aspartate ammonia ligase


Summary: An enzyme that catalyzes the formation of asparagine from ammonia and aspartic acid, in the presence of ATP. EC

Top Publications

  1. Hirasawa T, Wachi M, Nagai K. A mutation in the Corynebacterium glutamicum ltsA gene causes susceptibility to lysozyme, temperature-sensitive growth, and L-glutamate production. J Bacteriol. 2000;182:2696-701 pubmed
    ..These results indicate that the ltsA gene encodes a novel glutamine-dependent amidotransferase that is involved in the mechanisms of formation of rigid cell wall structure and in the L-glutamate production of C. glutamicum...
  2. Hughes C, Beard H, Matthews B. Molecular cloning and expression of two cDNAs encoding asparagine synthetase in soybean. Plant Mol Biol. 1997;33:301-11 pubmed
    ..AS transcript was expressed in all tissues examined, but higher levels were seen in stem and root of light-grown tissue and leaves of dark-treated tissue...
  3. Humbert R, Simoni R. Genetic and biomedical studies demonstrating a second gene coding for asparagine synthetase in Escherichia coli. J Bacteriol. 1980;142:212-20 pubmed
    ..Physiological studies showed that either enzyme alone is sufficient to allow a maximal growth rate under conditions of asparagine limitation. ..
  4. Yu Y, Wootton J, Altschul S. The compositional adjustment of amino acid substitution matrices. Proc Natl Acad Sci U S A. 2003;100:15688-93 pubmed
    ..Composition-specific substitution matrix adjustment is shown to be of utility for comparing compositionally biased proteins, including those of organisms with nucleotide-biased, and therefore codon-biased, genomes or isochores. ..
  5. Wong H, Chan H, Coruzzi G, Lam H. Correlation of ASN2 gene expression with ammonium metabolism in Arabidopsis. Plant Physiol. 2004;134:332-8 pubmed
    ..These results support the notion that ASN2 is closely correlated to ammonium metabolism in higher plants. ..
  6. Scofield M, Lewis W, Schuster S. Nucleotide sequence of Escherichia coli asnB and deduced amino acid sequence of asparagine synthetase B. J Biol Chem. 1990;265:12895-902 pubmed
    ..A purF type glutamine amide transfer domain was identified upon inspection of the amino-terminal amino acid sequence of the asparagine synthetase B protein. ..
  7. Boehlein S, Richards N, Schuster S. Glutamine-dependent nitrogen transfer in Escherichia coli asparagine synthetase B. Searching for the catalytic triad. J Biol Chem. 1994;269:7450-7 pubmed
    ..abstract truncated at 400 words) ..
  8. Abbatiello S, Pan Y, Zhou M, Wayne A, Veenstra T, Hunger S, et al. Mass spectrometric quantification of asparagine synthetase in circulating leukemia cells from acute lymphoblastic leukemia patients. J Proteomics. 2008;71:61-70 pubmed publisher
  9. Li Y, Yang F, Zhu C, Tang L. Effect and mechanism of RNAi targeting WWTR1 on biological activity of gastric cancer cells SGC7901. Mol Med Rep. 2017;: pubmed publisher
    ..In conclusion, WWTR1 promotes cell proliferation and inhibits apoptosis of GC cells by regulating cell cycle/apoptosis?associated factors, and effectors in the TGF?? pathway...

More Information


  1. Li B, Gu L, Luo C, Li W, Jiang L, Jiang H, et al. The downregulation of asparagine synthetase expression can increase the sensitivity of cells resistant to l-asparaginase. Leukemia. 2006;20:2199-201 pubmed
  2. Wu S, Li Y, Wang Y. [Expression of asparagine synthetase in relapsed or refractory extranodal NK/T cell lymphoma]. Nan Fang Yi Ke Da Xue Xue Bao. 2016;37:465-469 pubmed
    ..Asparaginasum-based chemotherapy regimens are recommended for treatment of relapsed or refractory extranodal NK/T cell lymphoma with low ASNS expressions. ..
