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Gene Review

SLC6A7  -  solute carrier family 6 (neurotransmitter...

Homo sapiens

Synonyms: PROT, Sodium-dependent proline transporter, Solute carrier family 6 member 7
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Disease relevance of SLC6A7

  • Tocopherol content in liver tissue is significantly decreased in cirrhosis (0.26 + 0.03 micromol/g prot., mean + SEM, P < .001) and in cirrhotic areas of the HCC group (0.31 + 0.02, P < .002), with respect to its content in liver specimens of healthy controls (0.46 + 0.03) and in healthy areas of the same organ in patients with LM (0.41 + 0.03) [1].
  • Two hundred and twenty primary ductal breast carcinomas assayed by this method showed a log normal distribution with a modal value of 8 fmol/mg prot., a mean at 18 and a median at 13 fmol/mg prot [2].
  • Tazobactam was able to inactivate intracellular beta-lactamase in Prot. vulgaris and Morganella morganii, confirming its ability to penetrate the cell membrane of these species [3].
  • The cephalosporins were less effective against the Bacteroides fragilis group, Prot. vulgaris and M. morganii, but had advantages in the case of Escherichia coli, Klebsiella spp. and C. diversus [4].
  • Preoperatively, in the patients with ruptured intracranial aneurysms, there was a greater increase in %Prot in eight patients classified (according to Fischer) as having a Group 3 or 4 subarachnoid hemorrhage (SAH) on computerized tomography than in five patients classified as having a Group 1 or 2 SAH [5].

Psychiatry related information on SLC6A7

  • However, within PROT diet, differences in psychometric performance correlated with glucose (p = 0.05) and insulin concentrations (p = 0.04), and the tyrosine:large neutral amino acid ratio correlated with alertness (p = 0.05) [6].

High impact information on SLC6A7

  • The Na+/Cl(-)-dependent proline transporter (PROT) belongs to a large superfamily of neurotransmitter transporters and is expressed in regions of the brain that contain glutamanergic neurons [7].
  • The delivery of PROT to the plasma membrane by exocytosis could play a critical role in the plasticity of certain glutamatergic pathways [8].
  • Immunogold labeling for PROT was detected in close contact with membranes of small synaptic vesicles (SSVs) and more rarely with the plasma membrane in these axon terminals [8].
  • Subcellular fractionation studies confirmed the preferential distribution of PROT to synaptic vesicles [8].
  • To gain insights into potential sites where PROT may function, we used a C-terminal domain antipeptide antibody to determine the regional distribution and subcellular localization of PROT in rat forebrain [8].

Chemical compound and disease context of SLC6A7


Biological context of SLC6A7

  • The topology of PROT in synaptic vesicles was found to be inverted with respect to the plasma membrane, suggesting that PROT-containing vesicles are generated by a process involving endocytosis from the plasma membrane [8].
  • These findings indicate that enkephalins competitively inhibit mammalian brain PROT through a direct interaction with the transporter protein at or near the L-proline binding site [10].
  • The brain-specific expression of PROT in a subset of putative glutamatergic pathways implies a specialized function for this novel transporter and its presumed natural substrate L-proline in excitatory synaptic transmission [10].
  • Introduction of tryptophan mutants into the bacterial expression vector pRT6H/NB-PROT showed that RTs containing W401A or W401L substitutions (but not W401F) and W414L were defective for dimerization in vitro [11].
  • To test this hypothesis, we examined the interactions of beta-carotene and cigarette smoke condensate (tar) on the formation of lipid peroxidation products in rat lung microsomal membranes enriched in vitro with varying beta-carotene concentrations (from 1 to 10 nmol/mg prot) and then incubated with tar (6-25 mug/ml) under different pO(2) [12].

