The 6TMS Neutral Amino Acid Transporter (NAAT) Family
TC# 2.A.95
is a family of transporters belonging to the Lysine Exporter (LysE) Superfamily. Homologues are found in numerous

Gram-negative Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...

and

Gram-positive bacteria In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bact ...

including many human pathogens. Several

archaea Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaebac ...

also encode MarC (see below) homologues. Some of these organisms have 2 or more

paralogues Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a s ...

. Most of these proteins are of about the same size (180-230 aas) although a few are larger. They exhibit 6 (or in some cases, possibly 5) putative TMSs. A representative list of members belonging to the NAAT family can be found in th
Transporter Classification Database

SnatA

A gene encoding a small neutral amino acid transporter was cloned from the genome of the

hyperthermophilic A hyperthermophile is an organism that thrives in extremely hot environments—from 60 °C (140 °F) upwards. An optimal temperature for the existence of hyperthermophiles is often above 80 °C (176 °F). Hyperthermophiles are often within the doma ...

archaeon ''Thermococcus'' sp. KS-1. The cloned gene, , encodes a protein of 216 amino acid residues, SnatA
TC# 2.A.95.1.4
, with six membrane-spanning segments (TMSs). Competition studies indicated that SnatA transports various L-type neutral amino acids. It has also been noted that glycine transport is inhibited by a

protonophore A protonophore, also known as a proton translocator, is an ionophore that moves protons across lipid bilayers or other type of membranes. This would otherwise not occur as protons cations (H+) have positive charge and hydrophilic properties, making ...

, FCCP, or

valinomycin Valinomycin is a naturally occurring dodecadepsipeptide used in the transport of potassium and as an antibiotic. Valinomycin is obtained from the cells of several '' Streptomyces'' species, '' S. fulvissimus'' being a notable one. It is a member ...

plus

nigericin Nigericin is an antibiotic derived from '' Streptomyces hygroscopicus''. Its isolation was described in the 1950s, and in 1968 the structure could be elucidated by X-ray crystallography. The structure and properties of nigericin are similar to th ...

, indicating that the process is dependent on an electrochemical potential of H⁺. The generalized reaction catalyzed by SnatA is:

Amino acid (in) → Amino acid (out)

MarC

MarC is encoded by a gene at the multiple antibiotic resistance (''mar'') locus. The ''mar'' locus consists of two divergently positioned transcriptional units that flank the operator, ''marO,'' in both ''E. coli'' and ''Salmonella typhimurium.'' One transcription unit encodes MarC, an integral inner membrane protein with 6 established TMSs with the N- and C-termini in the cytoplasm. Its function is unknown. The other unit consists of an operon, ''marRAB,'' encoding (1) the MarR repressor which binds ''marO'' and negatively regulates ''marRAB'' expression, (2) MarA, a transcriptional activator that activates expression of other genes such as ''acrAB'' (encoding the principal ''E. coli'' multidrug efflux pump of the RND superfamily
TC #2.A.6.2
) and the ''mar'' regulon itself, and (3) MarB, a small protein of 71 amino acyl residues of unknown function. A periplasmic binding protein, MppA, essential for the uptake of the cell wall

murein Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like peptidoglycan layer outside the plasma membrane, the rigid cell wall (murein sacculus) characteristic of most ba ...

tripeptide, L-alanyl-γ-D-glutamyl-''meso''-diaminopimelate via the Opp permease, regulates ''mar'' regulon expression. Loss of MppA causes overproduction of MarA which activates ''acrAB'', causing pleiotropic drug resistance. MppA probably functions upstream of MarA in a signal transduction pathway that negatively controls expression of the ''marRAB'' operon.

References

Protein families Solute carrier family {{membrane-protein-stub