two light chain subunits, respectively. The  interaction between the two units is mediated by dimerization of the heavy chain subunits and does not include participation of the light chain subunits (Wu et al. 2020). The b((0,+))AT1 transporter adopts a LeuT fold and is in an inward-facing conformation. An amino-acid-binding pocket is formed by transmembrane helices 1, 6, and 10 and is conserved among SLC7 transporters.  L-arginine and its (patho-)physiologically active derivatives, L-homoarginine and asymmetric dimethylarginine (ADMA), show differences in their renal clearance (Banjarnahor et al. 2024).  The human heteromeric transporter b^0,+AT-rBAT (encoded by the SLC7A9 and SLC3A1 genes) is a potential candidate because it is localized in the luminal membrane of human proximal tubule cells and is capable of mediating the cellular uptake of amino acids, including L-arginine. Double-transfected Madin-Darby canine kidney (MDCK) cells stably expressing human b^0,+AT-rBAT exhibited uptake of L-arginine and L-homoarginine, with apparent K_m values of 512.6 and 197.0 μM, respectively. ADMA uptake was not saturated up to 4000 μM, with a transport rate > 5 nmol × mg protein^-1 × min^-1. With an IC₅₀ value of 115.8 μM, L-arginine inhibited L-homoarginine uptake. Conversely, L-arginine only exhibited a partial inhibitory effect on ADMA uptake (Banjarnahor et al. 2024). SLC7A9 is a potential biomarker for lymph node metastasis of esophageal squamous cell carcinoma (Baba et al. 2022). 

Animals

SLC7A9 of Homo sapiens

L-type neutral amino acid transporter, ASUR4 (Na⁺-independent) of 507 aas and 12 TMSs. Pregabalin (PGB), a drug for the treatment of epilepsy, neuropathic pain, fibromyalgia, and generalized anxiety disorder, may be transported by L-type transporters (Su et al. 2005).

Animals

ASUR4 of Xenopus laevis (O13020)

Large neutral amino acids transporter small subunit 2 (L-type amino acid transporter 2) (hLAT2) (Solute carrier family 7 member 8). Certain detergents stabilize and allow purification of the 4F2hc-LAT2 complex, allowing the measurement of substrate binding. In addition, an improved 3D map could be obtained (Meury et al. 2014).  Transports many amino acids including thyroid hormones 3',3-T2 and T3 (Hinz et al. 2015; Kinne et al. 2015).  LAT2 associates with SLC3A2 to form a functional heterodimeric complex that translocates small and large neutral amino acids with broad specificity and a stoichiometry of 1:1. The system functions as amino acid antiporter mediating the influx of extracellular essential amino acids mainly in exchange with the efflux of highly concentrated intracellular amino acids (Rodriguez et al. 2021).  Involved in the uptake of methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes, and hence plays a role in metal ion homeostasis and toxicity (Simmons-Willis et al. 2002).Ii is involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the transmembrane (Li and Whorton 2005).  It also imports the thyroid hormone diiodothyronine (T2) and to a smaller extent triiodothyronine (T3) but not rT 3 or thyroxine (T4).  Mediates the uptake of L-DOPA

Animals

SLC7A8 of Homo sapiens

Y+L amino acid transporter 1 (Monocyte amino acid permease 2) (MOP-2) (Solute carrier family 7 member 7) (y(+)L-type amino acid transporter 1) (Y+LAT1) (y+LAT-1).  It transports cationic amino acids such as arginine and lysine out of the cell. Arginine, in particular, is critical for T-cell activation and function in the immune response, and Y+L   plays a role in the pathogenesis of T-cell acute lymphoblastic leukemia (Ji et al. 2018).

Animals

SLC7A7 of Homo sapiens

Y+L amino acid transporter 2 (Cationic amino acid transporter, y+ system) (Solute carrier family 7 member 6) (y(+)L-type amino acid transporter 2) (Y+LAT2) (y+LAT-2).  Transports certain thyroid hormones and their derivatives as well as multiple amino acids(Krause and Hinz 2017).

