Gene Symbol: aanat2
Description: arylalkylamine N-acetyltransferase 2
Alias: AA-NAT, arylalkylamine N-acetyltransferase, serotonin N-acetyltransferase-2
Species: zebrafish

Top Publications

  1. Zilberman Peled B, Benhar I, Coon S, Ron B, Gothilf Y. Duality of serotonin-N-acetyltransferase in the gilthead seabream (Sparus aurata): molecular cloning and characterization of recombinant enzymes. Gen Comp Endocrinol. 2004;138:139-47 pubmed
    ..The presence of two AANATs, AANAT1 and AANAT2, has been previously demonstrated in three fresh water teleosts...
  2. Ziv L, Levkovitz S, Toyama R, Falcon J, Gothilf Y. Functional development of the zebrafish pineal gland: light-induced expression of period2 is required for onset of the circadian clock. J Neuroendocrinol. 2005;17:314-20 pubmed
    ..These experiments indicated that light-induced zper2 expression is crucial for establishment of the clock-controlled zfaanat2 rhythm in the zebrafish pineal gland. ..
  3. Toyama R, Chen X, Jhawar N, Aamar E, Epstein J, Reany N, et al. Transcriptome analysis of the zebrafish pineal gland. Dev Dyn. 2009;238:1813-26 pubmed publisher
    ..Among the multiple candidate genes suggested by these data, we note the identification of a tissue-specific form of the unc119 gene with a possible role in pineal development. ..
  4. Ziv L, Gothilf Y. Circadian time-keeping during early stages of development. Proc Natl Acad Sci U S A. 2006;103:4146-51 pubmed
    ..The 24-h rhythm is then maintained throughout rapid proliferation and, remarkably, differentiation...
  5. Dickmeis T, Lahiri K, Nica G, Vallone D, Santoriello C, Neumann C, et al. Glucocorticoids play a key role in circadian cell cycle rhythms. PLoS Biol. 2007;5:e78 pubmed
    ..Instead, they act in concert with a systemic signaling environment of which glucocorticoids are an essential part. ..
  6. Falc n J, Coon S, Besseau L, Cazam a Catalan D, Fuent s M, Magnanou E, et al. Drastic neofunctionalization associated with evolution of the timezyme AANAT 500 Mya. Proc Natl Acad Sci U S A. 2014;111:314-9 pubmed publisher
    ..This scenario is consistent with the hypotheses that the advent of VT-AANAT contributed to the evolution of the pineal gland and lateral eyes from a common ancestral photodetector and that it was not a posthoc recruitment...
  7. Appelbaum L, Anzulovich A, Baler R, Gothilf Y. Homeobox-clock protein interaction in zebrafish. A shared mechanism for pineal-specific and circadian gene expression. J Biol Chem. 2005;280:11544-51 pubmed
    ..OTX5-BMAL/CLOCK may act through this mechanism to simultaneously control pineal-specific and rhythmic expression of zfaanat2 and possibly also other pineal and retinal genes. ..
  8. Smadja Storz S, Tovin A, Mracek P, Alon S, Foulkes N, Gothilf Y. Casein kinase 1? activity: a key element in the zebrafish circadian timing system. PLoS ONE. 2013;8:e54189 pubmed publisher
    ..Moreover, the addition of the CK1?/? inhibitor disrupted rhythms of aanat2 mRNA expression in the pineal gland...
  9. Delaunay F, Thisse C, Thisse B, Laudet V. Differential regulation of Period 2 and Period 3 expression during development of the zebrafish circadian clock. Gene Expr Patterns. 2003;3:319-24 pubmed
    ..This differential spatio-temporal expression patterns suggest specific roles for Per2 and Per3 in the establishment of the embryonic circadian system. ..

More Information


  1. Appelbaum L, Toyama R, Dawid I, Klein D, Baler R, Gothilf Y. Zebrafish serotonin-N-acetyltransferase-2 gene regulation: pineal-restrictive downstream module contains a functional E-box and three photoreceptor conserved elements. Mol Endocrinol. 2004;18:1210-21 pubmed
    ..These results indicate that pineal specificity of zfaanat-2 is determined by the dual functionality of the PRDM and the interaction between upstream regulatory region and downstream photoreceptor conserved elements and E-box element. ..
