2.A.18 The Amino Acid/Auxin Permease (AAAP) Family

The AAAP family includes hundreds of proteins from plants, animals, yeast and fungi. Individual permeases of the AAAP family transport auxin (indole-3-acetic acid), a single amino acid or multiple amino acids. Some of these permeases exhibit very broad specificities transporting all twenty amino acids naturally found in proteins. Some also transport D-amino acids. There are 7 AAAP paralogues in Saccharomyces cerevisiae, at least 9 in Arabidopsis thaliana and at least 5 in Caenorhabditis elegans. Six AAPs in A. thaliana transport neutral and charged amino acids with varying specificities and affinities (Fischer et al., 2002). All transport neutral amino acids and some acidic amino acids, always with just one proton. AAP3 and AAP5 are the only ones transporting basic amino acids, and only AAP6 transports aspartate (Fischer et al., 2002).

AAAP family proteins, all from eukaryotes, vary from 376 to 713 amino acyl residues in length, but most are of 400-500 residues. Most of the size variation occurs as a result of the presence of long N-terminal hydrophilic extensions in some of the proteins. Some of the yeast proteins are particularly long. Variation in the loops and the C-termini also occurs. These proteins exhibit 11 (or 10) putative transmembrane α-helical spanners. One homologue, AAP1 of A. thaliana (TC #2.A.18.2.1), has 11 established TMSs (Chang and Bush, 1997).

Members of the AAAP family exhibit limited sequence similarity with members of the large APC family (TC #2.A.3). Thus, the AAAP family may be distantly related to the APC family.

Among animal AAAP family members are numerous growth regulating System A and System N isoforms, each exhibiting distinctive tissue and subcellular localizations. The different isoforms also exhibit different relative affinities for the amino acid substrates. Some catalyze H+ antiport and can function bidirectionally. Since Systems A are electrogenic which Systems N are not, the amino acid:cation stoichiometries may differ (Chaudhry et al., 2001, 2002; Varoqui et al., 2000).

The generalized transport reaction catalyzed by the proteins of the AAAP family is:

Substrate (out) + nH+ (out) → Substrate (in) + nH+ (in)

This family belongs to the APC Superfamily.
 

References:

