ALAS2 explained

Delta-aminolevulinate synthase 2 also known as ALAS2 is a protein that in humans is encoded by the ALAS2 gene.^{[1] [2] [3]} ALAS2 is an aminolevulinic acid synthase.

The product of this gene specifies an erythroid-specific mitochondrially located enzyme. The encoded protein catalyzes the first step in the heme biosynthetic pathway. Defects in this gene cause X-linked pyridoxine-responsive sideroblastic anemia. Alternatively spliced transcript variants encoding different isoforms have been identified.^[3]

Its gene contains an IRE in its 5'-UTR region on which an IRP binds if the iron level is too low, thus inhibiting its translation.

References

Further reading

• Han L, Zhong Y, Huang B, Han L, Pan L, Xu X, Wang X, Huang B, Lu J . Sodium butyrate activates erythroid-specific 5-aminolevulinate synthase gene through Sp1 elements at its promoter . Blood Cells, Molecules & Diseases . 41 . 2 . 148–53 . 2008 . 18555711 . 10.1016/j.bcmd.2008.04.002 .
• Kaneko K, Furuyama K, Aburatani H, Shibahara S . Hypoxia induces erythroid-specific 5-aminolevulinate synthase expression in human erythroid cells through transforming growth factor-beta signaling . The FEBS Journal . 276 . 5 . 1370–82 . Mar 2009 . 19187226 . 10.1111/j.1742-4658.2009.06878.x . free .
• Cox TC, Sadlon TJ, Schwarz QP, Matthews CS, Wise PD, Cox LL, Bottomley SS, May BK . The major splice variant of human 5-aminolevulinate synthase-2 contributes significantly to erythroid heme biosynthesis . The International Journal of Biochemistry & Cell Biology . 36 . 2 . 281–95 . Feb 2004 . 14643893 . 10.1016/S1357-2725(03)00246-2 .
• Harigae H, Furuyama K, Kudo K, Hayashi N, Yamamoto M, Sassa S, Sasaki T . A novel mutation of the erythroid-specific gamma-Aminolevulinate synthase gene in a patient with non-inherited pyridoxine-responsive sideroblastic anemia . American Journal of Hematology . 62 . 2 . 112–4 . Oct 1999 . 10577279 . 10.1002/(SICI)1096-8652(199910)62:2<112::AID-AJH9>3.0.CO;2-L . free .
• Hurford MT, Marshall-Taylor C, Vicki SL, Zhou JZ, Silverman LM, Rezuke WN, Altman A, Tsongalis GJ . A novel mutation in exon 5 of the ALAS2 gene results in X-linked sideroblastic anemia . Clinica Chimica Acta; International Journal of Clinical Chemistry . 321 . 1–2 . 49–53 . Jul 2002 . 12031592 . 10.1016/S0009-8981(02)00095-5 .
• Bekri S, May A, Cotter PD, Al-Sabah AI, Guo X, Masters GS, Bishop DF . A promoter mutation in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causes X-linked sideroblastic anemia . Blood . 102 . 2 . 698–704 . Jul 2003 . 12663458 . 10.1182/blood-2002-06-1623 . free .
• Astner I, Schulze JO, van den Heuvel J, Jahn D, Schubert WD, Heinz DW . Crystal structure of 5-aminolevulinate synthase, the first enzyme of heme biosynthesis, and its link to XLSA in humans . The EMBO Journal . 24 . 18 . 3166–77 . Sep 2005 . 16121195 . 1224682 . 10.1038/sj.emboj.7600792 .
• Cazzola M, May A, Bergamaschi G, Cerani P, Ferrillo S, Bishop DF . Absent phenotypic expression of X-linked sideroblastic anemia in one of 2 brothers with a novel ALAS2 mutation . Blood . 100 . 12 . 4236–8 . Dec 2002 . 12393718 . 10.1182/blood-2002-03-0685 . free .
• Sussman NL, Lee PL, Dries AM, Schwartz MR, Barton JC . Multi-organ iron overload in an African-American man with ALAS2 R452S and SLC40A1 R561G . Acta Haematologica . 120 . 3 . 168–73 . 2008 . 19066423 . 10.1159/000181183 . 10636344 .