  2. Pierce L, Noche R, Ponomareva O, Chang C, Liang J. Novel functions for Period 3 and Exo-rhodopsin in rhythmic transcription and melatonin biosynthesis within the zebrafish pineal organ. Brain Res. 2008;1223:11-24 pubmed publisher
    ..Exorh, expression of the exorh gene itself and of the melatonin synthesis gene serotonin N-acetyl transferase 2 (aanat2) are significantly reduced...
  3. Gothilf Y, Coon S, Toyama R, Chitnis A, Namboodiri M, Klein D. Zebrafish serotonin N-acetyltransferase-2: marker for development of pineal photoreceptors and circadian clock function. Endocrinology. 1999;140:4895-903 pubmed
    ..The observations described here suggest that zfAANAT-2 mRNA may be a useful marker to study development of the pineal gland and of circadian clock mechanisms in zebrafish. ..
  4. B gay V, Falc n J, Cahill G, Klein D, Coon S. Transcripts encoding two melatonin synthesis enzymes in the teleost pineal organ: circadian regulation in pike and zebrafish, but not in trout. Endocrinology. 1998;139:905-12 pubmed publisher
  5. Vuilleumier R, Besseau L, Boeuf G, Piparelli A, Gothilf Y, Gehring W, et al. Starting the zebrafish pineal circadian clock with a single photic transition. Endocrinology. 2006;147:2273-9 pubmed
    ..the photopigment exorhodopsin and the other the melatonin synthesizing enzyme arylalkylamine N-acetyltransferase (AANAT2)...
  6. Vatine G, Vallone D, Appelbaum L, Mracek P, Ben Moshe Z, Lahiri K, et al. Light directs zebrafish period2 expression via conserved D and E boxes. PLoS Biol. 2009;7:e1000223 pubmed publisher
    ..These findings extend the general understanding of the mechanism whereby the clock is entrained by light and how the regulation of clock gene expression by light has evolved in vertebrates...
  7. Falcon J, Gothilf Y, Coon S, Boeuf G, Klein D. Genetic, temporal and developmental differences between melatonin rhythm generating systems in the teleost fish pineal organ and retina. J Neuroendocrinol. 2003;15:378-82 pubmed
    ..We review the fish pineal and retinal melatonin rhythm generating systems and consider the evolutional pressures and other factors which led to these differences. ..
  8. Ben Moshe Z, Alon S, Mracek P, Faigenbloom L, Tovin A, Vatine G, et al. The light-induced transcriptome of the zebrafish pineal gland reveals complex regulation of the circadian clockwork by light. Nucleic Acids Res. 2014;42:3750-67 pubmed publisher
    ..to downregulate e4bp4-6 mRNA through a 3'UTR target site, and importantly, to regulate the rhythmic mRNA levels of aanat2, the key enzyme in melatonin synthesis...
  9. Chen S, Oikonomou G, Chiu C, Niles B, Liu J, Lee D, et al. A large-scale in vivo analysis reveals that TALENs are significantly more mutagenic than ZFNs generated using context-dependent assembly. Nucleic Acids Res. 2013;41:2769-78 pubmed publisher
    ..The higher mutation rates and ability to target essentially any sequence make TALENs the superior technology for targeted mutagenesis in zebrafish, and likely other animal models. ..
  10. Collery R, McLoughlin S, Vendrell V, Finnegan J, Crabb J, Saari J, et al. Duplication and divergence of zebrafish CRALBP genes uncovers novel role for RPE- and Muller-CRALBP in cone vision. Invest Ophthalmol Vis Sci. 2008;49:3812-20 pubmed publisher
    ..Recent evidence suggests a role for Müller glia in an alternate cone visual cycle. In this study, the role of RPE- and Müller-CRALBP in cone vision was characterized...
  11. Egg M, Paulitsch M, Ennemoser Y, Wüstenhagen A, Schwerte T, Sandbichler A, et al. Chronodisruption increases cardiovascular risk in zebrafish via reduced clearance of senescent erythrocytes. Chronobiol Int. 2014;31:680-9 pubmed publisher
    ..The results might shed new light on the etiology of the increased cardiovascular risk observed among shiftworkers. ..
  12. Zhang Y, Bonilla S, Chong L, Leung Y. Irx7, a Smarca4-regulated gene for retinal differentiation, regulates other genes controlled by Smarca4 in zebrafish retinas. Gene Expr Patterns. 2013;13:177-82 pubmed publisher
    ..This study reports an investigation of the regulatory role of irx7 on 13 genes including aanat2, barhl2, bhlhe22, cdh11, ckmt1, gnat1, irx4a, ndrg1a, nme2l, pbx1a, rcv1, robo2 and tfap2a...
