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Gene Review

SLC33A1  -  solute carrier family 33 (acetyl-CoA...

Homo sapiens

Synonyms: ACATN, AT-1, AT1, Acetyl-CoA transporter 1, Acetyl-coenzyme A transporter 1, ...
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Disease relevance of SLC33A1

  • Although homologs of this family of proteins have been identified in lower organisms, such as Escherichia coli, Drosophila melanogaster, and Caenorhabditis. elegans, currently only one member of this SLC33A1 family has been identified in humans [1].
  • The AT-1 gene, originally named ACATN (acetyl-CoA transporter), was cloned from human melanoma cells [1].
  • CONCLUSIONS: These findings indicate that chronic blockade of Ang II receptors by either site-selective or balanced AT1/AT2 antagonists is insufficient to inhibit intimal hyperplasia after experimental coronary vascular injury in the pig [2].
  • OBJECTIVES: Treatment with erythropoietin and AT1 blockers is protective in experimental acute cerebral ischemia, with promising results in pilot clinical studies in human stroke [3].
  • Secondary rise of albuminuria under AT1-receptor blockade--what is the potential role of aldosterone escape [4]?

High impact information on SLC33A1

  • Immunohistochemical study with an antibody specific to the AT-1 protein suggested that it is most probably expressed in the endoplasmic reticulum membrane [5].
  • By expression cloning using COS-1 cells stably transfected with GD3-synthase (COS-1/GD3+) as a recipient cell line, we have isolated a cDNA, termed AT-1, encoding a novel protein required for the formation of O-acetylated (Ac) gangliosides [5].
  • METHODS AND RESULTS: In separate studies, three Ang II receptor antagonists, including AT1 selective (L-158,809), balanced AT1/AT2 (L-163,082), and AT2 selective (L-164,282) agents, were evaluated for their ability to inhibit vascular intimal thickening in a porcine coronary artery model of vascular injury [2].
  • The change in PKC epsilon distribution and in TnI phosphorylation in diabetic animals was completely prevented by rendering the animals euglycemic with insulin or by concomitant treatment with a specific angiotensin II type-1 receptor (AT1) antagonist [6].
  • Promoters for cell death pathway, death receptor 5, cyclins A1 and C, and caspases-1, -3, and -9, were upregulated, whereas cell death inhibitors, acetyl-CoA transporter, and NF-kappaB were also upregulated [7].

Chemical compound and disease context of SLC33A1


Biological context of SLC33A1

  • METHODS: Gene expression of the AT1 receptor was analysed by quantitative RT-PCR and protein expression was determined by immunoblot analysis in human right atrial myocardium [13].
  • Selective AT1 receptor antagonism enhances sympathetically mediated vasoconstriction in man [14].
  • Ultrasound induced a 55- (Mewo) to 220-fold (AT1) stimulation resulting in transfection efficiencies in vitro between 2% (Mewo) and 12% (AT1) [15].
  • CONCLUSION: The results explain why physiological concentrations of free Ang II far below the equilibrium dissociation constant of its reaction with AT1 receptors are sufficient to increase vascular resistance, and why a correlation between blood pressure and the concentration of free Ang II is often difficult to demonstrate [16].
  • This pre-receptor stimulus amplification (PRESTAMP) mechanism is sustained by AT1 receptor-mediated endocytosis and receptor recycling [16].

Anatomical context of SLC33A1

  • CONCLUSIONS/INTERPRETATION: AT1 receptor expression in myocardium of type 2 diabetic patients is dynamic, depending on the level of glycaemic control and the activity of the RAS [13].
  • Using Chinese hamster ovary (CHO) cells expressing cloned Kv7.2 + 7.3 heteromultimers and AT1 receptors studied under perforated patch clamp, angioII induced a strong suppression of the Kv7.2/7.3 current that returned to near baseline within 10 min of stimulation [17].
  • Losartan, a selective inhibitor of subtype AT1 receptors for angiotensin II, inhibits neutrophil recruitment in the lung triggered by fMLP [18].
  • Using an in vivo radioligand competition assay, in which receptor occupancy is demonstrated via competitive blockade of the in vivo binding of [125I][Sar1,Ile8]angiotensin II to AT1 receptors in rat kidney cortex, we demonstrated that the in vivo pharmacologic potencies reflect receptor occupancy [19].
  • The glucuronidation of the AT1 nonpeptide angiotensin II receptor antagonist, SR 47436 (BMS 186295), was investigated in hepatic microsomes prepared from various species, i.e., Sprague-Dawley rat, Cynomolgus monkey and Caucasian humans [20].