Bennett, M.J., A. Marchant, H.G. Green, S.T. May, S.P. Ward, P.A. Millner, A.R. Walker, B. Schulz, and K.A. Feldmann. (1996). Arabidopsis AUX1 gene: a permease-like regulator of root gravitropism. Science 273: 948-950.
Boll, M., M. Foltz, I. Rubio-Aliaga, G. Kottra, and H. Daniel. (2002). Functional characterization of two novel mammalian electrogenic proton-dependent amino acid cotransporters. J. Biol. Chem. 277: 22966-22973.
Chang, H.C. and D.R. Bush. (1997). Topology of NAT2 (AAP1): a prototypical example of a new family of amino acid transporters. J. Biol. Chem. 272: 30552-30557.
Chaudhry, F.A., D. Krizaj, P. Larsen, R.J. Reimer, J. Storm-Mathiesen, D.R. Copenhagen, M.P. Kavanaugh, and R.H. Edwards. (2001). Coupled and uncoupled proton movement regulates amino acid transport by System N. EMBO J. 20: 7041-7051.
Chaudhry, F.A., D. Schmitz, R.J. Reimer, P. Larsson, A.T. Gray, R. Nicoll, M. Kavanaugh, and R.H. Edwards. (2002). Glutamine uptake by neurons: interaction of protons with system A transporters. J. Neurosci. 22: 62-72.
Chen, L. and D.R. Bush. (1997). LHT1, a lysine- and histidine-specific amino acid transporter in arabidopsis. Plant Physiol. 115: 1127-1134.
Fei, Y., M. Sugawara, T. Nakanishi, W. Huang, H. Wang, P.D. Prasad, F.H. Leibach, and V. Ganapathy. (2000). Primary structure, genomic organization, and functional and electrogenic characteristics of human system N1, a Na+- and H+-coupled glutamine transporter. J. Biol. Chem. 275: 23707-23717.
Fischer, W-N., M. Kwart, S. Hummel, and W.B. Frommer. (1995). Substrate specificity and expression profile of amino acid transporters (AAPs) in Arabidopsis. J. Biol. Chem. 270: 16315-16320.
Fischer, W.-N., D.D.F. Loo, W. Koch, U. Ludewig, K.J. Boorer, M. Tegeder, D. Rentsch, E.M. Wright, and W.B. Frommer. (2002). Low and high affinity amino acid H+-cotransporters for cellular import of neutral and charged amino acids. Plant J. 29: 717-731.
Gu, S., H.L. Roderick, P. Camacho, and J.X. Jiang. (2000). Identification and characterization of an amino acid transporter expressed differentially in liver. Proc. Natl. Acad. Sci. USA 97: 3230-3235.
Hatanaka, T., W. Huang, H. Wang, M. Sugawara, P.D. Prasad, F.H. Leibach, and V. Ganapathy. (2000). Primary structure, functional characteristics and tissue expression pattern of human ATA2, a subtype of amino acid transport system A. Biochim. Biophys. Acta 1467: 1-6.
McIntire, S.L., R.J. Reimer, K. Schuske, R.H. Edwards, and E.M. Jorgensen. (1997). Identification and characterization of the vesicular GABA transporter. Nature 389: 870-876.
Okumoto, S., R. Schmidt, M. Tegeder, W.N. Fischer, D. Rentsch, W.B. Frommer, and W. Koch. (2002). High affinity amino acid transporters specifically expressed in xylem parenchyma and developing seeds of Arabidopsis. J. Biol. Chem. 277: 45338-45346.
Reimer, R.J., F.A. Chaudhury, A.T. Gray, and R.H. Edwards. (2000). Amino acid transport System A resembles System N in sequence but differs in mechanism. Proc. Natl. Acad. Sci. USA 97: 7715-7720.
Reinhardt, D., E.-R. Pesce, P. Stieger, T. Mandel, K. Baltensperger, M. Bennett, J. Traas, J. Friml, and C. Kuhlemeier. (2003). Regulation of phyllotaxis by polar auxin transport. Nature 426: 255-260.
Rentsch, D., B. Hirner, E. Schmeizer, and W.B. Frommer. (1996). Salt stress-induced proline transporters and salt stress-repressed broad specificity amino acid permeases identified by suppression of a yeast amino acid permease-targeting mutant. Plant Cell 8: 1437-1446.
Rubio-Aliaga, I., M. Boll, D.M.V. Weisenhorn, M. Foltz, G. Kottra, and H. Daniel. (2004). The proton/amino acid cotransporter PAT2 is expressed in neurons with a different subcellular localization than its paralog PAT1. J. Biol. Chem. 279: 2754-2760.
Russnak, R., D. Konczal, and S.L. McIntire. (2001). A family of yeast proteins mediating bidirectional vacuolar amino acid transport. J. Biol. Chem. 276: 23849-23857.
Sugawara, M., T. Nakanishi, Y-J. Fei, W. Huang, M.E. Ganapathy, F.H. Leibach, and V. Ganapathy. (2000). Cloning of an amino acid transporter with functional characteristics and tissue expression pattern identical to that of system A. J. Biol. Chem. 275: 16473-16477.
Varoqui, H., H. Zhu, D. Yao, H. Ming, and J.D. Erickson. (2000). Cloning and functional identification of a neuronal glutamine transporter. J. Biol. Chem. 275: 4049-4054.
Williams, L.E. and A.J. Miller. (2001). Transporters responsible for the uptake and partitioning of nitrogenous solutes. Annu. Rev. Plant Physiol. Plant Mol. Biol. 52: 659-688.
Wipf, D., U. Ludewig, M. Tegeder, D. Rentsch, W. Koch, and W.B. Frommer. (2002). Conservation of amino acid transporters in fungi, plants and animals. Trends Biochem. Sci. 27: 139-147.
Yao, D., B. Mackenzie, H. Ming, H. Varoqui, H. Zhu, M.A. Hediger, and J.D. Erickson. (2000). A novel system A isoform mediating Na+/neutral amino acid cotransport. J. Biol. Chem. 275: 22790-22797.
Young, G.B., D.L. Jack, D.W. Smith, and M.H. Saier, Jr. (1999). The amino acid/auxin:proton symport permease family. Biochim. Biophys. Acta 1415: 306-322.
 