Anatomical context of SLC6A7

  • The pharmacological specificity, kinetic properties, and ionic requirements of hPROT clearly distinguish this carrier from the other Na(+)-dependent plasma membrane carriers that transport L-proline [13].
  • An antipeptide antiserum directed against the carboxy-terminus of the predicted hPROT protein identified a single, broad immunoreactive protein of 68 kDa on immunoblots of synaptosomal membranes from various human brain regions [13].
  • A differential distribution of hPROT mRNA and protein was observed in the human corpus striatum, consistent with the hypothesis that the hPROT protein is synthesized in neuronal cell bodies in an extrastriatal location and axonally transported to the corpus striatum [13].
  • A differential distribution of PROT mRNA and protein was observed in rat striatum, suggesting that the transporter protein is synthesized in neuronal cell bodies in the cortex and exported to axon terminals in the caudate putamen [14].
  • Deglycosylation of rat hippocampal membranes with peptide-N-glycosidase F reduced the apparent molecular mass of the native PROT protein from 68 to 53 kDa, the size of the primary PROT translation product determined by in vitro translation of the rat PROT cDNA in the absence of microsomes [14].

Associations of SLC6A7 with chemical compounds

  • In all regions examined by electron microscopy (cortex, CPN, and the stratum oriens of CA1), PROT labeling was observed primarily within subpopulations of axon terminals forming asymmetric excitatory-type synapses [8].
  • Histamine type 2 receptor-bearing T cells inhibited Prot A PFC induction, but not Tg PFC induction, in the autologous T-B MC system [15].
  • The digitoxin-insensitive NA influx for cells in the presence of 10% FBS is 22.9 +/- 1.1 (n = 6) mumol/g prot/min [16].
  • In addition, a xanthine oxidase activity of 21.5 10(-6) U/mg prot could be observed by a direct assay in cells after H but not in control cells, thus confirming the previous conclusions of xanthine oxidase as a potent source of free radicals in these conditions [17].
  • The production of O2.(-) and of H2O2 by endothelial cells was directly estimated to be, respectively, of 0.17 and 0.035 mumol/min/mg prot during the R period [17].

Analytical, diagnostic and therapeutic context of SLC6A7

  • We report the molecular cloning, functional expression, and chromosomal localization of a human brain-specific high affinity L-proline transporter (hPROT) [13].
  • Sequence analysis of a cDNA containing the gag and prot regions of the soybean retrovirus-like element, SIRE-1 [18].
  • On the basis of X-ray diffraction determined secondary structures, the original data set used (Perczel, A., Hollosi, M., Tusnady, G. Fasman, G.D. Convex constraint analysis: A natural deconvolution of circular dichroism curves of proteins, Prot. Eng., 4:669-679, 1991), was improved by the addition of proteins with high beta-pleated sheet content [19].
  • We have used the CE structure alignment program (Shindyalov and Bourne, Prot Eng 1998;11:739) to derive sequence alignments for all superfamily and family-level related proteins in the SCOP domain database [20].
  • Prot A7, a polypeptidic proteinoid composed of seven different amino acids, was synthesized and microspheres of 1-5 microm size were prepared by the self-assembly process [21].