  3. Stams W, den Boer M, Beverloo H, van Wering E, Pieters R. Upregulation of asparagine synthetase and cell cycle arrest in t(12;21)-positive ALL. Leukemia. 2005;19:318-9; author reply 319-21 pubmed
  4. Olea F, P rez Garc a A, Cant n F, Rivera M, Ca as R, Avila C, et al. Up-regulation and localization of asparagine synthetase in tomato leaves infected by the bacterial pathogen Pseudomonas syringae. Plant Cell Physiol. 2004;45:770-80 pubmed
  5. Fujita Y, Ito M, Nozawa Y, Yoneda M, Oshida Y, Tanaka M. CHOP (C/EBP homologous protein) and ASNS (asparagine synthetase) induction in cybrid cells harboring MELAS and NARP mitochondrial DNA mutations. Mitochondrion. 2007;7:80-8 pubmed
    ..These results suggest that the presence of mtDNA mutations elicits upregulation of CHOP and ASNS genes through the elevation of ATF4 expression and its binding to the AARE and NSRE-1, respectively. ..
  6. Nakano Y, Naito Y, Nakano T, Ohtsuki N, Suzuki K. NSR1/MYR2 is a negative regulator of ASN1 expression and its possible involvement in regulation of nitrogen reutilization in Arabidopsis. Plant Sci. 2017;263:219-225 pubmed publisher
    ..Therefore, the present results suggest that NSR1/MYR2 plays a role in N reutilization as a negative regulator through controlling ASN1 expression. ..
  7. Zhou Q, Gao J, Zhang R, Zhang R. Ammonia stress on nitrogen metabolism in tolerant aquatic plant-Myriophyllum aquaticum. Ecotoxicol Environ Saf. 2017;143:102-110 pubmed publisher
    ..The results of the present study may support the studies on detoxification of high ammonium ion content in NH4+-tolerant submerged macrophytes and exploration of tissue-specific expression systems. ..
  8. Møller M, Taylor C, Rasmussen S, Holm P. Molecular cloning and characterisation of two genes encoding asparagine synthetase in barley (Hordeum vulgare L.). Biochim Biophys Acta. 2003;1628:123-32 pubmed
    ..A polyclonal antibody was raised against the HvAS1 protein and used in Western blot analysis. The AS protein accumulated during a 48-h period of dark treatment, following the increase in HvAS1 transcript. ..
  9. Ramos F, Wiame J. Two asparagine synthetases in Saccharomyces cerevisiae. Eur J Biochem. 1980;108:373-7 pubmed
    ..Neither one is located in mitochondria and both are probably cytosolic. Their identification so far lies only in their behaviour on ion-exchange chromatography and in the encoding genes. ..
  10. Williams D. A new mechanism of leukemia drug resistance?. N Engl J Med. 2007;357:77-8 pubmed
  11. Stams W, den Boer M, Holleman A, Appel I, Beverloo H, van Wering E, et al. Asparagine synthetase expression is linked with L-asparaginase resistance in TEL-AML1-negative but not TEL-AML1-positive pediatric acute lymphoblastic leukemia. Blood. 2005;105:4223-5 pubmed
    ..009). We conclude that resistance to l-asparaginase and relapse risk are associated with high expression of AS in TEL-AML1-negative but not TEL-AML1-positive B-lineage ALL. ..
  12. Koroniak L, Ciustea M, Gutierrez J, Richards N. Synthesis and characterization of an N-acylsulfonamide inhibitor of human asparagine synthetase. Org Lett. 2003;5:2033-6 pubmed
    ..These observations provide the basis for the discovery of new compounds with application in the treatment of drug-resistant leukemia. ..
  13. Lam H, Hsieh M, Coruzzi G. Reciprocal regulation of distinct asparagine synthetase genes by light and metabolites in Arabidopsis thaliana. Plant J. 1998;16:345-53 pubmed
    ..The distinct regulation of ASN1 and ASN2 genes combined with their distinct encoded isoenzymes suggest that they may play different roles in nitrogen metabolism, as discussed in this paper. ..
