ALAS2

Aminolevulinate, delta-, synthase 2
Identifiers
Symbols	ALAS2; ALAS-E; ALASE; ANH1; ASB; FLJ93603; XLDPP; XLSA
External IDs	OMIM: 301300 MGI: 87990 HomoloGene: 17 GeneCards: ALAS2 Gene
EC number	2.3.1.37
Gene Ontology Molecular function • 5-aminolevulinate synthase activity • protein binding • acyltransferase activity • glycine binding • transferase activity, transferring nitrogenous groups • pyridoxal phosphate binding • coenzyme binding Cellular component • mitochondrion • mitochondrial inner membrane • mitochondrial matrix Biological process • response to hypoxia • porphyrin metabolic process • heme biosynthetic process • heme biosynthetic process • heme biosynthetic process • cellular iron ion homeostasis • biosynthetic process • erythrocyte differentiation • erythrocyte differentiation • oxygen homeostasis • tetrapyrrole biosynthetic process • hemoglobin biosynthetic process Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	212	11656
Ensembl	ENSG00000158578	ENSMUSG00000025270
UniProt	P22557	P08680
RefSeq (mRNA)	NM_000032.4	NM_009653
RefSeq (protein)	NP_000023.2	NP_001095916
Location (UCSC)	Chr X: 55.04 – 55.06 Mb	Chr X: 146.98 – 147.01 Mb
PubMed search	[1]	[2]

Delta-aminolevulinate synthase 2 also known as ALAS2 is a protein that in humans is encoded by the ALAS2 gene. 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.

External links

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

Further reading

• Ross MT, Grafham DV, Coffey AJ, et al. (2005). "The DNA sequence of the human X chromosome". Nature 434 (7031): 325–37. doi:10.1038/nature03440. PMC 2665286. PMID 15772651. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2665286. 
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• Han L, Zhong Y, Huang B, et al. (2008). "Sodium butyrate activates erythroid-specific 5-aminolevulinate synthase gene through Sp1 elements at its promoter". Blood Cells Mol. Dis. 41 (2): 148–53. doi:10.1016/j.bcmd.2008.04.002. PMID 18555711. 
• Kaneko K, Furuyama K, Aburatani H, Shibahara S (2009). "Hypoxia induces erythroid-specific 5-aminolevulinate synthase expression in human erythroid cells through transforming growth factor-beta signaling". FEBS J. 276 (5): 1370–82. doi:10.1111/j.1742-4658.2009.06878.x. PMID 19187226. 
• Cox TC, Sadlon TJ, Schwarz QP, et al. (2004). "The major splice variant of human 5-aminolevulinate synthase-2 contributes significantly to erythroid heme biosynthesis". Int. J. Biochem. Cell Biol. 36 (2): 281–95. doi:10.1016/S1357-2725(03)00246-2. PMID 14643893. 
• Harigae H, Furuyama K, Kudo K, et al. (1999). "A novel mutation of the erythroid-specific gamma-Aminolevulinate synthase gene in a patient with non-inherited pyridoxine-responsive sideroblastic anemia". Am. J. Hematol. 62 (2): 112–4. doi:10.1002/(SICI)1096-8652(199910)62:2<112::AID-AJH9>3.0.CO;2-L. PMID 10577279. 
• Hurford MT, Marshall-Taylor C, Vicki SL, et al. (2002). "A novel mutation in exon 5 of the ALAS2 gene results in X-linked sideroblastic anemia". Clin. Chim. Acta 321 (1–2): 49–53. doi:10.1016/S0009-8981(02)00095-5. PMID 12031592. 
• Bekri S, May A, Cotter PD, et al. (2003). "A promoter mutation in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causes X-linked sideroblastic anemia". Blood 102 (2): 698–704. doi:10.1182/blood-2002-06-1623. PMID 12663458. 
• Astner I, Schulze JO, van den Heuvel J, et al. (2005). "Crystal structure of 5-aminolevulinate synthase, the first enzyme of heme biosynthesis, and its link to XLSA in humans". EMBO J. 24 (18): 3166–77. doi:10.1038/sj.emboj.7600792. PMC 1224682. PMID 16121195. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1224682. 
• Cazzola M, May A, Bergamaschi G, et al. (2002). "Absent phenotypic expression of X-linked sideroblastic anemia in one of 2 brothers with a novel ALAS2 mutation". Blood 100 (12): 4236–8. doi:10.1182/blood-2002-03-0685. PMID 12393718. 
• Sussman NL, Lee PL, Dries AM, et al. (2008). "Multi-organ iron overload in an African-American man with ALAS2 R452S and SLC40A1 R561G". Acta Haematol. 120 (3): 168–73. doi:10.1159/000181183. PMID 19066423. 
• Whatley SD, Ducamp S, Gouya L, et al. (2008). "C-Terminal Deletions in the ALAS2 Gene Lead to Gain of Function and Cause X-linked Dominant Protoporphyria without Anemia or Iron Overload". Am. J. Hum. Genet. 83 (3): 408–14. doi:10.1016/j.ajhg.2008.08.003. PMC 2556430. PMID 18760763. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2556430. 
• Furuyama K, Sassa S (2000). "Interaction between succinyl CoA synthetase and the heme-biosynthetic enzyme ALAS-E is disrupted in sideroblastic anemia". J. Clin. Invest. 105 (6): 757–64. doi:10.1172/JCI6816. PMC 377455. PMID 10727444. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=377455. 
• Suzuki Y, Yamashita R, Shirota M, et al. (2004). "Sequence Comparison of Human and Mouse Genes Reveals a Homologous Block Structure in the Promoter Regions". Genome Res. 14 (9): 1711–8. doi:10.1101/gr.2435604. PMC 515316. PMID 15342556. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=515316. 
• Lee PL, Barton JC, Rao SV, et al. (2006). "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 Mol. Dis. 36 (2): 292–7. doi:10.1016/j.bcmd.2005.12.004. PMID 16446107. 
• Bergmann AK, Campagna DR, McLoughlin EM, et al. (2010). "Systematic Molecular Genetic Analysis of Congenital Sideroblastic Anemia: Evidence for Genetic Heterogeneity and Identification of Novel Mutations". Pediatr Blood Cancer 54 (2): 273–8. doi:10.1002/pbc.22244. PMC 2843911. PMID 19731322. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2843911. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Rabstein S, Unfried K, Ranft U, et al. (2008). "Lack of association of delta-aminolevulinate dehydratase polymorphisms with blood lead levels and hemoglobin in Romanian women from a lead-contaminated region". J. Toxicol. Environ. Health Part A 71 (11–12): 716–24. doi:10.1080/15287390801985190. PMID 18569569. 
• Abu-Farha M, Niles J, Willmore WG (2005). "Erythroid-specific 5-aminolevulinate synthase protein is stabilized by low oxygen and proteasomal inhibition". Biochem. Cell Biol. 83 (5): 620–30. doi:10.1139/o05-045. PMID 16234850. 
• Nachman MW, D'Agostino SL, Tillquist CR, et al. (2004). "Nucleotide variation at Msn and Alas2, two genes flanking the centromere of the X chromosome in humans". Genetics 167 (1): 423–37. doi:10.1534/genetics.167.1.423. PMC 1470878. PMID 15166166. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1470878. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.