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Gene Review

AANAT  -  aralkylamine N-acetyltransferase

Gallus gallus

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Psychiatry related information on AANAT


High impact information on AANAT


Biological context of AANAT

  • Here we determined that the chicken AA-NAT mRNA is detectable in follicular pineal cells and retinal photoreceptors and that it exhibits a circadian rhythm, with peak levels at night [6].
  • The nucleic acid sequence of a 400 bp cDNA clone obtained by RT-PCR manifested 78 and 95% homology compared to the rat and chicken AANAT cDNA, respectively, while the deduced amino acid sequence homology was 82 and 99%, respectively [7].
  • The purpose of the present study was to examine the conditions of AANAT and HIOMT gene activation, relative to that of selected phototransduction markers (alpha-transducin and opsins), in both in vivo and in vitro differentiating photoreceptors of the chicken retina [8].
  • Culture conditions were modified to test the effects of cell density, serum concentration, incubation temperature, S-(4-nitrobenzyl)-6-thioinosine (NBTI), and taurine on AANAT activity [9].
  • Related studies indicate that the clock-dependent nocturnal increase in AA-NAT mRNA requires gene expression but not de novo protein synthesis, and that AA-NAT mRNA levels are suppressed at all times of the day by a rapidly turning over protein [5].

Anatomical context of AANAT

  • The AA-NAT mRNA rhythm in the pineal gland and retina persists in constant darkness (DD) and constant lighting (LL) [6].
  • AANAT mRNA was also detected in the testis, but did not display a rhythmic change over a 24 hr period [7].
  • In cells incubated in this manner, a 2-h light pulse in the middle of the subjective night suppressed AANAT activity, indicating that the enzyme activity in the cultured cells is acutely suppressed by light, as it is in vivo [10].
  • Photoreceptor-enriched cell cultures prepared from chick embryo retina and entrained to a daily light-dark (LD) cycle exhibit circadian rhythms of cAMP levels and the activity of arylalkylamine N-acetyltransferase (AANAT), a key regulatory enzyme in melatonin synthesis [11].
  • In contrast to the external regulation of pineal rhythms in mammals by the suprachiasmatic nucleus, rhythmic changes in AA-NAT activity in cultured chick pineal cells are controlled by an oscillator located in the pineal cells themselves [5].

Associations of AANAT with chemical compounds

  • Avian melatonin synthesis: photic and circadian regulation of serotonin N-acetyltransferase mRNA in the chicken pineal gland and retina [6].
  • The UV-A light-evoked decline in pineal AANAT activity was blocked by cAMP protagonists (forskolin and dibutyryl-cAMP) and by inhibitors of the proteasomal degradation pathway (MG-132, proteasome inhibitor I, and lactacystin) [12].
  • The effect of light on AANAT activity was reversed by Bay K 8644, 8Br-cAMP, and the proteasome inhibitor lactacystin [13].
  • The effect of Bay K 8644 was antagonized by the adenylyl cyclase inhibitor MDL 12330A, suggesting a link between Ca(2+) influx, cAMP formation, and AANAT activity in retinal cells [13].
  • In the present study, we investigated the circadian and photic regulation of adenosine 3',5'-monophosphate (cAMP) in cultured retinal cells entrained to a daily light-dark (LD) cycle, as well as the role of Ca(2+) and cAMP in the regulation of AANAT activity [13].

Regulatory relationships of AANAT

  • These rhythms appear to reflect circadian clock control of AA-NAT mRNA abundance and independent effects of light and darkness on both mRNA levels and enzyme activity [14].

Other interactions of AANAT

  • The CREM product, ICER, is rhythmically expressed and participates in a transcriptional autoregulatory loop which also controls the amplitude of oscillations of serotonin N-acetyl transferase (AANAT), the rate-limiting enzyme of melatonin synthesis [15].
  • Development of light-dark regulation of AANAT activity appears to precede the circadian clock-control of enzyme activity [10].
  • The iodopsin and AANAT mRNA rhythms re-emerged in the cultured retinas within 24 h of removal of the compounds [16].
  • METHODS: Neural retina RNA was obtained between embryonic day 7 (E7) and posthatch day 8 (P8) and analyzed on northern blots with cDNA probes to AANAT, HIOMT, visinin, alpha-transducin, rhodopsin, and the four cone opsins [8].
  • Systemic or intravitreal administration of muscimol, a GABA-A receptor agonist, to light-exposed chicks at the beginning of the dark phase of the light/dark cycle increased retinal melatonin levels and the activity of serotonin N-acetyltransferase (NAT), a key regulatory enzyme of the melatonin biosynthetic pathway [17].

Analytical, diagnostic and therapeutic context of AANAT

  • Tissue homogenates were prepared, AA-NAT enzyme activity was measured, and immunoreactive protein was estimated by Western blot using an anti-chicken AA-NAT(1-21) serum [18].
  • By size-exclusion chromatography, ANAT was confirmed to be 30-35 kDa, and SNAT was estimated at 15-20 kDa [19].
  • In addition to that, the nocturnal increase in pineal and, to a lower extent, retinal AA-NAT activity was significantly lower in dexamethasone-treated birds when compared with the respective control groups [20].