Associations of SLC33A1 with chemical compounds

  • The acetyl-CoA (Ac-CoA) transporter (AT-1) is a multiple transmembrane protein in the endoplasmic reticulum [1].
  • Losartan, an antagonist of Ang II receptor (AT1), abolishes the agonist-dependent stimulation of IRE/protein interaction and the consequent increase in MLC-2v gene transcription [21].
  • RESULTS: MAP responses to AT1 receptor inhibition and exogenous Ang II were attenuated in castrated NZGH [22].
  • In the first set of experiments, rats eating a low-sodium diet were infused with the AT1 blocker, candesartan, or vehicle [23].
  • High-performance liquid chromatographic analysis of anionic phospholipids in CHO cells stably expressing AT1 receptors revealed that PIP2 and phosphatidylinositol 4-phosphate levels are to be strongly depleted after 2 min of stimulation with angioII, with a partial rebound after 10 min [17].

Analytical, diagnostic and therapeutic context of SLC33A1


  1. The acetyl-CoA transporter family SLC33. Hirabayashi, Y., Kanamori, A., Nomura, K.H., Nomura, K. Pflugers Arch. (2004) [Pubmed]
  2. Effects of subtype-selective and balanced angiotensin II receptor antagonists in a porcine coronary artery model of vascular restenosis. Huckle, W.R., Drag, M.D., Acker, W.R., Powers, M., McFall, R.C., Holder, D.J., Fujita, T., Stabilito, I.I., Kim, D., Ondeyka, D.L., Mantlo, N.B., Chang, R.S., Reilly, C.F., Schwartz, R.S., Greenlee, W.J., Johnson, R.G. Circulation (1996) [Pubmed]
  3. Synergistic protective effects of erythropoietin and olmesartan on ischemic stroke survival and post-stroke memory dysfunctions in the gerbil. Faure, S., Oudart, N., Javellaud, J., Fournier, A., Warnock, D.G., Achard, J.M. J. Hypertens. (2006) [Pubmed]
  4. Secondary rise of albuminuria under AT1-receptor blockade--what is the potential role of aldosterone escape? Rump, L.C. Nephrol. Dial. Transplant. (2007) [Pubmed]
  5. Expression cloning and characterization of a cDNA encoding a novel membrane protein required for the formation of O-acetylated ganglioside: a putative acetyl-CoA transporter. Kanamori, A., Nakayama, J., Fukuda, M.N., Stallcup, W.B., Sasaki, K., Fukuda, M., Hirabayashi, Y. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  6. Experimental diabetes is associated with functional activation of protein kinase C epsilon and phosphorylation of troponin I in the heart, which are prevented by angiotensin II receptor blockade. Malhotra, A., Reich, D., Reich, D., Nakouzi, A., Sanghi, V., Geenen, D.L., Buttrick, P.M. Circ. Res. (1997) [Pubmed]
  7. Gene expression profile of spinal motor neurons in sporadic amyotrophic lateral sclerosis. Jiang, Y.M., Yamamoto, M., Kobayashi, Y., Yoshihara, T., Liang, Y., Terao, S., Takeuchi, H., Ishigaki, S., Katsuno, M., Adachi, H., Niwa, J., Tanaka, F., Doyu, M., Yoshida, M., Hashizume, Y., Sobue, G. Ann. Neurol. (2005) [Pubmed]
  8. Effect of losartan on right ventricular hypertrophy and cardiac angiotensin I-converting enzyme activity in pulmonary hypertensive rats. Kreutz, R., Fernandez-Alfonso, M.S., Ganten, D., Paul, M. Clin. Exp. Hypertens. (1996) [Pubmed]
  9. The angiotensin II receptor antagonist valsartan enhances lipoprotein lipase mass in preheparin serum in type 2 diabetes with hypertension. Saiki, A., Ohira, M., Endo, K., Koide, N., Oyama, T., Murano, T., Miyashita, Y., Shirai, K. Diabetes Res. Clin. Pract. (2006) [Pubmed]
  10. Expression of angiotensin II type 1 receptor in human cirrhotic livers: Its relation to fibrosis and portal hypertension. Ikura, Y., Ohsawa, M., Shirai, N., Sugama, Y., Fukushima, H., Suekane, T., Hirayama, M., Ehara, S., Naruko, T., Ueda, M. Hepatol. Res. (2005) [Pubmed]