Animals

SLC7A6 of Homo sapiens

Large neutral amino acids transporter small subunit 1 (4F2 light chain) (4F2 LC) (4F2LC) (CD98 light chain; SLC3A2; LAT1) (Integral membrane protein E16) (L-type amino acid transporter 1) (hLAT1) (Solute carrier family 7 member 5) (y+ system cationic and neutral amino acid transporter).  The heavy chain, CD98hc, modulates integrin signaling, plays a role in cell-to-cell fusion, and is essential for Brucella infection (Keriel et al. 2015).  In addition to several large neutral L-amino acids, Lat1 in conjunction with 4F2hc, transports S-nitroso-L-cysteine (Li and Whorton 2007), is important for transport of certain drugs into the brain, and is important for cancer (Lee et al. 2019). LAT1/CD98 mediates a Na⁺ and pH-independent antiport of amino acids (Scalise et al. 2018). It has been demonstrated that the preferred substrate is histidine, but many large amino acids are also sustrates. CD98 is not required for transport, being plausibly involved in routing LAT1 to the plasma membrane. Homology models have been built on the basis of the AdiC transporter from E.coli. Crucial residues for substrate recognition and gating have been identified using a combined approach of bioinformatics and site-directed mutagenesis coupled to functional assays. LAT1 is involved in important human diseases such as neurological disorders and cancer (Scalise et al. 2018). The cryo-EM structure of the human LAT1-CD98hc heterodimer at 3.3-A resolution has been determined (Lee et al. 2019). LAT1 features a canonical Leu T-fold and exhibits an unusual loop structure on transmembrane helix 6, creating an extended cavity that might accommodate bulky amino acids and drugs. CD98hc engages with LAT1 through extracellular, transmembrane and putative cholesterol-mediated interactions. The SLC7A5 (LAT1) gene, which encodes the main transmembrane transporter of large neutral amino acids and of thyroid hormones, exists as variants, one of which is responsible for obesity in patients with phenylketonuria (Bik-Multanowski et al. 2020). SLC7A5 functions in mTORC1 ativation in late endosomes (Jin et al. 2021). It is the main transporter for phenylalanine, and management precautions for risk of obesity are necessary among infants with PKU carrying the rs113883650 variant of the LAT1 gene (Bik-Multanowski et al. 2022). CD98hc is expressed in pancreatic ductal adenocarcinomas in increased amounts (Bianconi et al. 2022). Human LAT1 (SLC7A5) transports amino acids, thyroid hormones, and drugs such as the Parkinson's disease drug levodopa (L-Dopa). It is found in the blood-brain barrier, testis, bone marrow, and placenta, and its dysregulation has been associated with various neurological diseases, such as autism and epilepsy, as well as cancer (Hutchinson et al. 2022). The inhibitor specificities of LAT1 have been described (Hutchinson et al. 2022). SLC7A5 and SLC7A11 can be manipuated to eliminate the barrier to successful CAR-T therapy (Panetti et al. 2022).  Targeting glutamine metabolic reprogramming of SLC7A5 enhances the efficacy of anti-PD-1 in triple-negative breast cancer (Huang et al. 2023). The human LAT1-4F2hc (SLC7A5-SLC3A2) transporter complex has been implicated in physiological and pathophysiological characteristics (Kahlhofer and Teis 2022).  Four cholesterol-binding sites (CHOL1-4) were identified in a recent LAT1-apo inward-open conformation cryo-EM structure. Hutchinson and Schlessinger 2024 explored the interactions between LAT1 and cholesterol. Their findings suggested that CHOL3 forms the most stable and favorable interactions within LAT1. Fat mass and obesity-associated protein (FTO) mediated m⁶A modification of circFAM192A promotes gastric cancer proliferation by suppressing SLC7A5 decay (Wu et al. 2024). FXR, MRP-1 and SLC7A5 are new targets for the treatment of hepatocellular carcinoma (Zhang et al. 2024).  LAT1 supports mitotic progression through Golgi unlinking in an amino acid transport activity-independent manner (Yanagida et al. 2024).

Animals

SLC7A5 of Homo sapiens

Unchracterized transporter

Actinobacteria

Uncharacterized permease of Streptomyces coelicolor

Amino acid transporter 6 (AAT-6). Interacts with NRFL-1, the C. elegans NHERF orthologue to promote localization to the intestinal luminal membrane (Hagiwara et al. 2012).

Animals

AAT-6 of Caenorhabditis elegans

Serine/threonine exchanger, SteT

Bacteriodetes

SteT of Cecembia lonarensis

Cationic amino acid transporter, y+LAT1.  95% identical to a characterized carp orthologue (Yang et al. 2013).

Animals

y+LAT1 cationic amino acid transporter of Danio rerio (Zebra fish)

Putative amino acid porter of 512 aas and 14 TMSs.

Crenarchaea

Amino acid porter of Sulfolobus islandica

Putative polyamine transporter of 537 aas and 12 TMSs

Tenericutes

Putative polyamine porter of Mycoplasma (Acholeplasma) florum

Large neutral amino acid transporter, CD98lc (LAT), of 442 aas.  Functions with CD98hc (TC# 8.A.9.2.3) (Reynolds et al. 2009).  CD98hc also modulates integrin signaling (Prager et al. 2007), plays a role in cell-to-cell fusion, and is essential for Brucella infection (Keriel et al. 2015).

Animals

CD98lc of Drosophila melanogaster

L-methionine transporter, MUP1.  Also transports selenomethionine (SeMet) (Kitajima et al. 2010).