Examples:

TC#NameOrganismal TypeExample
2.A.18.1.1Auxin:H+ symporter (auxin influx) (Reinhardt et al., 2003)Plants Aux-1 of Arabidopsis thaliana
 
2.A.18.2.1General amino acid permease 1, AAP1 (transports most neutral and acidic amino acids but not aspartate or the basic amino acids) Plants AAP1 of Arabidopsis thaliana
 
2.A.18.2.2Lysine/histidine transporter, LHT1 Plants LHT1 of Arabidopsis thaliana
 
2.A.18.2.3General amino acid transporter 3, AAP3 (transports all neutral, acidic and basic amino acids tested)PlantsAAP3 of Arabidopsis thaliana
 
2.A.18.2.4General amino acid transporter 6, AAP6 (transports all neutral and acidic amino acids tested including aspartate, and basic amino acids are transported with low affinity) (Okumoto et al., 2002)PlantsAAP6 of Arabidopsis thaliana
 
2.A.18.2.5General amino acid transporter 8, AAP8 (transports all amino acids, but the basic amino acids are transported
with low affinity (Okumoto et al., 2002))		PlantsAAP8 of Arabidopsis thaliana
 
2.A.18.3.1Proline permease 1 Plants Prt1 of Arabidopsis thaliana
 
2.A.18.3.2Proline/GABA/glycine betaine permease, ProT1PlantsProT1 of Lycopersicon esculentum
 
2.A.18.4.1Neutral amino acid permease Fungi AAP1 of Neurospora crassa
 
2.A.18.5.1Vesicular γ-amino butyric acid (GABA) transporter Animals UNC-47 of Caenorhabditis elegans
 
2.A.18.5.2The vacuolar amino acid transporter AVT1 (catalyzes uptake into yeast vacuoles of large neutral amino acids including tyr, gln, asn, leu and ile)YeastAVT1 of Saccharomyces cerevisiae
 
2.A.18.6.1Neuronal glutamine (System A-like) transporter, GlnT Animals GlnT of Rattus norvegicus
 
2.A.18.6.2Liver histidine and glutamine specific system N-like, Na+-dependent amino acid transporter, mNAT Animals mNAT of Mus musculus
 
2.A.18.6.3System N1 [glutamine/histidine/asparagine/alanine]:[Na+ + H+] sym/antiporter (1 aa + 2 Na+ cotransported against 1 H+ antiported out) (probable orthologue of mNAT). Li+ can substitute for Na+; system N1 can function bidirectionally. Animals SN1 of Homo sapiens
 
2.A.18.6.4Plasma membrane System A-like neutral amino acid transporter, SA1 or SAT2 (transports small, neutral aliphatic amino acids including α-(methylamino)isobutyrate, mAIB with Na+ (1:1 stoichiometry; Km = 200-500 μM))Animals SAT2 of Rattus norvegicus
 
2.A.18.6.5Na+-dependent system A-like transporter, System A2 or ATA2 (transports neutral amino acids with decreasing affinity in the order: MeAIB, Ala, Gly, Ser, Pro, Met, Asn, Gln, Thr, Leu and Phe). The neuronal system A2 has been reported to transport Asn and Gln with higher affinity than for other neutral amino acids.Animals ATA2 of Homo sapiens
 
2.A.18.6.6The vacuolar amino acid transporter, AVT6 (catalyzes efflux from yeast vacuoles of acidic amino acids, Asp and Glu)YeastAVT6 of Saccharomyces cerevisiae
 
2.A.18.7.1The vacuolar amino acid transporter, AVT3 (catalyzes efflux from yeast vacuoles of large neutral amino acids such as tyr, gln, asn, leu and ile)YeastAVT3 of Saccharomyces cerevisiae
 
2.A.18.8.1The electrogenic, proton-dependent amino acid:H+ symporter, PAT1 (catalyzes uptake of L-Gly, L-Ala, L-Pro, γ-amino butyrate, and short chain D-amino acids) (proline: H+ = 1:1) (found in lysosomes)AnimalsmPAT1 of Mus musculus
 
2.A.18.8.2Electrogenic, proton-coupled, amino acid symporter 2 (PAT2; Tramdorin-1) (transports small amino acids: glycine, alanine and proline; found in the ER, not in lysosomes, of neuronal cells in the brain and spinal cord; it can catalyze bidirectional transport depending on the driving force) (Rubio-Aliaga et al., 2004)AnimalsPAT2 of Mus musculus (AAH44800)