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Gene Review

Alas2  -  aminolevulinic acid synthase 2, erythroid

Mus musculus

Synonyms: 5-aminolevulinate synthase, 5-aminolevulinate synthase, erythroid-specific, mitochondrial, 5-aminolevulinic acid synthase 2, ALAS, ALAS-E, ...
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Disease relevance of Alas2


High impact information on Alas2


Chemical compound and disease context of Alas2


Biological context of Alas2

  • Sb1.8 was sublocalized to band F of the mouse X chromosome, distal to Alas2 and proximal to DXPas1, which confirms a region of conservation between band Xp11.21-p11.22 in human and band XF in mouse [10].
  • Mice with the Alas2-null phenotype showed massive cytoplasmic, but not mitochondrial, iron accumulation in their primitive erythroblasts [7].
  • Apex2 consists of six exons and is flanked on the 3' end by Alas2 on X chromosome 63 [11].
  • These findings thus indicate that heme formation, which is determined by the level of ALAS-E, plays an essential role on gene expression of many proteins necessary for erythroid development [12].
  • This could lead to up-regulation of globin gene transcription, thereby releasing iron that in turn controls production of ferritins, and further up-regulating aminolevulinate synthase 2 (Alas2) [13].

Anatomical context of Alas2


Associations of Alas2 with chemical compounds

  • In MEL cells in which an antisense ALAS-E RNA was expressed (AS clone), sense ALAS-E mRNA levels in both untreated and dimethylsulfoxide (DMSO)-treated cells were decreased compared with their respective controls [12].
  • While recent reports have clearly demonstrated that GATA-1 is involved in the induction of erythroid cell-specific forms of 5-aminolevulinate synthase (ALAS-2) and porphobilinogen (PBG) deaminase and that cellular iron status plays a regulatory role for ALAS-2, little is known about regulation of the remainder of the pathway [16].
  • 5-Aminolevulinate synthase (ALAS), a pyridoxal 5'-phosphate-dependent enzyme, catalyzes the first, and regulatory, step of the heme biosynthetic pathway in nonplant eukaryotes and some bacteria [17].
  • Both ALAS-E and ALAS-N mRNAs were detected in a clone of dimethyl sulfoxide (Me2SO)-sensitive MEL cells, termed DS-19, without cross-hybridization [2].
  • 5-Aminolevulinate synthase is a dimeric protein having an ordered kinetic mechanism with glycine binding before succinyl-CoA and with aminolevulinate release after CoA and carbon dioxide [17].

Regulatory relationships of Alas2

  • These findings suggest that ALAS-E and ALAS-N mRNAs are under separate controls and that the expression of ALAS-E mRNA is a critical event in erythroid differentiation [18].

Other interactions of Alas2


Analytical, diagnostic and therapeutic context of Alas2

  • Although the roles of defined amino acids in the active site and catalytic mechanism have been recently explored using site-directed mutagenesis, much less is known about the role of the 5-aminolevulinate synthase polypeptide chain arrangement in folding, structure, and ultimately, function [23].
  • To examine the roles heme plays during hematopoiesis and to create animal models of XLSA, we disrupted the mouse ALAS-E gene [24].


