Expansion of the APC superfamily of secondary carriers

Abstract

The Amino acid-Polyamine-organoCation (APC) superfamily is the second largest superfamily of secondary carriers currently known. In the current study, we establish homology between previously recognized APC superfamily members and proteins of seven new families. These families include the PAAP (Putative Amino Acid Permease), LIVCS (Branched Chain Amino Acid:Cation Symporter), NRAMP (Natural Resistance-Associated Macrophage Protein), CstA (Carbon starvation A protein), KUP (K+ Uptake Permease), BenE (Benzoate:H+ Symporter) and AE (Anion Exchanger). The topology of the well-characterized human Anion Exchanger 1 (AE1) conforms to a UraA-like topology of 14 TMSs (12 α-helical TMSs and 2 mixed coil/helical TMSs). All functionally characterized members of the APC superfamily use cation symport for substrate accumulation except for members of the AE family which frequently use anion:anion exchange. We show how the different topologies fit into the framework of the common LeuT-like fold, defined earlier (Proteins. 2014 Feb;82(2):336–46), and determine that some of the new members contain previously undocumented topological variations. All new entries contain the two 5 or 7 TMS APC superfamily repeat units, sometimes with extra TMSs at the ends, the variations being greatest within the CstA family. New, functionally characterized members transport amino acids, peptides, and inorganic anions or cations. Except for anions, these are typical substrates of established APC superfamily members. Active site TMSs are rich in glycyl residues in variable but conserved constellations. This work expands the APC superfamily and our understanding of its topological variations.

CIPK23 regulates HAK5-mediated high-affinity K+ uptake in Arabidopsis roots

“…A report showed that, in K + -sufficient plants, HAK5 protein was mainly detected in the endoplasmic reticulum, while K + starvation produced an enrichment of HAK5 protein in the plasma membrane (Qi et al, 2008). In addition, the KT/HAK/KUP family of K + transporters belongs to the amino acid-polyamine-organocation (APC) superfamily of secondary carriers (Vastermark et al, 2014). Regulation of APC transporter activity in eukaryotes maintains strong similarities with those found here for HAK5.…”

The Aspergillus nidulans Proline Permease as a Model for Understanding the Factors Determining Substrate Binding and Specificity of Fungal Amino Acid Transporters

“…The majority of these proteins belong to the ubiquitous amino acid polyamine organocation (APC) 5 superfamily, one of the largest families of secondary transporters (1,2). The APC includes members that function as solute/cation symporters and solute/solute antiporters and are found in bacteria, archeae, fungi, protists, plants and animals (1,3). Fungal APC members belong to the yeast amino acid transporter (YAT) family (4).…”

Glutamate Transporter Homolog-based Model Predicts That Anion-π Interaction Is the Mechanism for the Voltage-dependent Response of Prestin

“…This group of transporters represents the most distant and distinct branch of the APC superfamily with the sulfate permease transporter family representing an outlying cluster. Typically, the APC transporters display a 2-fold pseudosymmetrical topology consisting of four to seven transmembrane (TM)-spanning regions (19). The benzoate transporter/permease, anion exchanger 1, and nucleobasecation symporter-2 transporters are furthermore unique within the APC superfamily hierarchy by exhibiting a 7-7 TM topology, which is supported by the available crystal structures for anion exchanger 1 (21) and UraA (22).…”

“…The SLC26A family of anion transporters has been included as a distant member in the amino acid-polyamine-organocation (APC) superfamily (17)(18)(19). Saier and co-workers (19,20) placed the sulfate permease family of transporters within the APC branch that includes the anion exchanger (SLC4), nucleobase-cation symporter-2 (SLC23), and benzoate transporter/ permease transporters.…”

“…Saier and co-workers (19,20) placed the sulfate permease family of transporters within the APC branch that includes the anion exchanger (SLC4), nucleobase-cation symporter-2 (SLC23), and benzoate transporter/ permease transporters. This group of transporters represents the most distant and distinct branch of the APC superfamily with the sulfate permease transporter family representing an outlying cluster.…”