  1. Regulation of pineal rhythms in chickens: refractory period and nonvisual light perception. Binkley, S., Macbride, S.E., Klein, D.C., Ralph, C.L. Endocrinology (1975) [Pubmed]
  2. Rhodopsin-like photosensitivity of isolated chicken pineal gland. Deguchi, T. Nature (1981) [Pubmed]
  3. Diurnal cycles in serotonin acetyltransferase activity and cyclic GMP content of cultured chick pineal glands. Wainwright, S.D. Nature (1980) [Pubmed]
  4. A circadian oscillator in cultured cells of chicken pineal gland. Deguchi, T. Nature (1979) [Pubmed]
  5. Chick pineal clock regulates serotonin N-acetyltransferase mRNA rhythm in culture. Bernard, M., Klein, D.C., Zatz, M. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  6. Avian melatonin synthesis: photic and circadian regulation of serotonin N-acetyltransferase mRNA in the chicken pineal gland and retina. Bernard, M., Iuvone, P.M., Cassone, V.M., Roseboom, P.H., Coon, S.L., Klein, D.C. J. Neurochem. (1997) [Pubmed]
  7. Regulation of the expression of serotonin N-acetyltransferase gene in Japanese quail (Coturnix japonica): I. Rhythmic pattern and effect of light. Kato, H., Fu, Z., Kotera, N., Sugahara, K., Kubo, T. J. Pineal Res. (1999) [Pubmed]
  8. Differential regulation of melatonin synthesis genes and phototransduction genes in embryonic chicken retina and cultured retinal precursor cells. Cailleau, V., Bernard, M., Morin, F., Guerlotte, J., Voisin, P. Mol. Vis. (2005) [Pubmed]
  9. Diurnal regulation of arylalkylamine N-acetyltransferase activity in chicken retinal cells in vitro: analysis of culture conditions. Haque, R., Alonso-Gómez, A.L., Chaurasia, S.S., Iuvone, P.M. Mol. Vis. (2003) [Pubmed]
  10. Melatonin synthesis in retina: circadian regulation of arylalkylamine N-acetyltransferase activity in cultured photoreceptor cells of embryonic chicken retina. Ivanova, T.N., Iuvone, P.M. Brain Res. (2003) [Pubmed]
  11. Circadian clockwork machinery in neural retina: Evidence for the presence of functional clock components in photoreceptor-enriched chick retinal cell cultures. Chaurasia, S.S., Pozdeyev, N., Haque, R., Visser, A., Ivanova, T.N., Iuvone, P.M. Mol. Vis. (2006) [Pubmed]
  12. UV-A light regulation of arylalkylamine N-acetyltransferase activity in the chick pineal gland: role of cAMP and proteasomal proteolysis. Rosiak, J., Michael Iuvone, P., Zawilska, J.B. J. Pineal Res. (2005) [Pubmed]
  13. Circadian rhythm and photic control of cAMP level in chick retinal cell cultures: a mechanism for coupling the circadian oscillator to the melatonin-synthesizing enzyme, arylalkylamine N-acetyltransferase, in photoreceptor cells. Ivanova, T.N., Iuvone, P.M. Brain Res. (2003) [Pubmed]
  14. Cellular and molecular regulation of serotonin N-acetyltransferase activity in chicken retinal photoreceptors. Iuvone, P.M., Bernard, M., Alonso-Gomez, A., Greve, P., Cassone, V.M., Klein, D.C. Biol. Signals (1997) [Pubmed]
  15. Rhythmic transcription: the molecular basis of circadian melatonin synthesis. Foulkes, N.S., Whitmore, D., Sassone-Corsi, P. Biol. Cell (1997) [Pubmed]
  16. Rhythmic expression of clock-controlled genes in retinal photoreceptors is sensitive to 18-beta-glycyrrhetnic acid and 18-alpha-glycyrrhetnic acid-3-hemisuccinate. Zhang, Y., Semple-Rowland, S.L. Brain Res. Mol. Brain Res. (2005) [Pubmed]
  17. Regulation of melatonin and dopamine biosynthesis in chick retina: the role of GABA. Kazula, A., Nowak, J.Z., Iuvone, P.M. Vis. Neurosci. (1993) [Pubmed]
  18. Retinal melatonin production: role of proteasomal proteolysis in circadian and photic control of arylalkylamine N-acetyltransferase. Iuvone, P.M., Brown, A.D., Haque, R., Weller, J., Zawilska, J.B., Chaurasia, S.S., Ma, M., Klein, D.C. Invest. Ophthalmol. Vis. Sci. (2002) [Pubmed]
  19. Properties of clock-controlled and constitutive N-acetyltransferases from chick pineal cells. Wolfe, M.S., Lee, N.R., Zatz, M. Brain Res. (1995) [Pubmed]
  20. Prolonged treatment with glucocorticoid dexamethasone suppresses melatonin production by the chick pineal gland and retina. Zawilska, J.B., Sadowska, M. Polish journal of pharmacology. (2002) [Pubmed]
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