  1. Heme deficiency in erythroid lineage causes differentiation arrest and cytoplasmic iron overload. Nakajima, O., Takahashi, S., Harigae, H., Furuyama, K., Hayashi, N., Sassa, S., Yamamoto, M. EMBO J. (1999) [Pubmed]
  2. Erythroleukemia differentiation. Distinctive responses of the erythroid-specific and the nonspecific delta-aminolevulinate synthase mRNA. Fujita, H., Yamamoto, M., Yamagami, T., Hayashi, N., Sassa, S. J. Biol. Chem. (1991) [Pubmed]
  3. Expression of mammalian 5-aminolevulinate synthase in Escherichia coli. Overproduction, purification, and characterization. Ferreira, G.C., Dailey, H.A. J. Biol. Chem. (1993) [Pubmed]
  4. Zinc mesoporphyrin represses induced hepatic 5-aminolevulinic acid synthase and reduces heme oxygenase activity in a mouse model of acute hepatic porphyria. Schuurmans, M.M., Hoffmann, F., Lindberg, R.L., Meyer, U.A. Hepatology (2001) [Pubmed]
  5. Pre-steady-state reaction of 5-aminolevulinate synthase. Evidence for a rate-determining product release. Hunter, G.A., Ferreira, G.C. J. Biol. Chem. (1999) [Pubmed]
  6. 5-Aminolevulinate synthase is at 3p21 and thus not the primary defect in X-linked sideroblastic anemia. Sutherland, G.R., Baker, E., Callen, D.F., Hyland, V.J., May, B.K., Bawden, M.J., Healy, H.M., Borthwick, I.A. Am. J. Hum. Genet. (1988) [Pubmed]
  7. Aberrant iron accumulation and oxidized status of erythroid-specific delta-aminolevulinate synthase (ALAS2)-deficient definitive erythroblasts. Harigae, H., Nakajima, O., Suwabe, N., Yokoyama, H., Furuyama, K., Sasaki, T., Kaku, M., Yamamoto, M., Sassa, S. Blood (2003) [Pubmed]
  8. Active site of 5-aminolevulinate synthase resides at the subunit interface. Evidence from in vivo heterodimer formation. Tan, D., Ferreira, G.C. Biochemistry (1996) [Pubmed]
  9. Pyridoxine refractory X-linked sideroblastic anemia caused by a point mutation in the erythroid 5-aminolevulinate synthase gene. Furuyama, K., Fujita, H., Nagai, T., Yomogida, K., Munakata, H., Kondo, M., Kimura, A., Kuramoto, A., Hayashi, N., Yamamoto, M. Blood (1997) [Pubmed]
  10. The mouse Sb1.8 gene located at the distal end of the X chromosome is subject to X inactivation. Sultana, R., Adler, D.A., Edelhoff, S., Carrel, L., Lee, K.H., Chapman, V.C., Willard, H.F., Disteche, C.M. Hum. Mol. Genet. (1995) [Pubmed]
  11. Characterization of the genomic structure and expression of the mouse Apex2 gene. Ide, Y., Tsuchimoto, D., Tominaga, Y., Iwamoto, Y., Nakabeppu, Y. Genomics (2003) [Pubmed]
  12. The role of the erythroid-specific delta-aminolevulinate synthase gene expression in erythroid heme synthesis. Meguro, K., Igarashi, K., Yamamoto, M., Fujita, H., Sassa, S. Blood (1995) [Pubmed]
  13. Light pulse-induced heme and iron-associated transcripts in mouse brain: a microarray analysis. Ben-Shlomo, R., Akhtar, R.A., Collins, B.H., Judah, D.J., Davies, R., Kyriacou, C.P. Chronobiol. Int. (2005) [Pubmed]
  14. Deficient heme and globin synthesis in embryonic stem cells lacking the erythroid-specific delta-aminolevulinate synthase gene. Harigae, H., Suwabe, N., Weinstock, P.H., Nagai, M., Fujita, H., Yamamoto, M., Sassa, S. Blood (1998) [Pubmed]
  15. Regulation of 5-aminolevulinate synthase in mouse erythroleukemic cells is different from that in liver. Elferink, C.J., Sassa, S., May, B.K. J. Biol. Chem. (1988) [Pubmed]
  16. Biphasic ordered induction of heme synthesis in differentiating murine erythroleukemia cells: role of erythroid 5-aminolevulinate synthase. Lake-Bullock, H., Dailey, H.A. Mol. Cell. Biol. (1993) [Pubmed]
  17. Transient state kinetic investigation of 5-aminolevulinate synthase reaction mechanism. Zhang, J., Ferreira, G.C. J. Biol. Chem. (2002) [Pubmed]
  18. Differential induction responses of delta-aminolevulinate synthase mRNAs during erythroid differentiation: use of nonradioactive in situ hybridization. Mitani, K., Fujita, H., Hayashi, N., Yamamoto, M., Sassa, S. Am. J. Hematol. (1992) [Pubmed]
  19. Transcriptional regulation of the murine erythroid-specific 5-aminolevulinate synthase gene. Kramer, M.F., Gunaratne, P., Ferreira, G.C. Gene (2000) [Pubmed]
  20. Fine genetic mapping of the Hyp mutation on mouse chromosome X. Du, L., Desbarats, M., Cornibert, S., Malo, D., Ecarot, B. Genomics (1996) [Pubmed]
  21. Effect of Griseofulvin on 5-aminolevulinate synthase and on ferrochelatase in mouse liver neoplastic nodules. Denk, H., Kalt, R., Abdelfattach-Gad, M., Meyer, U.A. Cancer Res. (1981) [Pubmed]
  22. Protein tyrosine phosphatase-dependent activation of beta-globin and delta-aminolevulinic acid synthase genes in the camptothecin-induced IW32 erythroleukemia cell differentiation. Wang, M.C., Liu, J.H., Wang, F.F. Mol. Pharmacol. (1997) [Pubmed]
  23. Circular permutation of 5-aminolevulinate synthase. Mapping the polypeptide chain to its function. Cheltsov, A.V., Barber, M.J., Ferreira, G.C. J. Biol. Chem. (2001) [Pubmed]
  24. Animal models for X-linked sideroblastic anemia. Yamamoto, M., Nakajima, O. Int. J. Hematol. (2000) [Pubmed]
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