  14. Irino T, Kitoh T, Koami K, Kashima T, Mukai K, Takeuchi E, et al. Establishment of real-time polymerase chain reaction method for quantitative analysis of asparagine synthetase expression. J Mol Diagn. 2004;6:217-24 pubmed
    ..Consequently, this method was useful enough in defining candidates for selective therapy that targets an AS deficiency. ..
  15. Schnizer H, Boehlein S, Stewart J, Richards N, Schuster S. Formation and isolation of a covalent intermediate during the glutaminase reaction of a class II amidotransferase. Biochemistry. 1999;38:3677-82 pubmed
    ..These studies represent the first description of a thioester intermediate for any class II amidotransferase and represent an important step in gaining further insight into the kinetic and chemical mechanisms of AS-B. ..
  16. Leslie M, Case M, Hall A, Coulthard S. Expression levels of asparagine synthetase in blasts from children and adults with acute lymphoblastic leukaemia. Br J Haematol. 2006;132:740-2 pubmed
    ..001) and adult ALL versus adult AML (P < 0.01) were all significant and support the hypothesis that selectivity to treatment with l-asparaginase is due, at least in part, to lower AS expression. ..
  17. Herrera Rodríguez M, Maldonado J, Pérez Vicente R. Role of asparagine and asparagine synthetase genes in sunflower (Helianthus annuus) germination and natural senescence. J Plant Physiol. 2006;163:1061-70 pubmed
    ..The absence of significant AS gene expression in cotyledon senescence differentiates leaf and cotyledon senescence, and suggests a cotyledon-specific regulation. ..
  18. Wang H, Liu D, Sun J, Zhang A. Asparagine synthetase gene TaASN1 from wheat is up-regulated by salt stress, osmotic stress and ABA. J Plant Physiol. 2005;162:81-9 pubmed publisher
    ..TaASN1 was dramatically induced by salinity, osmotic stress and exogenous abscisic acid (ABA) in wheat seedlings. TaASN2 transcripts were very low in all detected tissues and conditions and were only slightly induced by ABA in roots...
  19. Nakatsu T, Kato H, Oda J. Crystal structure of asparagine synthetase reveals a close evolutionary relationship to class II aminoacyl-tRNA synthetase. Nat Struct Biol. 1998;5:15-9 pubmed
    ..The functional and structural similarities of both enzymes suggest that new enzymatic activities would generally follow the recruitment of a protein catalyzing a similar chemical reaction. ..
  20. Krejci O, Starkova J, Otova B, Madzo J, Kalinova M, Hrusak O, et al. Upregulation of asparagine synthetase fails to avert cell cycle arrest induced by L-asparaginase in TEL/AML1-positive leukaemic cells. Leukemia. 2004;18:434-41 pubmed
    ..00028). Therefore, high AsnS levels in TEL/AML1[+] patients correlate with better prognosis, possibly reflecting the stretched metabolic demand of the lymphoblast. ..
  21. Lam H, Peng S, Coruzzi G. Metabolic regulation of the gene encoding glutamine-dependent asparagine synthetase in Arabidopsis thaliana. Plant Physiol. 1994;106:1347-57 pubmed
  22. Miller M, Bachmann B, Townsend C, Rosenzweig A. Structure of beta-lactam synthetase reveals how to synthesize antibiotics instead of asparagine. Nat Struct Biol. 2001;8:684-9 pubmed
    ..The structural data provide the opportunity to alter the synthetic potential of beta-LS, perhaps leading to the creation of new beta-lactamase inhibitors and beta-lactam antibiotics. ..
  23. Parra Peralbo E, Pineda M, Aguilar M. PVAS3, a class-II ubiquitous asparagine synthetase from the common bean (Phaseolus vulgaris). Mol Biol Rep. 2009;36:2249-58 pubmed publisher
    ..2%) and sunflower HAS2 (72.9%). A phylogenetic analysis revealed that PVAS3 belongs to class-II asparagine synthetases. Expression analysis by real-time RT-PCR revealed that PVAS3 is expressed ubiquitously and is not repressed by light...