  13. Alon S, Eisenberg E, Jacob Hirsch J, Rechavi G, Vatine G, Toyama R, et al. A new cis-acting regulatory element driving gene expression in the zebrafish pineal gland. Bioinformatics. 2009;25:559-62 pubmed publisher
    ..Ab initio motif detection algorithms have been extensively used in search of regulatory elements. Yet, their success in providing experimentally validated regulatory elements in vertebrates has been limited...
  14. Pavlou S, Astell K, Kasioulis I, Gakovic M, Baldock R, van Heyningen V, et al. Pleiotropic effects of Sox2 during the development of the zebrafish epithalamus. PLoS ONE. 2014;9:e87546 pubmed publisher
    ..Deviations from this strict control result in defects associated with abnormal habenular laterality, which we have documented and quantified in sox2 morphants. ..
  15. Ziv L, Gothilf Y. Period2 expression pattern and its role in the development of the pineal circadian clock in zebrafish. Chronobiol Int. 2006;23:101-12 pubmed
    ..Thus, a possible role for early photoreception and light-induced zper2 expression in the development of clock-controlled rhythms remains to be investigated. ..
  16. Lu P, Lund C, Khuansuwan S, Schumann A, Harney Tolo M, Gamse J, et al. Failure in closure of the anterior neural tube causes left isomerization of the zebrafish epithalamus. Dev Biol. 2013;374:333-44 pubmed publisher
    ..This mechanism fails when the two sides of the epithalamus are widely separated from one another, suggesting that it is dependent upon a signaling protein with limited range. ..
  17. Gandhi A, Mosser E, Oikonomou G, Prober D. Melatonin is required for the circadian regulation of sleep. Neuron. 2015;85:1193-9 pubmed publisher
    ..Here we use animals lacking melatonin due to mutation of arylalkylamine N-acetyltransferase 2 (aanat2) to show that melatonin is required for circadian regulation of sleep in zebrafish...
  18. Lahiri K, Froehlich N, Heyd A, Foulkes N, Vallone D. Developmental stage-specific regulation of the circadian clock by temperature in zebrafish. Biomed Res Int. 2014;2014:930308 pubmed publisher
    ..Furthermore, we show that following the 5-9 somite stage, the expression of zfper1b is regulated by acute temperature shifts. ..
  19. Appelbaum L, Gothilf Y. Mechanism of pineal-specific gene expression: the role of E-box and photoreceptor conserved elements. Mol Cell Endocrinol. 2006;252:27-33 pubmed
    ..These transcription factors drive enhanced expression of serotonin-N-acetyltransferase-2 (aanat2) in the pineal gland by synergistic interaction...
  20. Zilberman Peled B, Ron B, Gross A, Finberg J, Gothilf Y. A possible new role for fish retinal serotonin-N-acetyltransferase-1 (AANAT1): Dopamine metabolism. Brain Res. 2006;1073-1074:220-8 pubmed
    ..Rhythmic AANAT activity drives rhythmic melatonin production in these tissues. Two AANATs, AANAT1 and AANAT2, are present in teleost fish species...
  21. Cazaméa Catalan D, Besseau L, Falcón J, Magnanou E. The timing of Timezyme diversification in vertebrates. PLoS ONE. 2014;9:e112380 pubmed publisher
    ..We highlight a gene secondary loss of the AANAT2 in the Sarcopterygii, revealing for the first time that the AAANAT1/2 duplication occurred before the divergence ..
  22. Khan Z, Yumnamcha T, Rajiv C, Sanjita Devi H, Mondal G, Devi S, et al. Melatonin biosynthesizing enzyme genes and clock genes in ovary and whole brain of zebrafish (Danio rerio): Differential expression and a possible interplay. Gen Comp Endocrinol. 2016;233:16-31 pubmed publisher
    ..attempt to demonstrate the circadian mRNA expression of melatonin biosynthesizing enzyme genes (Tph1a, Aanat1, Aanat2 and Hiomt) and clock associated genes (Bmal1a, Clock1a, Per1b, Per2 and Cry2a) in the ovary with a comparison to ..
  23. Ren D, Ji C, Wang X, Wang H, Hu B. Endogenous melatonin promotes rhythmic recruitment of neutrophils toward an injury in zebrafish. Sci Rep. 2017;7:4696 pubmed publisher
    ..Here we generated a zebrafish annat2 mutant that lacks endogenous melatonin and, subsequently, a Tg(lyz:EGFP);aanat2 -/- transgenic line that allows for monitoring neutrophils migration visually in live zebrafish...
