Expansion of the APC superfamily of secondary carriers

Proteins. 2014 Oct;82(10):2797-811. doi: 10.1002/prot.24643. Epub 2014 Jul 31.


The amino acid-polyamine-organoCation (APC) superfamily is the second largest superfamily of secondary carriers currently known. In this 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⁺ Virginia 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 some 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.

Keywords: amino acid-polyamine-organoCation (APC) superfamily; anion exchanger 1; carbon starvation A protein; superfamily tree; transporter classification database.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Transport Systems / chemistry
  • Amino Acid Transport Systems / classification
  • Amino Acid Transport Systems / genetics
  • Amino Acid Transport Systems / metabolism
  • Animals
  • Antiporters / chemistry
  • Antiporters / classification
  • Antiporters / genetics
  • Antiporters / metabolism
  • Biological Transport
  • Cation Transport Proteins / chemistry
  • Cation Transport Proteins / classification
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism
  • Cluster Analysis
  • Computational Biology
  • Databases, Protein
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / classification
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Humans
  • Internet
  • Models, Molecular*
  • Organic Cation Transport Proteins / chemistry*
  • Organic Cation Transport Proteins / classification
  • Organic Cation Transport Proteins / genetics
  • Organic Cation Transport Proteins / metabolism
  • Phylogeny
  • Protein Isoforms / chemistry
  • Protein Isoforms / classification
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Structure, Secondary
  • Sequence Homology, Amino Acid
  • Software
  • Terminology as Topic
  • Trans-Activators / chemistry
  • Trans-Activators / classification
  • Trans-Activators / genetics
  • Trans-Activators / metabolism


  • Amino Acid Transport Systems
  • Antiporters
  • Cation Transport Proteins
  • Escherichia coli Proteins
  • Organic Cation Transport Proteins
  • Protein Isoforms
  • Trans-Activators
  • cstA protein, E coli
  • natural resistance-associated macrophage protein 1