• Whatley SD, Ducamp S, Gouya L, Grandchamp B, Beaumont C, Badminton MN, Elder GH, Holme SA, Anstey AV, Parker M, Corrigall AV, Meissner PN, Hift RJ, Marsden JT, Ma Y, Mieli-Vergani G, Deybach JC, Puy H . C-terminal deletions in the ALAS2 gene lead to gain of function and cause X-linked dominant protoporphyria without anemia or iron overload . American Journal of Human Genetics . 83 . 3 . 408–14 . Sep 2008 . 18760763 . 2556430 . 10.1016/j.ajhg.2008.08.003 .
• Furuyama K, Sassa S . Interaction between succinyl CoA synthetase and the heme-biosynthetic enzyme ALAS-E is disrupted in sideroblastic anemia . The Journal of Clinical Investigation . 105 . 6 . 757–64 . Mar 2000 . 10727444 . 377455 . 10.1172/JCI6816 .
• Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S . Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions . Genome Research . 14 . 9 . 1711–8 . Sep 2004 . 15342556 . 515316 . 10.1101/gr.2435604 .
• Lee PL, Barton JC, Rao SV, Acton RT, Adler BK, Beutler E . Three kinships with ALAS2 P520L (c. 1559 C --> T) mutation, two in association with severe iron overload, and one with sideroblastic anemia and severe iron overload . Blood Cells, Molecules & Diseases . 36 . 2 . 292–7 . 2006 . 16446107 . 10.1016/j.bcmd.2005.12.004 .
• Bergmann AK, Campagna DR, McLoughlin EM, Agarwal S, Fleming MD, Bottomley SS, Neufeld EJ . Systematic molecular genetic analysis of congenital sideroblastic anemia: evidence for genetic heterogeneity and identification of novel mutations . Pediatric Blood & Cancer . 54 . 2 . 273–8 . Feb 2010 . 19731322 . 2843911 . 10.1002/pbc.22244 .
• Rabstein S, Unfried K, Ranft U, Illig T, Kolz M, Mambetova C, Vlad M, Roman C, Weiss T, Becker D, Brüning T, Pesch B . Lack of association of delta-aminolevulinate dehydratase polymorphisms with blood lead levels and hemoglobin in Romanian women from a lead-contaminated region . Journal of Toxicology and Environmental Health. Part A . 71 . 11–12 . 716–24 . 2008 . 18569569 . 10.1080/15287390801985190 . 2008JTEHA..71..716R . 20337081 .
• Abu-Farha M, Niles J, Willmore WG . Erythroid-specific 5-aminolevulinate synthase protein is stabilized by low oxygen and proteasomal inhibition . Biochemistry and Cell Biology . 83 . 5 . 620–30 . Oct 2005 . 16234850 . 10.1139/o05-045 .
• Nachman MW, D'Agostino SL, Tillquist CR, Mobasher Z, Hammer MF . Nucleotide variation at Msn and Alas2, two genes flanking the centromere of the X chromosome in humans . Genetics . 167 . 1 . 423–37 . May 2004 . 15166166 . 1470878 . 10.1534/genetics.167.1.423 .

External links

• • GeneReviews/NCBI/NIH/UW entry on X-Linked Sideroblastic Anemia and Ataxia

Notes and References

1. Bishop DF, Henderson AS, Astrin KH . Human delta-aminolevulinate synthase: assignment of the housekeeping gene to 3p21 and the erythroid-specific gene to the X chromosome . Genomics . 7 . 2 . 207–14 . Jun 1990 . 2347585 . 10.1016/0888-7543(90)90542-3 .
2. Cotter PD, Willard HF, Gorski JL, Bishop DF . Assignment of human erythroid delta-aminolevulinate synthase (ALAS2) to a distal subregion of band Xp11.21 by PCR analysis of somatic cell hybrids containing X; autosome translocations . Genomics . 13 . 1 . 211–2 . May 1992 . 1577484 . 10.1016/0888-7543(92)90223-F . 2027.42/30074 . free .
3. Web site: Entrez Gene: Delta-aminolevulinate synthase 2 .