  11. Candesartan cilexetil on regular hemodialysis: inability to reduce excessive thirst, but good tolerance and efficacy in hypertensive patients. Rostoker, G., Griuncelli, M., Benmaadi, A. Renal failure. (2006) [Pubmed]
  12. Tumor oxygen dynamics: correlation of in vivo MRI with histological findings. Zhao, D., Ran, S., Constantinescu, A., Hahn, E.W., Mason, R.P. Neoplasia (2003) [Pubmed]
  13. The increased angiotensin II (type 1) receptor density in myocardium of type 2 diabetic patients is prevented by blockade of the renin-angiotensin system. Reuter, H., Adam, C., Gr??nke, S., Zobel, C., Frank, K.F., M??ller-Ehmsen, J., Brabender, J., Schwinger, R.H. Diabetologia (2006) [Pubmed]
  14. Selective AT1 receptor antagonism enhances sympathetically mediated vasoconstriction in man. Lyons, D., Jackson, S.H., Swift, C.G. Clin. Pharmacol. Ther. (2007) [Pubmed]
  15. In vitro and in vivo transfection of plasmid DNA in the Dunning prostate tumor R3327-AT1 is enhanced by focused ultrasound. Huber, P.E., Pfisterer, P. Gene Ther. (2000) [Pubmed]
  16. A local pre-receptor mechanism of hormone stimulus amplification: focus on angiotensin II in resistance blood vessels. Schalekamp, M.A. J. Hypertens. (2006) [Pubmed]
  17. Angiotensin II regulates neuronal excitability via phosphatidylinositol 4,5-bisphosphate-dependent modulation of Kv7 (M-type) K+ channels. Zaika, O., Lara, L.S., Gamper, N., Hilgemann, D.W., Jaffe, D.B., Shapiro, M.S. J. Physiol. (Lond.) (2006) [Pubmed]
  18. Losartan, a selective inhibitor of subtype AT1 receptors for angiotensin II, inhibits neutrophil recruitment in the lung triggered by fMLP. Raiden, S., Pereyra, Y., Nahmod, V., Alvarez, C., Castello, L., Giordano, M., Geffner, J. J. Leukoc. Biol. (2000) [Pubmed]
  19. In vivo receptor occupancy of the angiotensin II receptor by nonpeptide antagonists: relationship to in vitro affinities and in vivo pharmacologic potency. Beauchamp, H.T., Chang, R.S., Siegl, P.K., Gibson, R.E. J. Pharmacol. Exp. Ther. (1995) [Pubmed]
  20. In vitro N-glucuronidation of SB 47436 (BMS 186295), a new AT1 nonpeptide angiotensin II receptor antagonist, by rat, monkey and human hepatic microsomal fractions. Perrier, L., Bourrié, M., Marti, E., Tronquet, C., Massé, D., Berger, Y., Magdalou, J., Fabre, G. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
  21. A ternary complex of transcription factors, Nishéd and NFATc4, and co-activator p300 bound to an intronic sequence, intronic regulatory element, is pivotal for the up-regulation of myosin light chain-2v gene in cardiac hypertrophy. Mathew, S., Mascareno, E., Siddiqui, M.A. J. Biol. Chem. (2004) [Pubmed]
  22. Androgens potentiate renal vascular responses to angiotensin II via amplification of the Rho kinase signaling pathway. Song, J., Kost, C.K., Martin, D.S. Cardiovasc. Res. (2006) [Pubmed]
  23. Long-term regulation of proximal tubule acid-base transporter abundance by angiotensin II. Turban, S., Beutler, K.T., Morris, R.G., Masilamani, S., Fenton, R.A., Knepper, M.A., Packer, R.K. Kidney Int. (2006) [Pubmed]
  24. Expression of renal and vascular angiotensin II receptor subtypes in children. Viswanathan, M., Selby, D.M., Ray, P.E. Pediatr. Nephrol. (2000) [Pubmed]
  25. Immunocytochemical localization of muscarinic, adrenergic and AT1 receptors. Schulze, W., Fu, M.L. Blood pressure. Supplement. (1996) [Pubmed]
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