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Sodium- and chloride-dependent neutral and basic amino acid transporter (SLC6A14) (SLC6A14)

Target
SLC6A14
Molecular classification
Transporter, Solute carrier family (SLC6 family), Neurotransmitter:sodium symporter (NSS) family
01

Overview

SLC6A14 (system B^0,+ or ATB^0,+) is a sodium- and chloride-dependent amino acid transporter that mediates the concentrative uptake of a broad range of neutral and cationic (basic) amino acids, including all essential amino acids[1][2][3][5]. It uses an electrochemical gradient of Na^+ and Cl^− to facilitate transport across the plasma membrane[5]. SLC6A14 is highly unusual among mammalian transporters for its broad substrate specificity and ability to transport 18 of the 20 proteinogenic amino acids (excluding aspartate and glutamate)[3]. It is thus critical for nutrient absorption, particularly in the intestine, and is upregulated in certain cancers (notably ER-positive breast cancer), where it supports increased amino acid demand for growth and metabolic activity[1][3]. Pharmacologic inhibition of SLC6A14 (e.g., with α-methyl-DL-tryptophan) can suppress tumor cell growth by inducing amino acid deprivation, mTOR inhibition, autophagy, and apoptosis, making it an emerging therapeutic target in oncology[1][4]. Additionally, SLC6A14's broad substrate selectivity enables its potential use in prodrug strategies for drug delivery[4].

Other names
Amino acid transporter ATB^0,+ATB^0,+System B^0,+Sodium- and chloride-dependent neutral and basic amino acid transporter
02

Mechanism of action

Transport inhibition leading to amino acid deprivation (notably via α-MT, which blocks SLC6A14)[1] Downstream suppression of mTOR signaling and induction of autophagy and apoptosis in target cells[1]

03

Biological functions

Amino acid uptake and transportNutrient absorption in the intestineModulation of amino acid availability for cellular metabolismSupply of essential and non-essential amino acids for growth, biosynthesis, and energy metabolism
04

Disease associations

Cancer (notably estrogen receptor-positive breast cancer)Potential roles in cystic fibrosis and metabolic disordersOther (due to broad tissue expression and substrate range)
05

Safety considerations

Potential for non-specific effects due to broad substrate range and expression in normal tissuesTherapeutic blockade may impact normal amino acid absorption/metabolism
06

Interacting drugs

α-Methyl-DL-tryptophan (α-MT)

2 more in the full profile.

07

Biomarkers

SLC6A14 overexpression as a marker for some estrogen receptor-positive breast cancers[1]Potential biomarker for intestinal and certain metabolic disorders

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