  24. Gupta N, Tewari V, Kumar M, Langeh N, Gupta A, Mishra P, et al. Asparagine Synthetase deficiency-report of a novel mutation and review of literature. Metab Brain Dis. 2017;32:1889-1900 pubmed publisher
    ..We add another case from India which harbored a novel homozygous missense variation in exon 11 and compare the current case with previously reported cases. ..
  25. Sun J, McGillivray A, Pinner J, Yan Z, Liu F, Bratkovic D, et al. Diaphragmatic Eventration in Sisters with Asparagine Synthetase Deficiency: A Novel Homozygous ASNS Mutation and Expanded Phenotype. JIMD Rep. 2017;34:1-9 pubmed publisher
    ..Like all previously reported patients, these cases were diagnosed with WES, highlighting the clinical utility of next generation sequencing in the diagnosis of rare, difficult to recognise disorders. ..
  26. Hashimoto K, Suzuki F, Sakagami H. Declined asparagine synthetase mRNA expression and enhanced sensitivity to asparaginase in HL-60 cells committed to monocytic differentiation. Anticancer Res. 2009;29:1303-8 pubmed
  27. Felton J, Michaelis S, Wright A. Mutations in two unlinked genes are required to produce asparagine auxotrophy in Escherichia coli. J Bacteriol. 1980;142:221-8 pubmed
    ..asnA is the previously mapped ilv-linked asn locus, whiich is between uncB and rbs. E. coli C also has two asn genes, corresponding to asnA and asnB. ..
  28. Horikoshi A, Takei K, Iriyama N, Uenogawa K, Ishizuka H, Shiraiwa H, et al. Effect of L-asparaginase combined with vincristine and prednisolone on acute myeloblastic leukemia (M0) associated with non-Hodgkin lymphoma. Acta Haematol. 2009;122:54-7 pubmed publisher
    ..Complete remission (CR) of AML and NHL was achieved. CR of the AML lasted for 18 months without further consolidation therapy. We conclude that L-Asp can be an effective drug for the treatment of AML in which blasts are negative for AS. ..
  29. Peng H, Shen N, Qian L, Sun X, Koduru P, Goodwin L, et al. Hypermethylation of CpG islands in the mouse asparagine synthetase gene: relationship to asparaginase sensitivity in lymphoma cells. Partial methylation in normal cells. Br J Cancer. 2001;85:930-5 pubmed
    ..It was also tissue related, with methylation occurring rarely in liver cells. The relationship of these changes to oncogenesis is considered. ..
  30. Palmer E, Hayner J, Sachdev R, Cardamone M, Kandula T, Morris P, et al. Asparagine Synthetase Deficiency causes reduced proliferation of cells under conditions of limited asparagine. Mol Genet Metab. 2015;116:178-86 pubmed publisher
    ..These functional studies offer insight into the underlying pathophysiology of the dramatic progressive cerebral atrophy associated with Asparagine Synthetase Deficiency. ..
  31. Siu F, Chen C, Zhong C, Kilberg M. CCAAT/enhancer-binding protein-beta is a mediator of the nutrient-sensing response pathway that activates the human asparagine synthetase gene. J Biol Chem. 2001;276:48100-7 pubmed
    ..Collectively, the results provide both in vitro and in vivo evidence for a role of C/EBPbeta in the transcriptional activation of the AS gene in response to nutrient deprivation. ..
  32. Gjymishka A, Su N, Kilberg M. Transcriptional induction of the human asparagine synthetase gene during the unfolded protein response does not require the ATF6 and IRE1/XBP1 arms of the pathway. Biochem J. 2009;417:695-703 pubmed publisher
    ..Consequently, ASNS NSRE-1 and NSRE-2, in addition to ERSE (ER stress response element)-I, ERSE-II and the mUPRE (mammalian UPR element), function as mammalian ER-stress-responsive sequences. ..
