APC Family


The Amino Acid-Polyamine-Organocation Family of transport proteins includes members that function as solute:cation symporters and solute:solute antiporters. They occur in bacteria, archaea, fungi, unicellular eukaryotic protists, slime molds, plants and animals. They vary in length, being as small as 350 residues and as large as 850 residues. The smaller proteins are generally of prokaryotic origin while the larger ones are of eukaryotic origin. Most of them possess twelve transmembrane α-helical spanners but have a re-entrant loop involving TMSs 2 and 3. The APC Superfamily was established to encompass a wider range of homologues.

Members of APC Family

Members of one subfamily within the APC family are amino acid receptors rather than transporters and are truncated at their C-termini, relative to the transporters, having 10 TMSs.
The eukaryotic members of another subfamily and the members of a prokaryotic subfamily have 14 TMSs.
The larger eukaryotic and archaeal proteins possess N- and C-terminal hydrophilic extensions. Some animal proteins, for example, those in the LAT subfamily including ASUR4 and SPRM1 associate with a type 1 transmembrane glycoprotein that is essential for insertion or activity of the permease and forms a disulfide bridge with it. These glycoproteins include the CD98 heavy chain protein of Mus musculus and the orthologous 4F2 cell surface antigen heavy chain of Homo sapiens. The latter protein is required for the activity of the cystine/glutamate antiporter, which maintains cellular redox balance and cysteine/glutathione levels. They are members of the rBAT family of mammalian proteins.
Most S. cerevisiae amino acid permeases are members of the APC family. The majority of these permeases belong to the YAT sub-family and they have a broad range of overlapping specificities. Two additional permeases belong to the LAT sub-family and support methionine and cysteine intake. The final one identified is an ACT sub-family member, a GABA permease, present in both cell and vacuolar membranes; all others are found only in the cell membrane.
Two APC family members, LAT1 and LAT2, transport a neurotoxicant, the methylmercury-L-cysteine complex, by molecular mimicry.
Hip1 of S. cerevisiae has been implicated in heavy metal transport.

Subfamilies

Subfamilies of the APC family, and the proteins in these families, can be found in the Transporter Classification Database:
  • 2.A.3.1: The Amino Acid Transporter Family
  • 2.A.3.2: The Basic Amino Acid/Polyamine Antiporter Family
  • 2.A.3.3: The Cationic Amino Acid Transporter Family
  • 2.A.3.4: The Amino Acid/Choline Transporter Family
  • 2.A.3.5: The Ethanolamine Transporter Family
  • 2.A.3.6: The Archaeal/Bacterial Transporter Family
  • 2.A.3.7: The Glutamate:GABA Antiporter Family
  • 2.A.3.8: The L-type Amino Acid Transporter Family
  • 2.A.3.9: The Spore Germination Protein Family
  • 2.A.3.10: The Yeast Amino Acid Transporter Family
  • 2.A.3.11: The Aspartate/Glutamate Transporter Family
  • 2.A.3.12: The Polyamine:H+ Symporter Family
  • 2.A.3.13: The Amino Acid Efflux Family
  • 2.A.3.14: The Unknown APC-1 Family
  • 2.A.3.15: The Unknown APC-2 Family

    Structure and function

Based on 3-D structures of APC superfamily members, Rudnick has proposed the pathway for transport and suggested a "rocking bundle" mechanism.

Transport reactions

Transport reactions generally catalyzed by APC Superfamily members include:
Solute + nH+ → Solute + nH+ .
Solute-1 + Solute-2 ⇌ Solute-1 + Solute-2.