  1. Hepatic tocopherol content in primary hepatocellular carcinoma and liver metastases. Rocchi, E., Seium, Y., Camellini, L., Casalgrandi, G., Borghi, A., D'Alimonte, P., Cioni, G. Hepatology (1997) [Pubmed]
  2. A simplified immuno-enzymetric assay of the epidermal growth factor receptor in breast tumors: evaluation in 282 cases. Grimaux, M., Mady, E., Remvikos, Y., Laine-Bidron, C., Magdelenat, H. Int. J. Cancer (1990) [Pubmed]
  3. Inhibition of beta-lactamases by tazobactam and in-vitro antibacterial activity of tazobactam combined with piperacillin. Higashitani, F., Hyodo, A., Ishida, N., Inoue, M., Mitsuhashi, S. J. Antimicrob. Chemother. (1990) [Pubmed]
  4. In-vitro evaluation of ampicillin/brobactam and comparison with other beta-lactam antibiotics. Melchior, N.H., Keiding, J. J. Antimicrob. Chemother. (1991) [Pubmed]
  5. Hypermetabolism in the acute stage of hemorrhagic cerebrovascular disease. Touho, H., Karasawa, J., Shishido, H., Morisako, T., Yamada, K., Shibamoto, K. J. Neurosurg. (1990) [Pubmed]
  6. Effect of meal composition on alertness and performance of hospital night-shift workers. Do mood and performance have different determinants? Paz, A., Berry, E.M. Ann. Nutr. Metab. (1997) [Pubmed]
  7. Molecular biology of mammalian amino acid transporters. Malandro, M.S., Kilberg, M.S. Annu. Rev. Biochem. (1996) [Pubmed]
  8. The mammalian brain high-affinity L-proline transporter is enriched preferentially in synaptic vesicles in a subpopulation of excitatory nerve terminals in rat forebrain. Renick, S.E., Kleven, D.T., Chan, J., Stenius, K., Milner, T.A., Pickel, V.M., Fremeau, R.T. J. Neurosci. (1999) [Pubmed]
  9. Is morning urinary protein/creatinine ratio a reliable estimator of 24-hour proteinuria in patients with glomerulonephritis and different levels of renal function? Morales, J.V., Weber, R., Wagner, M.B., Barros, E.J. J. Nephrol. (2004) [Pubmed]
  10. A novel nonopioid action of enkephalins: competitive inhibition of the mammalian brain high affinity L-proline transporter. Fremeau, R.T., Velaz-Faircloth, M., Miller, J.W., Henzi, V.A., Cohen, S.M., Nadler, J.V., Shafqat, S., Blakely, R.D., Domin, B. Mol. Pharmacol. (1996) [Pubmed]
  11. Role of residues in the tryptophan repeat motif for HIV-1 reverse transcriptase dimerization. Tachedjian, G., Aronson, H.E., de los Santos, M., Seehra, J., McCoy, J.M., Goff, S.P. J. Mol. Biol. (2003) [Pubmed]
  12. Dual role of {beta}-carotene in combination with cigarette smoke aqueous extract on the formation of mutagenic lipid peroxidation products in lung membranes: dependence on pO2. Palozza, P., Serini, S., Trombino, S., Lauriola, L., Ranelletti, F.O., Calviello, G. Carcinogenesis (2006) [Pubmed]
  13. Human brain-specific L-proline transporter: molecular cloning, functional expression, and chromosomal localization of the gene in human and mouse genomes. Shafqat, S., Velaz-Faircloth, M., Henzi, V.A., Whitney, K.D., Yang-Feng, T.L., Seldin, M.F., Fremeau, R.T. Mol. Pharmacol. (1995) [Pubmed]
  14. Mammalian brain-specific L-proline transporter. Neuronal localization of mRNA and enrichment of transporter protein in synaptic plasma membranes. Velaz-Faircloth, M., Guadaño-Ferraz, A., Henzi, V.A., Fremeau, R.T. J. Biol. Chem. (1995) [Pubmed]
  15. Studies on thyroglobulin-specific suppressor T cell function in autoimmune thyroid disease. Mori, H., Hamada, N., DeGroot, L.J. J. Clin. Endocrinol. Metab. (1985) [Pubmed]
  16. Sodium fluxes in human fibroblasts: effect of serum, Ca+2, and amiloride. Villereal, M.L. J. Cell. Physiol. (1981) [Pubmed]
  17. Human umbilical vein endothelial cells submitted to hypoxia-reoxygenation in vitro: implication of free radicals, xanthine oxidase, and energy deficiency. Michiels, C., Arnould, T., Houbion, A., Remacle, J. J. Cell. Physiol. (1992) [Pubmed]
  18. Sequence analysis of a cDNA containing the gag and prot regions of the soybean retrovirus-like element, SIRE-1. Bi, Y.A., Laten, H.M. Plant Mol. Biol. (1996) [Pubmed]
  19. Deconvolution of the circular dichroism spectra of proteins: the circular dichroism spectra of the antiparallel beta-sheet in proteins. Perczel, A., Park, K., Fasman, G.D. Proteins (1992) [Pubmed]
  20. Large-scale comparison of protein sequence alignment algorithms with structure alignments. Sauder, J.M., Arthur, J.W., Dunbrack, R.L. Proteins (2000) [Pubmed]
  21. Preparation and characterization of pH-sensitive proteinoid microspheres for the oral delivery of methotrexate. Madhan Kumar, A.B., Panduranga Rao, K. Biomaterials (1998) [Pubmed]
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