  33. Sacharow S, Dudenhausen E, Lomelino C, Rodan L, El Achkar C, Olson H, et al. Characterization of a novel variant in siblings with Asparagine Synthetase Deficiency. Mol Genet Metab. 2018;123:317-325 pubmed publisher
    ..Collectively, the results suggest that the Arg49Gln variant affects the enzymatic function of ASNS. The clinical, cellular, and molecular observations from these siblings expand the known phenotypic spectrum of ASD. ..
  34. Lanvers Kaminsky C. Asparaginase pharmacology: challenges still to be faced. Cancer Chemother Pharmacol. 2017;79:439-450 pubmed publisher
  35. Dhawi F, Datta R, Ramakrishna W. Proteomics provides insights into biological pathways altered by plant growth promoting bacteria and arbuscular mycorrhiza in sorghum grown in marginal soil. Biochim Biophys Acta Proteins Proteom. 2017;1865:243-251 pubmed publisher
  36. Antunes F, Aguilar M, Pineda M, Sodek L. Nitrogen stress and the expression of asparagine synthetase in roots and nodules of soybean (Glycine max). Physiol Plant. 2008;133:736-43 pubmed publisher
    ..Regulation of nodule AS expression is quite different from that of the root, but nodule SAS1, at least, appears to involve a product of N assimilation rather than nitrate itself. ..
  37. Iwamoto S, Mihara K, Downing J, Pui C, Campana D. Mesenchymal cells regulate the response of acute lymphoblastic leukemia cells to asparaginase. J Clin Invest. 2007;117:1049-57 pubmed
    ..These results provide what we believe to be a new basis for understanding asparaginase resistance in ALL and indicate that MSC niches in the bone marrow can form a safe haven for leukemic cells. ..
  38. Herrera Rodríguez M, Maldonado J, Pérez Vicente R. Light and metabolic regulation of HAS1, HAS1.1 and HAS2, three asparagine synthetase genes in Helianthus annuus. Plant Physiol Biochem. 2004;42:511-8 pubmed
    ..Darkness and low C/N ratio conditions trigger the response of the specialized HAS1 and HAS1.1 genes which contribute to store the excess nitrogen as asparagine. Ammonium induces all three AS-genes which may favor its detoxification. ..
  39. De Marchis F, Bellucci M, Arcioni S. Measuring gene flow from two birdsfoot trefoil (Lotus corniculatus) field trials using transgenes as tracer markers. Mol Ecol. 2003;12:1681-5 pubmed
    ..As regards nontransgenic L. corniculatus plants, in one location flow of asnA transgene was detected up to 18 m from the 1.8 m2 donor plot. In the other location, pollen dispersal occurred up to 120 m from the 14 m2 pollinating plot. ..
  40. Poggio S, Domeinzain C, Osorio A, Camarena L. The nitrogen assimilation control (Nac) protein represses asnC and asnA transcription in Escherichia coli. FEMS Microbiol Lett. 2002;206:151-6 pubmed
    ..These results allow us to conclude that asnA transcription is regulated by two different mechanisms that respond to different effectors: nitrogen and asparagine availability. ..
  41. Mueller E, Palenchar P. Using genomic information to investigate the function of ThiI, an enzyme shared between thiamin and 4-thiouridine biosynthesis. Protein Sci. 1999;8:2424-7 pubmed
  42. Chen H, Kilberg M. Alignment of the transcription start site coincides with increased transcriptional activity from the human asparagine synthetase gene following amino acid deprivation of HepG2 cells. J Nutr. 2006;136:2463-7 pubmed
    ..To our knowledge, these results are the first example in a mammalian cell of transcription start selection by nutrient availability. ..