Yeast

MUP1 of Saccharomyces cerevisiae (P50276)

Cystine/glutamate antiporter, xCT (requires the 4F2hc protein (TC #8.A.9.2.1)). Functions in the generation of glutathione and plays a role in the oxidative stress response (Wang et al. 2015). xCT is involved in the export of intracellular glutamate in exchange for extracellular cystine. Glutamate is the main neurotransmitter in the retina and plays a key metabolic role as a major anaplerotic substrate in the tricarboxylic acid cycle to generate adenosine triphosphate (ATP) (Knight et al. 2023). Glutamate is also involved in the outer plexiform glutamate-glutamine cycle, which links photoreceptors and supporting Müller cells and assists in maintaining photoreceptor neurotransmitter supply. Knight et al. 2023 investigated the role of xCT, the light chain subunit responsible for antiporter function, in glutamate pathways in the mouse retina using an xCT knockout mouse. As xCT is a glutamate exporter, loss of xCT function could influence the presynaptic metabolism of photoreceptors and postsynaptic levels of glutamate, and this proved to be true. Loss of xCT function resulted in glutamate metabolic disruption through the accumulation of glutamate in photoreceptors and a reduced uptake of glutamate by Müller cells, which in turn decreases glutamine production. These findings support the idea that xCT plays a role in the presynaptic metabolism of photoreceptors and postsynaptic levels of glutamate and derived neurotransmitters in the retina. (Knight et al. 2023).  Loss of xCT function results in glutamate metabolic disruption through the accumulation of glutamate in photoreceptors and a reduced uptake of glutamate by Müller cells, which in turn decreases glutamine production.

Animals

xCT of Mus musculus (Q9WTR6)

L-type neutral amino acid transporter, LAT2 (Na⁺-independent with broad specificity for all L-isomers of neutral amino acids; preferred substrate: Phe, His, Trp, Ile, Val, Leu, Gln, Cys, Ser; catalyzes obligatory exchange with μM affinities on the outside and mM affinities on the inside [1000x difference]). Both LAT2 and LAT1 (2.A.3.8.1) catalyze uptake of S-nitro-L-cysteine (Li and Whorton, 2005). Also transports thyroid hormones (Kinne et al., 2011). Lat1 transports 26 biologically active ultrashort peptides (USPs) into cells as is also true of LAT2 and PEPT1 (Khavinson et al. 2023). The sizes and structures of ligand-binding sites of the amino acid transporters LAT1, LAT2, and of the peptide transporter PEPT1 are sufficient for the transport of the 26 biologically active di-, tri-, and tetra-peptides. Comparative analyses of the binding of all possible di- and tri-peptides (8400 compounds) at the binding sites of the LAT and PEPT family transporters was considered (Khavinson et al. 2023). The 26 biologically active USPs systematically showed higher binding scores to LAT1, LAT2, and PEPT1, as compared with di- and tri-peptides. Most of the 26 studied USPs were found to bind to the LAT1, LAT2, and PEPT1 transporters more efficiently than the previously known substrates or inhibitors of these transporters. Peptides ED, DS, DR, EDR, EDG, AEDR, AEDL, KEDP, and KEDG, and peptoids DS7 and KE17 with negatively charged Asp^- or Glu^- amino acid residues at the N-terminus and neutral or positively charged residues at the C-terminus of the peptide were found to be the most effective ligands of the transporters under investigation. It can be assumed that the antitumor effect of the KE, EW, EDG, and AEDG peptides could be associated with their ability to inhibit the LAT1, LAT2, and PEPT1 amino acid transporters (Khavinson et al. 2023).

Animals

LAT2 of Rattus norvegicus (Q9WVR6)

Heteromeric amino acid transporter #1 (transports most neutral aas with highest rates for Ala and Ser (Km≈100 μM)). They function by obligatory aa:aa exchange (Veljkovic et al., 2004b).

Animals

AAT1 of Caenorhabditis elegans (Q19834)

Spore germination protein A2 (AB) (amino acid [L-alanine] receptor.) GerAA, GerAB and GerAC form a receptor complex in the spore inner membrane. GerAC is a lipoprotein (Cooper and Moir, 2011). GerAB is an α-helical transmembrane protein containing a water channel. Alanine binds transiently to specific sites on GerAB, initiating L-alanine-mediated signaling by GerAB, which facilitates early events in spore germination (Blinker et al. 2021).

Gram-positive bacteria

GerAB of Bacillus subtilis (P07869)

YndE of Bacillus subtilis

Spore germination protein of 368 aas and 10 TMSs.  Maps adjacent to a putative ABC transporter of unknown specificity (F8FLY8, F8FLY7, F8FLY5). 

Firmicutes

SGP of Paenibacillus mucilaginosus