  24. Koyanagi M, Wada S, Kawano Yamashita E, Hara Y, Kuraku S, Kosaka S, et al. Diversification of non-visual photopigment parapinopsin in spectral sensitivity for diverse pineal functions. BMC Biol. 2015;13:73 pubmed publisher
    ..Furthermore, we found that PP2-expressing cells contain serotonin and aanat2, the key enzyme involved in melatonin synthesis from serotonin, whereas PP1-expressing cells do not contain either,..
  25. Du L, Darroch H, Keerthisinghe P, Ashimbayeva E, Astin J, Crosier K, et al. The innate immune cell response to bacterial infection in larval zebrafish is light-regulated. Sci Rep. 2017;7:12657 pubmed publisher
  26. Appelbaum L, Wang G, Yokogawa T, Skariah G, Smith S, Mourrain P, et al. Circadian and homeostatic regulation of structural synaptic plasticity in hypocretin neurons. Neuron. 2010;68:87-98 pubmed publisher
    ..This behavioral effect is consistent with NPTX2b-mediated increased activity of HCRT circuitry. These data provide real-time in vivo evidence of circadian and homeostatic regulation of structural synaptic plasticity. ..
  27. Appelbaum L, Wang G, Maro G, Mori R, Tovin A, Marin W, et al. Sleep-wake regulation and hypocretin-melatonin interaction in zebrafish. Proc Natl Acad Sci U S A. 2009;106:21942-7 pubmed publisher
    ..mRNA level of arylalkylamine-N-acetyltransferase (AANAT2), a key enzyme of melatonin synthesis, is reduced in hcrtr-/- pineal gland during the night...
  28. Li X, Zhang Y, Li X, Feng D, Zhang S, Zhao X, et al. Comparative analysis of biological effect of corannulene and graphene on developmental and sleep/wake profile of zebrafish larvae. Acta Biomater. 2017;55:271-282 pubmed publisher
    ..regulators such as hcrt, hcrt G-protein coupled receptor (hcrtr), and arylalkylamine N-acetyltransferase-2 (aanat2) was evaluated...
  29. Appelbaum L, Vallone D, Anzulovich A, Ziv L, Tom M, Foulkes N, et al. Zebrafish arylalkylamine-N-acetyltransferase genes - targets for regulation of the circadian clock. J Mol Endocrinol. 2006;36:337-47 pubmed
    ..Zebrafish possess two aanats, aanat1 and aanat2; the former is expressed only in the retina and the latter is expressed in both the retina and the pineal gland...
  30. Wang M, Zhong Z, Zhong Y, Zhang W, Wang H. The zebrafish period2 protein positively regulates the circadian clock through mediation of retinoic acid receptor (RAR)-related orphan receptor α (Rorα). J Biol Chem. 2015;290:4367-82 pubmed publisher
    ..constant darkness, and quantitative real time PCR analyses showed up-regulation of cry1aa, cry1ba, cry1bb, and aanat2 but down-regulation of per1b, per3, and bmal1b in per2 mutant zebrafish, suggesting that Per2 is essential for the ..
  31. Elbaz I, Zada D, Tovin A, Braun T, Lerer Goldshtein T, Wang G, et al. Sleep-Dependent Structural Synaptic Plasticity of Inhibitory Synapses in the Dendrites of Hypocretin/Orexin Neurons. Mol Neurobiol. 2017;54:6581-6597 pubmed publisher
    ..These results suggest that rhythmic structural plasticity of inhibitory synapses in Hcrt dendrites is independent of the circadian clock and is modulated by consolidated wake and sleep. ..
  32. Chen H, Leung T, Giger K, Stauffer A, Humbert J, Sinha S, et al. Expression of the G protein gammaT1 subunit during zebrafish development. Gene Expr Patterns. 2007;7:574-83 pubmed
    ..Taken together, these data indicate that pineal- and retinal-specific expression of the gngT1 gene are controlled by different transcription factors and exogenous signals. ..
  33. Noche R, Lu P, Goldstein Kral L, Glasgow E, Liang J. Circadian rhythms in the pineal organ persist in zebrafish larvae that lack ventral brain. BMC Neurosci. 2011;12:7 pubmed publisher
    ..Expression of two pineal rhythmic genes, exo-rhodopsin (exorh) and serotonin-N-acetyltransferase (aanat2), involved in photoreception and melatonin synthesis, respectively, is also similar between cyc embryos and their ..