  43. Meyer M, Gutierrez J, Raushel F, Richards N. A conserved glutamate controls the commitment to acyl-adenylate formation in asparagine synthetase. Biochemistry. 2010;49:9391-401 pubmed publisher
    ..Given the similarity of the chemistry catalyzed by AS-B, BLS, and CPS, our work highlights the difficulty of predicting the functional outcome of single site mutations on enzymes that catalyze almost identical chemical transformations. ..
  44. Stams W, den Boer M, Beverloo H, Meijerink J, Stigter R, van Wering E, et al. Sensitivity to L-asparaginase is not associated with expression levels of asparagine synthetase in t(12;21)+ pediatric ALL. Blood. 2003;101:2743-7 pubmed
    ..Furthermore, we contradict the general thought that leukemic cells specifically lack AS compared with normal bone marrow and blood cells. ..
  45. Lomelino C, Andring J, McKenna R, Kilberg M. Asparagine synthetase: Function, structure, and role in disease. J Biol Chem. 2017;292:19952-19958 pubmed publisher
    ..For some ASD patients, fibroblast cell culture studies have eliminated protein and mRNA synthesis or stability as the basis for decreased proliferation. ..
  46. Hutson R, Kilberg M. Cloning of rat asparagine synthetase and specificity of the amino acid-dependent control of its mRNA content. Biochem J. 1994;304 ( Pt 3):745-50 pubmed
    ..The data indicate that nutrient regulation of AS mRNA occurs by a general control mechanism that is responsive to a spectrum of amino acids. ..
  47. Li W, Dong C. Polymorphism in asparagine synthetase is associated with overall survival of hepatocellular carcinoma patients. BMC Gastroenterol. 2017;17:79 pubmed publisher
    ..003) and also an independent predictor of overall survival of HCC patients (P = 0.001). Taken together, these findings indicated that rs34050735 in ASNS may associate with HCC and may be a promising biomarker of HCC. ..
  48. Ding Y, Li Z, Broome J. Epigenetic changes in the repression and induction of asparagine synthetase in human leukemic cell lines. Leukemia. 2005;19:420-6 pubmed
    ..The lability of expression of ASY has potential significance in determining the sensitivity of leukemic cells to L-asparaginase. ..
  49. Wyrwa K, Książkiewicz M, Szczepaniak A, Susek K, Podkowinski J, Naganowska B. Integration of Lupinus angustifolius L. (narrow-leafed lupin) genome maps and comparative mapping within legumes. Chromosome Res. 2016;24:355-78 pubmed publisher
    ..This work provides a strong foundation for future comparative mapping among legumes and may facilitate understanding of mechanisms involved in shaping legume chromosomes. ..
  50. Estes D, Lovato D, Khawaja H, Winter S, Larson R. Genetic alterations determine chemotherapy resistance in childhood T-ALL: modelling in stage-specific cell lines and correlation with diagnostic patient samples. Br J Haematol. 2007;139:20-30 pubmed
  51. Leung Pineda V, Kilberg M. Role of Sp1 and Sp3 in the nutrient-regulated expression of the human asparagine synthetase gene. J Biol Chem. 2002;277:16585-91 pubmed
    ..Sp1 expression increased basal transcription but did not cause a further increase when SL2 cells were amino acid-deprived. Sp3 expression enhanced both the basal and the starvation-induced transcription. ..
  52. Osuna D, Galvez Valdivieso G, Piedras P, Pineda M, Aguilar M. Cloning, characterization and mRNA expression analysis of PVAS1, a type I asparagine synthetase gene from Phaseolus vulgaris. Planta. 2001;213:402-10 pubmed
    ..Unlike PVAS2, however, PVAS1 was not expressed in the nodule and was not repressed by light, suggesting different functions for these two AS genes. ..
  53. Zhang Y, Lambert M, Cairney A, Wills D, Ray P, Andrulis I. Molecular structure of the human asparagine synthetase gene. Genomics. 1989;4:259-65 pubmed
    ..Comparisons of the 5' upstream sequences of the human and hamster genes show limited similarity; however, both have a very high G + C content which may play a role in expression through DNA methylation. ..